91 research outputs found
A call to introduce newborn screening for spinal muscular atrophy (SMA) in Scotland
Peer reviewedPublisher PD
Introduction
LâidĂ©e dâ« art social » semble aussi prĂ©sente au xixe siĂšcle que demeurent difficiles Ă cerner son Ă©volution, sa polysĂ©mie et ses mises en Ćuvre artistiques, critiques et politiques. Si de nombreux chercheurs de la pĂ©riode 1830-1920 sây sont intĂ©ressĂ©s plus ou moins directement, aucune Ă©tude dâensemble des termes et concepts, des textes de rĂ©fĂ©rence ou des ancrages socio-historiques nâa Ă©tĂ© entreprise pour la totalitĂ© de la pĂ©riode. Pourtant, lâintĂ©rĂȘt portĂ© aux arts par des penseurs et milit..
LâArt social de la RĂ©volution Ă la Grande Guerre
DĂ©veloppĂ©e en France au lendemain de la RĂ©volution, lâidĂ©e dâart social, qui interroge la fonction de lâart dans une sociĂ©tĂ© postrĂ©volutionnaire, industrielle et marchande, recouvre des acceptions diverses. Si elle a dâabord participĂ© Ă lâabolition des classes sociales, contribuĂ© au dĂ©veloppement de lâĂ©ducation populaire et finalement renouvelĂ© le concept mĂȘme dâart, elle a pu aussi servir, sous la TroisiĂšme RĂ©publique, le maintien des hiĂ©rarchies existantes et ĂȘtre pensĂ©e dans le cadre de la politique artistique de lâĂtat. Ce nâest donc pas une mais des conceptions de lâart social qui ont Ă©tĂ© dĂ©fendues, soutenues par des thĂ©oriciens politiques, des philosophes et des artistes. Cette notion a fait lâobjet dâune recherche menĂ©e sous la direction de Neil McWilliam, Catherine MĂ©neux et Julie Ramos, et a dĂ©bouchĂ© sur deux publications : un volume de 23 essais qui permettent de mesurer la diversitĂ© et lâoriginalitĂ© des formes quâa pu revĂȘtir lâidĂ©e dâart social (coĂ©dition INHA-Presses universitaires de Rennes), et cette anthologie en ligne, riche de plus de 110 textes sources prĂ©sentĂ©s, commentĂ©s et illustrĂ©s
The expression of epidermal growth factor and transforming growth factor-α mRNA in the small intestine of suckling rats: organ culture study
AbstractEpidermal growth factor (EGF) and transforming growth factor-α (TGF-α) are associated with regulation of various gastrointestinal functions. In order to better understand their role in developing small intestine EGF, TGF-α and EGF-R steady-state mRNA levels and transcript stability were determined. Reverse transcription (RT) competitive-polymerase chain reaction (PCR) revealed that intestinal TGF-α mRNA levels were 10-fold higher in comparison with EGF mRNA. The primary intestinal culture technique was used to evaluate mRNA stability. The stability of TGF-α mRNA was remarkably lower than the stability of EGF mRNA. High levels of TGF-α mRNA accompanied by high degradation rate of this mRNA suggested a rapid turnover of intestinal TGF-α mRNA
Dementia Home Care Resources: How Are We Managing?
With the number of people living with dementia expected to more than double within the next 25 years, the demand for dementia home care services will increase. In this critical ethnographic study, we drew upon interview and participant data with persons with dementia, family caregivers, in-home providers, and case managers in nine dementia care networks to examine the management of dementia home care resources. Three interrelated, dialectical themes were identified: (1) finite formal care-inexhaustible familial care, (2) accessible resources rhetoric-Iinaccessible resources reality, and (3) diminishing care resources-increasing care needs. The development of policies and practices that provide available, accessible, and appropriate resources, ensuring equitable, not necessarily equal, distribution of dementia care resources is required if we are to meet the goal of aging in place now and in the future
Evolving the theory and praxis of knowledge translation through social interaction: a social phenomenological study
Background: As an inherently human process fraught with subjectivity, dynamic interaction, and change, social interaction knowledge translation (KT) invites implementation scientists to explore what might be learned from adopting the academic tradition of social constructivism and an interpretive research approach. This paper presents phenomenological investigation of the second cycle of a participatory action KT intervention in the home care sector to answer the question: What is the nature of the process of implementing KT through social interaction?
Methods: Social phenomenology was selected to capture how the social processes of the KT intervention were experienced, with the aim of representing these as typical socially-constituted patterns. Participants (n = 203), including service providers, case managers, administrators, and researchers organized into nine geographically-determined multi-disciplinary action groups, purposefully selected and audiotaped three meetings per group to capture their enactment of the KT process at early, middle, and end-of-cycle timeframes. Data, comprised of 36 hours of transcribed audiotapes augmented by researchers\u27 field notes, were analyzed using social phenomenology strategies and authenticated through member checking and peer review.
Results: Four patterns of social interaction representing organization, team, and individual interests were identified: overcoming barriers and optimizing facilitators; integrating \u27science push\u27 and \u27demand pull\u27 approaches within the social interaction process; synthesizing the research evidence with tacit professional craft and experiential knowledge; and integrating knowledge creation, transfer, and uptake throughout everyday work. Achieved through relational transformative leadership constituted simultaneously by both structure and agency, in keeping with social phenomenology analysis approaches, these four patterns are represented holistically in a typical construction, specifically, a participatory action KT (PAKT) model.
Conclusion: Study findings suggest the relevance of principles and foci from the field of process evaluation related to intervention implementation, further illuminating KT as a structuration process facilitated by evolving transformative leadership in an active and integrated context. The model provides guidance for proactively constructing a \u27fit\u27 between content, context, and facilitation in the translation of evidence informing professional craft knowledge
Identification and analysis of deletion breakpoints in four Mohr-TranebjĂŠrg syndrome (MTS) patients
Mohr-TranebjĂŠrg 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. By next-generation mate-pair sequencing we have mapped the chromosomal deletion breakpoints of one MTS case and three XLA-MTS cases and used breakpoint-spanning PCR to fine map the breakpoints by Sanger sequencing. Two of the XLA-MTS cases presented with large deletions (63.5 and 27.2Â kb), and the junctional regions were characterized by long stretches of microhomology, indicating that the events have emerged through homologous recombination. Conversely, the MTS case exhibited a small 2Â bp region of microhomology, and the regions were not characterized by extensive microhomology. The third XLA-MTS case had a more complex breakpoint, including a 59Â bp inverted insertion, thus at least four breakpoints were involved in this event. In conclusion, mate-pair library generation combined with next-generation sequencing is an efficient method for breakpoint identification, also in regions characterized by repetitive elements
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 ÎČ-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. Amino acids affected by likely pathogenic missense mutations are either crucial for the stability of the fold, forming part of a highly conserved symmetrically repeating hydrogen-bonded tetrad, or located at the top face of the ÎČ-propeller, where âhotspotâ residues affect the binding of ÎČ-catenin to the TBLR1 protein. In contrast, those altered by population variation are significantly less likely to be spatially clustered towards the top face or to be at buried or highly conserved residues. This result is useful not only for interpreting benign and pathogenic missense variants in this gene, but also in other WD40 domains, many of which are associated with disease
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. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features.
CONCLUSION
Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions
Fine-scale variability in coral bleaching and mortality during a marine heatwave
Coral bleaching and mortality can show significant spatial and taxonomic heterogeneity at local scales, highlighting the need to understand the fine-scale drivers and impacts of thermal stress. In this study, we used structure-from-motion photogrammetry to track coral bleaching, mortality, and changes in community composition during the 2019 marine heatwave in KÄneÊ»ohe Bay, HawaiÊ»i. We surveyed 30 shallow reef patches every 3 weeks for the duration of the bleaching event (August-December) and one year after, resulting in a total of 210 large-area, high-resolution photomosaics that enabled us to follow the fate of thousands of coral colonies through time. We also measured environmental variables such as temperature, sedimentation, depth, and wave velocity at each of these sites, and extracted estimates of habitat complexity (rugosity R and fractal dimension D) from digital elevation models to better understand their effects on patterns of bleaching and mortality. We found that up to 80% of corals experienced moderate to severe bleaching in this period, with peak bleaching occurring in October when heat stress (Degree Heating Weeks) reached its maximum. Mortality continued to accumulate as bleaching levels dropped, driving large declines in more heat-susceptible species (77% loss of Pocillopora cover) and moderate declines in heat-tolerant species (19% and 23% for Porites compressa and Montipora capitata, respectively). Declines in live coral were accompanied by a rapid increase in algal cover across the survey sites. Spatial differences in bleaching were significantly linked to habitat complexity and coral species composition, with reefs that were dominated by Pocillopora experiencing the most severe bleaching. Mortality was also influenced by species composition, fractal dimension, and site-level differences in thermal stress. Our results show that spatial heterogeneity in the impacts of bleaching are driven by a mix of environmental variation, habitat complexity, and differences in assemblage composition
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