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A fourth wave of the how to buy amoxil opioid epidemic is coming, a national expert on drug use and policy said during a virtual panel discussion this week hosted by the Berkshire County, Massachusetts, District Attorney’s Office and the Berkshire Opioid Addiction Prevention Collaborative.Dr. Daniel Ciccarone, a professor of family and community medicine at the University of California, San Francisco (UCSF) School of Medicine, said the next wave in the country’s opioid health emergency will focus on stimulants like methamphetamine and cocaine, and drug combinations where stimulants are used in conjunction with opioids.“The use of methamphetamines is back and it’s back big time,” said Ciccarone, whose most recent research has focused on heroin use.Previously, officials had said there were three waves of the opioid epidemic – the first being prescription pills, the second being heroin, and the third being synthetic drugs, like fentanyl.Now, Ciccarone said, what federal law enforcement and medical experts are seeing is an increase in the use of stimulants, especially methamphetamines.The increase in deaths due to stimulants how to buy amoxil may be attributed to a number of causes. The increase in supply, both imported and domestically produced, as well as the increase of the drugs’ potency.“Meth’s purity and potency has gone up to historical levels,” he said. €œAs of 2018, we’ve reached unseen heights of 97 percent potency and 97 percent purity how to buy amoxil.

In a prohibitionist world, we should not be seeing such high quality. This is almost pharmaceutical quality.”Additionally, law enforcement and public how to buy amoxil health experts like Ciccarone are seeing an increase in the co-use of stimulants with opioids, he said. Speedballs, cocaine mixed with heroin, and goofballs, methamphetamines used with heroin or fentanyl, are becoming more common from the Midwest into Appalachia and up through New England, he said.Federal law enforcement officials are recommending local communities prepare for the oncoming rise in illegal drugs coming into their communities.“Some people will use them both at the same time, but some may use them in some combination regularly,” he said. €œThey may use meth in the morning to go to work, and use heroin at night to come down.”The co-use, he said, was an organic response to the fentanyl overdose epidemic.“Some of the things that we heard … is that meth is popularly construed as helping how to buy amoxil to decrease heroin and fentanyl use.

Helping with heroin withdraw symptoms and helping how to buy amoxil with heroin overdoses,” he said. €œWe debated this for many years that people were using stimulants to reverse overdoses – we’re hearing it again.”“Supply is up, purity is up, price is down,” he said. €œWe know from economics that when drug patterns go in how to buy amoxil that direction, use is going up.”Ciccarone said that there should not be deaths because of stimulants, but that heroin/fentanyl is the deadly element in the equation.His recommendations to communities were not to panic, but to lower the stigma surrounding drug use in order to affect change. Additionally, he said, policies should focus on reduction.

supply how to buy amoxil reduction, demand reduction and harm reduction. But not focus on only one single drug.Additionally, he said that by addressing issues within communities and by healing communities socially, economically and spiritually, communities can begin to reduce demand.“We’ve got to fix the cracks in our society, because drugs fall into the cracks,” he said..

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AbstractBrazil is currently home to where can i buy amoxil over the counter the largest Japanese population look at here outside of Japan. In Brazil today, Japanese-Brazilians are considered to be successful members of Brazilian society. This was not where can i buy amoxil over the counter always the case, however, and Japanese immigrants to Brazil endured much hardship to attain their current level of prestige. This essay explores this community’s trajectory towards the formation of the Japanese-Brazilian identity and the issues of mental health that arise in this immigrant community.

Through the analysis of Japanese-Brazilian novels, TV shows, film and public health studies, I seek to disentangle the themes of gender and modernisation, and how these themes concurrently grapple with Japanese-Brazilian mental health issues. These fictional narratives provide where can i buy amoxil over the counter a lens into the experience of the Japanese-Brazilian community that is unavailable in traditional medical studies about their mental health.filmliterature and medicinemental health caregender studiesmedical humanitiesData availability statementData are available in a public, open access repository.Introduction and philosophical backgroundWork in the medical humanities has noted the importance of the ‘medical gaze’ and how it may ‘see’ the patient in ways which are specific, while possessing broad significance, in relation to developing medical knowledge. To diagnosis. And to the social position of the medical profession.1 Some authors have emphasised that vision is a distinctive modality of perception which merits its own consideration, and which where can i buy amoxil over the counter may have a particular role to play in medical education and understanding.2 3 The clothing we wear has a strong impact on how we are perceived.

For example, commentary in this journal on the ‘white coat’ observes that while it may rob the medical doctor of individuality, it nonetheless grants an elevated status4. In contrast, the patient hospital gown may rob patients of individuality in a way that stigmatises them,5 reducing their status in the ward, and ultimately dehumanises them, in conflict with the humanistic approaches seen as central to the best practice in the care of older patients, and particularly those living with dementia.6The broad context of our concern is the visibility of patients and their needs. We draw on observations made during an ethnographic study of the everyday care of people living with dementia within acute hospital wards, to consider how patients’ clothing may impact where can i buy amoxil over the counter on the way they were perceived by themselves and by others. Hence, we draw on this ethnography to contribute to discussion of the ‘medical gaze’ in a specific and informative context.The acute setting illustrates a situation in which there are great many biomedical, technical, recording, and timetabled routine task-oriented demands, organised and delivered by different staff members, together with demands for care and attention to particular individuals and an awareness of their needs.

Within this ward setting, we focus on patients who are living with dementia, since this group may be particularly vulnerable to a dehumanising gaze.6 We frame our discussion within the broader context of the general philosophical question of how we acquire knowledge of different types, and the moral consequences of this, particularly knowledge through visual perception.Debates throughout the history of philosophy raise questions about the nature and sources of our knowledge. Contrasts are often drawn between more reliable or less reliable knowledge where can i buy amoxil over the counter. And between knowledge that is more technical or ‘objective’, and knowledge that is more emotionally based or more ‘subjective’. A frequent point of where can i buy amoxil over the counter discussion is the reliability and characteristics of perception as a source of knowledge.

This epistemological discussion is mostly focused on vision, indicating its particular importance as a mode of perception to humans.7Likewise, in ethics, there is discussion of the origin of our moral knowledge and the particular role of perception.8 There is frequent recognition that the observer has some significant role in acquiring moral knowledge. Attention to qualities of the moral observer is not in itself a denial of moral reality. Indeed, it is the very essence of an ethical response to the world where can i buy amoxil over the counter to recognise the deep reality of others as separate persons. The nature of ethical attention to the world and to those around us is debated and has been articulated in various ways.

The quality of ethical attention may vary and achieving a high level of ethical attention may require certain conditions, certain virtues, and the time and mental space to attend to the situation and claims of the other.9Consideration has already been given to how different modes of attention to the world might be of relevance to the practice of medicine. Work that examines different ways of processing information, and of interacting with and being in the world, can be found in where can i buy amoxil over the counter Iain McGilchrist’s The Master and His Emissary,10 where he draws on neurological discoveries and applies his ideas to the development of human culture. McGilchrist has recently expanded on the relevance of understanding two different approaches to knowledge for the practice of medicine.11 He argues that task-oriented perception, and a wider, more emotionally attuned awareness of the environment are necessary partners, but may in some circumstances compete, with the competitive edge often being given to the narrower, task-based attention.There has been critique of McGilchrist’s arguments as well as much support. We find his work a useful framework for understanding where can i buy amoxil over the counter important debates in the ethics of medicine and of nursing about relationships of staff to patients.

In particular, it helps to illuminate the consequences of patients’ dress and personal appearance for how they are seen and treated.Dementia and personal appearanceOur work focuses on patients living with dementia admitted to acute hospital wards. Here, they are a large group, present alongside older patients unaffected by dementia, as well as younger patients. This mixed population provides a useful setting to consider the impact of personal appearance on different patient groups.The role of appearance in the presentation of the self has been explored extensively by Tseëlon,12 13 drawing where can i buy amoxil over the counter on Goffman’s work on stigma5 and the presentation of the self14 using interactionist approaches. Drawing on the experiences on women in the UK, Tseëlon argues Goffman’s interactionist approach best supports how we understand the relationship appearance plays in self presentation, and its relationships with other signs and interactions surrounding it.

Tseëlon suggests that understandings in this area, in the role appearance and clothing have in the presentation of the self, have been restricted by the perceived trivialities of the topic and limited to the field of fashion studies.15The personal appearance of older patients, and patients living with dementia in particular, has, more recently, been shown to be worthy of attention and of particular significance. Older people are often assumed to be left out of fashion, yet a concern with appearance remains.16 17 Lack of attention to clothing and to personal care may be one sign of the varied symptoms associated where can i buy amoxil over the counter with cognitive impairment or dementia, and so conversely, attention to appearance is one way of combatting the stigma associated with dementia. Families and carers may also feel the importance of personal appearance. The significant body of work by Twigg and Buse in this field in particular draws attention to the role clothing has on preserving the identity and dignity or people living with dementia, while also constraining and enabling elements of care within where can i buy amoxil over the counter long-term community settings.16–19 Within this paper, we examine the ways in which these phenomena can be even more acutely felt within the impersonal setting of the acute hospital.Work has also shown how people living with dementia strongly retain a felt, bodily appreciation for the importance of personal appearance.

The comfort and sensuous feel of familiar clothing may remain, even after cognitive capacities such as the ability to recognise oneself in a mirror, or verbal fluency, are lost.18 More strongly still, Kontos,20–22 drawing on the work of Merleau-Ponty and of Bourdieu, has convincingly argued that this attention to clothing and personal appearance is an important aspect of the maintenance of a bodily sense of self, which is also socially mediated, in part via such attention to appearance. Our observations lend support to Kontos’ hypothesis.Much of this previous work has considered clothing in the everyday life of people living with dementia in the context of community or long-term residential care.18 Here, we look at the visual impact of clothing and appearance in the different setting of the hospital ward and consider the consequent implications for patient care. This setting enables us to consider how the short-term and unfamiliar environments of the acute ward, together with the contrast between personal and institutional attire, impact on the perception of the patient by self and by others.There is a body of literature that examines the work of restoring the appearance of residents within long-term community care settings, for instance Ward et al’s work that demonstrates the importance of hair and grooming as a key component of care.23 24 The work of Iltanen-Tähkävuori25 examines the usage of garments designed for long-term care settings, exploring the conflict between clothing used to prevent undressing or facilitate the delivery of care, and the distress such clothing can cause, being powerfully symbolic of lower social status and associated where can i buy amoxil over the counter with reduced autonomy.26 27Within this literature, there has also been a significant focus on the role of clothing, appearance and the tasks of personal care surrounding it, on the older female body. A corpus of feminist literature has examined the ageing process and the use of clothing to conceal ageing, the presentation of a younger self, or a ‘certain’ age28 It argues that once the ability to conceal the ageing process through clothing and grooming has been lost, the aged person must instead conceal themselves, dressing to hide themselves and becoming invisible in the process.29 This paper will explore how institutional clothing within hospital wards affects both the male and female body, the presentation of the ageing body and its role in reinforcing the invisibility of older people, at a time when they are paradoxically most visible, unclothed and undressed, or wearing institutional clothing within the hospital ward.Institutional clothing is designed and used to fulfil a practical function.

Its use may therefore perhaps incline us towards a ‘task-based’ mode of attention, which as McGilchrist argues,10 while having a vital place in our understanding of the world, may on occasion interfere with the forms of attention that may be needed to deliver good person-oriented care responsive to individual needs.MethodsEthnography involves the in-depth study of people’s actions and accounts within their natural everyday setting, collecting relatively unstructured data from a range of sources.30 Importantly, it can take into account the perspectives of patients, carers and hospital staff.31 Our approach to ethnography is informed by the symbolic interactionist research tradition, which aims to provide an interpretive understanding of the social world, with an emphasis on interaction, focusing on understanding how action and meaning are constructed within a setting.32 The value of this approach is the depth of understanding and theory generation it can provide.33The goal of ethnography is to identify social processes within the data. There are multiple complex and nuanced interactions within these clinical settings that are capable of ‘communicating many messages at once, even of subverting on one level what it appears where can i buy amoxil over the counter to be “saying” on another’.34 Thus, it is important to observe interaction and performance. How everyday care work is organised and delivered. By obtaining observational data from within each institution on the everyday work of hospital wards, their family carers and the nursing and healthcare assistants (HCAs) who carry out this work, we can explore the ways in where can i buy amoxil over the counter which hospital organisation, procedures and everyday care impact on care during a hospital admission.

It remedies a common weakness in many qualitative studies, that what people say in interviews may differ from what they do or their private justifications to others.35Data collection (observations and interviews) and analysis were informed by the analytic tradition of grounded theory.36 There was no prior hypothesis testing and we used the constant comparative method and theoretical sampling whereby data collection (observation and interview data) and analysis are inter-related,36 37 and are carried out concurrently.38 39 The flexible nature of this approach is important, because it can allow us to increase the ‘analytic incisiveness’35 of the study. Preliminary analysis of data collected from individual sites informed the focus of later stages of sampling, data collection and analysis in other sites.Thus, sampling requires a flexible, pragmatic approach and purposive and maximum variation sampling (theoretical sampling) was used. This included five hospitals selected to represent a range of hospitals where can i buy amoxil over the counter types, geographies and socioeconomic catchments. Five hospitals were purposefully selected to represent a range of hospitals types.

Two large university teaching hospitals, two medium-sized general hospitals and one smaller general hospital. This included one urban, two inner city and two hospitals covering a mix of rural and suburban catchment where can i buy amoxil over the counter areas, all situated within England and Wales.These sites represented a range of expertise and interventions in caring for people with dementia, from no formal expertise to the deployment of specialist dementia workers. Fractures, nutritional disorders, urinary tract and pneumonia40 41 are among the principal causes of admission to acute hospital settings among people with dementia. Thus, we focused where can i buy amoxil over the counter observation within trauma and orthopaedic wards (80 days) and medical assessment units (MAU.

75 days).Across these sites, 155 days of observational fieldwork were carried out. At each of the five sites, a minimum of 30 days observation took place, split between the two ward types. Observations were carried out by two researchers, each working in clusters of 2–4 days over where can i buy amoxil over the counter a 6-week period at each site. A single day of observation could last a minimum of 2 hours and a maximum of 12 hours.

A total of 684 hours of observation were conducted for this study. This produced approximately 600 000 words of observational fieldnotes that were transcribed, cleaned and anonymised (by KF and where can i buy amoxil over the counter AN). We also carried out ethnographic (during observation) interviews with trauma and orthopaedic ward (192 ethnographic interviews and 22 group interviews) and MAU (222 ethnographic interviews) staff (including nurses, HCAs, auxiliary and support staff and medical teams) as they cared for this patient group. This allowed us to question what they are doing and why, and what are the caring practices of ward staff when interacting with people living with dementia.Patients within these settings with a diagnosis of dementia were identified through ward nursing handover notes, where can i buy amoxil over the counter patient records and board data with the assistance of ward staff.

Following the provision of written and verbal information about the study, and the expression of willingness to take part, written consent was taken from patients, staff and visitors directly observed or spoken to as part of the study.To optimise the generalisability of our findings,42 our approach emphasises the importance of comparisons across sites,43 with theoretical saturation achieved following the search for negative cases, and on exploring a diverse and wide range of data. When no additional empirical data were found, we concluded that the analytical categories were saturated.36 44Grounded theory and ethnography are complementary traditions, with grounded theory strengthening the ethnographic aims of achieving a theoretical interpretation of the data, while the ethnographic approach prevents a rigid application of grounded theory.35 Using an ethnographic approach can mean that everything within a setting is treated as data, which can lead to large volumes of unconnected data and a descriptive analysis.45 This approach provides a middle ground in which the ethnographer, often seen as a passive observer of the social world, uses grounded theory to provide a systematic approach to data collection and analysis that can be used to develop theory to address the interpretive realities of participants within this setting.35Patient and public involvementThe data presented in this paper are drawn from a wider ethnographic study supported by an advisory group of people living with dementia and their family carers. It was where can i buy amoxil over the counter this advisory group that informed us of the need of a better understanding of the impacts of the everyday care received by people living with dementia in acute hospital settings. The authors met with this group on a regular basis throughout the study, and received guidance on both the design of the study and the format of written materials used to recruit participants to the study.

The external oversight group for this study included, and was chaired, by carers of people living with dementia. Once data analysis was complete, the advisory group commented on our initial where can i buy amoxil over the counter findings and recommendations. During and on completion of the analysis, a series of public consultation events were held with people living with dementia and family carers to ensure their involvement in discussing, informing and refining our analysis.FindingsWithin this paper, we focus on exploring the medical gaze through the embedded institutional cultures of patient clothing, and the implications this have for patients living with dementia within acute hospital wards. These findings emerged from our wider analysis of our ethnographic study examining ward cultures of where can i buy amoxil over the counter care and the experiences of people living with dementia.

Here, we examine the ways in which the cultures of clothing within wards impact on the visibility of patients within it, what clothing and identity mean within the ward and the ways in which clothing can be a source of distress. We will look at how personal grooming and appearance can affect status within the ward, and finally explore the removal of clothing, and the impacts of its absence.Ward clothing culturesAcross our sites, there was variation in the cultures of patient clothing and dress. Within many wards, it was typical for all older patients to be dressed in hospital-issued institutional gowns and pyjamas (typically in pastel blue, pink, green or peach), paired with hospital where can i buy amoxil over the counter supplied socks (usually bright red, although there was some small variation) with non-slip grip soles, while in other wards, it was standard practice for people to be supported to dress in their own clothes. Across all these wards, we observed that younger patients (middle aged/working age) were more likely to be able to wear their own clothes while admitted to a ward, than older patients and those with a dementia diagnosis.Among key signifiers of social status and individuality are the material things around the person, which in these hospital wards included the accoutrements around the bedside.

Significantly, it was observed that people living with dementia were more likely to be wearing an institutional hospital gown or institutional pyjamas, and to have little to individuate the person at the bedside, on either their cabinet or the mobile tray table at their bedside. The wearing of institutional clothing was typically connected to fewer personal items on display or within reach of the patient, with any items tidied away where can i buy amoxil over the counter out of sight. In contrast, younger working age patients often had many personal belongings, cards, gadgets, books, media players, with young adults also often having a range of ‘get well soon’ gifts, balloons and so on from the hospital gift shop) on display. This both afforded some elements of familiarity, but also marked the person out as someone with individuality and a certain social standing and place.Visibility of patients on a wardThe significance of the obscurity or where can i buy amoxil over the counter invisibility of the patient in artworks depicting doctors has been commented on.4 Likewise, we observed that some patients within these wards were much more ‘visible’ to staff than others.

It was often apparent how the wearing of personal clothing could make the patient and their needs more readily visible to others as a person. This may be especially so given the contrast in appearance clothing may produce in this particular setting. On occasion, this may be remarked on by staff, and the resulting attention received favourably by the where can i buy amoxil over the counter patient.A member of the bay team returned to a patient and found her freshly dressed in a white tee shirt, navy slacks and black velvet slippers and exclaimed aloud and appreciatively, ‘Wow, look at you!. €™ The patient looked pleased as she sat and combed her hair [site 3 day 1].Such a simple act of recognition as someone with a socially approved appearance takes on a special significance in the context of an acute hospital ward, and for patients living with dementia whose personhood may be overlooked in various ways.46This question of visibility of patients may also be particularly important when people living with dementia may be less able to make their needs and presence known.

In this example, a whole bay of patients was seemingly ‘invisible’. Here, the ethnographer is observing a four-bed bay occupied by male patients living with dementia.The man in bed 17 is sitting in his bedside where can i buy amoxil over the counter chair. He is dressed in green hospital issue pyjamas and yellow grip socks. At 10 a.m., the physiotherapy team come and where can i buy amoxil over the counter see him.

The physiotherapist crouches down in front of him and asks him how he is. He says he is unhappy, and the physiotherapist explains that she’ll be back later to see him again. The nurse checks on him, asks him if he wants a pillow, and puts it behind his head explaining to him, ‘You need to sit in the where can i buy amoxil over the counter chair for a bit’. She pulls his bedside trolley near to him.

