Data evaluation and numerical modeling of hydrological interactions between active layer, lake and talik in a permafrost catchment, Western Greenland

SummaryThis study investigates annual water balance conditions and their spatiotemporal variability under a wide variety of atmospheric driving conditions in the periglacial permafrost catchment of Two Boat Lake in Western Greenland. The study uses and combines a comprehensive hydrological multi-parameter dataset measured at the site with site conceptualization and numerical model development, application and testing. The model result reproduces measured lake and groundwater levels, as well as observations made by time-lapse cameras. The results highlights the importance of numerical modeling that takes into account and combines evapotranspiration with other surface and subsurface hydrological processes at various depths, in order to quantitatively understand and represent the dynamics and complexity of the interactions between meteorology, active layer hydrology, lakes, and unfrozen groundwater below permafrost in periglacial catchments. Regarding these interactions, the water flow between the studied lake and a through talik within and beneath it is found to be small compared to other water balance components. The modeling results show that recharge and discharge conditions in the talik can shift in time, while the lake and active layer conditions in the studied catchment are independent of catchment-external landscape features, such as the unfrozen groundwater system below the permafrost and the nearby continental-scale ice sheet

Nesting doctoral students in collaborative North-South partnerships for health systems research

Background: The European Union (EU) supports North-South Partnerships and collaborative research projects through its Framework Programmes and Horizon 2020. There is limited research on how such projects can be harnessed to provide a structured platform for doctoral level studies as a way of strengthening health system research capacity in sub-Saharan Africa (SSA). Objective: The aim of this study was to explore the challenges of, and facilitating factors for, 'nesting' doctoral students in North South collaborative research projects. The term nesting refers to the embedding of the processes of recruiting, supervising, and coordinating doctoral students in the overall research plan and processes. Design: This cross-sectional qualitative study was undertaken by the EU-funded QUALMAT Project. A questionnaire was implemented with doctoral students, supervisors, and country principal investigators (PIs), and content analysis was undertaken. Results: Completed questionnaires were received from nine doctoral students, six supervisors, and three country PIs (86% responses rate). The doctoral students from SSA described high expectations about the input they would receive (administrative support, equipment, training, supervision). This contrasted with the expectations of the supervisors for proactivity and self-management on the part of the students. The rationale for candidate selection, and understandings of the purpose of the doctoral students in the project were areas of considerable divergence. There were some challenges associated with the use of the country PIs as co-supervisors. Doctoral student progress was at times impeded by delays in the release of funding instalments from the EU. The paper provides a checklist of essential requirements and a set of recommendations for effective nesting of doctoral students in joint North-South projects. Conclusion: There are considerable challenges to the effective nesting of doctoral students within major collaborative research projects. However, ways can be found to overcome them. The nesting process ultimately helped the institutions involved in this example to take better advantage of the opportunities that collaborative projects offer to foster North-South partnerships as a contribution to the strengthening of local research capacity

Deliberation, Representation, Equity

"What can we learn about the development of public interaction in e-democracy from a drama delivered by mobile headphones to an audience standing around a shopping center in a Stockholm suburb? In democratic societies there is widespread acknowledgment of the need to incorporate citizens’ input in decision-making processes in more or less structured ways. But participatory decision making is balancing on the borders of inclusion, structure, precision and accuracy. To simply enable more participation will not yield enhanced democracy, and there is a clear need for more elaborated elicitation and decision analytical tools. This rigorous and thought-provoking volume draws on a stimulating variety of international case studies, from flood risk management in the Red River Delta of Vietnam, to the consideration of alternatives to gold mining in Roșia Montană in Transylvania, to the application of multi-criteria decision analysis in evaluating the impact of e-learning opportunities at Uganda's Makerere University. Editors Love Ekenberg (senior research scholar, International Institute for Applied Systems Analysis [IIASA], Laxenburg, professor of Computer and Systems Sciences, Stockholm University), Karin Hansson (artist and research fellow, Department of Computer and Systems Sciences, Stockholm University), Mats Danielson (vice president and professor of Computer and Systems Sciences, Stockholm University, affiliate researcher, IIASA) and Göran Cars (professor of Societal Planning and Environment, Royal Institute of Technology, Stockholm) draw innovative collaborations between mathematics, social science, and the arts. They develop new problem formulations and solutions, with the aim of carrying decisions from agenda setting and problem awareness through to feasible courses of action by setting objectives, alternative generation, consequence assessments, and trade-off clarifications. As a result, this book is important new reading for decision makers in government, public administration and urban planning, as well as students and researchers in the fields of participatory democracy, urban planning, social policy, communication design, participatory art, decision theory, risk analysis and computer and systems sciences.

Deliberation, Representation, Equity

"What can we learn about the development of public interaction in e-democracy from a drama delivered by mobile headphones to an audience standing around a shopping center in a Stockholm suburb? In democratic societies there is widespread acknowledgment of the need to incorporate citizens’ input in decision-making processes in more or less structured ways. But participatory decision making is balancing on the borders of inclusion, structure, precision and accuracy. To simply enable more participation will not yield enhanced democracy, and there is a clear need for more elaborated elicitation and decision analytical tools. This rigorous and thought-provoking volume draws on a stimulating variety of international case studies, from flood risk management in the Red River Delta of Vietnam, to the consideration of alternatives to gold mining in Roșia Montană in Transylvania, to the application of multi-criteria decision analysis in evaluating the impact of e-learning opportunities at Uganda's Makerere University. Editors Love Ekenberg (senior research scholar, International Institute for Applied Systems Analysis [IIASA], Laxenburg, professor of Computer and Systems Sciences, Stockholm University), Karin Hansson (artist and research fellow, Department of Computer and Systems Sciences, Stockholm University), Mats Danielson (vice president and professor of Computer and Systems Sciences, Stockholm University, affiliate researcher, IIASA) and Göran Cars (professor of Societal Planning and Environment, Royal Institute of Technology, Stockholm) draw innovative collaborations between mathematics, social science, and the arts. They develop new problem formulations and solutions, with the aim of carrying decisions from agenda setting and problem awareness through to feasible courses of action by setting objectives, alternative generation, consequence assessments, and trade-off clarifications. As a result, this book is important new reading for decision makers in government, public administration and urban planning, as well as students and researchers in the fields of participatory democracy, urban planning, social policy, communication design, participatory art, decision theory, risk analysis and computer and systems sciences.

'How to know what you need to do': a cross-country comparison of maternal health guidelines in Burkina Faso, Ghana and Tanzania

Initiatives to raise the quality of care provided to mothers need to be given priority in Sub Saharan Africa (SSA). The promotion of clinical practice guidelines (CPGs) is a common strategy, but their implementation is often challenging, limiting their potential impact. Through a cross-country perspective, this study explored CPGs for maternal health in Burkina Faso, Ghana, and Tanzania. The objectives were to compare factors related to CPG use including their content compared with World Health Organization (WHO) guidelines, their format, and their development processes. Perceptions of their availability and use in practice were also explored. The overall purpose was to further the understanding of how to increase CPGs' potential to improve quality of care for mothers in SSA. The study was a multiple case study design consisting of cross-country comparisons using document review and key informant interviews. A conceptual framework to aid analysis and discussion of results was developed, including selected domains related to guidelines' implementability and use by health workers in practice in terms of usability, applicability, and adaptability. The study revealed few significant differences in content between the national guidelines for maternal health and WHO recommendations. There were, however, marked variations in the format of CPGs between the three countries. Apart from the Ghanaian and one of the Tanzanian CPGs, the levels of both usability and applicability were assessed as low or medium. In all three countries, the use of CPGs by health workers in practice was perceived to be limited. Our cross-country study suggests that it is not poor quality of content or lack of evidence base that constitute the major barrier for CPGs to positively impact on quality improvement in maternal care in SSA. It rather emphasises the need to prioritise the format of guidelines to increase their usability and applicability and to consider these attributes together with implementation strategies as integral to their development processes

Malaria Rapid Testing by Community Health Workers Is Effective and Safe for Targeting Malaria Treatment: Randomised Cross-Over Trial in Tanzania

Early diagnosis and prompt, effective treatment of uncomplicated malaria is critical to prevent severe disease, death and malaria transmission. We assessed the impact of rapid malaria diagnostic tests (RDTs) by community health workers (CHWs) on provision of artemisinin-based combination therapy (ACT) and health outcome in fever patients. Twenty-two CHWs from five villages in Kibaha District, a high-malaria transmission area in Coast Region, Tanzania, were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis (CD) only. Each CHW was randomly assigned to use either RDT or CD the first week and thereafter alternating weekly. Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7. The CHWs enrolled 2930 fever patients during five months of whom 1988 (67.8%) presented within 24 hours of fever onset. ACT was provided to 775 of 1457 (53.2%) patients during RDT weeks and to 1422 of 1473 (96.5%) patients during CD weeks (Odds Ratio (OR) 0.039, 95% CI 0.029-0.053). The CHWs adhered to the RDT results in 1411 of 1457 (96.8%, 95% CI 95.8-97.6) patients. More patients were referred on inclusion day during RDT weeks (10.0%) compared to CD weeks (1.6%). Referral during days 1-7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis. However, no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT, supporting the safety of withholding ACT to RDT negative patients. RDTs in the hands of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa.\ud \ud \ud \u

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Genomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risk

Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes. We traced association signals in a 200-kb region around genomic positions of genes interacting with glatiramer in up to 60 801 CAD cases and 123 504 controls. We validated the identified association in additional 21 934 CAD cases and 76 087 controls. We identified three new CAD risk alleles within the TGFB1 region on chromosome 19 that independently affect CAD risk. The lead SNP rs12459996 was genome-wide significantly associated with CAD in the extended meta-analysis (odds ratio 1.09, p = 1.58×10-12). The other two SNPs at the locus were not in linkage disequilibrium with the lead SNP and by a conditional analysis showed p-values of 4.05 × 10-10 and 2.21 × 10-6. Thus, studying genes reported to interact with glatiramer acetate we identified genetic variants that concordantly with the drug increase the risk of CAD. Of these, TGFB1 displayed signal for association. Indeed, the gene has been associated with CAD previously in both in vivo and in vitro studies. Here we establish genome-wide significant association with CAD in large human samples.This work was supported by grants from the Fondation Leducq (CADgenomics: Understanding CAD Genes, 12CVD02), the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (e:AtheroSysMed, grant 01ZX1313A-2014 and SysInflame, grant 01ZX1306A), and the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no HEALTH-F2-2013-601456 (CVgenes-at-target). Further grants were received from the DFG as part of the Sonderforschungsbereich CRC 1123 (B2). T.K. was supported by a DZHK Rotation Grant. I.B. was supported by the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ‘Inflammation at Interfaces’. F.W.A. is supported by a Dekker scholarship-Junior Staff Member 2014T001 - Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms