Research ethics capacity building in Sub-Saharan Africa: a review of NIH Fogarty-funded programs 2000–2012

The last fifteen years have witnessed a significant increase in investment in research ethics capacity development throughout the world. We examine nine research ethics training programs that are focused on Sub-Saharan Africa and supported by the US National Institutes of Health. We collected data from grants awards' documents and annual reports supplemented by questionnaires completed by the training program directors. Together, these programs provided long-term training in research ethics to 275 African professionals, strengthened research ethics committees in 19 countries in Sub-Saharan Africa, and created research ethics curricula at many institutions and bioethics centers within Africa. Trainees' leadership resulted in new national systems and policies on research ethics, human tissue storage and export, and methods of monitoring compliance with research ethics guidelines. Training programs adapted to challenges that arose due to varied trainees' background knowledge in ethics, duration of time available for training, spoken and written English language skills, administrative obstacles, and the need to sustain post-training research ethics activities. Our report showcases the development of awareness of research ethics and building/strengthening of basic research ethics infrastructure in Sub-Saharan Africa. Nevertheless, the increasing amount and complexity of health research being conducted in Sub-Saharan Africa suggests the need for continued investment in research ethics capacity development in this region. This paper is part of a collection of papers analyzing the Fogarty International Center's International Research Ethics Education and Curriculum Development program

Will high-resolution global ocean models benefit coupled predictions on short-range to climate timescales?

As the importance of the ocean in the weather and climate system is increasingly recognised, operational systems are now moving towards coupled prediction not only for seasonal to climate timescales but also for short-range forecasts. A three-way tension exists between the allocation of computing resources to refine model resolution, the expansion of model complexity/capability, and the increase of ensemble size. Here we review evidence for the benefits of increased ocean resolution in global coupled models, where the ocean component explicitly represents transient mesoscale eddies and narrow boundary currents. We consider lessons learned from forced ocean/sea-ice simulations; from studies concerning the SST resolution required to impact atmospheric simulations; and from coupled predictions. Impacts of the mesoscale ocean in western boundary current regions on the large-scale atmospheric state have been identified. Understanding of air-sea feedback in western boundary currents is modifying our view of the dynamics in these key regions. It remains unclear whether variability associated with open ocean mesoscale eddies is equally important to the large-scale atmospheric state. We include a discussion of what processes can presently be parameterised in coupled models with coarse resolution non-eddying ocean models, and where parameterizations may fall short. We discuss the benefits of resolution and identify gaps in the current literature that leave important questions unanswered

Saving lives beyond 2020: The next steps

Road safety analysis can be used to understand what has been successful in the past and what needs to be changed in order to be successful to reduce severe road trauma going forward and ultimately what\u27s needed to achieve zero. This chapter covers some of the tools used to retrospectively evaluate real-life benefits of road safety measures and methods used to predict the combined effects of interventions in a road safety action plan as well as to estimate if they are sufficient to achieve targets near-term and long-term. Included are also a brief overview of methods to develop boundary conditions on what constitutes a Safe System for different road users. Further to that, the chapter lists some arguments for the need of high-quality mass and in-depth data to ensure confidence in the results and conclusions from road safety analysis. Finally, a few key messages are summarized

Resolving and parameterising the ocean mesoscale in earth system models

Purpose of Review. Assessment of the impact of ocean resolution in Earth System models on the mean state, variability, and future projections and discussion of prospects for improved parameterisations to represent the ocean mesoscale. Recent Findings. The majority of centres participating in CMIP6 employ ocean components with resolutions of about 1 degree in their full Earth Systemmodels (eddy-parameterising models). In contrast, there are alsomodels submitted toCMIP6 (both DECK and HighResMIP) that employ ocean components of approximately 1/4 degree and 1/10 degree (eddy-present and eddy-rich models). Evidence to date suggests that whether the ocean mesoscale is explicitly represented or parameterised affects not only the mean state of the ocean but also the climate variability and the future climate response, particularly in terms of the Atlantic meridional overturning circulation (AMOC) and the Southern Ocean. Recent developments in scale-aware parameterisations of the mesoscale are being developed and will be included in future Earth System models. Summary. Although the choice of ocean resolution in Earth System models will always be limited by computational considerations, for the foreseeable future, this choice is likely to affect projections of climate variability and change as well as other aspects of the Earth System. Future Earth System models will be able to choose increased ocean resolution and/or improved parameterisation of processes to capture physical processes with greater fidelity

Estimating the burden of rhodesiense sleeping sickness during an outbreak in Serere, eastern Uganda

BACKGROUND: Zoonotic sleeping sickness, or HAT (Human African Trypanosomiasis), caused by infection with Trypanosoma brucei rhodesiense, is an under-reported and neglected tropical disease. Previous assessments of the disease burden expressed as Disability-Adjusted Life Years (DALYs) for this infection have not distinguished T.b. rhodesiense from infection with the related, but clinically distinct Trypanosoma brucei gambiense form. T.b. rhodesiense occurs focally, and it is important to assess the burden at the scale at which resource-allocation decisions are made. METHODS: The burden of T.b. rhodesiense was estimated during an outbreak of HAT in Serere, Uganda. We identified the unique characteristics affecting the burden of rhodesiense HAT such as age, severity, level of under-reporting and duration of hospitalisation, and use field data and empirical estimates of these to model the burden imposed by this and other important diseases in this study population. While we modelled DALYs using standard methods, we also modelled uncertainty of our parameter estimates through a simulation approach. We distinguish between early and late stage HAT morbidity, and used disability weightings appropriate for the T.b. rhodesiense form of HAT. We also use a model of under-reporting of HAT to estimate the contribution of un-reported mortality to the overall disease burden in this community, and estimate the cost-effectiveness of hospital-based HAT control. RESULTS: Under-reporting accounts for 93% of the DALY estimate of rhodesiense HAT. The ratio of reported malaria cases to reported HAT cases in the same health unit was 133:1, however, the ratio of DALYs was 3:1. The age productive function curve had a close correspondence with the HAT case distribution, and HAT cases occupied more patient admission time in Serere during 1999 than all other infectious diseases other than malaria. The DALY estimate for HAT in Serere shows that the burden is much greater than might be expected from its relative incidence. Hospital based control in this setting appears to be highly cost-effective, highlighting the value of increasing coverage of therapy and reducing under-reporting. CONCLUSION: We show the utility of calculating DALYs for neglected diseases at the local decision making level, and emphasise the importance of improved reporting systems for acquiring a better understanding of the burden of neglected zoonotic diseases

The Copernicus Marine Environment Monitoring Service Ocean State Report

The Copernicus Marine Environment Monitoring Service (CMEMS) Ocean State Report (OSR) provides an annual report of the state of the global ocean and European regional seas for policy and decision-makers with the additional aim of increasing general public awareness about the status of, and changes in, the marine environment. The CMEMS OSR draws on expert analysis and provides a 3-D view (through reanalysis systems), a view from above (through remote-sensing data) and a direct view of the interior (through in situ measurements) of the global ocean and the European regional seas. The report is based on the unique CMEMS monitoring capabilities of the blue (hydrography, currents), white (sea ice) and green (e.g. Chlorophyll) marine environment. This first issue of the CMEMS OSR provides guidance on Essential Variables, large-scale changes and specific events related to the physical ocean state over the period 1993–2015. Principal findings of this first CMEMS OSR show a significant increase in global and regional sea levels, thermosteric expansion, ocean heat content, sea surface temperature and Antarctic sea ice extent and conversely a decrease in Arctic sea ice extent during the 1993–2015 period. During the year 2015 exceptionally strong large-scale changes were monitored such as, for example, a strong El Niño Southern Oscillation, a high frequency of extreme storms and sea level events in specific regions in addition to areas of high sea level and harmful algae blooms. At the same time, some areas in the Arctic Ocean experienced exceptionally low sea ice extent and temperatures below average were observed in the North Atlantic Ocean

The global burden of injury: Incidence, mortality, disability-adjusted life years and time trends from the global burden of disease study 2013

Background The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disabilityadjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. Methods Injury mortality was estimated using the extensive GBD mortality database, corrections for illdefined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. Results In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. Conclusions Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made

Fluid percussion injury device for the precise control of injury parameters

BackgroundInjury to the brain can occur from a variety of physical insults and the degree of disability can greatly vary from person to person. It is likely that injury outcome is related to the biomechanical parameters of the traumatic event such as magnitude, direction and speed of the forces acting on the head.New methodTo model variations in the biomechanical injury parameters, a voice coil driven fluid percussion injury (FPI) system was designed and built to generate fluid percussion waveforms with adjustable rise times, peak pressures, and durations. Using this system, pathophysiological outcomes in the rat were investigated and compared to animals injured with the same biomechanical parameters using the pendulum based FPI system.Results in comparison with existing methodsImmediate post-injury behavior shows similar rates of seizures and mortality in adolescent rats and similar righting times, toe pinch responses and mortality rates in adult rats. Interestingly, post injury mortality in adult rats was sensitive to changes in injury rate. Fluoro-Jade labeling of degenerating neurons in the hilus and CA2-3 hippocampus were consistent between injuries produced with the voice coil and pendulum operated systems. Granule cell population spike amplitude to afferent activation, a measure of dentate network excitability, also showed consistent enhancement 1 week after injury using either system.ConclusionsOverall our results suggest that this new FPI device produces injury outcomes consistent with the commonly used pendulum FPI system and has the added capability to investigate pathophysiology associated with varying rates and durations of injury

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist