Systematics within Gyps vultures: a clade at risk

BACKGROUND: Populations of the Oriental White-backed Vulture (Gyps bengalensis) have declined by over 95% within the past decade. This decline is largely due to incidental consumption of the non-steroidal anti-inflammatory veterinary pharmaceutical diclofenac, commonly used to treat domestic livestock. The conservation status of other Gyps vultures in southern Asia is also of immediate concern, given the lack of knowledge regarding status of their populations and the continuing existence of taxonomic uncertainties. In this study, we assess phylogenetic relationships for all recognized species and the majority of subspecies within the genus Gyps. The continuing veterinary use of diclofenac is an unknown but potential risk to related species with similar feeding habits to Gyps bengalensis. Therefore, an accurate assessment of the phylogenetic relationships among Gyps vultures should aid in their conservation by clarifying taxonomic uncertainties, and enabling inference of their respective relatedness to susceptible G. bengalensis. RESULTS: Phylogenetic results using mitochondrial cytB, ND2 and control region sequence data indicate a recent and rapid diversification within the genus Gyps. All recognized species formed monophyletic groups with high statistical support, with the exception of the Eurasian Vulture, for which specimens identified as subspecies G. fulvus fulvescens appear closely related to the Himalayan Vulture (G. himalayensis). In all analyses, the earliest divergence separated the Oriental White-backed Vulture from other Gyps taxa, with the next diverging taxon being either the African White-backed Vulture (G. africanus), or the Himalayan Vulture. All analyses supported a sister relationship between the Eurasian Vulture (G. f. fulvus), and Rüppell's Vulture (G. rueppellii), with this clade being sister to another consisting of the two taxa of "Long-billed" Vulture (G. indicus indicus and G. i. tenuirostris), and the Cape Vulture (G. coprotheres). These molecular phylogenies strongly support the treatment of indicus and tenuirostris as separate species, as does morphological data showing that these two taxa of similar overall size differ in proportions, especially in rostral, alar, and pedal characters. In addition, grouping of bengalensis and africanus together in the genus Pseudogyps, as historically proposed, is not upheld based on mitochondrial data. CONCLUSION: Both molecular and morphological data provide strong support for considering the "Long-billed" Vulture to be comprised of two species (G. indicus and G. tenuirostris), and further analysis is warranted to determine the taxonomic distinctiveness of G. f. fulvescens. Our phylogenetic analyses and conservative estimates suggest the diversification of Gyps taxa to be within the past 6 million years. Diclofenac susceptibility has been previously demonstrated for four Gyps species (G. indicus, G. fulvus, G. africanus, G. bengalensis), and the phylogenetic position of these species each forming a sister relationship with at least one of the remaining species, support concern that other Gyps taxa may be susceptible as well. Determining genetic and evolutionary distinctiveness for Gyps lineages is increasingly important as a breeding program is being established to prevent extinction

A New Species of Muscicapa Flycatcher from Sulawesi, Indonesia

The Indonesian island of Sulawesi, a globally important hotspot of avian endemism, has been relatively poorly studied ornithologically, to the extent that several new bird species from the region have been described to science only recently, and others have been observed and photographed, but never before collected or named to science. One of these is a new species of Muscicapa flycatcher that has been observed on several occasions since 1997. We collected two specimens in Central Sulawesi in 2012, and based on a combination of morphological, vocal and genetic characters, we describe the new species herein, more than 15 years after the first observations. The new species is superficially similar to the highly migratory, boreal-breeding Gray-streaked Flycatcher Muscicapa griseisticta, which winters in Sulawesi; however, the new species differs strongly from M. griseisticta in several morphological characters, song, and mtDNA. Based on mtDNA, the new species is only distantly related to M. griseisticta, instead being a member of the M. dauurica clade. The new species is evidently widely distributed in lowland and submontane forest throughout Sulawesi. This wide distribution coupled with the species' apparent tolerance of disturbed habitats suggests it is not currently threatened with extinction.This project was funded by the National Geographic Society (NGS CRE 8919-11; granted to PCR), the Loke Wan Tho Memorial Foundation (granted to DLY), and an EIPR scholarship at the University of Adelaide (granted to JBCH). Labwork for this project was co-funded by a National University of Singapore Faculty of Science start-up grant to FER (WBS R-154-000-570-133). We thank RISTEK for issuing the national research permits (for 2011, 0215/SIP/FRP/VI/2011; for 2012, 183/SIP/FRP/SM/VI/2012) and Lore Lindu National Park for permit letters. The Research Centre for Biology-LIPI supported DMP and DDP in their field research and provided facilities for laboratory analysis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Cost-Effectiveness of Hypertension Therapy According to 2014 Guidelines

