It Depends: Defining Cooperation and Evaluating Effectiveness in Transboundary Waters

With the increasing international focus on transboundary cooperation as a part of the Sustainable Development Goal (SDG) Framework, there is global recognition of transboundary water cooperation as a tool for improved governance and management of transboundary surface and groundwaters. Yet, there is not an agreed upon definition of transboundary water cooperation in the literature. Most measures of transboundary water cooperation focus on agreements, particularly the number of agreements or their content. However, this generally does not measure or capture how actors behave in a cooperative process, nor whether the behavior had the intended consequences or outcomes (Daoudy and Kistin 2008). Therefore, we need further research on measures of the quality and outcomes of cooperative processes. This dissertation addresses these gaps by achieving three goals. First, it identifies the strengths and weaknesses of the methodology for SDG Indicator 6.5.2. The SDG Indicator 6.5.2 aims to measure “the proportion of transboundary basin area with an operational arrangement for water cooperation” (UN-Water 2017). It does this by comparing the UN-Water methodology to two other variations for measuring transboundary water cooperation. The comparison of the results from the three methods illustrates the variability in what is considered transboundary water cooperation. The second goal is to develop a clear, consistent, and representative definition of transboundary water cooperation. This goal proved challenging in that a statement-style definition of transboundary water cooperation has many limitations. Notably, they are broad and non-specific, which makes them less applicable to the variety of forms cooperation can take in basins and aquifers. Therefore, I develop the Four Frames of Cooperation, which is a neutral modular framework for developing context-specific explanatory definitions of transboundary water cooperation in basins and aquifers. The Four Frames of Cooperation are legal, institutional, relational, and outcome. The Four Frames of Cooperation framework forms the foundation for the third goal of this dissertation, which is to define effective transboundary water cooperation and operationalize a method to evaluate the effectiveness of cooperative processes over internationally shared waters. Overall, effective cooperation emphasizes the relational and outcome frames of cooperation, while working towards equitability and sustainability, which is operationalized by the Weighted Model of Effective Cooperation. This model has three stages: parameters, assessment, and evaluation, and together, they present a context-specific model for evaluating the effectiveness of transboundary water cooperation. This model presents a first step in qualitatively evaluating the effectiveness of transboundary water cooperation. Together, the Four Frames of Cooperation and the Weighted Model of Effective Cooperation aim to improve the understanding of cooperation and encourage a detailed evaluation of the quality, success, and effectiveness of cooperative processes

Physiotherapy informed by Acceptance and Commitment Therapy (PACT):Protocol for a randomised controlled trial of PACT versus usual physiotherapy care for adults with chronic low back pain

INTRODUCTION: Chronic low back pain (CLBP) is a common condition and source of significant suffering, disability and healthcare costs. Current physiotherapy treatment is moderately effective. Combining theory-based psychological methods with physiotherapy could improve outcomes for people with CLBP. The primary aim of this randomised controlled trial (RCT) is to evaluate the efficacy of Physiotherapy informed by Acceptance and Commitment Therapy (PACT) on functioning in patients with CLBP. METHODS AND ANALYSIS: The PACT trial is a two-armed, parallel-group, multicentre RCT to assess the efficacy of PACT in comparison with usual physiotherapy care (UC). 240 patients referred to physiotherapy with CLBP will be recruited from three National Health Service (NHS) hospitals trusts. Inclusion criteria are: age ≥18 years, CLBP ≥12-week duration, scoring ≥3 points on the Roland-Morris Disability Questionnaire (RMDQ) and adequate understanding of spoken and written English to participate. Patients will be randomised to PACT or UC (120 per arm stratified by centre) by an independent randomisation service and followed up at 3 and 12 months post randomisation. The sample size of 240 will provide adequate power to detect a standardised mean difference of 0.40 in the primary outcome (RMDQ; 5% significance, 80% power) assuming attrition of 20%. Analysis will be by intention to treat conducted by the trial statistician, blind to treatment group, following a prespecified analysis plan. Estimates of treatment effect at the follow-up assessments will use an intention-to-treat framework, implemented using a linear mixed-effects model. ETHICS AND DISSEMINATION: This trial has full ethical approval (14/SC/0277). It will be disseminated via peer-reviewed publications and conference presentations. The results will enable clinicians, patients and health service managers to make informed decisions regarding the efficacy of PACT for patients with CLBP. TRIAL REGISTRATION: number ISRCTN95392287; Pre-results

