Numerical and granulometric approaches to geophysical granular flows

Volcanic ash clouds can be fed by an upward-directed eruption column (Plinian column) or by elutriation from extensive pyroclastic-flows (coignimbrite cloud). For large-scale eruptions, there is considerable uncertainty about which mechanism is dominant. Here we analyze in a novel way a comprehensive grainsize database for pyroclastic deposits. We demonstrate that the Mount Pinatubo climactic eruption deposits were substantially derived from coignimbrite clouds, and not only by a Plinian cloud as generally thought. Coignimbrite ash-fall deposits are much richer in breathable <10 m ash (5–25 wt%) than pure Plinian ash at most distances from the source volcano. We also show that coignimbrite ash clouds, as at Pinatubo, are expected to be more water rich than Plinian clouds, leading to removal of more HCl prior to stratospheric injection, thereby reducing their atmospheric impact.

Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared

BACKGROUND: The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. METHODS AND FINDINGS: We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%-97%) in South Africa and 96% (94%-97%) in Switzerland, and 26% (22%-29%) and 27% (24%-31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2) during months 1-3 and 1.77 (0.90-3.50) during months 4-24. CONCLUSIONS: Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.

Computational and Biochemical Approaches to Molecular Epidemiology

Mining activity in Butte, Montana has taken place, or continues to take place, within the urban residence of Butte itself. This has led to urban areas with high concentrations of toxic metals such as arsenic, lead, copper, zinc, mercury and cadmium. Advances in protein study and gene sequencing has opened the possibility of finding molecular biomarkers whose presence, absence or morphological changes could indicate disease processes in populations exposed to environmental toxins. While in principle, biomarkers can be any chemicals or metabolites, as well as proteins and genes that are indicative of exposure to xenobiotics, this study seeks to identify changes in cellular pathways that suggest chronic (or acute) exposure to low-levels of metals associated with historical mining activities on the Butte Hill that could cause oxidative stress or other stress to the cell.

TB research at UT-Houston--a review of cord factor: new approaches to drugs, vaccines and the pathogenesis of tuberculosis.

Tuberculosis remains a major threat as drug resistance continues to increase. Pulmonary tuberculosis in adults is responsible for 80% of clinical cases and nearly 100% of transmission of infection. Unfortunately, since we have no animal models of adult type pulmonary tuberculosis, the most important type of disease remains largely out of reach of modern science and many fundamental questions remain unanswered. This paper reviews research dating back to the 1950's providing compelling evidence that cord factor (trehalose 6,6 dimycolate [TDM]) is essential for understanding tuberculosis. However, the original papers by Bloch and Noll were too far ahead of their time to have immediate impact. We can now recognize that the physical and biologic properties of cord factor are unprecedented in science, especially its ability to switch between two sets of biologic activities with changes in conformation. While TDM remains on organisms, it protects them from killing within macrophages, reduces antibiotic effectiveness and inhibits the stimulation of protective immune responses. If it comes off organisms and associates with lipid, TDM becomes a driver of tissue damage and necrosis. Studies emanating from cord factor research have produced (1) a rationale for improving vaccines, (2) an approach to new drugs that overcome natural resistance to antibiotics, (3) models of caseating granulomas that reproduce multiple manifestations of human tuberculosis. (4) evidence that TDM is a key T cell antigen in destructive lesions of tuberculosis, and (5) a new understanding of the pathology and pathogenesis of postprimary tuberculosis that can guide more informative studies of long standing mysteries of tuberculosis.