With the help of a Healthcare Assistant they make the bed. The Healthcare Assistant chats to him, puts cake out for him, and puts a where can i buy amoxil over the counter blanket over his legs. He is shaking slightly and I wonder if he is cold.The nurse explains to me, ‘The problem is this is a really unstimulating environment’, then says to the patient, ‘All done, let’s have a bit of a tidy up,’ before wheeling the equipment out.The neighbouring patient in bed 18, is now sitting in his bedside chair, wearing (his own) striped pyjamas. His eyes are open, and he where can i buy amoxil over the counter is looking around.

After a while, he closes his eyes and dozes. The team chat to patient 19 behind the curtains. He says he doesn’t want to sit, and they say that is fine unless the doctors tell where can i buy amoxil over the counter them otherwise.The nurse puts music on an old radio with a CD player which is at the doorway near the ward entrance. It sounds like music from a musical and the ward it is quite noisy suddenly.

She turns down the volume a bit, but it is very jaunty and upbeat. The man where can i buy amoxil over the counter in bed 19 quietly sings along to the songs. €˜I am going to see my baby when I go home on victory day…’At ten thirty, the nurse goes off on her break. The rest of the team are spread around the other bays and side where can i buy amoxil over the counter rooms.

There are long distances between bays within this ward. After all the earlier activity it is now very calm and peaceful in the bay. Patient 20 where can i buy amoxil over the counter is sitting in the chair tapping his feet to the music. He has taken out a large hessian shopping bag out of his cabinet and is sorting through the contents.

There is a lot of paperwork in it which he is reading through closely where can i buy amoxil over the counter and sorting.Opposite, patient 17 looks very uncomfortable. He is sitting with two pillows behind his back but has slipped down the chair. His head is in his hands and he suddenly looks in pain. He hasn’t touched where can i buy amoxil over the counter his tea, and is talking to himself.

The junior medic was aware that 17 was not comfortable, and it had looked like she was going to get some advice, but she hasn’t come back. 18 drinks his tea and looks at a wool twiddle mitt sleeve, puts it down, and dozes. 19 has finished all his coffee and manages to put the cup down on the trolley.Everyone is tapping their feet or where can i buy amoxil over the counter wiggling their toes to the music, or singing quietly to it, when a student nurse, who is working at the computer station in the corridor outside the room, comes in. She has a strong purposeful stride and looks irritated as she switches the music off.

It feels like a jolt to where can i buy amoxil over the counter the room. She turns and looks at me and says, ‘Sorry were you listening to it?. €™ I tell her that I think these gentlemen were listening to it.She suddenly looks very startled and surprised and looks at the men in the room for the first time. They have all stopped tapping their toes and stopped singing along where can i buy amoxil over the counter.

She turns it back on but asks me if she can turn it down. She leaves and goes back to her paperwork outside. Once it is turned back on everyone starts where can i buy amoxil over the counter tapping their toes again. The music plays on.

€˜There’ll be bluebirds over the white cliffs of Dover, just you wait and see…’[Site 3 day 3]The music was played by staff to help combat the drab and unstimulating environment of where can i buy amoxil over the counter this hospital ward for the patients, the very people the ward is meant to serve. Yet for this member of ward staff the music was perceived as a nuisance, the men for whom the music was playing seemingly did not register to her awareness. Only an individual of ‘higher’ status, the researcher, sitting at the end of this room was visible to her. This example illustrates the general question of the visibility where can i buy amoxil over the counter or otherwise of patients.

Focusing on our immediate topic, there may be complex pathways through which clothing may impact on how patients living with dementia are perceived, and on their self-perception.Clothing and identityOn these wards, we also observed how important familiar aspects of appearance were to relatives. Family members may be distressed if they find the person they knew so well, looking markedly different. In the example where can i buy amoxil over the counter below, a mother and two adult daughters visit the father of the family, who is not visible to them as the person they were so familiar with. His is not wearing his glasses, which are missing, and his daughters find this very difficult.

Even though he looks very different following his admission—he has lost a large amount of weight and has sunken cheekbones, and his skin has taken on a darker hue—it is his glasses which are a key concern for the family in their recognition of their father:As I enter the corridor to go back to the ward, I meet the wife and daughter of the patient in bed 2 in the hall and walk with them where can i buy amoxil over the counter back to the ward. Their father looks very frail, his head is back, and his face is immobile, his eyes are closed, and his mouth is open. His skin looks darker than before, and his cheekbones and eye sockets are extremely prominent from weight loss. €˜I am like a bird I want to fly away…’ where can i buy amoxil over the counter plays softly in the radio in the bay.

I sit with them for a bit and we chat—his wife holds his hand as we talk. His wife has to take two busses to get to the hospital and we talk about the potential care home they expect her husband will be discharged to. They hope it will be close because she does not where can i buy amoxil over the counter drive. He isn’t wearing his glasses and his daughter tells me that they can’t find them.

We look in the where can i buy amoxil over the counter bedside cabinet. She has never seen her dad without his glasses. €˜He doesn’t look like my dad without his glasses’ [Site 2 day 15].It was often these small aspects of personal clothing and grooming that prompted powerful responses from visiting family members. Missing glasses and where can i buy amoxil over the counter missing teeth were notable in this regard (and with the follow-up visits from the relatives of discharged patients trying to retrieve these now lost objects).

The location of these possessions, which could have a medical purpose in the case of glasses, dental prosthetics, hearing aids or accessories which contained personal and important aspects of a patient’s identity, such as wallets or keys, and particularly, for female patients, handbags, could be a prominent source of distress for individuals. These accessories to personal clothing were notable on these wards by their everyday absence, hidden away in bedside cupboards or simply not brought in with the patient at admission, and by the frequency with which patients requested and called out for them or tried to look for them, often in repetitive cycles that indicated their underlying anxiety about these belongings, but which would become invisible to staff, becoming an everyday background intrusion to the work of the wards.When considering the visibility and recognition of individual persons, missing glasses, especially glasses for distance vision, have a particular significance, for without them, a person may be less able to recognise and interact visually with others. Their presence facilitates the subject of the gaze, in gazing back, where can i buy amoxil over the counter and hence helps to ground meaningful and reciprocal relationships of recognition. This may be one factor behind the distress of relatives in finding their loved ones’ glasses to be absent.Clothing as a source of distressAcross all sites, we observed patients living with dementia who exhibited obvious distress at aspects of their institutional apparel and at the absence of their own personal clothing.

Some older patients were clearly able to verbalise their understandings where can i buy amoxil over the counter of the impacts of wearing institutional clothing. One patient remarked to a nurse of her hospital blue tracksuit. €˜I look like an Olympian or Wentworth prison in this outfit!. The latter I expect…’ The staff laughed as they walked her out of the bay (site 3 day 1).Institutional clothing may be a source of distress to where can i buy amoxil over the counter patients, although they may be unable to express this verbally.

Kontos has shown how people living with dementia may retain an awareness at a bodily level of the demands of etiquette.20 Likewise, in our study, a man living with dementia, wearing a very large institutional pyjama top, which had no collar and a very low V neck, continually tried to pull it up to cover his chest. The neckline was particularly low, because the pyjamas were far too large for him. He continued to fiddle with his very low-necked top even when his lunch tray was placed in front where can i buy amoxil over the counter of him. He clearly felt very uncomfortable with such clothing.

He continued using his hands to try to pull it up to cover his exposed chest, during and after the meal was finished (site 3 day 5).For some patients, the communication of this distress in relation to clothing may where can i buy amoxil over the counter be liable to misinterpretation and may have further impacts on how they are viewed within the ward. Here, a patient living with dementia recently admitted to this ward became tearful and upset after having a shower. She had no fresh clothes, and so the team had provided her with a pink hospital gown to wear.‘I want my trousers, where is my bra, I’ve got no bra on.’ It is clear she doesn’t feel right without her own clothes on. The one-to-one healthcare assistant assigned to this patient tells her, ‘Your bra is dirty, do you want to wear where can i buy amoxil over the counter that?.

€™ She replies, ‘No I want a clean one. Where are my trousers?. I want where can i buy amoxil over the counter them, I’ve lost them.’ The healthcare assistant repeats the explaination that her clothes are dirty, and asks her, ‘Do you want your dirty ones?. €™ She is very teary ‘No, I want my clean ones.’ The carer again explains that they are dirty.The cleaner who always works in the ward arrives to clean the floor and sweeps around the patient as she sits in her chair, and as he does this, he says ‘Hello’ to her.

She is very teary and explains that where can i buy amoxil over the counter she has lost her clothes. The cleaner listens sympathetically as she continues ‘I am all confused. I have lost my clothes. I am where can i buy amoxil over the counter all confused.

How am I going to go to the shops with no clothes on!. €™ (site 5 day 5).This person experienced significant distress because of her absent clothes, but this would often be simply attributed to confusion, seen as a feature of her dementia. This then may solidify staff perceptions of her where can i buy amoxil over the counter condition. However, we need to consider that rather than her condition (her diagnosis of dementia) causing distress about clothing, the direction of causation may be the reverse.

The absence where can i buy amoxil over the counter of her own familiar clothing contributes significantly to her distress and disorientation. Others have argued that people with limited verbal capacity and limited cognitive comprehension will have a direct appreciation of the grounding familiarity of wearing their own clothes, which give a bodily felt notion of comfort and familiarity.18 47 Familiar clothing may then be an essential prop to anchor the wearer within a recognisable social and meaningful space. To simply see clothing from a task-oriented point of view, as fulfilling a simply mechanical function, and that all clothing, whether personal or institutional have the same value and role, might be to interpret the desire to wear familiar clothing as an ‘optional extra’. However, for those patients most at risk of disorientation and distress within an unfamiliar environment, it could be a valuable necessity.Personal grooming and social statusIncluding in where can i buy amoxil over the counter our consideration of clothing, we observed other aspects of the role of personal grooming.

Personal grooming was notable by its absence beyond the necessary cleaning required for reasons of immediate hygiene and clinical need (such as the prevention of pressure ulcers). Older patients, and particular those living with dementia who were unable to carry out ‘self-care’ independently and were not able to request support with personal grooming, could, over their admission, become visibly unkempt and scruffy, hair could be left unwashed, uncombed and unstyled, while men could become hirsute through a lack of shaving. The simple act of a visitor dressing and grooming a patient as they prepared for discharge could transform their appearance and leave that patient looking more alert, appear to having increased capacity, than when sitting ungroomed where can i buy amoxil over the counter in their bed or bedside chair.It is important to consider the impact of appearance and of personal care in the context of an acute ward. Kontos’ work examining life in a care home, referred to earlier, noted that people living with dementia may be acutely aware of transgressions in grooming and appearance, and noted many acts of self-care with personal appearance, such as stopping to apply lipstick, and conformity with high standards of table manners.

Clothing, etiquette where can i buy amoxil over the counter and personal grooming are important indicators of social class and hence an aspect of belonging and identity, and of how an individual relates to a wider group. In Kontos’ findings, these rituals and standards of appearance were also observed in negative reactions, such as expressions of disgust, towards those residents who breached these standards. Hence, even in cases where an individual may be assessed as having considerable cognitive impairment, the importance of personal appearance must not be overlooked.For some patients within these wards, routine practices of everyday care at the bedside can increase the potential to influence whether they feel and appear socially acceptable. The delivery of routine timetabled care at the bedside can impact on people’s appearance in ways that may mark them out as failing to achieve accepted standards of where can i buy amoxil over the counter embodied personhood.

The task-oriented timetabling of mealtimes may have significance. It was a typical observed feature of this routine, when a mealtime has ended, that people living with dementia were left with visible signs and features of the mealtime through spillages on faces, clothes, bed sheets and bedsides, that leave them at risk of being assessed as less socially acceptable and marked as having reduced independence. For example, a volunteer attempts to ‘feed’ a person living with dementia, when she gives up and leave the bedside (this woman living with dementia has resisted her attempts and explicitly says ‘no’), remnants of the food is left spread around her mouth (site where can i buy amoxil over the counter E). In a different ward, the mealtime has ended, yet a large white plastic bib to prevent food spillages remains attached around the neck of a person living with dementia who is unable to remove it (site X).Of note, an adult would not normally wear a white plastic bib at home or in a restaurant.

It signifies a task-based apparel that is demeaning to an individual’s where can i buy amoxil over the counter social status. This example also contrasts poignantly with examples from Kontos’ work,20 such as that of a female who had little or no ability to verbalise, but who nonetheless would routinely take her pearl necklace out from under her bib at mealtimes, showing she retained an acute awareness of her own appearance and the ‘right’ way to display this symbol of individuality, femininity and status. Likewise, Kontos gives the example of a resident who at mealtimes ‘placed her hand on her chest, to prevent her blouse from touching the food as she leaned over her plate’.20Patients who are less robust, who have cognitive impairments, who may be liable to disorientation and whose agency and personhood are most vulnerable are thus those for whom appropriate and familiar clothing may be most advantageous. However, we found the where can i buy amoxil over the counter ‘Matthew effect’ to be frequently in operation.

To those who have the least, even that which they have will be taken away.48 Although there may be institutional and organisational rationales for putting a plastic cover over a patient, leaving it on for an extended period following a meal may act as a marker of dehumanising loss of social status. By being able to maintain familiar clothing and adornment to visually display social standing and identity, a person living with dementia may maintain a continuity of selfhood.However, it is also possible that dressing and grooming an older person may itself be a task-oriented institutional activity in certain contexts, as discussed by Lee-Treweek49 in the context of a nursing home preparing residents for ‘lounge view’ where visitors would see them, using residents to ‘create a visual product for others’ sometimes to the detriment of residents’ needs. Our observations regarding the importance of patient appearance must therefore be considered as part of the care of the whole person and a significant feature of the institutional culture.Patient status and where can i buy amoxil over the counter appearanceWithin these wards, a new grouping of class could become imposed on patients. We understand class not simply as socioeconomic class but as an indicator of the strata of local social organisation to which an individual belongs.

Those in the lowest classes may where can i buy amoxil over the counter have limited opportunities to participate in society, and we observed the ways in which this applied to the people living with dementia within these acute wards. The differential impact of clothing as signifiers of social status has also been observed in a comparison of the white coat and the patient gown.4 It has been argued that while these both may help to mask individuality, they have quite different effects on social status on a ward. One might say that the white coat increases visibility as a person of standing and the attribution of agency, the patient gown diminishes both of these. (Within these where can i buy amoxil over the counter wards, although white coats were not to be found, the dress code of medical staff did make them stand out.

For male doctors, for example, the uniform rarely strayed beyond chinos paired with a blue oxford button down shirt, sleeves rolled up, while women wore a wider range of smart casual office wear.) Likewise, we observed that the same arrangement of attire could be attributed to entirely different meanings for older patients with or without dementia.Removal of clothes and exposureWithin these wards, we observed high levels of behaviour perceived by ward staff as people living with dementia displaying ‘resistance’ to care.50 This included ‘resistance’ towards institutional clothing. This could include pulling up or removing hospital gowns, removing institutional pyjama trousers or pulling up gowns, and standing with gowns untied and exposed at the back (although this last example is an unavoidable design feature of the clothing itself). Importantly, the removal of clothing was limited to institutional gowns and pyjamas and we did not where can i buy amoxil over the counter see any patients removing their own clothing. This also included the removal of institutional bedding, with instances of patients pulling or kicking sheets from their bed.

These acts could and was often interpreted by ward staff as a patient’s where can i buy amoxil over the counter ‘resistance’ to care. There was some variation in this interpretation. However, when an individual patient response to their institutional clothing and bedding was repeated during a shift, it was more likely to be conceived by the ward team as a form of resistance to their care, and responded to by the replacement and reinforcement of the clothing and bedding to recover the person.The removal of gowns, pyjamas and bedsheets often resulted in a patient exposing their genitalia or continence products (continence pads could be visible as a large diaper or nappy or a pad visibly held in place by transparent net pants), and as such, was disruptive to the norms and highly visible to staff and other visitor to these wards. Notably, unlike other behaviours considered by staff to be disruptive or inappropriate within these wards such as shouting or crying out, the removal of bedsheets and the subsequent bodily exposure would always be where can i buy amoxil over the counter immediately corrected, the sheet replaced and the patient covered by either the nurse or HCA.

The act of removal was typically interpreted by ward staff as representing a feature of the person’s dementia and staff responses were framed as an issue of patient dignity, or the dignity and embarrassment of other patients and visitors to the ward. However, such responses to removal could lead to further where can i buy amoxil over the counter cycles of removal and replacement, leading to an escalation of distress in the person. This was important, because the recording of ‘refusal of care’, or presumed ‘confusion’ associated with this, could have significant impacts on the care and discharge pathways available and prescribed for the individual patient.Consider the case of a woman living with dementia who is 90 years old (patient 1), in the example below. Despite having no immediate medical needs, she has been admitted to the MAU from a care home (following her husband’s stroke, he could no longer care for her).

Across the previous evening and morning shift, she was shouting, refusing all food and care and has received assistance from the specialist where can i buy amoxil over the counter dementia care worker. However, during this shift, she has become calmer following a visit from her husband earlier in the day, has since eaten and requested drinks. Her care home would not readmit her, which meant she was not able to be discharged from the unit (an overflow unit due to a high number of admissions to the emergency department during a patch of exceptionally hot weather) until alternative arrangements could be made by social services.During our observations, she remains calm for the first 2 hours. When she does talk, she is very loud and high pitched, but this is normal where can i buy amoxil over the counter for her and not a sign of distress.

For staff working on this bay, their attention is elsewhere, because of the other six patients on the unit, one is ‘on suicide watch’ and another is ‘refusing their medication’ (but does not have a diagnosis of dementia). At 15:10 patient 1 begins to remove her sheets:15:10 where can i buy amoxil over the counter. The unit seems chaotic today. Patient 1 has begun to loudly drum her fingers on the tray table.

She still has not been brought more milk, which she requested from where can i buy amoxil over the counter the HCA an hour earlier. The bay that patient 1 is admitted to is a temporary overflow unit and as a result staff do not know where things are. 1 has moved her sheets off her legs, her bare knees peeking out over the top of piled sheets.15:15. The nurse where can i buy amoxil over the counter in charge says, ‘Hello,’ when she walks past 1’s bed.

1 looks across and smiles back at her. The nurse where can i buy amoxil over the counter in charge explains to her that she needs to shuffle up the bed. 1 asks the nurse about her husband. The nurse reminds 1 that her husband was there this morning and that he is coming back tomorrow.

1 says that where can i buy amoxil over the counter he hasn’t been and she does not believe the nurse.15:25. I overhear the nurse in charge question, under her breath to herself, ‘Why 1 has been left on the unit?. €™ 1 has started asking for somebody to come and see her. The nurse in charge tells 1 that she needs to do some jobs first and then where can i buy amoxil over the counter will come and talk to her.15:30.

1 has once again kicked her sheets off of her legs. A social worker comes onto the where can i buy amoxil over the counter unit. 1 shouts, ‘Excuse me’ to her. The social worker replies, ‘Sorry I’m not staff, I don’t work here’ and leaves the bay.15:40.

1 keeps where can i buy amoxil over the counter kicking sheets off her bed, otherwise the unit is quiet. She now whimpers whenever anyone passes her bed, which is whenever anyone comes through the unit’s door. 1 is the only elderly patient on the unit. Again, the nurse in charge is heard where can i buy amoxil over the counter sympathizing that this is not the right place for her.16:30.

A doctor approaches 1, tells her that she is on her list of people to say hello to, she is quite friendly. 1 tells her that she has been here for 3 days, (the where can i buy amoxil over the counter rest is inaudible because of pitch). The doctor tries to cover 1 up, raising her bed sheet back over the bed, but 1 loudly refuses this. The doctor responds by ending the interaction, ‘See you later’, and leaves the unit.16:40.

1 attempts where can i buy amoxil over the counter to talk to the new nurse assigned to the unit. She goes over to 1 and says, ‘What’s up my darling?. €™ It’s hard to follow 1 now as she sounds very upset. The RN’s first instinct, like with the doctor and the nurse in charge, is to cover up 1 s legs with her bed sheet where can i buy amoxil over the counter.

When 1 reacts to this she talks to her and they agree to cover up her knees. 1 is talking about how her husband won’t come and visit her, and where can i buy amoxil over the counter still sounds really upset about this. [Site 3, Day 13]Of note is that between days 6 and 15 at this site, observed over a particularly warm summer, this unit was uncomfortably hot and stuffy. The need to be uncovered could be viewed as a reasonable response, and in fact was considered acceptable for patients without a classification of dementia, provided they were otherwise clothed, such as the hospital gown patient 1 was wearing.

This is an example of an aspect of care where the choice and autonomy granted to patients assessed as having (or assumed to have) cognitive capacity is not available to people who are considered to have impaired cognitive capacity (a diagnosis of dementia) and carries the additional moral judgements of the appropriateness of where can i buy amoxil over the counter behaviour and bodily exposure. In the example given above, the actions were linked to the patient’s resistance to their admission to the hospital, driven by her desire to return home and to be with her husband. Throughout observations over this 10-day period, patients perceived by staff as rational agents were allowed to strip down their bedding for comfort, whereas patients living with dementia who responded in this way were often viewed by staff as ‘undressing’, which would be interpreted as a feature of their condition, to be challenged and corrected by staff.Note how the same visual data triggered opposing interpretations of personal autonomy. Just as where can i buy amoxil over the counter in the example above where distress over loss of familiar clothing may be interpreted as an aspect of confusion, yet lead to, or exacerbate, distress and disorientation.

So ‘deviant’ bedding may be interpreted, for some patients only, in ways that solidify notions of lack of agency and confusion, is another example of the Matthew effect48 at work through the organisational expectations of the clothed appearance of patients.Within wards, it is not unusual to see patients, especially those with a diagnosis of dementia or cognitive impairment, walking in the corridor inadvertently in some state of undress, typically exposed from behind by their hospital gowns. This exposure in itself is of course, an where can i buy amoxil over the counter intrinsic functional feature of the design of the flimsy back-opening institutional clothing the patient has been placed in. This task-based clothing does not even fulfil this basic function very adequately. However, this inadvertent exposure could often be interpreted as an overt act of resistance to the ward and towards staff, especially when it led to exposed genitalia or continence products (pads or nappies).We speculate that the interpretation of resistance may be triggered by the visual prompt of disarrayed clothing and the meanings assumed to follow, where lack of decorum in attire is interpreted as indicating more general behavioural incompetence, cognitive impairment and/or standing outside the social order.DiscussionPrevious studies examining the significance of the visual, particularly Twigg and Buse’s work16–19 exploring the materialities of appearance, emphasise its key role in self-presentation, visibility, dignity and autonomy for older people and especially those living with dementia in care home settings.

Similarly, care home studies have demonstrated that institutional clothing, designed to facilitate task-based care, can be potentially dehumanising or and distressing.25 26 Our findings resonate with this work, but find that for people living with dementia within a key site of care, the acute ward, the impact of institutional where can i buy amoxil over the counter clothing on the individual patient living with dementia, is poorly recognised, but is significant for the quality and humanity of their care.Our ethnographic approach enabled the researchers to observe the organisation and delivery of task-oriented fast-paced nature of the work of the ward and bedside care. Nonetheless, it should also be emphasised the instances in which staff such as HCAs and specialist dementia staff within these wards took time to take note of personal appearance and physical caring for patients and how important this can be for overall well-being. None of our observations should be read as critical of any individual staff, but reflects longstanding institutional cultures.Our previous work has examined how readily a person living with dementia within a hospital wards is vulnerable to dehumanisation,51 and to their behaviour within these wards being interpreted as a feature of their condition, rather than a response to the ways in which timetabled care is delivered at their bedside.50 We have also examined the ways in which visual stimuli within these wards in the form of signs and symbols indicating a diagnosis of dementia may inadvertently focus attention away from the individual patient and may incline towards simplified and inaccurate categorisation of both needs and the diagnostic category of dementia.52Our work supports the analysis of the two forms of attention arising from McGilchrist’s work.10 The institutional culture of the wards produces an organisational task-based technical attention, which we found appeared to compete with and reduce the opportunity for ward staff to seek a finer emotional attunement to the person they are caring for and their needs. Focus on where can i buy amoxil over the counter efficiency, pace and record keeping that measures individual task completion within a timetable of care may worsen all these effects.

Indeed, other work has shown that in some contexts, attention to visual appearance may itself be little more than a ‘task’ to achieve.49 McGilchrist makes clear, and we agree, that both forms of attention are vital, but more needs to be done to enable staff to find a balance.Previous work has shown how important appearance is to older people, and to people living with dementia in particular, both in terms of how they are perceived by others, but also how for this group, people living with dementia, clothing and personal grooming may act as a particularly important anchor into a familiar social world. These twin aspects of clothing and appearance—self-perception and perception by others—may be especially important in the where can i buy amoxil over the counter fast-paced context of an acute ward environment, where patients living with dementia may be struggling with the impacts of an additional acute medical condition within in a highly timetabled and regimented and unfamiliar environment of the ward, and where staff perceptions of them may feed into clinical assessments of their condition and subsequent treatment and discharge pathways. We have seen above, for instance, how behaviour in relation to appearance may be seen as ‘resisting care’ in one group of patients, but as the natural expression of personal preference in patients viewed as being without cognitive impairments. Likewise, personal grooming might impact favourably on a patient’s alertness, visibility and status within the ward.Prior work has demonstrated the importance of the medical gaze for the perceptions of the patient.

Other work has also shown how older people, and in particular people living with dementia, may be thought to where can i buy amoxil over the counter be beyond concern for appearance, yet this does not accurately reflect the importance of appearance we found for this patient group. Indeed, we argue that our work, along with the work of others such as Kontos,20 21 shows that if anything, visual appearance is especially important for people living with dementia particularly within clinical settings. In considering the task of washing the patient, Pols53 considered ‘dignitas’ in terms of aesthetic values, in comparison to humanitas conceived as citizen values of equality between persons. Attention to dignitas in the form of appearance may be a way of facilitating the treatment by others of a person with humanitas, and helping to realise dignity of patients.Data where can i buy amoxil over the counter availability statementNo data are available.

Data are unavailable to protect anonymity.Ethics statementsPatient consent for publicationNot required.Ethics approvalEthics committee approval for the study was granted by the NHS Research Ethics Service (15/WA/0191).AcknowledgmentsThe authors acknowledge funding support from the NIHR.Notes1. Devan Stahl where can i buy amoxil over the counter (2013). €œLiving into the imagined body. How the diagnostic image confronts the lived body.” Medical Humanities.

Medhum-2012–010286.2. Joyce Zazulak et al. (2017). "The art of medicine.

Arts-based training in observation and mindfulness for fostering the empathic response in medical residents.” Medical Humanities. Medhum-2016-011180.3. E Forde (2018). "Using photography to enhance GP trainees’ reflective practice and professional development." Medical Humanities.

Medhum-2017-011203.4. Caroline Wellbery and Melissa Chan (2014) “White coat, patient gown.” Medical Humanities. Medhum-2013–0 10 463.5. E Goffman (1990a).

Stigma. Notes on the management of spoiled identity, Penguin.6. J Bridges and C Wilkinson (2011). €œAchieving dignity for older people with dementia in hospital.” Nursing Standard 5 (29).7.

J Dancy (1985). Contemporary Epistemology, John Wiley and Sons.8. D McNaughton (1988). Moral Vision.

Blackwell.9. S Weil (1953). Gravity and Grace. U of Nebraska Press.10.

I McGilchrist (2009). The Master and his Emissary. The divided brain and the making of the western world. New Haven and London, Yale University Press.11.

Iain McGilchrist (2011). €œPaying attention to the bipartite brain.” The Lancet 377 (9771). 1068–1069.12. Efrat Tseëlon (1992).

€œSelf presentation through appearance. A manipulative vs a dramaturgical approach”. Symbolic Interaction, 15(4). 501–514.13.

E Tseëlon (1995). The masque of femininity. The presentation of woman in everyday life. London.

Sage.14. E Goffman (1990b). The Presentation of Self in Everyday Life Penguin15. Efrat Tseëlon (2001).

€œFashion research and its discontents”. Fashion Theory, 5 (4). 435–451.16. Julia Twigg (2010a).

€œClothing and dementia. A neglected dimension?. € Journal of Ageing Studies 24(4). 223–230.17.

Julia Twigg and Christina E Buse (2013). €œDress, dementia and the embodiment of identity.” Dementia 12(3). 326–336.18. C.

E Buse and J. Twigg (2015). €œClothing, embodied identity and dementia. Maintaining the self through dress.” Age, Culture, Humanities (2).19.

Christina Buse and Julia Twigg (2018). €œDressing disrupted. Negotiating care through the materiality of dress in the context of dementia.” Sociology of Health &. Illness, 40(2).

340-352.20. PIA C Kontos (2004). Ethnographic reflections on selfhood, embodiment and Alzheimer's disease. Ageing &.

Society, 24(6). 829–849.21. P. C Kontos (2005).

€œEmbodied selfhood in Alzheimer's disease. Rethinking person-centred care.” Dementia 4 (4). 553–570.22. P.

C Kontos and G. Naglie (2007). €œBridging theory and practice. Imagination, the body, and person-centred dementia care.” Dementia 6 (4).

549–569.23. Richard Ward et al. (2016a). €œâ€˜Gonna make yer gorgeous’.

Everyday transformation, resistance and belonging in the care-based hair salon.” Dementia, 15(3). 395–413.24. Richard Ward, Sarah Campbell, and John Keady (2016b). €œAssembling the salon.

Learning from alternative forms of body work in dementia care.” Sociology of Health &. Illness, 38(8). 1287–1302.25. Sonja Iltanen-Tähkävuori, Minttu Wikberg, and Päivi Topo (2012).

Design and dementia. A case of garments designed to prevent undressing. Dementia, 11(1). 49–59.26.

Päivi Topo and Sonja Iltanen-Tähkävuori (2010). €œScripting patienthood with patient clothing.” Social Science &. Medicine, 70(11). 1682–1689.27.

Julia Twigg (2010b). €œWelfare embodied. The materiality of hospital dress. A commentary on Topo and Iltanen-Tähkävuori”.

Social Science and Medicine, 70(11), 1690–1692.28. Kathleen Woodward (2006). €œPerforming age, performing gender” National Women’s Studies Association (NWSA) Journal 18(1). 162–89.29.

K.M Woodward (1999). Introduction. In K.M. Woodward (ed.), Figuring Age.

Women, Bodies and Generations (pp. Ix-xxix). Bloomington. Indiana University Press.30.

M Hammersley and P Atkinson (1989). Ethnography. Principles in practice. London.

Routledge.31. V. J Caracelli (2006). Enhancing the policy process through the use of ethnography and other study frameworks.

A mixed-method strategy. Research in the Schools, 13(1). 84–92.32. W Housley and P Atkinson (2003).

Interactionism, Sage33. M Hammersley (1987) What's Wrong with Ethnography?. Methodological Explorations. London.

Routledge34. V Turner and E Bruner (1986). The Anthropology of Experience New York. PAJ Publications.

2435. K Charmaz and RG Mitchell (2001). €˜Grounded theory in ethnography’ in Atkinson P. (Ed) Handbook of Ethnography, 2001.

160-174. Sage. London36. B Glaser and A Strauss (1967).

The Discovery of Grounded Theory. London. Weidenfeld and Nicholson, 24(25). 288–30437.

Juliet M. Corbin and Anselm Strauss (1990). Grounded theoryrResearch. Procedures, canons, and evaluative criteria.

J Green (1998). Commentary. Grounded theory and the constant comparative method. BMJ (Clinical research ed.), 316 (7137),:1064.39.

Roy Suddaby (2006). €œFrom the editors. What grounded theory is not.” Academy of management journal, 49(4). 633–642.40.

Elizabeth L Sampson et al. (2009). €œDementia in the acute hospital. Prospective cohort study of prevalence and mortality”.

British Journal of Psychiatry,195(1). 61–66. Doi:10.1192/bjp.bp.108.05533541. C Pinkert and B Holle (2012).

€œPeople with dementia in acute hospitals. Literature review of prevalence and reasons for hospital admission”. Z. Gerontol.

Geriatr. 45. 728–734.42. Robert E Herriott and William A.

Firestone (1983) “Multisite qualitative policy research. Optimising description and generalizability”. Education Research 12:14–1943. F Vogt (2002).

€œNo ethnography without comparison. The methodological significance of comparison in ethnographic research” Studies in Education Ethnography 6:23–4244. Benjamin Saunders et al. (2018).

€œSaturation in qualitative research. Exploring its conceptualization and operationalization.” Quality and Quantity 52 (4). 1893–1907.45. A Coffey and P Atkinson (1996).

Making sense of qualitative data. Complementary research strategies. Sage Publications, Inc.46. Paula Boddington and Katie Featherstone (2018).

€œThe canary in the coal mine. Continence care for people with dementia in acute hospital wards as a crisis of dehumanisation”. Bioethics, 32(4). 251–260.47.

Christina Buse et al. (2014). €œLooking “out of place”. Analysing the spatial and symbolic meanings of dementia care settings through dress.” International Journal of Ageing and Later Life 9 (1).

€œThe Matthew effect in science. The reward and communication systems of science are considered.” Science 159 (3810). 56–63.49. Geraldine Lee-Treweek (1997) “Women, resistance and care.

An ethnographic study of nursing auxiliary work” Work, Employment and Society, 11(1). 47–6350. Katie Featherstone et al. (2019b).

€œRefusal and resistance to care by people living with dementia being cared for within acute hospital wards. An ethnographic study” Health Service and Delivery Research51. Katie Featherstone, Andy Northcott, and Jackie Bridges (2019a). €œRoutines of resistance.

An ethnography of the care of people living with dementia in acute hospital wards and its consequences.” International Journal of Nursing Studies.52. K Featherstone, A Northcott, and P Boddington (2020). €œUsing signs and symbols to identify hospital patients with a dementia diagnosis. Help or hindrance to recognition and care?.

€ Narrative Inquiry in Bioethics53. Jeannette Pols (2013). €œWashing the patient. Dignity and aesthetic values in nursing care” Nursing Philosophy, 14(3).

AbstractBrazil is currently home to the largest Japanese population outside how to buy amoxil of Japan. In Brazil today, Japanese-Brazilians are considered to be successful members of Brazilian society. This was not always the case, however, and Japanese immigrants to Brazil endured much hardship to how to buy amoxil attain their current level of prestige.

This essay explores this community’s trajectory towards the formation of the Japanese-Brazilian identity and the issues of mental health that arise in this immigrant community. Through the analysis of Japanese-Brazilian novels, TV shows, film and public health studies, I seek to disentangle the themes of gender and modernisation, and how these themes concurrently grapple with Japanese-Brazilian mental health issues. These fictional narratives provide a lens into the experience of the Japanese-Brazilian community that is unavailable in traditional medical studies about their mental health.filmliterature and medicinemental health caregender studiesmedical humanitiesData availability statementData are available in a public, open access repository.Introduction and how to buy amoxil philosophical backgroundWork in the medical humanities has noted the importance of the ‘medical gaze’ and how it may ‘see’ the patient in ways which are specific, while possessing broad significance, in relation to developing medical knowledge.

To diagnosis. And to the social position of the medical profession.1 Some authors have emphasised that vision is a distinctive modality of perception which merits its own consideration, and which may have a particular role to play in medical education and understanding.2 3 The clothing we how to buy amoxil wear has a strong impact on how we are perceived. For example, commentary in this journal on the ‘white coat’ observes that while it may rob the medical doctor of individuality, it nonetheless grants an elevated status4.

In contrast, the patient hospital gown may rob patients of individuality in a way that stigmatises them,5 reducing their status in the ward, and ultimately dehumanises them, in conflict with the humanistic approaches seen as central to the best practice in the care of older patients, and particularly those living with dementia.6The broad context of our concern is the visibility of patients and their needs. We draw on observations made during an ethnographic study of the everyday care of people how to buy amoxil living with dementia within acute hospital wards, to consider how patients’ clothing may impact on the way they were perceived by themselves and by others. Hence, we draw on this ethnography to contribute to discussion of the ‘medical gaze’ in a specific and informative context.The acute setting illustrates a situation in which there are great many biomedical, technical, recording, and timetabled routine task-oriented demands, organised and delivered by different staff members, together with demands for care and attention to particular individuals and an awareness of their needs.

Within this ward setting, we focus on patients who are living with dementia, since this group may be particularly vulnerable to a dehumanising gaze.6 We frame our discussion within the broader context of the general philosophical question of how we acquire knowledge of different types, and the moral consequences of this, particularly knowledge through visual perception.Debates throughout the history of philosophy raise questions about the nature and sources of our knowledge. Contrasts are often drawn between more how to buy amoxil reliable or less reliable knowledge. And between knowledge that is more technical or ‘objective’, and knowledge that is more emotionally based or more ‘subjective’.

A frequent point of discussion is the reliability and characteristics of perception as a source of knowledge how to buy amoxil. This epistemological discussion is mostly focused on vision, indicating its particular importance as a mode of perception to humans.7Likewise, in ethics, there is discussion of the origin of our moral knowledge and the particular role of perception.8 There is frequent recognition that the observer has some significant role in acquiring moral knowledge. Attention to qualities of the moral observer is not in itself a denial of moral reality.

Indeed, it is the very essence of an ethical response to the world to recognise the deep reality how to buy amoxil of others as separate persons. The nature of ethical attention to the world and to those around us is debated and has been articulated in various ways. The quality of ethical attention may vary and achieving a high level of ethical attention may require certain conditions, certain virtues, and the time and mental space to attend to the situation and claims of the other.9Consideration has already been given to how different modes of attention to the world might be of relevance to the practice of medicine.

Work that how to buy amoxil examines different ways of processing information, and of interacting with and being in the world, can be found in Iain McGilchrist’s The Master and His Emissary,10 where he draws on neurological discoveries and applies his ideas to the development of human culture. McGilchrist has recently expanded on the relevance of understanding two different approaches to knowledge for the practice of medicine.11 He argues that task-oriented perception, and a wider, more emotionally attuned awareness of the environment are necessary partners, but may in some circumstances compete, with the competitive edge often being given to the narrower, task-based attention.There has been critique of McGilchrist’s arguments as well as much support. We find his work a useful framework for understanding important how to buy amoxil debates in the ethics of medicine and of nursing about relationships of staff to patients.

In particular, it helps to illuminate the consequences of patients’ dress and personal appearance for how they are seen and treated.Dementia and personal appearanceOur work focuses on patients living with dementia admitted to acute hospital wards. Here, they are a large group, present alongside older patients unaffected by dementia, as well as younger patients. This mixed population provides a useful setting to consider the impact of personal appearance on different patient groups.The role of appearance in the presentation of the self has how to buy amoxil been explored extensively by Tseëlon,12 13 drawing on Goffman’s work on stigma5 and the presentation of the self14 using interactionist approaches.

Drawing on the experiences on women in the UK, Tseëlon argues Goffman’s interactionist approach best supports how we understand the relationship appearance plays in self presentation, and its relationships with other signs and interactions surrounding it. Tseëlon suggests that understandings in this area, in the role appearance and clothing have in the presentation of the self, have been restricted by the perceived trivialities of the topic and limited to the field of fashion studies.15The personal appearance of older patients, and patients living with dementia in particular, has, more recently, been shown to be worthy of attention and of particular significance. Older people are often assumed to be left out of fashion, yet a how to buy amoxil concern with appearance remains.16 17 Lack of attention to clothing and to personal care may be one sign of the varied symptoms associated with cognitive impairment or dementia, and so conversely, attention to appearance is one way of combatting the stigma associated with dementia.

Families and carers may also feel the importance of personal appearance. The significant body of work by Twigg and Buse in this field in how to buy amoxil particular draws attention to the role clothing has on preserving the identity and dignity or people living with dementia, while also constraining and enabling elements of care within long-term community settings.16–19 Within this paper, we examine the ways in which these phenomena can be even more acutely felt within the impersonal setting of the acute hospital.Work has also shown how people living with dementia strongly retain a felt, bodily appreciation for the importance of personal appearance. The comfort and sensuous feel of familiar clothing may remain, even after cognitive capacities such as the ability to recognise oneself in a mirror, or verbal fluency, are lost.18 More strongly still, Kontos,20–22 drawing on the work of Merleau-Ponty and of Bourdieu, has convincingly argued that this attention to clothing and personal appearance is an important aspect of the maintenance of a bodily sense of self, which is also socially mediated, in part via such attention to appearance.

Our observations lend support to Kontos’ hypothesis.Much of this previous work has considered clothing in the everyday life of people living with dementia in the context of community or long-term residential care.18 Here, we look at the visual impact of clothing and appearance in the different setting of the hospital ward and consider the consequent implications for patient care. This setting enables us to consider how the short-term and unfamiliar environments of the acute ward, together with the contrast between personal and institutional attire, impact on the perception of the patient by self and by others.There is a body of literature that examines the work of restoring the appearance of residents within long-term community care settings, for instance Ward et al’s work that demonstrates the importance of hair and grooming as a key component of care.23 24 The work of Iltanen-Tähkävuori25 examines the usage of garments designed for long-term care settings, exploring the conflict between clothing used to prevent undressing or facilitate the delivery of care, and the distress such clothing can cause, being how to buy amoxil powerfully symbolic of lower social status and associated with reduced autonomy.26 27Within this literature, there has also been a significant focus on the role of clothing, appearance and the tasks of personal care surrounding it, on the older female body. A corpus of feminist literature has examined the ageing process and the use of clothing to conceal ageing, the presentation of a younger self, or a ‘certain’ age28 It argues that once the ability to conceal the ageing process through clothing and grooming has been lost, the aged person must instead conceal themselves, dressing to hide themselves and becoming invisible in the process.29 This paper will explore how institutional clothing within hospital wards affects both the male and female body, the presentation of the ageing body and its role in reinforcing the invisibility of older people, at a time when they are paradoxically most visible, unclothed and undressed, or wearing institutional clothing within the hospital ward.Institutional clothing is designed and used to fulfil a practical function.

Its use may therefore perhaps incline us towards a ‘task-based’ mode of attention, which as McGilchrist argues,10 while having a vital place in our understanding of the world, may on occasion interfere with the forms of attention that may be needed to deliver good person-oriented care responsive to individual needs.MethodsEthnography involves the in-depth study of people’s actions and accounts within their natural everyday setting, collecting relatively unstructured data from a range of sources.30 Importantly, it can take into account the perspectives of patients, carers and hospital staff.31 Our approach to ethnography is informed by the symbolic interactionist research tradition, which aims to provide an interpretive understanding of the social world, with an emphasis on interaction, focusing on understanding how action and meaning are constructed within a setting.32 The value of this approach is the depth of understanding and theory generation it can provide.33The goal of ethnography is to identify social processes within the data. There are multiple complex how to buy amoxil and nuanced interactions within these clinical settings that are capable of ‘communicating many messages at once, even of subverting on one level what it appears to be “saying” on another’.34 Thus, it is important to observe interaction and performance. How everyday care work is organised and delivered.

By obtaining observational data from within each institution on the everyday work of hospital wards, their family carers and the nursing and healthcare assistants (HCAs) who carry out this work, we how to buy amoxil can explore the ways in which hospital organisation, procedures and everyday care impact on care during a hospital admission. It remedies a common weakness in many qualitative studies, that what people say in interviews may differ from what they do or their private justifications to others.35Data collection (observations and interviews) and analysis were informed by the analytic tradition of grounded theory.36 There was no prior hypothesis testing and we used the constant comparative method and theoretical sampling whereby data collection (observation and interview data) and analysis are inter-related,36 37 and are carried out concurrently.38 39 The flexible nature of this approach is important, because it can allow us to increase the ‘analytic incisiveness’35 of the study. Preliminary analysis of data collected from individual sites informed the focus of later stages of sampling, data collection and analysis in other sites.Thus, sampling requires a flexible, pragmatic approach and purposive and maximum variation sampling (theoretical sampling) was used.

This included five hospitals selected to represent a range how to buy amoxil of hospitals types, geographies and socioeconomic catchments. Five hospitals were purposefully selected to represent a range of hospitals types. Two large university teaching hospitals, two medium-sized general hospitals and one smaller general hospital.

This included one urban, two inner city and two hospitals covering a mix of rural and suburban catchment areas, all situated within England and Wales.These sites represented a range of expertise and interventions in caring how to buy amoxil for people with dementia, from no formal expertise to the deployment of specialist dementia workers. Fractures, nutritional disorders, urinary tract and pneumonia40 41 are among the principal causes of admission to acute hospital settings among people with dementia. Thus, we focused observation how to buy amoxil within trauma and orthopaedic wards (80 days) and medical assessment units (MAU.

75 days).Across these sites, 155 days of observational fieldwork were carried out. At each of the five sites, a minimum of 30 days observation took place, split between the two ward types. Observations were carried out by two researchers, each working in clusters of 2–4 days over a how to buy amoxil 6-week period at each site.

A single day of observation could last a minimum of 2 hours and a maximum of 12 hours. A total of 684 hours of observation were conducted for this study. This produced approximately 600 000 words of observational fieldnotes that were how to buy amoxil transcribed, cleaned and anonymised (by KF and AN).

We also carried out ethnographic (during observation) interviews with trauma and orthopaedic ward (192 ethnographic interviews and 22 group interviews) and MAU (222 ethnographic interviews) staff (including nurses, HCAs, auxiliary and support staff and medical teams) as they cared for this patient group. This allowed us to question what they are doing and why, and what are the caring practices of ward staff when interacting with people living with dementia.Patients within these settings with a diagnosis of dementia were identified through ward nursing how to buy amoxil handover notes, patient records and board data with the assistance of ward staff. Following the provision of written and verbal information about the study, and the expression of willingness to take part, written consent was taken from patients, staff and visitors directly observed or spoken to as part of the study.To optimise the generalisability of our findings,42 our approach emphasises the importance of comparisons across sites,43 with theoretical saturation achieved following the search for negative cases, and on exploring a diverse and wide range of data.

When no additional empirical data were found, we concluded that the analytical categories were saturated.36 44Grounded theory and ethnography are complementary traditions, with grounded theory strengthening the ethnographic aims of achieving a theoretical interpretation of the data, while the ethnographic approach prevents a rigid application of grounded theory.35 Using an ethnographic approach can mean that everything within a setting is treated as data, which can lead to large volumes of unconnected data and a descriptive analysis.45 This approach provides a middle ground in which the ethnographer, often seen as a passive observer of the social world, uses grounded theory to provide a systematic approach to data collection and analysis that can be used to develop theory to address the interpretive realities of participants within this setting.35Patient and public involvementThe data presented in this paper are drawn from a wider ethnographic study supported by an advisory group of people living with dementia and their family carers. It was this advisory group that informed us of the need of a better understanding of the impacts of the how to buy amoxil everyday care received by people living with dementia in acute hospital settings. The authors met with this group on a regular basis throughout the study, and received guidance on both the design of the study and the format of written materials used to recruit participants to the study.

The external oversight group for this study included, and was chaired, by carers of people living with dementia. Once data analysis how to buy amoxil was complete, the advisory group commented on our initial findings and recommendations. During and on completion of the analysis, a series of public consultation events were held with people living with dementia and family carers to ensure their involvement in discussing, informing and refining our analysis.FindingsWithin this paper, we focus on exploring the medical gaze through the embedded institutional cultures of patient clothing, and the implications this have for patients living with dementia within acute hospital wards.

These findings emerged from our wider analysis of our ethnographic study examining ward cultures how to buy amoxil of care and the experiences of people living with dementia. Here, we examine the ways in which the cultures of clothing within wards impact on the visibility of patients within it, what clothing and identity mean within the ward and the ways in which clothing can be a source of distress. We will look at how personal grooming and appearance can affect status within the ward, and finally explore the removal of clothing, and the impacts of its absence.Ward clothing culturesAcross our sites, there was variation in the cultures of patient clothing and dress.

Within many wards, it was typical for all older patients to be dressed in hospital-issued institutional gowns and pyjamas (typically in pastel blue, pink, green or peach), paired with hospital supplied socks (usually bright red, although there was some small variation) with how to buy amoxil non-slip grip soles, while in other wards, it was standard practice for people to be supported to dress in their own clothes. Across all these wards, we observed that younger patients (middle aged/working age) were more likely to be able to wear their own clothes while admitted to a ward, than older patients and those with a dementia diagnosis.Among key signifiers of social status and individuality are the material things around the person, which in these hospital wards included the accoutrements around the bedside. Significantly, it was observed that people living with dementia were more likely to be wearing an institutional hospital gown or institutional pyjamas, and to have little to individuate the person at the bedside, on either their cabinet or the mobile tray table at their bedside.

The wearing of institutional clothing was typically connected how to buy amoxil to fewer personal items on display or within reach of the patient, with any items tidied away out of sight. In contrast, younger working age patients often had many personal belongings, cards, gadgets, books, media players, with young adults also often having a range of ‘get well soon’ gifts, balloons and so on from the hospital gift shop) on display. This both afforded some elements of familiarity, but also marked the person out as someone with individuality and a certain social standing and place.Visibility of patients on a wardThe significance of the obscurity or invisibility of the patient in artworks depicting doctors has been commented on.4 Likewise, we observed how to buy amoxil that some patients within these wards were much more ‘visible’ to staff than others.

It was often apparent how the wearing of personal clothing could make the patient and their needs more readily visible to others as a person. This may be especially so given the contrast in appearance clothing may produce in this particular setting. On occasion, this may be remarked on by staff, and the resulting attention received favourably by the how to buy amoxil patient.A member of the bay team returned to a patient and found her freshly dressed in a white tee shirt, navy slacks and black velvet slippers and exclaimed aloud and appreciatively, ‘Wow, look at you!.

€™ The patient looked pleased as she sat and combed her hair [site 3 day 1].Such a simple act of recognition as someone with a socially approved appearance takes on a special significance in the context of an acute hospital ward, and for patients living with dementia whose personhood may be overlooked in various ways.46This question of visibility of patients may also be particularly important when people living with dementia may be less able to make their needs and presence known. In this example, a whole bay of patients was seemingly ‘invisible’. Here, the ethnographer is observing a four-bed bay occupied by male patients living with dementia.The man in bed 17 is how to buy amoxil sitting in his bedside chair.

He is dressed in green hospital issue pyjamas and yellow grip socks. At 10 how to buy amoxil a.m., the physiotherapy team come and see him. The physiotherapist crouches down in front of him and asks him how he is.

He says he is unhappy, and the physiotherapist explains that she’ll be back later to see him again. The nurse how to buy amoxil checks on him, asks him if he wants a pillow, and puts it behind his head explaining to him, ‘You need to sit in the chair for a bit’. She pulls his bedside trolley near to him.

With the help of a Healthcare Assistant they make the bed. The Healthcare Assistant chats to him, puts cake out for him, and puts a blanket how to buy amoxil over his legs. He is shaking slightly and I wonder if he is cold.The nurse explains to me, ‘The problem is this is a really unstimulating environment’, then says to the patient, ‘All done, let’s have a bit of a tidy up,’ before wheeling the equipment out.The neighbouring patient in bed 18, is now sitting in his bedside chair, wearing (his own) striped pyjamas.

His eyes are open, and he is looking how to buy amoxil around. After a while, he closes his eyes and dozes. The team chat to patient 19 behind the curtains.

He says how to buy amoxil he doesn’t want to sit, and they say that is fine unless the doctors tell them otherwise.The nurse puts music on an old radio with a CD player which is at the doorway near the ward entrance. It sounds like music from a musical and the ward it is quite noisy suddenly. She turns down the volume a bit, but it is very jaunty and upbeat.

The man in bed 19 how to buy amoxil quietly sings along to the songs. €˜I am going to see my baby when I go home on victory day…’At ten thirty, the nurse goes off on her break. The rest of the team how to buy amoxil are spread around the other bays and side rooms.

There are long distances between bays within this ward. After all the earlier activity it is now very calm and peaceful in the bay. Patient 20 is sitting in the chair tapping his feet to the music how to buy amoxil.

He has taken out a large hessian shopping bag out of his cabinet and is sorting through the contents. There is a lot of paperwork in it which he is reading through how to buy amoxil closely and sorting.Opposite, patient 17 looks very uncomfortable. He is sitting with two pillows behind his back but has slipped down the chair.

His head is in his hands and he suddenly looks in pain. He hasn’t how to buy amoxil touched his tea, and is talking to himself. The junior medic was aware that 17 was not comfortable, and it had looked like she was going to get some advice, but she hasn’t come back.

18 drinks his tea and looks at a wool twiddle mitt sleeve, puts it down, and dozes. 19 has how to buy amoxil finished all his coffee and manages to put the cup down on the trolley.Everyone is tapping their feet or wiggling their toes to the music, or singing quietly to it, when a student nurse, who is working at the computer station in the corridor outside the room, comes in. She has a strong purposeful stride and looks irritated as she switches the music off.

It feels how to buy amoxil like a jolt to the room. She turns and looks at me and says, ‘Sorry were you listening to it?. €™ I tell her that I think these gentlemen were listening to it.She suddenly looks very startled and surprised and looks at the men in the room for the first time.

They have how to buy amoxil all stopped tapping their toes and stopped singing along. She turns it back on but asks me if she can turn it down. She leaves and goes back to her paperwork outside.

Once it is turned back on everyone starts tapping their how to buy amoxil toes again. The music plays on. €˜There’ll be bluebirds over the white cliffs of Dover, just you wait and see…’[Site 3 day 3]The music was played by staff to help combat the drab and unstimulating environment of this hospital ward for the patients, how to buy amoxil the very people the ward is meant to serve.

Yet for this member of ward staff the music was perceived as a nuisance, the men for whom the music was playing seemingly did not register to her awareness. Only an individual of ‘higher’ status, the researcher, sitting at the end of this room was visible to her. This example illustrates the general question of the how to buy amoxil visibility or otherwise of patients.

Focusing on our immediate topic, there may be complex pathways through which clothing may impact on how patients living with dementia are perceived, and on their self-perception.Clothing and identityOn these wards, we also observed how important familiar aspects of appearance were to relatives. Family members may be distressed if they find the person they knew so well, looking markedly different. In the example below, a mother and two adult how to buy amoxil daughters visit the father of the family, who is not visible to them as the person they were so familiar with.

His is not wearing his glasses, which are missing, and his daughters find this very difficult. Even though he looks how to buy amoxil very different following his admission—he has lost a large amount of weight and has sunken cheekbones, and his skin has taken on a darker hue—it is his glasses which are a key concern for the family in their recognition of their father:As I enter the corridor to go back to the ward, I meet the wife and daughter of the patient in bed 2 in the hall and walk with them back to the ward. Their father looks very frail, his head is back, and his face is immobile, his eyes are closed, and his mouth is open.

His skin looks darker than before, and his cheekbones and eye sockets are extremely prominent from weight loss. €˜I am like a bird I want to how to buy amoxil fly away…’ plays softly in the radio in the bay. I sit with them for a bit and we chat—his wife holds his hand as we talk.

His wife has to take two busses to get to the hospital and we talk about the potential care home they expect her husband will be discharged to. They hope it how to buy amoxil will be close because she does not drive. He isn’t wearing his glasses and his daughter tells me that they can’t find them.

We look in the bedside how to buy amoxil cabinet. She has never seen her dad without his glasses. €˜He doesn’t look like my dad without his glasses’ [Site 2 day 15].It was often these small aspects of personal clothing and grooming that prompted powerful responses from visiting family members.

Missing glasses and missing teeth were notable in this regard (and with the follow-up visits from the relatives of discharged patients trying to retrieve these now lost objects) how to buy amoxil. The location of these possessions, which could have a medical purpose in the case of glasses, dental prosthetics, hearing aids or accessories which contained personal and important aspects of a patient’s identity, such as wallets or keys, and particularly, for female patients, handbags, could be a prominent source of distress for individuals. These accessories to personal clothing were notable on these wards by their everyday absence, hidden away in bedside cupboards or simply not brought in with the patient at admission, and by the frequency with which patients requested and called out for them or tried to look for them, often in repetitive cycles that indicated their underlying anxiety about these belongings, but which would become invisible to staff, becoming an everyday background intrusion to the work of the wards.When considering the visibility and recognition of individual persons, missing glasses, especially glasses for distance vision, have a particular significance, for without them, a person may be less able to recognise and interact visually with others.

Their presence facilitates the subject of the gaze, in gazing back, and hence helps to ground meaningful and reciprocal relationships of recognition how to buy amoxil. This may be one factor behind the distress of relatives in finding their loved ones’ glasses to be absent.Clothing as a source of distressAcross all sites, we observed patients living with dementia who exhibited obvious distress at aspects of their institutional apparel and at the absence of their own personal clothing. Some older patients how to buy amoxil were clearly able to verbalise their understandings of the impacts of wearing institutional clothing.

One patient remarked to a nurse of her hospital blue tracksuit. €˜I look like an Olympian or Wentworth prison in this outfit!. The latter I expect…’ The staff laughed as they walked her out of the bay (site 3 day 1).Institutional clothing may be a source of distress to patients, how to buy amoxil although they may be unable to express this verbally.

Kontos has shown how people living with dementia may retain an awareness at a bodily level of the demands of etiquette.20 Likewise, in our study, a man living with dementia, wearing a very large institutional pyjama top, which had no collar and a very low V neck, continually tried to pull it up to cover his chest. The neckline was particularly low, because the pyjamas were far too large for him. He continued to fiddle with his very low-necked top even when his how to buy amoxil lunch tray was placed in front of him.

He clearly felt very uncomfortable with such clothing. He continued using his hands to try to pull it up to cover his exposed chest, during and after the meal was finished (site 3 day 5).For some patients, the communication of this distress in relation to clothing may be liable to misinterpretation and may have further impacts on how they are how to buy amoxil viewed within the ward. Here, a patient living with dementia recently admitted to this ward became tearful and upset after having a shower.

She had no fresh clothes, and so the team had provided her with a pink hospital gown to wear.‘I want my trousers, where is my bra, I’ve got no bra on.’ It is clear she doesn’t feel right without her own clothes on. The one-to-one healthcare assistant assigned how to buy amoxil to this patient tells her, ‘Your bra is dirty, do you want to wear that?. €™ She replies, ‘No I want a clean one.

Where are my trousers?. I want them, I’ve lost them.’ The healthcare assistant repeats the explaination that her clothes are dirty, and asks her, ‘Do how to buy amoxil you want your dirty ones?. €™ She is very teary ‘No, I want my clean ones.’ The carer again explains that they are dirty.The cleaner who always works in the ward arrives to clean the floor and sweeps around the patient as she sits in her chair, and as he does this, he says ‘Hello’ to her.

She is very teary and explains that she has lost her clothes how to buy amoxil. The cleaner listens sympathetically as she continues ‘I am all confused. I have lost my clothes.

I am how to buy amoxil all confused. How am I going to go to the shops with no clothes on!. €™ (site 5 day 5).This person experienced significant distress because of her absent clothes, but this would often be simply attributed to confusion, seen as a feature of her dementia.

This then may solidify staff perceptions how to buy amoxil of her condition. However, we need to consider that rather than her condition (her diagnosis of dementia) causing distress about clothing, the direction of causation may be the reverse. The absence how to buy amoxil of her own familiar clothing contributes significantly to her distress and disorientation.

Others have argued that people with limited verbal capacity and limited cognitive comprehension will have a direct appreciation of the grounding familiarity of wearing their own clothes, which give a bodily felt notion of comfort and familiarity.18 47 Familiar clothing may then be an essential prop to anchor the wearer within a recognisable social and meaningful space. To simply see clothing from a task-oriented point of view, as fulfilling a simply mechanical function, and that all clothing, whether personal or institutional have the same value and role, might be to interpret the desire to wear familiar clothing as an ‘optional extra’. However, for those how to buy amoxil patients most at risk of disorientation and distress within an unfamiliar environment, it could be a valuable necessity.Personal grooming and social statusIncluding in our consideration of clothing, we observed other aspects of the role of personal grooming.

