Characterisation of the transcriptome of a wild great tit Parus major population by next generation sequencing

Background: The recent development of next generation sequencing technologies has made it possible to generate very large amounts of sequence data in species with little or no genome information. Combined with the large phenotypic databases available for wild and non-model species, these data will provide an unprecedented opportunity to "genomicise" ecological model organisms and establish the genetic basis of quantitative traits in natural populations

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Can Evolution Supply What Ecology Demands?

A simplistic view of the adaptive process pictures a hillside along which a population can climb: when ecological ‘demands’ change, evolution ‘supplies’ the variation needed for the population to climb to a new peak. Evolutionary ecologists point out that this simplistic view can be incomplete because the fitness landscape changes dynamically as the population evolves. Geneticists meanwhile have identified complexities relating to the nature of genetic variation and its architecture, and the importance of epigenetic variation is under debate. In this review, we highlight how complexity in both ecological ‘demands’ and the evolutionary ‘supply’ influences organisms’ ability to climb fitness landscapes that themselves change dynamically as evolution proceeds, and encourage new synthetic effort across research disciplines towards ecologically realistic studies of adaptation

Age and gender variations in cancer diagnostic intervals in 15 cancers: analysis of data from the UK Clinical Practice Research Datalink

Background Time from symptomatic presentation to cancer diagnosis (diagnostic interval) is an important, and modifiable, part of the patient’s cancer pathway, and can be affected by various factors such as age, gender and type of presenting symptoms. The aim of this study was to quantify the relationships of diagnostic interval with these variables in 15 cancers diagnosed between 2007 and 2010 using routinely collected data from the Clinical Practice Research Datalink (CPRD) in the UK. Methods Symptom lists for each cancer were prepared from the literature and by consensus amongst the clinician researchers, which were then categorised into either NICE qualifying (NICE) or not (non-NICE) based on NICE Urgent Referral Guidelines for Suspected Cancer criteria. Multivariable linear regression models were fitted to examine the relationship between diagnostic interval (outcome) and the predictors: age, gender and symptom type. Results 18,618 newly diagnosed cancer patients aged ≥40 who had a recorded symptom in the preceding year were included in the analysis. Mean diagnostic interval was greater for older patients in four disease sites (difference in days per 10 year increase in age; 95% CI): bladder (10.3; 5.5 to 15.1; P<0.001), kidney (11.0; 3.4 to 18.6; P=0.004), leukaemia (18.5; 8.8 to 28.1; P<0.001) and lung (10.1; 6.7 to 13.4; P<0.001). There was also evidence of longer diagnostic interval in older patients with colorectal cancer (P<0.001). However, we found that mean diagnostic interval was shorter with increasing age in two cancers: gastric (-5.9; -11.7 to -0.2; P=0.04) and pancreatic (-6.0; -11.2 to -0.7; P=0.03). Diagnostic interval was longer for females in six of the gender non-specific cancers (mean difference in days; 95% CI): bladder (12.2; 0.8 to 23.6; P=0.04), colorectal (10.4; 4.3 to 16.5; P=0.001), gastric (14.3; 1.1 to 27.6; P=0.03), head and neck (31.3; 6.2 to 56.5; P=0.02), lung (8.0; 1.2 to 14.9; P=0.02), and lymphoma (19.2; 3.8 to 34.7; P=0.01). Evidence of longer diagnostic interval was found for patients presenting with non-NICE symptoms in 10 of 15 cancers (mean difference in days; 95% CI): bladder (62.9; 48.7 to 77.2; P<0.001), breast (115.1; 105.9 to 124.3; P<0.001), cervical (60.3; 31.6 to 89.0; P<0.001), colorectal (25.8; 19.6 to 31.9; P<0.001), gastric (24.1; 3.4 to 44.8; P=0.02), kidney (22.1; 4.5 to 39.7; P=0.01), oesophageal (67.0; 42.1 to 92.0; P<0.001), pancreatic (48.6; 28.1 to 69.1; P<0.001), testicular (36.7; 17.0 to 56.4; P< 0.001), and endometrial (73.8; 60.3 to 87.3; P<0.001). Pooled analysis across all cancers demonstrated highly significant evidence of differences overall showing longer diagnostic intervals with increasing age (7.8 days; 6.4 to 9.1; P<0.001); for females (8.9 days; 5.5 to 12.2; P<0.001); and in non-NICE symptoms (27.7 days; 23.9 to 31.5; P<0.001). Conclusions We found age and gender-specific inequalities in time to diagnosis for some but not all cancer sites studied. Whilst these need further explanation, these findings can inform the development and evaluation of interventions intended to achieve timely diagnosis and improved cancer outcomes, such as to provide equity across all age and gender groupings

CERN’s SRF Test Stand for Cavity Performance Measurements

Recent deployment of a digital LLRF system within the cavity testing framework of CERN’s vertical test cryostats has permitted a full revamp of cavity performance validation. With both full continuous and pulse mode operation, steady state a transient RF behaviour can be effectively probed. Due to direct and integrated control and monitoring of environmental test conditions, standard and novel RF measurement procedures have been developed and integrated into the testing infrastructure, along with a coherent data flow of high granularity measurement data. We present an overview of this cavity measurement system and address the underlying architectural structure, data handling and integration of user interfaces. In addition we highlight the benefits of variety of RF cavity measurements that can now be accommodated in our large 2 K cryostats

A Ferroelectric Fast Reactive Tuner (FE-FRT) to Combat Microphonics

A prototype Fast Reactive Tuner (FRT) for superconducting cavities has been developed, which allows the frequency to be controlled by application of a potential difference across a newly developed ultra-low loss ferro-electric material residing within the tuner. The tuner operates at room temperature, outside of the cryostat and coupled to the cavity via an antenna and co-axial cable. This technique allows for active compensation of microphonics, eliminating the need to design over-coupled fundamental power couplers and thus significantly reducing RF power particularly for low beam current applications. Modelling; simulation; and stability analysis, of the tuner; cavity; measurement system; and feedback loop, have been performed in the frequency and time domain, and are compared to the latest experimental results. The potential benefits of applying this techniques to ERLs, which are seen as one of the major use cases, are detailed both in general and with regards to specific projects. Ideas and designs for an improved next generation FRT are also discussed

Ferro-Electric Fast Reactive Tuner Applications for SRF Cavities

A Ferro-Electric fast Reactive Tuner (FE-FRT) is a novel type of RF cavity tuner containing a low loss ferroelectric material. FE-FRTs have no moving parts and allow cavity frequencies to be changed extremely quickly (on the timescale of 100s of ns or less). They are of particular interest for SRF cavities as they can be placed outside the liquid helium environment and without an FE-FRT it’s typically very difficult to tune SRF cavities quickly. FE-FRTs can be used for a wide variety of use cases including microphonics suppression, RF switching, and transient beam loading compensation. This promises entirely new operational capabilities, increased performance and cost savings for a variety of existing and proposed accelerators. An overview of the theory and potential applications will be discussed in detail

Contribution to the modelling of chocolate tempering process

The chocolate tempering process based on seeding the melted chocolate with the solid chocolate grains is studied. A model is developed to enhance the understanding and the control of the process. This model aims to predict temperature field during melting and crystallization of the product. The heat transfer problem is simplified by using an effective thermal conductivity for modeling the mixing obtained with a newly designed stirrer. The parameter value is fitted on the experimental results. The heat conduction equation is solved using Comsol. The melting of cocoa butter particles serving as seeds is added to the model using a sink term having the form of a kinetic reaction whose parameters are identified from an adiabatic melting experiment. The resulting model gives an accurate prediction of the cooling rate and the temperature field within the melted chocolate seeded with small solid grains.info:eu-repo/semantics/publishe

A Ferroelectric Fast Reactive Tuner for Superconducting Cavities

A prototype FerroElectric Fast Reactive Tuner (FE-FRT) for superconducting cavities has been developed, which allows the frequency to be controlled by application of a potential difference across a ferroelectric residing within the tuner. This technique has now become practically feasible due to the recent development of a new extremely low loss ferroelectric material. In a world first, CERN has tested the prototype FE-FRT with a superconducting cavity, and frequency tuning has been successfully demonstrated. This is a significant first step in the development of an entirely new class of tuner. These will allow electronic control of cavity frequencies, by a device operating at room temperature, within timescales that will allow active compensation of microphonics. For many applications this could eliminate the need to use over-coupled fundamental power couplers, thus significantly reducing RF amplifier power