On Nigeria Big Bet: 2019 Evaluation Report

Since 2015, the MacArthur Foundation's On Nigeria strategy has sought to reduce corruption by supporting Nigerian-led efforts that strengthen accountability, transparency, and participation. Its theory of change builds on Jonathan Fox's "sandwich theory," which leverages the interplay between a push from below, by which citizens demand change ("voice"), and a squeeze from above to encourage public and private institutions to develop and enforce laws and regulations ("teeth").As of January 2020, the On Nigeria strategy has made 138 grants (totaling $66.8 million) that are a proving ground to develop and test a range of tactics and entry points for addressing corruption. Corruption is complex and ever-evolving, and progress toward the goal of reducing it will most certainly not be linear nor simple. Thus, On Nigeria reflects a multilayered strategy, comprising five areas of targeted programming, or modules—the Home Grown School Feeding (HGSF) Program, the Universal Basic Education Commission (UBEC) Intervention Fund, Electricity Distribution, Criminal Justice, and Media and Journalism; and three cross-cutting areas—behavior and social norm change, civil society pressure for government accountability, and election-related efforts.The goal of this paper is to provide the latest information from the ongoing evaluation of On Nigeria, facilitate learning, and serve as one input to determine the next stage of programming. The evidence presented explores the strategy's progress to date, the validity of its theory of change, and status of windows of opportunity in the strategy's landscape

X-ray emitting young stars in the Orion Nebula

The Orion Nebula Cluster and the molecular cloud in its vicinity have been observed with the ACIS-I detector on board the Chandra X-ray Observatory with 23 hours exposure. We detect 1075 X-ray sources: 91% are spatially associated with known stellar members of the cluster, and 7% are newly identified deeply embedded cloud members. This provides the largest X-ray study of a pre-main sequence stellar population. We examine here the X-ray properties of Orion young stars as a function of mass. Results include: (a) the discovery of rapid variability in the O9.5 31 M_o star \theta^2A Ori, and several early B stars, inconsistent with the standard model of X-ray production in small wind shocks; (b) support for the hypothesis that intermediate-mass mid-B through A type stars do not themselves produce significant X-ray emission; (c) confirmation that low-mass G- through M-type T Tauri stars exhibit powerful flaring but typically at luminosities considerably below the `saturation' level; (d) confirmation that the presence or absence of a circumstellar disk has no discernable effect on X-ray emission; (e) evidence that T Tauri plasma temperatures are often very high with T >= 100 MK, even when luminosities are modest and flaring is not evident; and (f) detection of the largest sample of pre-main sequence very low mass objects showing high flaring levels and a decline in magnetic activity as they evolve into L- and T-type brown dwarfs.Comment: 82 pages, 16 figures, 6 tables. To appear in the Astrophysical Journal. For a version with high quality images and electronic tables, see ftp://ftp.astro.psu.edu/pub/edf/orion1

Stillbirths: ending preventable deaths by 2030

Efforts to achieve the new worldwide goals for maternal and child survival will also prevent stillbirth and improve health and developmental outcomes. However, the number of annual stillbirths remains unchanged since 2011 and is unacceptably high: an estimated 2·6 million in 2015. Failure to consistently include global targets or indicators for stillbirth in post-2015 initiatives shows that stillbirths are hidden in the worldwide agenda. This Series paper summarises findings from previous papers in this Series, presents new analyses, and proposes specific criteria for successful integration of stillbirths into post-2015 initiatives for women’s and children’s health. Five priority areas to change the stillbirth trend include intentional leadership; increased voice, especially of women; implementation of integrated interventions with commensurate investment; indicators to measure effect of interventions and especially to monitor progress; and investigation into crucial knowledge gaps. The post-2015 agenda represents opportunities for all stakeholders to act together to end all preventable deaths, including stillbirths

HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer

Introduction: Metastases to the brain from breast cancer have a high mortality, and basal-like breast cancers have a propensity for brain metastases. However, the mechanisms that allow cells to colonize the brain are unclear.Methods: We used morphology, immunohistochemistry, gene expression and somatic mutation profiling to analyze 39 matched pairs of primary breast cancers and brain metastases, 22 unmatched brain metastases of breast cancer, 11 non-breast brain metastases and 6 autopsy cases of patients with breast cancer metastases to multiple sites, including the brain.Results: Most brain metastases were triple negative and basal-like. the brain metastases over-expressed one or more members of the HER family and in particular HER3 was significantly over-expressed relative to matched primary tumors. Brain metastases from breast and other primary sites, and metastases to multiple organs in the autopsied cases, also contained somatic mutations in EGFR, HRAS, KRAS, NRAS or PIK3CA. This paralleled the frequent activation of AKT and MAPK pathways. in particular, activation of the MAPK pathway was increased in the brain metastases compared to the primary tumors.Conclusions: Deregulated HER family receptors, particularly HER3, and their downstream pathways are implicated in colonization of brain metastasis. the need for HER family receptors to dimerize for activation suggests that tumors may be susceptible to combinations of anti-HER family inhibitors, and may even be effective in the absence of HER2 amplification (that is, in triple negative/basal cancers). However, the presence of activating mutations in PIK3CA, HRAS, KRAS and NRAS suggests the necessity for also specifically targeting downstream molecules.Ludwig Institute of Cancer ResearchNational Breast Cancer FoundationUniv Queensland, Clin Res Ctr, Brisbane, Qld 4029, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, AustraliaUniversidade Federal de São Paulo, EPM, Dept Anat Patol, BR-04024000 São Paulo, BrazilGriffith Univ, Brisbane, Qld 4011, AustraliaUniv Queensland, Ctr Magnet Resonance, Brisbane, Qld 4072, AustraliaEijkman Inst, Jakarta 10430, IndonesiaInst Nacl Canc, Dept Patol, BR-20230130 Rio de Janeiro, BrazilLab Salomao & Zoppi, Dept Patol, BR-04104000 São Paulo, BrazilCharles Univ Prague, Fac Med, Dept Pathol, Plzen 30605, Czech RepublicUniv Sydney, Inst Clin Pathol & Med Res, Sydney W Area Hlth Serv, Sydney, NSW 2145, AustraliaUniv Sydney, Westmead Millennium Inst, Sydney W Area Hlth Serv, Sydney, NSW 2145, AustraliaPeter MacCallum Canc Ctr, Dept Pathol, Melbourne, Vic 3002, AustraliaUniv Queensland, Queensland Brain Inst, Brisbane, Qld 4072, AustraliaRoyal Brisbane & Womens Hosp, Brisbane, Qld 4029, AustraliaUniversidade Federal de São Paulo, EPM, Dept Anat Patol, BR-04024000 São Paulo, BrazilWeb of Scienc

Demography and Life Histories of Sympatric Patas Monkeys, Erythrocebus patas, and Vervets, Cercopithecus aethiops, in Laikipia, Kenya

Mortality patterns are thought to be strong selective forces on life history traits, with high adult mortality and low immature mortality favoring early and rapid reproduction. Patas monkeys (Erythrocebus patas) have the highest potential rates of population increase for their body size of any haplorhine primate because they reproduce both earlier and more often. We report here 10 yr of comparative demographic data on a population of patas monkeys and a sympatric population of vervet monkeys (Cercopithecus aethiops), a closely related species differing in aspects of social system, ecology, and life history. The data reveal that 1) adult female patas monkeys have significantly higher mortality than adult female vervets; 2) infant mortality in patas monkeys is relatively low compared to the norm for mammals because it is not significantly different from that of adult female patas monkeys; and 3) infant mortality is significantly higher than adult female mortality in vervets. For both species, much of the mortality could be attributed to predation. An epidemic illness was also a major contributor to the mortality of adult female patas monkeys whereas chronic exposure to pathogens in a cold and damp microenvironment may have contributed to the mortality of infant vervets. Both populations experienced large fluctuations during the study period. Our results support the prediction from demographic models of life history evolution that high adult mortality relative to immature mortality selects for early maturation

Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

Background So far, more than 170 loci have been associated with circulating lipid levels through genomewide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. Methods We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ~60 000 individuals in the discovery stage and ~90 000 samples in the replication stage. Results Our study resu

Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery

Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF