Tuberculosis incidence correlates with sunshine : an ecological 28-year time series study

Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis. Methods: We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models. Results: There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). Discussion and Conclusion: A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence

What is macroecology?

The symposium 'What is Macroecology?' was held in London on 20 June 2012. The event was the inaugural meeting of the Macroecology Special Interest Group of the British Ecological Society and was attended by nearly 100 scientists from 11 countries. The meeting reviewed the recent development of the macroecological agenda. The key themes that emerged were a shift towards more explicit modelling of ecological processes, a growing synthesis across systems and scales, and new opportunities to apply macroecological concepts in other research fields

Incidence, Predictors, and Prognostic Impact of Late Bleeding Complications After Transcatheter Aortic Valve Replacement

AbstractBackgroundThe incidence and prognostic impact of late bleeding complications after transcatheter aortic valve replacement (TAVR) are unknown.ObjectivesThe aim of this study was to identify the incidence, predictors, and prognostic impact of major late bleeding complications (MLBCs) (≥30 days) after TAVR.MethodsClinical and echocardiographic outcomes of patients who underwent TAVR within the randomized cohorts and continued access registries in the PARTNER (Placement of Aortic Transcatheter Valves) trial were analyzed after stratifying by the occurrence of MLBCs. Predictors of MLBCs and their association with 30-day to 1-year mortality were assessed.ResultsAmong 2,401 patients who underwent TAVR and survived to 30 days, MLBCs occurred in 142 (5.9%) at a median time of 132 days (interquartile range: 71 to 230 days) after the index procedure. Gastrointestinal complications (n = 58 [40.8%]), neurological complications (n = 22 [15.5%]), and traumatic falls (n = 11 [7.8%]) were identified as the most frequent types of MLBCs. Independent predictors of MLBCs were the presence of low hemoglobin at baseline, atrial fibrillation or flutter at baseline or 30 days, the presence of moderate or severe paravalvular leak at 30 days, and greater left ventricular mass at 30 days. MLBCs were identified as a strong independent predictor of mortality between 30 days and 1 year (adjusted hazard ratio: 3.91; 95% confidence interval: 2.67 to 5.71; p < 0.001).ConclusionsMLBCs after TAVR were frequent and associated with increased mortality. Better individualized and risk-adjusted antithrombotic therapy after TAVR is urgently needed in this high-risk population. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894

Dynamical differential expression (DyDE) reveals the period control mechanisms of the Arabidopsis circadian oscillator.

The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The mechanistic basis underlying the adjustment of circadian rhythms to changing external conditions, however, has yet to be clearly elucidated. We explored the mechanism of action of nicotinamide in Arabidopsis thaliana, a metabolite that lengthens the period of circadian rhythms, to understand the regulation of circadian period. To identify the key mechanisms involved in the circadian response to nicotinamide, we developed a systematic and practical modeling framework based on the identification and comparison of gene regulatory dynamics. Our mathematical predictions, confirmed by experimentation, identified key transcriptional regulatory mechanisms of circadian period and uncovered the role of blue light in the response of the circadian oscillator to nicotinamide. We suggest that our methodology could be adapted to predict mechanisms of drug action in complex biological systems

How the love of muscle can break a heart: Impact of anabolic androgenic steroids on skeletal muscle hypertrophy, metabolic and cardiovascular health.

It is estimated 6.4% of males and 1.6% of females globally use anabolic-androgenic steroids (AAS), mostly for appearance and performance enhancing reasons. In combination with resistance exercise, AAS use increases muscle protein synthesis resulting in skeletal muscle hypertrophy and increased performance. Primarily through binding to the androgen receptor, AAS exert their hypertrophic effects via genomic, non-genomic and anti-catabolic mechanisms. However, chronic AAS use also has a detrimental effect on metabolism ultimately increasing the risk of cardiovascular disease (CVD). Much research has focused on AAS effects on blood lipids and lipoproteins, with abnormal concentrations of these associated with insulin resistance, hypertension and increased visceral adipose tissue (VAT). This clustering of interconnected abnormalities is often referred as metabolic syndrome (MetS). Therefore, the aim of this review is to explore the impact of AAS use on mechanisms of muscle hypertrophy and markers of MetS. AAS use markedly decreases high-density lipoprotein cholesterol (HDL-C) and increases low-density lipoprotein cholesterol (LDL-C). Chronic AAS use also appears to cause higher fasting insulin levels and impaired glucose tolerance and possibly higher levels of VAT; however, research is currently lacking on the effects of AAS use on glucose metabolism. While cessation of AAS use can restore normal lipid levels, it may lead to withdrawal symptoms such as depression and hypogonadism that can increase CVD risk. Research is currently lacking on effective treatments for withdrawal symptoms and further long-term research is warranted on the effects of AAS use on metabolic health in males and females

The Great American Biotic Interchange: Dispersals, Tectonics, Climate, Sea Level and Holding Pens

The biotic and geologic dynamics of the Great American Biotic Interchange are reviewed and revised. Information on the Marine Isotope Stage chronology, sea level changes as well as Pliocene and Pleistocene vegetation changes in Central and northern South America add to a discussion of the role of climate in facilitating trans-isthmian exchanges. Trans-isthmian land mammal exchanges during the Pleistocene glacial intervals appear to have been promoted by the development of diverse non-tropical ecologies

Cherenkov radiation control via self-accelerating wave-packets

Cherenkov radiation is a ubiquitous phenomenon in nature. It describes electromagnetic radiation from a charged particle moving in a medium with a uniform velocity larger than the phase velocity of light in the same medium. Such a picture is typically adopted in the investigation of traditional Cherenkov radiation as well as its counterparts in different branches of physics, including nonlinear optics, spintronics and plasmonics. In these cases, the radiation emitted spreads along a “cone”, making it impractical for most applications. Here, we employ a self-accelerating optical pump wave-packet to demonstrate controlled shaping of one type of generalized Cherenkov radiation - dispersive waves in optical fibers. We show that, by tuning the parameters of the wave-packet, the emitted waves can be judiciously compressed and focused at desired locations, paving the way to such control in any physical system

Targeted prevention of common mental health disorders in university students: randomised controlled trial of a transdiagnostic trait-focused web-based intervention

Background: A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders.&lt;p&gt;&lt;/p&gt; Aims: To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students.&lt;p&gt;&lt;/p&gt; Method: Students were recruited online (n = 1047, age: M = 21.8, SD = 4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n = 519) or a control intervention (n = 528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes.&lt;p&gt;&lt;/p&gt; Results: Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p&#60;.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p = .018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating.&lt;p&gt;&lt;/p&gt; Conclusions This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention

The convective storm initiation project

Copyright @ 2007 AMSThe Convective Storm Initiation Project (CSIP) is an international project to understand precisely where, when, and how convective clouds form and develop into showers in the mainly maritime environment of southern England. A major aim of CSIP is to compare the results of the very high resolution Met Office weather forecasting model with detailed observations of the early stages of convective clouds and to use the newly gained understanding to improve the predictions of the model. A large array of ground-based instruments plus two instrumented aircraft, from the U.K. National Centre for Atmospheric Science (NCAS) and the German Institute for Meteorology and Climate Research (IMK), Karlsruhe, were deployed in southern England, over an area centered on the meteorological radars at Chilbolton, during the summers of 2004 and 2005. In addition to a variety of ground-based remote-sensing instruments, numerous rawin-sondes were released at one- to two-hourly intervals from six closely spaced sites. The Met Office weather radar network and Meteosat satellite imagery were used to provide context for the observations made by the instruments deployed during CSIP. This article presents an overview of the CSIP field campaign and examples from CSIP of the types of convective initiation phenomena that are typical in the United Kingdom. It shows the way in which certain kinds of observational data are able to reveal these phenomena and gives an explanation of how the analyses of data from the field campaign will be used in the development of an improved very high resolution NWP model for operational use.This work is funded by the National Environment Research Council following an initial award from the HEFCE Joint Infrastructure Fund

Identification of structurally conserved residues of proteins in absence of structural homologs using neural network ensemble

Motivation: So far various bioinformatics and machine learning techniques applied for identification of sequence and functionally conserved residues in proteins. Although few computational methods are available for the prediction of structurally conserved residues from protein structure, almost all methods require homologous structural information and structure-based alignments, which still prove to be a bottleneck in protein structure comparison studies. In this work, we developed a neural network approach for identification of structurally important residues from a single protein structure without using homologous structural information and structural alignment