Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features.

BACKGROUND: Cohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits. METHODS: Clinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations. RESULTS: We identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population. CONCLUSION: We suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup.

Differences in participation according to specific cognitive deficits following a stroke.

This study compared participation following a stroke according to the presence of specific cognitive deficits. Participation is defined as the involvement of a person in daily activities and social roles. Three weeks after being discharged home, 197 older adults (aged 65 years and older) who had a stroke were evaluated using the Assessment of Life Habits, which includes 12 domains of daily activities and social roles. The presence of a cognitive deficit was determined by the scores obtained on tests assessing memory, visual perception, language, unilateral attention, and the inhibition component of executive functions. After adjusting for depressive symptoms, time since stroke, and comorbidities, five of the domains of participation are significantly more restricted by some cognitive deficits. Memory deficits affect the communication (p = .006) and leisure (p = .032) domains. In the presence of visual perception deficits, the nutrition (p = .019), communication (p = .004), and responsibilities (p < .0005) domains are more limited. Language deficits have an impact on several domains of participation, namely communication (p < .0005), responsibilities (p < .0005), community life (p = .001), and leisure (p = .021). Unilateral neglect and deficits in the inhibition component of executive functions are not found to restrict participation. Overall, participation after stroke is related to cognitive function. Looking carefully at individual domains of activities and roles provides essential information in guiding rehabilitation interventions aimed at enhancing participation after discharge.

Leisure activities following a lower limb amputation.

PURPOSE: The aim of this study was to describe leisure activities, leisure satisfaction and constraints on participation in leisure following a unilateral lower limb amputation due to vascular disease. METHOD: This study used a mixed-method approach where 15 individuals with lower limb amputation completed the individual leisure profile 2-3 months post-discharge from rehabilitation. A subsample (n = 8) also participated in semi-structured interviews analysed using the Miles and Huberman analytic method. RESULTS: Results show that participants were involved in 12 different leisure activities on average. Compared to before the amputation, a decrease in participation was observed in all categories of leisure activity, and especially crafts, nature and outdoor activities, mechanics, sports and physical activities. Nonetheless, overall satisfaction was high. The most important constraints on participation in leisure were lack of accessibility, material considerations, functional abilities, affective constraints and social constraints. CONCLUSION: A decrease in leisure activity participation and the presence of constraints do not automatically translate into low levels of leisure satisfaction.

[A useful test for evaluating the needs for support of family members--help for an aged parent at home: a tool with potential application in French-speaking Europe]. / Mise à l'essai d'un outil d'évaluation des besoins de soutien des proches--aidants d'un parent âgé à domicile: un outil ayant un potentiel d'application en Europe francophone.

The Family Caregivers Support Agreement (FCSA) tool, based on a caregiver-service provider partnership approach to assess the support needs of family caregivers of a home-living aging relative, was field-tested to document its relevance for use in Quebec (Canada) practice settings. The FCSA tool is a modified version of the Carers Outcome Assessment Tool, initially developed as the result of an Anglo-Swedish Study. The field test was conducted with 17 French- and English-speaking caregivers and revealed numerous unmet caregiver needs, especially of a psycho-educational nature. The use of the FCSA tool lead to an identification of homecare support services which corresponded to caregiver needs and expectations. According to the homecare services providers interviewed, the FCSA tool offers a structured and flexible approach that facilitates the identification of services sensitive to caregiver needs. The instrument allows concretizing the partnership process, in particular, by bringing to light the unique needs of individual caregivers, empowering caregivers by considering them active participants in decision making, and fostering a proper fit between services and needs. Results are in line with those of other studies, suggesting that the caregiver role entails common core needs and that the impact of the FCSA tool is comparable regardless of practice setting. All told, the FCSA tool could potentially be applied in the French-speaking Europe.

Development of an intervention program for Alzheimer's family caregivers following diagnostic disclosure.

The purpose of this qualitative study was to develop a pro-active psycho-educational intervention program for Alzheimer's family caregivers following diagnostic disclosure. Based on a theoretical model of role transitions and a participatory approach, the study comprised four steps: (a) exploring caregiver needs; (b) developing and validating a program proposal based on caregiver-expressed needs; (c) formalizing program through intervention mapping; and (d) testing and qualitatively evaluating the program. The psycho-educational program consisted of seven individual sessions aimed at fostering knowledge and skills required to ensure successful transition to the caregiver role. The approach used in this study can serve as a guide for the development of nursing intervention programs. Intervention mapping allowed, in particular, integrating theoretical and empirical elements in a formal intervention model.

[Development of an adapted leisure education program for persons with dementia]. / Développement d'un programme d'éducation au loisir adapté comme moyen de soutien à l'implication d'aidants d'un proche atteint de démence.

Leisure represents a positive way to keep relationships satisfactory between caregivers and a person with dementia. Adapted leisure education is a promising approach to assist the family to discover new ways to share good times with their relatives. This study aimed to develop an adapted leisure education program. It included an evaluation of the caregivers' needs, the program content development, and a pilot study to experiment with the content of the program. Three focus groups of dementia caregivers (n = 19) were conducted to investigate caregivers needs. Based on content analysis of these focus groups and a literature review, the content of the program was developed. The pilot study (n = 4) included a quasi-experimental trial and an implementation evaluation. This study led to the development of an adapted leisure education program that puts caregiver support in a new perspective, focusing on positive aspects rather than the burden of caregiving.

[Validation of a tool for family caregivers]. / Validation d'un outil pour les proches-aidants.

The purpose of this transcultural study was to translate and adapt for the province of Quebec (Canada) a tool for assessing the support needs of family caregivers of aging persons, as well as to validate the relevance and feasibility of its utilization in Quebec homecare services. Developed jointly in the United Kingdom and Sweden and based on a caregiver-service provider partnership process, the Carers Outcome Agreement Tool (COAT) is presently the focus of a large-scale implementation study in Sweden. Following parallel back-translation and adaptation, the tool, entitled Entente sur le Soutien aux Proches-Aidants (ESPA) in French, was validated in terms of relevance and feasibility via focus groups with service providers and interviews with family caregivers. Results show the ESPA to be a culturally sensitive tool that systematically identifies the support needs of caregivers and indicates the type of help best suited to meet these needs. As with other European studies, the results suggest that the caregiver role comprises a common core of needs and highlights the tool's potential for transfer to the cultural context of French-speaking Europe.

Correlates of the perceived need for institutionalisation among older adults without cognitive impairment.

BACKGROUND: While many studies investigate the factors that influence the institutionalisation of older persons, only a few consider one of its most important predictors, namely, the perceived need for institutionalisation. Also referred to as 'desire for institutionalisation', it has mainly been investigated for informal caregivers of older adults suffering from dementia. Not many studies target caregivers of people without dementia; even fewer have been interested in the older adult's own perceived need. OBJECTIVE: To measure the prevalence and identify the correlates of the perceived need for institutionalisation among community-dwelling older adults without cognitive impairment. METHODS: During the fourth wave of the longitudinal PRISMA study, cognitive-impairment-free participants (78 years or older and at risk of functional decline) were presented with three questions assessing their perceived need for institutionalisation. Correlates were identified through multivariable logistic regression analyses. Analyses were conducted separately for two types of home living arrangements: individual and collective dwellings. RESULTS: 27% of the older adults at least thought about institutionalisation, irrespective of their current living arrangements. For homeowners/tenants, age ranging from 80 to 85, transfer and vision problems, the absence or advanced age of the informal caregiver, and the use of the ER or help for home maintenance during the past year led them to think about institutionalisation. Seniors living in collective dwellings think about institutionalisation after experiencing a recent highly significant functional decline, when feeling that their current environment fails to meet needs, and after requiring the use of voluntary services during the past year. CONCLUSIONS: The percentage of community-dwelling older adults considering institutionalisation is the same for people currently in individual or collective settings. Factors related to physical disabilities and insufficiencies of resources are important correlates, with specific factors differing between the two types of current living arrangements.

Empowerment interventions, knowledge translation and exchange: perspectives of home care professionals, clients and caregivers.

BACKGROUND: Few studies have examined empowerment interventions as they actually unfold in home care in the context of chronic health problems. This study aims to document the empowerment process as it plays out in interventions with adults receiving home care services. METHODS/DESIGN: The qualitative design chosen is a fourth generation evaluation combined with case studies. A home care team of a health and social services center situated in the Eastern Townships (Québec, Canada) will be involved at every step in the study. A sample will be formed of 15 health care professionals and 30 of their home care clients and caregiver. Semi-structured interviews, observations of home care interventions and socio-demographic questionnaires will be used to collect the data. Nine instruments used by the team in prior studies will be adapted and reviewed. A personal log will document the observers' perspectives in order to foster objectivity and the focus on the intervention. The in-depth qualitative analysis of the data will illustrate profiles of enabling interventions and individual empowerment. DISCUSSION: The ongoing process to transform the health care and social services network creates a growing need to examine intervention practices of health care professionals working with clients receiving home care services. This study will provide the opportunity to examine how the intervention process plays out in real-life situations and how health care professionals, clients and caregivers experience it. The intervention process and individual empowerment examined in this study will enhance the growing body of knowledge about empowerment.

Defining spirituality and giving meaning to occupation: the perspective of community-dwelling older adults with autonomy loss.

BACKGROUND: In the Canadian Model of Occupational Performance, meaningful occupation involves interaction between spirituality and environment. However little research exists on the process of giving meaning to occupation. PURPOSE: This study explored both meaningful occupation and the definition of spirituality from the perspective of community-dwelling older adults with autonomy loss. METHOD: Using a qualitative approach, grounded theory method of Glaser and Strauss (1967), eight cognitively intact persons were interviewed individually. RESULTS: The process of giving meaning to occupation involves an intrinsic link between identity and meaningful occupation, with identity being central to the person. Following autonomy loss, a process of adjusting identity, involving social, psychological and spiritual aspects, occurs over time. Spirituality is defined in terms of its close links to religion and belief in a benevolent greater power. IMPLICATIONS OF RESEARCH: This study contributes to the discussion of the concepts of spirituality, identity and meaning in occupational therapy.

Concordance of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization Using Tissue Microarray in Breast Cancer.

AIM: Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are common methods for assessment of human epidermal growth factor receptor 2 (HER2) in breast cancer. MATERIALS AND METHODS: In a cohort of 498 consecutive patients with breast cancer, we examined concordance between IHC and FISH for HER2 on tissue microarray (TMA) sections. In a subset of 116 specimens, we examined HER2 concordance from the block used for diagnostics and a randomly-chosen additional block (a proxy of the core biopsy). RESULTS: Overall concordance between both methods on TMA sections was 93.8% and between HER2, determined on diagnostic and additional blocks, was 93.6% for IHC and 98.0% for FISH. CONCLUSION: Since some cases were discordant, we suggest that both methods be used for HER2 assessment. The lower concordance rate between diagnostic and additional blocks using IHC compared to FISH suggests a greater variability of IHC staining across tumor regions than for FISH results.

Older husbands as caregivers of their wives: a descriptive study of the context and relational aspects of care.

The purpose of this study was to describe the context and relational aspects that characterize male caregiving. The sample comprised 323 older husbands caring for their wives in Quebec (Canada). Nearly 60% of them spent at least 84 h/week caregiving and about 40% regularly performed personal care and instrumental tasks. Family provided emotional support above all and service utilization was limited for certain services. Husbands perceived relational deprivation but also personal gain relative to their role. Conflicts seldom occurred with family members. Comparisons between husbands of wives with and without memory problems revealed selected differences on context and relational variables. This study contributes to knowledge on male caregivers and provides directions for nursing practice and research.

Deciding on institutionalization for a relative with dementia: the most difficult decision for caregivers.

The decision to move a family member with dementia to a nursing home is a difficult experience for caregivers. Complex psychosocial factors are involved and knowledge of predictive factors alone is insufficient. Using grounded theory, this study explores the decision-making process with regards to institutionalization, from the perspective of family caregivers. Fourteen people who moved a relative to long-term care in the preceding 6 months were interviewed. Data analysis using comparative analysis and line-by-line dimensional analysis was used to develop a theoretical model of the decision-making process. Three factors within the model were central to the process: (a) caregivers' perceptions of their ability to provide care, (b) caregivers' evaluations of their relatives' ability to make care decisions, and (c) the evolving influence of contextual factors and interactions with healthcare professionals. The contribution of these findings to new conceptualizations of institutionalization is discussed.

Tissue Microarray Is a Reliable Tool for the Evaluation of HER2 Amplification in Breast Cancer.

AIM: We examined an economical method for evaluating the amplification of the human epidermal growth factor receptor 2 (HER2) gene in breast cancer specimens. MATERIALS AND METHODS: We compared HER2 amplification determined by fluorescence in situ hybridization (FISH) on whole-tissue (WT) blocks used for diagnostic and on tissue microarray (TMA) sections for a cohort of 521 consecutive patients with breast cancer. In a subset of 116 patients, we examined HER2 concordance from the WT section and a TMA section from a randomly chosen additional block (a proxy of the core biopsy). RESULTS: Overall concordance for HER2 amplification between WT and TMA sections was 98.2%, and between sections from WT and from the additional block was 99.0%. CONCLUSION: The high concordance rates support the use of TMA for the evaluation of HER2 amplification in breast cancer and suggest that FISH can be used to assess HER2 using core biopsies.

Deciding whether to continue, share, or relinquish caregiving: caregiver views.

Using grounded theory, the authors explore informal caregiving and develop the beginnings of a substantive caregiving theory explaining some of the decision making involved in providing care to an older family member. Sixteen caregivers (CGs) participated in the study. Line-by-line and dimensional analyses reveal various purposes of caregiving for an older family member. These purposes influence whether and how CGs continue to provide the care or decide to share or relinquish caregiving to health care providers. This study suggests that a broader conceptualization of caregiving is needed to illuminate fully the complexity involved in providing care to older adults.

Validation of EP1 antibody clone for estrogen receptor immunohistochemistry in breast cancer.

Estrogen receptor (ER) tumor's status is critical for breast cancer management. A new rabbit antibody clone, EP1, is now available for ER status determination. The objective was to validate the EP1 antibody clone for its use in breast cancer ER status determination in a clinical setting against the previous standard, SP1. EP1 clone was assessed in 130 consecutive cases, including 50 ER-negative (<1% ER expression), 13 ER-low-positive (1% to 9% ER expression), and 67 ER-positive (≥10% ER expression). Using EP1 versus SP1, positive agreement (sensibility) was 92.5% and negative agreement (specificity) was 100%, leading to an overall agreement of 95.4%. All discordant cases (n=6) were ER-low-positive. SP1 was remeasured in 13 ER-low-positive and in 11 ER-negative cases. Overall agreement between SP1 initial tumor status and reassessment was 70.8% in those negative and low-positive cases. In conclusion, EP1 antibody has been validated for use in breast cancer with a positive agreement ≥90% and a negative agreement ≥95%, as recommended. Also, overall agreement between EP1 and SP1 was as good as between the SP1 initial status and SP1 reassessment.

Veridical mapping in savant abilities, absolute pitch, and synesthesia: an autism case study.

An enhanced role and autonomy of perception are prominent in autism. Furthermore, savant abilities, absolute pitch, and synesthesia are all more commonly found in autistic individuals than in the typical population. The mechanism of veridical mapping has been proposed to account for how enhanced perception in autism leads to the high prevalence of these three phenomena and their structural similarity. Veridical mapping entails functional rededication of perceptual brain regions to higher order cognitive operations, allowing the enhanced detection and memorization of isomorphisms between perceptual and non-perceptual structures across multiple scales. In this paper, we present FC, an autistic individual who possesses several savant abilities in addition to both absolute pitch and synesthesia-like associations. The co-occurrence in FC of abilities, some of them rare, which share the same structure, as well as FC's own accounts of their development, together suggest the importance of veridical mapping in the atypical range and nature of abilities displayed by autistic people.

Validation of a new classifier for the automated analysis of the human epidermal growth factor receptor 2 (HER2) gene amplification in breast cancer specimens.

Amplification of the human epidermal growth factor receptor 2 (HER2) is a prognostic marker for poor clinical outcome and a predictive marker for therapeutic response to targeted therapies in breast cancer patients. With the introduction of anti-HER2 therapies, accurate assessment of HER2 status has become essential. Fluorescence in situ hybridization (FISH) is a widely used technique for the determination of HER2 status in breast cancer. However, the manual signal enumeration is time-consuming. Therefore, several companies like MetaSystem have developed automated image analysis software. Some of these signal enumeration software employ the so called "tile-sampling classifier", a programming algorithm through which the software quantifies fluorescent signals in images on the basis of square tiles of fixed dimensions. Considering that the size of tile does not always correspond to the size of a single tumor cell nucleus, some users argue that this analysis method might not completely reflect the biology of cells. For that reason, MetaSystems has developed a new classifier which is able to recognize nuclei within tissue sections in order to determine the HER2 amplification status on nuclei basis. We call this new programming algorithm "nuclei-sampling classifier". In this study, we evaluated the accuracy of the "nuclei-sampling classifier" in determining HER2 gene amplification by FISH in nuclei of breast cancer cells. To this aim, we randomly selected from our cohort 64 breast cancer specimens (32 nonamplified and 32 amplified) and we compared results obtained through manual scoring and through this new classifier. The new classifier automatically recognized individual nuclei. The automated analysis was followed by an optional human correction, during which the user interacted with the software in order to improve the selection of cell nuclei automatically selected. Overall concordance between manual scoring and automated nuclei-sampling analysis was 98.4% (100% for nonamplified cases and 96.9% for amplified cases). However, after human correction, concordance between the two methods was 100%. We conclude that the nuclei-based classifier is a new available tool for automated quantitative HER2 FISH signals analysis in nuclei in breast cancer specimen and it can be used for clinical purposes.

Cognitive appraisal and perceived benefits of dysvascular lower limb amputation: a longitudinal study.

This study aimed to: (i) compare the adjustment of individuals who have a positive appraisal of their amputation with those who have a negative appraisal; and (ii) identify the perceived benefits of amputation. Sixteen individuals who had a lower limb amputation (nine men and seven women) completed questionnaires during hospitalization (T1), rehabilitation (T2) and after discharge (T3). A subsample (n=10) also participated in semi-structured interviews. Participants who had a positive appraisal of their amputation showed greater functional independence (T1) and greater body image satisfaction (T3) than those with negative appraisal. From interviews, the perceived benefits identified were less pain, more social contacts, fewer health concerns and fewer demands from family and friends. Positive appraisal of the amputation is experienced by many people, thus requiring more attention in future research.