Assessing the sustainability of water governance systems: the sustainability wheel

We present and test a conceptual and methodological approach for interdisciplinary sustainability assessments of water governance systems based on what we call the sustainability wheel. The approach combines transparent identification of sustainability principles, their regional contextualization through sub-principles (indicators), and the scoring of these indicators through deliberative dialogue within an interdisciplinary team of researchers, taking into account their various qualitative and quantitative research results. The approach was applied to a sustainability assessment of a complex water governance system in the Swiss Alps. We conclude that the applied approach is advantageous for structuring complex and heterogeneous knowledge, gaining a holistic and comprehensive perspective on water sustainability, and communicating this perspective to stakeholders.

The dermatologists' role in managing psoriatic arthritis: results of a swiss delphi exercise intended to improve collaboration with rheumatologists.

BACKGROUND Psoriatic arthritis (PsA) substantially impacts the management of psoriatic disease. OBJECTIVE This study aimed to generate an interdisciplinary national consensus on recommendations of how PsA should be managed. METHODS Based on a systematic literature search, an interdisciplinary expert group identified important domains and went through 3 rounds of a Delphi exercise, followed by a nominal group discussion to generate specific recommendations. RESULTS A strong consensus was reached on numerous central messages regarding the impact of PsA, screening procedures, organization of the interaction between dermatologists and rheumatologists, and treatment goals. CONCLUSION These recommendations can serve as a template for similar initiatives in other countries. At the same time, they highlight the need to take into account the impact of the respective national health care system. © 2015 S. Karger AG, Basel.

A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells

The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs) express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

Snow shielding factors for cosmogenic nuclide dating inferred from long-term neutron detector monitoring

The depth-dependent attenuation of the secondary cosmic-ray particle flux due to snow cover and its effects on production rates of cosmogenic nuclides constitutes a potential source of uncertainty for studies conducted in regions characterized by frequent seasonal snow burial. Recent experimental and numerical modelling studies have yielded new constraints on the effect of hydrogen-rich media on the production rates of cosmogenic nuclides by low- and high-energy neutrons (<10(-3) MeV and >10(2) MeV, respectively). Here we present long-term neutron-detector monitoring data from a natural setting that we use to quantify the effect of snow cover on the attenuation of fast neutrons (0.1-10 MeV), which are responsible for the production of Ne-21 from Mg and Cl-36 from K. We use data measured between July 2001 and May 2008 at seven stations located throughout the Ecrins-Pelvoux massif (French Western Alps) and its surroundings, at elevations ranging from 200 to 2500 m a.s.l. From the cosmic-ray fluxes recorded during summer, when snow is absent, we infer an apparent attenuation length of 148 g cm(-2) in the atmosphere at a latitude of similar to 45 degrees N and for altitudes ranging from similar to 200 to 2500 m a.s.l. Using snow water-equivalent (SWE) values obtained through snow-coring campaigns that overlap in time the neutron monitoring for five stations, we show that fast neutrons are much more strongly attenuated in snow than predicted by a conventional mass-shielding formulation and the attenuation length estimated in the atmosphere. We suggest that such strong attenuation results from boundary effects at the atmosphere/snow interface induced by the high efficiency of water as a neutron moderator. Finally, we propose an empirical model that allows calculating snow-shielding correction factors as a function of SWE for studies using Ne-21 and Cl-36 analyses in Mg- and K-rich minerals, respectively. This empirical model is of interest for studies with a focus on cosmic-ray exposure dating, particularly if the target rocks are made up of mafic to ultramafic units where seasonal snow-cover is a common phenomenon.

Legal Aspects of Sino-­African Tied Aid: The Art of Playing with a Legal Grey Area

Sino-African trade has seen a fifty-fold increase in the years 1999 to 2008. In some African regions, particularly in sub-Saharan Africa, China has even replaced the US as the most important trading partner today. But China holds not a single FTA on the African continent, while other major trading partners of African economies rely on an extensive framework of different trade agreements. What is, thus, the legal basis of the recent increase of Sino-African trade? Interestingly, Sino-African trade has seen a particularly strong increase in countries that have entered into tied aid agreements with China. These agreements are commonly known under the term ‘Angola-Model’ and consist of a multifaceted network of barter-trading-systems, aspects of tied aid and concessions for oil and other commodities linked with a state loan. It is likely that these agreements have an impact on the trade-flows between African countries and China. This paper discusses the legal character of this new form of economic cooperation, or modern version of tied aid. Critical legal aspects related to this form of tied aid refer to violation of the principle of most-favoured nation (MFN), illegitimate export subsidies, market access, public procurement and transparency in the international trading system. However, despite the recent outcry of the foremost Western community against the strategy of the Chinese government on the African continent, the practice of the Angola-Model based tied aid is not entirely new, and neither is it against the law. The case of tied aid is situated in a legal grey area that should be examined thoroughly in order to strengthen the international trading system and to support developing countries in their attempt to gain from tied aid arrangements.

Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts.

BACKGROUND HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004-2013. METHODS Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. FINDINGS Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine VL, 1·21 (1·13-1·30) for targeted VL and 0·49 (0·43-0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114-133 cells/µl). INTERPRETATION Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing.

Climatic and anthropogenic changes in Western Switzerland: Impacts on water stress

Recent observed hydro-climatic changes in mountainous areas are of concern as they may directly affect capacity to fulfill water needs. The canton of Vaud in Western Switzerland is an example of such a region as it has experienced water shortage episodes during the past decade. Based on an integrated modeling framework, this study explores how hydro-climatic conditions and water needs could evolve in mountain environments and assesses their potential impacts on water stress by the 2060 horizon. Flows were simulated based on a daily semi-distributed hydrological model. Future changes were derived from Swiss climate scenarios based on two regional climate models. Regarding water needs, the authorities of the canton of Vaud provided a population growth scenario while irrigation and livestock trends followed a business-as-usual scenario. Currently, the canton of Vaud experiences moderate water stress from June to August, except in its Alpine area where no stress is noted. In the 2060 horizon, water needs could exceed 80% of the rivers' available resources in low- to mid-altitude environments in mid-summer. This arises from the combination of drier and warmer climate that leads to longer and more severe low flows, and increasing urban (+ 40%) and irrigation (+ 25%) water needs. Highlighting regional differences supports the development of sustainable development pathways to reduce water tensions. Based on a quantitative assessment, this study also calls for broader impact studies including water quality issues.

Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs

BACKGROUND Pinschers and other dogs with coat color dilution show a characteristic pigmentation phenotype. The fur colors are a lighter shade, e.g. silvery grey (blue) instead of black and a sandy color (Isabella fawn) instead of red or brown. In some dogs the coat color dilution is sometimes accompanied by hair loss and recurrent skin inflammation, the so called color dilution alopecia (CDA) or black hair follicular dysplasia (BHFD). In humans and mice a comparable pigmentation phenotype without any documented hair loss is caused by mutations within the melanophilin gene (MLPH). RESULTS We sequenced the canine MLPH gene and performed a mutation analysis of the MLPH exons in 6 Doberman Pinschers and 5 German Pinschers. A total of 48 sequence variations was identified within and between the breeds. Three families of dogs showed co-segregation for at least one polymorphism in an MLPH exon and the dilute phenotype. No single polymorphism was identified in the coding sequences or at splice sites that is likely to be causative for the dilute phenotype of all dogs examined. In 18 German Pinschers a mutation in exon 7 (R199H) was consistently associated with the dilute phenotype. However, as this mutation was present in homozygous state in four dogs of other breeds with wildtype pigmentation, it seems unlikely that this mutation is truly causative for coat color dilution. In Doberman Pinschers as well as in Large Munsterlanders with BHFD, a set of single nucleotide polymorphisms (SNPs) around exon 2 was identified that show a highly significant association to the dilute phenotype. CONCLUSION This study provides evidence that coat color dilution is caused by one or more mutations within or near the MLPH gene in several dog breeds. The data on polymorphisms that are strongly associated with the dilute phenotype will allow the genetic testing of Pinschers to facilitate the breeding of dogs with defined coat colors and to select against Large Munsterlanders carrying BHFD.

Tools for mass screening of G6PD deficiency: validation of the WST8/1-methoxy-PMS enzymatic assay in Uganda.

BACKGROUND The distribution of the enzymopathy glucose-6-phosphate dehydrogenase (G6PD) deficiency is linked to areas of high malaria endemicity due to its association with protection from disease. G6PD deficiency is also identified as the cause of severe haemolysis following administration of the anti-malarial drug primaquine and further use of this drug will likely require identification of G6PD deficiency on a population level. Current conventional methods for G6PD screening have various disadvantages for field use. METHODS The WST8/1-methoxy PMS method, recently adapted for field use, was validated using a gold standard enzymatic assay (R&D Diagnostics Ltd ®) in a study involving 235 children under five years of age, who were recruited by random selection from a cohort study in Tororo, Uganda. Blood spots were collected by finger-prick onto filter paper at routine visits, and G6PD activity was determined by both tests. Performance of the WST8/1-methoxy PMS test under various temperature, light, and storage conditions was evaluated. RESULTS The WST8/1-methoxy PMS assay was found to have 72% sensitivity and 98% specificity when compared to the commercial enzymatic assay and the AUC was 0.904, suggesting good agreement. Misclassifications were at borderline values of G6PD activity between mild and normal levels, or related to outlier haemoglobin values (<8.0 gHb/dl or >14 gHb/dl) associated with ongoing anaemia or recent haemolytic crises. Although severe G6PD deficiency was not found in the area, the test enabled identification of low G6PD activity. The assay was found to be highly robust for field use; showing less light sensitivity, good performance over a wide temperature range, and good capacity for medium-to-long term storage. CONCLUSIONS The WST8/1-methoxy PMS assay was comparable to the currently used standard enzymatic test, and offers advantages in terms of cost, storage, portability and use in resource-limited settings. Such features make this test a potential key tool for deployment in the field for point of care assessment prior to primaquine administration in malaria-endemic areas. As with other G6PD tests, outlier haemoglobin levels may confound G6PD level estimation.