HIV prevention trial design in an era of effective pre-exposure prophylaxis

Pre-exposure prophylaxis (PrEP) has demonstrated remarkable effectiveness protecting at-risk individuals from HIV-1 infection. Despite this record of effectiveness, concerns persist about the diminished protective effect observed in women compared with men and the influence of adherence and risk behaviors on effectiveness in targeted subpopulations. Furthermore, the high prophylactic efficacy of the first PrEP agent, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), presents challenges for demonstrating the efficacy of new candidates. Trials of new agents would typically require use of non-inferiority (NI) designs in which acceptable efficacy for an experimental agent is determined using pre-defined margins based on the efficacy of the proven active comparator (i.e. TDF/FTC) in placebo-controlled trials. Setting NI margins is a critical step in designing registrational studies. Under- or over-estimation of the margin can call into question the utility of the study in the registration package. The dependence on previous placebo-controlled trials introduces the same issues as external/historical controls. These issues will need to be addressed using trial design features such as re-estimated NI margins, enrichment strategies, run-in periods, crossover between study arms, and adaptive re-estimation of sample sizes. These measures and other innovations can help to ensure that new PrEP agents are made available to the public using stringent standards of evidence

Sibling interaction as a facilitator for talent development in sport

While current research has begun to address parental influences on talent development in sport, sibling interaction remains relatively under-examined. Therefore, this study aimed to explore the underpinning mechanisms through which sibling interaction impacts on talent development. Retrospective phenomenological interviews were conducted with four sets of siblings (N = 9), where at least one sibling had competed to an elite level. Findings revealed several higher-order themes that impacted positively on the talented athletes’ development: regularity of interaction in sport, emotional interpersonal skills, rivalry, resilience, co-operation and separation. Separation appeared as the athlete reached elite status, suggesting that these former mechanisms primarily impact during the development phase. Such findings support and extend the sibling, elite sport and talent development literature and provide valuable insight for both practitioners and academics. Importantly, coaches should consider a sibling’s role as an important mechanism outside of the formal coaching structure for talent development

Opto-mechanical design for sight windows under high loads

In this study, the design aspects of optically accessible pressure vessels are investigated via a case study of a High Pressure Combustor experimental rig. The rig was designed to take optical measurements of combustion, simulating the conditions found in internal combustion engines and turbines. Although, it is not new to equip chambers and reactors with sight windows, important aspects of design and relevant information regarding optical access is missing or are insufficiently explored or not readily accessible in the existing literature. A comprehensive review of requirements for optical access to such high-pressure, high-temperature systems has been conducted. It is shown in a readily-navigable format as function of application and precision, with data and technical correlations hitherto not found in a ‘user-friendly’ style. The material selection procedure is detailed and supported by a complete comparison of optical materials and relevant properties. The review revealed a significant inconsistency in mechanical properties claimed in the literature for optical materials. As a response to this, increased safety factor values are suggested as function of level of uncertainties and effects of failure, typically three to four times higher than the industrial standard. Moreover, newly developed equations are presented linking performance analysis to the design criteria

Radiocarbon analysis reveals expanded diet breadth associates with the invasion of a predatory ant

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Health surveillance of deployed military personnel occasionally leads to unexpected findings

Post-traumatic stress disorder (PTSD) can be caused by life threatening illness, such as cancer and coronary events. The study by Forbes et al. made the unexpected finding that military personnel evacuation with medical illness have similar rates of PTSD to those evacuated with combat injuries. It may be that the illness acts as a nonspecific stressor that interacts with combat exposures to increase the risk of PTSD. Conversely, the inflammatory consequence of systemic illness may augment the effects to traumatic stress and facilitate the immunological abnormalities that are now being associated with PTSD and depression. The impact of the stress on cytokine systems and their role in the onset of PTSD demands further investigation. Military personnel evacuated due to physical illness require similar screening and monitoring for the risk of PTSD to those injured who are already known to be at high risk.Alexander C McFarlan

Clustering patients on the basis of their individual course of low back pain over a six month period

<p>Abstract</p> <p>Background</p> <p>Several researchers have searched for subgroups in the heterogeneous population of patients with non-specific low back pain (LBP). To date, subgroups have been identified based on psychological profiles and the variation of pain.</p> <p>Methods</p> <p>This multicentre prospective observational study explored the 6- month clinical course with measurements of bothersomeness that were collected from weekly text messages that were sent by 176 patients with LBP. A hierarchical cluster analysis, Ward's method, was used to cluster patients according to the development of their pain.</p> <p>Results</p> <p>Four clusters with distinctly different clinical courses were described and further validated against clinical baseline variables and outcomes. Cluster 1, a "stable" cluster, where the course was relatively unchanged over time, contained young patients with good self- rated health. Cluster 2, a group of "fast improvers" who were very bothered initially but rapidly improved, consisted of patients who rated their health as relatively poor but experienced the fewest number of days with bothersome pain of all the clusters. Cluster 3 was the "typical patient" group, with medium bothersomeness at baseline and an average improvement over the first 4-5 weeks. Finally, cluster 4 contained the "slow improvers", a group of patients who improved over 12 weeks. This group contained older individuals who had more LBP the previous year and who also experienced most days with bothersome pain of all the clusters.</p> <p>Conclusions</p> <p>It is possible to define clinically meaningful clusters of patients based on their individual course of LBP over time. Future research should aim to reproduce these clusters in different populations, add further clinical variables to distinguish the clusters and test different treatment strategies for them.</p

How Sensory Experiences Affect Adolescents with an Autistic Spectrum Condition within the Classroom

Sensory processing difficulties are consistently reported amongst individuals with an autistic spectrum condition (ASC); these have a significant impact on daily functioning. Evidence in this area comes from observer reports and first-hand accounts; both have limitations. The current study used the Adolescent/Adult Sensory Profile (AASP; Brown and Dunn in The Adolescent/Adult Sensory Profile: self questionnaire. Pearson, 2002a), and a qualitative questionnaire to investigate sensory issues in school children with ASC. The AASP found that the participants’ mean scores were outside normal parameters. Participants reported difficulties in at least one sensory domain, with hearing affecting them the most. Content analysis revealed sensory sensitivity to affect the participant’s learning and that sensory experiences were largely negative. Results suggest that schools need to create sensory profiles for each individual with ASC

Prevalence and correlates of foot pain in a population-based study: the North West Adelaide health study

Background: Few population-based studies have examined the prevalence of foot pain in thegeneral community. The aims of this study were therefore to determine the prevalence, correlatesand impact of foot pain in a population-based sample of people aged 18 years and over living in the northwest region of Adelaide, South Australia.Methods: The North West Adelaide Health Study is a representative longitudinal cohort study ofn = 4,060 people randomly selected and recruited by telephone interview. The second stage of datacollection on this cohort was undertaken between mid 2004 and early 2006. In this phase,information regarding the prevalence of musculoskeletal conditions was included. Overall, n = 3,206 participants returned to the clinic during the second visit, and as part of the assessment were asked to report whether they had pain, aching or stiffness on most days in either of their feet. Data were also collected on body mass index (BMI); major medical conditions; other joint symptoms and health-related quality of life (the Medical Outcomes Study Short Form 36 [SF-36]).Results: Overall, 17.4% (95% confidence interval 16.2 – 18.8) of participants indicated that theyhad foot pain, aching or stiffness in either of their feet. Females, those aged 50 years and over,classified as obese and who reported knee, hip and back pain were all significantly more likely to report foot pain. Respondents with foot pain scored lower on all domains of the SF-36 afteradjustment for age, sex and BMI.Conclusion: Foot pain affects nearly one in five of people in the community, is associated withincreased age, female sex, obesity and pain in other body regions, and has a significant detrimental impact on health-related quality of life.Catherine L Hill, Tiffany K Gill, Hylton B Menz and Anne W Taylo

The Power of Exercise: Buffering the Effect of Chronic Stress on Telomere Length

Background: Chronic psychological stress is associated with detrimental effects on physical health, and may operate in part through accelerated cell aging, as indexed by shorter telomeres at the ends of chromosomes. However, not all people under stress have distinctly short telomeres, and we examined whether exercise can serve a stress-buffering function. We predicted that chronic stress would be related to short telomere length (TL) in sedentary individuals, whereas in those who exercise, stress would not have measurable effects on telomere shortening. Methodology and Principal Findings: 63 healthy post-menopausal women underwent a fasting morning blood draw for whole blood TL analysis by a quantitative polymerase chain reaction method. Participants completed the Perceived Stress Scale (Cohen et al., 1983), and for three successive days reported daily minutes of vigorous activity. Participants were categorized into two groups-sedentary and active (those getting Centers for Disease Control-recommended daily amount of activity). The likelihood of having short versus long telomeres was calculated as a function of stress and exercise group, covarying age, BMI and education. Logistic regression analyses revealed a significant moderating effect of exercise. As predicted, among non-exercisers a one unit increase in the Perceived Stress Scale was related to a 15-fold increase in the odds of having short telomeres (p,.05), whereas in exercisers, perceived stress appears to be unrelated to TL (B = 2.59, SE =.78, p =.45)

Foot and ankle surgery in Australia: a descriptive analysis of the Medicare Benefits Schedule database, 1997–2006

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