Geographical distribution of fertility rates in 70 low-income, lower-middle-income, and upper-middle-income countries, 2010–16: a subnational analysis of cross-sectional surveys

Background Understanding subnational variation in age-specific fertility rates (ASFRs) and total fertility rates (TFRs), and geographical clustering of high fertility and its determinants in low-income and middle-income countries, is increasingly needed for geographical targeting and prioritising of policy. We aimed to identify variation in fertility rates, to describe patterns of key selected fertility determinants in areas of high fertility. Methods We did a subnational analysis of ASFRs and TFRs from the most recent publicly available and nationally representative cross-sectional Demographic and Health Surveys and Multiple Indicator Cluster Surveys collected between 2010 and 2016 for 70 low-income, lower-middle-income, and upper-middle-income countries, across 932 administrative units. We assessed the degree of global spatial autocorrelation by using Moran's I statistic and did a spatial cluster analysis using the Getis-Ord Gi* local statistic to examine the geographical clustering of fertility and key selected fertility determinants. Descriptive analysis was used to investigate the distribution of ASFRs and of selected determinants in each cluster. Findings TFR varied from below replacement (2·1 children per women) in 36 of the 932 subnational regions (mainly located in India, Myanmar, Colombia, and Armenia), to rates of 8 and higher in 14 subnational regions, located in sub-Saharan Africa and Afghanistan. Areas with high-fertility clusters were mostly associated with areas of low prevalence of women with secondary or higher education, low use of contraception, and high unmet needs for family planning, although exceptions existed. Interpretation Substantial within-country variation in the distribution of fertility rates highlights the need for tailored programmes and strategies in high-fertility cluster areas to increase the use of contraception and access to secondary education, and to reduce unmet need for family planning. Funding Wellcome Trust, the UK Foreign, Commonwealth and Development Office, and the Bill & Melinda Gates Foundation

Contrasting signals from multiple markers illuminate population connectivity in a marine fish

Recent advances in molecular biology and bioinformatics have helped to unveil striking and previously unrecognized patterns of geographic genetic structure in marine populations. Largely driven by the pressing needs of fisheries management and conservation, studies on marine fish populations have played a pivotal role in testing the efficiency of a range of approaches to explore connectivity and dispersal at sea. Here, we employed nuclear and mitochondrial DNA markers and parasitic infestations to examine the nature and patterns of population structure in a warm-temperate coastal marine teleost across major putative biogeographic barriers in the Mediterranean Sea and Eastern Atlantic Ocean. We detected deep genetic divergence between mitochondrial lineages, likely caused by dramatic climatic and geological transformations before and during the Pleistocene. Such long-diverged lineages later came into secondary contact and can now be found in sympatry. More importantly, microsatellite data revealed that these lineages, after millions of years of independent evolution, now interbreed extensively. By combining genetic and parasite data, we were able to identify at least five independent demographic units. While the different genetic and parasite-based methods produce notably contrasting signals and may complicate the reconstruction of connectivity dynamics, we show that by tailoring the correct interpretation to each of the descriptors used, it is possible to achieve a deeper understanding of the micro-evolutionary process and, consequently, resolve population structure

TDP-43 Identified from a Genome Wide RNAi Screen for SOD1 Regulators

Amyotrophic Lateral Sclerosis (ALS) is a late-onset, progressive neurodegenerative disease affecting motor neurons in the brain stem and spinal cord leading to loss of voluntary muscular function and ultimately, death due to respiratory failure. A subset of ALS cases are familial and associated with mutations in superoxide dismutase 1 (SOD1) that destabilize the protein and predispose it to aggregation. In spite of the fact that sporadic and familial forms of ALS share many common patho-physiological features, the mechanistic relationship between SOD1-associated and sporadic forms of the disease if any, is not well understood. To better understand any molecular connections, a cell-based protein folding assay was employed to screen a whole genome RNAi library for genes that regulate levels of soluble SOD1. Statistically significant hits that modulate SOD1 levels, when analyzed by pathway analysis revealed a highly ranked network containing TAR DNA binging protein (TDP-43), a major component of aggregates characteristic of sporadic ALS. Biochemical experiments confirmed the action of TDP-43 on SOD1. These results highlight an unexpected relationship between TDP-43 and SOD1 which may have implications in disease pathogenesis

Dry and Humid Periods Reconstructed from Tree Rings in the Former Territory of Sogdiana (Central Asia) and Their Socio-economic Consequences over the Last Millennium

One of the richest societies along the Silk Road developed in Sogdiana, located in present-day Tajikistan, Uzbekistan, and Kyrgyzstan. This urban civilisation reached its greatest prosperity during the golden age of the Silk Road (sixth to ninth century ce). Rapid political and economic changes, accelerated by climatic variations, were observed during last millennium in this region. The newly developed tree-ring-based reconstruction of precipitation for the pastmillennium revealed a series of dry and wet stages. During the Medieval Climate Anomaly (MCA), two dry periods occurred (900–1000 and 1200–1250), interrupted by a phase of wetter conditions. Distinct dry periods occurred around 1510–1650, 1750–1850, and 1920–1970, respectively. The juniper tree-ring record of moisture changes revealed that major dry and pluvial episodes were consistent with those indicated by hydroclimatic proxy data from adjacent areas. These climate fluctuations have had longand short term consequences for human history in the territory of former Sogdiana

Identification of ORC1/CDC6-Interacting Factors in Trypanosoma brucei Reveals Critical Features of Origin Recognition Complex Architecture

DNA Replication initiates by formation of a pre-replication complex on sequences termed origins. In eukaryotes, the pre-replication complex is composed of the Origin Recognition Complex (ORC), Cdc6 and the MCM replicative helicase in conjunction with Cdt1. Eukaryotic ORC is considered to be composed of six subunits, named Orc1–6, and monomeric Cdc6 is closely related in sequence to Orc1. However, ORC has been little explored in protists, and only a single ORC protein, related to both Orc1 and Cdc6, has been shown to act in DNA replication in Trypanosoma brucei. Here we identify three highly diverged putative T. brucei ORC components that interact with ORC1/CDC6 and contribute to cell division. Two of these factors are so diverged that we cannot determine if they are eukaryotic ORC subunit orthologues, or are parasite-specific replication factors. The other we show to be a highly diverged Orc4 orthologue, demonstrating that this is one of the most widely conserved ORC subunits in protists and revealing it to be a key element of eukaryotic ORC architecture. Additionally, we have examined interactions amongst the T. brucei MCM subunits and show that this has the conventional eukaryotic heterohexameric structure, suggesting that divergence in the T. brucei replication machinery is limited to the earliest steps in origin licensing

Cutaneous lesions of the nose

Skin diseases on the nose are seen in a variety of medical disciplines. Dermatologists, otorhinolaryngologists, general practitioners and general plastic and dermatologic surgeons are regularly consulted regarding cutaneous lesions on the nose. This article is the second part of a review series dealing with cutaneous lesions on the head and face, which are frequently seen in daily practice by a dermatologic surgeon. In this review, we focus on those skin diseases on the nose where surgery or laser therapy is considered a possible treatment option or that can be surgically evaluated

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