Enhanced magnetic Purcell effect in room-temperature masers

Recently, the world’s first room-temperature maser was demonstrated. The maser consisted of a sapphire ring housing a crystal of pentacene-doped p-terphenyl, pumped by a pulsed rhodamine-dye laser. Stimulated emission of microwaves was aided by the high quality factor and small magnetic mode volume of the maser cavity yet the peak optical pumping power was 1.4 kW. Here we report dramatic miniaturization and 2 orders of magnitude reduction in optical pumping power for a room-temperature maser by coupling a strontium titanate resonator with the spin-polarized population inversion provided by triplet states in an optically excited pentacene-doped p-terphenyl crystal. We observe maser emission in a thimble-sized resonator using a xenon flash lamp as an optical pump source with peak optical power of 70 W. This is a significant step towards the goal of continuous maser operation

Dual-gated bilayer graphene hot electron bolometer

Detection of infrared light is central to diverse applications in security, medicine, astronomy, materials science, and biology. Often different materials and detection mechanisms are employed to optimize performance in different spectral ranges. Graphene is a unique material with strong, nearly frequency-independent light-matter interaction from far infrared to ultraviolet, with potential for broadband photonics applications. Moreover, graphene's small electron-phonon coupling suggests that hot-electron effects may be exploited at relatively high temperatures for fast and highly sensitive detectors in which light energy heats only the small-specific-heat electronic system. Here we demonstrate such a hot-electron bolometer using bilayer graphene that is dual-gated to create a tunable bandgap and electron-temperature-dependent conductivity. The measured large electron-phonon heat resistance is in good agreement with theoretical estimates in magnitude and temperature dependence, and enables our graphene bolometer operating at a temperature of 5 K to have a low noise equivalent power (33 fW/Hz1/2). We employ a pump-probe technique to directly measure the intrinsic speed of our device, >1 GHz at 10 K.Comment: 5 figure

A mobile phone app to support young people in making shared decisions in therapy (Power Up): study protocol

Background: Evidence suggests that young people want to be active participants in their care and involved in decisions about their treatment. However, there is a lack of digital shared decision-making tools available to support young people in child and adolescent mental health services (CAMHS). Objective: The primary aim of this paper is to present the protocol of a feasibility trial for Power Up, a mobile phone app to empower young people in CAMHS to make their voices heard and participate in decisions around their care. Methods: In the development phase, 30 young people, parents, and clinicians will take part in interviews and focus groups to elicit opinions on an early version of the app. In the feasibility testing phase, 60 young people from across 7 to 10 London CAMHS sites will take part in a trial looking at the feasibility and acceptability of measuring the impact of Power Up on shared decision making. Results: Data collection for the development phase ended in December 2016. Data collection for the feasibility testing phase will end in December 2017. Conclusions: Findings will inform the planning of a cluster controlled trial and contribute to the development and implementation of a shared decision-making app to be integrated into CAMHS

Genes Suggest Ancestral Colour Polymorphisms Are Shared across Morphologically Cryptic Species in Arctic Bumblebees

email Suzanne orcd idCopyright: © 2015 Williams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. METHODS: We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium(R) HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. CONCLUSION: This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy

Heterostyly: speciation within a species

Almost all organisms in nature show nonrandom mating to different degrees. Two extreme results of nonrandom mating are speciation and sexual differentiation. Heterostyly is a form of sexual differentiation considered to have evolved to resolve conflicts between male and female functions of hermaphrodite flowers. Our study examines necessary and sufficient conditions for establishment of heterostyly using a configuration individual-based model. Previous models assume invasion of a mutant phenotype into a population with monomorphic wild phenotype. In contrast, our model demonstrates that heterostyly can be established from a population with continuous phenotypic variation, a proposition that requires simpler assumptions than the previous hypotheses. Results of our simulation show that genetic linkage between stigma and anther heights is essential for establishment of heterostyly. Dominance effects on the genes for stamen or stigma heights are not necessary, but they promote evolution of heterostyly. Probability of evolution of heterostyly also depends on the functional relationship between stigma–anther distance and strength of sexual interference, and the distance and probability of pollen deposition success. Parallelity and difference between speciation and sexual differentiation are also discussed

Digital IAPT: the effectiveness & cost-effectiveness of internet-delivered interventions for depression and anxiety disorders in the Improving Access to Psychological Therapies programme: study protocol for a randomised control trial

BACKGROUND: Depression and anxiety are common mental health disorders worldwide. The UK's Improving Access to Psychological Therapies (IAPT) programme is part of the National Health Service (NHS) designed to provide a stepped care approach to treating people with anxiety and depressive disorders. Cognitive Behavioural Therapy (CBT) is widely used, with computerised and internet-delivered cognitive behavioural therapy (cCBT and iCBT, respectively) being a suitable IAPT approved treatment alternative for step 2, low- intensity treatment. iCBT has accumulated a large empirical base for treating depression and anxiety disorders. However, the cost-effectiveness and impact of these interventions in the longer-term is not routinely assessed by IAPT services. The current study aims to evaluate the clinical and cost-effectiveness of internet-delivered interventions for symptoms of depression and anxiety disorders in IAPT. METHODS: The study is a parallel-groups, randomised controlled trial examining the effectiveness and cost-effectiveness of iCBT interventions for depression and anxiety disorders, against a waitlist control group. The iCBT treatments are of 8 weeks duration and will be supported by regular post-session feedback by Psychological Wellbeing Practitioners. Assessments will be conducted at baseline, during, and at the end of the 8-week treatment and at 3, 6, 9, and 12-month follow-up. A diagnostic interview will be employed at baseline and 3-month follow-up. Participants in the waitlist control group will complete measures at baseline and week 8, at which point they will receive access to the treatment. All adult users of the Berkshire NHS Trust IAPT Talking Therapies Step 2 services will be approached to participate and measured against set eligibility criteria. Primary outcome measures will assess anxiety and depressive symptoms using the GAD-7 and PHQ-9, respectively. Secondary outcome measures will allow for the evaluation of long-term outcomes, mediators and moderators of outcome, and cost-effectiveness of treatment. Analysis will be conducted on a per protocol and intention-to-treat basis. DISCUSSION: This study seeks to evaluate the immediate and longer-term impact, as well as the cost effectiveness of internet-delivered interventions for depression and anxiety. This study will contribute to the already established literature on internet-delivered interventions worldwide. The study has the potential to show how iCBT can enhance service provision, and the findings will likely be generalisable to other health services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN ISRCTN91967124. DOI: https://doi.org/10.1186/ISRCTN91967124 . Web: http://www.isrctn.com/ISRCTN91967124 . Clinicaltrials.gov : NCT03188575. Trial registration date: June 8, 2017 (prospectively registered)

Beyond the security paradox:Ten criteria for a socially informed security policy

This article is based on a research that has been funded by the EU project “SurPriSe: Surveillance, Privacy and Security: A large scale participatory assessment of criteria and factors determining acceptability and acceptance of security technologies in Europe”, which received funding from the FP7 program, under the grant number: 285492.This article investigates the normative and procedural criteria adopted by European citizens to assess the acceptability of surveillance-oriented security technologies. It draws on qualitative data gathered at 12 citizen summits in nine European countries. The analysis identifies 10 criteria, generated by citizens themselves, for a socially informed security policy. These criteria not only reveal the conditions, purposes and operation rules that would make current European security policies and technologies more consistent with citizens’ priorities. They also cast light on an interesting paradox: although people feel safe in their daily lives, they believe security could, and should, be improved.PostprintPeer reviewe

Comparative cardiometabolic safety and effectiveness of aripiprazole in people with severe mental illness: A target trial emulation

Background There is limited and conflicting evidence on the comparative cardiometabolic safety and effectiveness of aripiprazole in the management of severe mental illness. We investigated the hypothesis that aripiprazole has a favourable cardiometabolic profile, but similar effectiveness when compared to olanzapine, quetiapine, and risperidone. Methods and findings We conducted an observational emulation of a head-to-head trial of aripiprazole versus olanzapine, quetiapine, and risperidone in UK primary care using data from the Clinical Practice Research Datalink. We included adults diagnosed with severe mental illness (i.e., bipolar disorder, schizophrenia, and other non-organic psychoses) who were prescribed a new anti-psychotic between 2005 and 2017, with a 2-year follow-up to 2019. The primary outcome was total cholesterol at 1 year (cardiometabolic safety). The main secondary outcome was psychiatric hospitalisation (effectiveness). Other outcomes included body weight, blood pressure, all-cause discontinuation, and mortality. Analyses adjusted for baseline confounders, including sociodemographics, diagnoses, concomitant medications, and cardiometabolic parameters. We included 26,537 patients (aripiprazole, n= 3,573, olanzapine, n= 8,554, quetiapine, n= 8,289, risperidone, n= 6,121). Median (IQR) age was 53 (42−67) years, 55.4% were female, 82.3% White, and 18.0% were diagnosed with schizophrenia. Patients prescribed aripiprazole had similar total cholesterol levels after 1 year to those prescribed olanzapine (adjusted mean difference [aMD], −0.03, 95% CI, −0.09 to 0.02, p= 0.261), quetiapine (aMD, −0.03, 95% CI, −0.09 to 0.03, p= 0.324), and risperidone (aMD, −0.01, 95% CI, −0.08 to 0.05, p = 0.707). However, there was evidence that patients prescribed aripiprazole had better outcomes on other cardiometabolic parameters, such as body weight and blood pressure, especially compared to olanzapine. After additional adjustment for prior hospitalisation, patients prescribed aripiprazole had similar rates of psychiatric hospitalisation as those prescribed olanzapine (adjusted hazard ratio [aHR], 0.91, 95% CI, 0.82–1.01, p = 0.078), quetiapine (aHR, 0.94, 95% CI, 0.85–1.04, p = 0.230), or risperidone (aHR, 1.01, 95% CI, 0.91–1.12, p = 0.854). Conclusions Data from our large, powered, diverse, real-world target trial emulation sample, followed over 2 years, suggest that adults diagnosed with severe mental illness prescribed aripiprazole have similar total cholesterol 1 year after first prescription compared to those prescribed olanzapine, quetiapine, and risperidone. However, patients prescribed aripiprazole had better outcomes on some other cardiometabolic parameters, and there was little evidence of differences in effectiveness. Our findings inform a common clinical dilemma and contribute to the evidence base for real-world clinical decision-making on antipsychotic choice for patients diagnosed with severe mental illness