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Alcohol use is influenced by genetic and environmental factors. We examined the interactive effects between genome-wide polygenic risk scores for alcohol use (alc-PRS) and social support in relation to alcohol use among European American (EA) and African American (AA) adults across sex and developmental stages (emerging adulthood, young adulthood, and middle adulthood). Data were drawn from 4,011 EA and 1,274 AA adults from the Collaborative Study on the Genetics of Alcoholism who were between ages 18–65 and had ever used alcohol. Participants completed the Semi-Structured Assessment for the Genetics of Alcoholism and provided saliva or blood samples for genotyping. Results indicated that social support from friends, but not family, moderated the association between alc-PRS and alcohol use among EAs and AAs (only in middle adulthood for AAs); alc-PRS was associated with higher levels of alcohol use when friend support was low, but not when friend support was high. Associations were similar across sex but differed across developmental stages. Findings support the important role of social support from friends in buffering genetic risk for alcohol use among EA and AA adults and highlight the need to consider developmental changes in the role of social support in relation to alcohol use.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Patients with chronic kidney disease (CKD) have more cognitive impairments. However, the etiologies are not fully clear. Plasma homocysteine levels and vascular burden rise in CKD; meanwhile, high homocysteine levels and vascular factors are known risk factors of dementia in non-CKD patients. Thus, we aimed to investigate the association between homocysteine, vascular burden and cognitive impairment in CKD and to see if the effect of elevated homocysteine on cognitive impairment mediated by vascular factor.
146 patients with CKD and 69 normal comparisons were recruited. Cognitive function was evaluated by comprehensive neuropsychological tests assessing processing speed, executive function, language, visuospatial function, memory, and attention domains. Vascular burden was assessed by Framinghan cardiovascular risk scale (FCRS) which indicates risk of atherosclerotic diseases including stroke.
In controlled analysis, patients with CKD had lower scores in all cognitive domains, and had higher homocysteine levels (18.5±6.4 vs. 9.8±2.9, p< 0.0001) and FCRS(17.0±4.7 vs. 14.0±4.7, p< 0.0001). Among patients with CKD, higher homocysteine levels (p=0.026) were associated with lower score on digit symbol task which is related to processing speed and executive function with controlling for age, sex, education and stage of CKD. The association persisted (p=0.047) after controlling for vascular risks.
Patients with CKD had extensive cognitive impairments. Elevated homocysteine levels may be an risk factor, which is independent of vascular burden, of cognitive impairment on processing speed and executive function. Further studies to investigate if normalization of homocysteine can improve cognitive function will be suggested.
Personality and its potential role in mediating risk of psychiatric disorders and suicidality are assessed by sexual orientation, using data collected among young Swiss men (n = 5875) recruited while presenting for mandatory military conscription. Mental health outcomes were analyzed by sexual attraction using logistic regression, controlling for five-factor model personality traits and socio-demographics. Homo/bisexual men demonstrated the highest scores for neuroticism-anxiety but the lowest for sociability and sensation seeking, with no differences for aggression-hostility. Among homo/bisexual men, 10.2% fulfilled diagnostic criteria for major depression in the past 2 weeks, 10.8% for ADHD in the past 12 months, 13.8% for lifetime anti-social personality disorder (ASPD), and 6.0% attempted suicide in the past 12 months. Upon adjusting (AOR) for personality traits, their odds ratios (OR) for major depression (OR = 4.78, 95% CI 2.81–8.14; AOR = 1.46, 95% CI 0.80–2.65) and ADHD (OR = 2.17, 95% CI = 1.31–3.58; AOR = 1.00, 95% CI 0.58–1.75) lost statistical significance, and the odds ratio for suicide attempt was halved (OR = 5.10, 95% CI 2.57–10.1; AOR = 2.42, 95% CI 1.16–5.02). There are noteworthy differences in personality traits by sexual orientation, and much of the increased mental morbidity appears to be accounted for by such underlying differences, with important implications for etiology and treatment.
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.
This study proposed the application of a novel immersed boundary method (IBM) for the treatment of irregular geometries using Cartesian computational grids for high speed compressible gas flows modelled using the unsteady Euler equations. Furthermore, the method is accelerated through the use of multiple Graphics Processing Units – specifically using Nvidia’s CUDA together with MPI - due to the computationally intensive nature associated with the numerical solution to multi-dimensional continuity equations. Due to the high degree of locality required for efficient multiple GPU computation, the Split Harten-Lax-van-Leer (SHLL) scheme is employed for vector splitting of fluxes across cell interfaces. NVIDIA visual profiler shows that our proposed method having a computational speed of 98.6 GFLOPS and 61% efficiency based on the Roofline analysis that provides the theoretical computing speed of reaching 160 GLOPS with an average 2.225 operations/byte. To demonstrate the validity of the method, results from several benchmark problems covering both subsonic and supersonic flow regimes are presented. Performance testing using 96 GPU devices demonstrates a speed up of 89 times that of a single GPU (i.e. 92% efficiency) for a benchmark problem employing 48 million cells. Discussions regarding communication overhead and parallel efficiency for varying problem sizes are also presented.
Genetic predispositions play an important role in the development of internalizing and externalizing behaviors. Understanding the mechanisms through which genetic risk unfolds to influence these developmental outcomes is critical for developing prevention and intervention efforts, capturing key elements of Irv's research agenda and scientific legacy. In this study, we examined the role of parenting and personality in mediating the effect of genetic risk on adolescents’ major depressive disorder and conduct disorder symptoms. Longitudinal data were drawn from a sample of 709 European American adolescents and their mothers from the Collaborative Studies on Genetics of Alcoholism. Results from multivariate path analysis indicated that adolescents’ depressive symptoms genome-wide polygenic scores (DS_GPS) predicted lower parental knowledge, which in turn was associated with more subsequent major depressive disorder and conduct disorder symptoms. Adolescents’ DS_GPS also had indirect effects on these outcomes via personality, with a mediating effect via agreeableness but not via other dimensions of personality. Findings revealed that the pattern of associations was similar across adolescent gender. Our findings emphasize the important role of evocative gene–environment correlation processes and intermediate phenotypes in the pathways of risk from genetic predispositions to complex adolescent outcomes.
Using a large and nationally representative sample, we examined how adolescents’ 5-HTTLPR genotype and perceived parenting quality independently and interactively associated with trajectories of alcohol use from early adolescence to young adulthood and whether/how gender may moderate these associations. The sample for this study included 13,749 adolescents (53.3% female; 56.3% non-Hispanic White, 21.5% Black, 16.0% Hispanic, and 6.1% Asian) followed prospectively from adolescence to young adulthood. Using growth mixture modeling, we identified four distinct trajectories of alcohol use (i.e., persistent heavy alcohol use, developmentally limited alcohol use, late-onset heavy alcohol use, and non/light alcohol use). Results indicated that the short allele of 5-HTTLPR was associated with higher risk of membership in the persistent and the late-onset heavy alcohol use trajectories. Parenting quality was associated with lower likelihoods of following the persistent heavy and the developmentally limited alcohol use trajectories but was not associated with risk of membership for the late-onset heavy drinking trajectory. 5-HTTLPR interacted with parenting quality to predict membership in the persistent heavy alcohol use trajectory for males but not for females. Findings highlighted the importance of considering the heterogeneity in trajectories of alcohol use across development and gender in the study of Gene Environment interactions in alcohol use.
In our attempt to investigate the basic active galactic nucleus (AGN) paradigm requiring a centrally located supermassive black hole (SMBH), a close to Keplerian accretion disk and a jet perpendicular to its plane, we have searched for radio continuum in galaxies with H2O megamasers in their disks. We observed 18 such galaxies with the Very Large Baseline Array in C band (5 GHz, ~2 mas resolution) and we detected 5 galaxies at 8 σ or higher levels. For those sources for which the maser data is available, the positions of masers and those of the 5 GHz radio continuum sources coincide within the uncertainties, and the radio continuum is perpendicular to the maser disk’s orientation within the position angle uncertainties.
Introduction: In 2015, there were 476 apparent illicit drug overdose deaths, prompting BC’s Provincial Health Officer to declare a public health emergency on 14 Apr 2016. Paramedics of BC’s Ambulance Service (BCAS) are on the front lines in this crisis. Here we examine recent trends in the number of suspected overdose events attended by the BCAS and the use of naloxone, an opioid antagonist, by BCAS paramedics. Methods: The BC Centre for Disease Control receives a weekly data feed from BC Emergency Health Services that includes all records from the BCAS Patient Care Record where: naloxone was administered by paramedics; the primary impression code indicates poisoning or overdose; or, the originating call is associated with ingestion poisoning (‘card 23’). Here, we report a descriptive analysis of these data for suspected drug overdose events during the period January 1, 2010 to September 30, 2016. Results: Between January 2010 and September 2016 BCAS paramedics attended 164,227 suspected overdose events; 12% of these events (n=16,944) included naloxone administration by BCAS paramedics. Paralleling the rise in illicit drug overdose deaths in BC, naloxone administration by paramedics has been increasing rapidly, doubling from approximately 180/month in 2014, to 370/month in 2016. When naloxone was administered by paramedics, 90% of these patients were transported, whereas 77% were transported when naloxone was not administered. Administrations occurred most frequently on Friday and Saturday evenings. Almost half (46%) of all naloxone administrations by paramedics were recorded as being in a home or residence; 18% were recorded as occurring on a street or highway. The proportion of naloxone administrations among males has increased yearly. In 2010, 58% of naloxone administrations were in males compared to 69% in 2016. Conclusion: The number of overdose deaths in BC has risen drastically in recent years and the proportion of ambulance calls requiring administration of naloxone by BCAS has climbed correspondingly. The vast majority of overdose cases-especially those requiring naloxone-are transported to the emergency department. With the overdose crisis showing little sign of abating, the administration of naloxone by BC paramedics will continue to be a critical element of the provincial response.
We made dynamical black hole mass measurements from nineteen Seyfert 2 galaxies which host sub-parsec H2O maser disks using the H2O megamaser technique. The nearly perfect Keplerian rotation curves in many of these maser systems guarantee the high accuracy and precision of the black hole mass measurements. With the stellar velocity dispersion (σ∗) of the galaxy bulges measured with the Dupont 2.5 m telescope at Las Campanas Observatory in the South and the Apache Point Observatory (APO) 3.5m telescope in the North, we found that H2O maser galaxies, most of which host pseudo bulges rather than classical bulges, do not all follow the MBH–σ∗ relation shown in the literature. This result is well consistent with the latest findings by Kormendy & Ho (2013) that only early type galaxies and galaxies with classical bulges follow a tight MBH–σ∗ relation. Such a tight correlation may not exist in pseudo bulge galaxies.
Transcritical flow of a stratified fluid past a broad localised topographic obstacle is studied analytically in the framework of the forced extended Korteweg–de Vries, or Gardner, equation. We consider both possible signs for the cubic nonlinear term in the Gardner equation corresponding to different fluid density stratification profiles. We identify the range of the input parameters: the oncoming flow speed (the Froude number) and the topographic amplitude, for which the obstacle supports a stationary localised hydraulic transition from the subcritical flow upstream to the supercritical flow downstream. Such a localised transcritical flow is resolved back into the equilibrium flow state away from the obstacle with the aid of unsteady coherent nonlinear wave structures propagating upstream and downstream. Along with the regular, cnoidal undular bores occurring in the analogous problem for the single-layer flow modelled by the forced Korteweg–de Vries equation, the transcritical internal wave flows support a diverse family of upstream and downstream wave structures, including kinks, rarefaction waves, classical undular bores, reversed and trigonometric undular bores, which we describe using the recent development of the nonlinear modulation theory for the (unforced) Gardner equation. The predictions of the developed analytic construction are confirmed by direct numerical simulations of the forced Gardner equation for a broad range of input parameters.
Water vapor megamasers from the center of active galaxies provide a powerful tool to trace accretion disks at sub-parsec resolution and, through an entirely geometrical method, measure direct distances to galaxies up to 200 Mpc. The Megamaser Cosmology Project (MCP) is formed by a team of astronomers with the aim of identifying new maser systems, and mapping their emission at high angular resolution to determine their distance. Two types of observations are necessary to measure a distance: single-dish monitoring to measure the acceleration of gas in the disk, and sensitive VLBI imaging to measure the angular size of the disk, measure the rotation curve, and model radial displacement of the maser feature. The ultimate goal of the MCP is to make a precise measurement of H0 by measuring such distances to at least 10 maser galaxies in the Hubble flow. We present here the preliminary results from a new maser system, Mrk 1419. Through a model of the rotation from the systemic masers assuming a narrow ring, and combining these results with the acceleration measurement from the Green Bank Telescope, we determine a distance to Mrk 1419 of 81 ± 10 Mpc. Given that the disk shows a significant warp that may not be entirely traced by our current observations, more sensitive observations and more sophisticated disk modeling will be essential to improve our distance estimation to this galaxy.
The Hubble constant H0 describes not only the expansion of local space at redshift z ~ 0, but is also a fundamental parameter determining the evolution of the universe. Recent measurements of H0 anchored on Cepheid observations have reached a precision of several percent. However, this problem is so important that confirmation from several methods is needed to better constrain H0 and, with it, dark energy and the curvature of space. A particularly direct method involves the determination of distances to local galaxies far enough to be part of the Hubble flow through water vapor (H2O) masers orbiting nuclear supermassive black holes. The goal of this article is to describe the relevance of H0 with respect to fundamental cosmological questions and to summarize recent progress of the ‘Megamaser Cosmology Project’ (MCP) related to the Hubble constant.
The present study aimed to (a) characterize 10-year trajectory patterns of depressive symptoms and (b) investigate the association between depressive trajectory and subsequent obesity, metabolic function and cortisol level.
In a prospective study of Taiwanese adults aged ⩾60 years (n=3922) between 1989 and 1999, depression was assessed using a 10-item short-form of the Center for Epidemiologic Studies Depression Scale and information on body mass index (BMI) was collected by self-report. A subsample (n=445) of the original cohort in 1989 was drawn to assess metabolic variables and cortisol levels in a 2000 follow-up. After trajectory analyses were performed, multinomial logistic regression analyses were used to estimate the association estimates.
We identified four distinctive trajectories of depressive symptoms: class 1 (persistent low, 41.8%); class 2 (persistent mild, 46.8%); class 3 (late peak, 4.2%); and class 4 (high-chronic, 7.2%). The results from both complete cases and multiple imputation analyses indicated that the odds of obesity were lower in the class 2, 3 or 4 elderly, as compared with those in class 1, while the odds of underweight were higher. The classes of older adults with more and persistent depressive symptoms showed a trend toward having both a lower BMI (p=0.01) and a higher cortisol level (p=0.04) compared with those with low depressive symptoms.
Incremental increases in depressive symptoms over time were associated with reduced risk of obesity and higher cortisol levels.
A coupled structural and fluid flow analysis was performed to assess the hydroelastic behavior of a composite marine propeller. The finite element method and lifting surface theory were applied in the structural and fluid analyses, respectively. A coupled equation derived from the Bernoulli equation and the hydrostatic pressure in terms of the blade deflection and strength of the vortex was solved by Newton-Raphson procedure. A MAU 3–60 propeller was analyzed with different stacking sequences of composite layup. The hydroelastic behaviors of the propeller with balanced and unbalanced stacking sequences were investigated and discussed. The unbalanced Stacking sequences were shown to influence the performance of the composite propeller, especially in the region in which the advanced coefficient is low.
Outlined here is a technique for sub-wavelength infrared surface imaging
performed using a phase matched optical parametric oscillator laser and an
atomic force microscope as the detection mechanism. The technique uses a
novel surface excitation illumination approach to perform simultaneously
chemical mapping and AFM topography imaging with an image resolution of 200 nm. This method was demonstrated by imaging polystyrene micro-structures.
To establish the Fe status of pregnant women and their neonates in the Republic of Seychelles.
A prospective study.
Republic of Seychelles.
Pregnant women were recruited and blood samples taken at enrolment and post-delivery along with cord blood samples. Ferritin and soluble transferrin receptor (sTfR) were measured in maternal (n 220) and cord blood (n 123) samples.
Maternal Fe deficiency (ferritin < 15 ng/ml, sTfR > 28 nmol/l) was present in 6 % of subjects at enrolment and in 20 % at delivery. There was no significant decrease in maternal ferritin. A significant increase in sTfR was observed between enrolment and delivery (P < 0·001). Maternal BMI and use of Fe supplements at 28 weeks’ gestation were associated with improved maternal Fe status at delivery, whereas parity had a negative effect on sTfR and ferritin at delivery.
Fe status of pregnant Seychellois women was, on average, within normal ranges. The incidence of Fe deficiency throughout pregnancy in this population was similar to that in a Westernised population. Increased awareness of the importance of adequate Fe intake during pregnancy, particularly in multiparous women, is warranted.