Biomarkers of chemical exposure: state of the art.

Establishing associations between environmental agents and disease presents challenges to both epidemiologists and toxicologists, particularly in cases of complex gene-environment interactions and when there is a long latency between exposure and disease. Biologic markers, physiological signals that reflect exposure, early cellular response, or inherent or acquired susceptibilities, provide a new strategy for resolving some of these problems. Biomarker research assumes that toxicant-induced diseases are progressive and that injury proceeds from entry of the toxicant into target cells, which induces subcellular biochemical events, to cell- and organ-level events that eventually induce irreversible or persistent organism dysfunction. The epidemiologic value of a biomarker lies in its ability to predict backward toward exposure and forward toward risk of clinical outcome, which is largely unknown. Research in mechanistic toxicology will advance the range of useful biomarkers in epidemiology and clinical medicine

Fitness and Adiposity Are Independently Associated with Cardiometabolic Risk in Youth

Purpose. The purpose of the study was to examine the independent associations of adiposity and cardiorespiratory fitness with clustered cardiometabolic risk. Methods. A cross-sectional sample of 192 adolescents (118 boys), aged 14–16 years, was recruited from a South Lanarkshire school in the West of Scotland. Anthropometry and blood pressure were measured, and blood samples were taken. The 20 m multistage fitness test was the indicator of cardiorespiratory fitness (CRF). A clustered cardiometabolic risk score was constructed from HDL-C (inverted), LDL-C, HOMA, systolic blood pressure, and triglycerides. Interleukin-6, C-reactive protein, and adiponectin were also measured and examined relative to the clustered cardiometabolic risk score, CRF, and adiposity. Results. Although significant, partial correlations between BMI and waist circumference (WC) and both CRF and adiponectin were negative and weak to moderate, while correlations between the BMI and WC and CRP were positive but weak to moderate. Weak to moderate negative associations were also evident for adiponectin with CRP, IL-6, and clustered cardiometabolic risk. WC was positively associated while CRF was negatively associated with clustered cardiometabolic risk. With the additional adjustment for either WC or CRF, the independent associations with cardiometabolic risk persisted. Conclusion. WC and CRF are independently associated with clustered cardiometabolic risk in Scottish adolescent

Controlled release of human growth hormone fused with a human hybrid Fc fragment through a nanoporous polymer membrane

Nanotechnology has been applied to the development of more effective and compatible drug delivery systems for therapeutic proteins. Human growth hormone (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human IgD and IgG(4) to produce a long-acting fusion protein. The fusion protein, hGH-hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B lymphocyte and to exhibit an almost identical circular dichroism spectrum to that of the original hGH-hyFc, suggesting that the released fusion protein should maintain the functional and structural integrity of hGH. Thus, the nanoporous release device could be a potential delivery system for the long-term controlled release of therapeutic proteins fused with the hybrid Fc fragment.X111313sciescopu

Who will use pre-exposure prophylaxis (PrEP) and why?: Understanding PrEP awareness and acceptability amongst men who have sex with men in the UK – a mixed methods study

Background: Recent clinical trials suggest that pre-exposure prophylaxis (PrEP) may reduce HIV transmission by up to 86% for men who have sex with men (MSM), whilst relatively high levels of PrEP acceptability have been reported to date. This study examines PrEP awareness amongst sub-groups of MSM communities and acceptability amongst MSM in a low prevalence region (Scotland, UK), using a mixed methods design. Methods: Quantitative surveys of n = 690 MSM recruited online via social and sociosexual media were analysed using descriptive statistics and multivariate logistic regression. In addition, n = 10 in-depth qualitative interviews with MSM were analysed thematically. Results: Under one third (29.7%) of MSM had heard of PrEP, with awareness related to living in large cities, degree level education, commercial gay scene use and reporting an HIV test in the last year. Just under half of participants (47.8%) were likely to use PrEP if it were available but there was no relationship between PrEP acceptability and previous PrEP awareness. Younger men (18–25 years) and those who report higher risk UAI were significantly more likely to say they would use PrEP. Qualitative data described specific PrEP scenarios, illustrating how risk, patterns of sexual practice and social relationships could affect motivation for and nature of PrEP use. Conclusion: These findings suggest substantial interest PrEP amongst MSM reporting HIV risk behaviours in Scotland. Given the Proud results, there is a strong case to investigate PrEP implementation within the UK. However, it appears that disparities in awareness have already emerged along traditional indicators of inequality. Our research identifies the need for comprehensive support when PrEP is introduced, including a key online component, to ensure equity of awareness across diverse MSM communities (e.g. by geography, education, gay scene use and HIV proximity), as well as to responding to the diverse informational and sexual health needs of all MSM communities

Exploring Graphs with Time Constraints by Unreliable Collections of Mobile Robots

A graph environment must be explored by a collection of mobile robots. Some of the robots, a priori unknown, may turn out to be unreliable. The graph is weighted and each node is assigned a deadline. The exploration is successful if each node of the graph is visited before its deadline by a reliable robot. The edge weight corresponds to the time needed by a robot to traverse the edge. Given the number of robots which may crash, is it possible to design an algorithm, which will always guarantee the exploration, independently of the choice of the subset of unreliable robots by the adversary? We find the optimal time, during which the graph may be explored. Our approach permits to find the maximal number of robots, which may turn out to be unreliable, and the graph is still guaranteed to be explored. We concentrate on line graphs and rings, for which we give positive results. We start with the case of the collections involving only reliable robots. We give algorithms finding optimal times needed for exploration when the robots are assigned to fixed initial positions as well as when such starting positions may be determined by the algorithm. We extend our consideration to the case when some number of robots may be unreliable. Our most surprising result is that solving the line exploration problem with robots at given positions, which may involve crash-faulty ones, is NP-hard. The same problem has polynomial solutions for a ring and for the case when the initial robots' positions on the line are arbitrary. The exploration problem is shown to be NP-hard for star graphs, even when the team consists of only two reliable robots

The Conformal Anomaly of M5-Branes

We show that the conformal anomaly for N M5-branes grows like $N^3$. The method we employ relates Coulomb branch interactions in six dimensions to interactions in four dimensions using supersymmetry. This leads to a relation between the six-dimensional conformal anomaly and the conformal anomaly of N=4 Yang-Mills. Along the way, we determine the structure of the four derivative interactions for the toroidally compactified (2,0) theory, while encountering interesting novelties in the structure of the six derivative interactions.Comment: 38 pages, LaTeX; references adde