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Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
To characterize associations between exposures within and outside the medical workplace with healthcare personnel (HCP) SARS-CoV-2 infection, including the effect of various forms of respiratory protection.
We collected data from international participants via an online survey.
In total, 1,130 HCP (244 cases with laboratory-confirmed COVID-19, and 886 controls healthy throughout the pandemic) from 67 countries not meeting prespecified exclusion (ie, healthy but not working, missing workplace exposure data, COVID symptoms without lab confirmation) were included in this study.
Respondents were queried regarding workplace exposures, respiratory protection, and extra-occupational activities. Odds ratios for HCP infection were calculated using multivariable logistic regression and sensitivity analyses controlling for confounders and known biases.
HCP infection was associated with non–aerosol-generating contact with COVID-19 patients (adjusted OR, 1.4; 95% CI, 1.04–1.9; P = .03) and extra-occupational exposures including gatherings of ≥10 people, patronizing restaurants or bars, and public transportation (adjusted OR range, 3.1–16.2). Respirator use during aerosol-generating procedures (AGPs) was associated with lower odds of HCP infection (adjusted OR, 0.4; 95% CI, 0.2–0.8, P = .005), as was exposure to intensive care and dedicated COVID units, negative pressure rooms, and personal protective equipment (PPE) observers (adjusted OR range, 0.4–0.7).
COVID-19 transmission to HCP was associated with medical exposures currently considered lower-risk and multiple extra-occupational exposures, and exposures associated with proper use of appropriate PPE were protective. Closer scrutiny of infection control measures surrounding healthcare activities and medical settings considered lower risk, and continued awareness of the risks of public congregation, may reduce the incidence of HCP infection.
Little is known about methylphenidate (MPH) use and mortality outcomes.
To investigate the association between MPH use and mortality among children with an attention-deficit hyperactivity disorder (ADHD) diagnosis.
This population-based cohort study analysed data from Taiwan's National Health Insurance Research Database (NHIRD). A total of 68 096 children and adolescents aged 4–17 years with an ADHD diagnosis and prescribed MPH between 2000 and 2010 were compared with 68 096 without an MPH prescription, matched on age, gender and year of first ADHD diagnosis. All participants were followed to death, migration, withdrawal from the National Health Insurance programme or 31 December 2013. MPH prescriptions were measured on a yearly basis during the study period, and the association between MPH use and mortality was analysed using a repeated-measures time-dependent Cox regression model. The outcome measures included all-cause, unnatural-cause (including suicide, accident and homicide) and natural-cause mortality, obtained from linkage to the National Mortality Register in Taiwan.
The MPH group had lower unadjusted all-cause, natural-, unnatural- and accident-cause mortality than the comparison group. After controlling for potential confounders, MPH use was associated with a significantly lower all-cause mortality (adjusted hazard ratio AHR = 0.81, 95% CI 0.67–0.98, P = 0.027), delayed use of MPH was associated with higher mortality (AHR = 1.05, 95% CI 1.01–1.09) and longer MPH use was associated with lower mortality (AHR = 0.83, 95% CI 0.70–0.98).
MPH use is associated with a reduced overall mortality in children with ADHD in this cohort study, but unmeasured confounding cannot be excluded absolutely.
The link between schizophrenia and cigarette smoking has been well established through observational studies. However, the cause–effect relationship remains unclear.
We conducted Mendelian randomisation analyses to assess any causal relationship between genetic variants related to four smoking-related traits and the risk of schizophrenia.
We performed a two-sample Mendelian randomisation using summary statistics from genome-wide association studies (GWAS) of smoking-related traits and schizophrenia (7711 cases, 18 327 controls) in East Asian populations. Single nucleotide polymorphisms (SNPs) correlated with smoking behaviours (smoking initiation, smoking cessation, age at smoking initiation and quantity of smoking) were investigated in relation to schizophrenia using the inverse-variance weighted (IVW) method. Further sensitivity analyses, including Mendelian randomisation-Egger (MR-Egger), weighted median estimates and leave-one-out analysis, were used to test the consistency of the results.
The associated SNPs for the four smoking behaviours were not significantly associated with schizophrenia status. Pleiotropy did not inappropriately affect the results.
Cigarette smoking is a complex behaviour in people with schizophrenia. Understanding factors underlying the observed association remains important; however, our findings do not support a causal role of smoking in influencing risk of schizophrenia.
Glacial retreat in response to warming climates in the arid Xinjiang region of northwestern China directly impacts downstream water resources available for local communities. We used high-resolution satellite imagery from 1969 to 2014 to delineate spatial changes in 54 active glaciers in the upper Kaidu River Basin in the Tian Shan as well as their past expanses during the Little Ice Age (LIA). We manually delineated their boundaries based on the interpretation of glacial, geomorphic and topographic features. From the total glacier surface area, we estimated glacier volume and mass. From 1969 to 2014, glacier area decreased by 10.1 ± 1.0 km2 (relative loss of 34.2 ± 3.5%) and mass by 1.025 ± 0.108 Gt (relative loss of 43 ± 4.6%). From the LIA maximum (est. 1586 CE) to 1969, relative losses were less (25.7 ± 4.3% area loss and 33.1 ± 5.7% mass loss). Our results indicate that glacier recession is accelerating over time and that the glaciers are currently losing over 1.5 times more relative area than elsewhere in the Tian Shan. Using linear and non-linear projections, we estimate that these glaciers may disappear between 2050 and 2150 CE if climatic warming continues at the same pace.
Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk.
Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk.
Polygenic risk showed a dose–response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk.
Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion – an index of perceived support and morale – was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.
Posttraumatic stress disorder (PTSD) is associated with higher risk of incident hypertension, but it is unclear whether specific aspects of PTSD are particularly cardiotoxic. PTSD is a heterogeneous disorder, comprising dimensions of fear and dysphoria. Because elevated fear after trauma may promote autonomic nervous system dysregulation, we hypothesized fear would predict hypertension onset, and associations with hypertension would be stronger with fear than dysphoria.
We examined fear and dysphoria symptom dimensions in relation to incident hypertension over 24 years in 2709 trauma-exposed women in the Nurses’ Health Study II. Posttraumatic fear and dysphoria symptom scores were derived from a PTSD diagnostic interview. We used proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for each symptom dimension (quintiles) with new-onset hypertension events (N = 925), using separate models. We also considered lower-order symptom dimensions of fear and dysphoria.
Higher levels of fear (P-trend = 0.02), but not dysphoria (P-trend = 0.22), symptoms were significantly associated with increased hypertension risk after adjusting for socio-demographics and family history of hypertension. Women in the highest v. lowest fear quintile had a 26% higher rate of developing hypertension [HR = 1.26 (95% CI 1.02–1.57)]; the increased incidence associated with greater fear was similar when further adjusted for biomedical and health behavior covariates (P-trend = 0.04) and dysphoria symptoms (P-trend = 0.04). Lower-order symptom dimension analyses provided preliminary evidence that the re-experiencing and avoidance components of fear were particularly associated with hypertension.
Fear symptoms associated with PTSD may be a critical driver of elevated cardiovascular risk in trauma-exposed individuals.
In 2010, we published our stroke prevention clinic’s performance as compared to Canadian stroke prevention guidelines. We now compare our clinic’s adherence with guidelines to our previous results, following the implementation of an electronic documentation form.
All new patients referred to our clinic (McGill University Health Center) for recent transient ischemic attack (TIA) or ischemic stroke between 2014 and 2017 were included. We compared adherence to guidelines to our previous report (N=408 patients for period 2008–2010) regarding vascular risk management and treatment.
Three hundred and ninety-two patients were included, of which 36% had a TIA and 64% had an ischemic stroke, with a mean age of 70 years and 43% female. Although the more recent cohort has shown a higher proportion of cardioembolic stroke compared to previous (19.1% vs. 14.7%) following new guidelines regarding prolonged cardiac monitoring, increased popularity in CT angiography has not translated into greater proportion of large-artery stroke subtype (26.3% vs. 26.2%). Blood pressure (BP) targets were achieved in 83% compared with 70% in our previous report (p<0.01). Attainment of low-density lipoprotein cholesterol target was also improved in our recent study (66% vs. 46%, p<0.01). No significant difference was found in the consistency of antithrombotic use (97.7% vs. 99.8%, p=0.08). However, there was a decline in smoking cessation (35% vs. 73%, p=0.02). Overall, optimal therapy status was better attained in the present cohort compared to the previous one (52% vs. 22%, p<0.01). The male sex was associated with better attainment of optimal therapy status (odds ratio, 1.61; 95% confidence interval, 1.04–2.51). The number of follow-up visits and the length of follow-up were not associated with attainment of stroke prevention targets.
Our study shows improvement in attainment of therapeutic goals as recommended by Canadian stroke prevention guidelines, possibly attributed in part to the implementation of electronic medical recording in our clinic. Areas for improvement include smoking cessation counseling and diabetes screening.
Abnormal thyroid function is prevalent among women and has been linked to increased risk of chronic disease. Posttraumatic stress disorder (PTSD) has been linked to thyroid dysfunction in some studies; however, the results have been inconsistent. Thus, we evaluated trauma exposure and PTSD symptoms in relation to incident thyroid dysfunction in a large longitudinal cohort of civilian women.
We used data from 45 992 women from the ongoing Nurses’ Health Study II, a longitudinal US cohort study that began in 1989. In 2008, history of trauma and PTSD were assessed with the Short Screening Scale for Diagnostic and Statistical Manual of Mental Disorders, fourth edition, PTSD, and incident thyroid dysfunction was determined by participants’ self-report in biennial questionnaires of physician-diagnosed hypothyroidism and Graves’ hyperthyroidism. The study period was from 1989 to 2013. Proportional hazard models were used to estimate multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) for incident hypothyroidism and Graves’ hyperthyroidism.
In multivariable-adjusted models, we found significant associations for PTSD only with hypothyroidism [p-trend <0.001; trauma with no PTSD symptoms, 1.08 (95% CI 1.02–1.15); 1–3 PTSD symptoms, 1.12 (95% CI 1.04–1.21); 4–5 PTSD symptoms, 1.23 (95% CI 1.13–1.34); and 6–7 PTSD symptoms, 1.26 (95% CI 1.14–1.40)]. PTSD was not associated with risk of Graves’ hyperthyroidism (p-trend = 0.34). Associations were similar in sensitivity analyses restricted to outcomes with onset after 2008, when PTSD was assessed.
PTSD was associated with higher risk of hypothyroidism in a dose-dependent fashion. Highlighted awareness for thyroid dysfunction may be especially important in women with PTSD.
The impact of an ageing workforce on the workplace is a concern internationally. Governments are increasingly encouraging the continued labour market participation of older workers, seeking to remove previous barriers to the extension of working lives and give more choice to workers. Despite these legislative drivers, research has consistently found a lack of systematic approaches by employers to prepare and benefit from these demographic and labour market changes. In this paper, qualitative research is drawn upon to examine how managers and older workers think about age and ageing in the workplace; the support put in place for older workers, as well as future priorities; and the lived experiences of the older workers. It is highlighted that employees’ age and fitness for work is treated on an individual basis, rather than having formal plans to manage the workplace for older workers. This thus indicates a hands-off approach from management.
Prenatal adversity shapes child neurodevelopment and risk for later mental health problems. The quality of the early care environment can buffer some of the negative effects of prenatal adversity on child development. Retrospective studies, in adult samples, highlight epigenetic modifications as sentinel markers of the quality of the early care environment; however, comparable data from pediatric cohorts are lacking. Participants were drawn from the Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) study, a longitudinal cohort with measures of infant attachment, infant development, and child mental health. Children provided buccal epithelial samples (mean age = 6.99, SD = 1.33 years, n = 226), which were used for analyses of genome-wide DNA methylation and genetic variation. We used a series of linear models to describe the association between infant attachment and (a) measures of child outcome and (b) DNA methylation across the genome. Paired genetic data was used to determine the genetic contribution to DNA methylation at attachment-associated sites. Infant attachment style was associated with infant cognitive development (Mental Development Index) and behavior (Behavior Rating Scale) assessed with the Bayley Scales of Infant Development at 36 months. Infant attachment style moderated the effects of prenatal adversity on Behavior Rating Scale scores at 36 months. Infant attachment was also significantly associated with a principal component that accounted for 11.9% of the variation in genome-wide DNA methylation. These effects were most apparent when comparing children with a secure versus a disorganized attachment style and most pronounced in females. The availability of paired genetic data revealed that DNA methylation at approximately half of all infant attachment-associated sites was best explained by considering both infant attachment and child genetic variation. This study provides further evidence that infant attachment can buffer some of the negative effects of early adversity on measures of infant behavior. We also highlight the interplay between infant attachment and child genotype in shaping variation in DNA methylation. Such findings provide preliminary evidence for a molecular signature of infant attachment and may help inform attachment-focused early intervention programs.