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Proper stem cell differentiation relies on a balance between cellular growth and terminal differentiation, but the mechanisms coordinating these processes remain elusive. Recent studies indicate that ribosome biogenesis (RiBi) and protein synthesis, two of the most energy-consuming cellular processes supporting growth, are tightly regulated and yet can be uncoupled during stem cell fate transitions1–6. Here, using the Drosophila adult female germline stem cell (GSC) and larval neuroblast (NB) systems, we show that Mei-P26 and Brat7, two Drosophila TRIM-NHL paralogues of the mammalian TRIM32 protein family, are responsible for uncoupling RiBi and protein synthesis during GSC and NB differentiation, respectively. This is achieved by TRIM-NHL-mediated activation of the Target of rapamycin (Tor) kinase and concomitant repression of RiBi specifically during stem cell differentiation. In consequence, the anabolic reprogramming established by TRIM-NHL activity creates the conditions for terminal differentiation. In agreement with this, depletion of mei-P26 or brat, which results in excessive cellular growth and defective terminal differentiation8–10, can be counterbalanced by ectopic activation of Tor together with suppression of RiBi, allowing completion of differentiation. Our work indicates that TRIM-NHL proteins uncouple RiBi and translation activities to coordinate growth and differentiation, and proposes that the control of cellular resources provides a meter for terminal differentiation.

Summary Background To move towards ending AIDS by 2030, HIV resources should be allocated cost-effectively. We used the Optima HIV model to estimate how global HIV resources could be retargeted for greatest epidemiological effect and how many additional new infections could be averted by 2030. Methods We collated standard data used in country modelling exercises (including demographic, epidemiological, behavioural, programmatic, and expenditure data) from Jan 1, 2000, to Dec 31, 2015 for 44 countries, capturing 80% of people living with HIV worldwide. These data were used to parameterise separate subnational and national models within the Optima HIV framework. To estimate optimal resource allocation at subnational, national, regional, and global levels, we used an adaptive stochastic descent optimisation algorithm in combination with the epidemic models and cost functions for each programme in each country. Optimal allocation analyses were done with international HIV funds remaining the same to each country and by redistributing these funds between countries. Findings Without additional funding, if countries were to optimally allocate their HIV resources from 2016 to 2030, we estimate that an additional 7·4 million (uncertainty range 3·9 million–14·0 million) new infections could be averted, representing a 26% (uncertainty range 13–50%) incidence reduction. Redistribution of international funds between countries could avert a further 1·9 million infections, which represents a 33% (uncertainty range 20–58%) incidence reduction overall. To reduce HIV incidence by 90% relative to 2010, we estimate that more than a three-fold increase of current annual funds will be necessary until 2030. The most common priorities for optimal resource reallocation are to scale up treatment and prevention programmes targeting key populations at greatest risk in each setting. Prioritisation of other HIV programmes depends on the epidemiology and cost-effectiveness of service delivery in each setting as well as resource availability. Interpretation Further reductions in global HIV incidence are possible through improved targeting of international and national HIV resources. Funding World Bank and Australian NHMRC.

International audience; We review the mechanisms established by the Ramsar Convention for reporting on the status and change in the ecological character of wetlands. We assess the extent of their implementation and compliance, but not issues of the adequacy of their design nor the consequences of their extent of implementation. We conclude that, with the exception of qualitative national-scale reporting in triennial Contracting Party National Reports, there is inadequate implementation and compliance with most of these mechanisms, notably concerning required reporting under Article 3.2 of the Convention and the updating of the Information Sheet on Ramsar Wetlands (RIS). This limits the ability of the Convention to assess the status, and trends in status, of designated Wetlands of International Importance (Ramsar Sites), and to inform future decision-making and priority-setting for the wise use of all wetlands. As has been recognised by the Ramsar Convention, unless compliance with these mechanisms is improved, sufficient information will not be gathered through the mechanisms of Ramsar Convention to assess fully the Sustainable Development Goal 6.6.1 indicator supported by the Convention on change in the extent of water-related ecosystems over time.

We assessed trends in the ecological character of wetlands generally and of Ramsar Sites reported in 2011, 2014 and 2017 by the Contracting Parties to the Ramsar Convention on Wetlands in their national reports. There was more widespread deterioration than improvement in the ecological character of wetlands generally, with deterioration increasingly more widespread between 2011 and 2017. The ecological-character trends in Ramsar Sites were significantly better than those of wetlands generally, but an increasingly more widespread deterioration of ecological character was reported between 2011 and 2017. Trends in the ecological character of wetlands generally, and of Ramsar Sites were worst in Africa and Latin America and the Caribbean, and recently also in Oceania, and better in North America and Europe. Deterioration in the ecological character of Ramsar Site was more widespread in countries with a large average area of their Ramsar Sites. This information on trends of wetland ecological character can contribute to assessing the achievement of the 2030 Sustainable Development Goal Target 6.6 and Aichi Biodiversity Target 5. Our analysis indicated that the 1971 aim of the Ramsar Convention to stem the degradation of wetlands has not yet been achieved.

INTRODUCTION: Globally, there is increased focus on getting the greatest impact from available health funding. However, the pursuit of overall welfare maximization may mean some are left worse off than before. Pareto efficiency takes welfare shifts into account by ruling out funding reallocations that worsen outcomes for any person or group. METHODS: Using the Optima HIV model, studies of HIV response efficiency were conducted in Sudan in 2014 and Togo in 2015. In this article, we estimate the welfare maximizing and Pareto efficient allocations for these two national HIV budgets, using data from the original studies. RESULTS: We estimate that, if the 2013 HIV budget for Sudan was annually available to 2020 but with funds reallocated according to the welfare maximizing allocation, a 36% reduction in cumulative new infections could be achieved between 2014 and 2020. We also find that this is Pareto efficient. In Togo, however, we find that it is possible to reduce overall new infections but applying the Pareto efficiency criterion means that shifts in emphases cannot occur in the HIV response without additional resources. DISCUSSION: Protecting service coverage for key population groups is not necessarily equivalent to protecting health outcomes. In some cases, requiring Pareto efficiency may reduce the potential for population-wide welfare gains, but this is not always the case. CONCLUSION: Pareto efficiency may be an appropriate addition to the quantitative toolset for evaluating HIV responses.

Introduction With limited funds available, meeting global health targets requires countries to both mobilize and prioritize their health spending. Within this context, countries have recognized the importance of allocating funds for HIV as efficiently as possible to maximize impact. Over the past six years, the governments of 23 countries in Africa, Asia, Eastern Europe and Latin America have used the Optima HIV tool to estimate the optimal allocation of HIV resources. Methods Each study commenced with a request by the national government for technical assistance in conducting an HIV allocative efficiency study using Optima HIV. Each study team validated the required data, calibrated the Optima HIV epidemic model to produce HIV epidemic projections, agreed on cost functions for interventions, and used the model to calculate the optimal allocation of available funds to best address national strategic plan targets. From a review and analysis of these 23 country studies, we extract common themes around the optimal allocation of HIV funding in different epidemiological contexts. Results and discussion The optimal distribution of HIV resources depends on the amount of funding available and the characteristics of each country's epidemic, response and targets. Universally, the modelling results indicated that scaling up treatment coverage is an efficient use of resources. There is scope for efficiency gains by targeting the HIV response towards the populations and geographical regions where HIV incidence is highest. Across a range of countries, the model results indicate that a more efficient allocation of HIV resources could reduce cumulative new HIV infections by an average of 18% over the years to 2020 and 25% over the years to 2030, along with an approximately 25% reduction in deaths for both timelines. However, in most countries this would still not be sufficient to meet the targets of the national strategic plan, with modelling results indicating that budget increases of up to 185% would be required. Conclusions Greater epidemiological impact would be possible through better targeting of existing resources, but additional resources would still be required to meet targets. Allocative efficiency models have proven valuable in improving the HIV planning and budgeting process.

The paper argues for an integrated approach to the management of water-related disasters that becomes a full part of the political decision-making process at the earliest possible moment and focuses on preparedness, mitigating their negative impacts and also considering their positive impacts, particularly those of floods. By doing this, there is an opportunity to consider the three pillars of sustainable development, and understand the options that exist and the trade-offs that may need to be made between economic efficiency, environmental sustainability and social equity. Within the post-2015 agenda, water-related disasters are addressed by targets under a number of different Sustainable Development Goals (SDGs). As climate change becomes an ever-more-present reality, whose impacts are often experienced through water-related disasters such as floods and droughts, there is an urgent need to build disaster-resilient societies through more integrated policies and practices, including stakeholders' perspectives and a partnership approach. The paper provides stakeholder perspectives and approaches from around the world that are putting these ideas into practice.

Multilayer actuators (MLAs) offer an increase of force per unit area, a reduction in power consumption, and a reduction in required driving voltages compared with singlelayer actuators. For example, switching from a single 0.5- or 1.0-μm layer of PZT to multiple 250-nm-thick layers would enable a 2/3 to 3/4 reduction in actuation voltage and an increase of 2 to 3 times in actuation force per area for a PZT MEMS switches and robotics. Efforts have been focused on developing actuators using four 250-nm-thick layers of PZT with a Zr/Ti ratio of 52/48 (i.e., the morphotropic phase boundary). The PZT films used a previously established method of achieving greater than 98% (001/100) oriented PZT by chemical solution deposition (CSD). By performing X-ray diffraction measurements between each layer, the texture within the films could be monitored during the growth process. To electrically measure the quality of the PZT multilayer stack, a series of six-sided capacitors were fabricated. The devices were connected in parallel with an average dielectric constant of 1150 for each PZT layer and an average total capacitance of 45 nF. In addition to capacitors, cantilever actuators were fabricated to measure the piezoelectric induced deformation. Comparisons with 100-μm-long cantilever between a single 1-μm-thick PZT and four 250-nm-thick layer PZT stack have shown comparable displacements of |3.7| μm and |4.0| μm, respectively, with an applied electric field of 10 V/μm across the film. These measurements on MLA PZT films demonstrate high piezoelectric coefficients that are suitable for tactile radio and milimeterscale robotic devices.

This paper investigates total ionizing dose (TID) effects on the piezoelectric properties of lead zirconate titanate (PZT). The capacitance and contact voltage of thin-film, PZT-based relays were measured following incremental 60Co TID irradiations. The devices were held in several different bias conditions, during exposure. The direction of the biasing electric field during exposure, along with the polarization prior to exposure, has a measurable impact on post-irradiation operating voltage of the relay. In all cases, the switching voltage, as obtained via the peak values in a capacitance versus voltage sweep, shifted in a direction that would minimize the switching electric field in the direction of pre-exposure polarization. These effects were observed to be both significantly greater than the shifts experienced by a set of control samples, as well as reversible via aging at room temperature. The devices display remarkable robustness, operating during active TID exposure [dose rate = 855.6 rad(Si)/s], failing at a TID greater than 15 Mrad(Si).

Background Of the 5.54 million stillbirths and neonatal deaths occurring globally each year, a significant amount of these occur in the setting of inadequate intrapartum care. The introduction of universal umbilical artery lactate (UA) measurements in this setting may improve outcomes by providing an objective measurement of quality of care and stimulating case reflection, audit, and practice change. It is important that consideration is given to the barriers and facilitators to implementing this tool outside of a research setting. Methods During the period 16/11/2014 -13/01/2015, we conducted a training course in cardiotocograph (CTG) interpretation, fetal physiology, and the sampling and analysing of UA lactate, with a pre and post questionnaire aimed at assessing the barriers and facilitators to the introduction of universal UA lactate in a district hospital in the Eastern Cape, South Africa. Results Thirty-five pre-training questionnaires available (overall response rate 95 %) and 22 post training questionnaires (response rate 63 %) were available for analysis. Prior to training, the majority gave positive responses (strongly agree or agree) that measuring UA lactate assists neonatal care, is protective for staff medicolegally, and improves opportunities for audit and teaching of maternity practice (n = 33, 30, 32; 94.4 %, 85.7 %, 91.4 % respectively). Respondents remained positive about the benefits post training. An increased workload on medical or midwifery staff was less likely to be seen as barrier following training (71 vs. 38.9 % positive response, p = 0.038). A higher rate of respondents felt that expense and lack of equipment were likely to be barriers after completing training, although this wasn’t significant. There was a trend towards lack of time and expertise being less likely to be seen as barriers post training. Conclusion The majority of participants providing intrapartum care in this setting are positive about the role of universal UA lactate analysis and the potential benefits it provides. Training aids in overcoming some of the perceived barriers to implementation of universal UA lactate analysis.

Men who have sex with men (MSM) have higher rates of poor sexual health. The National Institute for Health and Care Excellence has produced guidance on increasing the uptake of HIV testing to reduce undiagnosed infection in MSM. We report the results of a pilot outreach sexually transmitted infection service using nurse-delivered screening and self-sampled postal testing at a sex on premises venue with comparison made against a sexual health clinic service. Thirty men were included in each group. Users of the nurse-delivered and postal services were older (nurse service median age 57.5 years vs. postal kit service 47 years vs. clinic 35.5 years, p ≤ 0.001). Outreach groups were less likely to have undertaken sexually transmitted infection testing previously than the clinic group (53.3% and 60% vs. 93.3%, p ≤ 0.001). Chlamydia trachomatis and Neisseria gonorrhoeae testing uptake was comparable across groups (nurse outreach 86.6%, ‘do it yourself’ postal kit 100% vs. clinic 100%, p = 0.032), but uptake for blood tests was lower in the postal kit group (nurse outreach 83.3%, postal kit 53.3% vs. clinic 100%, p ≤ 0.001). No significant difference in active sexually transmitted infection positivity across the groups was observed. This combination outreach screening approach is effective in targeting MSM who use sex on premises venues.