Promoting Development in Shared River Basins : Case Studies from International Experience

Transboundary freshwater systems create inevitable linkages and interdependencies between countries. The use of shared water resources by one country will, in most cases, impact other countries sharing the same system. At the same time, coordination among countries in the development of transboundary basins can yield greater benefits than would be available to individual countries pursuing individual development. UN Sustainable Development Goal 6 Target 5 recognizes this potential, calling on the world community to implement integrated water resources management at all levels, ‘including through transboundary cooperation as appropriate’. With a growing number of basins in which water use and demand permanently or temporarily exceeds the amount of renewable water available, and uncertainty from climate change, SDG Target 6.5 becomes increasingly relevant to development interventions designed to secure availability of supplies and create resilience. This is a companion document to the study "Promoting Development in Shared River Basins: Tools for Enhancing Transboundary Basin Management," which aims to contribute to relevant knowledge for achieving SDG Target 6.5. It presents six case studies from international experience on coordinated management in transboundary basins: Kura-Araks Basin; Columbia Basin; Chu and Talas Basins; Vuoksi Basin; Douro Basin; and Rhône Basin. The case studies demonstrate real-world application of selecting appropriate tools for individual transboundary situations along a three-stage process of coordinated basin development, which is detailed in the main study

The potential of behavioural activation for the treatment of chronic pain: An exploratory review

Background: A substantial proportion of the population have a persistent pain condition. In addition to considerable personal suffering, these conditions have a massive economic cost at a society level in terms of health expenditure and lost productivity. To address this immense public health problem, treatment approaches are needed that are based on scientifically supported theories and that are easy to disseminate and scalable. Method: An exploratory qualitative review of literature concerning the operant model of chronic pain, related psychological interventions, and a synopsis of existing intervention studies with a behavioural activation (BA) approach was undertaken. Results: Current treatments for chronic pain are multimodal, however early research showed promising results for operant-based behavioural intervention alone. Although originally developed for depression, BA is a good theoretical match for operant conceptions of chronic pain. Further, because of its relative simplicity, BA is appealing in terms of its potential ease of dissemination. Two case studies have used BA for individuals suffering from fibromyalgia and produced promising treatment outcomes. Conclusions: Further research investigating the efficacy of BA for chronic pain is justified. Such work should begin with more single subject experimental designs to explore how BA might be best applied and the generalisability of the approach

Site and Strain-Specific Variation in Gut Microbiota Profiles and Metabolism in Experimental Mice

The gastrointestinal tract microbiota (GTM) of mammals is a complex microbial consortium, the composition and activities of which influences mucosal development, immunity, nutrition and drug metabolism. It remains unclear whether the composition of the dominant GTM is conserved within animals of the same strain and whether stable GTMs are selected for by host-specific factors or dictated by environmental variables.The GTM composition of six highly inbred, genetically distinct strains of mouse (C3H, C57, GFEC, CD1, CBA nu/nu and SCID) was profiled using eubacterial -specific PCR-DGGE and quantitative PCR of feces. Animals exhibited strain-specific fecal eubacterial profiles that were highly stable (c. >95% concordance over 26 months for C57). Analyses of mice that had been relocated before and after maturity indicated marked, reproducible changes in fecal consortia and that occurred only in young animals. Implantation of a female BDF1 mouse with genetically distinct (C57 and Agoutie) embryos produced highly similar GTM profiles (c. 95% concordance) between mother and offspring, regardless of offspring strain, which was also reflected in urinary metabolite profiles. Marked institution-specific GTM profiles were apparent in C3H mice raised in two different research institutions.Strain-specific data were suggestive of genetic determination of the composition and activities of intestinal symbiotic consortia. However, relocation studies and uterine implantation demonstrated the dominance of environmental influences on the GTM. This was manifested in large variations between isogenic adult mice reared in different research institutions

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND) : a multicentre, parallel, randomised controlled trial in the UK

Background Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease. Methods We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391). Findings Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22–1·10]; d=0·46 [0·16–0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention. Interpretation ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services

Brazilian cave heritage under siege

info:eu-repo/semantics/publishe

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties