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Sufficient quantities of water for household use, including for drinking, food preparation and hygiene, are needed to protect public health and for well-being and prosperity. This second edition reviews the evidence about the relationships between water quantity, water accessibility and health. The effects of water reliability, continuity and price on water use, are also covered. Updated guidance, including recommended targets, is provided on domestic water supply to ensure beneficial health outcomes.

Reliable safe water supply is a pillar of society and a key to public health. The Nordic countries have an abundance of clean fresh water as a source for drinking water supplies. They have followed developments in safeguarding water, both the recommendations of the World Health Organization framework for safe drinking water and European legislation. Worldwide, including the Nordic countries, small water supplies are less compliant with water safety regulation. The forthcoming EU directive on drinking water require risk-based approaches and improved transparency on water quality. This research looks at the Nordic frameworks for safe water supply, with emphasis on risk-based approaches and smaller systems. We analyzed the legal frameworks for safe water, the structure of the water sector across the Nordic countries and explored how prepared these countries are to meet these requirements. Our findings show that, while legal requirements are mostly in place, delivery of information to the public needs to be improved. Most Nordic countries are in the process of implementing risk-based management in large and medium size water supplies, whereas small supplies are lagging. We conclude that a key to success is increased training and support for small supplies. We suggest wider adoption of the Nordic model of cooperation with benchmarking of safe water for all to transfer knowledge between the countries. This work provides insights into challenges and opportunities for the Nordic countries and provides insights relevant to countries worldwide in their effort towards realization of SDG Target 6.1.

Slow-wave sleep is thought to be important for retuning cortical synapses, but the cellular mechanisms remain unresolved. During slow-wave activity, cortical neurons display synchronized transitions between depolarized Up states and hyperpolarized Down states. Here, using recordings from LIII pyramidal neurons from acute slices of mouse medial entorhinal cortex, we find that subthreshold inputs arriving during the Up state undergo synaptic weakening. This does not reflect a process of global synaptic downscaling, as it is dependent on presynaptic spiking, with network state encoded in the synaptically evoked spine Ca2+ responses. Our data indicate that the induction of synaptic weakening is under postsynaptic control, as it can be prevented by correlated postsynaptic spiking activity, and depends on postsynaptic NMDA receptors and GSK3β activity. This provides a mechanism by which slow-wave activity might bias synapses towards weakening, while preserving the synaptic connections within active neuronal assemblies., Slow oscillations between cortical Up and Down states are a defining feature of deep sleep, but their function is not well understood. Here the authors study Up/Down states in acute slices of entorhinal cortex, and find that Up states promote the weakening of subthreshold synaptic inputs, while suprathreshold inputs are preserved or strengthened.

Evidence on sanitation and hygiene program costs is used for many purposes. The few studies that report costs use top-down costing methods that are inaccurate and inappropriate. Community-led total sanitation (CLTS) is a participatory behavior-change approach that presents difficulties for cost analysis. We used implementation tracking and bottom-up, activity-based costing to assess the process, program costs, and local investments for four CLTS interventions in Ghana and Ethiopia. Data collection included implementation checklists, surveys, and financial records review. Financial costs and value-of-time spent on CLTS by different actors were assessed. Results are disaggregated by intervention, cost category, actor, geographic area, and project month. The average household size was 4.0 people in Ghana, and 5.8 people in Ethiopia. The program cost of CLTS was $30.34–$81.56 per household targeted in Ghana, and $14.15–$19.21 in Ethiopia. Most program costs were from training for three of four interventions. Local investments ranged from $7.93–$22.36 per household targeted in Ghana, and $2.35–$3.41 in Ethiopia. This is the first study to present comprehensive, disaggregated costs of a sanitation and hygiene behavior-change intervention. The findings can be used to inform policy and finance decisions, plan program scale-up, perform cost-effectiveness and benefit studies, and compare different interventions. The costing method is applicable to other public health behavior-change programs.

Purpose Minimal residual disease (MRD) and genetic abnormalities are important risk factors for outcome in acute lymphoblastic leukemia. Current risk algorithms dichotomize MRD data and do not assimilate genetics when assigning MRD risk, which reduces predictive accuracy. The aim of our study was to exploit the full power of MRD by examining it as a continuous variable and to integrate it with genetics. Patients and Methods We used a population-based cohort of 3,113 patients who were treated in UKALL2003, with a median follow-up of 7 years. MRD was evaluated by polymerase chain reaction analysis of Ig/TCR gene rearrangements, and patients were assigned to a genetic subtype on the basis of immunophenotype, cytogenetics, and fluorescence in situ hybridization. To examine response kinetics at the end of induction, we log-transformed the absolute MRD value and examined its distribution across subgroups. Results MRD was log normally distributed at the end of induction. MRD distributions of patients with distinct genetic subtypes were different (P < .001). Patients with good-risk cytogenetics demonstrated the fastest disease clearance, whereas patients with high-risk genetics and T-cell acute lymphoblastic leukemia responded more slowly. The risk of relapse was correlated with MRD kinetics, and each log reduction in disease level reduced the risk by 20% (hazard ratio, 0.80; 95% CI, 0.77 to 0.83; P < .001). Although the risk of relapse was directly proportional to the MRD level within each genetic risk group, absolute relapse rate that was associated with a specific MRD value or category varied significantly by genetic subtype. Integration of genetic subtype–specific MRD values allowed more refined risk group stratification. Conclusion A single threshold for assigning patients to an MRD risk group does not reflect the response kinetics of the different genetic subtypes. Future risk algorithms should integrate genetics with MRD to accurately identify patients with the lowest and highest risk of relapse.

We conducted a study to evaluate the sustainability of community-led total sanitation (CLTS) outcomes in Ethiopia and Ghana. Plan International, with local actors, implemented four CLTS interventions from 2012 to 2014: health extension worker-facilitated CLTS and teacher-facilitated CLTS in Ethiopia, and NGO-facilitated CLTS with and without training for natural leaders in Ghana. We previously evaluated these interventions using survey data collected immediately after implementation ended, and concluded that in Ethiopia health extension workers were more effective facilitators than teachers, and that in Ghana training natural leaders improved CLTS outcomes. For this study, we resurveyed 3831 households one year after implementation ended, and analyzed latrine use and quality to assess post-intervention changes in sanitation outcomes, to determine if our original conclusions were robust. In one of four interventions evaluated (health extension worker-facilitated CLTS in Ethiopia), there was an 8 percentage point increase in open defecation in the year after implementation ended, challenging our prior conclusion on their effectiveness. For the other three interventions, the initial decreases in open defecation of 8–24 percentage points were sustained, with no significant changes occurring in the year after implementation. On average, latrines in Ethiopia were lower quality than those in Ghana. In the year following implementation, forty-five percent of households in Ethiopia repaired or rebuilt latrines that had become unusable, while only 6% did in Ghana possibly due to higher latrine quality. Across all four interventions and three survey rounds, most latrines remained unimproved. Regardless of the intervention, households in villages higher latrine use were more likely to have sustained latrine use, which together with the high latrine repair rates indicates a potential social norm. There are few studies that revisit villages after an initial evaluation to assess sustainability of sanitation outcomes. This study provides new evidence that CLTS outcomes can be sustained in the presence of training provided to local actors, and strengthens previous recommendations that CLTS is not appropriate in all settings and should be combined with efforts to address barriers households face to building higher quality latrines.

The functions of sleep are diverse and still poorly understood, but a strong effect on cognition is evident. An impressive number of studies suggest that particularly deep sleep, with characteristic cortical slow-wave activity, mediates some important beneficial effects on learning and memory, such as memory consolidation and integration. In the light of this, it is surprising how little we know about the specific rules of synaptic plasticity associated with characteristic activity patterns of different sleep stages. Therefore, using whole-cell recordings from single or synaptically coupled principal cells and two-photon Ca2+ imaging of dendritic spines, I explored how the ongoing network state might promote activity-dependent synaptic plasticity in an in vitro model of the medial entorhinal cortex. This experimental setup allowed precise control over Up-Down state oscillations (cellular membrane potential fluctuations associated with slow-wave activity) – a methodological advantage that is difficult to achieve in vivo. I found that evoking subthreshold synaptic inputs during the Up state phase of cortical slow-wave activity induced N-methyl-D-aspartate receptor-dependent synaptic weakening. In fact, the spontaneous, intrinsically generated recurrent network activity that underlies cortical Up states was able to depress the very inputs that help maintain it. These findings are in agreement with the synaptic homeostasis hypothesis of sleep, a proposal for which descriptions of clear molecular and cellular mechanisms have been missing. Next, I investigated spike-timing dependent plasticity during Up state periods. I found that input-correlated postsynaptic spiking can prevent synaptic weakening. This suggests that while subthreshold synaptic inputs become continuously weaker during slow-wave activity, correlated inputs become relatively more dominant – a process that could be related to memory consolidation. Finally, I investigated Ca2+ signalling in dendritic spines during Up- Down state oscillations using a novel multi-photon microscope based on the remotefocusing technology. These experiments identified a biochemical signature that could drive the observed plasticity rules.

Objective: To assess the impact of inadequate water and sanitation on diarrhoeal disease in low- and middle-income settings. Methods: The search strategy used Cochrane Library, MEDLINE & PubMed, Global Health, Embase and BIOSIS supplemented by screening of reference lists from previously published systematic reviews, to identify studies reporting on interventions examining the effect of drinking water and sanitation improvements in low- and middle-income settings published between 1970 and May 2013. Studies including randomised controlled trials, quasi-randomised trials with control group, observational studies using matching techniques and observational studies with a control group where the intervention was well defined were eligible. Risk of bias was assessed using a modified Ottawa-Newcastle scale. Study results were combined using meta-analysis and meta-regression to derive overall and intervention-specific risk estimates. Results: Of 6819 records identified for drinking water, 61 studies met the inclusion criteria, and of 12 515 records identified for sanitation, 11 studies were included. Overall, improvements in drinking water and sanitation were associated with decreased risks of diarrhoea. Specific improvements, such as the use of water filters, provision of high-quality piped water and sewer connections, were associated with greater reductions in diarrhoea compared with other interventions. Conclusions: The results show that inadequate water and sanitation are associated with considerable risks of diarrhoeal disease and that there are notable differences in illness reduction according to the type of improved water and sanitation implemented. © 2014 John Wiley & Sons Ltd The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.