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Electronic health records (EHRs), increasingly available in low- and middle-income countries (LMICs), provide an opportunity to study transdiagnostic features of serious mental illness (SMI) and its trajectories.
Aims
Characterise transdiagnostic features and diagnostic trajectories of SMI using an EHR database in an LMIC institution.
Method
We conducted a retrospective cohort study using EHRs from 2005–2022 at Clínica San Juan de Dios Manizales, a specialised mental health facility in Colombia, including 22 447 patients with schizophrenia (SCZ), bipolar disorder (BPD) or severe/recurrent major depressive disorder (MDD). Using diagnostic codes and clinical notes, we analysed the frequency of suicidality and psychosis across diagnoses, patterns of diagnostic switching and the accumulation of comorbidities. Mixed-effect logistic regression was used to identify factors influencing diagnostic stability.
Results
High frequencies of suicidality and psychosis were observed across diagnoses of SCZ, BPD and MDD. Most patients (64%) received multiple diagnoses over time, including switches between primary SMI diagnoses (19%), diagnostic comorbidities (30%) or both (15%). Predictors of diagnostic switching included mentions of delusions (odds ratio = 1.47, 95% CI 1.34–1.61), prior diagnostic switching (odds ratio = 4.01, 95% CI 3.7–4.34) and time in treatment, independent of age (log of visit number; odds ratio = 0.57, 95% CI 0.54–0.61). Over 80% of patients reached diagnostic stability within 6 years of their first record.
Conclusions
Integrating structured and unstructured EHR data reveals transdiagnostic patterns in SMI and predictors of disease trajectories, highlighting the potential of EHR-based tools for research and precision psychiatry in LMICs.
Spotted-wing drosophila, Drosophila suzukii, is a global pest of soft fruits that is capable of reproducing on a wide range of cultivated and wild plant species. In Canada, D. suzukii was first reported in British Columbia in 2009 and is now widespread across the country. Understanding the genetic structure of D. suzukii populations could be important for pest management if there are phenotypic differences between genetically distinct populations. For example, insect pest populations could respond differently to directional selection imposed by insecticides, differ in their host plant preferences, and vary in their susceptibility to biological control agents. Here, we used double-digest restriction site–associated DNA sequencing to examine large- and fine-scale patterns of the genetic structure of D. suzukii reared from fruit hosts in Canada. We found that this species has a large-scale spatial genetic structure; the flies collected formed two distinct genetic clusters, one of which was distinct to western Canada and the other to eastern Canada. At the local scale, D. suzukii populations showed no evidence of host-associated structuring in British Columbia, suggesting that pest management tactics may be best applied at the landscape level. Our results highlight the need to investigate phenotypic differences between western and eastern D. suzukii populations in Canada.
To assess whether measurement and feedback of chlorhexidine gluconate (CHG) skin concentrations can improve CHG bathing practice across multiple intensive care units (ICUs).
Design:
A before-and-after quality improvement study measuring patient CHG skin concentrations during 6 point-prevalence surveys (3 surveys each during baseline and intervention periods).
Setting:
The study was conducted across 7 geographically diverse ICUs with routine CHG bathing.
Participants:
Adult patients in the medical ICU.
Methods:
CHG skin concentrations were measured at the neck, axilla, and inguinal region using a semiquantitative colorimetric assay. Aggregate unit-level CHG skin concentration measurements from the baseline period and each intervention period survey were reported back to ICU leadership, which then used routine education and quality improvement activities to improve CHG bathing practice. We used multilevel linear models to assess the impact of intervention on CHG skin concentrations.
Results:
We enrolled 681 (93%) of 736 eligible patients; 92% received a CHG bath prior to survey. At baseline, CHG skin concentrations were lowest on the neck, compared to axillary or inguinal regions (P < .001). CHG was not detected on 33% of necks, 19% of axillae, and 18% of inguinal regions (P < .001 for differences in body sites). During the intervention period, ICUs that used CHG-impregnated cloths had a 3-fold increase in patient CHG skin concentrations as compared to baseline (P < .001).
Conclusions:
Routine CHG bathing performance in the ICU varied across multiple hospitals. Measurement and feedback of CHG skin concentrations can be an important tool to improve CHG bathing practice.
One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The coronavirus [coronavirus disease 2019 (COVID-19)] pandemic has introduced extraordinary life changes and stress, particularly in adolescents and young adults. Initial reports suggest that depression and anxiety are elevated during COVID-19, but no prior study has explored changes at the within-person level. The current study explored changes in depression and anxiety symptoms from before the pandemic to soon after it first peaked in Spring 2020 in a sample of adolescents and young adults (N = 451) living in Long Island, New York, an early epicenter of COVID-19 in the U.S.
Methods
Depression (Children's Depression Inventory) and anxiety symptoms (Screen for Child Anxiety Related Symptoms) were assessed between December 2014 and July 2019, and, along with COVID-19 experiences, symptoms were re-assessed between March 27th and May 15th, 2020.
Results
Across participants and independent of age, there were increased generalized anxiety and social anxiety symptoms. In females, there were also increased depression and panic/somatic symptoms. Multivariable linear regression indicated that greater COVID-19 school concerns were uniquely associated with increased depression symptoms. Greater COVID-19 home confinement concerns were uniquely associated with increased generalized anxiety symptoms, and decreased social anxiety symptoms, respectively.
Conclusions
Adolescents and young adults at an early epicenter of the COVID-19 pandemic in the U.S. experienced increased depression and anxiety symptoms, particularly amongst females. School and home confinement concerns related to the pandemic were independently associated with changes in symptoms. Overall, this report suggests that the COVID-19 pandemic is having multifarious adverse effects on the mental health of youth.
Identify risk factors that could increase progression to severe disease and mortality in hospitalized SARS-CoV-2 patients in the Southeast region of the United States.
Design, setting, and participants:
Multicenter, retrospective cohort including 502 adults hospitalized with laboratory-confirmed COVID-19 between March 1, 2020, and May 8, 2020 within 1 of 15 participating hospitals in 5 health systems across 5 states in the Southeast United States.
Methods:
The study objectives were to identify risk factors that could increase progression to hospital mortality and severe disease (defined as a composite of intensive care unit admission or requirement of mechanical ventilation) in hospitalized SARS-CoV-2 patients in the Southeast United States.
Results:
In total, 502 patients were included, and 476 of 502 (95%) had clinically evaluable outcomes. The hospital mortality rate was 16% (76 of 476); 35% (177 of 502) required ICU admission and 18% (91 of 502) required mechanical ventilation. By both univariate and adjusted multivariate analyses, hospital mortality was independently associated with age (adjusted odds ratio [aOR], 2.03 for each decade increase; 95% confidence interval [CI], 1.56-–2.69), male sex (aOR, 2.44; 95% CI, 1.34–4.59), and cardiovascular disease (aOR, 2.16; 95% CI, 1.15–4.09). As with mortality, risk of severe disease was independently associated with age (aOR, 1.17 for each decade increase; 95% CI, 1.00–1.37), male sex (aOR, 2.34; 95% CI, 1.54–3.60), and cardiovascular disease (aOR, 1.77; 95% CI, 1.09–2.85).
Conclusions:
In an adjusted multivariate analysis, advanced age, male sex, and cardiovascular disease increased risk of severe disease and mortality in patients with COVID-19 in the Southeast United States. In-hospital mortality risk doubled with each subsequent decade of life.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Background. This paper examines genetic and environmental contributions to risk of cannabis dependence.
Method. Symptoms of cannabis dependence and measures of social, family and individual risk factors were assessed in a sample of 6265 young adult male and female Australian twins born 1964–1971.
Results. Symptoms of cannabis dependence were common: 11·0% of sample (15·1% of men and 7·8% of women) reported two or more symptoms of dependence. Correlates of cannabis dependence included educational attainment, exposure to parental conflict, sexual abuse, major depression, social anxiety and childhood conduct disorder. However, even after control for the effects of these factors, there was evidence of significant genetic effects on risk of cannabis dependence. Standard genetic modelling indicated that 44·7% (95% CI = 15–72·2) of the variance in liability to cannabis dependence could be accounted for by genetic factors, 20·1% (95% CI = 0–43·6) could be attributed to shared environment factors and 35·3% (95% CI = 26·4–45·7) could be attributed to non-shared environmental factors. However, while there was no evidence of significant gender differences in the magnitude of genetic and environmental influences, a model which assumed both genetic and shared environmental influences on risks of cannabis dependence among men and shared environmental but no genetic influences among women provided an equally good fit to the data.
