Extending the phenotypes associated with TRIO gene variants in a cohort of 25 patients and review of the literature.

The TRIO gene encodes a rho guanine exchange factor, the function of which is to exchange GDP to GTP, and hence to activate Rho GTPases, and has been described to impact neurodevelopment. Specific genotype-to-phenotype correlations have been established previously describing striking differentiating features seen in variants located in specific domains of the TRIO gene that are associated with opposite effects on RAC1 activity. Currently, 32 cases with a TRIO gene alteration have been published in the medical literature.

Identification and analysis of deletion breakpoints in four Mohr-Tranebjærg syndrome (MTS) patients.

Mohr-Tranebjærg syndrome is an X-linked syndrome characterized by sensorineural hearing impairment in childhood, followed by progressive neurodegeneration leading to a broad phenotypic spectrum. Genetically MTS is caused by pathogenic variants in the TIMM8A gene, including gene deletions and larger contiguous gene deletions. Some of the latter involve the neighboring gene BTK, resulting in agammaglobulinemia.

Complex skills are required for new primary health care researchers: a training program responds.

Background: Current dimensions of the primary health care research (PHC) context, including the need for contextualized research methods to address complex questions, and the co-creation of knowledge through partnerships with stakeholders - require PHC researchers to have a comprehensive set of skills for engaging effectively in high impact research.

Main Body: In 2002 we developed a unique program to respond to these needs - Transdisciplinary Understanding and Training on Research - Primary Health Care (TUTOR-PHC). The program's goals are to train a cadre of PHC researchers, clinicians, and decision makers in interdisciplinary research to aid them in tackling current and future challenges in PHC and in leading collaborative interdisciplinary research teams.

Developing and testing a principle-based fidelity index for peer support in mental health services.

Purpose: Evidence suggests that the distinctive relational qualities of peer support-compared to clinical-patient relationships-can be eroded in regulated healthcare environments. Measurement of fidelity in trials of peer support is lacking. This paper reports the development and testing of a fidelity index for one-to-one peer support in mental health services, designed to assess fidelity to principles that characterise the distinctiveness of peer support.

The prevalence of faecal incontinence in myotonic dystrophy type 1.

Faecal incontinence is recognised as a feature of myotonic dystrophy along with other symptoms of bowel dysfunction, but its prevalence is poorly defined. We have surveyed 152 unselected myotonic dystrophy patients. We identified issues with bowel control in 104 (68% of the study population).

Co-producing Randomized Controlled Trials: How Do We Work Together?

In the light of the declaration "Nothing about us without us" (Charlton, 2000), interest in co-production, and coproduced research is expanding. Good work has been done establishing principles for co-production (Hickey et al., 2018) and for good quality involvement (Involve, 2013; 4Pi, 2015) and describing how this works in practice in mental health research (Gillard et al.

Discourses Reproducing Gender Inequities in Hospice Palliative Home Care.

Background: As home is a site where gendered attitudes, beliefs, and practices are reproduced, it is imperative that policies and practices promote gender equity in end-of-life care at home.

Purpose: The purpose of this study was to critically analyze gender relations in the sociopolitical context of hospice palliative home care.

Methods: Using a critical feminist perspective, we examined gender relations between and among clients with cancer, their family caregivers, and nurses in hospice palliative home care.

De novo repeat interruptions are associated with reduced somatic instability and mild or absent clinical features in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a multisystem disorder, caused by expansion of a CTG trinucleotide repeat in the 3'-untranslated region of the DMPK gene. The repeat expansion is somatically unstable and tends to increase in length with time, contributing to disease progression. In some individuals, the repeat array is interrupted by variant repeats such as CCG and CGG, stabilising the expansion and often leading to milder symptoms.

Evaluating dementia home care practices: The reification of care norms.

This critical ethnographic study examined how power relations shape the nature and enactment of caregivers' evaluation of home-based dementia care practices. As the home care sector continues to evolve and prepare itself as a key element in caring for people living with dementia and their families, this study grounds our understanding of how dementia home care practices are enacted and evaluated, particularly at the interface of formal and familial caregiving. The critical finding from our data is that not all evaluations of care practices were considered equally meaningful or relevant, and, moreover, their significance depended on whether the evaluation was made by someone in a position of power.

Correction: Elevated plasma levels of cardiac troponin-I predict left ventricular systolic dysfunction in patients with myotonic dystrophy type 1: A multicentre cohort follow-up study.

[This corrects the article DOI: 10.1371/journal.pone.

Elevated plasma levels of cardiac troponin-I predict left ventricular systolic dysfunction in patients with myotonic dystrophy type 1: A multicentre cohort follow-up study.

Objective: High sensitivity plasma cardiac troponin-I (cTnI) is emerging as a strong predictor of cardiac events in a variety of settings. We have explored its utility in patients with myotonic dystrophy type 1 (DM1).

Methods: 117 patients with DM1 were recruited from routine outpatient clinics across three health boards.

Structural impact on gendered expectations and exemptions for family caregivers in hospice palliative home care.

Evidence of gender differences in the amount and type of care provided by family caregivers in hospice palliative home care suggests potential inequities in health and health care experiences. As part of a larger critical ethnographic study examining gender relations among clients with cancer, their family caregivers and primary nurses, this article describes gendered expectations and exemptions for family caregivers within the sociopolitical context of end-of-life at home. Data were collected from in-depth interviews (n = 25), observations of agency home care visits (n = 9) and analyses of policy and home care agency documents (n = 12).

Integrating population variation and protein structural analysis to improve clinical interpretation of missense variation: application to the WD40 domain.

We present a generic, multidisciplinary approach for improving our understanding of novel missense variants in recently discovered disease genes exhibiting genetic heterogeneity, by combining clinical and population genetics with protein structural analysis. Using six new de novo missense diagnoses in TBL1XR1 from the Deciphering Developmental Disorders study, together with population variation data, we show that the β-propeller structure of the ubiquitous WD40 domain provides a convincing way to discriminate between pathogenic and benign variation. Children with likely pathogenic mutations in this gene have severely delayed language development, often accompanied by intellectual disability, autism, dysmorphology and gastrointestinal problems.

Gendered Processes in Hospice Palliative Home Care for Seniors With Cancer and Their Family Caregivers.

There has been limited investigation into the processes that shape gender (in)equities in hospice palliative home care. As part of a larger critical ethnographic study, we examined how and why gender relations occur in this context. Using a critical feminist lens, we conducted in-depth interviews with clients living with terminal cancer, their family caregivers and primary nurses; observations of agency home visits; and review of institutional documents.

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy.

Objective: To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene.

Methods: Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1.

Results: We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations.

Enacting Fall Prevention in Community Outreach Care.

Despite increased international concern about fall prevention throughout the past 20 years, only limited attention has been paid to the experiences and perspectives of health care providers who deliver fall prevention programs. The purpose of this interpretive phenomenological study was to explore the meaning of the experience of enacting fall prevention, through individual semistructured interviews, among 6 members of an interprofessional geriatric outreach team in Ontario, Canada. Findings suggest that enacting careful practice was essential to the experience of enacting fall prevention, represented by four interrelated phenomenological themes: caring fully for older clients, carefully seeing older clients in their life contexts, enacting therapeutic relationships, and experiential learning in interprofessional teams.

An evaluation of the effectiveness of engaging Canadian clients as partners in in-home care.

This exploratory quasi-experimental evaluation assessed the effectiveness of the use of a concrete discussion guide to promote organisation-wide application of a partnering approach to engage older home-care clients with chronic disease/disabilities as care partners. A post-test-only design with an independent pre-test sample was used to compare selected outcomes with those of standard in-home care. The theoretically informed discussion guide portrayed how to go about the process of empowering partnering by using language and open-ended conversational leads to construct partnering, partnering effort and health as a resource for everyday living through social interaction.

Social-Interaction Knowledge Translation for In-Home Management of Urinary Incontinence and Chronic Care.

Although urinary incontinence (UI) can be managed conservatively, it is a principal reason for the breakdown of in-home family care. This study explored the social interaction processes of knowledge translation (KT) related to how UI management knowledge might be translated within in-home care. In-depth interview data were collected from a theoretical sample of 23 family caregivers, older home care recipients, and home care providers.

Making care decisions in home-based dementia care: why context matters.

The hours of unpaid elder care by family members are projected to triple by 2038. Because living with dementia can inhibit decision-making abilities, family members are often besought to assist in this process. In this ethnographic study, relationships within home-based dementia care were critically examined through face-to-face interviews and participant observations with clients, family caregivers, and home care providers (n = 51).

The meaning of a positive client-nurse relationship for senior home care clients with chronic disease.

This study explored the meaning of a positive client-nurse relationship for seniors with chronic disease receiving in-home care. In this phenomenological study, eight participants aged 65 to 86 were purposefully selected from the Southwest Community Care Access Centre (SW-CCAC) in London, Ontario. Narrative data were collected through audiotaped, in-depth interviews using a semi-structured interview guide.

Relational experiences of family caregivers providing home-based end-of-life care.

The multiple relationships involved in home-based end-of-life care have received little systematic analysis. As part of a focused ethnographic study examining client-caregiver-provider relational care experiences within the sociocultural context of home-based end-of-life care, this article describes the provision of end-of-life care to older adults with advanced cancer from the perspective of family caregivers. Data were collected through in-depth interviews (n = 16) with 4 family caregivers and participant observations in each of the 4 households over a 6- to 8-month period.

Negotiating relational practice patterns in palliative home care.

Providing palliative care in the home presents a variety of challenges for nurses and other care providers. As part of a focused ethnographic study examining client/caregiver/care-provider relationships within the socio-cultural context of home-based palliative care, this paper describes the provision of palliative care to Canadian seniors with advanced cancer from the perspective of nurses. Data were collected through in-depth interviews (n=19) with three palliative care nurses and participant observations in four households over a six-to-eight-month period.