Seasonality, water use and community management of water systems in rural settings: Qualitative evidence from Ghana, Kenya, and Zambia

The sustainability of rural, community-managed water systems in sub-Saharan Africa depends in part on the ability of local water committees to repair breakdowns and carry out the operation and maintenance (O&M) of the system. Much of sub-Saharan Africa has two distinct seasons that affect the availability of water sources and how people use water. Little is known about how seasonality affects water system management. This qualitative study is based on 320 interviews and focus group discussions and examines the effects of season on community water use and management in Ghana, Kenya and Zambia. Participants revealed that seasonality affects water availability, water system breakdowns, resource mobilization, committee activity, and external support availability. In the rainy season, participants typically reported spending less time and money on water collection because rainwater harvesting and seasonal streams, ponds, wells and reservoirs are available. In the dry season, people used improved groundwater sources more often and spent more money and time collecting water. Although seasonal changes in household water demand and use have been examined previously, our data suggest that seasonality also influences community management through differential water system use, system breakdowns and management characteristics. We found that water committees generally have less money, time and access to external support during the rainy season, making them less able to carry out O&M. Our results suggest that community engagement should take place over a long period of time so that seasonal patterns in management can be understood and incorporated into water committee training. External support actors should make a more targeted effort to understand the cultural and economic patterns in a community in order to train committees with appropriate management strategies

Metabolic reconstitution of germ-free mice by a gnotobiotic microbiota varies over the circadian cycle.

The capacity of the intestinal microbiota to degrade otherwise indigestible diet components is known to greatly improve the recovery of energy from food. This has led to the hypothesis that increased digestive efficiency may underlie the contribution of the microbiota to obesity. OligoMM12-colonized gnotobiotic mice have a consistently higher fat mass than germ-free (GF) or fully colonized counterparts. We therefore investigated their food intake, digestion efficiency, energy expenditure, and respiratory quotient using a novel isolator-housed metabolic cage system, which allows long-term measurements without contamination risk. This demonstrated that microbiota-released calories are perfectly balanced by decreased food intake in fully colonized versus gnotobiotic OligoMM12 and GF mice fed a standard chow diet, i.e., microbiota-released calories can in fact be well integrated into appetite control. We also observed no significant difference in energy expenditure after normalization by lean mass between the different microbiota groups, suggesting that cumulative small differences in energy balance, or altered energy storage, must underlie fat accumulation in OligoMM12 mice. Consistent with altered energy storage, major differences were observed in the type of respiratory substrates used in metabolism over the circadian cycle: In GF mice, the respiratory exchange ratio (RER) was consistently lower than that of fully colonized mice at all times of day, indicative of more reliance on fat and less on glucose metabolism. Intriguingly, the RER of OligoMM12-colonized gnotobiotic mice phenocopied fully colonized mice during the dark (active/eating) phase but phenocopied GF mice during the light (fasting/resting) phase. Further, OligoMM12-colonized mice showed a GF-like drop in liver glycogen storage during the light phase and both liver and plasma metabolomes of OligoMM12 mice clustered closely with GF mice. This implies the existence of microbiota functions that are required to maintain normal host metabolism during the resting/fasting phase of circadian cycle and which are absent in the OligoMM12 consortium

Rac1 Deletion Causes Thymic Atrophy

The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Rethinking Heritage : A guide to help make your site more dementia-friendly

Enjoyable activities, feeling welcome at heritage sites, having fun, meeting new people during a trip to a beautiful place. Sounds great, doesn’t it? Whilst most of us expect these opportunities to be available for children as part of formal or informal learning, growing evidence1 shows that having access to high quality cultural activities is important for all age groups, especially people with ill health such as dementia2. You may already be aware of imaginative, co-produced heritage projects involving people living with dementia, carers, friends and family taking place across the UK. These inspiring partnerships in parks, museums and many other visitor attractions, both outside and indoors, all promote enjoyable, active learning and also improve our sense of connectedness with each other. But what are the aims of these projects? What are the challenges? How can we learn with each other, including people living with dementia to make active partnerships sustainable and truly participatory? What does success look like and how can we demonstrate this success? This resource is the result of the generous sharing of expertise in making heritage sites more dementia-friendly. Contributions have been made by both individuals and organisations, underpinned by the recognition of inclusion as an active process yet to be perfected. The resource is a result of meetings in 2016-17 by heritage professionals and allies at the Alzheimer’s Society, Scouts Association and many others. Everyone involved in producing this resource recognises the challenges as well as opportunities in effective partnership working - and the finite limits of local and national funding contexts. As a funder, the Heritage Lottery Fund (HLF) is proud to have inclusion as an organisational priority and is active in building inclusive heritage ambition, both within HLF and with our grantees3. We recognise the process of achieving inclusive heritage where people living with dementia are welcomed, is not only based on funding but relies on senior, strategic commitment from heritage organisations. We know that participatory heritage projects also require support and knowledge from health charities, local Dementia Friends networks, local businesses and other partners to embed sustainable best practice for everyone. This resource is ambitious but also realistic. All contributors recognise that for dementia friendly heritage sites to develop, an active dialogue is required. The benefits to be had from connecting with each other through enjoyable, sociable activities in amazing heritage places have never been clearer!Final Published versio

Effectiveness of Selective Laser Trabeculoplasty Applied to 360° vs. 180° of the Angle

Purpose. To compare the effectiveness and safety of 360° and 180° of Selective Laser Trabeculoplasty (SLT) for the treatment of elevated intraocular pressure (IOP). Methods. Retrospective cohort study. The main outcome measure was the Kaplan–Meier analysis comparing the cumulative probabilities of survival between the 360° and 180° SLT groups in terms of IOP reduction. Success was defined as ≥20% IOP reduction from baseline with an IOP between 5–18 mmHg and ≤1 glaucoma medication added postoperatively. Additional outcome measures included changes in average IOP, number of glaucoma medications, and the incidence of postoperative IOP spikes. Measurements were obtained at 6 weeks, 1 year, and 2 years postoperatively. Results. Two hundred and fifty-eight eyes of 258 patients were included in the 360° group, and 196 eyes of 196 patients were included in the 180° group. The mean IOP reductions at 2 years were 2.21 ± 2.02 mmHg and 2.43 ± 1.81 mmHg (p=0.33) in the 180° and 360° groups, respectively. There were no significant differences in the incidence of postoperative IOP spikes between the two groups. There was a significant difference in the survival curves of the two groups (p=0.035). The Cox proportional-hazard model indicated that 360° of SLT application was a significant predictor of long-term success (p=0.030). Conclusions. 360° of SLT application seems to provide for greater long-term IOP control than 180° of application without putting patients at an elevated risk for postoperative IOP spikes