Conclusions. There was consistent evidence that genetic risk factors are important determinants of risk of cannabis dependence among men. However, it remains uncertain whether there are genetic influences on liability to cannabis dependence among women.
Scholars attribute the growth and decline of Classic period (AD 200–900) settlements in the semi-arid northern frontier zone of Mesoamerica to rainfall cycles that controlled the extent of arable land. However, there is little empirical evidence to support this claim. We present phytolith, organic carbon, and magnetic susceptibility analyses of a 4000-yr alluvial record of climate and human land use from the Malpaso Valley, the site of one such Classic frontier community. The earliest farming occupation is detected around 500 BC and appears related to a slight increase of aridity, similar to the level of the modern day valley. By AD 500, the valley's Classic period Mesoamerican settlements were founded under these same dry conditions, which continued into the Postclassic period. This indicates that the La Quemada occupation did not develop during a period of increased rainfall, but rather an arid phase. The most dramatic changes detected in the valley resulted from the erosion associated with Spanish Colonial grazing and deforestation that began in the 16th century. The landscape of the modern Malpaso Valley is thus primarily the product of a series of intense and rapid transformations that were concentrated within the last 400 yr.
We present an overview of the survey for radio emission from active stars that has been in progress for the last six years using the observatories at Fleurs, Molonglo, Parkes and Tidbinbilla. The role of complementary optical observations at the Anglo-Australian Observatory, Mount Burnett, Mount Stromlo and Siding Spring Observatories and Mount Tamborine are also outlined. We describe the different types of star that have been included in our survey and discuss some of the problems in making the radio observations.
Childhood maltreatment (CM) has consistently been linked with adverse outcomes including substance use disorders and adult sexual revictimization. Adult sexual victimization itself has been linked with psychopathology but has predominately been studied in women. The current investigation examines the impact of CM and co-occurring psychopathology on adult sexual victimization in men and women, replicating findings in three distinct samples.
Method
We investigated the association between continuous CM factor scores and adult sexual victimization in the Childhood Trauma Study (CTS) sample (N = 2564). We also examined the unique relationship between childhood sexual abuse (CSA) and adult sexual victimization while adjusting for co-occurring substance dependence and psychopathology. We replicated these analyses in two additional samples: the Comorbidity and Trauma Study (CATS; N = 1981) and the Australian Twin-Family Study of Alcohol Use Disorders (OZ-ALC; N = 1537).
Results
Analyses revealed a significant association with CM factor scores and adult sexual victimization for both men and women across all three samples. The CSA factor score was strongly associated with adult sexual victimization after adjusting for substance dependence and psychopathology; higher odds ratios were observed in men (than women) consistently across the three samples.
Conclusions
A continuous measure of CSA is independently associated with adult sexual trauma risk across samples in models that included commonly associated substance dependence and psychopathology as covariates. The strength of the association between this CSA measure and adult sexual victimization is higher in magnitude for men than women, pointing to the need for further investigation of sexual victimization in male community samples.
Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses.
Method.
Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24–37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder.
Results.
Additive genetic (a2 = 0.48–0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a2 = 0.39) and shared environmental (c2 = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38–0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40–73% of the genetic variance per substance.
Conclusions.
Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols.
We present multidimensional modeling of convection and oscillations in main-sequence stars somewhat more massive than the Sun, using three separate approaches: 1) Using the 3-D planar StellarBox radiation hydrodynamics code to model the envelope convection zone and part of the radiative zone. Our goals are to examine the interaction of stellar pulsations with turbulent convection in the envelope, excitation of acoustic modes, and the role of convective overshooting; 2) Applying the spherical 3-D MHD ASH (Anelastic Spherical Harmonics) code to simulate the core convection and radiative zone. Our goal is to determine whether core convection can excite low-frequency gravity modes, and thereby explain the presence of low frequencies for some hybrid γ Dor/δ Sct variables for which the envelope convection zone is too shallow for the convective blocking mechanism to drive gravity modes; 3) Applying the ROTORC 2-D stellar evolution and dynamics code to calculate evolution with a variety of initial rotation rates and extents of core convective overshooting. The nonradial adiabatic pulsation frequencies of these nonspherical models are calculated using the 2-D pulsation code NRO. We present new insights into pulsations of 1-2 M⊙ stars gained by multidimensional modeling.