Transboundary cooperation a potential route to sustainable development in the Indus basin

With a rapidly growing population of 250 million, the Indus river basin in South Asia is one of the most intensively cultivated regions on Earth, highly water stressed and lacking energy security. Yet, most studies advising sustainable development policy have lacked multi-sectoral and cross-country perspectives. Here we show how the countries in the Indus basin could lower costs for development and reduce soil pollution and water stress by cooperating on water resources and electricity and food production. According to this analysis, Indus basin countries need to increase investments to US$10 billion per yr to mitigate water scarcity issues and ensure improved access to resources by 2050. These costs could shrink to US$2 billion per yr, with economic gains for all, if countries pursued more collaborative policies. Downstream regions would benefit most, with reduced food and energy costs and improved water access, while upstream regions would benefit from new energy investments. Using integrated water–energy–land analysis, this study quantifies the potential benefits of novel avenues to sustainable development arising from greater international cooperation

Balancing clean water-climate change mitigation tradeoffs

Energy systems support technical solutions fulfilling the United Nations’ Sustainable Development 2 Goal for clean water and sanitation (SDG6), with implications for future energy demands and greenhouse 3 gas emissions. The energy sector is also a large consumer of water, making water efficiency targets in4 grained in SDG6 important constraints for long-term energy planning. Here, we apply a global integrated 5 assessment model to quantify the cost and characteristics of infrastructure pathways balancing SDG6 tar6 gets for water access, scarcity, treatment and efficiency with long-term energy transformations limiting climate warming to 1.5 ◦ 7 C. Under a mid-range human development scenario, we find that approximately 8 1 trillion USD2010 per year is required to close water infrastructure gaps and operate water systems consistent with achieving SDG6 goals by 2030. Adding a 1.5 ◦ 9 C climate policy constraint increases these costs by up to 8 %. In the reverse direction, when the SDG6 targets are added on top of the 1.5 ◦ 10 C policy 11 constraint, the cost to transform and operate energy systems increases 2 to 9 % relative to a baseline 1.5 ◦ 12 C scenario that does not achieve the SDG6 targets by 2030. Cost increases in the SDG6 pathways 13 are due to expanded use of energy-intensive water treatment and costs associated with water conserva14 tion measures in power generation, municipal, manufacturing and agricultural sectors. Combined global spending (capital and operational expenditures) in the integrated SDG6-1.5 ◦ 15 C scenarios to 2030 on water and energy systems increases 92 to 125 % relative to a baseline scenario without 1.5 ◦ 16 C and SDG6 17 constraints. Evaluation of the multi-sectoral policies underscores the importance of water conservation 18 and integrated water-energy planning for avoiding costs from interacting water, energy and climate goals

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology