Do In-Vehicle Advance Signs Benefit Older and Younger Driver Intersection Performance?

An experimental study was conducted to determine if intersection behavior of those 18 to 24 and 65+ benefited from advanced in-vehicle signs presented in a head-up display (HUD) format. The University of Calgary Driving Simulator (UCDS) was used to determine whether intersection performance improved in the presence of several advanced signs or whether unwanted adaptive behaviors occurred (e.g., increasing speed to run the light instead of stopping). Invehicle signs facilitated an increase in stopping occurrences for both younger and older drivers at intersections with relatively short yellow onsets. In addition, eye movement analysis revealed significant age effects with regard to vertical and horizontal gaze variablity, with younger drivers showing increases in vertical gaze variability compared to the older drivers. Younger drivers also looked more often and had longer percentage of durations fixating on the HUD compared to the older drivers

How informed is declared altruism in clinical trials? A qualitative interview study of patient decision-making about the QUEST trials (Quality of Life after Mastectomy and Breast Reconstruction)

Background Randomised controlled trials (RCTs) often fail to recruit sufficient participants, despite altruism being cited as their motivation. Previous investigations of factors influencing participation decisions have been methodologically limited. This study evaluated how women weigh up different motivations after initially expressing altruism, and explored their understanding of a trial and its alternatives. The trial was the 'Quality of Life after Mastectomy and Breast Reconstruction' (QUEST) trial.Methods Thirty-nine women participated in qualitative interviews 1 month post-surgery. Twenty-seven women (10 trial decliners and 17 acceptors) who spontaneously mentioned 'altruism' were selected for thematic analysis. Verbatim transcripts were coded independently by two researchers. Participants' motivations to accept or decline randomisation were cross-referenced with their understanding of the QUEST trials and the process of randomisation.Results The seven emerging themes were: (1) altruism expressed by acceptors and decliners; (2) overriding personal needs in decliners; (3) pure altruism in acceptors; (4) 'hypothetical altruism' amongst acceptors; (5) weak altruism amongst acceptors; (6) conditional altruism amongst acceptors; and (7) sense of duty to participate. Poor understanding of the trial rationale and its implications was also evident.Conclusions Altruism was a motivating factor for participation in the QUEST randomised controlled trials where the main outcomes comprised quality of life and allocated treatments comprised established surgical procedures. Women's decisions were influenced by their understanding of the trial. Both acceptors and decliners of the trial expressed 'altruism', but most acceptors lacked an obvious treatment preference, hoped for personal benefits regarding a treatment allocation, or did not articulate complete understanding of the trial.Trial registration QUEST A, ISRCTN38846532 ; Date assigned 6 January 2010. QUEST B, ISRCTN92581226 ; Date assigned 6 January 2010

Botulinum toxins for the prevention of migraine in adults

BackgroundMigraine occurs in around 15% of adults and is ranked as the seventh most disabling disease amongst all diseases globally. Despite the available treatments many people suffer prolonged and frequent attacks which have a major impact on their quality of life. Chronic migraine is defined as 15 or more days of headache per month, at least eight of those days being migraine. People with episodic migraine have fewer than 15 headache days per month. Botulinum toxin type A has been licensed in some countries for chronic migraine treatment, due to the results of just two trials.ObjectivesTo assess the effects of botulinum toxins versus placebo or active treatment for the prevention or reduction in frequency of chronic or episodic migraine in adults.Search methodsWe searched CENTRAL, MEDLINE & MEDLINE in Process, Embase, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry (to December 2017). We examined reference lists and carried out citation searches on key publications. We sent correspondence to major manufacturers of botulinum toxin.Selection criteriaRandomised, double‐blind, controlled trials of botulinum toxin (any sero‐type) injections into the head and neck for prophylaxis of chronic or episodic migraine in adults. Eligible comparators were placebo, alternative prophylactic agent or different dose of botulinum toxin.Data collection and analysisTwo review authors independently selected trials and extracted data. For continuous outcomes we used mean change data when available. For dichotomous data we calculated risk ratios (RRs). We used data from the 12‐week post‐treatment follow‐up time point. We assessed the evidence using GRADE and created two 'Summary of findings' tables.Main resultsDescription of trialsWe found 90 articles describing 28 trials (4190 participants), which were eligible for inclusion. The longest treatment duration was three rounds of injections with three months between treatments, so we could not analyse long‐term effects. For the primary analyses, we pooled data from both chronic and episodic participant populations. Where possible, we also separated data into chronic migraine, episodic migraine and ‘mixed group’ classification subgroups. Most trials (21 out of 28) were small (fewer than 50 participants per trial arm). The risk of bias for included trials was low or unclear across most domains, with some trials reporting a high risk of bias for incomplete outcome data and selective outcome reporting.Botulinum toxin versus placeboTwenty‐three trials compared botulinum toxin with placebo. Botulinum toxin may reduce the number of migraine days per month in the chronic migraine population by 3.1 days (95% confidence interval (CI) ‐4.7 to ‐1.4, 4 trials, 1497 participants, low‐quality evidence). This was reduced to ‐2 days (95% CI ‐2.8 to ‐1.1, 2 trials, 1384 participants; moderate‐quality evidence) when we removed small trials.A single trial of people with episodic migraine (N = 418) showed no difference between groups for this outcome measure (P = 0.49).In the chronic migraine population, botulinum toxin reduces the number of headache days per month by 1.9 days (95% CI ‐2.7 to ‐1.0, 2 trials, 1384 participants, high‐quality evidence). We did not find evidence of a difference in the number of migraine attacks for both chronic and episodic migraine participants (6 trials, N = 2004, P = 0.30, low‐quality evidence). For the population of both chronic and episodic migraine participants a reduction in severity of migraine rated during clinical visits, on a 10 cm visual analogue scale (VAS) of 3.3 cm (95% CI ‐4.2 to ‐2.5, very low‐quality evidence) in favour of botulinum toxin treatment came from four small trials (N = 209); better reporting of this outcome measure from the additional eight trials that recorded it may have improved our confidence in the pooled estimate. Global assessment and quality‐of‐life measures were poorly reported and it was not possible to carry out statistical analysis of these outcome measures. Analysis of adverse events showed an increase in the risk ratio with treatment with botulinum toxin over placebo 30% (RR 1.28, 95% CI 1.12 to 1.47, moderate‐quality evidence). For every 100 participants 60 experienced an adverse event in the botulinum toxin group compared with 47 in the placebo group.Botulinum toxin versus other prophylactic agentThree trials studied comparisons with alternative oral prophylactic medications. Meta‐analyses were not possible for number of migraine days, number of headache days or number of migraine attacks due to insufficient data, but individually trials reported no differences between groups for a variety of efficacy measures in the population of both chronic and episodic migraine participants. The global impression of disease measured using Migraine Disability Assessment (MIDAS) scores were reported from two trials that showed no difference between groups. Compared with oral treatments, botulinum toxin showed no between‐group difference in the risk of adverse events (2 trials, N = 114, very low‐quality evidence). The relative risk reduction (RRR) for withdrawing from botulinum toxin due to adverse events compared with the alternative prophylactic agent was 72% (P = 0.02, 2 trials, N = 119).Dosing trialsThere were insufficient data available for the comparison of different doses.Quality of the evidenceThe quality of the evidence assessed using GRADE methods was varied but mostly very low; the quality of the evidence for the placebo and active control comparisons was low and very low, respectively for the primary outcome measure. Small trial size, high risk of bias and unexplained heterogeneity were common reasons for downgrading the quality of the evidence.Authors' conclusionsIn chronic migraine, botulinum toxin type A may reduce the number of migraine days per month by 2 days compared with placebo treatment. Non‐serious adverse events were probably experienced by 60/100 participants in the treated group compared with 47/100 in the placebo group. For people with episodic migraine, we remain uncertain whether or not this treatment is effective because the quality of this limited evidence is very low. Better reporting of outcome measures in published trials would provide a more complete evidence base on which to draw conclusions

Holocene climate and environmental change in north-eastern Kamchatka (Russian Far East), inferred from a multi-proxy study of lake sediments

The study was supported by the Swedish Research Council through grants 621-2004-5224 and 621-2005-4444 to K.D. Bennett. A. Self and N. Solovieva acknowledge S. Brooks and V. Jones and were supported by NERC grant NE/H008160/1.A sediment record from a small lake in the north-eastern part of the Kamchatka Peninsula has been investigated in a multi-proxy study to gain knowledge of Holocene climatic and environmental change. Pollen, diatoms, chironomids and selected geochemical parameters were analysed and the sediment record was dated with radiocarbon. The study shows Holocene changes in the terrestrial vegetation as well as responses of the lake ecosystem to catchment maturity and multiple stressors, such as climate change and volcanic eruptions. Climate change is the major driving force resulting in the recorded environmental changes in the lake, although recurrent tephra deposition events also contributed. The sediment record has an age at the base of about 10,000 cal yrs BP, and during the first 400 years the climate was cold and the lake exhibited extensive ice-cover during winter and relatively low primary production. Soils in the catchment were poor with shrub alder and birches dominating the vegetation surrounding the lake. At about 9600–8900 cal yrs BP the climate was cold and moist, and strong seasonal wind stress resulted in reduced ice-cover and increased primary production. After ca. 8900 cal yrs BP the forest density increased around the lake, runoff decreased in a generally drier climate resulting in decreased primary production in the lake until ca. 7000 cal yrs BP. This generally dry climate was interrupted by a brief climatic perturbation, possibly attributed to the 8.2 ka event, indicating increasingly windy conditions with thick snow cover, reduced ice-cover and slightly elevated primary production in the lake. The diatom record shows maximum thermal stratification at ca. 6300–5800 cal yrs BP and indicates together with the geochemical proxies a dry and slightly warmer climate resulting in a high productive lake. The most remarkably change in the catchment vegetation occurred at ca. 4200 cal yrs BP in the form of a conspicuous increase in Siberian dwarf pine (Pinus pumila), indicating a shift to a cooler climate with a thicker and more long-lasting snow cover. This vegetational change was accompanied by marked shifts in the diatom and chironomid stratigraphies, which are also indicative of colder climate and more extensive ice-cover.Publisher PDFPeer reviewe

Maternal Anti-Dengue IgG Fucosylation Predicts Susceptibility to Dengue Disease in Infants

Infant mortality from dengue disease is a devastating global health burden that could be minimized with the ability to identify susceptibility for severe disease prior to infection. Although most primary infant dengue infections are asymptomatic, maternally derived anti-dengue immunoglobulin G (IgGs) present during infection can trigger progression to severe disease through antibody-dependent enhancement mechanisms. Importantly, specific characteristics of maternal IgGs that herald progression to severe infant dengue are unknown. Here, we define \u3e /=10% afucosylation of maternal anti-dengue IgGs as a risk factor for susceptibility of infants to symptomatic dengue infections. Mechanistic experiments show that afucosylation of anti-dengue IgGs promotes FcgammaRIIIa signaling during infection, in turn enhancing dengue virus replication in FcgammaRIIIa(+) monocytes. These studies identify a post-translational modification of anti-dengue IgGs that correlates with risk for symptomatic infant dengue infections and define a mechanism by which afucosylated antibodies and FcgammaRIIIa enhance dengue infections

Biotinylated photocleavable semiconductor colloidal quantum dot supraparticle microlaser

Luminescent supraparticles of colloidal semiconductor nanocrystals can act as microscopic lasers and are hugely attractive for biosensing, imaging, and drug delivery. However, biointerfacing these to increase functionality while retaining their main optical properties remains an unresolved challenge. Here, we propose and demonstrate red-emitting, silica-coated CdS xSe 1−x/ZnS colloidal quantum dot supraparticles functionalized with a biotinylated photocleavable ligand. The success of each step of the synthesis is confirmed by scanning electron microscopy, energy dispersive X-ray and Fourier transform infrared spectroscopy, ζ-potential, and optical pumping measurements. The capture and release functionality of the supraparticle system is proven by binding to a neutravidin functionalized glass slide and subsequently cleaving off after UV-A irradiation. The biotinylated supraparticles still function as microlasers; e.g., a 9 μm diameter supraparticle has oscillating modes around 625 nm at a threshold of 58 mJ/cm 2. This work is a first step toward using supraparticle lasers as enhanced labels for bionano applications

Protocol for PRImary care Management of lower Urinary tract Symptoms in men:Protocol for development and validation of a diagnostic and clinical decision support tool (The PriMUS Study)

Introduction Lower urinary tract symptoms (LUTS) is a bothersome condition affecting older men which can lead to poor quality of life. General practitioners (GPs) currently have no easily available assessment tools to help effectively diagnose causes of LUTS and aid discussion of treatment with patients. Men are frequently referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinician decision tools are needed to facilitate accurate and effective patient management of LUTS in primary care. Methods and analysis PRImary care Management of lower Urinary tract Symptoms (PriMUS) is a prospective diagnostic accuracy study based in primary care. The study will determine which of a number of index tests used in combination best predict three urodynamic observations in men who present to their GP with LUTS. These are detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity. Two cohorts of participants, one for development of the prototype diagnostic tool and other for validation, will undergo a series of simple index tests and the invasive reference standard (invasive urodynamics). We will develop and validate three diagnostic prediction models based on each condition and then combine them with management recommendations to form a clinical decision support tool. Ethics and dissemination Ethics approval is from the Wales Research Ethics Committee 6. Findings will be disseminated through peer-reviewed journals and conferences, and results will be of interest to professional and patient stakeholders