Prevalence, morbidity and service need among South Asian and white adults with intellectual disability in Leicestershire, UK

Background Previous reports have suggested that South Asian and white UK populations have different prevalences of intellectual disability (ID), related psychological morbidity and service use. The aim of the present study was to compare these rates among South Asian and white adults in Leicestershire, UK. Method This cross‐sectional study is comprised of two parts. The analysis of prevalence is based on data from all South Asian and white adults known to the Leicestershire Learning Disabilities Register in 1991, with population denominators being drawn from the 1991 census. The other analyses use data collected from the most recent semi‐structured home interviews, carried out between 1987 and 1998, with 206 South Asian and 2334 white adults. Results The prevalence of ID in adults in Leicestershire is 3.20 per 1000 in South Asians and 3.62 per 1000 in whites. Among adults with ID, South Asians have similar prevalences of disabilities to whites and significantly lower skill levels. South Asians show similar levels of psychological morbidity, but make significantly lower use than whites of psychiatric services, residential care and respite care. South Asians use community services as extensively as whites, but feel that they have a substantially greater unmet need, especially with regard to social services. Conclusion South Asian and white populations have similar prevalences of ID and related psychological morbidity. Culturally appropriate services for South Asian adults may need to focus on skill development and community care.     

Physical aggression towards others in adults with learning disabilities: prevalence and associated factors

Background Many people with learning disabilities (LD) show aggressive behaviour, but the extent of the problem and its associated factors and effects are unclear. Methods A cross‐sectional analysis was carried out using interview data from 3065 adults with LD on the Leicestershire LD Register. Physical aggression towards others was defined as carers reporting frequent (more than three times per week) and/or severe episodes. Individuals with and without aggression were compared using multiple logistic regression models for potential physical and psychological factors. Results Carers reported that 443 (14%) of adults were physically aggressive towards others. Men (P = 0.001), younger individuals (P < 0.001), people with more severe LD (P < 0.001) and those in institutional settings (P < 0.001) had a significantly higher prevalence of physical aggression. People with Down syndrome had a lower prevalence of physical aggression (P < 0.001). After adjustment, we found no relationship between aggression and the presence of epilepsy or autism. Among psychological factors, symptoms of frustration (P < 0.001) and mood swings (P < 0.001) were associated with higher levels of aggression. Failure to cope among carers was reported by 14% overall: 42% of people caring for adults with aggression said they were unable to cope compared with 10% of those caring for adults without aggression. Conclusions Physical aggression towards other people presents a significant challenge to carers of adults with LD. Further research is needed to identify aetiological factors with a view to finding effective interventions to reduce, and improve management of, this behaviour.     

Bivalent non-typhoidal Salmonella outer membrane vesicles immunized mice sera confer passive protection against gastroenteritis in a suckling mice model

Invasive non-typhoidal Salmonella (iNTS) serovars, especially Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE), cause gastroenteritis worldwide. Due to the emergence of multi-drug resistance in iNTS, a broad-spectrum vaccine is urgently needed for the prevention of iNTS infection. Currently, there is no effective licensed vaccine against iNTS available in the market. We have formulated an outer membrane vesicles (OMVs) based bivalent immunogen as a vaccine candidate to generate broad-spectrum protective immunity against both recently circulating prevalent ST and SE. We have isolated OMVs from ST and SE and formulated the immunogen by mixing both OMVs (1:1 ratio). Three doses of bivalent immunogen significantly induced humoral immune responses against lipopolysaccharides (LPSs) and outer membrane proteins (OMPs) as well as a cell-mediated immune response in adult mice. We also observed that proteins of OMVs act as an adjuvant for generation of high levels of anti-LPS antibodies through T cell activation. We then characterized the one-day old suckling mice model for both ST and SE mediated gastroenteritis and used the model for a passive protection study. In the passive protection study, we found the passive transfer of bivalent OMVs immunized sera significantly reduced ST and SE mediated colonization and gastroenteritis symptoms in the colon of suckling mice compared to non-immunized sera recipients. The overall study demonstrated that OMVs based bivalent vaccine could generate broad-spectrum immunity against prevalent iNTS mediated gastroenteritis. This study also established the suckling mice model as a suitable animal model for vaccine study against iNTS mediated gastroenteritis.     

Bilateral basal ganglia lucencies following acute febrile illness

Bilateral striatal necrosis in children without damage elsewhere in the brain can present as an acute neurological disorder or as a progressive disorder. Three children of 6, 7 and 12 years age developed dystonic posture of limbs without any cranial nerve involvement or alteration of sensorium soon after recovery from acute high grade febrile illness of 3–4 days duration. Computerized tomographic scan of head showed bilateral necrosis of basal ganglia. We think that these patients probably constitute a clinically and radiologically distinct subgroup of disorder that prouce bilateral striatal necrosis in children. The cause of the syndrome is unknown.     

Sample size determination for longitudinal designs with binary response

In this article, we develop appropriate statistical methods for determining the required sample size while comparing the efficacy of an intervention to a control with repeated binary response outcomes. Our proposed methodology incorporates the complexity of the hierarchical nature of underlying designs and provides solutions when varying attrition rates are present over time. We explore how the between‐subject variability and attrition rates jointly influence the computation of sample size formula. Our procedure also shows how efficient estimation methods play a crucial role in power analysis. A practical guideline is provided when information regarding individual variance component is unavailable. The validity of our methods is established by extensive simulation studies. Results are illustrated with the help of two randomized clinical trials in the areas of contraception and insomnia. Copyright © 2014 John Wiley & Sons, Ltd.     

Arsenic induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue culture

Arsenic at a nonlethal level in drinking water consumed over a period of time has been reported to produce chronic toxicity and various types of health problems ranging from skin cancer to disturbance in memory. Neurotoxic effects have been reported in clinical cases with chronic exposure to arsenic. Physiological detoxication of arsenic occurs partially through methylation. Arsenic and its methylated derivatives are distributed in different organs and systems. The present study examined the possible interference in the neuronal development and differentiation due to the exposure to arsenic during gestation. The experiments were carried out to examine short and long term effects of arsenic on brain explants and cells grown and maintained in tissue culture system. The effects of arsenic exposure showed changes in brain cell membrane function indicated by generation and release of reactive oxygen-nitrogen intermediates. On the morphological aspect the explants' growth was reduced, ground matrix was lost and neural networking was inhibited. Cells showed signs of apoptotic changes. Arsenic toxicity may induce damage to brain cells prior to more visible clinical conditions. The deleterious effects also pass from the maternal to fetal tissue across the transplacental barrier.     

Molecular imaging of gene expression in living subjects by spliceosome-mediated RNA trans-splicing

Spliceosome-mediated RNA trans-splicing (SMaRT) provides an effective means to reprogram mRNAs and the proteins they encode. SMaRT technology has a broad range of applications, including RNA repair and molecular imaging, each governed by the nature of the sequences delivered by the pre-trans-splicing molecule. Here, we show the ability of SMaRT to optically image the expression of an exogenous gene at the level of pre-mRNA splicing in cells and living animals. Because of the modular design of pre-trans-splicing molecules, there is great potential to employ SMaRT to image the expression of any arbitrary gene of interest in living subjects. In this report, we describe a model system that demonstrates the feasibility of imaging gene expression by transsplicing in small animals. This represents a previously undescribed approach to molecular imaging of mRNA levels in living subjects.