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Due to their high frame rates and dynamic range, large area coverage, and high signal-to-noise ratio, hybrid silicon pixel detectors are an established standard for photon science applications at X-ray energies between 2 keV and 20 keV. These properties also make hybrid detectors interesting for experiments with soft X-rays between 200 eV and 2 keV. In this energy range, however, standard hybrid detectors are limited by the quantum efficiency of the sensor and the noise of the readout electronics. These limitations can be overcome by utilizing inverse Low-Gain Avalanche Diode (iLGAD) sensors with an optimized X-ray entrance window. We have developed and characterized a prototype soft X-ray iLGAD sensor bonded to the charge integrating 75 µm pixel JUNGFRAU chip. Cooled to −22°C, the system multiplication factor of the signal generated by an impinging photon is ≥ 11. With this gain, the effective equivalent noise charge of the system is ≤5.5 electrons root-mean-square at a 5 µs integration time. We show that by cooling the system below −50°C, single photon resolution at 200 eV becomes feasible with a signal-to-noise ratio better than 5.

Abstract Development can be altered to match phenotypes with the environment, and the genetic mechanisms that direct such alternative phenotypes are beginning to be elucidated. Yet, the rules that govern environmental sensitivity vs. invariant development, and potential epigenetic memory, remain unknown. Here, we show that plasticity of nematode mouth forms is determined by histone 4 lysine 5 and 12 acetylation (H4K5/12ac). Acetylation in early larval stages provides a permissive chromatin state, which is susceptible to induction during the critical window of environmental sensitivity. As development proceeds deacetylation shuts off switch gene expression to end the critical period. Inhibiting deacetylase enzymes leads to fixation of prior developmental trajectories, demonstrating that histone modifications in juveniles can carry environmental information to adults. Finally, we provide evidence that this regulation was derived from an ancient mechanism of licensing developmental speed. Altogether, our results show that H4K5/12ac enables epigenetic regulation of developmental plasticity that can be stored and erased by acetylation and deacetylation, respectively.

Hybrid pixel detectors have become indispensable at synchrotron and X-ray free-electron laser facilities thanks to their large dynamic range, high frame rate, low noise, and large area. However, at energies below 3 keV, the detector performance is often limited because of the poor quantum efficiency of the sensor and the difficulty in achieving single-photon resolution due to the low signal-to-noise ratio. In this paper, we address the quantum efficiency of silicon sensors by refining the design of the entrance window, mainly by passivating the silicon surface and optimizing the dopant profile of the n+ region. We present the measurement of the quantum efficiency in the soft X-ray energy range for silicon sensors with several process variations in the fabrication of planar sensors with thin entrance windows. The quantum efficiency for 250 eV photons is increased from almost 0.5% for a standard sensor to up to 62% as a consequence of these developments, comparable to the quantum efficiency of backside-illuminated scientific CMOS sensors. Finally, we discuss the influence of the various process parameters on quantum efficiency and present a strategy for further improvement.

Abstract Background Anxiety disorders are common among primary-school aged children, but few affected children receive evidence-based treatment. Identifying and supporting children who experience anxiety problems through schools would address substantial treatment access barriers that families and school staff often face. We have worked with families and school staff to co-design procedures that incorporate screening, feedback for parents, and the offer of a brief intervention in primary schools. This study sets out to assess the feasibility of a subsequent school-based cluster randomised controlled trial to evaluate these procedures. Our objectives are to ensure our procedures for identifying and supporting children with anxiety difficulties through primary schools are acceptable and there are no negative impacts, to estimate recruitment and retention rates, and to identify any changes needed to study procedures or measures. Methods We will recruit six primary/junior schools in England (2 classes per school), and invite all children (aged 8–9) (n = 360) and their parent/carer and class teacher in participating classes to take part. Children, parents and class teachers will complete questionnaires at baseline and 12-week follow-up. Children who ‘screen positive’ on a 2-item parent-report child anxiety screen at baseline will be the target population (expected n = 43). Parents receive feedback on screening questionnaire responses, and where the child screens positive the family is offered support (OSI: Online Support and Intervention for child anxiety). OSI is a brief, parent-led online intervention, supported by short telephone sessions with a Children’s Wellbeing Practitioner. Participants’ experiences of study procedures will be assessed through qualitative interviews/discussion groups. Discussion Evidence-based procedures for identifying and supporting children with anxiety difficulties through primary schools would improve children’s access to timely, effective intervention for anxiety difficulties. Trial registration ISRCTN registry: ISRCTN30032471 . Retrospectively registered on 18 May 2021.

IntroductionPrimary aldosteronism (PA) is associated with increased risk of cardiovascular events. However, treatment of PA has not been shown to improve left ventricular (LV) systolic function using the conventional assessment with LV ejection fraction (LVEF). We aim to use speckle-tracking echocardiography to assess for improvement in subclinical systolic function after treatment of PA.MethodsWe prospectively recruited 57 patients with PA, who underwent 24-h ambulatory blood pressure (BP) measurements and echocardiography, including global longitudinal strain (GLS) assessment of left ventricle, at baseline and 12 months post-treatment.ResultsAt baseline, GLS was low in 14 of 50 (28.0%) patients. On multivariable analysis, GLS was associated with diastolic BP (P = 0.038) and glomerular filtration rate (P = 0.026). GLS improved post-surgery by −2.3, 95% CI: −3.9 to −0.6, P = 0.010, and post-medications by −1.3, 95% CI: −2.6 to 0.03, P = 0.089, whereas there were no changes in LVEF in either group. Improvement in GLS was independently correlated with baseline GLS (P < 0.001) and increase in plasma renin activity (P = 0.007). Patients with post-treatment plasma renin activity ≥1 ng/ml/h had improvements in GLS (P = 0.0019), whereas patients with persistently suppressed renin had no improvement. Post-adrenalectomy, there were also improvements in LV mass index (P = 0.012), left atrial volume index (P = 0.002), and mitral E/e’ (P = 0.006), whereas it was not statistically significant in patients treated with medications.ConclusionTreatment of hyperaldosteronism is effective in improving subclinical LV systolic dysfunction. Elevation of renin levels after treatment, which reflects adequate reversal of sodium overload state, is associated with better systolic function after treatment.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT03174847.

Abstract Background Recent estimates suggest that one in ten young people worldwide experiences a diagnosable mental health disorder, with many more suffering subsyndromal levels of psychological distress. As young people spend much of their time in schools, the role of educational settings in the delivery of mental health provision is increasingly recognised. Advances in neurodevelopmental research have highlighted the important and complex role of peer influence on adolescent behaviours, suggesting peer-led support schemes have high potential utility. Schools worldwide have implemented peer-led interventions with mixed results, but the global evidence base on their effectiveness remains limited. This systematic review aims to examine the evidence base of the outcomes of school-based peer-led interventions on the mental health of young people aged 4–18. Methods Eligible studies will be randomised controlled trials and observational studies that report on the mental health outcomes of a peer-led school-based intervention. Eligible participants will be aged 4–18 and will be current students of the intervention school. Individual- and group-based interventions will be included. The following 11 databases will be screened based upon their reach in healthcare and education: PsycINFO, MEDLINE, EMBASE, CINAHL, CENTRAL, BEI, Scopus, Web of Science, ERIC, SSCI and Social Care Online. There will be no restriction placed on publication period, original language or country of publication. Papers will be systematically screened for eligibility by two review authors. Data will be presented as a descriptive report. A meta-analysis will be carried out if a subset of studies allows, given the anticipated high levels of heterogeneity. Discussion This systematic review will be the first to synthesise the global evidence on the mental health outcomes of peer-led interventions for children and adolescents in a school setting. It will analyse the available data in order to understand the role of these interventions in schools, inform future developers of peer support programmes and identify gaps in current research. This review will be of value to policy makers, health and education services, researchers and those involved in delivering peer support initiatives. Systematic review registration PROSPERO CRD42018116243

Schools worldwide have implemented many different peer-led interventions with mixed results, but the evidence base on their effectiveness as mental health interventions remains limited. This study combines a scoping review and systematic review to map the variations of peer-led interventions in schools and to evaluate the quality of the existing evidence base. This scoping review and systematic review evaluated the existing literature across 11 academic databases. Studies were included if they reported a peer-led intervention that aimed to address a mental health or wellbeing issue using a peer from the same school setting. Data were extracted from published and unpublished reports and presented as a narrative synthesis. 54 studies met eligibility criteria for the scoping review, showing that peer-led interventions have been used to address a range of mental health and wellbeing issues globally. 11 studies met eligibility criteria for the systematic review with a total of 2,239 participants eligible for analysis (929 peer leaders; 1,310 peer recipients). Two studies out of seven that looked at peer leaders showed significant improvements in self-esteem and social stress, with one study showing an increase in guilt. Two studies out of five that looked at peer recipient outcomes showed significant improvements in self-confidence and in a quality of life measure, with one study showing an increase in learning stress and a decrease in overall mental health scores. The findings from these reviews show that despite widespread use of peer-led interventions, the evidence base for mental health outcomes is sparse. There appear to be better documented benefits of participation for those who are chosen and trained to be a peer leader, than for recipients. However, the small number of included studies means any conclusions about effectiveness are tentative.

BackgroundDiabetes mellitus is associated with inadequate delivery of oxygen to tissues. Cellular hypoxia is associated with mitochondrial dysfunction which increases oxidative stress and hyperglycaemia. Hyperbaric oxygenation therapy, which was shown to improve insulin sensitivity, is impractical for regular use. We evaluated the effects of water which is stably-enriched with oxygen (ELO water) to increase arterial blood oxygen levels, on mitochondrial function in the presence of normal- or high-glucose environments, and as glucose-lowering therapy in humans.MethodsWe compared arterial blood oxygen levels in Sprague-Dawley rats after 7 days of ad libitum ELO or tap water consumption. Mitochondrial stress testing, and flow cytometry analysis of mitochondrial mass and membrane potential, were performed on human HepG2 cells cultured in four Dulbecco's Modified Eagle Medium media, made with ELO water or regular (control) water, at normal (5.5 mM) or high (25 mM) glucose concentrations. We also randomized 150 adults with type 2 diabetes (mean age 53 years, glycated haemoglobin HbA1c 8.9% [74 mmol/mol], average duration of diabetes 12 years) to drink 1.5 litres daily of bottled ELO water or drinking water.ResultsELO water raised arterial oxygen tension pO2 significantly (335 ± 26 vs. 188 ± 18 mmHg, p = 0.006) compared with tap water. In cells cultured in control water, mitochondrial mass and membrane potential were both significantly lower at 25 mM glucose compared with 5.5 mM glucose; in contrast, mitochondrial mass and membrane potential did not differ significantly at normal or high glucose concentrations in cells cultured in ELO water. The high-glucose environment induced a greater mitochondrial proton leak in cells cultured in ELO water compared to cells cultured in control medium at similar glucose concentration. In type 2 diabetic adults, HbA1c decreased significantly (p = 0.002) by 0.3 ± 0.7% (4 ± 8 mmol/mol), with ELO water after 12 weeks of treatment but was unchanged with placebo.ConclusionsELO water raises arterial blood oxygen levels, appears to have a protective effect on hyperglycaemia-induced reduction in mitochondrial mass and mitochondrial dysfunction, and may be effective adjuvant therapy for type 2 diabetes.

Microbial degradation is a useful tool for inhibiting or preventing polycyclic aromatic hydrocarbons (PAHs) widely distributed in marine environment after oil spill accidents. This study aimed to evaluate the potential and diversity of bacteria Bacillus sp. PAH-2 on Benzo (a) anthracene (BaA), Pyrene (Pyr), and Benzo (a) pyrene (BaP), their composite system, aromatic components system, and crude oil. The seven-day degradation rates against BaA, Pyr, and BaP were 20.6%, 12.83%, and 17.49%, respectively. Further degradation study of aromatic components demonstrated PAH-2 had a high degradation rate of substances with poor stability of molecular structure. In addition, the degradation of PAHs in crude oil suggested PAH-2 not only made good use of PAHs in such a more complex structure of pollutants but the saturated hydrocarbons in the crude oil also showed a good application potential.

Purpose: Despite making up 20-25% of hand surgeons with subspecialty certification in the field, little data exists characterizing the clinical practice of hand surgery among plastic surgeons. This study sought to evaluate hand surgery cases in the national Tracking Operations and Outcomes for Plastic Surgeons (TOPS) database. Methods: All hand procedures logged in the TOPS database between 2002 and 2016 were identified by CPT code and/or “upper extremity” anatomic classification. Trends in the total number and types of procedures, facility type, admission type, modes and providers of anesthesia, and patient demographics were reviewed. Results: A total of 182,137 hand procedures performed on 82,811 patients were logged during the 15-year period reviewed. Sixty-eight percent of procedures were classified as involving soft tissue only, and 22.7% involved only bone and/or joint. The most common procedure categories included: wound closure/coverage (15.8%), debridement/drainage (15.3%), nerve (13.2%), tendon (12.9%), and fracture/dislocation (12.9%). This category breakdown remained relatively stable over time. Evaluation of longitudinal trends identified an increase over time in procedures performed in the ambulatory and office-based settings and the use of local anesthetic, as well as a transition from the procedural surgeon providing anesthesia to the use of anesthesiologists and nurse anesthetists. The average patient ASA increased from 1.27 to 1.83. Conculsions: Plastic surgeons play an important role in the field of hand surgery, performing a large breadth of procedure types, which has remained stable over time. The trends in facility type and anesthesia characteristics have, however, varied.

Summary: MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8+ MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel of cytokines to include TNF-superfamily member TL1A. RNA-seq experiments revealed that TCR-dependent and TCR-independent signals drive MAIT cells to exert overlapping and specific effector functions, affecting both host defense and tissue homeostasis. Although TCR triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells showed specific enrichment of tissue-repair functions at the gene and protein levels and in in vitro assays. Altogether, these data indicate the blend of TCR-dependent and TCR-independent signaling to CD8+ MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair. : Leng et al. explore the consequences of activation of human MAIT cells via their TCR and/or cytokines, including the gut-associated TNF-superfamily member TL1A. TCR triggering reveals a transcriptional program linked to tissue-repair functions seen in vivo, consistent with a homeostatic role for these cells in epithelia. Keywords: MAIT cells, effector functions, TCR signaling, cytokines, tissue repair