Testosterone for the aging male; current evidence and recommended practice

An international consensus document was recently published and provides guidance on the diagnosis, treatment and monitoring of late-onset hypogonadism (LOH) in men. The diagnosis of LOH requires biochemical and clinical components. Controversy in defining the clinical syndrome continues due to the high prevalence of hypogonadal symptoms in the aging male population and the non-specific nature of these symptoms. Further controversy surrounds setting a lower limit of normal testosterone, the limitations of the commonly available total testosterone result in assessing some patients and the unavailability of reliable measures of bioavailable or free testosterone for general clinical use. As with any clinical intervention testosterone treatment should be judged on a balance of risk versus benefit. The traditional benefits of testosterone on sexual function, mood, strength and quality of life remain the primary goals of treatment but possible beneficial effects on other parameters such as bone density, obesity, insulin resistance and angina are emerging and will be reviewed. Potential concerns regarding the effects of testosterone on prostate disease, aggression and polycythaemia will also be addressed. The options available for treatment have increased in recent years with the availability of a number of testosterone preparations which can reliably produce physiological serum concentrations

A New Approach to Environmental Valuation for New Zealand

New Zealand’s Resource Management Act is frequently criticised for the costs and delays it imposes on activities, but less attention is given to the consistency of values it applies to environmental effects through its decisions. The wide variety of parties who exercise decision roles under the act lack guidance on the economic value of the environment, and non-market valuation studies are too costly to be widely used and too few and varied to infer reliable generic values. Drawing on experience in estimating the public value of safety improvements, this article proposes an alternative approach that measures people’s aversion to the risk of environmental impacts of different scales and severity which could yield values sufficiently generic to be widely used, and outlines its uses both within and beyond the RMA applications

Towards optimum smoking cessation interventions during pregnancy: a household model to explore cost‐effectiveness

BACKGROUND AND AIMS: Previous economic evaluations of smoking cessation interventions for pregnant women are limited to single components, which do not in isolation offer sufficient potential impact to address smoking cessation targets. To inform the development of more appropriate complex interventions, we (1) describe the development of the Economics of Smoking in Pregnancy: Household (ESIP.H) model for estimating the life‐time cost‐effectiveness of smoking cessation interventions aimed at pregnant women and (2) use a hypothetical case study to demonstrate how ESIP.H can be used to identify the characteristics of optimum smoking cessation interventions. METHODS: The hypothetical intervention was based on current evidence relating to component elements, including financial incentives, partner smoking, intensive behaviour change support, cigarettes consumption and duration of support to 12 months post‐partum. ESIP.H was developed to assess the life‐time health and cost impacts of multi‐component interventions compared with standard National Health Service (NHS) care in England. ESIP.H considers cigarette consumption, partner smoking and some health conditions (e.g. obesity) that were not included in previous models. The Markov model's parameters were estimated based on published literature, expert judgement and evidence‐based assumptions. The hypothetical intervention was evaluated from an NHS perspective. RESULTS: The hypothetical intervention was associated with an incremental gain in quitters (mother and partner) at 12 months postpartum of 249 [95% confidence interval (CI) = 195–304] per 1000 pregnant smokers. Over the long‐term, it had an incremental negative cost of £193 (CI = –£779 to 344) and it improved health, with a 0.50 (CI = 0.36–0.69) increase in quality‐adjusted life years (QALYs) for mothers, partners and offspring, with a 100% probability of being cost‐effective. CONCLUSIONS: The Economics of Smoking in Pregnancy: Household model for estimating cost‐effectiveness of smoking cessation interventions aimed at pregnant women found that a hypothetical smoking cessation intervention would greatly extend reach, reduce smoking and be cost‐effective

The global distribution of Bacillus anthracis and associated anthrax risk to humans, livestock and wildlife.

Bacillus anthracis is a spore-forming, Gram-positive bacterium responsible for anthrax, an acute infection that most significantly affects grazing livestock and wild ungulates, but also poses a threat to human health. The geographic extent of B. anthracis is poorly understood, despite multi-decade research on anthrax epizootic and epidemic dynamics; many countries have limited or inadequate surveillance systems, even within known endemic regions. Here, we compile a global occurrence dataset of human, livestock and wildlife anthrax outbreaks. With these records, we use boosted regression trees to produce a map of the global distribution of B. anthracis as a proxy for anthrax risk. We estimate that 1.83 billion people (95% credible interval (CI): 0.59-4.16 billion) live within regions of anthrax risk, but most of that population faces little occupational exposure. More informatively, a global total of 63.8 million poor livestock keepers (95% CI: 17.5-168.6 million) and 1.1 billion livestock (95% CI: 0.4-2.3 billion) live within vulnerable regions. Human and livestock vulnerability are both concentrated in rural rainfed systems throughout arid and temperate land across Eurasia, Africa and North America. We conclude by mapping where anthrax risk could disrupt sensitive conservation efforts for wild ungulates that coincide with anthrax-prone landscapes

Testosterone stimulates cholesterol clearance from human macrophages by activating LXRα

Aims Low testosterone in men is associated with increased cardiovascular events and mortality. Testosterone has beneficial effects on several cardiovascular risk factors including cholesterol, endothelial dysfunction and inflammation as key mediators of atherosclerosis. Although evidence suggests testosterone is anti-atherogenic, its mechanism of action is unknown. The present study investigates whether testosterone exerts anti-atherogenic effects by stimulating cholesterol clearance from macrophages via activation of liver X receptor (LXRα), a nuclear master regulator of cellular cholesterol homeostasis, lipid regulation, and inflammation. Main methods Using human monocyte THP-1 cells differentiated into macrophages, the effect of testosterone (1–10 nM) treatment (24–72 h) on the expression of LXRα and LXR- targets apolipoprotein E (APOE), ATP-binding cassette transporter A1 (ABCA1), sterol regulatory element-binding transcription factor 1 (SREBF1) and fatty acid synthase (FAS), was investigated via qPCR and western blotting, with or without androgen receptor blockade with flutamide or LXR antagonism with CPPSS-50. Cholesterol clearance was measured by monitoring fluorescent dehydroergosterol (DHE) cellular clearance and ABCA1 cellular translocation was observed via immunocytochemistry in testosterone treated macrophages. Key findings Testosterone increased mRNA and protein expression of LXRα, APOE, ABCA1, SREBF1 and FAS. These effects were blocked by flutamide and independently by LXR antagonism with CPPSS-50. Furthermore testosterone stimulated cholesterol clearance from the macrophages and promoted the translocation of ABCA1 toward the cell membrane. Significance Testosterone acts via androgen receptor-dependent pathways to stimulate LXRα and downstream targets to induce cholesterol clearance in human macrophages. This may, in part, explain the anti-atherogenic effects of testosterone frequently seen clinically

Simultaneous resonant x-ray diffraction measurement of polarization inversion and lattice strain in polycrystalline ferroelectrics

International audienceStructure-property relationships in ferroelectrics extend over several length scales from the individual unit cell to the macroscopic device, and with dynamics spanning a broad temporal domain. Characterizing the multi-scale structural origin of electric field-induced polarization reversal and strain in ferroelectrics is an ongoing challenge that so far has obscured its fundamental behaviour. By utilizing small intensity differences between Friedel pairs due to resonant scattering, we demonstrate a time-resolved X-ray diffraction technique for directly and simultaneously measuring both lattice strain and, for the first time, polarization reversal during in-situ electrical perturbation. This technique is demonstrated for BaTiO3-BiZn0.5Ti0.5O3 (BT-BZT) polycrystalline ferroelectrics, a prototypical lead-free piezoelectric with an ambiguous switching mechanism. This combines the benefits of spectroscopic and diffraction-based measurements into a single and robust technique with time resolution down to the ns scale, opening a new door to in-situ structure-property characterization that probes the full extent of the ferroelectric behaviou

The Role of the Private Sector in Supporting Malaria Control in Resource Development Settings.

Industrial operations of the private sector, such as extraction, agriculture, and construction, can bring large numbers of people into new settlement areas and cause environmental change that promotes the transmission of vector-borne diseases. Industry-related workers and communities unduly exposed to infection risk typically lack the knowledge and means to protect themselves. However, there is a strong business rationale for protecting local resident employees through integrated vector control programs, as well as an ethical responsibility to care for these individuals and the affected communities. We discuss the role and challenges of the private sector in developing malaria control programs, which can include extensive collaborations with the public sector that go on to form the basis of national vector control programs or more broadly support local healthcare systems

The seasonal cycle of carbonate system processes in Ryder Bay, West Antarctic Peninsula

The carbon cycle in seasonally sea-ice covered waters remains poorly understood due to both a lack of observational data and the complexity of the system. Here we present three consecutive seasonal cycles of upper ocean dissolved inorganic carbon (DIC) and total alkalinity measurements from Ryder Bay on the West Antarctic Peninsula. We attribute the observed changes in DIC to four processes: mixing of water masses, air–sea CO2 flux, calcium carbonate precipitation/dissolution and photosynthesis/respiration. This approach enables us to resolve the main drivers of the seasonal DIC cycle and also investigate the mechanisms behind interannual variability in the carbonate system. We observe a strong, asymmetric seasonal cycle in the carbonate system, driven by physical processes and primary production. In summer, melting glacial ice and sea ice and a reduction in mixing with deeper water reduce the concentration of DIC in surface waters. The dominant process affecting the carbonate system is net photosynthesis which reduces DIC and the fugacity of CO2, making the ocean a net sink of atmospheric CO2. In winter, mixing with deeper, carbon-rich water and net heterotrophy increase surface DIC concentrations, resulting in pH as low as 7.95 and aragonite saturation states close to 1. We observe no clear seasonal cycle of calcium carbonate precipitation/dissolution but some short-lived features of the carbonate time series strongly suggest that significant precipitation of calcium carbonate does occur in the Bay. The variability observed in this study demonstrates that changes in mixing and sea-ice cover significantly affect carbon cycling in this dynamic environment. Maintaining this unique time series will allow the carbonate system in seasonally sea-ice covered waters to be better understood