Age at menarche and current substance use among Canadian adolescent girls: results of a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Substance use is among the key public health threats that find its genesis during adolescence. Timing of puberty has been lately researched as a potential predictor of subsequent substance abuse. The present study, therefore, aims to assess the effect of age at menarche on current practices of smoking, alcohol drinking and drug use among 14-15 year old Canadian girls.</p> <p>Methods</p> <p>The analysis of the study was based on all female respondents aged 14 to 15 years during Cycle 4 (2000/2001) of the National Longitudinal Survey of Children & Youth (NLSCY). The main independent variable was age at menarche assessed as the month and year of the occurrence of the first menstrual cycle. The dependent variables were current smoking, heavy alcohol drinking in the past 12 months and drug use in the past 12 months. Three logistic regression models were performed to investigate the association between age at menarche and each of the substance use outcomes, adjusting for possible confounders. Bootstrapping was performed to account for the complex sampling design.</p> <p>Results</p> <p>The total weighted sample included in the analysis represented 295,042 Canadian girls. The prevalence of current smokers, heavy drinkers (drunk in the past 12 months) and drug users in the past 12 months was approximately 22%, 38% and 26%, respectively. After adjusting of all potential confounders, no association was found between age at menarche and any of the substance use outcomes. School performance and relationship with the father, however, stood out as the main variables to be associated with smoking, heavy drinking and drug use.</p> <p>Conclusions</p> <p>Qualitative studies understanding the social and psychological changes experienced by early maturing Canadian adolescents are warranted to identify other correlates or pathways to substance use in this higher risk population.</p

A trial protocol for the effectiveness of digital interventions for preventing depression in adolescents : The Future Proofing Study

Background: Depression frequently first emerges during adolescence, and one in five young people will experience an episode of depression by the age of 18 years. Despite advances in treatment, there has been limited progress in addressing the burden at a population level. Accordingly, there has been growing interest in prevention approaches as an additional pathway to address depression. Depression can be prevented using evidence-based psychological programmes. However, barriers to implementing and accessing these programmes remain, typically reflecting a requirement for delivery by clinical experts and high associated delivery costs. Digital technologies, specifically smartphones, are now considered a key strategy to overcome the barriers inhibiting access to mental health programmes. The Future Proofing Study is a large-scale school-based trial investigating whether cognitive behaviour therapies (CBT) delivered by smartphone application can prevent depression. Methods: A randomised controlled trial targeting up to 10,000 Year 8 Australian secondary school students will be conducted. In Stage I, schools will be randomised at the cluster level either to receive the CBT intervention app (SPARX) or to a non-active control group comparator. The primary outcome will be symptoms of depression, and secondary outcomes include psychological distress, anxiety and insomnia. At the 12-month follow-up, participants in the intervention arm with elevated depressive symptoms will participate in an individual-level randomised controlled trial (Stage II) and be randomised to receive a second CBT app which targets sleep difficulties (Sleep Ninja) or a control condition. Assessments will occur post intervention (both trial stages) and at 6, 12, 24, 36, 48 and 60 months post baseline. Primary analyses will use an intention-to-treat approach and compare changes in symptoms from baseline to follow-up relative to the control group using mixed-effect models. Discussion: This is the first trial testing the effectiveness of smartphone apps delivered to school students to prevent depression at scale. Results from this trial will provide much-needed insight into the feasibility of this approach. They stand to inform policy and commission decisions concerning if and how such programmes should be deployed in school-based settings in Australia and beyond

Interactive effects of obesity and physical fitness on risk of ischemic heart disease

Background/Objectives:Obesity and low physical fitness are known risk factors for ischemic heart disease (IHD), but their interactive effects are unclear. Elucidation of interactions between these common, modifiable risk factors may help inform more effective preventive strategies. We examined interactive effects of obesity, aerobic fitness and muscular strength in late adolescence on risk of IHD in adulthood in a large national cohort.Subjects/Methods:We conducted a national cohort study of all 1 547 407 military conscripts in Sweden during 1969-1997 (97-98% of all 18-year-old males each year). Aerobic fitness, muscular strength and body mass index (BMI) measurements were examined in relation to IHD identified from outpatient and inpatient diagnoses through 2012 (maximum age 62 years).Results:There were 38 142 men diagnosed with IHD in 39.7 million person years of follow-up. High BMI or low aerobic fitness (but not muscular strength) was associated with higher risk of IHD, adjusting for family history and socioeconomic factors. The combination of high BMI (overweight/obese vs normal) and low aerobic fitness (lowest vs highest tertile) was associated with highest IHD risk (incidence rate ratio, 3.11; 95% confidence interval (CI), 2.91-3.31; P<0.001). These exposures had no additive and a negative multiplicative interaction (that is, their combined effect was less than the product of their separate effects). Low aerobic fitness was a strong risk factor even among those with normal BMI.Conclusions:In this large cohort study, low aerobic fitness or high BMI at age 18 was associated with higher risk of IHD in adulthood, with a negative multiplicative interaction. Low aerobic fitness appeared to account for a similar number of IHD cases among those with normal vs high BMI (that is, no additive interaction). These findings suggest that interventions to prevent IHD should begin early in life and include not only weight control but aerobic fitness, even among persons of normal weight

