Core-Shell Hydrogel Microcapsules for Improved Islets Encapsulation

Islets microencapsulation holds great promise to treat type 1 diabetes. Currently used alginate microcapsules often have islets protruding outside capsules, leading to inadequate immuno-protection. A novel design of microcapsules with core–shell structures using a two-fluid co-axial electro-jetting is reported. Improved encapsulation and diabetes correction is achieved in a single step by simply confining the islets in the core region of the capsules.Juvenile Diabetes Research Foundation International (grant 17-2007-1063)National Institutes of Health (U.S.) (Postdoctoral Fellowship F32 EB011580- 01)Tayebati Family Foundatio

An empirical investigation of the emergent issues around OER adoption in Sub-Saharan Africa

In the past few years, Africa has joined the rest of the world as an active participant in the Open Educational Resource (OER) movement with a number of home-grown and externally driven initiatives. These have the potential to make an immense contribution to teaching and learning in Sub-Saharan Africa (SSA). However, certain barriers prevent full participation. This paper reports on qualitative research that sought to investigate SSA's readiness to adopt OERs. This study involves three case studies based in higher education institutions involved in OER projects and located in Kenya, Uganda and South Africa. Contrary to the popular belief, findings indicate that low technological levels in Africa do not necessarily impede the adoption of such educational technologies; the real challenges facing the readiness to adopt OERs appear to be related to socio-economic, cultural, institutional and national issues. This paper argues for a complete mind shift in how people perceive OERs. It also proposes raising awareness of OERs at all levels, involving institutions and government, versioning OERs for the African context and conducting more research on OER adoption

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Weighing the Association Between BMI Change and Suicide Mortality

OBJECTIVE: Suicide rates continue to rise, necessitating the identification of risk factors. Obesity and suicide mortality rates have been examined, but associations among weight change, death by suicide, and depression among adults in the United States remain unclear. METHODS: Data from 387 people who died by suicide in 2000-2015 with a recorded body mass index (BMI) in the first and second 6 months preceding their death ( index date ) were extracted from the Mental Health Research Network. Each person was matched with five people in a control group (comprising individuals who did not die by suicide) by age, sex, index year, and health care site (N=1,935). RESULTS: People who died by suicide were predominantly male (71%), White (69%), and middle aged (mean age=57 years) and had a depression diagnosis (55%) and chronic health issues (57%) (corresponding results for the control group: 71% male, 66% White, 14% with depression diagnosis, and 43% with chronic health issues; mean age=56 years). Change in BMI within the year before the index date statistically significantly differed between those who died by suicide (mean change=-0.72±2.42 kg/m(2)) and the control group (mean change=0.06±4.99 kg/m(2)) (p\u3c0.001, Cohen\u27s d=0.17). A one-unit BMI decrease was associated with increased risk for suicide after adjustment for demographic characteristics, mental disorders, and Charlson comorbidity score (adjusted odds ratio=1.11, 95% confidence interval=1.05-1.18, p\u3c0.001). For those without depression, a BMI change was significantly associated with suicide (p\u3c0.001). CONCLUSIONS: An increased suicide mortality rate was associated with weight loss in the year before a suicide after analyses accounted for general and mental health indicators

The meso scale as a frontier in interdisciplinary modeling of sustainability from local to global scales

Achieving sustainable development requires understanding how human behavior and the environment interact across spatial scales. In particular, knowing how to manage tradeoffs between the environment and the economy, or between one spatial scale and another, necessitates a modeling approach that allows these different components to interact. Existing integrated local and global analyses provide key insights, but often fail to capture 'meso-scale' phenomena that operate at scales between the local and the global, leading to erroneous predictions and a constrained scope of analysis. Meso-scale phenomena are difficult to model because of their complexity and computational challenges, where adding additional scales can increase model run-time exponentially. These additions, however, are necessary to make models that include sufficient detail for policy-makers to assess tradeoffs. Here, we synthesize research that explicitly includes meso-scale phenomena and assess where further efforts might be fruitful in improving our predictions and expanding the scope of questions that sustainability science can answer. We emphasize five categories of models relevant to sustainability science, including biophysical models, integrated assessment models, land-use change models, earth-economy models and spatial downscaling models. We outline the technical and methodological challenges present in these areas of research and discuss seven directions for future research that will improve coverage of meso-scale effects. Additionally, we provide a specific worked example that shows the challenges present, and possible solutions, for modeling meso-scale phenomena in integrated earth-economy models

Delivery of physiotherapy and occupational therapy standards of care for Duchenne muscular dystrophy: Key recommendations based on UK web-based survey

\ua9 2025Duchenne muscular dystrophy is a neuromuscular disorder which has benefited from the implementation of key management strategies embedded in International Standards of Care. This study was prompted by the need for more practical, implementable guidance for physiotherapists and occupational therapists than were presented in the international guidelines. Using two web-based surveys, we explored how therapy is currently being delivered in the UK at specialist neuromuscular clinics as well as in community settings, and how it could be improved. The surveys showed that a significant proportion of families report they are not accessing any physiotherapy in either neuromuscular centres (23 %) or in the community (33 %) and that occupational therapy was particularly limited in neuromuscular centres (lacking in 70 %) but also in the community (33 %). There was evidence that, although much is reported as positive about appointments, key gaps are evident. The feedback from families and therapists indicates that care could be better delivered by improving communication, alongside upskilling and education of therapists and families. It demonstrated the value of and real need for a guide for therapists for Duchenne muscular dystrophy as well as a simultaneous family guide to facilitate the improvements identified

Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man

Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy

Glucocorticoid ultradian rhythmicity differentially regulates mood and resting state networks in the human brain: A randomised controlled clinical trial

Adrenal glucocorticoid secretion into the systematic circulation is characterised by a complex rhythm, composed of the diurnal variation, formed by changes in pulse amplitude of an underlying ultradian rhythm of short duration hormonal pulses. To elucidate the potential neurobiological significance of glucocorticoid pulsatility in man, we have conducted a randomised, double-blind, placebo-controlled, three-way crossover clinical trial on 15 healthy volunteers, investigating the impact of different glucocorticoid rhythms on measures of mood and neural activity under resting conditions by recruiting functional neuroimaging, computerised behavioural tests and ecological momentary assessments. Endogenous glucocorticoid biosynthesis was pharmacologically suppressed, and plasma levels of corticosteroid restored by hydrocortisone replacement in three different regimes, either mimicking the normal ultradian and circadian profile of the hormone, or retaining the normal circadian but abolishing the ultradian rhythm of the hormone, or by our current best oral replacement regime which results in a suboptimal circadian and ultradian rhythm. Our results indicate that changes in the temporal mode of glucocorticoid replacement impact (i) the morning levels of self-perceived vigour, fatigue and concentration, (ii) the diurnal pattern of mood variation, (iii) the within-network functional connectivity of various large-scale resting state networks of the human brain, (iv) the functional connectivity of the default-mode, salience and executive control networks with glucocorticoid-sensitive nodes of the corticolimbic system, and (v) the functional relationship between mood variation and underlying neural networks. The findings indicate that the pattern of the ultradian glucocorticoid rhythm could affect cognitive psychophysiology under non-stressful conditions and opens new pathways for our understanding on the neuropsychological effects of cortisol pulsatility with relevance to the goal of optimising glucocorticoid replacement strategies

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource