Lifestyle factors associated with sex differences in Kaposi sarcoma incidence among adult black South Africans: A case-control study

Kaposi Sarcoma (KS) is endemic in several countries in Southern and Eastern Africa, relatively rare worldwide but a leading cancer among people living with HIV. KS has always been more common in adult males than females. We assessed the prevalence of known cancer modifying factors (parity, hormonal contraceptive use in females, sex-partners, smoking and alcohol consumption in both sexes), and their relationship to KS, and whether any of these could account for the unequal KS sex ratios. We calculated logistic regression case-control adjusted odds ratios (ORadj), and 95% confidence intervals (95%CI), between KS and each of the modifying factors, using appropriate comparison controls. Controls were cancer types that had no known relationship to exposures of interest (infection or alcohol or smoking or contraceptive use). The majority of the 1275 KS cases were HIV positive (97%), vs. 15.7% in 10,309 controls. The risk of KS among those with HIV was high in males (ORadj=116.70;95%CI=71.35–190.88) and females (ORadj=93.91;95%CI=54.22–162.40). Among controls, the prevalence of smoking and alcohol consumption was five and three times higher in males vs. females. We found a positive association between KS and heavy vs. non-drinking (ORadj=1.31;95%CI=1.03–1.67), and in current heavy vs. never smokers (ORadj=1.82;95%CI=1.07–3.10). These associations remained positive for alcohol consumption (but with wider CIs) after stratification by sex, and restriction to HIV positive participants. We found no evidence of interactions of smoking and alcohol by sex. Smoking and alcohol consumption may provide a possible explanation for the KS sex differences, given both exposures are more common in men, but confounding and bias cannot be fully ruled out. The role smoking and alcohol play in relation to viral loads of HIV/KSHV, differences in immunological responses or other genetic differences between males and females warrant further studies

Epidemiology of Kaposi's sarcoma in sub-Saharan Africa

Kaposi's sarcoma (KS) has become a common AIDS-defining cancer in sub-Saharan Africa. Kaposi's sarcoma-associated human herpesvirus strongly modulated by HIV-related immune suppression are the principal causes of this cancer. No other risk factors have been identified as playing a strong role. HIV prevention programs and good coverage of antiretroviral therapy (ART) in developed countries resulted in a remarkable decline in HIV-KS incidence and better KS prognosis. By contrast, in sub-Saharan Africa, population ART rollout has lagged, but clinical studies have shown positive results in reduction of KS incidence and better KS prognosis. However, the effect of ART rollout in relation to population KS incidence is unclear. We describe the incidence of KS in sub-Saharan Africa, in four time-periods, (1) before 1980 (before HIV/AIDS era); (2) 1981–2000 (early HIV/AIDS era, limited or no ART coverage); (3) 2001–2010 (early ART coverage period); and (4) 2011–2016 (fair to good ART coverage period). We used KS incidence data available from WHO-International Agency for Research on Cancer (IARC) publications and the Africa Cancer Registry Network. National HIV prevalence and ART coverage data were derived from UNAIDS/WHO. A rapid increase in KS incidence was observed throughout sub-Saharan Africa as the HIV epidemic progressed, reaching peak incidences in Period 2 (pre-ART rollout) of 50.8 in males and 20.3 per 100 000 in females (Zimbabwe, Harare). The overall unweighted average decline in KS incidence between 2000 and 2010 and 2011–2016 was 27%, but this decline was not statistically significant across the region. ART rollout coincides with a decline in KS incidence across several regions in sub-Saharan Africa. The importance of other risk factors such as reductions in HIV incidence could not be ascertained

An acoustic on-chip goniometer for room temperature macromolecular crystallography

This paper describes the design, development and succesful use of an on-chip goniometer for room-temperature macromolecular crystallography via acoustically induced rotations. We present for the first time a low cost, rate-tunable, acoustic actuator for randomised in-fluid sample orientation and its utilisation for protein structure determination on a synchrotron beamline. The device enables the efficient collection of diffraction data via a rotation method from a sample within a surface confined droplet. This method facillitates efficient macromolecular structural data acquisition in fluid environments for dynamical studies

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

Comparative Lipidomics of Azole Sensitive and Resistant Clinical Isolates of Candida albicans Reveals Unexpected Diversity in Molecular Lipid Imprints

Although transcriptome and proteome approaches have been applied to determine the regulatory circuitry behind multidrug resistance (MDR) in Candida, its lipidome remains poorly characterized. Lipids do acclimatize to the development of MDR in Candida, but exactly how the acclimatization is achieved is poorly understood. In the present study, we have used a high-throughput mass spectrometry-based shotgun approach and analyzed the lipidome of genetically matched clinical azole-sensitive (AS) and -resistant (AR) isolates of C. albicans. By comparing the lipid profiling of matched isolates, we have identified major classes of lipids and determined more than 200 individual molecular lipid species among these major classes. The lipidome analysis has been statistically validated by principal component analysis. Although each AR isolate was similar with regard to displaying a high MIC to drugs, they had a distinct lipid imprint. There were some significant commonalities in the lipid profiles of these pairs, including molecular lipid species ranging from monounsaturated to polyunsaturated fatty acid-containing phosphoglycerides. Consistent fluctuation in phosphatidyl serine, mannosylinositolphosphorylceramides, and sterol esters levels indicated their compensatory role in maintaining lipid homeostasis among most AR isolates. Notably, overexpression of either CaCdr1p or CaMdr1p efflux pump proteins led to a different lipidomic response among AR isolates. This study clearly establishes the versatility of lipid metabolism in handling azole stress among various matched AR isolates. This comprehensive lipidomic approach will serve as a resource for assessing strategies aimed at disrupting the functions of Candida lipids, particularly the functional interactions between lipids and MDR determinants

Ten years of major equestrian injury: are we addressing functional outcomes?

YesFunding provided by the Open Access Authors Fund

Invasion of the Red Seaweed \u3cem\u3eHeterosiphonia japonica\u3c/em\u3e Spans Biogeographic Provinces in the Western North Atlantic Ocean

The recent invasion of the red alga Heterosiphonia japonica in the western North Atlantic Ocean has provided a unique opportunity to study invasion dynamics across a biogeographical barrier. Native to the western North Pacific Ocean, initial collections in 2007 and 2009 restricted the western North Atlantic range of this invader to Rhode Island, USA. However, through subtidal community surveys, we document the presence of Heterosiphonia in coastal waters from Maine to New York, USA, a distance of more than 700 km. This geographical distribution spans a well-known biogeographical barrier at Cape Cod, Massachusetts. Despite significant differences in subtidal community structure north and south of Cape Cod, Heterosiphonia was found at all but two sites surveyed in both biogeographic provinces, suggesting that this invader is capable of rapid expansion over broad geographic ranges. Across all sites surveyed, Heterosiphonia comprised 14% of the subtidal benthic community. However, average abundances of nearly 80% were found at some locations. As a drifting macrophyte, Heterosiphonia was found as intertidal wrack in abundances of up to 65% of the biomass washed up along beaches surveyed. Our surveys suggest that the high abundance of Heterosiphonia has already led to marked changes in subtidal community structure; we found significantly lower species richness in recipient communities with higher Heterosiphona abundances. Based on temperature and salinity tolerances of the European populations, we believe Heterosiphonia has the potential to invade and alter subtidal communities from Florida to Newfoundland in the western North Atlantic

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Operationalising the concept of ecosystem collapse for conservation practice

Concern is growing about ecosystem collapse, namely the abrupt decline or loss of an ecosystem resulting from human activities. While efforts to assess the risk of ecosystem collapse have developed at large spatial scales, less attention has been given to the local scales at which conservation management decisions are typically made. Development of appropriate management responses to ecosystem collapse has been limited by uncertainty regarding how collapse may best be identified, together with its underlying causes. Here we operationalise ecosystem collapse for conservation practice by providing a robust definition of collapse, in a form that is relevant to the scale of conservation decision-making. We provide an overview of different causes of collapse, and then explore the implications of this understanding for conservation practice, by examining potential management responses. This is achieved through development of a decision tree, which we illustrate through a series of case studies. We also explore the role of indicators for the early detection of collapse and for monitoring the effectiveness of management responses. Ecosystem collapse represents a significant challenge to conservation practice, as abrupt changes in ecosystem structure, function and composition can occur with little warning, leading to profound impacts on both biodiversity and human society. The risks of ecosystem collapse are likely to increase in future, as multiple forms of environmental change continue to intensify. We suggest that selection of management responses should be based on an understanding of the causal mechanisms responsible for collapse, which can be identified through appropriate monitoring and research activities