Personal grooming was notable by its absence beyond the necessary cleaning required for reasons of immediate hygiene and clinical need (such as the prevention of pressure ulcers). Older patients, and particular those living with dementia who were unable to carry out ‘self-care’ independently and were not able to request support with personal grooming, could, over their admission, become visibly unkempt and scruffy, hair could be left unwashed, uncombed and unstyled, while men could become hirsute through a lack of shaving. The simple act of a visitor dressing and grooming a patient as they prepared for discharge could transform their appearance and leave that patient looking how to buy amoxil more alert, appear to having increased capacity, than when sitting ungroomed in their bed or bedside chair.It is important to consider the impact of appearance and of personal care in the context of an acute ward.

Kontos’ work examining life in a care home, referred to earlier, noted that people living with dementia may be acutely aware of transgressions in grooming and appearance, and noted many acts of self-care with personal appearance, such as stopping to apply lipstick, and conformity with high standards of table manners. Clothing, etiquette and personal grooming how to buy amoxil are important indicators of social class and hence an aspect of belonging and identity, and of how an individual relates to a wider group. In Kontos’ findings, these rituals and standards of appearance were also observed in negative reactions, such as expressions of disgust, towards those residents who breached these standards.

Hence, even in cases where an individual may be assessed as having considerable cognitive impairment, the importance of personal appearance must not be overlooked.For some patients within these wards, routine practices of everyday care at the bedside can increase the potential to influence whether they feel and appear socially acceptable. The delivery of routine timetabled care at the bedside can impact on people’s appearance in how to buy amoxil ways that may mark them out as failing to achieve accepted standards of embodied personhood. The task-oriented timetabling of mealtimes may have significance.

It was a typical observed feature of this routine, when a mealtime has ended, that people living with dementia were left with visible signs and features of the mealtime through spillages on faces, clothes, bed sheets and bedsides, that leave them at risk of being assessed as less socially acceptable and marked as having reduced independence. For example, a volunteer attempts to ‘feed’ a person living with dementia, when she gives up and leave the bedside (this woman living with dementia has resisted her attempts and explicitly says ‘no’), how to buy amoxil remnants of the food is left spread around her mouth (site E). In a different ward, the mealtime has ended, yet a large white plastic bib to prevent food spillages remains attached around the neck of a person living with dementia who is unable to remove it (site X).Of note, an adult would not normally wear a white plastic bib at home or in a restaurant.

It signifies how to buy amoxil a task-based apparel that is demeaning to an individual’s social status. This example also contrasts poignantly with examples from Kontos’ work,20 such as that of a female who had little or no ability to verbalise, but who nonetheless would routinely take her pearl necklace out from under her bib at mealtimes, showing she retained an acute awareness of her own appearance and the ‘right’ way to display this symbol of individuality, femininity and status. Likewise, Kontos gives the example of a resident who at mealtimes ‘placed her hand on her chest, to prevent her blouse from touching the food as she leaned over her plate’.20Patients who are less robust, who have cognitive impairments, who may be liable to disorientation and whose agency and personhood are most vulnerable are thus those for whom appropriate and familiar clothing may be most advantageous.

However, we how to buy amoxil found the ‘Matthew effect’ to be frequently in operation. To those who have the least, even that which they have will be taken away.48 Although there may be institutional and organisational rationales for putting a plastic cover over a patient, leaving it on for an extended period following a meal may act as a marker of dehumanising loss of social status. By being able to maintain familiar clothing and adornment to visually display social standing and identity, a person living with dementia may maintain a continuity of selfhood.However, it is also possible that dressing and grooming an older person may itself be a task-oriented institutional activity in certain contexts, as discussed by Lee-Treweek49 in the context of a nursing home preparing residents for ‘lounge view’ where visitors would see them, using residents to ‘create a visual product for others’ sometimes to the detriment of residents’ needs.

Our observations regarding the importance of patient appearance must therefore be considered as part of the care of the whole person and a significant feature of the institutional culture.Patient status and appearanceWithin these wards, how to buy amoxil a new grouping of class could become imposed on patients. We understand class not simply as socioeconomic class but as an indicator of the strata of local social organisation to which an individual belongs. Those in the lowest how to buy amoxil classes may have limited opportunities to participate in society, and we observed the ways in which this applied to the people living with dementia within these acute wards.

The differential impact of clothing as signifiers of social status has also been observed in a comparison of the white coat and the patient gown.4 It has been argued that while these both may help to mask individuality, they have quite different effects on social status on a ward. One might say that the white coat increases visibility as a person of standing and the attribution of agency, the patient gown diminishes both of these. (Within these wards, although white how to buy amoxil coats were not to be found, the dress code of medical staff did make them stand out.

For male doctors, for example, the uniform rarely strayed beyond chinos paired with a blue oxford button down shirt, sleeves rolled up, while women wore a wider range of smart casual office wear.) Likewise, we observed that the same arrangement of attire could be attributed to entirely different meanings for older patients with or without dementia.Removal of clothes and exposureWithin these wards, we observed high levels of behaviour perceived by ward staff as people living with dementia displaying ‘resistance’ to care.50 This included ‘resistance’ towards institutional clothing. This could include pulling up or removing hospital gowns, removing institutional pyjama trousers or pulling up gowns, and standing with gowns untied and exposed at the back (although this last example is an unavoidable design feature of the clothing itself). Importantly, the removal of clothing was limited to institutional gowns and pyjamas and we did not see any patients how to buy amoxil removing their own clothing.

This also included the removal of institutional bedding, with instances of patients pulling or kicking sheets from their bed. These acts could and was often interpreted by ward staff as a patient’s ‘resistance’ to how to buy amoxil care. There was some variation in this interpretation.

However, when an individual patient response to their institutional clothing and bedding was repeated during a shift, it was more likely to be conceived by the ward team as a form of resistance to their care, and responded to by the replacement and reinforcement of the clothing and bedding to recover the person.The removal of gowns, pyjamas and bedsheets often resulted in a patient exposing their genitalia or continence products (continence pads could be visible as a large diaper or nappy or a pad visibly held in place by transparent net pants), and as such, was disruptive to the norms and highly visible to staff and other visitor to these wards. Notably, unlike other behaviours considered by staff to be disruptive or inappropriate within these wards such as shouting or crying out, the removal of bedsheets and the subsequent bodily exposure would always be immediately corrected, the sheet replaced and the patient covered by either the nurse or HCA how to buy amoxil. The act of removal was typically interpreted by ward staff as representing a feature of the person’s dementia and staff responses were framed as an issue of patient dignity, or the dignity and embarrassment of other patients and visitors to the ward.

However, such responses to removal could lead to how to buy amoxil further cycles of removal and replacement, leading to an escalation of distress in the person. This was important, because the recording of ‘refusal of care’, or presumed ‘confusion’ associated with this, could have significant impacts on the care and discharge pathways available and prescribed for the individual patient.Consider the case of a woman living with dementia who is 90 years old (patient 1), in the example below. Despite having no immediate medical needs, she has been admitted to the MAU from a care home (following her husband’s stroke, he could no longer care for her).

Across the previous evening and morning how to buy amoxil shift, she was shouting, refusing all food and care and has received assistance from the specialist dementia care worker. However, during this shift, she has become calmer following a visit from her husband earlier in the day, has since eaten and requested drinks. Her care home would not readmit her, which meant she was not able to be discharged from the unit (an overflow unit due to a high number of admissions to the emergency department during a patch of exceptionally hot weather) until alternative arrangements could be made by social services.During our observations, she remains calm for the first 2 hours.

When she how to buy amoxil does talk, she is very loud and high pitched, but this is normal for her and not a sign of distress. For staff working on this bay, their attention is elsewhere, because of the other six patients on the unit, one is ‘on suicide watch’ and another is ‘refusing their medication’ (but does not have a diagnosis of dementia). At 15:10 patient 1 begins to remove how to buy amoxil her sheets:15:10.

The unit seems chaotic today. Patient 1 has begun to loudly drum her fingers on the tray table. She still has not been brought more how to buy amoxil milk, which she requested from the HCA an hour earlier.

The bay that patient 1 is admitted to is a temporary overflow unit and as a result staff do not know where things are. 1 has moved her sheets off her legs, her bare knees peeking out over the top of piled sheets.15:15. The nurse in charge says, ‘Hello,’ when she walks past 1’s how to buy amoxil bed.

1 looks across and smiles back at her. The nurse in charge explains to her that she needs to how to buy amoxil shuffle up the bed. 1 asks the nurse about her husband.

The nurse reminds 1 that her husband was there this morning and that he is coming back tomorrow. 1 says that he hasn’t how to buy amoxil been and she does not believe the nurse.15:25. I overhear the nurse in charge question, under her breath to herself, ‘Why 1 has been left on the unit?.

€™ 1 has started asking for somebody to come and see her. The nurse in charge tells 1 that she needs to do some jobs first and then will come and talk to her.15:30 how to buy amoxil. 1 has once again kicked her sheets off of her legs.

A social worker comes how to buy amoxil onto the unit. 1 shouts, ‘Excuse me’ to her. The social worker replies, ‘Sorry I’m not staff, I don’t work here’ and leaves the bay.15:40.

1 keeps kicking sheets off her bed, otherwise the unit is quiet how to buy amoxil. She now whimpers whenever anyone passes her bed, which is whenever anyone comes through the unit’s door. 1 is the only elderly patient on the unit.

Again, the nurse in charge is heard sympathizing that this is not the right place for how to buy amoxil her.16:30. A doctor approaches 1, tells her that she is on her list of people to say hello to, she is quite friendly. 1 tells her that she has been here for 3 days, (the rest how to buy amoxil is inaudible because of pitch).

The doctor tries to cover 1 up, raising her bed sheet back over the bed, but 1 loudly refuses this. The doctor responds by ending the interaction, ‘See you later’, and leaves the unit.16:40. 1 attempts to talk to the new nurse assigned to how to buy amoxil the unit.

She goes over to 1 and says, ‘What’s up my darling?. €™ It’s hard to follow 1 now as she sounds very upset. The RN’s first instinct, like with the doctor and the nurse in charge, is to cover up 1 s legs with her how to buy amoxil bed sheet.

When 1 reacts to this she talks to her and they agree to cover up her knees. 1 is talking about how her husband won’t come and visit her, and still sounds really upset about this how to buy amoxil. [Site 3, Day 13]Of note is that between days 6 and 15 at this site, observed over a particularly warm summer, this unit was uncomfortably hot and stuffy.

The need to be uncovered could be viewed as a reasonable response, and in fact was considered acceptable for patients without a classification of dementia, provided they were otherwise clothed, such as the hospital gown patient 1 was wearing. This is an example of an aspect of care where the choice and autonomy granted to patients assessed as having (or assumed to how to buy amoxil have) cognitive capacity is not available to people who are considered to have impaired cognitive capacity (a diagnosis of dementia) and carries the additional moral judgements of the appropriateness of behaviour and bodily exposure. In the example given above, the actions were linked to the patient’s resistance to their admission to the hospital, driven by her desire to return home and to be with her husband.

Throughout observations over this 10-day period, patients perceived by staff as rational agents were allowed to strip down their bedding for comfort, whereas patients living with dementia who responded in this way were often viewed by staff as ‘undressing’, which would be interpreted as a feature of their condition, to be challenged and corrected by staff.Note how the same visual data triggered opposing interpretations of personal autonomy. Just as how to buy amoxil in the example above where distress over loss of familiar clothing may be interpreted as an aspect of confusion, yet lead to, or exacerbate, distress and disorientation. So ‘deviant’ bedding may be interpreted, for some patients only, in ways that solidify notions of lack of agency and confusion, is another example of the Matthew effect48 at work through the organisational expectations of the clothed appearance of patients.Within wards, it is not unusual to see patients, especially those with a diagnosis of dementia or cognitive impairment, walking in the corridor inadvertently in some state of undress, typically exposed from behind by their hospital gowns.

This exposure how to buy amoxil in itself is of course, an intrinsic functional feature of the design of the flimsy back-opening institutional clothing the patient has been placed in. This task-based clothing does not even fulfil this basic function very adequately. However, this inadvertent exposure could often be interpreted as an overt act of resistance to the ward and towards staff, especially when it led to exposed genitalia or continence products (pads or nappies).We speculate that the interpretation of resistance may be triggered by the visual prompt of disarrayed clothing and the meanings assumed to follow, where lack of decorum in attire is interpreted as indicating more general behavioural incompetence, cognitive impairment and/or standing outside the social order.DiscussionPrevious studies examining the significance of the visual, particularly Twigg and Buse’s work16–19 exploring the materialities of appearance, emphasise its key role in self-presentation, visibility, dignity and autonomy for older people and especially those living with dementia in care home settings.

Similarly, care home studies have demonstrated that institutional clothing, designed to facilitate task-based care, can be potentially dehumanising or and distressing.25 26 Our findings resonate with this work, but find that for people living with dementia within a key site of care, the acute ward, the impact of institutional clothing on the individual patient living with dementia, is poorly recognised, but is significant for the quality and humanity of their care.Our ethnographic approach enabled the researchers how to buy amoxil to observe the organisation and delivery of task-oriented fast-paced nature of the work of the ward and bedside care. Nonetheless, it should also be emphasised the instances in which staff such as HCAs and specialist dementia staff within these wards took time to take note of personal appearance and physical caring for patients and how important this can be for overall well-being. None of our observations should be read as critical of any individual staff, but reflects longstanding institutional cultures.Our previous work has examined how readily a person living with dementia within a hospital wards is vulnerable to dehumanisation,51 and to their behaviour within these wards being interpreted as a feature of their condition, rather than a response to the ways in which timetabled care is delivered at their bedside.50 We have also examined the ways in which visual stimuli within these wards in the form of signs and symbols indicating a diagnosis of dementia may inadvertently focus attention away from the individual patient and may incline towards simplified and inaccurate categorisation of both needs and the diagnostic category of dementia.52Our work supports the analysis of the two forms of attention arising from McGilchrist’s work.10 The institutional culture of the wards produces an organisational task-based technical attention, which we found appeared to compete with and reduce the opportunity for ward staff to seek a finer emotional attunement to the person they are caring for and their needs.

Focus on efficiency, pace and how to buy amoxil record keeping that measures individual task completion within a timetable of care may worsen all these effects. Indeed, other work has shown that in some contexts, attention to visual appearance may itself be little more than a ‘task’ to achieve.49 McGilchrist makes clear, and we agree, that both forms of attention are vital, but more needs to be done to enable staff to find a balance.Previous work has shown how important appearance is to older people, and to people living with dementia in particular, both in terms of how they are perceived by others, but also how for this group, people living with dementia, clothing and personal grooming may act as a particularly important anchor into a familiar social world. These twin aspects of clothing and appearance—self-perception and perception by others—may be especially important in the fast-paced context of an acute ward environment, where patients living with dementia may be struggling with the impacts of an additional how to buy amoxil acute medical condition within in a highly timetabled and regimented and unfamiliar environment of the ward, and where staff perceptions of them may feed into clinical assessments of their condition and subsequent treatment and discharge pathways.

We have seen above, for instance, how behaviour in relation to appearance may be seen as ‘resisting care’ in one group of patients, but as the natural expression of personal preference in patients viewed as being without cognitive impairments. Likewise, personal grooming might impact favourably on a patient’s alertness, visibility and status within the ward.Prior work has demonstrated the importance of the medical gaze for the perceptions of the patient. Other work has also shown how older people, and in particular people living with dementia, may be thought to be beyond how to buy amoxil concern for appearance, yet this does not accurately reflect the importance of appearance we found for this patient group.

Indeed, we argue that our work, along with the work of others such as Kontos,20 21 shows that if anything, visual appearance is especially important for people living with dementia particularly within clinical settings. In considering the task of washing the patient, Pols53 considered ‘dignitas’ in terms of aesthetic values, in comparison to humanitas conceived as citizen values of equality between persons. Attention to dignitas in the form of appearance may be a how to buy amoxil way of facilitating the treatment by others of a person with humanitas, and helping to realise dignity of patients.Data availability statementNo data are available.

Data are unavailable to protect anonymity.Ethics statementsPatient consent for publicationNot required.Ethics approvalEthics committee approval for the study was granted by the NHS Research Ethics Service (15/WA/0191).AcknowledgmentsThe authors acknowledge funding support from the NIHR.Notes1. Devan Stahl how to buy amoxil (2013). €œLiving into the imagined body.

How the diagnostic image confronts the lived body.” Medical Humanities. Medhum-2012–010286.2. Joyce Zazulak et al.

(2017). "The art of medicine. Arts-based training in observation and mindfulness for fostering the empathic response in medical residents.” Medical Humanities.

Medhum-2016-011180.3. E Forde (2018). "Using photography to enhance GP trainees’ reflective practice and professional development." Medical Humanities.

Medhum-2017-011203.4. Caroline Wellbery and Melissa Chan (2014) “White coat, patient gown.” Medical Humanities. Medhum-2013–0 10 463.5.

E Goffman (1990a). Stigma. Notes on the management of spoiled identity, Penguin.6.

J Bridges and C Wilkinson (2011). €œAchieving dignity for older people with dementia in hospital.” Nursing Standard 5 (29).7. J Dancy (1985).

Contemporary Epistemology, John Wiley and Sons.8. D McNaughton (1988). Moral Vision.

Blackwell.9. S Weil (1953). Gravity and Grace.

U of Nebraska Press.10. I McGilchrist (2009). The Master and his Emissary.

The divided brain and the making of the western world. New Haven and London, Yale University Press.11. Iain McGilchrist (2011).

€œPaying attention to the bipartite brain.” The Lancet 377 (9771). 1068–1069.12. Efrat Tseëlon (1992).

€œSelf presentation through appearance. A manipulative vs a dramaturgical approach”. Symbolic Interaction, 15(4).

501–514.13. E Tseëlon (1995). The masque of femininity.

The presentation of woman in everyday life. London. Sage.14.

E Goffman (1990b). The Presentation of Self in Everyday Life Penguin15. Efrat Tseëlon (2001).

€œFashion research and its discontents”. Fashion Theory, 5 (4). 435–451.16.

Julia Twigg (2010a). €œClothing and dementia. A neglected dimension?.

€ Journal of Ageing Studies 24(4). 223–230.17. Julia Twigg and Christina E Buse (2013).

€œDress, dementia and the embodiment of identity.” Dementia 12(3). 326–336.18. C.

E Buse and J. Twigg (2015). €œClothing, embodied identity and dementia.

Maintaining the self through dress.” Age, Culture, Humanities (2).19. Christina Buse and Julia Twigg (2018). €œDressing disrupted.

Negotiating care through the materiality of dress in the context of dementia.” Sociology of Health &. Illness, 40(2). 340-352.20.

PIA C Kontos (2004). Ethnographic reflections on selfhood, embodiment and Alzheimer's disease. Ageing &.

C Kontos (2005). €œEmbodied selfhood in Alzheimer's disease. Rethinking person-centred care.” Dementia 4 (4).

Naglie (2007). €œBridging theory and practice. Imagination, the body, and person-centred dementia care.” Dementia 6 (4).

549–569.23. Richard Ward et al. (2016a).

€œâ€˜Gonna make yer gorgeous’. Everyday transformation, resistance and belonging in the care-based hair salon.” Dementia, 15(3). 395–413.24.

Richard Ward, Sarah Campbell, and John Keady (2016b). €œAssembling the salon. Learning from alternative forms of body work in dementia care.” Sociology of Health &.

Illness, 38(8). 1287–1302.25. Sonja Iltanen-Tähkävuori, Minttu Wikberg, and Päivi Topo (2012).

Design and dementia. A case of garments designed to prevent undressing. Dementia, 11(1).

49–59.26. Päivi Topo and Sonja Iltanen-Tähkävuori (2010). €œScripting patienthood with patient clothing.” Social Science &.

Medicine, 70(11). 1682–1689.27. Julia Twigg (2010b).

€œWelfare embodied. The materiality of hospital dress. A commentary on Topo and Iltanen-Tähkävuori”.

Social Science and Medicine, 70(11), 1690–1692.28. Kathleen Woodward (2006). €œPerforming age, performing gender” National Women’s Studies Association (NWSA) Journal 18(1).

162–89.29. K.M Woodward (1999). Introduction.

In K.M. Woodward (ed.), Figuring Age. Women, Bodies and Generations (pp.

