Neutron-Unbound Excited States of 23N

Neutron unbound states in 23N were populated via proton knockout from an 83.4 MeV/nucleon 24O beam on a liquid deuterium target. The two-body decay energy displays two peaks at E1∼100keV and E2∼1MeV with respect to the neutron separation energy. The data are consistent with shell model calculations predicting resonances at excitation energies of ∼3.6MeV and ∼4.5MeV. The selectivity of the reaction implies that these states correspond to the first and second 3/2− states. The energy of the first state is about 1.3 MeV lower than the first excited 2+ in 24O. This decrease is largely due to coupling with the πp−13/2 hole along with a small reduction of the N=16 shell gap in 23N

Two-Neutron Sequential Decay of 24^{24}O

A two-neutron unbound excited state of $^{24}$O was populated through a (d,d') reaction at 83.4 MeV/nucleon. A state at $E = 715 \pm 110$ (stat) $\pm 45$ (sys) keV with a width of $\Gamma < 2$ MeV was observed above the two-neutron separation energy placing it at 7.65 $\pm$ 0.2 MeV with respect to the ground state. Three-body correlations for the decay of $^{24}$O $\rightarrow$ $^{22}$O + $2n$ show clear evidence for a sequential decay through an intermediate state in $^{23}$O. Neither a di-neutron nor phase-space model for the three-body breakup were able to describe these correlations

A note on conformal symmetry in projective superspace

We describe a sufficient condition for actions constructed in projective superspace to possess an SU(2) R-symmetry. We check directly that this condition implies that the corresponding hyperkahler varieties, constructed by means of the generalized Legendre transform, have a Swann bundle structure.Comment: 21 pages, added reference

Stratification of adolescents across mental phenomena emphasizes the importance of transdiagnostic distress: a replication in two general population cohorts

Characterizing patterns of mental phenomena in epidemiological studies of adolescents can provide insight into the latent organization of psychiatric disorders. This avoids the biases of chronicity and selection inherent in clinical samples, guides models of shared aetiology within psychiatric disorders and informs the development and implementation of interventions. We applied Gaussian mixture modelling to measures of mental phenomena from two general population cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC, n=3,018) and the Neuroscience in Psychiatry Network (NSPN, n=2,023). We defined classes according to their patterns of both positive (e.g. wellbeing and self-esteem) and negative (e.g. depression, anxiety, psychotic experiences) phenomena. Subsequently, we characterized classes by considering the distribution of diagnoses and sex split across classes. Four well-separated classes were identified within each cohort. Classes primarily differed by overall severity of transdiagnostic distress rather than particular patterns of phenomena akin to diagnoses. Further, as overall severity of distress increased, so did within-class variability, the proportion of individuals with operational psychiatric diagnoses. These results suggest that classes of mental phenomena in the general population of adolescents may not be the same as those found in clinical samples. Classes differentiated only by overall severity support the existence of a general, transdiagnostic mental distress factor and have important implications for intervention

Examining pathways between genetic liability for schizophrenia and patterns of tobacco and cannabis use in adolescence

Background It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies. Methods Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes. Results The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses. Conclusions Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population

Examining pathways between genetic liability for schizophrenia and patterns of tobacco and cannabis use in adolescence

Background It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies. Methods Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes. Results The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses. Conclusions Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population

Association between maternal depression symptoms across the first eleven years of their child’s life and subsequent offspring suicidal ideation

Depression is common, especially in women of child-bearing age; prevalence estimates for this group range from 8% to 12%, and there is robust evidence that maternal depression is associated with mental health problems in offspring. Suicidal behaviour is a growing concern amongst young people and those exposed to maternal depression are likely to be especially at high risk. The aim of this study was to utilise a large, prospective population cohort to examine the relationship between depression symptom trajectories in mothers over the first eleven years of their child’s life and subsequent adolescent suicidal ideation. An additional aim was to test if associations were explained by maternal suicide attempt and offspring depressive disorder. Data were utilised from a population-based birth cohort: the Avon Longitudinal Study of Parents and Children. Maternal depression symptoms were assessed repeatedly from pregnancy to child age 11 years. Offspring suicidal ideation was assessed at age 16 years. Using multiple imputation, data for 10,559 families were analysed. Using latent class growth analysis, five distinct classes of maternal depression symptoms were identified (minimal, mild, increasing, sub-threshold, chronic-severe). The prevalence of past-year suicidal ideation at age 16 years was 15% (95% CI: 14-17%). Compared to offspring of mothers with minimal symptoms, the greatest risk of suicidal ideation was found for offspring of mothers with chronic-severe symptoms [OR 3.04 (95% CI 2.19,4.21)], with evidence for smaller increases in risk of suicidal ideation in offspring of mothers with sub-threshold, increasing and mild symptoms. These associations were not fully accounted for by maternal suicide attempt or offspring depression diagnosis. Twenty-six percent of non-depressed offspring of mothers with chronic-severe depression symptoms reported suicidal ideation. Risk for suicidal ideation should be considered in young people whose mothers have a history of sustained high levels of depression symptoms, even when the offspring themselves do not have a depression diagnosis

Modelling the impact of wastewater flows and management practices on antimicrobial resistance in dairy farms

Dairy slurry is a major source of environmental contamination with antimicrobial resistant genes and bacteria. We developed mathematical models and conducted on-farm research to explore the impact of wastewater flows and management practices on antimicrobial resistance (AMR) in slurry. Temporal fluctuations in cephalosporin-resistant Escherichia coli were observed and attributed to farm activities, specifically the disposal of spent copper and zinc footbath into the slurry system. Our model revealed that resistance should be more frequently observed with relevant determinants encoded chromosomally rather than on plasmids, which was supported by reanalysis of sequenced genomes from the farm. Additionally, lower resistance levels were predicted in conditions with lower growth and higher death rates. The use of muck heap effluent for washing dirty channels did not explain the fluctuations in cephalosporin resistance. These results highlight farm-specific opportunities to reduce AMR pollution, beyond antibiotic use reduction, including careful disposal or recycling of waste antimicrobial metals. Antimicrobial resistance (AMR) is one of the most important global public health problems. It is estimated that 1.27 million deaths were attributed to AMR bacteria globally in 2019 1 , and, unless suitable countermeasures are taken, that number is predicted to rise to 10 million by 2050 2. AMR is driven by antibiotic use; the majority (73%) of antibiotic (Ab) sales are for use for food-producing livestock 3. The use of Abs in agriculture can result in drug-resistant strains infecting human populations through the food chain 4,5 , or may lead to the transfer of antibiotic resistance genes (ARGs) from livestock-associated bacteria to human-acquired infections 6-8. The importance of mitigating the risks of AMR in the agricultural sector has been recognised by many countries, including the UK, the European Union and the UN 2,9 , with reductions and restrictions being imposed on Ab use in agriculture, particularly on human critical antibiotics. However, despite a 55% reduction in Ab use in the UK agriculture sector since 2014 10 , use remains high, representing 36% of the total UK Ab use 11 , with consequent risk of spread of ARGs and AMR. In addition to antibiotics, other antimicrobials such as metals (copper and zinc) and other chemicals (e.g., formalin, disinfectants) are widely used across farms globally, particularly in footbaths to prevent lameness in livestock-a prevalent concern in dairy and sheep farming 12. Metals and other antimicrobial agents (such as formalin and glutaraldehyde) are known to have a co-selective effect on antibiotic resistance, allowing for th

De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability