Interferometry

The following recommended programs are reviewed: (1) infrared and optical interferometry (a ground-based and space programs); (2) compensation for the atmosphere with adaptive optics (a program for development and implementation of adaptive optics); and (3) gravitational waves (high frequency gravitational wave sources (LIGO), low frequency gravitational wave sources (LAGOS), a gravitational wave observatory program, laser gravitational wave observatory in space, and technology development during the 1990's). Prospects for international collaboration and related issues are also discussed

Cost analysis of noninvasive blood-based microRNA testing versus CT scans for follow-up in patients with testicular germ-cell tumors

BACKGROUND: Our group has developed a noninvasive blood-based microRNA (miRNA) test for improving diagnosis, disease monitoring, and relapse detection in malignant testicular germ-cell tumors (TGCTs). Performance analysis suggests the test is likely to have comparable sensitivity and specificity in detecting TGCT as computed tomography (CT), thus reducing the need for serial CT scans for follow-up monitoring, with associated reductions in cumulative radiation burden and second cancer risk. To facilitate clinical adoption, we undertook a cost analysis to identify the budget impact of replacing CT scans with miRNA testing within health care systems. METHODS: The TGCT aftercare pathway was mapped out using National Comprehensive Cancer Network guidelines. A Markov model was built to simulate the impact of the miRNA test on TGCT aftercare costs. Incidence, treatment probabilities, relapse rate, and death rate data were collected from published studies to populate the model. RESULTS: Applying our model to the US health care system, the miRNA test has the potential to save up to $69 million per year in aftercare expenses related to TGCT treatment, with exact savings depending on the adoption rate and test price. CONCLUSION: This analysis demonstrates the potential positive budget impact of adopting miRNA testing in place of CT scans in the clinical management of TGCTs

Scope for Credit Risk Diversification

This paper considers a simple model of credit risk and derives the limit distribution of losses under different assumptions regarding the structure of systematic risk and the nature of exposure or firm heterogeneity. We derive fat-tailed correlated loss distributions arising from Gaussian risk factors and explore the potential for risk diversification. Where possible the results are generalised to non-Gaussian distributions. The theoretical results indicate that if the firm parameters are heterogeneous but come from a common distribution, for sufficiently large portfolios there is no scope for further risk reduction through active portfolio management. However, if the firm parameters come from different distributions, then further risk reduction is possible by changing the portfolio weights. In either case, neglecting parameter heterogeneity can lead to underestimation of expected losses. But, once expected losses are controlled for, neglecting parameter heterogeneity can lead to overestimation of risk, whether measured by unexpected loss or value-at-risk

Economic Evaluation of Transperineal versus Transrectal Devices for Local Anaesthetic Prostate Biopsies

Abstract: Background: Biopsy of the prostate for suspected cancer is usually performed transrectally under local anaesthesia in the outpatient clinic setting. As this involves piercing the bowel wall, the procedure is associated with a risk of infection. Recently, devices that facilitate transperineal biopsy approaches have been developed that avoid piercing the bowel and so should reduce the risk of infection. Objective: The aim of this study was to estimate the cost effectiveness of transperineal versus transrectal ultrasound-guided local anaesthesia procedures for prostate biopsy from the perspective of the UK NHS and to estimate the value of further research in the area. Methods: a) Decision tree and Markov model synthesising all relevant evidence estimating the life-time costs and QALYs accrued from each biopsy mode. b) Value of information analysis to predict the return from further research and thus guide future research efforts. Results: Transperineal biopsy yields an ICER below £20,000 per QALY gained at a per-procedure device acquisition cost below £81, or £41 for cost-neutrality. These results are driven by differences in consumables cost, reduced cost of treating infections, and QALY gains associated with reduced infections. There is value in future research on the diagnostic accuracy of transperineal versus transrectal biopsies and the incidence of iatrogenic infection and sepsis; consideration should be given to enriching the patient population with men with intermediate-risk disease. Conclusions: Transperineal biopsy devices may be cost effective compared with transrectal biopsy at per-procedure acquisition costs below £81 and cost-neutral if under £41. Future research is required to confirm or refute these findings, particularly randomised comparisons of the diagnostic accuracy and infection risks between the methods

Self-Monitoring and Management of Blood Pressure in Patients with Stroke or TIA: An Economic Evaluation of TEST-BP, A Randomised Controlled Trial

Abstract: Background: Prevention of secondary stroke following initial ictus is an important focus of after-stroke care. Blood pressure (BP) is a key risk factor, so usual care following stroke or transient ischaemic attack includes regular BP checks and monitoring of anti-hypertensive medication. This is traditionally carried out in primary care, but the evidence supporting self-monitoring and self-guided management of BP in the general population with hypertension is growing. Objective: Our objective was to estimate the cost effectiveness of treatment as usual (TAU) versus (1) self-monitoring of BP (S-MON) and (2) self-monitoring and guided self-management of anti-hypertensive medication (S-MAN). Methods: This was a within-trial economic evaluation of a randomised controlled trial estimating the incremental cost per 1 mmHg BP reduction and per quality-adjusted life-year (QALY) gained over a 6-month time horizon from the perspective of the UK National Health Service (NHS). Results: Data were evaluable for 140 participants. Costs per patient were £473, £853 and £1035; mean reduction in systolic BP (SBP) was 3.6, 6.7 and 6.1 mmHg, and QALYs accrued were 0.427, 0.422 and 0.423 for TAU, S-MON and S-MAN, respectively. No statistically significant differences in incremental costs or outcomes were detected. On average, S-MAN was dominated or extended dominated. The incremental cost per 1 mmHg BP reduction from S-MON versus TAU was £137. Conclusion: On average, S-MAN is an inefficient intervention. S-MON may be cost effective, depending on the willingness to pay for a 1 mmHg BP reduction, although it yielded fewer QALYs over the within-trial time horizon. Decision modelling is required to explore the longer-term costs and outcomes

Pre-vaccination prevalence of anogenital and oral human papillomavirus in young HIV-infected men who have sex with men.

The aims of this study were to: 1) determine prevalence of anogenital and oral HPV, 2) determine concordance between HPV at anal, perianal, scrotal/penile, and oral sites; and 3) describe factors associated with anogenital HPV types targeted by the 9-valent vaccine. Data were collected from 2012 to 2015 among men who have sex with men 18-26 years of age enrolled in a vaccine trial (N = 145). Penile/scrotal, perianal, anal, and oral samples were tested for 61 HPV types. Logistic regression was used to identify factors associated with types in the 9-valent vaccine. Participants' mean age was 23.0 years, 55.2% were African-American, and 26.2% were Hispanic; 93% had anal, 40% penile, and 6% oral HPV. Among those with anogenital infection, 18% had HPV16. Concordance was low between anogenital and oral sites. Factors independently associated with a 9-valent vaccine-type HPV were: race (African-American vs. White, OR=2.67, 95% CI=1.11-6.42), current smoking (yes vs. no, OR=2.37, 95% CI=1.03-5.48), and number of recent receptive anal sex partners (2+ vs. 0, OR=3.47, 95% CI=1.16-10.4). Most MSM were not infected with HPV16 or HPV18, suggesting that they may still benefit from HPV vaccination, but anogenital HPV was very common, highlighting the importance of vaccinating men before sexual initiation. CLINICAL TRIAL NUMBER: NCT01209325

Effectiveness and cost-effectiveness of the GoActive intervention to increase physical activity among UK adolescents: A cluster randomised controlled trial

Background: Less than 20% of adolescents globally meet recommended levels of physical activity, and not meeting these recommended levels is associated with social disadvantage and rising disease risk. The determinants of physical activity in adolescents are multilevel and poorly understood, but the school’s social environment likely plays an important role. We conducted a cluster randomised controlled trial to assess the effectiveness of a school-based programme (GoActive) to increase moderate-to-vigorous physical activity (MVPA) among adolescents. Methods and findings: Non-fee-paying, co-educational schools including Year 9 students in the UK counties of Cambridgeshire and Essex were eligible for inclusion. Within participating schools (n = 16), all Year 9 students were eligible and invited to participate. Participants were 2,862 13- to 14-year-olds (84% of eligible students). After baseline assessment, schools were computer-randomised, stratified by school-level pupil premium funding (below/above county-specific median) and county (control: 8 schools, 1,319 participants, mean [SD] participants per school n = 165 [62]; intervention: 8 schools, 1,543 participants, n = 193 [43]). Measurement staff were blinded to allocation. The iteratively developed, feasibility-tested 12-week intervention, aligned with self-determination theory, trained older adolescent mentors and in-class peer-leaders to encourage classes to conduct 2 new weekly activities. Students and classes gained points and rewards for engaging in any activity in or out of school. The primary outcome was average daily minutes of accelerometer-assessed MVPA at 10-month follow-up; a mixed-methods process evaluation evaluated implementation. Of 2,862 recruited participants (52.1% male), 2,167 (76%) attended 10-month follow-up measurements; we analysed the primary outcome for 1,874 participants (65.5%). At 10 months, there was a mean (SD) decrease in MVPA of 8.3 (19.3) minutes in the control group and 10.4 (22.7) minutes in the intervention group (baseline-adjusted difference [95% confidence interval] −1.91 minutes [−5.53 to 1.70], p = 0.316). The programme cost £13 per student compared with control; it was not cost-effective. Overall, 62.9% of students and 87.3% of mentors reported that GoActive was fun. Teachers and mentors commented that their roles in programme delivery were unclear. Implementation fidelity was low. The main methodological limitation of this study was the relatively affluent and ethnically homogeneous sample. Conclusions: In this study, we observed that a rigorously developed school-based intervention was no more effective than standard school practice at preventing declines in adolescent physical activity. Interdisciplinary research is required to understand educational-setting-specific implementation challenges. School leaders and authorities should be realistic about expectations of the effect of school-based physical activity promotion strategies implemented at scale. Trial registration: ISRCTN Registry ISRCTN31583496

Large emissions from floodplain trees close the Amazon methane budget

Wetlands are the largest global source of atmospheric methane (CH4), a potent greenhouse gas. However, methane emission inventories from the Amazon floodplain, the largest natural geographic source of CH4 in the tropics, consistently underestimate the atmospheric burden of CH4 determined via remote sensing and inversion modelling, pointing to a major gap in our understanding of the contribution of these ecosystems to CH4 emissions. Here we report CH4 fluxes from the stems of 2,357 individual Amazonian floodplain trees from 13 locations across the central Amazon basin. We find that escape of soil gas through wetland trees is the dominant source of regional CH4 emissions. Methane fluxes from Amazon tree stems were up to 200 times larger than emissions reported for temperate wet forests6 and tropical peat swamp forests, representing the largest non-ebullitive wetland fluxes observed. Emissions from trees had an average stable carbon isotope value (δ13C) of −66.2 ± 6.4 per mil, consistent with a soil biogenic origin. We estimate that floodplain trees emit 15.1 ± 1.8 to 21.2 ± 2.5 teragrams of CH4 a year, in addition to the 20.5 ± 5.3 teragrams a year emitted regionally from other sources. Furthermore, we provide a ‘top-down’ regional estimate of CH4 emissions of 42.7 ± 5.6 teragrams of CH4 a year for the Amazon basin, based on regular vertical lower-troposphere CH4 profiles covering the period 2010–2013. We find close agreement between our ‘top-down’ and combined ‘bottom-up’ estimates, indicating that large CH4 emissions from trees adapted to permanent or seasonal inundation can account for the emission source that is required to close the Amazon CH4 budget. Our findings demonstrate the importance of tree stem surfaces in mediating approximately half of all wetland CH4 emissions in the Amazon floodplain, a region that represents up to one-third of the global wetland CH4 source when trees are combined with other emission sources

GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk

Male pattern baldness (MPB) or androgenetic alopecia is one of the most common conditions affecting men, reaching a prevalence of similar to 50% by the age of 50; however, the known genes explain little of the heritability. Here, we present the results of a genome-wide association study including more than 70,000 men, identifying 71 independently replicated loci, of which 30 are novel. These loci explain 38% of the risk, suggesting that MPB is less genetically complex than other complex traits. We show that many of these loci contain genes that are relevant to the pathology and highlight pathways and functions underlying baldness. Finally, despite only showing genome-wide genetic correlation with height, pathway-specific genetic correlations are significant for traits including lifespan and cancer. Our study not only greatly increases the number of MPB loci, illuminating the genetic architecture, but also provides a new approach to disentangling the shared biological pathways underlying complex diseases