Ix-xxix). Bloomington. Indiana University Press.30.

M Hammersley and P Atkinson (1989). Ethnography. Principles in practice.

J Caracelli (2006). Enhancing the policy process through the use of ethnography and other study frameworks. A mixed-method strategy.

Research in the Schools, 13(1). 84–92.32. W Housley and P Atkinson (2003).

Interactionism, Sage33. M Hammersley (1987) What's Wrong with Ethnography?. Methodological Explorations.

London. Routledge34. V Turner and E Bruner (1986).

The Anthropology of Experience New York. PAJ Publications. 2435.

K Charmaz and RG Mitchell (2001). €˜Grounded theory in ethnography’ in Atkinson P. (Ed) Handbook of Ethnography, 2001.

B Glaser and A Strauss (1967). The Discovery of Grounded Theory. London.

Weidenfeld and Nicholson, 24(25). 288–30437. Juliet M.

Corbin and Anselm Strauss (1990). Grounded theoryrResearch. Procedures, canons, and evaluative criteria.

Grounded theory and the constant comparative method. BMJ (Clinical research ed.), 316 (7137),:1064.39. Roy Suddaby (2006).

€œFrom the editors. What grounded theory is not.” Academy of management journal, 49(4). 633–642.40.

Elizabeth L Sampson et al. (2009). €œDementia in the acute hospital.

Prospective cohort study of prevalence and mortality”. British Journal of Psychiatry,195(1). 61–66.

Doi:10.1192/bjp.bp.108.05533541. C Pinkert and B Holle (2012). €œPeople with dementia in acute hospitals.

Literature review of prevalence and reasons for hospital admission”. Z. Gerontol.

Robert E Herriott and William A. Firestone (1983) “Multisite qualitative policy research. Optimising description and generalizability”.

Education Research 12:14–1943. F Vogt (2002). €œNo ethnography without comparison.

The methodological significance of comparison in ethnographic research” Studies in Education Ethnography 6:23–4244. Benjamin Saunders et al. (2018).

€œSaturation in qualitative research. Exploring its conceptualization and operationalization.” Quality and Quantity 52 (4). 1893–1907.45.

A Coffey and P Atkinson (1996). Making sense of qualitative data. Complementary research strategies.

Sage Publications, Inc.46. Paula Boddington and Katie Featherstone (2018). €œThe canary in the coal mine.

Continence care for people with dementia in acute hospital wards as a crisis of dehumanisation”. Bioethics, 32(4). 251–260.47.

Christina Buse et al. (2014). €œLooking “out of place”.

Analysing the spatial and symbolic meanings of dementia care settings through dress.” International Journal of Ageing and Later Life 9 (1). 69–95.48. R.

K. Merton (1968). €œThe Matthew effect in science.

The reward and communication systems of science are considered.” Science 159 (3810). 56–63.49. Geraldine Lee-Treweek (1997) “Women, resistance and care.

An ethnographic study of nursing auxiliary work” Work, Employment and Society, 11(1). 47–6350. Katie Featherstone et al.

(2019b). €œRefusal and resistance to care by people living with dementia being cared for within acute hospital wards. An ethnographic study” Health Service and Delivery Research51.

Katie Featherstone, Andy Northcott, and Jackie Bridges (2019a). €œRoutines of resistance. An ethnography of the care of people living with dementia in acute hospital wards and its consequences.” International Journal of Nursing Studies.52.

K Featherstone, A Northcott, and P Boddington (2020). €œUsing signs and symbols to identify hospital patients with a dementia diagnosis. Help or hindrance to recognition and care?.

€ Narrative Inquiry in Bioethics53. Jeannette Pols (2013). €œWashing the patient.

Dignity and aesthetic values in nursing care” Nursing Philosophy, 14(3). 186–200.

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AbstractIntroduction. We report a very rare case of familial breast cancer and diffuse gastric cancer, with germline pathogenic variants in both BRCA1 and CDH1 genes. To the best of our knowledge, this is the first report of such an association.Family description. The proband is a woman diagnosed with breast cancer at the age of 52 years.

She requested genetic counselling in 2012, at the age of 91 years, because of a history of breast cancer in her daughter, her sister, her niece and her paternal grandmother and was therefore concerned about her relatives. Her sister and maternal aunt also had gastric cancer. She was tested for several genes associated with hereditary breast cancer.Results. A large deletion of BRCA1 from exons 1 to 7 and two CDH1 pathogenic cis variants were identified.Conclusion.

This complex situation is challenging for genetic counselling and management of at-risk individuals.cancer. Breastcancer. Gastricclinical geneticsgenetic screening/counsellingmolecular geneticsIntroductionGLI-Kruppel family member 3 (GLI3) encodes for a zinc finger transcription factor which plays a key role in the sonic hedgehog (SHH) signalling pathway essential in both limb and craniofacial development.1 2 In hand development, SHH is expressed in the zone of polarising activity (ZPA) on the posterior side of the handplate. The ZPA expresses SHH, creating a gradient of SHH from the posterior to the anterior side of the handplate.

In the presence of SHH, full length GLI3-protein is produced (GLI3A), whereas absence of SHH causes cleavage of GLI3 into its repressor form (GLI3R).3 4 Abnormal expression of this SHH/GLI3R gradient can cause both preaxial and postaxial polydactyly.2Concordantly, pathogenic DNA variants in the GLI3 gene are known to cause multiple syndromes with craniofacial and limb involvement, such as. Acrocallosal syndrome5 (OMIM. 200990), Greig cephalopolysyndactyly syndrome6 (OMIM. 175700) and Pallister-Hall syndrome7 (OMIM.

146510). Also, in non-syndromic polydactyly, such as preaxial polydactyly-type 4 (PPD4, OMIM. 174700),8 pathogenic variants in GLI3 have been described. Out of these diseases, Pallister-Hall syndrome is the most distinct entity, defined by the presence of central polydactyly and hypothalamic hamartoma.9 The other GLI3 syndromes are defined by the presence of preaxial and/or postaxial polydactyly of the hand and feet with or without syndactyly (Greig syndrome, PPD4).

Also, various mild craniofacial features such as hypertelorism and macrocephaly can occur. Pallister-Hall syndrome is caused by truncating variants in the middle third of the GLI3 gene.10–12 The truncation of GLI3 causes an overexpression of GLI3R, which is believed to be the key difference between Pallister-Hall and the GLI3-mediated polydactyly syndromes.9 11 Although multiple attempts have been made, the clinical and genetic distinction between the GLI3-mediated polydactyly syndromes is less evident. This has for example led to the introduction of subGreig and the formulation of an Oro-facial-digital overlap syndrome.10 Other authors, suggested that we should not regard these diseases as separate entities, but as a spectrum of GLI3-mediated polydactyly syndromes.13Although phenotype/genotype correlation of the different syndromes has been cumbersome, clinical and animal studies do provide evidence that distinct regions within the gene, could be related to the individual anomalies contributing to these syndromes. First, case studies show isolated preaxial polydactyly is caused by both truncating and non-truncating variants throughout the GLI3 gene, whereas in isolated postaxial polydactyly cases truncating variants at the C-terminal side of the gene are observed.12 14 These results suggest two different groups of variants for preaxial and postaxial polydactyly.

Second, recent animal studies suggest that posterior malformations in GLI3-mediated polydactyly syndromes are likely related to a dosage effect of GLI3R rather than due to the influence of an altered GLI3A expression.15Past attempts for phenotype/genotype correlation in GLI3-mediated polydactyly syndromes have directly related the diagnosed syndrome to the observed genotype.10–12 16 Focusing on individual hand phenotypes, such as preaxial and postaxial polydactyly and syndactyly might be more reliable because it prevents misclassification due to inconsistent use of syndrome definition. Subsequently, latent class analysis (LCA) provides the possibility to relate a group of observed variables to a set of latent, or unmeasured, parameters and thereby identifying different subgroups in the obtained dataset.17 As a result, LCA allows us to group different phenotypes within the GLI3-mediated polydactyly syndromes and relate the most important predictors of the grouped phenotypes to the observed GLI3 variants.The aim of our study was to further investigate the correlation of the individual phenotypes to the genotypes observed in GLI3-mediated polydactyly syndromes, using LCA. Cases were obtained by both literature review and the inclusion of local clinical cases. Subsequently, we identified two subclasses of limb anomalies that relate to the underlying GLI3 variant.

We provide evidence for two different phenotypic and genotypic groups with predominantly preaxial and postaxial hand and feet anomalies, and we specify those cases with a higher risk for corpus callosum anomalies.MethodsLiterature reviewThe Human Gene Mutation Database (HGMD Professional 2019) was reviewed to identify known pathogenic variants in GLI3 and corresponding phenotypes.18 All references were obtained and cases were included when they were diagnosed with either Greig or subGreig syndrome or PPD4.10–12 Pallister-Hall syndrome and acrocallosal syndrome were excluded because both are regarded distinct syndromes and rather defined by the presence of the non-hand anomalies, than the presence of preaxial or postaxial polydactyly.13 19 Isolated preaxial or postaxial polydactyly were excluded for two reasons. The phenotype/genotype correlations are better understood and both anomalies can occur sporadically which could introduce falsely assumed pathogenic GLI3 variants in the analysis. Additionally, cases were excluded when case-specific phenotypic or genotypic information was not reported or if these two could not be related to each other. Families with a combined phenotypic description, not reducible to individual family members, were included as one case in the analysis.Clinical casesThe Sophia Children’s Hospital Database was reviewed for cases with a GLI3 variant.

Within this population, the same inclusion criteria for the phenotype were valid. Relatives of the index patients were also contacted for participation in this study, when they showed comparable hand, foot, or craniofacial malformations or when a GLI3 variant was identified. Phenotypes of the hand, foot and craniofacial anomalies of the patients treated in the Sophia Children's Hospital were collected using patient documentation. Family members were identified and if possible, clinically verified.

Alternatively, family members were contacted to verify their phenotypes. If no verification was possible, cases were excluded.PhenotypesThe phenotypes of both literature cases and local cases were extracted in a similar fashion. The most frequently reported limb and craniofacial phenotypes were dichotomised. The dichotomised hand and foot phenotypes were preaxial polydactyly, postaxial polydactyly and syndactyly.

Broad halluces or thumbs were commonly reported by authors and were dichotomised as a presentation of preaxial polydactyly. The extracted dichotomised craniofacial phenotypes were hypertelorism, macrocephaly and corpus callosum agenesis. All other phenotypes were registered, but not dichotomised.Pathogenic GLI3 variantsAll GLI3 variants were extracted and checked using Alamut Visual V.2.14. If indicated, variants were renamed according to standard Human Genome Variation Society nomenclature.20 Variants were grouped in either missense, frameshift, nonsense or splice site variants.

In the group of frameshift variants, a subgroup with possible splice site effect were identified for subgroup analysis when indicated. Similarly, nonsense variants prone for nonsense mediated decay (NMD) and nonsense variants with experimentally confirmed NMD were identified.21 Deletions of multiple exons, CNVs and translocations were excluded for analysis. A full list of included mutations is available in the online supplementary materials.Supplemental materialThe location of the variant was compared with five known structural domains of the GLI3 gene. (1) repressor domain, (2) zinc finger domain, (3) cleavage site, (4) activator domain, which we defined as a concatenation of the separately identified transactivation zones, the CBP binding domain and the mediator binding domain (MBD) and (5) the MID1 interaction region domain.1 6 22–24 The boundaries of each of the domains were based on available literature (figure 1, exact locations available in the online supplementary materials).

The boundaries used by different authors did vary, therefore a consensus was made.In this figure the posterior probability of an anterior phenotype is plotted against the location of the variant, stratified for the type of mutation that was observed. For better overview, only variants with a location effect were displayed. The full figure, including all variant types, can be found in the online supplementary figure 1. Each mutation is depicted as a dot, the size of the dot represents the number of observations for that variant.

If multiple observations were made, the mean posterior odds and IQR are plotted. For the nonsense variants, variants that were predicted to produce nonsense mediated decay, are depicted using a triangle. Again, the size indicates the number of observations." data-icon-position data-hide-link-title="0">Figure 1 In this figure the posterior probability of an anterior phenotype is plotted against the location of the variant, stratified for the type of mutation that was observed. For better overview, only variants with a location effect were displayed.

The full figure, including all variant types, can be found in the online supplementary figure 1. Each mutation is depicted as a dot, the size of the dot represents the number of observations for that variant. If multiple observations were made, the mean posterior odds and IQR are plotted. For the nonsense variants, variants that were predicted to produce nonsense mediated decay, are depicted using a triangle.

Again, the size indicates the number of observations.Supplemental materialLatent class analysisTo cluster phenotypes and relate those to the genotypes of the patients, an explorative analysis was done using LCA in R (R V.3.6.1 for Mac. Polytomous variable LCA, poLCA V.1.4.1.). We used our LCA to detect the number of phenotypic subgroups in the dataset and subsequently predict a class membership for each case in the dataset based on the posterior probabilities.In order to make a reliable prediction, only phenotypes that were sufficiently reported and/or ruled out were feasible for LCA, limiting the analysis to preaxial polydactyly, postaxial polydactyly and syndactyly of the hands and feet. Only full cases were included.

To determine the optimal number of classes, we fitted a series of models ranging from a one-class to a six-class model. The optimal number of classes was based on the conditional Akaike information criterion (cAIC), the non adjusted and the sample-size adjusted Bayesian information criterion (BIC and aBIC) and the obtained entropy.25 The explorative LCA produces both posterior probabilities per case for both classes and predicted class membership. Using the predicted class membership, the phenotypic features per class were determined in a univariate analysis (χ2, SPSS V.25). Using the posterior probabilities on latent class (LC) membership, a scatter plot was created using the location of the variant on the x-axis and the probability of class membership on the y-axis for each of the types of variants (Tibco Spotfire V.7.14).

Using these scatter plots, variants that give similar phenotypes were clustered.Genotype/phenotype correlationBecause an LC has no clinical value, the correlation between genotypes and phenotypes was investigated using the predictor phenotypes and the clustered phenotypes. First, those phenotypes that contribute most to LC membership were identified. Second those phenotypes were directly related to the different types of variants (missense, nonsense, frameshift, splice site) and their clustered locations. Quantification of the relation was performed using a univariate analysis using a χ2 test.

Because of our selection criteria, meaning patients at least have two phenotypes, a multivariate using a logistic regression analysis was used to detect the most significant predictors in the overall phenotype (SPSS V.25). Finally, we explored the relation of the clustered genotypes to the presence of corpus callosum agenesis, a rare malformation in GLI3-mediated polydactyly syndromes which cannot be readily diagnosed without additional imaging.ResultsWe included 251 patients from the literature and 46 local patients,10–12 16 21 26–43 in total 297 patients from 155 different families with 127 different GLI3 variants, 32 of which were large deletions, CNVs or translocations. In six local cases, the exact variant could not be retrieved by status research.The distribution of the most frequently observed phenotypes and variants are presented in table 1. Other recurring phenotypes included developmental delay (n=22), broad nasal root (n=23), frontal bossing or prominent forehead (n=16) and craniosynostosis (n=13), camptodactyly (n=8) and a broad first interdigital webspace of the foot (n=6).View this table:Table 1 Baseline phenotypes and genotypes of selected populationThe LCA model was fitted using the six defined hand/foot phenotypes.

Model fit indices for the LCA are displayed in table 2. Based on the BIC, a two-class model has the best fit for our data. The four-class model does show a gain in entropy, however with a higher BIC and loss of df. Therefore, based on the majority of performance statistics and the interpretability of the model, a two-class model was chosen.

Table 3 displays the distribution of phenotypes and genotypes over the two classes.View this table:Table 2 Model fit indices for the one-class through six-class model evaluated in our LCAView this table:Table 3 Distribution of phenotypes and genotypes in the two latent classes (LC)Table 1 depicts the baseline phenotypes and genotypes in the obtained population. Note incomplete data especially in the cranium phenotypes. In total 259 valid genotypes were present. In total, 289 cases had complete data for all hand and foot phenotypes (preaxial polydactyly, postaxial polydactyly and syndactyly) and thus were available for LCA.

Combined, for phenotype/genotype correlation 258 cases were available with complete genotypes and complete hand and foot phenotypes.Table 2 depicts the model fit indices for all models that have been fitted to our data.Table 3 depicts the distribution of phenotypes and genotypes over the two assigned LCs. Hand and foot phenotypes were used as input for the LCA, thus are all complete cases. Malformation of the cranium and genotypes do have missing cases. Note that for the LCA, full case description was required, resulting in eight cases due to incomplete phenotypes.

Out of these eight, one also had a genotype that thus needed to be excluded. Missingness of genotypic data was higher in LC2, mostly due to CNVs (table 1).In 54/60 cases, a missense variant produced a posterior phenotype. Likewise, splice site variants show the same phenotype in 23/24 cases (table 3). For both frameshift and nonsense variants, this relation is not significant (52 anterior vs 54 posterior and 26 anterior vs 42 posterior, respectively).

Therefore, only for nonsense and frameshift variants the location of the variant was plotted against the probability for LC2 membership in figure 1. A full scatterplot of all variants is available in online supplementary figure 1.Figure 1 reveals a pattern for these nonsense and frameshift variants that reveals that variants at the C-terminal of the gene predict anterior phenotypes. When relating the domains of the GLI3 protein to the observed phenotype, we observe that the majority of patients with a nonsense or frameshift variant in the repressor domain, the zinc finger domain or the cleavage site had a high probability of an LC2/anterior phenotype. This group contains all variants that are either experimentally determined to be subject to NMD (triangle marker in figure 1) or predicted to be subject to NMD (diamond marker in figure 1).

Frameshift and nonsense variants in the activator domain result in high probability for an LC1/posterior phenotype. These variants will be further referred to as truncating variants in the activator domain.The univariate relation of the individual phenotypes to these two groups of variants are estimated and presented in table 4. In our multivariate analysis, postaxial polydactyly of the foot and hand are the strongest predictors (Beta. 2.548, p<0001 and Beta.

1.47, p=0.013, respectively) for patients to have a truncating variant in the activator domain. Moreover, the effect sizes of preaxial polydactyly of the hand and feet (Beta. ˆ’0.797, p=0123 and −1.772, p=0.001) reveals that especially postaxial polydactyly of the foot is the dominant predictor for the genetic substrate of the observed anomalies.View this table:Table 4 Univariate and multivariate analysis of the phenotype/genotype correlationTable 4 shows exploration of the individual phenotypes on the genotype, both univariate and multivariate. The multivariate analysis corrects for the presence of multiple phenotypes in the underlying population.Although the craniofacial anomalies could not be included in the LCA, the relation between the observed anomalies and the identified genetic substrates can be studied.

The prevalence of hypertelorism was equally distributed over the two groups of variants (47/135 vs 21/47 respectively, p<0.229). However for corpus callosum agenesis and macrocephaly, there was a higher prevalence in patients with a truncating variant in the activator domain (3/75 vs 11/41, p<0.001. OR. 8.8, p<0.001) and 42/123 vs 24/48, p<0.05).

Noteworthy is the fact that 11/14 cases with corpus callosum agenesis in the dataset had a truncating variant in the activator domain.DiscussionIn this report, we present new insights into the correlation between the phenotype and the genotype in patients with GLI3-mediated polydactyly syndromes. We illustrate that there are two LCs of patients, best predicted by postaxial polydactyly of the hand and foot for LC1, and the preaxial polydactyly of the hand and foot and syndactyly of the foot for LC2. Patients with postaxial phenotypes have a higher risk of having a truncating variant in the activator domain of the GLI3 gene which is also related to a higher risk of corpus callosum agenesis. These results suggest a functional difference between truncating variants on the N-terminal and the C-terminal side of the GLI3 cleavage site.Previous attempts of phenotype to genotype correlation have not yet provided the clinical confirmation of these assumed mechanisms in the pathophysiology of GLI3-mediated polydactyly syndromes.

Johnston et al have successfully determined the Pallister-Hall region in which truncating variants produce a Pallister-Hall phenotype rather than Greig syndrome.11 However, in their latest population study, subtypes of both syndromes were included to explain the full spectrum of observed malformations. In 2015, Demurger et al reported the higher incidence of corpus callosum agenesis in the Greig syndrome population with truncating mutations in the activator domain.12 Al-Qattan in his review summarises the concept of a spectrum of anomalies dependent on haplo-insufficiency (through different mechanisms) and repressor overexpression.13 However, he bases this theory mainly on reviewed experimental data. Our report is the first to provide an extensive clinical review of cases that substantiate the phenotypic difference between the two groups that could fit the suggested mechanisms. We agree with Al-Qattan et al that a variation of anomalies can be observed given any pathogenic variant in the GLI3 gene, but overall two dominant phenotypes are present.

A population with predominantly preaxial anomalies and one with postaxial anomalies. The presence of preaxial or postaxial polydactyly and syndactyly is not mutually exclusive for one of these two subclasses. Meaning that preaxial polydactyly can co-occur with postaxial polydactyly. However, truncating mutations in the activator domain produce a postaxial phenotype, as can be derived from the risk in table 4.

The higher risk of corpus callosum agenesis in this population shows that differentiating between a preaxial phenotype and a postaxial phenotype, instead of between the different GLI3-mediated polydactyly syndromes, might be more relevant regarding diagnostics for corpus callosum agenesis.We chose to use LCA as an exploratory tool only in our population for two reasons. First of all, LCA can be useful to identify subgroups, but there is no ‘true’ model or number of subgroups you can detect. The best fitting model can only be estimated based on the available measures and approximates the true subgroups that might be present. Second, LC membership assignment is a statistical procedure based on the posterior probability, with concordant errors of the estimation, rather than a clinical value that can be measured or evaluated.

Therefore, we decided to use our LCA only in an exploratory tool, and perform our statistics using the actual phenotypes that predict LC membership and the associated genotypes. Overall, this method worked well to differentiate the two subgroups present in our dataset. However, outliers were observed. A qualitative analysis of these outliers is available in the online supplementary data.The genetic substrate for the two phenotypic clusters can be discussed based on multiple experiments.

Overall, we hypothesise two genetic clusters. One that is due to haploinsufficiency and one that is due to abnormal truncation of the activator. The hypothesised cluster of variants that produce haploinsufficiency is mainly based on the experimental data that confirms NMD in two variants and the NMD prediction of other nonsense variants in Alamut. For the frameshift variants, it is also likely that the cleavage of the zinc finger domain results in functional haploinsufficiency either because of a lack of signalling domains or similarly due to NMD.

Missense variants could cause haploinsufficiency through the suggested mechanism by Krauss et al who have illustrated that missense variants in the MID1 domain hamper the functional interaction with the MID1-α4-PP2A complex, leading to a subcellular location of GLI3.24 The observed missense variants in our study exceed the region to which Krauss et al have limited the MID-1 interaction domain. An alternative theory is suggested by Zhou et al who have shown that missense variants in the MBD can cause deficiency in the signalling of GLI3A, functionally implicating a relative overexpression of GLI3R.22 However, GLI3R overexpression would likely produce a posterior phenotype, as determined by Hill et al in their fixed homo and hemizygous GLI3R models.15 Therefore, our hypothesis is that all included missense variants have a similar pathogenesis which is more likely in concordance with the mechanism introduced by Krauss et al. To our knowledge, no splice site variants have been functionally described in literature. However, it is noted that the 15 and last exon encompasses the entire activator domain, thus any splice site mutation is by definition located on the 5′ side of the activator.

Based on the phenotype, we would suggest that these variants fail to produce a functional protein. We hypothesise that the truncating variants of the activator domain lead to overexpression of GLI3R in SHH rich areas. In normal development, the presence of SHH prevents the processing of full length GLI34 into GLI3R, thus producing the full length activator. In patients with a truncating variant of the activator domain of GLI3, thus these variants likely have the largest effect in SHH rich areas, such as the ZPA located at the posterior side of the hand/footplate.

Moreover, the lack of posterior anomalies in the GLI3∆699/- mouse model (hemizygous fixed repressor model) compared with the GLI3∆699/∆699 mouse model (homozygous fixed repressor model), suggesting a dosage effect of GLI3R to be responsible for posterior hand anomalies.15 These findings are supported by Lewandowski et al, who show that the majority of the target genes in GLI signalling are regulated by GLI3R rather than GLI3A.44 Together, these findings suggest a role for the location and type of variant in GLI3-mediated syndromes.Interestingly, the difference between Pallister-Hall syndrome and GLI3-mediated polydactyly syndromes has also been attributed to the GLI3R overexpression. However, the difference in phenotype observed in the cases with a truncating variant in the activator domain and Pallister-Hall syndrome suggest different functional consequences. When studying figure 1, it is noted that the included truncating variants on the 3′ side of the cleavage site seldomly affect the CBP binding region, which could provide an explanation for the observed differences. This binding region is included in the Pallister-Hall region as defined by Johnston et al and is necessary for the downstream signalling with GLI1.10 11 23 45 Interestingly, recent reports show that pathogenic variants in GLI1 can produce phenotypes concordant with Ellis von Krefeld syndrome, which includes overlapping features with Pallister-Hall syndrome.46 The four truncating variants observed in this study that do affect the CBP but did not result in a Pallister-Hall phenotype are conflicting with this theory.

Krauss et al postulate an alternative hypothesis, they state that the MID1-α4-PP2A complex, which is essential for GLI3A signalling, could also be the reason for overlapping features of Opitz syndrome, caused by variants in MID1, and Pallister-Hall syndrome. Further analysis is required to fully appreciate the functional differences between truncating mutations that cause Pallister-Hall syndrome and those that result in GLI3-mediated polydactyly syndromes.For the clinical evaluation of patients with GLI3-mediated polydactyly syndromes, intracranial anomalies are likely the most important to predict based on the variant. Unfortunately, the presence of corpus callosum agenesis was not routinely investigated or reported thus this feature could not be used as an indicator phenotype for LC membership. Interestingly when using only hand and foot phenotypes, we did notice a higher prevalence of corpus callosum agenesis in patients with posterior phenotypes.

The suggested relation between truncating mutations in the activator domain causing these posterior phenotypes and corpus callosum agenesis was statistically confirmed (OR. 8.8, p<0.001). Functionally this relation could be caused by the GLI3-MED12 interaction at the MBD. Pathogenic DNA variants in MED12 can cause Opitz-Kaveggia syndrome, a syndrome in which presentation includes corpus callosum agenesis, broad halluces and thumbs.47In conclusion, there are two distinct phenotypes within the GLI3-mediated polydactyly population.

Patients with more posteriorly and more anteriorly oriented hand anomalies. Furthermore, this difference is related to the observed variant in GLI3. We hypothesise that variants that cause haploinsufficiency produce anterior anomalies of the hand, whereas variants with abnormal truncation of the activator domain have more posterior anomalies. Furthermore, patients that have a variant that produces abnormal truncation of the activator domain, have a greater risk for corpus callosum agenesis.

Thus, we advocate to differentiate preaxial or postaxial oriented GLI3 phenotypes to explain the pathophysiology as well as to get a risk assessment for corpus callosum agenesis.Data availability statementData are available upon reasonable request.Ethics statementsPatient consent for publicationNot required.Ethics approvalThe research protocol was approved by the local ethics board of the Erasmus MC University Medical Center (MEC 2015-679)..

AbstractIntroduction. We report a very rare case of familial breast cancer and diffuse gastric cancer, with germline pathogenic variants in both BRCA1 and CDH1 genes. To the best of our knowledge, this is the first report of such an association.Family description. The proband is a woman diagnosed with breast cancer at the age of 52 years.

She requested genetic counselling in 2012, at the age of 91 years, because of a history of breast cancer in her daughter, her sister, her niece and her paternal grandmother and was therefore concerned about her relatives. Her sister and maternal aunt also had gastric cancer. She was tested for several genes associated with hereditary breast cancer.Results. A large deletion of BRCA1 from exons 1 to 7 and two CDH1 pathogenic cis variants were identified.Conclusion.

This complex situation is challenging for genetic counselling and management of at-risk individuals.cancer. Breastcancer. Gastricclinical geneticsgenetic screening/counsellingmolecular geneticsIntroductionGLI-Kruppel family member 3 (GLI3) encodes for a zinc finger transcription factor which plays a key role in the sonic hedgehog (SHH) signalling pathway essential in both limb and craniofacial development.1 2 In hand development, SHH is expressed in the zone of polarising activity (ZPA) on the posterior side of the handplate. The ZPA expresses SHH, creating a gradient of SHH from the posterior to the anterior side of the handplate.

In the presence of SHH, full length GLI3-protein is produced (GLI3A), whereas absence of SHH causes cleavage of GLI3 into its repressor form (GLI3R).3 4 Abnormal expression of this SHH/GLI3R gradient can cause both preaxial and postaxial polydactyly.2Concordantly, pathogenic DNA variants in the GLI3 gene are known to cause multiple syndromes with craniofacial and limb involvement, such as. Acrocallosal syndrome5 (OMIM. 200990), Greig cephalopolysyndactyly syndrome6 (OMIM. 175700) and Pallister-Hall syndrome7 (OMIM.

146510). Also, in non-syndromic polydactyly, such as preaxial polydactyly-type 4 (PPD4, OMIM. 174700),8 pathogenic variants in GLI3 have been described. Out of these diseases, Pallister-Hall syndrome is the most distinct entity, defined by the presence of central polydactyly and hypothalamic hamartoma.9 The other GLI3 syndromes are defined by the presence of preaxial and/or postaxial polydactyly of the hand and feet with or without syndactyly (Greig syndrome, PPD4).

Also, various mild craniofacial features such as hypertelorism and macrocephaly can occur. Pallister-Hall syndrome is caused by truncating variants in the middle third of the GLI3 gene.10–12 The truncation of GLI3 causes an overexpression of GLI3R, which is believed to be the key difference between Pallister-Hall and the GLI3-mediated polydactyly syndromes.9 11 Although multiple attempts have been made, the clinical and genetic distinction between the GLI3-mediated polydactyly syndromes is less evident. This has for example led to the introduction of subGreig and the formulation of an Oro-facial-digital overlap syndrome.10 Other authors, suggested that we should not regard these diseases as separate entities, but as a spectrum of GLI3-mediated polydactyly syndromes.13Although phenotype/genotype correlation of the different syndromes has been cumbersome, clinical and animal studies do provide evidence that distinct regions within the gene, could be related to the individual anomalies contributing to these syndromes. First, case studies show isolated preaxial polydactyly is caused by both truncating and non-truncating variants throughout the GLI3 gene, whereas in isolated postaxial polydactyly cases truncating variants at the C-terminal side of the gene are observed.12 14 These results suggest two different groups of variants for preaxial and postaxial polydactyly.

Second, recent animal studies suggest that posterior malformations in GLI3-mediated polydactyly syndromes are likely related to a dosage effect of GLI3R rather than due to the influence of an altered GLI3A expression.15Past attempts for phenotype/genotype correlation in GLI3-mediated polydactyly syndromes have directly related the diagnosed syndrome to the observed genotype.10–12 16 Focusing on individual hand phenotypes, such as preaxial and postaxial polydactyly and syndactyly might be more reliable because it prevents misclassification due to inconsistent use of syndrome definition. Subsequently, latent class analysis (LCA) provides the possibility to relate a group of observed variables to a set of latent, or unmeasured, parameters and thereby identifying different subgroups in the obtained dataset.17 As a result, LCA allows us to group different phenotypes within the GLI3-mediated polydactyly syndromes and relate the most important predictors of the grouped phenotypes to the observed GLI3 variants.The aim of our study was to further investigate the correlation of the individual phenotypes to the genotypes observed in GLI3-mediated polydactyly syndromes, using LCA. Cases were obtained by both literature review and the inclusion of local clinical cases. Subsequently, we identified two subclasses of limb anomalies that relate to the underlying GLI3 variant.

We provide evidence for two different phenotypic and genotypic groups with predominantly preaxial and postaxial hand and feet anomalies, and we specify those cases with a higher risk for corpus callosum anomalies.MethodsLiterature reviewThe Human Gene Mutation Database (HGMD Professional 2019) was reviewed to identify known pathogenic variants in GLI3 and corresponding phenotypes.18 All references were obtained and cases were included when they were diagnosed with either Greig or subGreig syndrome or PPD4.10–12 Pallister-Hall syndrome and acrocallosal syndrome were excluded because both are regarded distinct syndromes and rather defined by the presence of the non-hand anomalies, than the presence of preaxial or postaxial polydactyly.13 19 Isolated preaxial or postaxial polydactyly were excluded for two reasons. The phenotype/genotype correlations are better understood and both anomalies can occur sporadically which could introduce falsely assumed pathogenic GLI3 variants in the analysis. Additionally, cases were excluded when case-specific phenotypic or genotypic information was not reported or if these two could not be related to each other. Families with a combined phenotypic description, not reducible to individual family members, were included as one case in the analysis.Clinical casesThe Sophia Children’s Hospital Database was reviewed for cases with a GLI3 variant.

Within this population, the same inclusion criteria for the phenotype were valid. Relatives of the index patients were also contacted for participation in this study, when they showed comparable hand, foot, or craniofacial malformations or when a GLI3 variant was identified. Phenotypes of the hand, foot and craniofacial anomalies of the patients treated in the Sophia Children's Hospital were collected using patient documentation. Family members were identified and if possible, clinically verified.

Alternatively, family members were contacted to verify their phenotypes. If no verification was possible, cases were excluded.PhenotypesThe phenotypes of both literature cases and local cases were extracted in a similar fashion. The most frequently reported limb and craniofacial phenotypes were dichotomised. The dichotomised hand and foot phenotypes were preaxial polydactyly, postaxial polydactyly and syndactyly.

Broad halluces or thumbs were commonly reported by authors and were dichotomised as a presentation of preaxial polydactyly. The extracted dichotomised craniofacial phenotypes were hypertelorism, macrocephaly and corpus callosum agenesis. All other phenotypes were registered, but not dichotomised.Pathogenic GLI3 variantsAll GLI3 variants were extracted and checked using Alamut Visual V.2.14. If indicated, variants were renamed according to standard Human Genome Variation Society nomenclature.20 Variants were grouped in either missense, frameshift, nonsense or splice site variants.

In the group of frameshift variants, a subgroup with possible splice site effect were identified for subgroup analysis when indicated. Similarly, nonsense variants prone for nonsense mediated decay (NMD) and nonsense variants with experimentally confirmed NMD were identified.21 Deletions of multiple exons, CNVs and translocations were excluded for analysis. A full list of included mutations is available in the online supplementary materials.Supplemental materialThe location of the variant was compared with five known structural domains of the GLI3 gene. (1) repressor domain, (2) zinc finger domain, (3) cleavage site, (4) activator domain, which we defined as a concatenation of the separately identified transactivation zones, the CBP binding domain and the mediator binding domain (MBD) and (5) the MID1 interaction region domain.1 6 22–24 The boundaries of each of the domains were based on available literature (figure 1, exact locations available in the online supplementary materials).

The boundaries used by different authors did vary, therefore a consensus was made.In this figure the posterior probability of an anterior phenotype is plotted against the location of the variant, stratified for the type of mutation that was observed. For better overview, only variants with a location effect were displayed. The full figure, including all variant types, can be found in the online supplementary figure 1. Each mutation is depicted as a dot, the size of the dot represents the number of observations for that variant.

If multiple observations were made, the mean posterior odds and IQR are plotted. For the nonsense variants, variants that were predicted to produce nonsense mediated decay, are depicted using a triangle. Again, the size indicates the number of observations." data-icon-position data-hide-link-title="0">Figure 1 In this figure the posterior probability of an anterior phenotype is plotted against the location of the variant, stratified for the type of mutation that was observed. For better overview, only variants with a location effect were displayed.

The full figure, including all variant types, can be found in the online supplementary figure 1. Each mutation is depicted as a dot, the size of the dot represents the number of observations for that variant. If multiple observations were made, the mean posterior odds and IQR are plotted. For the nonsense variants, variants that were predicted to produce nonsense mediated decay, are depicted using a triangle.

Again, the size indicates the number of observations.Supplemental materialLatent class analysisTo cluster phenotypes and relate those to the genotypes of the patients, an explorative analysis was done using LCA in R (R V.3.6.1 for Mac. Polytomous variable LCA, poLCA V.1.4.1.). We used our LCA to detect the number of phenotypic subgroups in the dataset and subsequently predict a class membership for each case in the dataset based on the posterior probabilities.In order to make a reliable prediction, only phenotypes that were sufficiently reported and/or ruled out were feasible for LCA, limiting the analysis to preaxial polydactyly, postaxial polydactyly and syndactyly of the hands and feet. Only full cases were included.

To determine the optimal number of classes, we fitted a series of models ranging from a one-class to a six-class model. The optimal number of classes was based on the conditional Akaike information criterion (cAIC), the non adjusted and the sample-size adjusted Bayesian information criterion (BIC and aBIC) and the obtained entropy.25 The explorative LCA produces both posterior probabilities per case for both classes and predicted class membership. Using the predicted class membership, the phenotypic features per class were determined in a univariate analysis (χ2, SPSS V.25). Using the posterior probabilities on latent class (LC) membership, a scatter plot was created using the location of the variant on the x-axis and the probability of class membership on the y-axis for each of the types of variants (Tibco Spotfire V.7.14).

Using these scatter plots, variants that give similar phenotypes were clustered.Genotype/phenotype correlationBecause an LC has no clinical value, the correlation between genotypes and phenotypes was investigated using the predictor phenotypes and the clustered phenotypes. First, those phenotypes that contribute most to LC membership were identified. Second those phenotypes were directly related to the different types of variants (missense, nonsense, frameshift, splice site) and their clustered locations. Quantification of the relation was performed using a univariate analysis using a χ2 test.

Because of our selection criteria, meaning patients at least have two phenotypes, a multivariate using a logistic regression analysis was used to detect the most significant predictors in the overall phenotype (SPSS V.25). Finally, we explored the relation of the clustered genotypes to the presence of corpus callosum agenesis, a rare malformation in GLI3-mediated polydactyly syndromes which cannot be readily diagnosed without additional imaging.ResultsWe included 251 patients from the literature and 46 local patients,10–12 16 21 26–43 in total 297 patients from 155 different families with 127 different GLI3 variants, 32 of which were large deletions, CNVs or translocations. In six local cases, the exact variant could not be retrieved by status research.The distribution of the most frequently observed phenotypes and variants are presented in table 1. Other recurring phenotypes included developmental delay (n=22), broad nasal root (n=23), frontal bossing or prominent forehead (n=16) and craniosynostosis (n=13), camptodactyly (n=8) and a broad first interdigital webspace of the foot (n=6).View this table:Table 1 Baseline phenotypes and genotypes of selected populationThe LCA model was fitted using the six defined hand/foot phenotypes.

Model fit indices for the LCA are displayed in table 2. Based on the BIC, a two-class model has the best fit for our data. The four-class model does show a gain in entropy, however with a higher BIC and loss of df. Therefore, based on the majority of performance statistics and the interpretability of the model, a two-class model was chosen.

Table 3 displays the distribution of phenotypes and genotypes over the two classes.View this table:Table 2 Model fit indices for the one-class through six-class model evaluated in our LCAView this table:Table 3 Distribution of phenotypes and genotypes in the two latent classes (LC)Table 1 depicts the baseline phenotypes and genotypes in the obtained population. Note incomplete data especially in the cranium phenotypes. In total 259 valid genotypes were present. In total, 289 cases had complete data for all hand and foot phenotypes (preaxial polydactyly, postaxial polydactyly and syndactyly) and thus were available for LCA.

Combined, for phenotype/genotype correlation 258 cases were available with complete genotypes and complete hand and foot phenotypes.Table 2 depicts the model fit indices for all models that have been fitted to our data.Table 3 depicts the distribution of phenotypes and genotypes over the two assigned LCs. Hand and foot phenotypes were used as input for the LCA, thus are all complete cases. Malformation of the cranium and genotypes do have missing cases. Note that for the LCA, full case description was required, resulting in eight cases due to incomplete phenotypes.

Out of these eight, one also had a genotype that thus needed to be excluded. Missingness of genotypic data was higher in LC2, mostly due to CNVs (table 1).In 54/60 cases, a missense variant produced a posterior phenotype. Likewise, splice site variants show the same phenotype in 23/24 cases (table 3). For both frameshift and nonsense variants, this relation is not significant (52 anterior vs 54 posterior and 26 anterior vs 42 posterior, respectively).

Therefore, only for nonsense and frameshift variants the location of the variant was plotted against the probability for LC2 membership in figure 1. A full scatterplot of all variants is available in online supplementary figure 1.Figure 1 reveals a pattern for these nonsense and frameshift variants that reveals that variants at the C-terminal of the gene predict anterior phenotypes. When relating the domains of the GLI3 protein to the observed phenotype, we observe that the majority of patients with a nonsense or frameshift variant in the repressor domain, the zinc finger domain or the cleavage site had a high probability of an LC2/anterior phenotype. This group contains all variants that are either experimentally determined to be subject to NMD (triangle marker in figure 1) or predicted to be subject to NMD (diamond marker in figure 1).

Frameshift and nonsense variants in the activator domain result in high probability for an LC1/posterior phenotype. These variants will be further referred to as truncating variants in the activator domain.The univariate relation of the individual phenotypes to these two groups of variants are estimated and presented in table 4. In our multivariate analysis, postaxial polydactyly of the foot and hand are the strongest predictors (Beta. 2.548, p<0001 and Beta.

1.47, p=0.013, respectively) for patients to have a truncating variant in the activator domain. Moreover, the effect sizes of preaxial polydactyly of the hand and feet (Beta. ˆ’0.797, p=0123 and −1.772, p=0.001) reveals that especially postaxial polydactyly of the foot is the dominant predictor for the genetic substrate of the observed anomalies.View this table:Table 4 Univariate and multivariate analysis of the phenotype/genotype correlationTable 4 shows exploration of the individual phenotypes on the genotype, both univariate and multivariate. The multivariate analysis corrects for the presence of multiple phenotypes in the underlying population.Although the craniofacial anomalies could not be included in the LCA, the relation between the observed anomalies and the identified genetic substrates can be studied.

The prevalence of hypertelorism was equally distributed over the two groups of variants (47/135 vs 21/47 respectively, p<0.229). However for corpus callosum agenesis and macrocephaly, there was a higher prevalence in patients with a truncating variant in the activator domain (3/75 vs 11/41, p<0.001. OR. 8.8, p<0.001) and 42/123 vs 24/48, p<0.05).

Noteworthy is the fact that 11/14 cases with corpus callosum agenesis in the dataset had a truncating variant in the activator domain.DiscussionIn this report, we present new insights into the correlation between the phenotype and the genotype in patients with GLI3-mediated polydactyly syndromes. We illustrate that there are two LCs of patients, best predicted by postaxial polydactyly of the hand and foot for LC1, and the preaxial polydactyly of the hand and foot and syndactyly of the foot for LC2. Patients with postaxial phenotypes have a higher risk of having a truncating variant in the activator domain of the GLI3 gene which is also related to a higher risk of corpus callosum agenesis. These results suggest a functional difference between truncating variants on the N-terminal and the C-terminal side of the GLI3 cleavage site.Previous attempts of phenotype to genotype correlation have not yet provided the clinical confirmation of these assumed mechanisms in the pathophysiology of GLI3-mediated polydactyly syndromes.

Johnston et al have successfully determined the Pallister-Hall region in which truncating variants produce a Pallister-Hall phenotype rather than Greig syndrome.11 However, in their latest population study, subtypes of both syndromes were included to explain the full spectrum of observed malformations. In 2015, Demurger et al reported the higher incidence of corpus callosum agenesis in the Greig syndrome population with truncating mutations in the activator domain.12 Al-Qattan in his review summarises the concept of a spectrum of anomalies dependent on haplo-insufficiency (through different mechanisms) and repressor overexpression.13 However, he bases this theory mainly on reviewed experimental data. Our report is the first to provide an extensive clinical review of cases that substantiate the phenotypic difference between the two groups that could fit the suggested mechanisms. We agree with Al-Qattan et al that a variation of anomalies can be observed given any pathogenic variant in the GLI3 gene, but overall two dominant phenotypes are present.

A population with predominantly preaxial anomalies and one with postaxial anomalies. The presence of preaxial or postaxial polydactyly and syndactyly is not mutually exclusive for one of these two subclasses. Meaning that preaxial polydactyly can co-occur with postaxial polydactyly. However, truncating mutations in the activator domain produce a postaxial phenotype, as can be derived from the risk in table 4.

The higher risk of corpus callosum agenesis in this population shows that differentiating between a preaxial phenotype and a postaxial phenotype, instead of between the different GLI3-mediated polydactyly syndromes, might be more relevant regarding diagnostics for corpus callosum agenesis.We chose to use LCA as an exploratory tool only in our population for two reasons. First of all, LCA can be useful to identify subgroups, but there is no ‘true’ model or number of subgroups you can detect. The best fitting model can only be estimated based on the available measures and approximates the true subgroups that might be present. Second, LC membership assignment is a statistical procedure based on the posterior probability, with concordant errors of the estimation, rather than a clinical value that can be measured or evaluated.

Therefore, we decided to use our LCA only in an exploratory tool, and perform our statistics using the actual phenotypes that predict LC membership and the associated genotypes. Overall, this method worked well to differentiate the two subgroups present in our dataset. However, outliers were observed. A qualitative analysis of these outliers is available in the online supplementary data.The genetic substrate for the two phenotypic clusters can be discussed based on multiple experiments.

Overall, we hypothesise two genetic clusters. One that is due to haploinsufficiency and one that is due to abnormal truncation of the activator. The hypothesised cluster of variants that produce haploinsufficiency is mainly based on the experimental data that confirms NMD in two variants and the NMD prediction of other nonsense variants in Alamut. For the frameshift variants, it is also likely that the cleavage of the zinc finger domain results in functional haploinsufficiency either because of a lack of signalling domains or similarly due to NMD.

Missense variants could cause haploinsufficiency through the suggested mechanism by Krauss et al who have illustrated that missense variants in the MID1 domain hamper the functional interaction with the MID1-α4-PP2A complex, leading to a subcellular location of GLI3.24 The observed missense variants in our study exceed the region to which Krauss et al have limited the MID-1 interaction domain. An alternative theory is suggested by Zhou et al who have shown that missense variants in the MBD can cause deficiency in the signalling of GLI3A, functionally implicating a relative overexpression of GLI3R.22 However, GLI3R overexpression would likely produce a posterior phenotype, as determined by Hill et al in their fixed homo and hemizygous GLI3R models.15 Therefore, our hypothesis is that all included missense variants have a similar pathogenesis which is more likely in concordance with the mechanism introduced by Krauss et al. To our knowledge, no splice site variants have been functionally described in literature. However, it is noted that the 15 and last exon encompasses the entire activator domain, thus any splice site mutation is by definition located on the 5′ side of the activator.

Based on the phenotype, we would suggest that these variants fail to produce a functional protein. We hypothesise that the truncating variants of the activator domain lead to overexpression of GLI3R in SHH rich areas. In normal development, the presence of SHH prevents the processing of full length GLI34 into GLI3R, thus producing the full length activator. In patients with a truncating variant of the activator domain of GLI3, thus these variants likely have the largest effect in SHH rich areas, such as the ZPA located at the posterior side of the hand/footplate.

Moreover, the lack of posterior anomalies in the GLI3∆699/- mouse model (hemizygous fixed repressor model) compared with the GLI3∆699/∆699 mouse model (homozygous fixed repressor model), suggesting a dosage effect of GLI3R to be responsible for posterior hand anomalies.15 These findings are supported by Lewandowski et al, who show that the majority of the target genes in GLI signalling are regulated by GLI3R rather than GLI3A.44 Together, these findings suggest a role for the location and type of variant in GLI3-mediated syndromes.Interestingly, the difference between Pallister-Hall syndrome and GLI3-mediated polydactyly syndromes has also been attributed to the GLI3R overexpression. However, the difference in phenotype observed in the cases with a truncating variant in the activator domain and Pallister-Hall syndrome suggest different functional consequences. When studying figure 1, it is noted that the included truncating variants on the 3′ side of the cleavage site seldomly affect the CBP binding region, which could provide an explanation for the observed differences. This binding region is included in the Pallister-Hall region as defined by Johnston et al and is necessary for the downstream signalling with GLI1.10 11 23 45 Interestingly, recent reports show that pathogenic variants in GLI1 can produce phenotypes concordant with Ellis von Krefeld syndrome, which includes overlapping features with Pallister-Hall syndrome.46 The four truncating variants observed in this study that do affect the CBP but did not result in a Pallister-Hall phenotype are conflicting with this theory.

Krauss et al postulate an alternative hypothesis, they state that the MID1-α4-PP2A complex, which is essential for GLI3A signalling, could also be the reason for overlapping features of Opitz syndrome, caused by variants in MID1, and Pallister-Hall syndrome. Further analysis is required to fully appreciate the functional differences between truncating mutations that cause Pallister-Hall syndrome and those that result in GLI3-mediated polydactyly syndromes.For the clinical evaluation of patients with GLI3-mediated polydactyly syndromes, intracranial anomalies are likely the most important to predict based on the variant. Unfortunately, the presence of corpus callosum agenesis was not routinely investigated or reported thus this feature could not be used as an indicator phenotype for LC membership. Interestingly when using only hand and foot phenotypes, we did notice a higher prevalence of corpus callosum agenesis in patients with posterior phenotypes.

The suggested relation between truncating mutations in the activator domain causing these posterior phenotypes and corpus callosum agenesis was statistically confirmed (OR. 8.8, p<0.001). Functionally this relation could be caused by the GLI3-MED12 interaction at the MBD. Pathogenic DNA variants in MED12 can cause Opitz-Kaveggia syndrome, a syndrome in which presentation includes corpus callosum agenesis, broad halluces and thumbs.47In conclusion, there are two distinct phenotypes within the GLI3-mediated polydactyly population.

Patients with more posteriorly and more anteriorly oriented hand anomalies. Furthermore, this difference is related to the observed variant in GLI3. We hypothesise that variants that cause haploinsufficiency produce anterior anomalies of the hand, whereas variants with abnormal truncation of the activator domain have more posterior anomalies. Furthermore, patients that have a variant that produces abnormal truncation of the activator domain, have a greater risk for corpus callosum agenesis.

Thus, we advocate to differentiate preaxial or postaxial oriented GLI3 phenotypes to explain the pathophysiology as well as to get a risk assessment for corpus callosum agenesis.Data availability statementData are available upon reasonable request.Ethics statementsPatient consent for publicationNot required.Ethics approvalThe research protocol was approved by the local ethics board of the Erasmus MC University Medical Center (MEC 2015-679)..

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Language used beginning in FY00).It also prohibits UNFPA from using any funds from the U.S. Contribution in their programming in China.UNFPA Funding. AbortionFunds made available to UNFPAYes, in effect.Included in annual State-Foreign Ops.UNFPA Dollar-for-Dollar Withholding of Amount UNFPA Plans to Spend in China During Fiscal Year (1994)Reduces the U.S. Contribution to UNFPA by one dollar for every dollar that UNFPA spends on its programming in China.UNFPA FundingFunds made available to UNFPAYes, in effect.Typically included in annual State-Foreign Ops.Tiahrt Amendment (1998)Prohibits the use of targets/quotas and financial incentives in family planning projects and requires projects to provide comprehensible information on family planning methods. Protects people who choose not to use family planning from being denied rights or benefits and requires experimental family planning methods be provided only in the context of a scientific study.

Intended to “promote voluntarism and prevent coercion in family planning programs,” it specifically prohibits three types of targets. Total number of births, number of family planning acceptors, and acceptors of a particular method of family planning.Voluntarism/Informed Choice &. Consent. Incentives and DisincentivesAll FP funds under State-Foreign Ops.Yes, in effect.Included in annual State-Foreign Ops.Reallocation of Funds Not Made Available to UNFPA (2004)Provides for funds not made available to UNFPA to be reallocated to USAID’s family planning, maternal, and reproductive health activities/services (and, in some years, assistance to vulnerable children and victims of trafficking in persons).UNFPA FundingFunds appropriated for UNFPAYes, in effect.Typically included in annual State-Foreign Ops.Medically Accurate Information on Condoms (2005)Ensures that information provided by U.S.-supported programs about the use of condoms is medically accurate information and includes the public health benefits and failure rates of such use.CondomsAll funds under State-Foreign Ops.Yes, in effect.Typically included in annual State-Foreign Ops.POLICYUSAID Policy Paper on Population Assistance (1982)Outlines the longstanding USAID guidelines surrounding its fundamental programmatic principles of voluntarism and informed choice and consent.Voluntarism/Informed Choice &. ConsentAll FP/RH assistance provided by USAIDYes, in effect.Policy Determination 3 (PD-3) and Addendum.

USAID Policy Guidelines on Voluntary Sterilization (1982)Describes guidelines for informed consent and voluntarism specifically for voluntary sterilization services, including provisions to ensure ready access to other contraceptive methods and prohibiting incentive payments that might induce a person to select voluntary sterilization over another method.Voluntarism/Informed Choice &. Consent. Voluntary SterilizationAll FP/RH assistance provided by USAIDYes, in effect.Mexico City Policy (“Global Gag Rule”, 1984) As a condition for receiving U.S. Family planning assistance and, now, also other global health assistance (see “Applies to”), requires foreign NGOs to certify that they will not perform or promote abortion as a method of family planning using funds from any source. Under the Trump administration, it was called “Protecting Life in Global Health Assistance” policy.Abortion1984- 2003.

When in effect, was applied to FP assistance at USAID only. In 2003, expanded to include all FP assistance at USAID and the State Dept., exempting multilateral organizations and HIV/AIDS funding under PEPFAR. 2009-17. Not in effect. 2017-21.

Applied to all global health assistance. 2021-present. Not in effect.No, not in effect.Not currently in force.USAID Post-Abortion Care Policy (2001)Clarifies that post-abortion care – the treatment of injuries or illnesses caused by legal or illegal abortion – is permitted under the Helms Amendment and that any restrictions under the Mexico City Policy, when in force, do not limit organizations from treating injuries or illnesses caused by legal or illegal abortions (i.e., providing post-abortion care). Notes USAID does not finance manual vacuum aspiration equipment purchase/distribution for any purpose.Post-Abortion CareAll FP/RH assistance provided by USAIDYes, in effect.Guidance on the Definition and Use of the Global Health Programs Account. Section on Allowable Uses of Funds for Family Planning/Reproductive Health (2014)Outlines allowable uses of funds for FP/RH by providing a description of activities allowed and examples of activities not allowed, addressing not only FP/RH activities but also family planning activities’ integration with other global health and multisectoral activities.FP/RH Activities.

FP/RH System Strengthening Activities. Integrated FP ActivitiesAll FP/RH assistance provided by USAIDYes, in effect.Updated periodically.PEPFAR FY 2021 Country and Regional Operational Plan GuidanceOutlines certain FP/RH activities that may be reported under specific PEPFAR budget categories, such as youth-friendly sexual and RH services that are part of prevention for adolescent girls and young women.HIV/AIDS Program Linkages with FP/RH Activities. Abortion“Wraparound” PEPFAR activities related to FP/RHYes, in effect.Updated annually.NOTES. PEPFAR= U.S. President’s Emergency Plan for AIDS Relief.

UNFPA= United Nations Population Fund. USAID= U.S. Agency for International Development..

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Funds be provided to organizations that offer, either directly or through referral to, information about access to a broad range of family planning methods and services. See Livingston-Obey Amendment (1986) below.Voluntarism/Informed ChoiceAll FP funds under State-Foreign Ops.Yes, in effect.Included in annual State-Foreign Ops.Kemp-Kasten Amendment (1985)Prohibits funding any organization or program, as determined by the President, that supports or participates in the management of a program of coercive abortion or involuntary sterilization.UNFPA Funding. Abortion.

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Language used beginning in FY00).It also prohibits UNFPA from using any funds from the U.S. Contribution in their programming in China.UNFPA Funding. AbortionFunds made available to UNFPAYes, in effect.Included in annual State-Foreign Ops.UNFPA Dollar-for-Dollar Withholding of Amount UNFPA Plans to Spend in China During Fiscal Year (1994)Reduces the U.S.

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Total number of births, number of family planning acceptors, and acceptors of a particular method of family planning.Voluntarism/Informed Choice &. Consent. Incentives and DisincentivesAll FP funds under State-Foreign Ops.Yes, in effect.Included in annual State-Foreign Ops.Reallocation of Funds Not Made Available to UNFPA (2004)Provides for funds not made available to UNFPA to be reallocated to USAID’s family planning, maternal, and reproductive health activities/services (and, in some years, assistance to vulnerable children and victims of trafficking in persons).UNFPA FundingFunds appropriated for UNFPAYes, in effect.Typically included in annual State-Foreign Ops.Medically Accurate Information on Condoms (2005)Ensures that information provided by U.S.-supported programs about the use of condoms is medically accurate information and includes the public health benefits and failure rates of such use.CondomsAll funds under State-Foreign Ops.Yes, in effect.Typically included in annual State-Foreign Ops.POLICYUSAID Policy Paper on Population Assistance (1982)Outlines the longstanding USAID guidelines surrounding its fundamental programmatic principles of voluntarism and informed choice and consent.Voluntarism/Informed Choice &.

ConsentAll FP/RH assistance provided by USAIDYes, in effect.Policy Determination 3 (PD-3) and Addendum. USAID Policy Guidelines on Voluntary Sterilization (1982)Describes guidelines for informed consent and voluntarism specifically for voluntary sterilization services, including provisions to ensure ready access to other contraceptive methods and prohibiting incentive payments that might induce a person to select voluntary sterilization over another method.Voluntarism/Informed Choice &. Consent.

Voluntary SterilizationAll FP/RH assistance provided by USAIDYes, in effect.Mexico City Policy (“Global Gag Rule”, 1984) As a condition for receiving U.S. Family planning assistance and, now, also other global health assistance (see “Applies to”), requires foreign NGOs to certify that they will not perform or promote abortion as a method of family planning using funds from any source. Under the Trump administration, it was called “Protecting Life in Global Health Assistance” policy.Abortion1984- 2003.

When in effect, was applied to FP assistance at USAID only. In 2003, expanded to include all FP assistance at USAID and the State Dept., exempting multilateral organizations and HIV/AIDS funding under PEPFAR. 2009-17.

Not in effect. 2017-21. Applied to all global health assistance.

2021-present. Not in effect.No, not in effect.Not currently in force.USAID Post-Abortion Care Policy (2001)Clarifies that post-abortion care – the treatment of injuries or illnesses caused by legal or illegal abortion – is permitted under the Helms Amendment and that any restrictions under the Mexico City Policy, when in force, do not limit organizations from treating injuries or illnesses caused by legal or illegal abortions (i.e., providing post-abortion care). Notes USAID does not finance manual vacuum aspiration equipment purchase/distribution for any purpose.Post-Abortion CareAll FP/RH assistance provided by USAIDYes, in effect.Guidance on the Definition and Use of the Global Health Programs Account.

Section on Allowable Uses of Funds for Family Planning/Reproductive Health (2014)Outlines allowable uses of funds for FP/RH by providing a description of activities allowed and examples of activities not allowed, addressing not only FP/RH activities but also family planning activities’ integration with other global health and multisectoral activities.FP/RH Activities. FP/RH System Strengthening Activities. Integrated FP ActivitiesAll FP/RH assistance provided by USAIDYes, in effect.Updated periodically.PEPFAR FY 2021 Country and Regional Operational Plan GuidanceOutlines certain FP/RH activities that may be reported under specific PEPFAR budget categories, such as youth-friendly sexual and RH services that are part of prevention for adolescent girls and young women.HIV/AIDS Program Linkages with FP/RH Activities.

Abortion“Wraparound” PEPFAR activities related to FP/RHYes, in effect.Updated annually.NOTES. PEPFAR= U.S. President’s Emergency Plan for AIDS Relief.

UNFPA= United Nations Population Fund. USAID= U.S. Agency for International Development..

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