Podoconiosis treatment in northern Ethiopia (GoLBet): study protocol for a randomised controlled trial

BACKGROUND Podoconiosis is one of the forgotten types of leg swelling (elephantiasis) in the tropics. Unlike the other, better-known types of leg swelling, podoconiosis is not caused by any parasite, virus or bacterium, but by an abnormal reaction to minerals found in the clay soils of some tropical highland areas. Non-governmental Organizations (NGOs) have been responsible for the development of simple treatment methods without systematic evaluation of its effectiveness. It is essential that a large scale, fully controlled, pragmatic trial of the intervention is conducted. We aim to test the hypothesis that community-based treatment of podoconiosis lymphoedema reduces the frequency of acute dermatolymphangioadenitis episodes ('acute attacks') and improves other clinical, social and economic outcomes. METHODS/DESIGN This is a pragmatic, individually randomised controlled trial. We plan to randomly allocate 680 podoconiosis patients from the East Gojjam Zone in northern Ethiopia to one of two groups: 'Standard Treatment' or 'Delayed Treatment'. Those randomised to standard treatment will receive the hygiene and foot-care intervention from May 2015 for one year, whereas those in the control arm will be followed through 2015 and be offered the intervention in 2016. The trial will be preceded by an economic context survey and a Rapid Ethical Assessment to identify optimal methods of conveying information about the trial and the approaches to obtaining informed consent preferred by the community. The primary outcome will be measured by recording patient recall and using a simple, patient-held diary that will be developed to record episodes of acute attacks. Adherence to treatment, clinical stage of disease, quality of life, disability and stigma will be considered secondary outcome measures. Other outcomes will include adverse events and economic productivity. Assessments will be made at baseline and at 3, 6, 9 and 12 months thereafter. DISCUSSION The evidence is highly likely to inform implementation of the new master plan for integrated control of Neglected Tropical Diseases (NTDs), in which podoconiosis is identified as one of eight NTDs prioritised for control. Potentially, an estimated 3 million patients in Ethiopia will therefore benefit from the results of this trial. TRIAL REGISTRATION International Standard Randomised Controlled Trial Number. REGISTRATION NUMBER ISRCTN67805210 . Date of registration: 24 January 2013

Geomorphological impacts of a glacier lake outburst flood in the high arctic Zackenberg River, NE Greenland

Glacier lake outburst floods (GLOFs), especially those in the Arctic, can deliver exceptionally high volumes of sediment and solutes to fjords and shallow-marine settings, in comparison to typical seasonal river flows. These sediments and solutes strongly affect coastal geomorphology and aquatic ecosystems, yet are rarely observed. In this study, we have quantified the short-term geomorphological response of the most distal part of the Zackenberg River (northeast Greenland), where it enters Young Sund, to a glacier lake outburst flood that occurred on August 6th 2017. The main aims were to: (1) quantify riverbank and floodplain geomorphology changes that occurred as a consequence of the flood; (2) analyse the spatial patterns of those geomorphological changes and suggest the key controls on them. We used a time-series of very high-resolution UAV-generated images taken on the 5th, 6th, and 8th of August 2017, which enabled us to compare pre- and post-flood fluvial geomorphology. The GLOF induced intense and widespread geomorphological changes, which was surprising because several floods of a similar magnitude have occurred along this river. Approximately 30% of the area of interest experienced changes that were larger than the minimum level of detection (0.15 m). Lateral erosion reached almost 10 m in some places. The total volume loss from bank erosion was at least 26,561 m3 (+/− 14%), whereas the deposition was at least 7745 m3 (+/− 39%). Such an intensive geomorphological response resulted from a combination of factors; namely: (1) bank geometry; (2) composition of bank material; (3) time of occurrence of the event; (4) presence of permafrost; (6) channel geometry; and (7) multitude and diversity of geomorphological processes. We speculate the severity of the geomorphological impact relative to that from previous floods could have been due to warming air temperatures that provided sediment from thawed permafrost, and to an aggrading delta that raised the river base level. Overall, we contend that climate warming will not only make outburst floods from glaciers more likely but that those floods will achieve more geomorphological work with mechanical erosion of permafrost. Erosion and gravitational failures during future flood events will perhaps become even more widespread and intense

Common Susceptibility Loci for Male Breast Cancer

BACKGROUND: The etiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC. METHODS: We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate variants with P values less than 1 × 10-06. Genetic correlation with FBC was evaluated using linkage disequilibrium score regression, by comprehensively examining the associations of published FBC risk loci with risk of MBC and by assessing associations between a FBC polygenic risk score and MBC. All statistical tests were 2-sided. RESULTS: The genome-wide association study identified 3 novel MBC susceptibility loci that attained genome-wide statistical significance (P < 5 × 10-08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen receptor-positive FBC. Men in the top quintile of genetic risk had a fourfold increased risk of breast cancer relative to those in the bottom quintile (odds ratio = 3.86, 95% confidence interval = 3.07 to 4.87, P = 2.08 × 10-30). CONCLUSIONS: These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic etiology with FBC and identifying a fourfold high-risk group of susceptible men