The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve

Impact of home-based management of malaria on health outcomes in Africa: a systematic review of the evidence

BACKGROUND: Home-based management of malaria (HMM) is promoted as a major strategy to improve prompt delivery of effective malaria treatment in Africa. HMM involves presumptively treating febrile children with pre-packaged antimalarial drugs distributed by members of the community. HMM has been implemented in several African countries, and artemisinin-based combination therapies (ACTs) will likely be introduced into these programmes on a wide scale. CASE PRESENTATIONS: The published literature was searched for studies that evaluated the health impact of community- and home-based treatment for malaria in Africa. Criteria for inclusion were: 1) the intervention consisted of antimalarial treatment administered presumptively for febrile illness; 2) the treatment was administered by local community members who had no formal education in health care; 3) measured outcomes included specific health indicators such as malaria morbidity (incidence, severity, parasite rates) and/or mortality; and 4) the study was conducted in Africa. Of 1,069 potentially relevant publications identified, only six studies, carried out over 18 years, were identified as meeting inclusion criteria. Heterogeneity of the evaluations, including variability in study design, precluded meta-analysis. DISCUSSION AND EVALUATION: All trials evaluated presumptive treatment with chloroquine and were conducted in rural areas, and most were done in settings with seasonal malaria transmission. Conclusions regarding the impact of HMM on morbidity and mortality endpoints were mixed. Two studies showed no health impact, while another showed a decrease in malaria prevalence and incidence, but no impact on mortality. One study in Burkina Faso suggested that HMM decreased the proportion of severe malaria cases, while another study from the same country showed a decrease in the risk of progression to severe malaria. Of the four studies with mortality endpoints only one from Ethiopia showed a positive impact, with a reduction in the under-5 mortality rate of 40.6% (95% CI 29.2 - 50.6). CONCLUSION: Currently the evidence base for HMM in Africa, particularly regarding use of ACTs, is narrow and priorities for further research are discussed. To optimize treatment and maximize health benefits, drug regimens and delivery strategies in HMM programmes may need to be tailored to local conditions. Additional research could help guide programme development, policy decision-making, and implementation

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children.

Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa but little is known about the role of human genetics in susceptibility. We conducted a genome-wide association study of bacteremia susceptibility in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2 (WTCCC2). Both the blood-culture-proven bacteremia case subjects and healthy infants as controls were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and was thus the focus of this study. We identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) gene (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (p combined = 1.69 × 10(-9); OR = 2.47, 95% CI = 1.84-3.31). The susceptibility allele is African specific, derived rather than ancestral, and occurs at low frequency (2.7% in control subjects and 6.4% in case subjects). Our further studies showed AC011288.2 expression only in neutrophils, a cell type that is known to play a major role in pneumococcal clearance. Identification of this novel association will further focus research on the role of lincRNAs in human infectious disease.Wellcome Trust (Grant ID: 084716/Z/08/Z)This is the final version of the article. It first appeared from Cell Press/Elsevier via http://dx.doi.org/10.1016/j.ajhg.2016.03.02

Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

Peer reviewe

P2RX7 Purinoceptor: A Therapeutic Target for Ameliorating the Symptoms of Duchenne Muscular Dystrophy

open access articleDuchenne muscular dystrophy (DMD) is the most common inherited muscle disease, leading to severe disability and death in young men. Death is caused by the progressive degeneration of striated muscles aggravated by sterile inflammation. The pleiotropic effects of the mutant gene also include cognitive and behavioral impairments and low bone density. Current interventions in DMD are palliative only as no treatment improves the long-term outcome. Therefore, approaches with a translational potential should be investigated, and key abnormalities downstream from the absence of the DMD product, dystrophin, appear to be strong therapeutic targets. We and others have demonstrated that DMD mutations alter ATP signaling and have identified P2RX7 purinoceptor up-regulation as being responsible for the death of muscles in the mdx mouse model of DMD and human DMD lymphoblasts. Moreover, the ATP–P2RX7 axis, being a crucial activator of innate immune responses, can contribute to DMD pathology by stimulating chronic inflammation. We investigated whether ablation of P2RX7 attenuates the DMD model mouse phenotype to assess receptor suitability as a therapeutic target

Effects of storm events on mobilisaton and in-stream processing of dissolved organic matter (DOM) in a Welsh peatland catchment.

Peatlands are important contributors of dissolved organic matter (DOM) to downstream aquatic systems. We investigated the effects of storm events on dissolved organic carbon (DOC) concentrations and DOM quality in a stream draining a Welsh peatland catchment. Intensive stream samples were collected and analysed for pH, DOC, dissolved organic nitrogen (DON), absorbance and fluorescence. Soil water samples and samples of sphagnum pore water were also collected, and a simple end-member mixing model was applied to account for changes occurring during the events. Fluorescence data were interpreted using parallel factor analysis (PARAFAC). DOC concentrations increased and pH decreased during the storm events. The soil water data and the mixing model indicated that this was due to a change of flow paths and draining of the DOC-rich acrotelm. Absorbance indices and the DOC/DON ratio suggested that the DOM released during events was less degraded. There was a striking, inversely related diurnal pattern in absorbance and fluorescence after the discharge peak. The diurnal pattern and a lack of fit with the mixing model suggested that fluorescing DOM was mainly produced in-stream. Fluorescence has been found to peak in the morning and decline during day-time due to photo-bleaching. We hypothesise that the input of additional DOM during events causes a change in the diurnal pattern, giving a peak at mid-day, when the processing of the additional DOM is highest