Overlap of heritable influences between Cannabis Use Disorder, frequency of use and opportunity to use cannabis: Trivariate twin modelling and implications for genetic design

Background: The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use. Methods: A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype. Results: Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58–0.70] and E = 0.36 (95% CI 0.29–0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66–0.80) and E = 0.26 (95% CI 0.20–0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65–0.88) and E = 0.22 (95% CI 0.12–0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency. Conclusions: There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology

The First Quiescent Galaxies in TNG300

We identify the first quiescent galaxies in TNG300, the largest volume of the IllustrisTNG cosmological simulation suite, and explore their quenching processes and time evolution to z=0. We find that the first quiescent galaxies with stellar masses M_* > 3 x 10^{10} M_sun and specific star formation rates sSFR < 10^{-11} yr^{-1} emerge at z~4.2 in TNG300. Suppression of star formation in these galaxies begins with a thermal mode of AGN feedback at z~6, and a kinetic feedback mode acts in each galaxy by z~4.7 to complete the quenching process, which occurs on a time-scale of ~0.35 Gyr. Surprisingly, we find that the majority of these galaxies are not the main progenitors of their z=0 descendants; instead, four of the five galaxies fall into more massive galaxies in subsequent mergers at a range of redshifts 2.5 < z < 0.2. By z=0, these descendants are the centres of galaxy clusters with average stellar masses of 8 x 10^{11} M_sun. We make predictions for the first quenched galaxies to be located by the James Webb Space Telescope (JWST).Comment: 6 pages, 4 figure

Family Caregiver Perspectives on Symptoms and Treatments for Patients Dying From Complications of Cystic Fibrosis

Most patients with advanced cystic fibrosis (CF) die from respiratory failure and experience distressing symptoms as lung disease progresses. Little has been reported about symptom management and the continuation of disease-specific treatments near the end of life for patients with CF

Caregiver Perspectives on Discussions About the Use of Intensive Treatments in Cystic Fibrosis

Intensive treatments intended to sustain life are often used for patients with advanced cystic fibrosis (CF). There are no guidelines for selecting patients whose survival and quality of life may be enhanced by such treatments or for communication with patients and caregivers about possible treatment outcomes

Caregivers' Perspectives on Decision Making about Lung Transplantation in Cystic Fibrosis

Lung transplantation extends survival for some patients with advanced cystic fibrosis, but it is complicated, has many potential risks, and its outcomes are difficult to predict. No standards exist for informed decision making about transplantation

Urban–Rural Differences in Older Adult Depression: A Systematic Review and Meta-analysis of Comparative Studies

Context: Depression among older adults (aged 60 years or older) is a problem that could be exacerbated by global trends in urbanization and population aging. The study purpose was to assess whether urban, relative to rural, residence is associated with depression among older adults and whether associations differ in countries with developed versus developing economies. Evidence acquisition: In 2017, the authors identified and extracted information from comparative studies of urban–rural depression prevalence among older adults. Studies were identified in PubMed, PsychINFO, and Web of Science and limited to English language articles published after 1985. Eighteen studies met inclusion criteria. Random effects meta-analysis was conducted to produce weighted pooled ORs estimating the association between urban–rural residence and depression for all study participants (N=31,598) and sub-analyses were conducted for developed (n=12,728) and developing (n=18,870) countries. Evidence synthesis: Depression prevalence was significantly higher among urban residents in ten studies and significantly higher among rural residents in three studies (all three conducted in China). Associations between urban–rural residence and depression generally remained significant after adjusting for covariates. In developed countries, the odds of depression were significantly higher among urban than rural residents (pooled OR=1.44, 95% CI=1.10, 1.88). However, in developing countries, this association was not observed (pooled OR=0.91, 95% CI=0.46, 1.77). Conclusions: Converging trends of urbanization and population aging could increase the global burden of depression among older adults. The pathways through which urban–rural residence influences depression risk among older adults might differ by country context. Future research should focus on measuring variation in these contexts

Depression and alcohol misuse among older adults: exploring mechanisms and policy impacts using agent-based modelling

Purpose: To: (1) explore how multi-level factors impact the longitudinal prevalence of depression and alcohol misuse among urban older adults (≥ 65 years), and (2) simulate the impact of alcohol taxation policies and targeted interventions that increase social connectedness among excessive drinkers, socially isolated and depressed older adults; both alone and in combination. Methods: An agent-based model was developed to explore the temporal co-evolution of depression and alcohol misuse prevalence among older adults nested in a spatial network. The model was based on Los Angeles and calibrated longitudinally using data from the Multi-Ethnic Study of Atherosclerosis. Results: Interventions with a social component targeting depressed and socially isolated older adults appeared more effective in curbing depression prevalence than those focused on excessive drinkers. Targeting had similar impacts on alcohol misuse, though the effects were marginal compared to those on depression. Alcohol taxation alone had little impact on either depression or alcohol misuse trajectories. Conclusions: Interventions that improve social connectedness may reduce the prevalence of depression among older adults. Targeting considerations could play an important role in determining the success of such efforts

Examining the possible impact of daily transport on depression among older adults using an agent-based model

_Objectives:_ Daily transport may impact depression risk among older adults through several pathways including facilitating the ability to meet basic needs, enabling and promoting contact with other people and nature, and promoting physical activity (e.g. through active transportation such as walking or walking to public transit). Both daily transport and depression are influenced by the neighborhood environment. To provide insights into how transport interventions may affect depression in older adults, we developed a pilot agent-based model to explore the contribution of daily transport and neighborhood environment to older adults’ depression in urban areas. _Method:_ The model includes about 18,500 older adults (i.e. agents) between the ages of 65 and 85 years old, living in a hypothetical city. The city has a grid space with a number of neighborhoods and locations. Key dynamic processes in the model include aging, daily transport use and feedbacks, and the development of depression. Key parameters were derived from US data sources. The model was validated using empirical studies. _Results:_ An intervention that combines a decrease in bus fares, shorter bus waiting times, and more bus lines and stations is most effective at reducing depression. Lower income groups are likely to be more sensitive to the public transit-oriented intervention. _Conclusion:_ Preliminary results suggest that promoting public transit use may be a promising strategy to increase daily transport and decrease depression. Our results may have implications for transportation policies and interventions to prevent depression in older adults

A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing

As genome-scale sequencing is increasingly applied in clinical scenarios, a wide variety of genomic findings will be discovered as secondary or incidental findings, and there is debate about how they should be handled. The clinical actionability of such findings varies, necessitating standardized frameworks for a priori decision making about their analysis

UNCOVER: A NIRSpec Identification of a Broad-line AGN at z = 8.50

Deep observations with the James Webb Space Telescope (JWST) have revealed an emerging population of red pointlike sources that could provide a link between the postulated supermassive black hole seeds and observed quasars. In this work, we present a JWST/NIRSpec spectrum from the JWST Cycle 1 UNCOVER Treasury survey of a massive accreting black hole at z = 8.50 displaying a clear broad-line component as inferred from the Hβ line with FWHM = 3439 ± 413 km s−1, typical of the broad-line region of an active galactic nucleus (AGN). The AGN nature of this object is further supported by high ionization, as inferred from emission lines, and a point-source morphology. We compute a black hole mass of and a bolometric luminosity of Lbol ∼ 6.6 × 1045 erg s−1. These values imply that our object is accreting at ∼40% of the Eddington limit. Detailed modeling of the spectral energy distribution in the optical and near-infrared, together with constraints from ALMA, indicate an upper limit on the stellar mass of , which would lead to an unprecedented ratio of black hole to host mass of at least ∼30%. This is orders of magnitude higher compared to the local QSOs but consistent with recent AGN studies at high redshift with JWST. This finding suggests that a nonnegligible fraction of supermassive black holes either started out from massive seeds and/or grew at a super-Eddington rate at high redshift. Given the predicted number densities of high-z faint AGN, future NIRSpec observations of larger samples will allow us to further investigate galaxy–black hole coevolution in the early Universe