Estimating the burden of disease attributable to four selected environmental risk factors in South Africa

The first South African National Burden of Disease study quantified the underlying causes of premature mortality and morbidity experienced in South Africa in the year 2000. This was followed by a Comparative Risk Assessment to estimate the contributions of 17 selected risk factors to burden of disease in South Africa. This paper describes the health impact of exposure to four selected environmental risk factors: unsafe water, sanitation and hygiene; indoor air pollution from household use of solid fuels; urban outdoor air pollution and lead exposure.The study followed World Health Organization comparative risk assessment methodology. Population-attributable fractions were calculated and applied to revised burden of disease estimates (deaths and disability adjusted life years, [DALYs]) from the South African Burden of Disease study to obtain the attributable burden for each selected risk factor. The burden attributable to the joint effect of the four environmental risk factors was also estimated taking into account competing risks and common pathways. Monte Carlo simulation-modeling techniques were used to quantify sampling, uncertainty.Almost 24 000 deaths were attributable to the joint effect of these four environmental risk factors, accounting for 4.6% (95% uncertainty interval 3.8-5.3%) of all deaths in South Africa in 2000. Overall the burden due to these environmental risks was equivalent to 3.7% (95% uncertainty interval 3.4-4.0%) of the total disease burden for South Africa, with unsafe water sanitation and hygiene the main contributor to joint burden. The joint attributable burden was especially high in children under 5 years of age, accounting for 10.8% of total deaths in this age group and 9.7% of burden of disease.This study highlights the public health impact of exposure to environmental risks and the significant burden of preventable disease attributable to exposure to these four major environmental risk factors in South Africa. Evidence-based policies and programs must be developed and implemented to address these risk factors at individual, household, and community levels

Replication Fork Polarity Gradients Revealed by Megabase-Sized U-Shaped Replication Timing Domains in Human Cell Lines

In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late replication at centers. Significant overlap is observed between U-domains of different cell lines and also with germline replication domains exhibiting a N-shaped nucleotide compositional skew. From the demonstration that the average fork polarity is directly reflected by both the compositional skew and the derivative of the replication timing profile, we argue that the fact that this derivative displays a N-shape in U-domains sustains the existence of large-scale gradients of replication fork polarity in somatic and germline cells. Analysis of chromatin interaction (Hi-C) and chromatin marker data reveals that U-domains correspond to high-order chromatin structural units. We discuss possible models for replication origin activation within U/N-domains. The compartmentalization of the genome into replication U/N-domains provides new insights on the organization of the replication program in the human genome

Microsurgery can cure most intracranial dural arteriovenous fistulae of the sinus and non-sinus type

There is consensus that intracranial dural arteriovenous fistulae (dAVF) with direct (non-sinus-type) or indirect (sinus-type) retrograde filling of a leptomeningeal vein should be treated due to the high risk of neurological deficits and hemorrhage. No consensus exists on treatment modality (surgery and/or embolization) and, if surgery is performed, on the best surgical strategy. This series aims to evaluate the role of surgery in the management of aggressive dAVFs. Forty-two patients underwent surgery. Opening and packing the sinus with thrombogenic material was performed in 9 of the 12 sinus-type dAVFs. In two sinus-type fistulae of the cavernous sinus and 1 of the torcular, microsurgery was used as prerequisite for subsequent embolization by providing access to the sinus. In the 30 non-sinus-type dAVFs, surgery consisted of interruption of the draining vein at the intradural entry point. In 41 patients undergoing 43 operations, elimination of the dAVF was achieved (97.6%). In one case, a minimal venous drainage persisted after surgery. The transient surgical morbidity was 11.9% (n = 5) and the permanent surgical morbidity 7.1% (n = 3). Our surgical strategy was to focus on the arterialized leptomeningeal vein in the non-sinus-type and on the arterialized sinus segment in the sinus-type dAVFs allowing us to obliterate all but one dAVF with a low morbidity rate. We therefore propose that microsurgery should be considered early in the treatment of both types of aggressive dAVFs. In selected cases of cavernous sinus dAVFs, the role of microsurgery is reduced to that of an adjunct to endovascular therapy

Global Assessment of Extinction Risk to Populations of Sockeye Salmon Oncorhynchus nerka

BACKGROUND: Concern about the decline of wild salmon has attracted the attention of the International Union for the Conservation of Nature (IUCN). The IUCN applies quantitative criteria to assess risk of extinction and publishes its results on the Red List of Threatened Species. However, the focus is on the species level and thus may fail to show the risk to populations. The IUCN has adapted their criteria to apply to populations but there exist few examples of this type of assessment. We assessed the status of sockeye salmon Oncorhynchus nerka as a model for application of the IUCN population-level assessments and to provide the first global assessment of the status of an anadromous Pacific salmon. METHODS/PRINCIPAL FINDINGS: We found from demographic data that the sockeye salmon species is not presently at risk of extinction. We identified 98 independent populations with varying levels of risk within the species' range. Of these, 5 (5%) are already extinct. We analyzed the risk for 62 out of 93 extant populations (67%) and found that 17 of these (27%) are at risk of extinction. The greatest number and concentration of extinct and threatened populations is in the southern part of the North American range, primarily due to overfishing, freshwater habitat loss, dams, hatcheries, and changing ocean conditions. CONCLUSIONS/SIGNIFICANCE: Although sockeye salmon are not at risk at the species-level, about one-third of the populations that we analyzed are at risk or already extinct. Without an understanding of risk to biodiversity at the level of populations, the biodiversity loss in salmon would be greatly underrepresented on the Red List. We urge government, conservation organizations, scientists and the public to recognize this limitation of the Red List. We also urge recognition that about one-third of sockeye salmon global population diversity is at risk of extinction or already extinct

Surviving in isolation: genetic variation, bottlenecks and reproductive strategies in the Canarian endemic Limonium macrophyllum (Plumbaginaceae)

Oceanic archipelagos are typically rich in endemic taxa, because they offer ideal conditions for diversification and speciation in isolation. One of the most remarkable evolutionary radiations on the Canary Islands comprises the 16 species included in Limonium subsection Nobiles, all of which are subject to diverse threats, and legally protected. Since many of them are single-island endemics limited to one or a few populations, there exists a risk that a loss of genetic variation might limit their longterm survival. In this study, we used eight newly developed microsatellite markers to characterize the levels of genetic variation and inbreeding in L. macrophyllum, a species endemic to the North-east of Tenerife that belongs to Limonium subsection Nobiles. We detected generally low levels of genetic variation over all populations (HT = 0.363), and substantial differentiation among populations (FST = 0.188;RST = 0.186) coupled with a negligible degree of inbreeding (F = 0.042). Obligate outcrossing may have maintained L. macrophyllum relatively unaffected by inbreeding despite the species’ limited dispersal ability and the genetic bottlenecks likely caused by a prolonged history of grazing. Although several factors still constitute a risk for the conservation of L. macrophyllum, the lack of inbreeding and the recent positive demographic trends observed in the populations of this species are factors that favour its future persistence

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)