Diagnostic aids in the screening of oral cancer

The World Health Organization has clearly indentified prevention and early detection as major objectives in the control of the oral cancer burden worldwide. At the present time, screening of oral cancer and its pre-invasive intra-epithelial stages, as well as its early detection, is still largely based on visual examination of the mouth. There is strong available evidence to suggest that visual inspection of the oral mucosa is effective in reducing mortality from oral cancer in individuals exposed to risk factors. Simple visual examination, however, is well known to be limited by subjective interpretation and by the potential, albeit rare, occurrence of dysplasia and early OSCC within areas of normal-looking oral mucosa. As a consequence, adjunctive techniques have been suggested to increase our ability to differentiate between benign abnormalities and dysplastic/malignant changes as well as to identify areas of dysplasia/early OSCC that are not visible to naked eye. These include the use of toluidine blue, brush biopsy, chemiluminescence and tissue autofluorescence. The present paper reviews the evidence supporting the efficacy of the aforementioned techniques in improving the identification of dysplastic/malignant changes of the oral mucosa. We conclude that available studies have shown promising results, but strong evidence to support the use of oral cancer diagnostic aids is still lacking. Further research with clear objectives, well-defined population cohorts, and sound methodology is strongly required

Family Businesses and Adaptation: A Dynamic Capabilities Approach

The main objective of this research was to propose a framework centred on the dynamic capabilities approach, and to be applied in the context of family businesses’ adaption to their changing business environment. Data were gathered through interviews with ten FBs operating in Western Australia. Based on the findings, the clusters of activities, sensing, seizing, and transforming emerged as key factors for firms’ adaptation, and were reinforced by firms’ open culture, signature processes, idiosyncratic knowledge, and valuable, rare, inimitable and non-substitutable attributes. Thus, the usefulness of the proposed framework was confirmed. Implications and future research opportunities are presented. © 2018, The Author(s)

Self-oligomerization regulates stability of survival motor neuron protein isoforms by sequestering an SCF^Slmb degron

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCFSlmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCFSlmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. Substitution of a conserved serine (S270A) interferes with SCFSlmb binding and stabilizes SMNΔ7. SMA-causing missense mutations that block multimerization of full-length SMN are also stabilized in the degron mutant background. Overexpression of SMNΔ7S270A, but not wild-type (WT) SMNΔ7, provides a protective effect in SMA model mice and human motor neuron cell culture systems. Our findings support a model wherein the degron is exposed when SMN is monomeric and sequestered when SMN forms higher-order multimers

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3$\sigma$ (5$\sigma$) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3$\sigma$ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE

This document presents the concept and physics case for a magnetized gaseous argon-based detector system (ND-GAr) for the Deep Underground Neutrino Experiment (DUNE) Near Detector. This detector system is required in order for DUNE to reach its full physics potential in the measurement of CP violation and in delivering precision measurements of oscillation parameters. In addition to its critical role in the long-baseline oscillation program, ND-GAr will extend the overall physics program of DUNE. The LBNF high-intensity proton beam will provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to discover new particles and search for new interactions and symmetries beyond those predicted in the Standard Model

Snowmass Neutrino Frontier: DUNE Physics Summary

The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment with a primary physics goal of observing neutrino and antineutrino oscillation patterns to precisely measure the parameters governing long-baseline neutrino oscillation in a single experiment, and to test the three-flavor paradigm. DUNE's design has been developed by a large, international collaboration of scientists and engineers to have unique capability to measure neutrino oscillation as a function of energy in a broadband beam, to resolve degeneracy among oscillation parameters, and to control systematic uncertainty using the exquisite imaging capability of massive LArTPC far detector modules and an argon-based near detector. DUNE's neutrino oscillation measurements will unambiguously resolve the neutrino mass ordering and provide the sensitivity to discover CP violation in neutrinos for a wide range of possible values of δCP. DUNE is also uniquely sensitive to electron neutrinos from a galactic supernova burst, and to a broad range of physics beyond the Standard Model (BSM), including nucleon decays. DUNE is anticipated to begin collecting physics data with Phase I, an initial experiment configuration consisting of two far detector modules and a minimal suite of near detector components, with a 1.2 MW proton beam. To realize its extensive, world-leading physics potential requires the full scope of DUNE be completed in Phase II. The three Phase II upgrades are all necessary to achieve DUNE's physics goals: (1) addition of far detector modules three and four for a total FD fiducial mass of at least 40 kt, (2) upgrade of the proton beam power from 1.2 MW to 2.4 MW, and (3) replacement of the near detector's temporary muon spectrometer with a magnetized, high-pressure gaseous argon TPC and calorimeter