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Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Timely access to care services is crucial to support people with dementia and their family carers to live well. Carers of people with dementia (N = 390), recruited from eight countries, completed semi-structured interviews about their experiences of either accessing or not using formal care services over a 12-month period in the Access to Timely Formal Care (Actifcare) study. Participant responses were summarised using content analysis, categorised into clusters and frequencies were calculated. Less than half of the participants (42.3%) reported service use. Of those using services, 72.8 per cent reported timely access and of those not using services 67.2 per cent were satisfied with this situation. However, substantial minorities either reported access at the wrong time (27.2%), or feeling dissatisfied or mixed feelings about not accessing services (32.8%). Reasons for not using services included use not necessary yet, the carer provided support or refusal. Reasons given for using services included changes in the condition of the person with dementia, the service's ability to meet individual needs, not coping or the opportunity to access services arose. Facilitators and barriers to service use included whether participants experienced supportive professionals, the speed of the process, whether the general practitioner was helpful, participant's own proactive attitude and the quality of information received. To achieve timely support, simplified pathways to use of formal care services are needed.
Species distribution models (SDMs) are statistical tools used to develop continuous predictions of species occurrence. ‘Integrated SDMs’ (ISDMs) are an elaboration of this approach with potential advantages that allow for the dual use of opportunistically collected presence-only data and site-occupancy data from planned surveys. These models also account for survey bias and imperfect detection through the use of a hierarchical modelling framework that separately estimates the species–environment response and detection process. This is particularly helpful for conservation applications and predictions for rare species, where data are often limited and prediction errors may have significant management consequences. Despite this potential importance, ISDMs remain largely untested under a variety of scenarios. We performed an exploration of key modelling decisions and assumptions on an ISDM using the endangered Baird’s tapir (Tapirus bairdii) as a test species. We found that site area had the strongest effect on the magnitude of population estimates and underlying intensity surface and was driven by estimates of model intercepts. Selecting a site area that accounted for the individual movements of the species within an average home range led to population estimates that coincided with expert estimates. ISDMs that do not account for the individual movements of species will likely lead to less accurate estimates of species intensity (number of individuals per unit area) and thus overall population estimates. This bias could be severe and highly detrimental to conservation actions if uninformed ISDMs are used to estimate global populations of threatened and data-deficient species, particularly those that lack natural history and movement information. However, the ISDM was consistently the most accurate model compared to other approaches, which demonstrates the importance of this new modelling framework and the ability to combine opportunistic data with systematic survey data. Thus, we recommend researchers use ISDMs with conservative movement information when estimating population sizes of rare and data-deficient species. ISDMs could be improved by using a similar parameterization to spatial capture–recapture models that explicitly incorporate animal movement as a model parameter, which would further remove the need for spatial subsampling prior to implementation.
A constraint on Solar System formation is the high 26Al/27Al abundance ratio, 17 times higher than the average Galactic ratio, while the 60Fe/56Fe value was lower than the Galactic value. This challenges the assumption that a nearby supernova was responsible for the injection of these short-lived radionuclides into the early Solar System. We suggest that the Solar System was formed by triggered star formation at the edge of a Wolf-Rayet (W-R) bubble. We discuss the details of various processes within the model using numerical simulations, and analytic and semi-analytic calculations, and conclude that it is a viable model that can explain the initial abundances of 26Al and 60Fe. We estimate that 1%-16% of all Sun-like stars could have formed in such a setting.
In this study, we report on the mechanical cleavage of conductive metal-based aluminum diboride (AlB2) flakes. The cleavage resulted in a highly single crystalline 2D material and had an atomically flat and smooth surface as shown by atomic force microscopy (AFM) and secondary ion mass spectrometry. Nanoindentation and AFM imaging of freshly cleaved specimens revealed sub-nm roughness and 30% improvement in the nanomechanical properties as compared to the as-grown AlB2 flakes. Once exposed to ambient air, the cleaved AlB2 flakes formed a superficial oxidation layer of less than 1 nm thickness within 5 min. Owing to the smooth surface, ultra-thin and stable oxide layer, and the excellent mechanical and electrical characteristics of AlB2, the cleaved flakes present an ideal 2D material for emerging applications in microfabrication such as the growth of epitaxial thin films. To prove the sub-nm surface characteristics of cleaved AlB2, a 10-nm thick TiO2 film was deposited on a freshly cleaved AlB2 using atomic layer deposition. Surface roughness and compositional consistency of this film were compared with a control sample deposited on Si. The TiO2 film on AlB2 showed a distinct thin interface layer with fewer defects than TiO2 on Si and superior flatness.
Children with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.
Materials and methods
We sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation.
A total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; p<0.001), even after adjusting for patient and provider differences (adjusted odds ratio 1.79; p=0.03). Multiple intubation attempts occurred less often in cardiac patients (p=0.04), and oxygen desaturations occurred more often, even after excluding patients with cyanotic heart disease.
The overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.
Texture-engineered ceramics enable access to a vast array of novel texture-property relations leading to property values ranging between those of single crystals and isotropic bulk ceramics. Recently developed templated grain growth and magnetic alignment texturing methods yield high quality crystallographic texture, and thus significant advances in achievable texture-engineered properties in magnetic, piezoelectric, electronic, optical, thermoelectric, and structural ceramics. In this paper, we outline the fundamental basis for these texture-engineered properties and review recent contributions to the field of texture-engineered ceramics with an update on the properties of textured lead-free and lead-based piezoelectrics. We propose that further property improvements can be realized through development of processes that improve crystallographic alignment of the grain structure, create biaxial texture, and explore a wider array of crystallographic orientations. There is a critical need to model the physics of texture-engineered ceramics, and more comprehensively characterize texture, thus enabling testing of texture orientation-property relations and materials performance. We believe that in situ measurements of texture evolution can lead to a more fundamental and comprehensive understanding of the mechanisms of texture development.
Irreversible monoamine oxidase inhibitor (MAOI) antidepressants have significant efficacy in treatment-resistant unipolar depression, but in some instances patients may not achieve remission. Among the adjunctive and augmentation strategies, certain second-generation antipsychotics (SGAs) have approval for inadequate responders to antidepressant therapy, including aripiprazole, brexpiprazole, and quetiapine, with lurasidone and the olanzapine/fluoxetine combination indicated for bipolar depression. Clinicians may eschew SGA options in part due to the limited literature on SGA–MAOI combinations, with only one published case involving aripiprazole, and none for olanzapine, lurasidone, or brexpiprazole. In addition to the limited publication history on SGA–MAOI treatment, clinicians may also be deterred by uncertainty regarding SGA mechanisms and the risk of serotonin syndrome or other adverse outcomes. This paper describes the case of a 54-year-old male with a history of psychotic unipolar depression treated with a combination of phenelzine, aripiprazole, and quetiapine, and reviews the 12 published cases of SGA–MAOI combination therapy with a focus on the pharmacological basis for serotonin syndrome, and the SGA mechanisms that should not be associated with a risk for this syndrome.
In most developed countries, children in lone parent families face a high risk of poverty. A partial solution commonly sought in English-speaking nations is to increase the amounts of private child maintenance paid by the other parent. However, where lone parent families are in receipt of social assistance benefits, some countries hold back a portion of the child maintenance to reduce public expenditures. This partial ‘pass-through’ treats child maintenance as a substitute for cash benefits which conceivably neutralises its poverty reduction potential. Such neutralising effects are not well understood and can be obscured further when more subtle interactions between child maintenance systems and social security systems operate. This research makes a unique contribution to knowledge by exposing the hidden interaction effects operating in similar child maintenance systems across four countries: the United Kingdom, United States (Wisconsin), Australia and New Zealand. We found that when child maintenance is counted as income in calculating benefit entitlements, it can reduce the value of cash benefits. Using model lone parent families with ten different employment and income scenarios, we show how the poverty reduction potential of child maintenance is affected by whether it is treated as a substitute for, or a complement to, cash benefits.