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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.
Critics have long debated the origins and influences on what might be called the McCarthian universe of violence. This chapter argues for a rethinking of the place of American literary naturalism – particularly the works of Stephen Crane, Frank Norris, Jack London, and Theodore Dreiser – as a key influence on McCarthy’s understanding of the omnipresence and inescapability of violence in human existence. Reading both McCarthy’s and the literary naturalists’ connections to the pessimistic philosophy of Arthur Schopenhauer and the evolutionary theory of Charles Darwin in the mid-nineteenth century, the chapter marks striking similarities between the judge’s philosophy in Blood Meridian of “before man was, war waited for him” and the naturalist philosophy (as perhaps most purely articulated in Dreiser’s The Financier) that “life was war.” Both McCarthy and the naturalists, then, display an acceptance of a world and universe in which morality and justice no longer held any sway, violence, degradation, corruption, and indifference are the only constants, and human beings are little more than flickering, momentary flashes, either subject to or reveling in these violent characteristics.
To determine the effect of three psycholinguistic variables—lexical frequency, age of acquisition (AoA), and neighborhood density (ND)—on lexical-semantic processing in individuals with non-fluent (nfvPPA), logopenic (lvPPA), and semantic primary progressive aphasia (svPPA). Identifying the scope and independence of these features can provide valuable information about the organization of words in our mind and brain.
We administered a lexical decision task—with words carefully selected to permit distinguishing lexical frequency, AoA, and orthographic ND effects—to 41 individuals with PPA (13 nfvPPA, 14 lvPPA, 14 svPPA) and 25 controls.
Of the psycholinguistic variables studied, lexical frequency had the largest influence on lexical-semantic processing, but AoA and ND also played an independent role. The results reflect a brain-language relationship with different proportional effects of frequency, AoA, and ND in the PPA variants, in a pattern that is consistent with the organization of the mental lexicon. Individuals with nfvPPA and lvPPA experienced an ND effect consistent with the role of inferior frontal and temporoparietal regions in lexical analysis and word form processing. By contrast, individuals with svPPA experienced an AoA effect consistent with the role of the anterior temporal lobe in semantic processing.
The findings are in line with a hierarchical mental lexicon structure with a conceptual (semantic) and a lexeme (word-form) level, such that a selective deficit at one of these levels of the mental lexicon manifests differently in lexical-semantic processing performance, consistent with the affected language-specific brain region in each PPA variant.
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.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Recent work on US policymaking argues that responsiveness to public opinion is distorted by money, in that the preferences of the rich matter much more than those of lower-income Americans. A second distortion—partisan biases in responsiveness—has been less well studied and is often ignored or downplayed in the literature on affluent influence. We are the first to evaluate, in tandem, these two potential distortions in representation. We do so using 49 Senate roll-call votes from 2001 to 2015. We find that affluent influence is overstated and itself contingent on partisanship—party trumps the purse when senators have to take sides. The poor get what they want more often from Democrats. The rich get what they want more often from Republicans, but only if Republican constituents side with the rich. Thus, partisanship induces, shapes, and constrains affluent influence.
Folic acid should be taken at a daily dose of 400 mcg or, in those who are obese, 5 mg. There is debate about the restriction of fertility treatment to women who are overweight, although there is no doubt that obesity has a significant adverse impact on reproductive outcome. It influences not only the chance of conception but also the response to fertility treatment and increases the risk of miscarriage, congenital anomalies and pregnancy complications . The British Fertility Society guidance suggests that treatment should be deferred until the BMI is less than 35 kg/m2, although in those with more time (e.g. less than 37 years, normal ovarian reserve) a weight reduction to a BMI of less than 30 kg/m2 is preferable . Even a moderate weight loss of 5–10% of body weight can be sufficient to restore fertility and improve metabolic parameters.
Conventional ovulation induction (OI) treatments are highly effective in achieving pregnancy when anovulation is the only factor in a couple’s conception delay. Fertility declines with female age and lifestyle factors including smoking, alcohol intake and body weight negatively influence the success of treatment. Careful planning and monitoring of treatment is necessary to avoid complications such as multiple pregnancy and ovarian hyperstimulation syndrome (OHSS).
Quality Improvement and Patient Safety (QIPS) plays an important role in addressing shortcomings in optimal healthcare delivery. However, there is little published guidance available for emergency department (ED) teams with respect to developing their own QIPS programs. We sought to create recommendations for established and aspiring ED leaders to use as a pathway to better patient care through programmatic QIPS activities, starting internally and working towards interdepartmental collaboration.
An expert panel comprised of ten ED clinicians with QIPS and leadership expertise was established. A scoping review was conducted to identify published literature on establishing QIPS programs and frameworks in healthcare. Stakeholder consultations were conducted among Canadian healthcare leaders, and recommendations were drafted by the expert panel based on all the accumulated information. These were reviewed and refined at the 2018 CAEP Academic Symposium in Calgary using in-person and technologically-supported feedback.
Recommendations include: creating a sense of urgency for improvement; engaging relevant stakeholders and leaders; creating a formal local QIPS Committee; securing funding and resources; obtaining local data to guide the work; supporting QIPS training for team members; encouraging interprofessional, cross-departmental, and patient collaborations; using an established QIPS framework to guide the work; developing reward mechanisms and incentive structures; and considering to start small by focusing on a project rather than a program.
A list of 10 recommendations is presented as guiding principles for the establishment and sustainable deployment of QIPS activities in EDs throughout Canada and abroad. ED leaders are encouraged to implement our recommendations in an effort to improve patient care.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
This paper presents the design of an elliptical shape ultra-wide band antenna for imaging of wood. The antenna is constructed comprising an elliptical shape of patch loaded by a stub to resonate at lower bands, strip loading at the back, and chamfered ground. Despite having miniaturized dimensions of 20 mm × 20 mm, the proposed antenna shows better results compared to recent studies. The simulation results depict a good ultra-wide bandwidth from 2.68 to 16 GHz, and 18.2–20 GHz. Besides, the proposed antenna has two low-frequency bands at 0.89–0.92 and 1.52–1.62 GHz, maximum gain of 5.48 dB, and maximum directivity of 6.9 dBi. The measurement outcomes are performed in air, plywood, and high-density wood and show a good agreement with the simulated results done using electromagnetic simulator CST. In addition to that, the measurement results of S-parameters, transmitted and received signals show a good agreement with the simulated results. Besides, the measured results illustrate a good isolation and uniform illumination among arrays as well as the received signals' shapes do not change in different environments, but only the amplitude. Hence, the proposed antenna seems to be adequate for microwave imaging of wood.
Buoyant jets or forced plumes are discharged into a turbulent ambient in many natural and engineering applications. The background turbulence generally affects the mixing characteristics of the buoyant jet, and the extent of the influence depends on the characteristics of both the jet discharge and ambient. Previous studies focused on the experimental investigation of the problem (for pure jets or plumes), but the findings were difficult to generalize because suitable scales for normalization of results were not known. A model to predict the buoyant jet mixing in the presence of background turbulence, which is essential in many applications, is also hitherto not available even for a background of homogeneous and isotropic turbulence (HIT). We carried out experimental and theoretical investigations of a buoyant jet discharging into background HIT. Buoyant jets were designed to be in the range of
is the momentum length scale, with
representing the asymptotic cases of pure jets and plumes, respectively. The background turbulence was generated using a random synthetic jet array, which produced a region of approximately isotropic and homogeneous field of turbulence to be used in the experiments. The velocity scale of the jet was initially much higher, and the length scale smaller, than that of the background turbulence, which is typical in most applications. Comprehensive measurements of the buoyant jet mixing characteristics were performed up to the distance where jet breakup occurred. Based on the experimental findings, a critical length scale
was identified to be an appropriate normalizing scale. The momentum flux of the buoyant jet in background HIT was found to be conserved only if the second-order turbulence statistics of the jet were accounted for. A general integral jet model including the background HIT was then proposed based on the conservation of mass (using the entrainment assumption), total momentum and buoyancy fluxes, and the decay function of the jet mean momentum downstream. Predictions of jet mixing characteristics from the new model were compared with experimental observation, and found to be generally in agreement with each other.
The effects of growing pinto peanut mixed with elephant grass-based pastures are still little known. The aim of the current research was to evaluate the performance of herbage yield, nutritive value of forage and animal responses to levels of pinto peanut forage mass mixed with elephant grass in low-input systems. Three grazing systems were evaluated: (i) elephant grass-based (control); (ii) pinto peanut, low-density forage yield (63 g/kg of dry matter – DM) + elephant grass; and (iii) pinto peanut, high-density dry matter forage yield (206 g/kg DM) + elephant grass. The experimental design was completely randomized with the three treatments (grazing systems) and three replicates (paddocks) in split-plot grazing cycles. Forage samples were collected to evaluate the pasture and animal responses. Leaf blades of elephant grass and the other companion grasses of pinto peanut were collected to analyse the crude protein, in vitro digestible organic matter and total digestible nutrients. The pinto peanut, high-density dry matter forage yield + elephant grass treatment was found to give the best results in terms of herbage yield, forage intake and stocking rate, as well as having higher crude protein contents for both elephant grass and the other grasses, followed by pinto peanut with low-density forage yield + elephant grass and finally elephant grass alone. Better results were found with the grass–legume system for pasture and animal responses.
Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.
Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.
Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?
Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.