The importance of changing climatic variability for tropical wildlife population growth rates

Oral Session: Global change biologyMuch interest in the population impact of climate change has focused on the widespread increases in mean temperature, but little attention has been paid to the less homogeneous and less predictable changes in temperature variability. Well-established demographic theories have long pointed to a potential impact of environmental variability on population growth rates, but these have rarely been tested in practice, and the limited evidence available has suggested only minor effects. Using long-term data on tropical bird populations, we demonstrate that the prevailing levels of temperature variability are large enough to have a major impact; reducing population growth rates by up to half ...postprin

A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve.

AimsThe mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling.Materials and resultsRandomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041).ConclusionsIn this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects.Trial registrationclinicaltrials.gov Identifier: NCT01342029

Quantifying the daily economic impact of extreme space weather due to failure in electricity transmission infrastructure

Extreme space weather due to coronal mass ejections has the potential to cause considerable disruption to the global economy by damaging the transformers required to operate electricity transmission infrastructure. However, expert opinion is split between the potential outcome being one of a temporary regional blackout and of a more prolonged event. The temporary blackout scenario proposed by some is expected to last the length of the disturbance, with normal operations resuming after a couple of days. On the other hand, others have predicted widespread equipment damage with blackout scenarios lasting months. In this paper we explore the potential costs associated with failure in the electricity transmission infrastructure in the U.S. due to extreme space weather, focusing on daily economic loss. This provides insight into the direct and indirect economic consequences of how an extreme space weather event may affect domestic production, as well as other nations, via supply chain linkages. By exploring the sensitivity of the blackout zone, we show that on average the direct economic cost incurred from disruption to electricity represents only 49% of the total potential macroeconomic cost. Therefore, if indirect supply chain costs are not considered when undertaking cost-benefit analysis of space weather forecasting and mitigation investment, the total potential macroeconomic cost is not correctly represented. The paper contributes to our understanding of the economic impact of space weather, as well as making a number of key methodological contributions relevant for future work. Further economic impact assessment of this threat must consider multiday, multiregional events.The authors acknowledge partial financial support from American International Group during the research and especially thank Brad Fischtrom, Siddhartha Dalal, and their team for providing useful comments and insights as the research progressed. We also thank attendees of the workshop held at the Cambridge Judge Business School in July 2015. Three anonymous reviewers are acknowledged for providing useful comments and feedback on the paper. Oughton was partially supported by the UK Engineering and Physical Science Research Council under grant EP/N017064/1: Multiscale InfraSTRucture systems AnaLytics. Horne and Thomson would like to acknowledge the support of the Natural Environment Research Council (NERC). This paper is published by permission of the Executive Director, British Geological Survey (NERC)

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Effects of short-term treatment with atorvastatin in smokers with asthma - a randomized controlled trial

<b>Background</b> The immune modulating properties of statins may benefit smokers with asthma. We tested the hypothesis that short-term treatment with atorvastatin improves lung function or indices of asthma control in smokers with asthma.<p></p> <b>Methods</b> Seventy one smokers with mild to moderate asthma were recruited to a randomized double-blind parallel group trial comparing treatment with atorvastatin (40 mg per day) versus placebo for 4 weeks. After 4 weeks treatment inhaled beclometasone (400 ug per day) was added to both treatment arms for a further 4 weeks. The primary outcome was morning peak expiratory flow after 4 weeks treatment. Secondary outcome measures included indices of asthma control and airway inflammation.<p></p> <b>Results</b> At 4 weeks, there was no improvement in the atorvastatin group compared to the placebo group in morning peak expiratory flow [-10.67 L/min, 95% CI -38.70 to 17.37, p=0.449], but there was an improvement with atorvastatin in asthma quality of life score [0.52, 95% CI 0.17 to 0.87 p=0.005]. There was no significant improvement with atorvastatin and inhaled beclometasone compared to inhaled beclometasone alone in outcome measures at 8 weeks.<p></p> <b>Conclusions</b> Short-term treatment with atorvastatin does not alter lung function but may improve asthma quality of life in smokers with mild to moderate asthma. Clinicaltrials.gov identifier: NCT0046382

P06-08. Building an African HIV preventive trial network

Africa is a crucial setting for preventive HIV clinical trials. We present our experience of setting up a collaborative network of African clinical research centers (CRC)

Interventions to Promote Cancer Awareness and Early Presentation: Systematic Review

Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research. We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled studies of interventions delivered to communities. We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation. We found limited evidence that public education campaigns reduce stage at presentation of breast cancer, malignant melanoma and retinoblastoma