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Protecting the world’s freshwater resources requires diagnosing threats over a broad range of scales, from global to local. Here we present the first worldwide synthesis to jointly consider human and biodiversity perspectives on water security using a spatial framework that quantifies multiple stressors and accounts for downstream impacts. We find that nearly 80% of the world’s population is exposed to high levels of threat to water security. Massive investment in water technology enables rich nations to offset high stressor levels without remedying their underlying causes, whereas less wealthy nations remain vulnerable. A similar lack of precautionary investment jeopardizes biodiversity, with habitats associated with 65% of continental discharge classified as moderately to highly threatened. The cumulative threat framework offers a tool for prioritizing policy and management responses to this crisis, and underscores the necessity of limiting threats at their source instead of through costly remediation of symptoms in order to assure global water security for both humans and freshwater biodiversity. Dual threat to river biodiversity and water security Access to fresh water is essential for all life forms, but water security for humans and biodiversity are often seen as competing priorities. A new analysis of the threats to the world's rivers breaks new ground by accounting for a broad array of stressors and their downstream effects, from both human and biodiversity perspectives. A subsequent analysis of investments in water resources offers insights into the sources of global disparities in human water security that separate rich from poor. The authors conclude that rivers are in a state of crisis, and that nearly 80% of humanity lives in areas where threat levels are relatively high. River-dwelling species face similarly great challenges around the world. Achieving a sustainable solution to these problems, the authors say, will require creative solutions that jointly address water security for humans and biodiversity, and that treat underlying causes rather than merely symptoms. Water security affects human wellbeing both directly and indirectly, through its effects on biodiversity. Here, a global map has been generated that shows threats to both direct and indirect water security from a full range of potential stressors. Technological investments have also been incorporated. The map shows that nearly 80% of the world's population is exposed to high levels of threat to water security. Investment enables rich nations to offset high stressor levels, but less wealthy nations remain vulnerable.

Fishing and resource use continues to be an essential aspect of life for many Aboriginal communities throughout Australia. It is important for dietary sustenance, and also retains deep social, cultural and economic significance, playing a fundamental role in maintaining group cohesion, transferring cultural knowledge and affirming Indigenous identities. We surveyed approximately 20% of the Gumbaynggirr Aboriginal community of Nambucca Heads, New South Wales, Australia. This paper explores Gumbaynggirr Connection to Country and engagement in cultural practice. It quantifies fishing efforts and consumption of seafood within the community. We found 95% of the sample group fish, with the highest rate of fishing being 2-3 times a week (27%). Furthermore, 98% of participants eat seafood weekly or more frequently, up to more than once a day (24%). Survey results revealed that Myxus elongatus (Sand mullet) and naturally recruited Saccostrea glomerata (Sydney rock oysters) continue to be important wild resources to the Gumbaynggirr community. Trace metals were measured in M. elongatus and S. glomerata samples collected by community participants in this study. Maximum levels prescribed in the Australia New Zealand Food Standards Code were not exceeded in the edible tissue for either species, however both species exceeded the generally expected levels for zinc and copper and S. glomerata samples exceeded the generally expected level for selenium. Furthermore the average dietary exposure to trace metals from consuming seafood was calculated for the surveyed population. Trace metal intake was then compared to the provisional tolerable weekly intake prescribed by the Joint Expert Committee on Food Additives. This process revealed that copper and selenium intake were both within the provisional tolerable weekly intake, while there is no guideline for zinc. Furthermore, participants relying heavily on wild resources from the Nambucca River estuary may exceed the provisional tolerable weekly intake for cadmium. This suggests the need for further investigation of this issue to minimize any possible health risk.

Studies with rodents infected with Trichinella spiralis, Heligmosomoides polygyrus, Nippostrongylus brasiliensis, and Trichuris muris have provided considerable information about immune mechanisms that protect against parasitic gastrointestinal nematodes. Four generalizations can be made: 1. CD4C T cells are critical for host protection; 2. IL-12 and IFN- inhibit protective immunity; 3. IL-4 can: (a) be required for host protection, (b) limit severity of infection, or (c) induce redundant protective mechanisms; and 4. Some cytokines that are stereotypically produced in response to gastrointestinal nematode infections fail to enhance host protection against some of the parasites that elicit their production. Host protection is redundant at two levels: 1. IL-4 has multiple effects on the immune system and on gut physiology (discussed in this review), more than one of which may protect against a particular parasite; and 2. IL-4 is often only one of multiple stimuli that can induce protection. Hosts may have evolved the ability to recognize features that characterize parasitic gastrointestinal nematodes as a class as triggers for a stereotypic cytokine response, but not the ability to distinguish features of individual parasites as stimuli for more specific protective cytokine responses. As a result, hosts deploy a set of defense mechanisms against these parasites that together control infection by most members of that class, even though a specific defense mechanism may not be required to defend against a particular parasite and may even damage a host infected with that parasite.

Adaptive management favours management practices that are sufficiently robust and flexible to cope with the uncertainties and inevitable surprises that are endemic in natural resource planning. In NeWater, adaptive management has been portrayed as a 'systematic process for improving management policies and practices by learning from the outcomes of implemented management strategies' (Pahl-Wostl, 2007).

Nothing characterizes adaptive management better than the call to embrace uncertainty, and to be proactive in the design of better policies to avoid unpleasant surprises. Firstly, this means that uncertainty of all forms is acknowledged, and its consequences explored. Secondly, by taking on the challenges this uncertainty poses, we can take full advantage of the opportunities for better analysis, robust and flexible policy design, and efficient learning institutions. Finally, the implementation of adaptive water management (AWM) provides greater resilience in the face of those unexpected conditions and uncontrollable, possibly irreversible changes, which inevitably may give rise to huge negative impacts on both ecosystems and society. Accepting this, we need to consider the measurable outputs and outcomes that research and policy are supposed to deliver.

Rising 3300m above sea level in the steep Maloti Mountains of eastern Lesotho, and flowing for some 2300km though an increasingly arid landscape until it reaches the Atlantic Ocean, the Orange River (or the Senqu, as it is known in Lesotho) is one of the largest river basins in the world. In South Africa itself, the Vaal River is considered to be the most important tributary, providing crucial water resources to the urban industrialized conglomeration of Johannesburg and Pretoria.

Data from the Genetic Association Information Network (GAIN) genome-wide association study (GWAS) in major depressive disorder (MDD) were used to explore previously reported candidate gene and single-nucleotide polymorphism (SNP) associations in MDD. A systematic literature search of candidate genes associated with MDD in case–control studies was performed before the results of the GAIN MDD study became available. Measured and imputed candidate SNPs and genes were tested in the GAIN MDD study encompassing 1738 cases and 1802 controls. Imputation was used to increase the number of SNPs from the GWAS and to improve coverage of SNPs in the candidate genes selected. Tests were carried out for individual SNPs and the entire gene using different statistical approaches, with permutation analysis as the final arbiter. In all, 78 papers reporting on 57 genes were identified, from which 92 SNPs could be mapped. In the GAIN MDD study, two SNPs were associated with MDD: C5orf20 (rs12520799; P =0.038; odds ratio (OR) AT=1.10, 95% CI 0.95–1.29; OR TT=1.21, 95% confidence interval (CI) 1.01–1.47) and NPY (rs16139; P =0.034; OR C allele=0.73, 95% CI 0.55–0.97), constituting a direct replication of previously identified SNPs. At the gene level, TNF (rs76917; OR T=1.35, 95% CI 1.13–1.63; P =0.0034) was identified as the only gene for which the association with MDD remained significant after correction for multiple testing. For SLC6A2 (norepinephrine transporter (NET)) significantly more SNPs (19 out of 100; P =0.039) than expected were associated while accounting for the linkage disequilibrium (LD) structure. Thus, we found support for involvement in MDD for only four genes. However, given the number of candidate SNPs and genes that were tested, even these significant may well be false positives. The poor replication may point to publication bias and false-positive findings in previous candidate gene studies, and may also be related to heterogeneity of the MDD phenotype as well as contextual genetic or environmental factors.

Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2×109 (n=12), or 2×1010 (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses.

Signaling by the transcription factor nuclear factor kappa B (NF-κB) involves its release from inhibitor kappa B (IκB) in the cytosol, followed by translocation into the nucleus. NF-κB regulation of IκBα transcription represents a delayed negative feedback loop that drives oscillations in NF-κB translocation. Single-cell time-lapse imaging and computational modeling of NF-κB (RelA) localization showed asynchronous oscillations following cell stimulation that decreased in frequency with increased IκBα transcription. Transcription of target genes depended on oscillation persistence, involving cycles of RelA phosphorylation and dephosphorylation. The functional consequences of NF-κB signaling may thus depend on number, period, and amplitude of oscillations.

Objective: To examine weight loss maintenance among previous participants of a university-based behavioral weight management program and to compare behavioral strategies and perceived barriers between successful and unsuccessful maintainers. Method: Previous program participants ( n =179) completed mailed surveys assessing current weight, weight control behaviors and perceived barriers to weight loss maintenance. Results: At 14.1±10.8 months following completion of treatment, survey respondents were on average 12.6±12.6 kg, or 11.3±10.7%, below baseline weight; 76.5% of respondents had successfully maintained weight, defined as maintaining a weight loss of at least 5% below baseline. Compared to unsuccessful maintainers, successful maintainers reported practicing four dietary and three physical activity weight control strategies more often and experiencing five barriers to healthy eating and exercise less often. After accounting for time since treatment and maximum weight loss while in treatment, the strongest correlates of successful weight loss maintenance were frequent exercise and perceived difficulty of weight management. Conclusions: Clinically meaningful weight loss maintenance was achieved by the majority of participants. Findings support the literature indicating that physical activity is one of the strongest predictors of successful weight loss maintenance. Findings also suggest that strategies to reduce the level of perceived effort required for long-term weight control may improve maintenance outcomes.