Developing Executive Functions through Mindfulness Training in School-Aged Children

Well-developed executive functions are necessary for successful classroom functioning. Students with executive function deficits can fall behind academically as well as socially and emotionally, relative to their same-aged peers. Effective interventions for developing executive functions within the school environment are essential for addressing this issue. This study examines changes in students’ executive functions as a result of their participation in a mindfulness training intervention. Participants included four ten-year old elementary school boys who took part in a ten-week mindfulness training intervention. The data were generated through pre and post assessments with an executive function teacher rating scale and a Goal-Attainment Scale completed by the participants. Results suggest that all four participants demonstrated self-perceived increases in executive functions as indicated by reaching their self-set goals. Teacher reports indicated an increase in some measured executive function capacities; however, results were not consistent across subjects

B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma

B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma

eRAPID electronic patient self-Reporting of Adverse-events: Patient Information and aDvice: a pilot study protocol in pelvic radiotherapy.

Background: An estimated 17,000 patients are treated annually in the UK with radical radiotherapy (RT) for pelvic cancer. New treatment approaches in RT have increased survivorship and changed the subjective toxicity profile for patients who experience acute and long-term pelvic-related adverse events (AE). Multi-disciplinary follow-up creates difficulty for monitoring and responding to these events during treatment and beyond. Originally developed for use in systemic oncology therapy eRAPID (electronic patient self-Reporting of Adverse-events: Patient Information and aDvice) is an online system for patients to report AEs from home. eRAPID enables patient data to be integrated into the electronic patient records for use in clinical practice, provides patient management advice for mild and moderate AE and advice to contact the hospital for severe AE. The system has now been developed for pelvic RT patients, and we aim to test the intervention in a pilot study with staff and patients to inform a future randomised controlled trial (RCT). Methods: Eligible patients are those attending St James's University hospital cancer centre and The Christie Hospital Manchester undergoing pelvic radiotherapy+/-chemotherapy/hormonotherapy for prostate, lower gastrointestinal and gynaecological cancers. A prospective 1:1 randomised (intervention or usual care) parallel group design with repeated measures and mixed methods will be employed. We aim to recruit 168 patients following recommendations for sample size estimates for pilot studies. Participants using eRAPID will report AE (at least weekly) from home weekly for 6 weeks and 6 weeks post-treatment (12-week total) then at 18 and 24 weeks. Hospital staff will review eRAPID reports and use information during consultations. Notifications will be sent to the relevant clinical team when severe symptoms are reported. We will measure patient-reported outcomes using validated questionnaires (Functional Assessment in Cancer Therapy Scale-General (FACT-G), European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC-QLQ-C30), process of care impact (hospital records of patient contacts and admissions) and economic variables (EQ5D-5L, patient use of resources)). Staff and patient experiences will be explored via semi-structured interviews. Discussion: The objectives are to establish feasibility, recruitment, integrity of the system and attrition rates, determine effect sizes and aid selection of the primary outcome measure for a future RCT. We will also refine the intervention by exploring staff and patient views. The overall goal of this complex intervention is to improve the safe delivery of cancer treatments, enhance patient care and standardise documentation of AE within the clinical datasets. Trial registration: ClinicalTrials.gov NCT02747264

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe