Offspring sex ratio and gonadal irradiation in the British Childhood Cancer Survivor Study

We investigated offspring sex ratio among 6232 offspring born to 3218 survivors of childhood cancer in relation to therapeutic irradiation, and pooled our data with those from two other large-scale studies giving a total of 9685 offspring. Exposure to high-dose gonadal irradiation was not associated with a significant alteration in offspring sex ratio compared to low doses (men: P=0.58, women: P=0.66). There was also no evidence that the ratio varied with time since cancer diagnosis when comparing survivors treated with radiotherapy vs those without (men: P=0.51; women: P=0.46). This, the largest study to date, finds no evidence that exposure to radiation affects the offspring sex ratio among survivors of childhood cancer

Beliefs about the Minds of Others Influence How We Process Sensory Information

Attending where others gaze is one of the most fundamental mechanisms of social cognition. The present study is the first to examine the impact of the attribution of mind to others on gaze-guided attentional orienting and its ERP correlates. Using a paradigm in which attention was guided to a location by the gaze of a centrally presented face, we manipulated participants' beliefs about the gazer: gaze behavior was believed to result either from operations of a mind or from a machine. In Experiment 1, beliefs were manipulated by cue identity (human or robot), while in Experiment 2, cue identity (robot) remained identical across conditions and beliefs were manipulated solely via instruction, which was irrelevant to the task. ERP results and behavior showed that participants' attention was guided by gaze only when gaze was believed to be controlled by a human. Specifically, the P1 was more enhanced for validly, relative to invalidly, cued targets only when participants believed the gaze behavior was the result of a mind, rather than of a machine. This shows that sensory gain control can be influenced by higher-order (task-irrelevant) beliefs about the observed scene. We propose a new interdisciplinary model of social attention, which integrates ideas from cognitive and social neuroscience, as well as philosophy in order to provide a framework for understanding a crucial aspect of how humans' beliefs about the observed scene influence sensory processing

Smoke-free legislation and child health

In this paper, we aim to present an overview of the scientific literature on the link between smoke-free legislation and early-life health outcomes. Exposure to second-hand smoke is responsible for an estimated 166 ,000 child deaths each year worldwide. To protect people from tobacco smoke, the World Health Organization recommends the implementation of comprehensive smoke-free legislation that prohibits smoking in all public indoor spaces, including workplaces, bars and restaurants. The implementation of such legislation has been found to reduce tobacco smoke exposure, encourage people to quit smoking and improve adult health outcomes. There is an increasing body of evidence that shows that children also experience health benefits after implementation of smoke-free legislation. In addition to protecting children from tobacco smoke in public, the link between smoke-free legislation and improved child health is likely to be mediated via a decline in smoking during pregnancy and reduced exposure in the home environment. Recent studies have found that the implementation of smoke-free legislation is associated with a substantial decrease in the number of perinatal deaths, preterm births and hospital attendance for respiratory tract infections and asthma in children, although such benefits are not found in each study. With over 80% of the world’s population currently unprotected by comprehensive smoke-free laws, protecting (unborn) children from the adverse impact of tobacco smoking and SHS exposure holds great potential to benefit public health and should therefore be a key priority for policymakers and health workers alike

Conventional heart failure therapy in cardiac ATTR amyloidosis

BACKGROUND AND AIMS: The aims of this study were to assess prescription patterns, dosages, discontinuation rates and association with prognosis of conventional heart failure (HF) medications in patients with transthyretin cardiac amyloidosis (ATTR-CA). METHODS: A retrospective analysis of all consecutive patients diagnosed with ATTR-CA at the National Amyloidosis Centre between 2000-2022 identified 2371 patients with ATTR-CA. RESULTS: Prescription of HF medications was greater among patients with a more severe cardiac phenotype, comprising beta-blockers in 55.4%, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin-II receptor blockers (ARB) in 57.4%, and mineralocorticoid receptor antagonists (MRAs) in 39.0% of cases. During a median follow-up of 27.8 months (IQR 10.6-51.3), 21.7% had beta-blockers discontinued, and 32.9% had ACEi/ARB discontinued. In contrast, only 7.5% had MRAs discontinued. Propensity score-matched analysis demonstrated that treatment with MRAs was independently associated with a reduced risk of mortality in the overall population (HR 0.77 [95% CI 0.66-0.89], P40% (HR 0.75 [95% CI 0.63-0.90], P=0.002); and treatment with low-dose beta-blockers was independently associated with a reduced risk of mortality in a pre-specified subgroup of patients with a LVEF ≤40% (HR 0.61 [95% CI 0.45-0.83], P=0.002). No convincing differences were found for treatment with ACEi/ARBs. CONCLUSIONS: Conventional HF medications are currently not widely prescribed in ATTR-CA, and those that received medication had more severe cardiac disease. Beta-blockers and ACEi/ARBs were often discontinued, but low-dose beta-blockers were associated with reduced risk of mortality in patients with a LVEF ≤40%. In contrast, MRAs were rarely discontinued and were associated with reduced risk of mortality in the overall population; but these findings require confirmation in prospective randomized controlled trials

Tobacco control policies and perinatal health:A national quasi-experimental study

We investigated whether changes in perinatal outcomes occurred following introduction of key tobacco control policies in the Netherlands: smoke-free legislation in workplaces plus a tobacco tax increase and mass media campaign (January-February 2004); and extension of the smoke-free law to the hospitality industry, accompanied by another tax increase and mass media campaign (July 2008). This was a national quasi-experimental study using Netherlands Perinatal Registry data (2000-2011; registration: ClinicalTrials.gov NCT02189265). Primary outcome measures were: perinatal mortality, preterm birth, and being small-for-gestational age (SGA). The association with timing of the tobacco control policies was investigated using interrupted time series logistic regression analyses with adjustment for confounders. Among 2,069,695 singleton births, there were 13,027 (0.6%) perinatal deaths, 116,043 (5.6%) preterm live-births and 187,966 (9.1%) SGA live-births. The 2004 policies were not associated with significant changes in the odds of developing any of the primary outcomes. After the 2008 policy change, a -4.4% (95% CI -2.4; -6.4, p < 0.001) decrease in odds of being SGA was observed. A reduction in SGA births, but not preterm birth or perinatal mortality, was observed in the Netherlands after extension of the smoke-free workplace law to bars and restaurants in conjunction with a tax increase and mass media campaign

The effectiveness of problem solving therapy for stroke patients: Study protocol for a pragmatic randomized controlled trial

Background: Coping style is one of the determinants of health-related quality of life after stroke. Stroke patients make less use of active problem-oriented coping styles than other brain damaged patients. Coping styles can be influenced by means of intervention. The primary aim of this study is to investigate if Problem Solving Therapy is an effective group intervention for improving coping style and health-related quality of life in stroke patients. The secondary aim is to determine the effect of Problem Solving Therapy on depression, social participation, health care consumption, and to determine the cost-effectiveness of the intervention.Methods/design: We strive to include 200 stroke patients in the outpatient phase of rehabilitation treatment, using a multicenter pragmatic randomized controlled trial with one year follow-up. Patients in the intervention group will receive Problem Solving Therapy in addition to the standard rehabilitation program. The intervention will be provided in an open group design, with a continuous flow of patients. Primary outcome measures are coping style and health-related quality of life. Secondary outcome measures are depression, social participation, health care consumption, and the cost-effectiveness of the intervention.Discussion: We designed our study as close to the implementation in practice as possible, using a pragmatic randomized trial and open group design, to represent a realistic estimate of the effectiveness of the intervention. If effective, Problem Solving Therapy is an inexpensive, deliverable and sustainable group intervention for stroke rehabilitation programs.Trial registration: Nederlands Trial Register, NTR2509

Using equity premium survey data to estimate future wealth

We present the first systematic methods for combining different experts' responses to equity premium surveys. These techniques are based on the observation that the survey data are approximately gamma distributed. This distribution has convenient analytical properties that enable us to address three important problems that investment managers must face. First, we construct probability density functions for the future values of equity index tracker funds. Second, we calculate unbiased and minimum least square error estimators of the future value of these funds. Third, we derive optimal asset allocation weights between equities and the risk-free asset for risk-averse investors. Our analysis allows for both herding and biasedness in expert responses. We show that, unless investors are highly uncertain about expert biases or forecasts are very highly correlated, many investment decisions can be based solely on the mean of the survey data minus any expected bias. We also make recommendations for the design of future equity premium surveys

Assessment of post-competition peak blood lactate in male and female master swimmers aged 40–79 years and its relationship with swimming performance

The main purpose of this study was to measure the postcompetition blood lactate concentration ([La]b) in master swimmers of both sexes aged between 40 and 79 years in order to relate it to age and swimming performance. One hundred and eight swimmers participating in the World Master Championships were assessed for [La]b and the average rate of lactate accumulation (La’;mmol l-1 s-1) was calculated. In addition, 77 of them were also tested for anthropometric measures. When the subjects were divided into 10-year age groups, males exhibited higher [La]b than women (factorial ANOVA, P < 0.01) and a steeper decline with ageing than female subjects. Overall, mean values (SD) of [La]b were 10.8 (2.8), 10.3 (2.0), 10.3 (1.9), 8.9 (3.2) mmol l-1 in women, and 14.2 (2.5), 12.4 (2.5), 11.0 (1.6), 8.2 (2.0) mmol l-1 in men for, respectively, 40–49, 50–59, 60–69, 70–79 years’ age groups. When, however, [La]b values were normalised for a ‘‘speed index’’, which takes into account swimming speed as a percentage of world record, these sex-related differences, although still present, were considerably attenuated. Furthermore, the differences in La’ between males and females were larger in the 40–49 age group (0.34 vs 0.20 mmol l-1 s-1 for 50-m distance) than in the 70–79 age group (0.12 vs 0.14 mmol l-1 s-1 for 50-m distance). Different physiological factors, supported by the considered anthropometric measurements, are suggested to explain the results

Energetic Selection of Topology in Ferredoxins

Models of early protein evolution posit the existence of short peptides that bound metals and ions and served as transporters, membranes or catalysts. The Cys-X-X-Cys-X-X-Cys heptapeptide located within bacterial ferredoxins, enclosing an Fe4S4 metal center, is an attractive candidate for such an early peptide. Ferredoxins are ancient proteins and the simple α+β fold is found alone or as a domain in larger proteins throughout all three kingdoms of life. Previous analyses of the heptapeptide conformation in experimentally determined ferredoxin structures revealed a pervasive right-handed topology, despite the fact that the Fe4S4 cluster is achiral. Conformational enumeration of a model CGGCGGC heptapeptide bound to a cubane iron-sulfur cluster indicates both left-handed and right-handed folds could exist and have comparable stabilities. However, only the natural ferredoxin topology provides a significant network of backbone-to-cluster hydrogen bonds that would stabilize the metal-peptide complex. The optimal peptide configuration (alternating αL,αR) is that of an α-sheet, providing an additional mechanism where oligomerization could stabilize the peptide and facilitate iron-sulfur cluster binding

'Relief of oppression': An organizing principle for researchers' obligations to participants in observational studies in the developing world

<p>Abstract</p> <p>Background</p> <p>A central question in the debate about exploitation in international research is whether investigators and sponsors from high-income countries (HIC) have obligations to address background conditions of injustice in the communities in which they conduct their research, beyond the healthcare and other research-related needs of participants, to aspects of their basic life circumstances.</p> <p>Discussion</p> <p>In this paper, we describe <b>t</b>he Majengo sexually transmitted disease (STD) Cohort study, a long-term prospective, observational cohort of sex workers in Nairobi, Kenya. Despite important scientific contributions and a wide range of benefits to the women of the cohort, most of the women have remained in the sex trade during their long-standing participation in the cohort, prompting allegations of exploitation. The Majengo STD cohort case extends the debate about justice in international research ethics beyond clinical trials into long-term observational research. We sketch the basic features of a new approach to understanding and operationalizing obligations of observational researchers, which we call 'relief of oppression'. 'Relief of oppression' is an organizing principle, analogous to the principle of harm reduction that is now widely applied in public health practice. Relief of oppression aims to help observational researchers working in conditions of injustice and deprivation to clarify their ethical obligations to participants. It aims to bridge the gap between a narrow, transaction-oriented account of avoiding exploitation and a broad account emphasizing obligations of reparation for historic injustices. We propose that relief of oppression might focus researchers' consideration of benefits on those that have some relevance to background conditions of injustice, and so elevate the priority of these benefits, in relation to others that might be considered and negotiated with participants, according to the degree to which the participating communities are constrained in their realization of fundamental freedoms.</p> <p>Summary</p> <p>The over-arching aim of relief of oppression is that, within the range of benefits negotiated over time with the local communities and organizations, an increasing proportion reflects a shared interest in improving participants' fundamental freedoms. We describe how harm reduction serves as a useful analogy for how we envision relief of oppression functioning in international research.</p