Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

The influence of anxiety on the initial selection of emotional faces presented in binocular rivalry

Neurocognitive theories of anxiety predict that threat-related information can be evaluated before attentional selection, and can influence behaviour differentially in high anxious compared to low anxious individuals. We investigate this further by presenting emotional and neutral faces in an adapted binocular rivalry paradigm. We show that the initial selection of emotional faces presented in binocular rivalry is highly influenced by self-reported state and trait anxiety-level. Heightened anxiety was correlated with increased perception of angry and fearful faces, and decreased perception of happy expressions. These results are consistent with recent evidence of involuntary selection of threat in anxiety.

High-level face adaptation without awareness

When a visual stimulus is suppressed from awareness, processing of the suppressed image is necessarily reduced. Although adaptation to simple image properties such as orientation still occurs, adaptation to high-level properties such as face identity is eliminated. Here we show that emotional facial expression continues to be processed even under complete suppression, as indexed by substantial facial expression aftereffects.

On the 'special' status of emotional faces... Comment on Yang, Hong, and Blake (2010)

A wealth of literature suggests that emotional faces are given special status as visual objects: Cognitive models suggest that emotional stimuli, particularly threat-relevant facial expressions such as fear and anger, are prioritized in visual processing and may be identified by a subcortical “quick and dirty” pathway in the absence of awareness (Tamietto & de Gelder, 2010). Both neuroimaging studies (Williams, Morris, McGlone, Abbott, & Mattingley, 2004) and backward masking studies (Whalen, Rauch, Etcoff, McInerney, & Lee, 1998) have supported the notion of emotion processing without awareness. Recently, our own group (Adams, Gray, Garner, & Graf, 2010) showed adaptation to emotional faces that were rendered invisible using a variant of binocular rivalry: continual flash suppression (CFS, Tsuchiya & Koch, 2005). Here we (i) respond to Yang, Hong, and Blake's (2010) criticisms of our adaptation paper and (ii) provide a unified account of adaptation to facial expression, identity, and gender, under conditions of unawareness

Faces and awareness: low-level, not emotional factors determine perceptual dominance

Threat-relevant stimuli such as fear faces are prioritized by the human visual system. Recent research suggests that this prioritization begins during unconscious processing: A specialized (possibly subcortical) pathway evaluates the threat relevance of visual input, resulting in preferential access to awareness for threat stimuli. Our data challenge this claim. We used a continuous flash suppression (CFS) paradigm to present emotional face stimuli outside of awareness. It has been shown using CFS that salient (e.g., high contrast) and recognizable stimuli (faces, words) become visible more quickly than less salient or less recognizable stimuli. We found that although fearful faces emerge from suppression faster than other faces, this was wholly explained by their low-level visual properties, rather than their emotional content. We conclude that, in the competition for visual awareness, the visual system prefers and promotes unconscious stimuli that are more “face-like,” but the emotional content of a face has no effect on stimulus salience.

Radically open-dialectical behavior therapy for adult anorexia nervosa: feasibility and outcomes from an inpatient program

Background Anorexia Nervosa (AN) is a highly life-threatening disorder that is extremely difficult to treat. There is evidence that family-based therapies are effective for adolescent AN, but no treatment has been proven to be clearly effective for adult AN. The methodological challenges associated with studying the disorder have resulted in recommendations that new treatments undergo preliminary testing prior to being evaluated in a randomized clinical trial. The aim of this study was to provide preliminary evidence on the effectiveness of a treatment program based on a novel adaptation of Dialectical Behavior Therapy (DBT) for adult Anorexia Nervosa (Radically Open-DBT; RO-DBT) that conceptualizes AN as a disorder of overcontrol. Methods Forty-seven individuals diagnosed with Anorexia Nervosa-restrictive type (AN-R; mean admission body mass index = 14.43) received the adapted DBT inpatient program (mean length of treatment = 21.7 weeks). Results Seventy-two percent completed the treatment program demonstrating substantial increases in body mass index (BMI; mean change in BMI = 3.57) corresponding to a large effect size (d = 1.91). Thirty-five percent of treatment completers were in full remission, and an additional 55% were in partial remission resulting in an overall response rate of 90%. These same individuals demonstrated significant and large improvements in eating-disorder related psychopathology symptoms (d = 1.17), eating disorder-related quality of life (d = 1.03), and reductions in psychological distress (d = 1.34). Conclusions RO-DBT was associated with significant improvements in weight gain, reductions in eating disorder symptoms, decreases in eating-disorder related psychopathology and increases in eating disorder-related quality of life in a severely underweight sample. These findings provide preliminary support for RO-DBT in treating AN-R suggesting the importance of further evaluation examining long-term outcomes using randomized controlled trial methodology.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

Is there a Rhythm Of The Rain? An analysis of weather in popular music

Weather is frequently used in music to frame events and emotions, yet quantitative analyses are rare. From a collated base set of 759 weather-related songs, 419 were analysed based on listings from a karaoke database. This article analyses the 20 weather types described, frequency of occurrence, genre, keys, mimicry, lyrics and songwriters. Vocals were the principal means of communicating weather: sunshine was the most common, followed by rain, with weather depictions linked to the emotions of the song. Bob Dylan, John Lennon and Paul McCartney wrote the most weather-related songs, partly following their experiences at the time of writing.

A comparison of duality and energy a posteriori estimates for $\mathrm {L}_{\infty }(0,T;\mathrm {L}_2(\varOmega ))$ in parabolic problems

We use the elliptic reconstruction technique in combination with a duality approach to prove a posteriori error estimates for fully discrete backward Euler scheme for linear parabolic equations. As an application, we combine our result with the residual based estimators from the a posteriori estimation for elliptic problems to derive space-error indicators and thus a fully practical version of the estimators bounding the error in the $ \mathrm {L}_{\infty }(0,T;\mathrm {L}_2(\varOmega ))$ norm. These estimators, which are of optimal order, extend those introduced by Eriksson and Johnson in 1991 by taking into account the error induced by the mesh changes and allowing for a more flexible use of the elliptic estimators. For comparison with previous results we derive also an energy-based a posteriori estimate for the $ \mathrm {L}_{\infty }(0,T;\mathrm {L}_2(\varOmega ))$-error which simplifies a previous one given by Lakkis and Makridakis in 2006. We then compare both estimators (duality vs. energy) in practical situations and draw conclusions.

Robustness despite uncertainty: regional climate data reveal the dominant role of humans in explaining global extinctions of Late Quaternary megafauna

Debate over the late Quaternary megafaunal extinctions has focussed on whether human colonisation or climatic changes were more important drivers of extinction, with few extinctions being unambiguously attributable to either. Most analyses have been geographically or taxonomically restricted and the few quantitative global analyses have been limited by coarse temporal resolution or overly simplified climate reconstructions or proxies. We present a global analysis of the causes of these extinctions which uses high-resolution climate reconstructions and explicitly investigates the sensitivity of our results to uncertainty in the palaeological record. Our results show that human colonisation was the dominant driver of megafaunal extinction across the world but that climatic factors were also important. We identify the geographic regions where future research is likely to have the most impact, with our models reliably predicting extinctions across most of the world, with the notable exception of mainland Asia where we fail to explain the apparently low rate of extinction found in in the fossil record. Our results are highly robust to uncertainties in the palaeological record, and our main conclusions are unlikely to change qualitatively following minor improvements or changes in the dates of extinctions and human colonisation.

Validation of a priori CME arrival predictions made using real-time heliospheric imager observations

Between December 2010 and March 2013, volunteers for the Solar Stormwatch (SSW) Citizen Science project have identified and analyzed coronal mass ejections (CMEs) in the near real-time Solar Terrestrial Relations Observatory Heliospheric Imager observations, in order to make “Fearless Forecasts” of CME arrival times and speeds at Earth. Of the 60 predictions of Earth-directed CMEs, 20 resulted in an identifiable Interplanetary CME (ICME) at Earth within 1.5–6 days, with an average error in predicted transit time of 22 h, and average transit time of 82.3 h. The average error in predicting arrival speed is 151 km s−1, with an average arrival speed of 425km s−1. In the same time period, there were 44 CMEs for which there are no corresponding SSW predictions, and there were 600 days on which there was neither a CME predicted nor observed. A number of metrics show that the SSW predictions do have useful forecast skill; however, there is still much room for improvement. We investigate potential improvements by using SSW inputs in three models of ICME propagation: two of constant acceleration and one of aerodynamic drag. We find that taking account of interplanetary acceleration can improve the average errors of transit time to 19 h and arrival speed to 77 km s−1.

The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling

The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.

Improving the health forecasting alert system for cold weather and heat-waves in England: a proof-of-concept using temperature-mortality relationships

Objectives In this study a prototype of a new health forecasting alert system is developed, which is aligned to the approach used in the Met Office’s (MO) National Severe Weather Warning Service (NSWWS). This is in order to improve information available to responders in the health and social care system by linking temperatures more directly to risks of mortality, and developing a system more coherent with other weather alerts. The prototype is compared to the current system in the Cold Weather and Heatwave plans via a case-study approach to verify its potential advantages and shortcomings. Method The prototype health forecasting alert system introduces an “impact vs likelihood matrix” for the health impacts of hot and cold temperatures which is similar to those used operationally for other weather hazards as part of the NSWWS. The impact axis of this matrix is based on existing epidemiological evidence, which shows an increasing relative risk of death at extremes of outdoor temperature beyond a threshold which can be identified epidemiologically. The likelihood axis is based on a probability measure associated with the temperature forecast. The new method is tested for two case studies (one during summer 2013, one during winter 2013), and compared to the performance of the current alert system. Conclusions The prototype shows some clear improvements over the current alert system. It allows for a much greater degree of flexibility, provides more detailed regional information about the health risks associated with periods of extreme temperatures, and is more coherent with other weather alerts which may make it easier for front line responders to use. It will require validation and engagement with stakeholders before it can be considered for use.

Up-scaled synthesis process of sulphur-based thermoelectric materials

The scale up of Spark Plasma Sintering (SPS) for the consolidation of large square monoliths (50 × 50 × 3 mm3) of thermoelectric material is demonstrated and the properties of the fabricated samples compared with those from laboratory scale SPS. The SPS processing of n-type TiS2 and p-type Cu10.4Ni1.6Sb4S13 produces highly dense compacts of phase pure material. Electrical and thermal transport property measurements reveal that the thermoelectric performance of the consolidated n- and p-type materials is comparable with that of material processed using laboratory scale SPS, with ZT values that approach 0.8 and 0.35 at 700 K for Cu10.4Ni1.6Sb4S13 and TiS2, respectively. Mechanical properties of the consolidated materials shows that large-scale SPS processing produces highly homogeneous materials with hardness and elastic moduli that deviate little from values obtained on materials processed on the laboratory scale.

Genomic evidence for the Pleistocene and recent population history of Native Americans

How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative “Paleoamerican” relict populations, including the historical Mexican Pericúes and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.