Re-Os geochronology and isotope systematics, and organic and sulfur geochemistry of the middle-late Paleocene Waipawa Formation, New Zealand: Insights into early Paleogene seawater Os isotope composition

In the middle–late Paleocene, a marine, organic-rich sedimentary unit (Waipawa Formation [Fm]) in which the organic matter was derived mainly from terrestrial plants was deposited in many of New Zealand's sedimentary basins. The unique organofacies of this formation has not been identified in any other time interval within the geological history of the Southwest Pacific, indicating that unusual climatic and oceanographic conditions likely prevailed during this time. It has, therefore, attracted wide scientific interest due to its significance for regional and global reconstruction of the early Paleogene transitional climate as well as potential for oil and gas production. Scarcity of age-diagnostic fossils, presence of unconformities and lack of volcanic interbeds have, however, hindered precise dating and correlations of all the known occurrences of the formation. Here, rhenium‑osmium (Re-Os) geochronology has yielded the first radiometric age for the formation (57.5 ± 3.5 Ma), which is consistent with available biostratigraphic age determinations (59.4–58.7 Ma). Further, a comparison of Re-Os, bulk pyrolysis, sulfur and palynofacies data for the Waipawa Fm with those of more typical marine sediments such as the underlying Whangai Fm supports the interpretation that the chelating precursors or fundamental binding sites responsible for uptake of Re and Os are present in all types of organic matter, and that these elements have a greater affinity for organic chelating sites than for sulfides. The results also indicate that sedimentation rate may not play a dominant role in enhanced uptake of Re and Os by organic-rich sedimentary rocks. The initial 187Os/188Os values for the Waipawa (~0.28) and Whangai (~0.36) formations are broadly similar to those reported for coeval pelagic sediments from the central Pacific Ocean, further constraining the low-resolution marine 187Os/188Os record of the Paleocene. We present a compilation of 187Os/188Os values from organic-rich sedimentary rocks spanning the period between 70 and 50 Ma which shows that seawater Os gradually became less radiogenic from the latest Cretaceous, reaching a minimum value in the earliest late Paleocene (~59 Ma) during the deposition of Waipawa Fm, and then increased through the later Paleocene and into the early Eocene. The composite Os isotope record broadly correlates with global temperature (δ18O and TEX86) and carbon isotope (δ13C) records from the middle Paleocene to early Eocene, which is inferred to reflect climate-modulated changes in continental weathering patterns

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

Effects of thymic selection of the T cell repertoire on HLA-class I associated control of HIV infection

Without therapy, most people infected with human immunodeficiency virus (HIV) ultimately progress to AIDS. Rare individuals (‘elite controllers’) maintain very low levels of HIV RNA without therapy, thereby making disease progression and transmission unlikely. Certain HLA class I alleles are markedly enriched in elite controllers, with the highest association observed for HLA-B57 (ref. 1). Because HLA molecules present viral peptides that activate CD8+ T cells, an immune-mediated mechanism is probably responsible for superior control of HIV. Here we describe how the peptide-binding characteristics of HLA-B57 molecules affect thymic development such that, compared to other HLA-restricted T cells, a larger fraction of the naive repertoire of B57-restricted clones recognizes a viral epitope, and these T cells are more cross-reactive to mutants of targeted epitopes. Our calculations predict that such a T-cell repertoire imposes strong immune pressure on immunodominant HIV epitopes and emergent mutants, thereby promoting efficient control of the virus. Supporting these predictions, in a large cohort of HLA-typed individuals, our experiments show that the relative ability of HLA-B alleles to control HIV correlates with their peptide-binding characteristics that affect thymic development. Our results provide a conceptual framework that unifies diverse empirical observations, and have implications for vaccination strategies.Mark and Lisa Schwartz FoundationNational Institutes of Health (U.S.) (Director’s Pioneer award)Philip T. and Susan M. Ragon FoundationJane Coffin Childs Memorial Fund for Medical ResearchBill & Melinda Gates FoundationNational Institute of Allergy and Infectious Diseases (U.S.)National Institutes of Health (U.S.) (contract no. HHSN261200800001E)National Institutes of Health (U.S.). Intramural Research ProgramNational Cancer Institute (U.S.)Center for Cancer Research (National Cancer Institute (U.S.)

Compensating control participants when the intervention is of significant value: experience in Guatemala, India, Peru and Rwanda

The Household Air Pollution Intervention Network (HAPIN) trial is a randomised controlled trial in Guatemala, India, Peru and Rwanda to assess the health impact of a clean cooking intervention in households using solid biomass for cooking. The HAPIN intervention—a liquefied petroleum gas (LPG) stove and 18-month supply of LPG—has significant value in these communities, irrespective of potential health benefits. For control households, it was necessary to develop a compensation strategy that would be comparable across four settings and would address concerns about differential loss to follow-up, fairness and potential effects on household economics. Each site developed slightly different, contextually appropriate compensation packages by combining a set of uniform principles with local community input. In Guatemala, control compensation consists of coupons equivalent to the LPG stove’s value that can be redeemed for the participant’s choice of household items, which could include an LPG stove. In Peru, control households receive several small items during the trial, plus the intervention stove and 1 month of fuel at the trial’s conclusion. Rwandan participants are given small items during the trial and a choice of a solar kit, LPG stove and four fuel refills, or cash equivalent at the end. India is the only setting in which control participants receive the intervention (LPG stove and 18 months of fuel) at the trial’s end while also being compensated for their time during the trial, in accordance with local ethics committee requirements. The approaches presented here could inform compensation strategy development in future multi-country trials

Lung Toxicity of Ambient Particulate Matter from Southeastern U.S. Sites with Different Contributing Sources: Relationships between Composition and Effects

BACKGROUND: Exposure to air pollution and, more specifically, particulate matter (PM) is associated with adverse health effects. However, the specific PM characteristics responsible for biological effects have not been defined. OBJECTIVES: In this project we examined the composition, sources, and relative toxicity of samples of PM with aerodynamic diameter ≥2.5 μm (PM(2.5)) collected from sites within the Southeastern Aerosol Research and Characterization (SEARCH) air monitoring network during two seasons. These sites represent four areas with differing sources of PM(2.5), including local urban versus regional sources, urban areas with different contributions of transportation and industrial sources, and a site influenced by Gulf of Mexico weather patterns. METHODS: We collected samples from each site during the winter and summer of 2004 for toxicity testing and for chemical analysis and chemical mass balance–based source apportionment. We also collected PM(2.5) downwind of a series of prescribed forest burns. We assessed the toxicity of the samples by instillation into rat lungs and assessed general toxicity, acute cytotoxicity, and inflammation. Statistical dose–response modeling techniques were used to rank the relative toxicity and compare the seasonal differences at each site. Projection-to-latent-surfaces (PLS) techniques examined the relationships among sources, chemical composition, and toxicologic end points. RESULTS AND CONCLUSIONS: Urban sites with high contributions from vehicles and industry were most toxic