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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.
There is an overabundance of microswimmers in nature, including bacteria, algae, mammalian cells and so on. They use flagellum, cilia or global shape changes (amoeboid motion) to move forward. In the presence of confining channels, these swimmers exhibit often non-trivial behaviours, such as accumulation at the wall, navigation and so on, and their swimming speed may be strongly influenced by the geometric confinement. Several numerical studies have reported that the presence of walls either enhances or reduces the swimming speed depending on the nature of the swimmer, and also on the confinement. The purpose of this paper is to provide an analytical explanation of several previously obtained numerical results. We treat the case of amoeboid swimmers and the case of squirmers having either a tangential (the classical situation) or normal velocity prescribed at the swimmer surface (pumper). For amoeboid motion we consider a quasi-circular swimmer which allows us to tackle the problem analytically and to extract the equations of the motion of the swimmer, with several explicit analytical or semi-analytical solutions. It is found that the deformation of the amoeboid swimmer as well as a high enough order effect due to confinement are necessary in order to account for previous numerical results. The analytical theory accounts for several features obtained numerically also for non-deformable swimmers.
Nighttime eating is often associated with a negative impact on weight management and cardiometabolic health. However, data from recent acute metabolic studies have implicated a benefit of ingesting a bedtime snack for weight management. The present study compared the impact of ingesting a milk snack containing either 10 (BS10) or 30 g (BS30) protein with a non-energetic placebo (BS0) 30 min before bedtime on next morning metabolism, appetite and energy intake in mildly overweight males (age: 24·3 (sem 0·8) years; BMI: 27·4 (sem 1·1) kg/m2). Next morning measurements of RMR, appetite and energy intake were measured using indirect calorimetry, visual analogue scales and an ad libitum breakfast, respectively. Bedtime milk ingestion did not alter next morning RMR (BS0: 7822 (sem 276) kJ/d, BS10: 7482 (sem 262) kJ/d, BS30: 7851 (sem 261) kJ/d, P=0·19) or substrate utilisation as measured by RER (P=0·64). Bedtime milk ingestion reduced hunger (P=0·01) and increased fullness (P=0·04) during the evening immediately after snack ingestion, but elicited no effect the next morning. Next morning breakfast (BS0: 2187 (sem 365) kJ, BS10: 2070 (sem 336) kJ, BS30: 2582 (sem 384) kJ, P=0·21) and 24 h post-trial (P=0·95) energy intake was similar between conditions. To conclude, in mildly overweight adults, compared with a non-energetic placebo, a bedtime milk snack containing 10 or 30 g of protein does not confer changes in next morning whole-body metabolism and appetite that may favour weight management.
Introduction: Survival from cardiac arrest has been linked to the quality of resuscitation care. Unfortunately, healthcare providers frequently underperform in these critical scenarios, with a well-documented deterioration in skills weeks to months following advanced life support courses. Improving initial training and preventing decay in knowledge and skills are a priority in resuscitation education. The spacing effect has repeatedly been shown to have an impact on learning and retention. Despite its potential advantages, the spacing effect has seldom been applied to organized education training or complex motor skill learning where it has the potential to make a significant impact. The purpose of this study was to determine if a resuscitation course taught in a spaced format compared to the usual massed instruction results in improved retention of procedural skills. Methods: EMS providers (Paramedics and Emergency Medical Technicians (EMT)) were block randomized to receive a Pediatric Advanced Life Support (PALS) course in either a spaced format (four 210-minute weekly sessions) or a massed format (two sequential 7-hour days). Blinded observers used expert-developed 4-point global rating scales to assess video recordings of each learner performing various resuscitation skills before, after and 3-months following course completion. Primary outcomes were performance on infant bag-valve-mask ventilation (BVMV), intraosseous (IO) insertion, infant intubation, infant and adult chest compressions. Results: Forty-eight of 50 participants completed the study protocol (26 spaced and 22 massed). There was no significant difference between the two groups on testing before and immediately after the course. 3-months following course completion participants in the spaced cohort scored higher overall for BVMV (2.2 ± 0.13 versus 1.8 ± 0.14, p=0.012) without statistically significant difference in scores for IO insertion (3.0 ± 0.13 versus 2.7± 0.13, p= 0.052), intubation (2.7± 0.13 versus 2.5 ± 0.14, p=0.249), infant compressions (2.5± 0.28 versus 2.5± 0.31, p=0.831) and adult compressions (2.3± 0.24 versus 2.2± 0.26, p=0.728) Conclusion: Procedural skills taught in a spaced format result in at least as good learning as the traditional massed format; more complex skills taught in a spaced format may result in better long term retention when compared to traditional massed training as there was a clear difference in BVMV and trend toward a difference in IO insertion.
Compulsory admission can be experienced as devaluing and stigmatising by people with mental illness. Emotional reactions to involuntary hospitalisation and stigma-related stress may affect recovery, but longitudinal data are lacking. We, therefore, examined the impact of stigma-related emotional reactions and stigma stress on recovery over a 2-year period.
Shame and self-contempt as emotional reactions to involuntary hospitalisation, stigma stress, self-stigma and empowerment, as well as recovery were assessed among 186 individuals with serious mental illness and a history of recent involuntary hospitalisation.
More shame, self-contempt and stigma stress at baseline were correlated with increased self-stigma and reduced empowerment after 1 year. More stigma stress at baseline was associated with poor recovery after 2 years. In a longitudinal path analysis more stigma stress at baseline predicted poorer recovery after 2 years, mediated by decreased empowerment after 1 year, controlling for age, gender, symptoms and recovery at baseline.
Stigma stress may have a lasting detrimental effect on recovery among people with mental illness and a history of involuntary hospitalisation. Anti-stigma interventions that reduce stigma stress and programs that enhance empowerment could improve recovery. Future research should test the effect of such interventions on recovery.
Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.
To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele.
Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.
ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.
The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.
Functional near-infrared spectroscopy (fNIRS) has been used in healthcare and medical research for the past two decades. In particular, the use of fNIRS in academic and clinical psychiatry has increased rapidly owing to its advantages over other neuroimaging modalities. fNIRS is a tool that can potentially supplement clinical interviews and mental state examinations to establish a psychiatric diagnosis and monitor treatment progress. This article provides a review of the theoretical background of fNIRS, key principles of its applications in psychiatry and its limitations, and shares a vision of its future applicability in psychiatric research and clinical practice.
• Understand the theoretical background, mechanism of action and clinical applications of fNIRS and compare it to other neuroimaging modalities
• Understand the use of fNIRS in academic and clinical psychiatry through current research findings
• Be able to evaluate the future potential of fNIRS and formulate new ideas for using fNIRS in academic and clinical psychiatry
Results are presented from our ongoing studies of Titan using ALMA during the period 2012-2015, including a confirmation of the previous detection of vinyl cyanide (C2H3CN), as well as the first spatial map for this species on Titan. Simultaneous mapping of HC3N, CH3CN and C2H5CN reveal characteristic abundance patterns for each species that provide insight into their individual photochemical lifetimes, and help inform our understanding of Titan’s unique, time-variable atmospheric chemistry and global circulation. A time-sequence of HC3N maps covering 38 months reveals a dramatic change in the distribution of this gas consistent with high-altitude photochemical production followed by advection towards the southern (winter) pole, combined with rapid loss in the north after Titan’s 2009 seasonal equinox. The 2015 C2H3CN and C2H5CN maps show abundance peaks in Titan’s southern hemisphere, similar to those observed for the short-lived HC3N molecule. The longer-lived CH3CN, on the other hand, remains more concentrated in the north.
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, yet the search for definite genetic etiologies remains elusive. Delineating ASD endophenotypes can boost the statistical power to identify the genetic etiologies and pathophysiology of ASD. We aimed to test for endophenotypes of neuroanatomy and associated intrinsic functional connectivity (iFC) via contrasting male youth with ASD, their unaffected brothers and typically developing (TD) males.
The 94 participants (aged 9–19 years) – 20 male youth with ASD, 20 unaffected brothers and 54 TD males – received clinical assessments, and undertook structural and resting-state functional magnetic resonance imaging scans. Voxel-based morphometry was performed to obtain regional gray and white matter volumes. A seed-based approach, with seeds defined by the regions demonstrating atypical neuroanatomy shared by youth with ASD and unaffected brothers, was implemented to derive iFC. General linear models were used to compare brain structures and iFC among the three groups. Assessment of familiality was investigated by permutation tests for variance of the within-family pair difference.
We found that atypical gray matter volume in the mid-cingulate cortex was shared between male youth with ASD and their unaffected brothers as compared with TD males. Moreover, reduced iFC between the mid-cingulate cortex and the right inferior frontal gyrus, and increased iFC between the mid-cingulate cortex and bilateral middle occipital gyrus were the shared features of male ASD youth and unaffected brothers.
Atypical neuroanatomy and iFC surrounding the mid-cingulate cortex may be a potential endophenotypic marker for ASD in males.
The collision between aqueous drops in air typically leads to coalescence after impact. Rebounding of the droplets with similar sizes at atmospheric conditions is not generated, unless with significantly large pressure or high impact parameters exhibiting near-grazing collision. Here we demonstrate experimentally the creation of a non-coalescent regime through addition of a small amount of water-soluble surfactant. We perform a direct simulation to account for the continuum and short-range flow dynamics of the approaching interfaces, as affected by the soluble surfactant. Based on the immersed-boundary formulation, a conservative scheme is developed for solving the coupled surface-bulk convection–diffusion concentration equations, which presents excellent mass preservation in the solvent as well as conservation of total surfactant mass. We show that the Marangoni effect, caused by non-uniform distributions of surfactant on the droplet surface and surface tension, induces stresses that oppose the draining of gas in the interstitial gap, and hence prohibits merging of the interfaces. In such gas–liquid systems, the repulsion caused by the addition of surfactant, as frequently observed in liquid–liquid systems such as emulsions in the form of an electric double-layer force, was found to be too weak to dominate in the attainable range of interfacial separation distances. These results thus identify the key mechanisms governing the impact dynamics of surfactant-coated droplets in air and imply the potential of using a small amount of surfactant to manipulate impact outcomes, for example, to prevent coalescence between droplets or interfaces in gases.
Little is known about time perception, its putative role as cognitive endophenotype, and its neuroanatomical underpinnings in adults with attention deficit hyperactivity disorder (ADHD).
Twenty adults with ADHD, 20 unaffected first-degree relatives and 20 typically developing controls matched for age and gender undertook structural magnetic resonance imaging scans. Voxel-based morphometry with DARTEL was performed to obtain regional grey-matter volumes. Temporal processing was investigated as a putative cognitive endophenotype using a temporal reproduction paradigm. General linear modelling was employed to examine the relationship between temporal reproduction performances and grey-matter volumes.
ADHD participants were impaired in temporal reproduction and unaffected first-degree relatives performed in between their ADHD probands and typically developing controls. Increased grey-matter volume in the cerebellum was associated with poorer temporal reproduction performance.
Adults with ADHD are impaired in time reproduction. Performances of the unaffected first-degree relatives are in between ADHD relatives and controls, suggesting that time reproduction might be a cognitive endophenotype for adult ADHD. The cerebellum is involved in time reproduction and might play a role in driving time performances.
The first large outbreak of hand, foot, and mouth disease (HFMD) with severe complications primarily caused by enterovirus 71 was reported in Taiwan in 1998. Surveillance of HFMD to evaluate the spread of HFMD with and without infection control policy is needed. We developed a new dynamic epidemic Susceptible-Infected-Recovered (SIR) model to fit the surveillance data on containing valuable information on the severity of HFMD in order to accurately estimate the basic reproductive number (R0) of HFMD. After fitting the empirical data, in conjunction with other relevant parameters extracted from the literature, the estimated transmission coefficients were close to 5 × 10−7 (per day) and the proportion of severe HFMD cases ranged between 0 and 0·0036 (per day). Taking into account the distribution of all parameters considered in our dynamic epidemic model, the R0 computed was 1·37 (95% confidence interval 0·24–5·84), suggesting a higher likelihood of the spread of HFMD if no infection control policy is provided. The isolation strategy against the spread of HFMD not only delayed the epidemic peak with the delayed time ranging from 4 weeks for only 20% isolation to 47 weeks for 100% isolation but also reduced total number of HFMD cases with the percentage of reduction ranging from 1·3% for only 20% isolation to 13·3% for 100% isolation. The proposed model can also be flexible for evaluating the effectiveness of two other possible policies for containing HFMD, quarantine and vaccination (if the vaccine can be developed).
A numerical scheme based on the immersed interface method (IIM) is developed to simulate the dynamics of an axisymmetric viscous drop under an electric field. In this work, the IIM is used to solve both the fluid velocity field and the electric potential field. Detailed numerical studies on the numerical scheme show a second-order convergence. Moreover, our numerical scheme is validated by the good agreement with previous analytical models, and numerical results from the boundary integral simulations. Our method can be extended to Navier-Stokes fluid flow with nonlinear inertia effects.
The Cognitive Abilities Screening Instrument – Short (CASI-S) is a brief cognitive screening test. However, there is limited information regarding its applicability in primary care.
To ascertain whether the CASI-S differentiates between dementia patients and normal controls in primary care; to examine its correlation with other cognitive instruments, to analyze its internal consistency, test-retest stability, and diagnostic accuracy.
In a case-control study, carried out at two Primary Care Units (PCUs) in the eastern region of the city of São Paulo, 47 older adults were diagnosed with dementia according to DSM-IV criteria (mean age = 76.81 ± 7.03 years), and 55 were classified as normal controls (mean age = 72.78 ± 7.37 years), by a multidisciplinary panel which had access to results from a comprehensive cognitive battery and the patients’ health data. The present analyses included results from the Mini-Mental State Examination (MMSE). The CASI-S was not used to determine diagnostic status.
The CASI-S was easily applied in the primary care setting. There was a significant performance difference (p < 0.001) between dementia patients (15.57 ± 7.40) and normal controls (26.67 ± 3.52) on the CASI-S. CASI-S scores correlated with age (ρ = −0.410, p < 0.001), educational level (ρ = 0.373, p < 0.001), and MMSE score (ρ = 0.793, p < 0.001). The internal consistency of the CASI-S was high (α = 0.848) and the correlation between test and retest was 0.688, suggesting adequate temporal stability. In the ROC curve analyses, scores of 22/23 generated an area under the curve of 0.907, with sensitivity of 93% and specificity of 81%.
The CASI-S can be useful for dementia screening in primary care in Brazil.
Few countries routinely collect comprehensive encephalitis data, yet understanding the epidemiology of this condition has value for clinical management, detecting novel and emerging pathogens, and guiding timely public health interventions. When this study was conducted there was no standardized diagnostic algorithm to aid identification of encephalitis or systematic surveillance for adult encephalitis. In July 2012 we tested three pragmatic surveillance options aimed at identifying possible adult encephalitis cases admitted to a major Australian hospital: hospital admissions searches, clinician notifications and laboratory test alerts (CSF herpes simplex virus requests). Eligible cases underwent structured laboratory investigation and a specialist panel arbitrated on the final diagnosis. One hundred and thirteen patients were initially recruited into the 10-month study; 20/113 (18%) met the study case definition, seven were diagnosed with infectious or immune-mediated encephalitis and the remainder were assigned alternative diagnoses. The laboratory alert identified 90% (102/113) of recruited cases including six of the seven cases of confirmed encephalitis suggesting that this may be a practical data source for case ascertainment. The application of a standardized diagnostic algorithm and specialist review by an expert clinical panel aided diagnosis of patients with encephalitis.
In this study the authors aimed to examine the differentiability of 5 factors that preschool teachers may perceive as essential for successful implementation of inclusive education in regular classrooms. The 5 hypothetically influential factors were teamwork, curriculum, school support, government support, and stakeholders’ attitudes. Teachers from half-day kindergarten and full-day childcare centre settings in Hong Kong with varying teaching experience were surveyed (N = 461). Confirmatory factor analysis defined the 5 distinct factors, all of which displayed high scores (Ms > 4 on a 5-point scale). A 2 (experience: low; high) x 2 (school type: half-day kindergarten; full-day childcare centre settings) multivariate analysis of variance (MANOVA) found some subtle group differences. Less experienced teachers found stakeholders’ attitudes to be important, and more so than more experienced teachers, whereas full-day childcare centre teachers found teamwork, curriculum, and stakeholders’ attitudes more important than did half-day kindergarten teachers. The findings imply that whereas all 5 factors are perceived by teachers as important for the success of inclusive education, some factors are of greater concern to teachers working in full-day childcare centres than teachers working in half-day kindergartens. The findings provide advice on how best to allocate limited resources across settings with the intention of promoting inclusive education.
Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted body image and are frequently co-morbid with each other, although their relationship remains little studied. While there is evidence of abnormalities in visual and visuospatial processing in both disorders, no study has directly compared the two. We used two complementary modalities – event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) – to test for abnormal activity associated with early visual signaling.
We acquired fMRI and ERP data in separate sessions from 15 unmedicated individuals in each of three groups (weight-restored AN, BDD, and healthy controls) while they viewed images of faces and houses of different spatial frequencies. We used joint independent component analyses to compare activity in visual systems.
AN and BDD groups demonstrated similar hypoactivity in early secondary visual processing regions and the dorsal visual stream when viewing low spatial frequency faces, linked to the N170 component, as well as in early secondary visual processing regions when viewing low spatial frequency houses, linked to the P100 component. Additionally, the BDD group exhibited hyperactivity in fusiform cortex when viewing high spatial frequency houses, linked to the N170 component. Greater activity in this component was associated with lower attractiveness ratings of faces.
Results provide preliminary evidence of similar abnormal spatiotemporal activation in AN and BDD for configural/holistic information for appearance- and non-appearance-related stimuli. This suggests a common phenotype of abnormal early visual system functioning, which may contribute to perceptual distortions.