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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.
Seed dispersal is an important ecological process that structures plant communities and influences ecosystem functioning. Loss of animal dispersers therefore poses a serious threat to forest ecosystems, particularly in the tropics where zoochory predominates. A prominent example is the near-total extinction of seed dispersers on the tropical island of Guam following the accidental introduction of the invasive brown tree snake (Boiga irregularis), negatively impacting seedling recruitment and forest regeneration. We investigated frugivory by a remnant population of Såli (Micronesian starling – Aplonis opaca) on Guam and two other island populations (Rota, Saipan) to evaluate their ecological role as a seed disperser in the Mariana archipelago. Using a combination of behavioural observations, nest contents and fecal samples, we documented frugivory of 37 plant species. Native plants comprised the majority (66%) of all species and 90% of all seeds identified in fecal and nest contents. Diet was highly similar across age classes and sampling years. In addition, plant species consumed by Såli comprised 88% of bird-dispersed adult trees and 54% of all adult trees in long-term forest monitoring plots, demonstrating the Såli’s broad diet and potential for restoring native forests. Overall, we provide the most comprehensive assessment to date of frugivory by the Såli and confirm its importance as a seed disperser on Guam and throughout the Marianas.
The Canadian Resident Matching Service (CaRMS) selection process has come under scrutiny due to the increasing number of unmatched medical graduates. In response, we outline our residency program's selection process including how we have incorporated best practices and novel techniques.
We selected file reviewers and interviewers to mitigate gender bias and increase diversity. Four residents and two attending physicians rated each file using a standardized, cloud-based file review template to allow simultaneous rating. We interviewed applicants using four standardized stations with two or three interviewers per station. We used heat maps to review rating discrepancies and eliminated rating variance using Z-scores. The number of person-hours that we required to conduct our selection process was quantified and the process outcomes were described statistically and graphically.
We received between 75 and 90 CaRMS applications during each application cycle between 2017 and 2019. Our overall process required 320 person-hours annually, excluding attendance at the social events and administrative assistant duties. Our preliminary interview and rank lists were developed using weighted Z-scores and modified through an organized discussion informed by heat mapped data. The difference between the Z-scores of applicants surrounding the interview invitation threshold was 0.18-0.3 standard deviations. Interview performance significantly impacted the final rank list.
We describe a rigorous resident selection process for our emergency medicine training program which incorporated simultaneous cloud-based rating, Z-scores, and heat maps. This standardized approach could inform other programs looking to adopt a rigorous selection process while providing applicants guidance and reassurance of a fair assessment.
Progesterone (P4) plays a key role in pregnancy establishment and maintenance; during early pregnancy, P4 stimulates the production and release of uterine secretions necessary for conceptus growth prior to implantation; therefore, exogenous P4 supplementation may improve embryo development. This study evaluated the effects of supplementation during early pregnancy with long-acting injectable progesterone or altrenogest on embryonic characteristics of sows and gilts. Thus, a total of 32 sows and 16 gilts were used. On day 6 of pregnancy sows and gilts were allocated to one of the following groups: non-supplemented; supplemented with 20 mg of altrenogest, orally, from days 6 to 12 of pregnancy; supplemented with 2.15 mg/kg of long-acting injectable progesterone on day 6 of pregnancy. Animals were killed on day 28 of pregnancy, and ovulation rate, embryo survival, embryo weight, crown-to-rump length, uterine glandular epithelium and endometrial vascularization were assessed. Treatments had no effect on pregnancy rate, embryo survival or endometrial vascular density (P > 0.05). Non-supplemented gilts presented larger and heavier embryos compared to gilts from supplemented groups (P < 0.05). Sows in the altrenogest group presented larger and heavier embryos compared to non-supplemented sows and sows supplemented with long-acting injectable progesterone. In conclusion, supplementation of sows and gilts with progestagen from day 6 of pregnancy can be used as a means to improve embryo survival without deleterious effects.
The MMPI has been a mainstay of psychological assessment for nearly eight decades, a testament to the richness and clinical utility of the test. We begin this chapter by tracing the history and evolution of the MMPI instruments, including the rationale for and development of the MMPI-2-RF. First, we provide an overview of the test scales and the documents available to guide its administration, scoring, and interpretation. Next, we give an overview of the psychometric features of the MMPI-2-RF scales and a review of the literature on its use in a broad of applied settings. We then review the literature on multicultural considerations when using the MMPI-2-RF. A brief description of the adolescent version of the inventory, the MMPI-A-RF, is followed by a concluding section that illustrates MMPI-2-RF interpretation with a case study.
Despite corruption’s effects on citizen welfare, there is substantial variation in when citizens are willing to sanction government wrongdoing. This paper uses a conjoint survey experiment, conducted in Uganda, to test how information about the position a corrupt official holds, and the details of an act of embezzlement affect citizens’ perceptions of corruption severity and willingness to punish. I find that the revenue source of stolen funds and the sector to which the funds had been allocated have the largest impact on perceived severity, followed by whether stolen funds are spent privately or recirculated through patronage or clientelism. The position the corrupt official holds has a smaller impact on severity, including whether the official was elected and whether he was a central or local official.
Change in the experience of oneself may lay the groundwork for the development of additional hallucinations and delusions in individuals with schizophrenia. However, to date, the course and symptom and functioning correlates of passivity symptoms (cf. thought insertion, thought withdrawal) have not been measured consistently over long periods of time. Information on the course and correlates of passivity symptoms is essential for developing models of their contribution to schizophrenic illness.
Eighty-two individuals diagnosed with schizophrenia or schizoaffective disorder were recruited at an index hospitalization and reassessed at three or more follow-ups over the following 18 years.
The results indicate that a small group of participants report passivity symptoms at all follow-ups, many reported passivity symptoms at some follow-ups, and the majority of individuals never reported passivity symptoms. The prevalence of passivity symptoms was similar to that for delusions of reference and persecutory delusions. Notably, when individuals did experience passivity symptoms, they also had a greater number of additional psychotic symptoms than individuals without passivity symptoms. Further, the presence of passivity symptoms was associated with work impairment at some assessments.
Passivity symptoms present episodically, at a similar rate as delusions of reference and persecutory delusions, and when present, they are associated with having a higher number of additional psychotic symptoms, as well as having some impact on work functioning. These results suggest that passivity symptoms may increase vulnerability to additional psychotic symptoms and greater work impairment.
Bloodstream infection (BSI) is a serious complication in immunocompromised hosts. This study compares epidemiological, clinical and microbiological characteristics of BSI among children with haematological malignancies (HM) and solid tumours (ST). The study was conducted from October 2012 through to November 2015 at a referral hospital for cancer care and included the first BSI episode detected in 210 patients aged 18 years or less. BSI cases were prospectively detected by daily laboratory-based surveillance. The Centers for Disease Control and Prevention definitions for primary or secondary BSI were used. A higher proportion of use of corticosteroids (P = 0.02), chemotherapy (P = 0.01) and antibiotics (P = 0.05) before the BSI diagnosis; as well as of neutropenia (P < 0.001) and mucositis (P < 0.001) at the time of BSI diagnosis was observed in patients with HM than with ST. Previous surgical procedures (P = 0.03), mechanical ventilation (P = 0.01) and bed confinement (P < 0.001) were more frequent among children with ST. The frequency of use of temporary (P = 0.01) and implanted vascular lines (P < 0.01) was significantly higher in children with ST than with HM while the tunnelled line (P = 0.01) use was more frequent in children with HM as compared to ST. Most (n = 181) BSI cases were primary BSI. BSI associated with a tunnelled catheter was more frequent in children with HM (P < 0.01), whereas BSI associated with an implanted (P < 0.01) or temporary central line (P < 0.02) was more common in patients with ST. BSI associated with mucosal barrier injury was more frequent (P = 0.01) in children with HM. Indication for intensive care was more frequent in children (P = 0.05) with ST. Mortality ratio was similar in children with ST and HM, and length of hospital stay after BSI was higher in patients with HM than with ST (median of 19 vs. 13 days; P = 0.02). Infection caused by Gram-negative bacteria (P = 0.04) and polymicrobial infections (P = 0.05) due to Gram-positive cocci plus fungus was more common in patients with HM. These findings suggest that the characteristics of BSI acquisition and mortality can be cancer-specific.
We examined Clostridioides difficile infection (CDI) prevention practices and their relationship with hospital-onset healthcare facility-associated CDI rates (CDI rates) in Veterans Affairs (VA) acute-care facilities.
From January 2017 to February 2017, we conducted an electronic survey of CDI prevention practices and hospital characteristics in the VA. We linked survey data with CDI rate data for the period January 2015 to December 2016. We stratified facilities according to whether their overall CDI rate per 10,000 bed days of care was above or below the national VA mean CDI rate. We examined whether specific CDI prevention practices were associated with an increased risk of a CDI rate above the national VA mean CDI rate.
All 126 facilities responded (100% response rate). Since implementing CDI prevention practices in July 2012, 60 of 123 facilities (49%) reported a decrease in CDI rates; 22 of 123 facilities (18%) reported an increase, and 41 of 123 (33%) reported no change. Facilities reporting an increase in the CDI rate (vs those reporting a decrease) after implementing prevention practices were 2.54 times more likely to have CDI rates that were above the national mean CDI rate. Whether a facility’s CDI rates were above or below the national mean CDI rate was not associated with self-reported cleaning practices, duration of contact precautions, availability of private rooms, or certification of infection preventionists in infection prevention.
We found considerable variation in CDI rates. We were unable to identify which particular CDI prevention practices (i.e., bundle components) were associated with lower CDI rates.
To examine the relationship between unit-wide Clostridium difficile infection (CDI) susceptibility and inpatient mobility and to create contagion centrality as a new predictive measure of CDI.
Retrospective cohort study.
A mobility network was constructed using 2 years of patient electronic health record data for a 739-bed hospital (n = 72,636 admissions). Network centrality measures were calculated for each hospital unit (node) providing clinical context for each in terms of patient transfers between units (ie, edges). Daily unit-wide CDI susceptibility scores were calculated using logistic regression and were compared to network centrality measures to determine the relationship between unit CDI susceptibility and patient mobility.
Closeness centrality was a statistically significant measure associated with unit susceptibility (P < .05), highlighting the importance of incoming patient mobility in CDI prevention at the unit level. Contagion centrality (CC) was calculated using inpatient transfer rates, unit-wide susceptibility of CDI, and current hospital CDI infections. The contagion centrality measure was statistically significant (P < .05) with our outcome of hospital-onset CDI cases, and it captured the additional opportunities for transmission associated with inpatient transfers. We have used this analysis to create easily interpretable clinical tools showing this relationship as well as the risk of hospital-onset CDI in real time, and these tools can be implemented in hospital EHR systems.
Quantifying and visualizing the combination of inpatient transfers, unit-wide risk, and current infections help identify hospital units at risk of developing a CDI outbreak and, thus, provide clinicians and infection prevention staff with advanced warning and specific location data to inform prevention efforts.
Our group has reported the imprint formation of biological material on polycarbonate nuclear track detectors by UV-C exposure, which is used as an approach to simultaneously visualize cell imprints and nuclear tracks coming from the boron neutron capture reaction. Considering that the cell nucleus has a higher UV-C absorption than the cytoplasm and that hematoxylin preferentially stains the nucleus, we proposed to enhance the contrast between these two main cell structures by hematoxylin staining before UV-C sensitization. In this study, several experiments were performed in order to optimize UV-C exposure parameters and chemical etching conditions for cell imprint formation using the SK-BR-3 breast cancer cell line. The proposed method improves significantly the resolution of the cell imprints. It allows clear differentiation of the nucleus from the rest of the cell, together with nuclear tracks pits. Moreover, it reduces considerably the UV-C exposure time, an important experimental issue. The proposed methodology can be applied to study the boron distribution independently from the chosen cell line and/or boron compounds.
Meat and dairy products derived from grassland carry premium values and sensory and nutritional qualities that aroused much interest for authentication methods to guarantee grassland origin claims. This article reviews the current state of knowledge on the authentication of meat and dairy of grassland origin from food analysis in both cattle and sheep. A range of methods alone or combined, involving analysis of elemental or molecular constituents of food product and fingerprinting profiling combined with chemometrics, have been developed and proved useful to differentiate contrasted feeding regimes and authenticate grass-fed meat and dairy. Their robustness and discriminatory reliability in more complex feeding conditions, such as in the case of dietary switches or when grass only makes up part of the animal’s diet, are under active investigation. Our review highlights the possibilities and limitations of these methods, the latter being chiefly posed by variations in the quantity, characteristics and composition of grassland feedstuffs consumed by animals, which are nevertheless inherent to grassland-based production systems, variations in animal responses within and across breeds, and difficulties in detecting the consumption of non-grass feedstuffs by the animal. It also highlights a number of issues for consideration, points of caution and caveats in applying these methods. Scientists agree that much of the research carried out so far has been a ‘proof of concept’ type and that efforts should be made in the future to develop more databases to help gain genericity and robustness.
Autonomous exploration requires the use of movable platforms that carry a payload of instruments with a certain level of autonomy and communication with the operators. This is particularly challenging in subsurface environments, which may be more dangerous for human access and where communication with the surface is limited. Subsurface robotic exploration, which has been to date very limited, is interesting not only for science but also for cost-effective industrial exploitation of resources and safety assessments in mines. Furthermore, it has a direct application to exploration of extra-terrestrial subsurface environments of astrobiological and geological significance such as caves, lava tubes, impact or volcanic craters and subglacial conduits, for deriving in-situ mineralogical resources and establishing preliminary settlements. However, the technological solutions are generally tailor-made and are therefore considered as costly, fragile and environment-specific, further hindering their extensive and effective applications. To demonstrate the advantages of rover exploration for a broad-community, we have developed KORE (KOmpact Rover for Exploration); a low-cost, re-usable, rover multi-purpose platform. The rover platform has been developed as a technological demonstration for extra-terrestrial subsurface exploration and terrestrial mining operations pertaining to geomorphological mapping, environmental monitoring, gas leak detections and search and rescue operations in case of an accident. The present paper, the first part of a series of two, focuses on describing the development of a robust rover platform to perform dedicated geomorphological, astrobiological and mining tasks. KORE was further tested in the Mine Analogue Research 6 (MINAR6) campaign during September 2018 in the Boulby mine (UK), the second deepest potash mine in Europe at a subsurface depth of 1.1 km, the results of which will be presented in the second paper of this series. KORE is a large, semi-autonomous rover weighing 160 kg with L × W × H dimensions 1.2 m × 0.8 m × 1 m and a payload carrying capacity of 100 kg using 800 W traction power that can power to a maximum speed of 8.4 km h−1. The rover can be easily dismantled in three parts facilitating its transportation to any chosen site of exploration. Presently, the main scientific payloads on KORE are: (1) a three-dimensional mapping camera, (2) a methane detection system, (3) an environmental station capable of monitoring temperature, relative humidity, pressure and gases such as NO2, SO2, H2S, formaldehyde, CO, CO2, O3, O2, volatile organic compounds and particulates and (4) a robotic arm. Moreover, the design of the rover allows for integration of more sensors as per the scientific requirements in future expeditions. At the MINAR6 campaign, the technical readiness of KORE was demonstrated during 6 days of scientific research in the mine, with a total of 22 h of operation.
The Kempen system is a dairy feeding system in which diet is provided in the form of a compound feed (CF) and hay offered ad libitum. Ad libitum access to CF and hay allows cows in this system to achieve a high DM intake (DMI). Out of physiological concerns, the voluntary hay intake could be increased and the consumption pattern of CF could be manipulated to maintain proper rumen functioning and health. This study investigated the effects of an artificial hay aroma and CF formulation on feed intake pattern, rumen function and milk production in mid- to late-lactating dairy cows. Twenty Holstein–Friesian cows were assigned to four treatments in a 4 × 4 Latin square design. Diet consisted of CF and grass hay (GH), fed separately, and both offered ad libitum, although CF supply was restricted in maximum meal size and speed of supply by an electronic system. Treatments were the combination of two CF formulations – high in starch (CHS) and fibre (CHF); and two GH – untreated (UGH) and the same hay treated with an artificial aroma (TGH). Meal criteria were determined using three-population Gaussian–Gaussian–Weibull density functions. No GH × CF interaction effects on feed intake pattern characteristics were found. Total DMI and CF intake, but not GH intake, were greater (P < 0.01) in TGH treatment, and feed intake was not affected by type of CF. Total visits to feeders per day, visits to the GH feeder, visits to the CF feeder and CF eating time (all P < 0.01) were significantly greater in cows fed with TGH. Meal frequency, meal size and meal duration were unaffected by treatments. Cows fed CHF had a greater milk fat (P = 0.02), milk urea content (P < 0.01) and a greater milk fat yield (P < 0.01). Cows fed TGH had a greater milk lactose content and lactose yield (P < 0.05), and milk urea content (P < 0.01). Cows fed TGH had smaller molar proportions of acetic acid and greater molar proportions of propionic acid compared with UGH. In conclusion, treatment of GH with an artificial aroma increased CF intake and total DMI, but did not affect hay intake. Additionally, GH treatment increased the frequency of visits to both feeders, and affected rumen volatile fatty acid profile. Type of CF did not affect meal patterns, ruminal pH, nor fermentation profiles.
Introduction: Recently, volumetric absorptive microsampling (VAMS) has been used for accurate sampling of a fixed peripheral blood volume (10 µL) on a volumetric swab, and long-term sample storage. The mPlex-Flu assay is a novel, high-throughput assay that simultaneously measures the concentration of antibodies against the hemagglutinin (HA) proteins from multiple influenza virus strains with ≤5 µL of serum. Here we describe combining these two methods to measure multidimensional anti-influenza IgG activity in whole blood samples collected by a finger stick and VAMS, with correction for serum volume based on simultaneous hemoglobin measurement. Methods: We compared capillary blood samples obtained from a finger stick using a VAMS device with serum samples collected by traditional phlebotomy from 20 subjects, with the influenza antibody profiles measured by the mPlex-Flu assay. Results: We found that results with the two sampling methods were highly correlated within subjects and across all influenza strains (mean R2 = 0.9470). Adjustment for serum volume, based on hemaglobin measurement, was used to estimate serum volume of samples and improved the accuracy. IgG measurements were stable over 3 weeks when VAMS samples were stored at room temperature or transported using a variety of shipping methods. Additionally, when volunteers performed finger-stick VAMS at-home by themselves, the comparison results of anti-HA antibody concentrations were highly consistent with sampling performed by study personnel on-site (R2 = 0.9496). Conclusions: This novel approach can provide a simple, accurate, and low-cost means for monitoring the IgG anti-influenza HA antibody responses in large population studies and clinical trials.
The resection of a subaortic membrane remains far from a curative operation. We sought to examine factors associated with reoperation and the degree of aortic valve regurgitation as a potential long-term source for reoperation.
All patients who underwent resection of an isolated subaortic membrane between 1995 and 2018 were included. Patients who underwent other procedures were excluded. Paired categorical data were compared using McNemar’s test. Univariate time-to-event analyses were performed using Kaplan–Meier methods with log-rank tests for categorical variables and univariate Cox models for continuous variables.
A total of 84 patients (median age 6.6, 31% females) underwent resection of isolated subaortic membrane. At a median follow-up of 9.3 years (interquartile range 0.6–22.5), 12 (14%) patients required one reoperation and 1 patient required two reoperations. Median time to first reoperation was 4.6 years. The degree of aortic valve regurgitation improved post-operatively from pre-operatively (p = 0.0007); however, the degree of aortic valve regurgitation worsened over the course of follow-up (p = 0.010) to equivalence with pre-operative aortic valve regurgitation (p = 0.18). Performance of a septal myectomy was associated with longer freedom from reoperation (p = 0.004).
In patients with isolated subaortic membranes, performance of a septal myectomy can minimise risk for reoperation. Patients should be serially monitored for degradation of the aortic valve, even if aortic regurgitation is not present post-operatively.
Ruminants are recognised to suffer from Cu-responsive disorders. Present understanding of Cu transport and metabolism is limited and inconsistent across vets and veterinary professionals. There has been much progress from the studies of the 1980s and early 1990s in cellular Cu transport and liver metabolism which has not been translated into agricultural practice. Cu metabolism operates in regulated pathways of Cu trafficking rather than in pools of Cu lability. Cu in the cell is chaperoned to enzyme production, retention within metallothionein or excretion via the Golgi into the blood. The hepatocyte differs in that Cu-containing caeruloplasmin can be synthesised to provide systemic Cu supply and excess Cu is excreted via bile. The aim of the present review is to improve understanding and highlight the relevant progress in relation to ruminants through the translation of newer findings from medicine and non-ruminant animal models into ruminants.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
We designed two practical, user-friendly, low-cost, aesthetically pleasing resources, with the goal of introducing residents and observers to a new Competence by Design assessment system based on entrustable professional activities. They included a set of rotation- and stage-specific entrustable professional activities reference cards for bedside use by residents and observers and a curriculum board to organize the entrustable professional activities reference cards by stages of training based on our program's curriculum map. A survey of 14 emergency medicine residents evaluated the utilization and helpfulness of these resources. They had a positive impact on our program's transition to Competence by Design and could be successfully incorporated into other residency programs to support the introduction of entrustable professional activities-based Competence by Design assessment systems.