Think twice before starting a new trial; what is the impact of recommendations to stop doing new trials?

ObjectivesIn evidence-based medicine, we base our conclusions on the effectiveness of interventions on the results of high-quality meta-analysis. If a new randomized controlled trial (RCT) is unlikely to change the pooled effect estimate, conducting the new trial is a waste of resources. We evaluated whether recommendations not to conduct further RCTs reduced the number of trials registered for two scenarios.MethodsAnalysis of registered trials on the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP). We regarded trial protocols relevant if they evaluated the effectiveness of (1) exercise for chronic low back pain (LBP) and (2) cognitive behavioural therapy (CBT) for chronic pain. We calculated absolute and relative numbers and change of registered trials in a pre-set time window before and after publication of the recommendations, both published in 2012.ResultsWe found 1,574 trials registered in the WHO trial registry for exercise in LBP (459 before 2012; 1,115 after) and 5,037 trials on chronic pain (1,564 before 2012; 3,473 after). Before 2012, 13 trials on exercise for LBP (out of 459) fit the selection criteria, compared to 42 trials (out of 1,115) after, which represents a relative increase of 33%. Twelve trials (out of 1,564) regarding CBT for chronic pain, fit the selection criteria before 2012 and 18 trials (out of 3,473) after, representing a relative decrease of 32%. We found that visibility, media exposure and strength of the recommendation were related to a decrease in registered trials.ConclusionsRecommendations not to conduct further RCTs might reduce the number of trials registered if these recommendations are strongly worded and combined with social media attention

Turnover rate of cerebrospinal fluid in female sheep: changes related to different light-dark cycles

<p>Abstract</p> <p>Background</p> <p>Sheep are seasonal breeders. The key factor governing seasonal changes in the reproductive activity of the ewe is increased negative feedback of estradiol at the level of the hypothalamus under long-day conditions. It has previously been demonstrated that when gonadotropin secretions are inhibited during long days, there is a higher concentration of estradiol in the cerebrospinal fluid (CSF) than during short days. This suggests an involvement of the CSF and choroid plexus in the neuroendocrine regulatory loop, but the mechanisms underlying this phenomenon remain unknown. One possible explanation of this difference in hormonal content is an effect of concentration or dilution caused by variations in CSF secretion rate. The aim of this study was thus to investigate changes in the CSF turnover rate related to light-dark cycles.</p> <p>Methods</p> <p>The turnover rate of the CSF was estimated by measuring the time taken for the recovery of intraventricular pressure (IVP) after removal of a moderate volume (0.5 to 2 ml) of CSF (slope in mmHg/min). The turnover rate was estimated three times in the same group of sheep: during a natural period of decreasing day-length corresponding to the initial period when gonadotropin activity is stimulated (SG1), during a long-day inhibitory period (IG), and finally during a short-day stimulatory period (SG2).</p> <p>Results</p> <p>The time taken and the speed of recovery of initial IVP differed between groups: 8 min 30 sec, 0.63 ± 0.07 mmHg/min(SG1), 11 min 1 sec, 0.38 ± 0.06 mmHg/min (IG) and 9 min 0 sec, 0.72 ± 0.15 mmHg/min (SG2). Time changes of IVP differed between groups (ANOVA, p < 0.005, SG1 different from IG, <it>p </it>< 0.05). The turnover rate in SG2: 183.16 ± 23.82 μl/min was not significantly different from SG1: 169. 23 ± 51.58 μl/min (Mann-Whitney test, <it>p </it>= 0.41), but was significantly different from IG: 71.33 ± 16.59 μl/min (<it>p </it>= 0.016).</p> <p>Conclusion</p> <p>This study shows that the turnover rate of CSF in ewes changes according to the light-dark cycle; it is increased during short day periods and reduced in long day periods. This phenomenon could account for differences in hormonal concentrations in the CSF in this seasonal species.</p

Deconstructing the lesbian, gay, bisexual, transgender victim of sex trafficking: Harm, exceptionality and religion–sexuality tensions

Contrary to widespread belief, sex trafficking also targets lesbian, gay, bisexual, transgender (LGBT) communities. Contemporary social and political constructions of victimhood lie at the heart of regulatory policies on sex trafficking. Led by the US Department of State, knowledge about LGBT victims of trafficking constitutes the newest frontier in the expansion of criminalization measures. These measures represent a crucial shift. From a burgeoning range of preemptive measures enacted to protect an amorphous class of ‘all potential victims’, now policies are heavily premised on the risk posed by traffickers to ‘victims of special interest’. These constructed identities, however, are at odds with established structures. Drawing on a range of literatures, the core task of this article is to confront some of the complexities and tensions surrounding constructions of LGBT trafficking victims. Specifically, the article argues that discourses of ‘exceptional vulnerability’ and the polarized notions of ‘innocence’ and ‘guilt’ inform hierarchies of victimhood. Based on these insights, the article argues for the need to move beyond monolithic understandings of victims, by reframing the politics of harm accordingly

Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

Building nonparametric nn-body force fields using Gaussian process regression

Constructing a classical potential suited to simulate a given atomic system is a remarkably difficult task. This chapter presents a framework under which this problem can be tackled, based on the Bayesian construction of nonparametric force fields of a given order using Gaussian process (GP) priors. The formalism of GP regression is first reviewed, particularly in relation to its application in learning local atomic energies and forces. For accurate regression it is fundamental to incorporate prior knowledge into the GP kernel function. To this end, this chapter details how properties of smoothness, invariance and interaction order of a force field can be encoded into corresponding kernel properties. A range of kernels is then proposed, possessing all the required properties and an adjustable parameter $n$ governing the interaction order modelled. The order $n$ best suited to describe a given system can be found automatically within the Bayesian framework by maximisation of the marginal likelihood. The procedure is first tested on a toy model of known interaction and later applied to two real materials described at the DFT level of accuracy. The models automatically selected for the two materials were found to be in agreement with physical intuition. More in general, it was found that lower order (simpler) models should be chosen when the data are not sufficient to resolve more complex interactions. Low $n$ GPs can be further sped up by orders of magnitude by constructing the corresponding tabulated force field, here named "MFF".Comment: 31 pages, 11 figures, book chapte

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

The EDKB: an established knowledge base for endocrine disrupting chemicals

<p>Abstract</p> <p>Background</p> <p>Endocrine disruptors (EDs) and their broad range of potential adverse effects in humans and other animals have been a concern for nearly two decades. Many putative EDs are widely used in commercial products regulated by the Food and Drug Administration (FDA) such as food packaging materials, ingredients of cosmetics, medical and dental devices, and drugs. The Endocrine Disruptor Knowledge Base (EDKB) project was initiated in the mid 1990’s by the FDA as a resource for the study of EDs. The EDKB database, a component of the project, contains data across multiple assay types for chemicals across a broad structural diversity. This paper demonstrates the utility of EDKB database, an integral part of the EDKB project, for understanding and prioritizing EDs for testing.</p> <p>Results</p> <p>The EDKB database currently contains 3,257 records of over 1,800 EDs from different assays including estrogen receptor binding, androgen receptor binding, uterotropic activity, cell proliferation, and reporter gene assays. Information for each compound such as chemical structure, assay type, potency, etc. is organized to enable efficient searching. A user-friendly interface provides rapid navigation, Boolean searches on EDs, and both spreadsheet and graphical displays for viewing results. The search engine implemented in the EDKB database enables searching by one or more of the following fields: chemical structure (including exact search and similarity search), name, molecular formula, CAS registration number, experiment source, molecular weight, etc. The data can be cross-linked to other publicly available and related databases including TOXNET, Cactus, ChemIDplus, ChemACX, Chem Finder, and NCI DTP. </p> <p>Conclusion</p> <p>The EDKB database enables scientists and regulatory reviewers to quickly access ED data from multiple assays for specific or similar compounds. The data have been used to categorize chemicals according to potential risks for endocrine activity, thus providing a basis for prioritizing chemicals for more definitive but expensive testing. The EDKB database is publicly available and can be found online at <url>http://edkb.fda.gov/webstart/edkb/index.html</url>.</p> <p><b>Disclaimer:</b><it>The views presented in this article do not necessarily reflect those of the US Food and Drug Administration.</it></p

A meta-analytic review of stand-alone interventions to improve body image

Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions

Minimal influence of the menstrual cycle or hormonal contraceptives on performance in female rugby league athletes

We examined performance across one menstrual cycle (MC) and 3 weeks of hormonal contraceptives (HC) use to identify whether known fluctuations in estrogen and progesterone/progestin are associated with functional performance changes. National Rugby League Indigenous Women's Academy athletes [n = 11 naturally menstruating (NM), n = 13 using HC] completed performance tests [countermovement jump (CMJ), squat jump (SJ), isometric mid‐thigh pull, 20 m sprint, power pass and Stroop test] during three phases of a MC or three weeks of HC usage, confirmed through ovulation tests alongside serum estrogen and progesterone concentrations. MC phase or HC use did not influence jump height, peak force, sprint time, distance thrown or Stroop effect. However, there were small variations in kinetic and kinematic CMJ/SJ outputs. NM athletes produced greater mean concentric power in MC phase four than one [+0.41 W·kg−1 (+16.8%), p = 0.021] during the CMJ, alongside greater impulse at 50 ms at phase one than four [+1.7 N·s (+4.7%), p = 0.031] during the SJ, without differences between tests for HC users. Among NM athletes, estradiol negatively correlated with mean velocity and power (r = −0.44 to −0.50, p &lt; 0.047), progesterone positively correlated with contraction time (r = 0.45, p = 0.045), and both negatively correlated with the rate of force development and impulse (r = −0.45 to −0.64, p &lt; 0.043) during the SJ. During the CMJ, estradiol positively correlated to 200 ms impulse (r = 0.45, p = 0.049) and progesterone to mean power (r = 0.51, p = 0.021). Evidence of changes in testing performance across a MC, or during active HC use, is insufficient to justify “phase‐based testing”; however, kinetic or kinematic outputs may be altered in NM athletes

The impact of a decision aid about heart disease prevention on patients' discussions with their doctor and their plans for prevention: a pilot randomized trial

BACKGROUND: Low utilization of effective coronary heart disease (CHD) prevention strategies may be due to many factors, but chief among them is the lack of patient involvement in prevention decisions. We undertook this study to test the effectiveness of an individually-tailored, computerized decision aid about CHD on patients' discussions with their doctor and their plans for CHD prevention. METHODS: We conducted a pilot randomized trial in a convenience sample of adults with no previous history of cardiovascular disease to test the effectiveness of an individually-tailored, computerized decision aid about CHD prevention against a risk factor list that patients could present to their doctor. RESULTS: We enrolled 75 adults. Mean age was 53. 59% were female, 73% white, and 23% African-American. 66% had some college education. 43% had a 10-year CHD risk of 0–5%, 25% a risk of 6–10%, 24% a risk of 11–20%, and 5% a risk of > 20%. 78% had at least one option to reduce their CHD risk, but only 45% accurately identified the strategies best supported by evidence. 41 patients received the decision aid, 34 received usual care. In unadjusted analysis, the decision aid increased the proportion of patients who discussed CHD risk reduction with their doctor from 24% to 40% (absolute difference 16%; 95% CI -4% to +37%) and increased the proportion who had a specific plan to reduce their risk from 24% to 37% (absolute difference 13%; 95% CI -7% to +34%). In pre-post testing, the decision aid also appeared to increase the proportion of patients with plans to intervene on their CHD risk (absolute increase ranging from 21% to 47% for planned medication use and 5% to 16% for planned behavioral interventions). CONCLUSION: Our study confirms patients' limited knowledge about their CHD risk and effective risk reduction options and provides preliminary evidence that an individually-tailored decision aid about CHD prevention might be expected to increase patients' discussions about CHD prevention with their doctor and their plans for CHD risk reduction. These findings should be replicated in studies with a larger sample size and patients at overall higher risk of CHD. Trial Registration: ClinicalTrials.gov NCT0031597