28 research outputs found
Intercellular adhesion mediated by human muscle neural cell adhesion molecule: effects of alternative exon use.
The effects of violence and aggression from parents on child protection workers' personal, family and professional lives
Creative Commons CC-BY: This article is distributed under the terms of the Creative Commons Attribution 3.0 License (http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).This article presents findings from a survey of the experiences of child protection workers in England when working with parents who exhibit aggression and violence. This work explores the effects on workers in their professional lives, and on themselves and their families in their private lives. The article examines workers’ thoughts and experiences about the effects of parental hostility on workers’ ability to protect children. The article also details workers’ experiences of the nature and effectiveness of training and support in this area. These findings are then examined in the light of the results of an analysis of the literature, including the findings from serious case review (SCR) reports in England (official inquiries into the causes of child deaths where the children are known to social and health services). The majority of the 590 respondents in the survey were social workers (n = 402; 68%), reflecting the fact that case management of child protection cases in the United Kingdom is the responsibility of social workers working in statutory agencies. This article addresses, from a consideration of the secondary analysis and the original research findings from the survey, how individual workers, managers, and agencies can best understand and then respond effectively to aggressive parental behaviors.Peer reviewe
The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients
The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis
Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study
Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation
Intercellular adhesion mediated by neural cell adhesion molecules in transfected 3T3 fibroblasts
An outreach geriatric medication advisory service in residential aged care: a randomised controlled trial of case conferencing
First published online: September 22, 2004Background: efficient strategies are needed to provide specialist advice in nursing homes to ensure quality medical care. We describe a case conference intervention involving a multidisciplinary team of health professionals. Objectives: to evaluate the impact of multidisciplinary case conferences on the appropriateness of medications and on patient behaviours in high-level residential aged care facilities. Design: cluster-randomised controlled trial. Setting: ten high-level aged care facilities. Participants: 154 residents with medication problems and/or challenging behaviours were selected for case conference by residential care staff. Intervention: two multidisciplinary case conferences involving the resident's general practitioner, a geriatrician, a pharmacist and residential care staff were held at the nursing home for each resident. Measurements: outcomes were assessed at baseline and 3 months. The primary outcome was the Medication Appropriateness Index (MAI). The behaviour of each resident was assessed via the Nursing Home Behaviour Problem Scale. Results: 45 residents died before follow-up. Medication appropriateness improved in the intervention group [MAI mean change 4.1, 95% confidence interval (CI) 2.1–6.1] compared with the control group (MAI mean change 0.4, 95% CI –0.4–1.2; P < 0.001). There was a significant reduction in the MAI for benzodiazepines (mean change control –0.38, 95% CI –1.02–0.27 versus intervention 0.73, 95% CI 0.16–1.30; P = 0.017). Resident behaviours were unchanged after the intervention and the improved medication appropriateness did not extend to other residents in the facility. Conclusion: multidisciplinary case conferences in nursing homes can improve care. Outreach specialist services can be delivered without direct patient contact and achieve improvements in prescribing.Maria Crotty, Julie Halbert, Debra Rowett, Lynne Giles, Robert Birks, Helena Williams and Craig Whitehea