High Performance Field Emitters.

The field electron emission performance of bulk, 1D, and 2D nanomaterials is here empirically compared in the largest metal-analysis of its type. No clear trends are noted between the turn-on electric field and maximum current density as a function of emitter work function, while a more pronounced correlation with the emitters dimensionality is noted. The turn-on field is found to be twice as large for bulk materials compared to 1D and 2D materials, empirically confirming the wider communities view that high aspect ratios, and highly perturbed surface morphologies allow for enhanced field electron emitters.M.T.C. thanks the Oppenheimer Trust, Cambridge University, for generous financial support. This work was supported by an EPSRC Impact Acceleration grant and an Innovate UK Advanced Materials Feasibility Study award. CC thanks the EPSRC Centre for Doctoral Training in Ultra Precision.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/advs.20150031

Genomic Approaches to Enhance Stress Tolerance for Productivity Improvements in Pearl Millet

Pearl millet [Pennisetum glaucum (L.) R. Br.], the sixth most important cereal crop (after rice, wheat, maize, barley, and sorghum), is grown as a grain and stover crop by the small holder farmers in the harshest cropping environments of the arid and semiarid tropical regions of sub-Saharan Africa and South Asia. Millet is grown on ~31 million hectares globally with India in South Asia; Nigeria, Niger, Burkina Faso, and Mali in western and central Africa; and Sudan, Uganda, and Tanzania in Eastern Africa as the major producers. Pearl millet provides food and nutritional security to more than 500 million of the world’s poorest and most nutritionally insecure people. Global pearl millet production has increased over the past 15 years, primarily due to availability of improved genetics and adoption of hybrids in India and expanding area under pearl millet production in West Africa. Pearl millet production is challenged by various biotic and abiotic stresses resulting in a significant reduction in yields. The genomics research in pearl millet lagged behind because of multiple reasons in the past. However, in the recent past, several efforts were initiated in genomic research resulting into a generation of large amounts of genomic resources and information including recently published sequence of the reference genome and re-sequencing of almost 1000 lines representing the global diversity. This chapter reviews the advances made in generating the genetic and genomics resources in pearl millet and their interventions in improving the stress tolerance to improve the productivity of this very important climate-smart nutri-cereal

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015

Background Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015. Methods For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification. Findings Global HIV incidence reached its peak in 1997, at 3.3 million new infections (95% uncertainty interval [UI] 3.1-3.4 million). Annual incidence has stayed relatively constant at about 2.6 million per year (range 2.5-2.8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38.8 million (95% UI 37.6-40.4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1.8 million deaths (95% UI 1.7-1.9 million) in 2005, to 1.2 million deaths (1.1-1.3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections. Interpretation Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licensePeer reviewe

Global, regional, and national levels of maternal mortality, 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015

Background In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015. Methods We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10-54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantified eight underlying causes of maternal death and four timing categories, improving estimation methods since GBD 2013 for adult all-cause mortality, HIV-related maternal mortality, and late maternal death. Secondary analyses then allowed systematic examination of drivers of trends, including the relation between maternal mortality and coverage of specific reproductive health-care services as well as assessment of observed versus expected maternal mortality as a function of Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Findings Only ten countries achieved MDG 5, but 122 of 195 countries have already met SDG 3.1. Geographical disparities widened between 1990 and 2015 and, in 2015, 24 countries still had a maternal mortality ratio greater than 400. The proportion of all maternal deaths occurring in the bottom two SDI quintiles, where haemorrhage is the dominant cause of maternal death, increased from roughly 68% in 1990 to more than 80% in 2015. The middle SDI quintile improved the most from 1990 to 2015, but also has the most complicated causal profile. Maternal mortality in the highest SDI quintile is mostly due to other direct maternal disorders, indirect maternal disorders, and abortion, ectopic pregnancy, and/or miscarriage. Historical patterns suggest achievement of SDG 3.1 will require 91% coverage of one antenatal care visit, 78% of four antenatal care visits, 81% of in-facility delivery, and 87% of skilled birth attendance. Interpretation Several challenges to improving reproductive health lie ahead in the SDG era. Countries should establish or renew systems for collection and timely dissemination of health data; expand coverage and improve quality of family planning services, including access to contraception and safe abortion to address high adolescent fertility; invest in improving health system capacity, including coverage of routine reproductive health care and of more advanced obstetric care-including EmOC; adapt health systems and data collection systems to monitor and reverse the increase in indirect, other direct, and late maternal deaths, especially in high SDI locations; and examine their own performance with respect to their SDI level, using that information to formulate strategies to improve performance and ensure optimum reproductive health of their population.Peer reviewe

The in vitro effect of cypermethrin on quality and oxidative stress indices of rainbow trout Oncorhynchus mykiss spermatozoa

There is limited information on the scientific literature about the effect of in vitro exposure of fish sperm to pesticides. In vitro effect of cypermethrin on sperm quality and oxidative stress has not yet been fully investigated. Therefore, the effects of cypermethrin, a type II pyrethroid insecticide, on quality and oxidative stress of spermatozoa were examined in vitro. To explore the potential in vitro toxicity of cypermethrin, fish spermatozoa were incubated with different concentrations of cypermethrin (1.025, 2.05 and 4.1 μg/l) for 2 h. The motility rate and duration of sperm were determined after exposure to cypermethrin. Reduced glutathione (GSH), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA) in spermatozoa were analyzed for determination of oxidant and antioxidant balance. Our results indicated that spermatozoa motility and duration significantly decreased with exposure to cypermethrin. Additionally, activity of GSH-Px (P < 0.05) and MDA and GSH levels increased in a concentration-dependent manner while CAT activity decreased (P < 0.05). Consequently, the oxidant and antioxidant status and sperm quality were affected by quantitative changes and different concentrations of cypermethrin

A structured review of psychiatric rehabilitation for individuals living with severe mental illness within three regions of the Asia-Pacific: Implications for practice and policy

INTRODUCTION: Psychiatric rehabilitation can provide and support recovery-oriented care by assisting individuals living with severe mental illness to lead full lives. Despite a well-established evidence-base, implementation and access to these interventions in clinical practice for people with severe mental illness in the Asia-Pacific region is low. We therefore aimed to evaluate prominent themes impacting on clinical practice, policy, and the implementation of psychiatric rehabilitation across the Asia-Pacific region. METHODS: A comprehensive review of relevant literature on psychiatric rehabilitation of three regions within the Asia-Pacific was conducted using a structured search of PubMed and other databases. Eligible articles were selected which focussed on how psychiatric rehabilitation is defined and implemented across the Asia-Pacific region, as well as the associated successes and challenges. Common themes were generated. RESULTS: Six themes emerged: the impact of policy, legislation, and human rights; access difficulties; the important role of family; the significance of culture, religion, and spiritual beliefs; the widespread impact of stigma; and the indigenous models of excellence being developed. DISCUSSION: Consideration of the six themes and their implications should help raise awareness of the issues involved in the provision of psychiatric rehabilitation in the Asia-Pacific region and may improve outcomes for people living with severe mental illness. Suggested strategies include: developing a shared understanding of psychiatric rehabilitation; establishing quality legislation that's well implemented; adapting evidence-based models to develop culturally appropriate services; implementing stigma reduction and empowerment-based interventions; and, ensuring coordinated action among all stakeholders, combined with effective leadership