Household Transmission of Leptospira Infection in Urban Slum Communities

Leptospirosis has emerged to become an urban slum health problem. Epidemics of severe leptospirosis, characterized by jaundice, acute renal failure and haemorrhage, are now reported in cities throughout the developing world due to rapid expansion of slum settlements, which in turn has produced the ecological conditions for rodent-borne transmission of the spirochete pathogen. A survey was performed in the city of Salvador, Brazil, to determine whether the risk of Leptospira infection clustered in households within slum communities in which a member had developed severe leptospirosis. We found that members of households with an index case of leptospirosis had more than five times the risk of having serologic evidence for a prior infection than members of neighbourhood households in the same communities. Increased risk of infection was found among all age groups who resided in these households. The finding that Leptospira infection clusters in specific slum households indicates that the factors associated with this environment are important determinants for transmission. Further research is needed to identify the sources of contamination and risk exposures which occur in the places where slum inhabitants reside such that effective community-based prevention of urban leptospirosis can be implemented

The novel mangrove environment and composition of the Amazon Delta

Both freshwater floodplain (várzeas and igapós) forests and brackish-saline mangroves are abundant and well-described ecosystems in Brazil.1 However, an interesting and unique wetland forest exists in the Amazon Delta where extensive mangroves occur in essentially freshwater tidal environments. Unlike the floodplain forests found upriver, the hydrology of these ecosystems is driven largely by large macro-tides of 4–8 m coupled with the significant freshwater discharge from the Amazon River. We explored these mangroves on the Amazon Delta (00°52ʹ N to 01°41ʹ N) and found surface water salinity to be consistently <5; soil pore water salinity in these mangrove forests ranged from 0 nearest the Amazon mouth to only 5–11 at the coastal margins to the north (01°41ʹ N, 49°55′ W). We also recorded a unique mix of mangrove-obligate (Avicennia sp., Rhizophora mangle) and facultative-wetland species (Mauritia flexuosa, Pterocarpus sp.) dominating these forests. This unique mix of plant species and soil porewater chemistry exists even along the coastal strands and active coastlines of the Atlantic Ocean. Part of these unique mangroves have escaped current global satellite mapping efforts, and we estimate that they may add over 180 km2 (20% increase in mangrove area) within the Amazon Delta. Despite having a unique structure and function, these freshwater-brackish ecosystems likely provide similar ecosystem services to most mangroves worldwide, such as sequestering large quantities of organic carbon, protection of shoreline ecosystems from erosion, and habitats to many terrestrial and aquatic species (monkeys, birds, crabs, and fish)

An inherited duplication at the gene p21 protein-activated Kinase 7 (PAK7) is a risk factor for psychosis

FUNDING Funding for this study was provided by the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z), the Wellcome Trust (072894/Z/03/Z, 090532/Z/09/Z and 075491/Z/04/B), NIMH grants (MH 41953 and MH083094) and Science Foundation Ireland (08/IN.1/B1916). We acknowledge use of the Trinity Biobank sample from the Irish Blood Transfusion Service; the Trinity Centre for High Performance Computing; British 1958 Birth Cohort DNA collection funded by the Medical Research Council (G0000934) and the Wellcome Trust (068545/Z/02) and of the UK National Blood Service controls funded by the Wellcome Trust. Chris Spencer is supported by a Wellcome Trust Career Development Fellowship (097364/Z/11/Z). Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust. ACKNOWLEDGEMENTS The authors sincerely thank all patients who contributed to this study and all staff who facilitated their involvement. We thank W. Bodmer and B. Winney for use of the People of the British Isles DNA collection, which was funded by the Wellcome Trust. We thank Akira Sawa and Koko Ishzuki for advice on the PAK7–DISC1 interaction experiment and Jan Korbel for discussions on mechanism of structural variation.Peer reviewedPublisher PD

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Nontrivial solutions for noncooperative elliptic systems at resonance

In this article we establish the existence of a nonzero solution for variational noncooperative elliptic systems under Dirichlet boundary conditions and a resonant condition at infinity. Situations where the problem is nonresonant and resonant at the origin are considered. The results are based on a version of a critical point theorem for strongly indefinite functionals which are asymptotically quadratic at infinity and do not satisfy any Palais-Smale type condition

The humoral immune response to allografts of foetal small intestine in mice.

The influence of the presence of "passenger leucocytes" on the production of anti-H2 antibodies has been studied in mice receiving allografts of foetal small intestine, adult skin or intradermally injected spleen cells. It was found that the humoral immune response to foetal intestine (a tissue without passenger leucocytes) was identical temporarily to that elicited by skin allografts and these responses differed from that following injection of allogeneic spleen cells in that antibodies to solid grafts took longer to appear. The humoral immune response to small intestine grafts was not evident until several days after the onset of graft rejection as assessed morphologicallymanti H2 antibody production was not observed in thymus deprived recipients of foetal small intestine allografts or allogeneic spleen cells, and this suggests that the humoral immune response to transplantation antigens is thymus dependent