To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
In eastern Africa, there are few long, high-quality records of environmental change at high altitudes, inhibiting a broader understanding of regional climate change. We investigated a Holocene lacustrine sediment archive from Lake Garba Guracha, Bale Mountains, Ethiopia, (3,950 m asl), and reconstructed high-altitude lake evaporation history using δ18O records derived from the analysis of compound-specific sugar biomarkers and diatoms. The δ18Odiatom and δ18Ofuc records are clearly correlated and reveal similar ranges (7.9‰ and 7.1‰, respectively). The lowest δ18O values occurred between 10–7 cal ka BP and were followed by a continuous shift towards more positive δ18O values. Due to the aquatic origin of the sugar biomarker and similar trends of δ18Odiatom, we suggest that our lacustrine δ18Ofuc record reflects δ18Olake water. Therefore, without completely excluding the influence of the ‘amount-effect’ and the ‘source-effect’, we interpret our record to reflect primarily the precipitation-to-evaporation ratio (P/E). We conclude that precipitation increased at the beginning of the Holocene, leading to an overflowing lake between ca. 10 and ca. 8 cal ka BP, indicated by low δ18Olake water values, which are interpreted as reduced evaporative enrichment. This is followed by a continuous trend towards drier conditions, indicating at least a seasonally closed lake system.
Among patients with schizophrenia (SZ) and bipolar I disorder (BD-I) treated with second-generation antipsychotics (SGAs), clinically-significant weight gain (CSWG) and treatment interruptions (TIs) are challenges that may result in morbidity/mortality.
CSWG and TIs were assessed among patients who initiated oral SGAs of moderate-to-high weight gain risk (no exposure to index SGAs/first-generation antipsychotics for =12 months) using medical records/claims (OM1 Data Cloud; January 2013-February 2020). Outcomes included CSWG (=7% increase in baseline weight) and TIs (switches [to SGAs of low weight gain risk/long-acting injectables] or discontinuations [no SGAs for >30 days]). Descriptive analyses included proportions of patients with CSWG and TIs, and median time to these outcomes.
Approximately three-quarters of patients were overweight/obese at baseline (SZ: N=8,174; BD-I: N=9,142). Within 3 months of SGA initiation, 12% of all patients experienced CSWG. For patients on treatment with index SGAs for >6 months (SZ: 29%; BD-I: 27%), 28% (SZ) and 30% (BD-I) experienced CSWG during follow-up. Median time to CSWG was 14 weeks. CSWG results were numerically similar among patients with SZ and BD-I.
Over 96% of patients had TIs during follow-up (median time of 12 [SZ] and 13 [BD-I] weeks). Among patients with CSWG and subsequent TIs and weight measurements, 74% did not return to baseline weight after interrupting treatment; the remainder returned to baseline weight with median times of 38 (SZ) and 39 (BD-I) weeks. Results suggest that most patients with CSWG do not return to baseline weight after stopping treatment with oral SGAs of moderate-to-high weight gain risk.
Additive manufacturing is a revolutionary three-dimensional (3D) printing technology that has applications in a vast number of fields from aerospace to biological engineering. In the field of bioengineering, it was recently discovered that the principles used in 3D bioprinting of organs and tissues could also be used to 3D print biological materials produced by genetically engineered bacteria. This new technology requires the development of modified bio-ink and optimized printing parameters to promote bacterial physiology while allowing printability. In this article, we highlight the recent advancements in additive manufacturing of engineered living materials using bacteria and their potential applications. We will discuss recent progress and significance of additive manufacturing of proteins and polypeptides produced in situ by engineered bacteria to make multifunctional materials. Finally, we discuss the challenges and prospects of this technology and highlight some of the biomaterials that may benefit from additive manufacturing with bacteria.
The coronavirus disease 2019 (COVID-19) pandemic forced American medical systems to adapt to high patient loads of respiratory disease. Its disruption of normal routines also brought opportunities for broader reform. The purpose of this article is to describe how the Carl R. Darnall Army Medical Center (CRDAMC), a medium-sized Army hospital, capitalized on opportunities to advance its strategic aims during the pandemic. Specifically, the hospital sequentially adopted virtual video visits, surged on preventative screenings, and made-over its image to appeal to patients seeking urgent care. These campaigns supported COVID-19 efforts and larger strategic goals simultaneously, and they will endure for years to come. Predictably, CRDAMC encountered obstacles in the course of its transformation. These obstacles and their follow-on lessons are provided to assist future medical leaders seeking quantum change in the opportunities made available by health crises.
This study explores the relationship between local government dissemination of COVID-19 information and partisanship. The unit of analysis is all official county government websites in the United States. In particular, we investigate if there is a correlation between the overall partisanship of a county and whether a county government's website (1) mentions COVID-19 and (2) provides safety instructions concerning COVID-19. We hypothesize that mass partisanship will impact the probability that a county government's website provides information related to the coronavirus. We find that a larger share of Democratic voters in a county is associated with an increase in the probability that a county government's website mentions COVID-19 and provides safety instructions for its residents. The results hold even after controlling for population density, internet subscriptions and COVID-19 cases and deaths. The finding indicates that citizens’ access to information, even on matters of public health, are partially a consequence of partisanship.
The Cal-DSH Diversion Guidelines provide 10 general guidelines that jurisdictions should consider when developing diversion programs for individuals with a serious mental illness (SMI) who become involved in the criminal justice system. Screening for SMI in a jail setting is reviewed. In addition, important treatment interventions for SMI and substance use disorders are highlighted with the need to address criminogenic risk factors highlighted.
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.