BACKGROUND: On the basis of the 2014 guidelines for hypertension therapy in the United States, many eligible adults remain untreated. We projected the cost-effectiveness of treating hypertension in U.S. adults according to the 2014 guidelines. METHODS: We used the Cardiovascular Disease Policy Model to simulate drug-treatment and monitoring costs, costs averted for the treatment of cardiovascular disease, and quality-adjusted life-years (QALYs) gained by treating previously untreated adults between the ages of 35 and 74 years from 2014 through 2024. We assessed cost-effectiveness according to age, hypertension level, and the presence or absence of chronic kidney disease or diabetes. RESULTS: The full implementation of the new hypertension guidelines would result in approximately 56,000 fewer cardiovascular events and 13,000 fewer deaths from cardiovascular causes annually, which would result in overall cost savings. The projections showed that the treatment of patients with existing cardiovascular disease or stage 2 hypertension would save lives and costs for men between the ages of 35 and 74 years and for women between the ages of 45 and 74 years. The treatment of men or women with existing cardiovascular disease or men with stage 2 hypertension but without cardiovascular disease would remain cost-saving even if strategies to increase medication adherence doubled treatment costs. The treatment of stage 1 hypertension was cost-effective (defined as <$50,000 per QALY) for all men and for women between the ages of 45 and 74 years, whereas treating women between the ages of 35 and 44 years with stage 1 hypertension but without cardiovascular disease had intermediate or low cost-effectiveness. CONCLUSIONS: The implementation of the 2014 hypertension guidelines for U.S. adults between the ages of 35 and 74 years could potentially prevent about 56,000 cardiovascular events and 13,000 deaths annually, while saving costs. Controlling hypertension in all patients with cardiovascular disease or stage 2 hypertension could be effective and cost-saving. (Funded by the National Heart, Lung, and Blood Institute and others.

The Global Programme to Eliminate Lymphatic Filariasis: Health Impact after 8 Years

Lymphatic filariasis (LF) is a vector-borne, chronically disabling parasitic infection causing elephantiasis, lymphedema, and hydrocele. The infection is endemic in 83 countries worldwide, with more than 1.2 billion people at risk and 120 million already infected. Since 1998, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) has targeted elimination of LF by 2020. In its first 8 operational years, the program has scaled-up to provide more than 1.9 billion treatments through annual, single-dose mass drug administration (MDA) to ∼570 million individuals living in 48 LF-endemic countries. Not only do the GPELF drugs prevent the spread of LF, they also stop the progression of disease in those already infected. In addition, since two of the three drugs used for LF elimination have broad anti-parasite properties, treated populations are freed from both intestinal worms and from skin infections with onchocerca, lice, and scabies. To better understand the public health benefit of this ongoing global health initiative, we undertook an analysis of Programme data made available to WHO by participating countries. Our conservative estimates show that the GPELF has had an unprecedented public health impact on both LF and other neglected tropical diseases; it justly deserves the accolade of ‘a best buy’ in global health

Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10−6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10−8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10−8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10−8; RREB1: p = 5.7×10−8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology