Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students

Background: Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk. Methods: We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h2SNP) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults. Results: Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h2SNP estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample. Conclusions: These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification

The political identities of neighbourhood planning in England

The rise of neighbourhood planning has been characterised as another step in a remorseless de-politicisation of the public sphere. A policy initiated by the Coalition Government in England to create the conditions for local communities to support housing growth, neighbourhood planning appears to evidence a continuing retreat from political debate and contestation. Clear boundaries are established for the holistic integration of participatory democracy into the strategic plan-making of the local authority. These boundaries seek to take politics out of development decisions and exclude all issues of contention from discussion. They achieve this goal at the cost of arming participatory democracy with a collective identity around which new antagonisms may develop. Drawing on the post-political theories of Chantal Mouffe this paper identifies the return of antagonism and conflict to participation in spatial planning. Key to its argument is the concept of the boundary or frontier that in Mouffe’s theoretical framework institutionalises conflict between political entities. Drawing on primary research with neighbourhood development plans in England the paper explores how boundary conditions and boundary designations generate antagonism and necessitate political action. The paper charts the development of the collective identities that result from these boundary lines and argues for the potential for neighbourhood planning to restore political conflict to the politics of housing development

Toxoplasma and Plasmodium protein kinases: roles in invasion and host cell remodelling

Some apicomplexan parasites have evolved distinct protein kinase families to modulate host cell structure and function. Toxoplasma gondii rhoptry protein kinases and pseudokinases are involved in virulence and modulation of host cell signalling. The proteome of Plasmodium falciparum contains a family of putative kinases called FIKKs, some of which are exported to the host red blood cell and might play a role in erythrocyte remodelling. In this review we will discuss kinases known to be critical for host cell invasion, intracellular growth and egress, focusing on (i) calcium-dependent protein kinases and (ii) the secreted kinases that are unique to Toxoplasma (rhoptry protein kinases and pseudokinases) and Plasmodium (FIKKs)

Synthesis of methylphosphonic acid by marine microbes: a source for methane in the aerobic ocean

Relative to the atmosphere, much of the aerobic ocean is supersaturated with methane; however, the source of this important greenhouse gas remains enigmatic. Catabolism of methylphosphonic acid by phosphorus-starved marine microbes, with concomitant release of methane, has been suggested to explain this phenomenon, yet methylphosphonate is not a known natural product, nor has it been detected in natural systems. Further, its synthesis from known natural products would require unknown biochemistry. Here we show that the marine archaeon Nitrosopumilus maritimus encodes a pathway for methylphosphonate biosynthesis and that it produces cell-associated methylphosphonate esters. The abundance of a key gene in this pathway in metagenomic data sets suggests that methylphosphonate biosynthesis is relatively common in marine microbes, providing a plausible explanation for the methane paradox

Overdensities of Y-dropout Galaxies from the Brightest-of-Reionizing Galaxies Survey: A Candidate Protocluster at Redshift z~8

Theoretical and numerical modeling of dark-matter halo assembly predicts that the most luminous galaxies at high redshift are surrounded by overdensities of fainter companions. We test this prediction with HST observations acquired by our Brightest of Reionizing Galaxies (BoRG) survey, which identified four very bright z~8 candidates as Y-dropout sources in four of the 23 non-contiguous WFC3 fields observed. We extend here the search for Y-dropouts to fainter luminosities (M_* galaxies with M_AB\sim-20), with detections at >5sigma confidence (compared to >8sigma confidence adopted earlier) identifying 17 new candidates. We demonstrate that there is a correlation between number counts of faint and bright Y-dropouts at >99.84% confidence. Field BoRG58, which contains the best bright z\sim8 candidate (M_AB=-21.3), has the most significant overdensity of faint Y-dropouts. Four new sources are located within 70arcsec (corresponding to 3.1 comoving Mpc at z=8) from the previously known brighter z\sim8 candidate. The overdensity of Y-dropouts in this field has a physical origin to high confidence (p>99.975%), independent of completeness and contamination rate of the Y-dropout selection. We modeled the overdensity by means of cosmological simulations and estimate that the principal dark matter halo has mass M_h\sim(4-7)x10^11Msun (\sim5sigma density peak) and is surrounded by several M_h\sim10^11Msun halos which could host the fainter dropouts. In this scenario, we predict that all halos will eventually merge into a M_h>2x10^14Msun galaxy cluster by z=0. Follow-up observations with ground and space based telescopes are required to secure the z\sim8 nature of the overdensity, discover new members, and measure their precise redshift.Comment: Minor revision: ApJ accepted [17 pages (emulateapj style), 7 figures, 2 tables

Design and Effectiveness of a Required Pre-Clinical Simulation-based Curriculum for Fundamental Clinical Skills and Procedures

For more than 20 years, medical literature has increasingly documented the need for students to learn, practice and demonstrate competence in basic clinical knowledge and skills. In 2001, the Louisiana State University Health Science Centers (LSUHSC) School of Medicine – New Orleans replaced its traditional Introduction in to Clinical Medicine (ICM) course with the Science and Practice of Medicine (SPM) course. The main component within the SPM course is the Clinical Skills Lab (CSL). The CSL teaches 30 plus skills to all pre-clinical medical students (Years 1 and 2). Since 2002, an annual longitudinal evaluation questionnaire was distributed to all medical students targeting the skills taught in the CSL. Students were asked to rate their self- confidence (Dreyfus and Likert-type) and estimate the number of times each clinical skill was performed (clinically/non-clinically). Of the 30 plus skills taught, 8 were selected for further evaluation. An analysis was performed on the eight skills selected to determine the effectiveness of the CSL. All students that participated in the CSL reported a significant improvement in self-confidence and in number performed in the clinically/non-clinically setting when compared to students that did not experience the CSL. For example, without CSL training, the percentage of students reported at the end of their second year self-perceived expertise as “novice” ranged from 21.4% (CPR) to 84.7% (GU catheterization). Students who completed the two-years CSL, only 7.8% rated their self-perceived expertise at the end of the second year as “novice” and 18.8% for GU catheterization. The CSL design is not to replace real clinical patient experiences. It's to provide early exposure, medial knowledge, professionalism and opportunity to practice skills in a patient free environment

DECam-GROWTH Search for the Faint and Distant Binary Neutron Star and Neutron Star-Black Hole Mergers in O3a

Synoptic searches for the optical counterpart to a binary neutron star (BNS) or neutron star-black hole (NSBH) merger can pose significant challenges towards the discovery of kilonovae and performing multi-messenger science. In this work, we describe the advantage of a global multi-telescope network towards this end, with a particular focus on the key and complementary role the Dark Energy Camera (DECam) plays in multi-facility follow-up. We describe the Global Relay of Observatories Watching Transients Happen (GROWTH) Target-of-Opportunity (ToO) Marshal, a common web application we built to ingest events, plan observations, search for transient candidates, and retrieve performance summary statistics for all of the telescopes in our network. Our infrastructure enabled us to conduct observations of two events during O3a, S190426c and S190510g. Furthermore, our analysis of deep DECam observations of S190814bv conducted by the DESGW team, and access to a variety of global follow-up facilities allowed us to place meaningful constraints on the parameters of the kilonova and the merging binary. We emphasize the importance of a global telescope network in conjunction with a power telescope like DECam in performing searches for the counterparts to gravitational-wave sources

The difference that tenure makes

This paper argues that housing tenures cannot be reduced to either production relations or consumption relations. Instead, they need to be understood as modes of housing distribution, and as having complex and dynamic relations with social classes. Building on a critique of both the productionist and the consumptionist literature, as well as of formalist accounts of the relations between tenure and class, the paper attempts to lay the foundations for a new theory of housing tenure. In order to do this, a new theory of class is articulated, which is then used to throw new light on the nature of class-tenure relations

System Dynamics modelling to formulate policy interventions to optimise antibiotic prescribing in hospitals

© 2020 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Multiple strategies have been used in the National Health System (NHS) in England to reduce inappropriate antibiotic prescribing and consumption in order to tackle antimicrobial resistance. These strategies have included, among others, restricting dispensing, introduction of prescribing guidelines, use of clinical audit, and performance reviews as well as strategies aimed at changing the prescribing behaviour of clinicians. However, behavioural interventions have had limited effect in optimising doctors’ antibiotic prescribing practices. This study examines the determinants of decision-making for antibiotic prescribing in hospitals in the NHS. A system dynamics model was constructed to capture structural and behavioural influences to simulate doctors’ prescribing practices. Data from the literature, patient records, healthcare professional interviews and survey responses were used to parameterise the model. The scenario simulation shows maximum improvements in guideline compliance are achieved when compliance among senior staff is increased, combined with fast laboratory turnaround of blood cultures, and microbiologist review. Improving guideline compliance of junior staff alone has limited impact. This first use of system dynamics modelling to study antibiotic prescribing decision-making demonstrates the applicability of the methodology for design and evaluation of future policies and interventions.Peer reviewe

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty