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School connectedness, a construct indexing supportive school relationships, has been posited to promote resilience to environmental adversity. Consistent with prominent calls in the field, we examined the protective nature of school connectedness against two dimensions of early adversity that index multiple levels of environmental exposure (violence exposure, social deprivation) when predicting both positive and negative outcomes in longitudinal data from 3,246 youth in the Fragile Families and Child Wellbeing Study (48% female, 49% African American). Child and adolescent school connectedness were promotive, even when accounting for the detrimental effects of early adversity. Additionally, childhood school connectedness had a protective but reactive association with social deprivation, but not violence exposure, when predicting externalizing symptoms and positive function. Specifically, school connectedness was protective against the negative effects of social deprivation, but the effect diminished as social deprivation became more extreme. These results suggest that social relationships at school may compensate for low levels of social support in the home and neighborhood. Our results highlight the important role that the school environment can play for youth who have been exposed to adversity in other areas of their lives and suggest specific groups that may especially benefit from interventions that boost school connectedness.
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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
SARS-CoV-2, which causes the disease COVID-19, generally has a mild disease course in children. However, a severe post-infectious inflammatory process known as multisystem inflammatory syndrome in children has been observed in association with COVID-19. This inflammatory process is a result of an abnormal immune response with similar clinical features to Kawasaki disease. It is well established that multisystem inflammatory syndrome in children is associated with myocardial dysfunction, coronary artery dilation or aneurysms, and occasionally arrhythmias. The most common electrocardiographic abnormalities seen include premature atrial or ventricular ectopy, variable degrees of atrioventricular block, and QTc prolongation, and rarely, haemodynamically significant arrhythmias necessitating extracorporeal membrane oxygenation support. However, presentation with fever, hypotension, and relative bradycardia with a left axis idioventricular rhythm has not been previously reported. We present a case of a young adolescent with multisystem inflammatory syndrome in children with myocarditis and a profoundly inappropriate sinus node response to shock with complete resolution following intravenous immunoglobulin.
ABSTRACT IMPACT: Understanding dietary patterns and nutrient intakes of the aging population may help address concerns and dietary guidelines regarding their nutritional needs. OBJECTIVES/GOALS: The objective of this study is to test the hypothesis that a healthy dietary pattern in the oldest old (aged 80 years and older) is related to greater compliance with dietary recommendations and better nutrient intake profiles. METHODS/STUDY POPULATION: We conducted a cross-sectional study of 122 participants aged 82 to 97 years old from the Geisinger Rural Aging Study (GRAS) cohort in rural Pennsylvania (n = 56 men and 66 women). The main outcome measures of the investigation were the daily nutrient intakes and food group intakes evaluated from the average of three 24-hour dietary recalls. The dietary patterns were determined by cluster analysis from 28 food groups. Diet quality and adherence to the Dietary Guidelines for Americans was assessed by the Healthy Eating Index (HEI)-2015 and the Dietary Screening Tool (DST). Recommended intakes were determined by the Recommended Dietary Allowances (RDAs) or Adequate Intakes (AIs). RESULTS/ANTICIPATED RESULTS: Less than 50% of participants met the dietary recommended intakes for vitamins D, E, K, B6, dietary fiber, zinc, potassium, and calcium. The more-nutrient-dense cluster was characterized by higher intakes of fruits and vegetables. The less-nutrient-dense cluster was characterized by higher intakes of foods including desserts and sweets. After adjusting for age, sex, and energy intake, participants in the more-nutrient-dense dietary pattern had a higher intake of vitamins A, D, K, C, fiber, and potassium (p < 0.05 for all). After adjusting for age and sex, participants in the more-nutrient-dense pattern had better diet quality assessed by the (HEI)-2015 (p < 0.001) and DST (p = 0.006). DISCUSSION/SIGNIFICANCE OF FINDINGS: Among the oldest old, many participants were found to have nutrient intakes lower than the recommended levels for fundamental nutrients suggesting that dietary guidance in addition to a dietary pattern more aligned with dietary guidelines may be beneficial for supporting healthy aging.
To examine associations between diet and risk of developing gastro-oesophageal reflux disease (GERD).
Prospective cohort with a median follow-up of 15·8 years. Baseline diet was measured using a FFQ. GERD was defined as self-reported current or history of daily heartburn or acid regurgitation beginning at least 2 years after baseline. Sex-specific logistic regressions were performed to estimate OR for GERD associated with diet quality scores and intakes of nutrients, food groups and individual foods and beverages. The effect of substituting saturated fat for monounsaturated or polyunsaturated fat on GERD risk was examined.
A cohort of 20 926 participants (62 % women) aged 40–59 years at recruitment between 1990 and 1994.
For men, total fat intake was associated with increased risk of GERD (OR 1·05 per 5 g/d; 95 % CI 1·01, 1·09; P = 0·016), whereas total carbohydrate (OR 0·89 per 30 g/d; 95 % CI 0·82, 0·98; P = 0·010) and starch intakes (OR 0·84 per 30 g/d; 95 % CI 0·75, 0·94; P = 0·005) were associated with reduced risk. Nutrients were not associated with risk for women. For both sexes, substituting saturated fat for polyunsaturated or monounsaturated fat did not change risk. For both sexes, fish, chicken, cruciferous vegetables and carbonated beverages were associated with increased risk, whereas total fruit and citrus were associated with reduced risk. No association was observed with diet quality scores.
Diet is a possible risk factor for GERD, but food considered as triggers of GERD symptoms might not necessarily contribute to disease development. Potential differential associations for men and women warrant further investigation.
In this article the erratic coupling that can occur in screeching supersonic twin jets is characterised. Non-stationary acoustic analysis is used to investigate the temporal behaviour of the coupling phenomena. The results show that where the phase between the jets is time varying, the screech tone experiences interruptions. The interruptions are either correlated and experienced by both jets or are anti-correlated and only by one. During the anti-correlated interruption, the uninterrupted jet screeches as an isolated jet. The instantaneous velocity field shows that for the majority of snapshots during an acoustic interruption, the jets do not exhibit a coupled oscillation. When the jets are uninterrupted, they are oscillating in either a coupled symmetric or anti-symmetric mode. This behaviour manifests at a condition between two operating points characterised by different coupling modes. It suggests the interruptions arise due to a competition between two global modes of the flow. Despite the existence of multiple acoustic tones in the region where these modes are competing, analysis of the individual jets reveals energetic structures with only a single wavelength. It is found that jets whose own oscillation is characterised by a single wavelength can, through coupling either symmetrically or anti-symmetrically about their symmetry plane, produce different acoustic tones. These findings are consistent across three experimental facilities. The observed modes are a function of the jet spacing and nozzle pressure, therefore future studies investigating other spacings must recharacterise the encountered coupled modes. This article provides the signatures to characterise the behaviour for future studies.
The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.
This paper discusses the evidence for periodic human activity in the Cairngorm Mountains of Scotland from the late 9th millennium to the early 4th millennium cal bc. While contemporary paradigms for Mesolithic Europe acknowledge the significance of upland environments, the archaeological record for these areas is not yet as robust as that for the lowland zone. Results of excavation at Chest of Dee, along the headwaters of the River Dee, are set into a wider context with previously published excavations in the area. A variety of site types evidences a sophisticated relationship between people and a dynamic landscape through a period of changing climate. Archaeological benefits of the project include the ability to examine novel aspects of the archaeology leading to a more comprehensive understanding of Mesolithic lifeways. It also offers important lessons in site survival, archaeological investigation, and the management of the upland zone.
Bipolar disorder (BD) is a familial psychiatric disorder associated with frontotemporal and subcortical brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about structural brain trajectories in those at risk.
Neuroimaging was conducted at baseline and at 2-year follow-up interval in 90 high-risk individuals with a first-degree BD relative (HR), and 56 participants with no family history of mental illness who could have non-BD diagnoses. All 146 subjects were aged 12–30 years at baseline. We examined longitudinal change in gray and white matter volume, cortical thickness, and surface area in the frontotemporal cortex and subcortical regions.
Compared to controls, HR participants showed accelerated cortical thinning and volume reduction in right lateralised frontal regions, including the inferior frontal gyrus, lateral orbitofrontal cortex, frontal pole and rostral middle frontal gyrus. Independent of time, the HR group had greater cortical thickness in the left caudal anterior cingulate cortex, larger volume in the right medial orbitofrontal cortex and greater area of right accumbens, compared to controls. This pattern was evident even in those without the new onset of psychopathology during the inter-scan interval.
This study suggests that differences previously observed in BD are developing prior to the onset of the disorder. The pattern of pathological acceleration of cortical thinning is likely consistent with a disturbance of molecular mechanisms responsible for normal cortical thinning. We also demonstrate that neuroanatomical differences in HR individuals may be progressive in some regions and stable in others.
To examine the global burden, associated point sources, and successful prevention and control measures for documented outbreaks of Burkholderia cepacia healthcare-associated infections (HAIs).
A review of all outbreaks of Burkholderia cepacia HAIs published in the peer-reviewed literature between January 1970 and October 2019 was conducted to identify the global burden, associated point sources, and successful prevention and control measures using the Guidelines for Outbreak Reports and Intervention Studies of Nosocomial Infections (ORION).
In total, we reviewed 125 documented outbreaks of Burkholderia cepacia–related HAIs worldwide. The reported B. cepacia HAIs for this period involved 3,287 patients. The point sources were identified in most outbreaks of B. cepacia HAIs (n = 93; 74.4%); they included medication vials, disinfectants, and antiseptics. Moreover, 95 of the outbreak reports (76%) described effective prevention and control measures, but only 33 reports indicated the use of a combination of environment-, patient- and staff-related measures. None of the outbreak reports used the ORION guidelines.
Outbreaks of Burkholderia cepacia HAIs are an ongoing challenge. They are often associated with immunocompromised patients who acquire the infection from exposure to contaminated medications, products, and equipment. These outbreaks are not infrequent, and a range of infection prevention and control measures have been effective in arresting spread. The use of ORION guidelines for outbreak reporting would improve the quality of information and data to generate evidence for translation into practice.
Twenty-four new optically stimulated luminescence (OSL) and radiocarbon ages from sediment cores in nine lakes associated with the Shipshewana and Sturgis moraines in northern Indiana and southern Michigan estimate when recession of the Saginaw Lobe of the Laurentide Ice Sheet was underway in the southern Great Lakes region, USA. Average OSL ages of 23.4 ± 2.2 ka for the Shipshewana Moraine and 19.7 ± 2.2 ka for the Sturgis Moraine are considered minimum limiting deglacial ages for these recessional moraines. The much younger radiocarbon ages are consistent with other regional radiocarbon ages from lakes, and record climate amelioration around ~16.5 cal ka BP. Early recession of the interlobate Saginaw Lobe was well underway by 23.4 ± 2.2 ka, when the adjacent Lake Michigan and Huron-Erie lobes were a few hundred kilometers farther south and near their maximum southerly limits. The results provide the first time constraints when sediment from the Lake Michigan and Huron-Erie lobes began filling the accommodation space left by the Saginaw Lobe. The difference between the oldest radiocarbon and OSL age is 7400 yr for the Shipshewana Moraine and 3400 yr for the Sturgis Moraine.
Antidepressants are amongst the most commonly prescribed classes of drugs and their use continues to grow. Adverse outcomes are part of the landscape in prescribing medications and therefore management of safety issues need to be an integral part of practice.
We have developed consensus guidelines for safety monitoring with antidepressant treatments.
To present an overview of screening and safety considerations for pharmacotherapy of clinical depressive disorders and make recommendations for safety monitoring.
Data were sourced by a literature search using Medline and a manual search of scientific journals to identify relevant articles. Draft guidelines were prepared and serially revised in an iterative manner until all co-authors gave final approval of content.
A guidelines document was produced after approval by all 19 co-authors. The final document gives guidance on; the decision to treat, baseline screening prior to commencement of treatment, and ongoing monitoring during antidepressant treatment. The guidelines state or reference screening protocols that may detect medical causes of depression as well as screening and monitoring protocols to investigate specific adverse effects associated with antidepressant treatments that may be reduced or identified earlier by baseline screening and agent-specific monitoring after commencing treatment.
The implementation of safety monitoring guidelines for treatment of clinical depression may significantly improve outcome, by improving a patient's overall physical health status.
The present study aims to investigate the effect of wholegrain and legume consumption on the incidence of age-related cataract in an older Australian population-based cohort. The Blue Mountains Eye Study (BMES) is a population-based cohort study of eye diseases among older adults aged 49 years or older (1992–1994, n 3654). Of 2334 participants of the second examination of the BMES (BMES 2, 1997–2000), 1541 (78·3 % of survivors) were examined 5 years later (BMES 3) who had wholegrain and legume consumption estimated from the FFQ at BMES 2. Cataract was assessed using photographs taken during examinations following the Wisconsin cataract grading system. Multivariable-adjusted logistic regression models were used to assess associations with the 5-year incidence of cataract from BMES 2 (baseline) to BMES 3. The 5-year incidence of cortical, nuclear and posterior subcapsular (PSC) cataract was 18·2, 16·5 and 5·9 %, respectively. After adjustment for age, sex and other factors, total wholegrain consumption at baseline was not associated with incidence of any type of cataract. High consumption of legumes showed a protective association for incident PSC cataract (5th quintile: adjusted OR 0·37; 95 % CI 0·15, 0·92). There was no significant trend of this association across quintiles (P = 0·08). In this older Australian population, we found no associations between wholegrain intake at baseline and the 5-year incidence of three cataract types. However, intake of legumes in the highest quintile, compared with the lowest quintile, may protect against PSC formation, a finding needing replication in other studies.
Worldwide, there is a trend towards increased herd sizes, and the animal-to-stockman ratio is increasing within the beef and dairy sectors; thus, the time available to monitoring individual animals is reducing. The behaviour of cows is known to change in the hours prior to parturition, for example, less time ruminating and eating and increased activity level and tail-raise events. These behaviours can be monitored non-invasively using animal-mounted sensors. Thus, behavioural traits are ideal variables for the prediction of calving. This study explored the potential of two sensor technologies for their capabilities in predicting when calf expulsion should be expected. Two trials were conducted at separate locations: (i) beef cows (n = 144) and (ii) dairy cows (n = 110). Two sensors were deployed on each cow: (1) Afimilk Silent Herdsman (SHM) collars monitoring time spent ruminating (RUM), eating (EAT) and the relative activity level (ACT) of the cow, and (2) tail-mounted Axivity accelerometers to detect tail-raise events (TAIL). The exact time the calf was expelled from the cow was determined by viewing closed-circuit television camera footage. Machine learning random forest algorithms were developed to predict when calf expulsion should be expected using single-sensor variables and by integrating multiple-sensor data-streams. The performance of the models was tested using the Matthew’s correlation coefficient (MCC), the area under the curve, and the sensitivity and specificity of predictions. The TAIL model was slightly better at predicting calving within a 5-h window for beef cows (MCC = 0.31) than for dairy cows (MCC = 0.29). The TAIL + RUM + EAT models were equally as good at predicting calving within a 5-h window for beef and dairy cows (MCC = 0.32 for both models). Combining data-streams from SHM and tail sensors did not substantially improve model performance over tail sensors alone; therefore, hour-by-hour algorithms for the prediction of time of calf expulsion were developed using tail sensor data. Optimal classification occurred at 2 h prior to calving for both beef (MCC = 0.29) and dairy cows (MCC = 0.25). This study showed that tail sensors alone are adequate for the prediction of parturition and that the optimal time for prediction is 2 h before expulsion of the calf.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
The late Miocene is a time of strong environmental change in SW Asia. Himalayan foreland stable isotope data show a shift in the dominant vegetation of the flood plains away from trees and shrubs towards more C4 grasslands at a time when oceanic upwelling increased along the Oman margin. We present integrated geochemical and colour spectral records from International Ocean Discovery Program Site U1456 in the eastern Arabian Sea to reconstruct changing chemical weathering and erosion, as well as relative humidity during this climatic transition. Increasing hematite/goethite ratios derived from spectral data are consistent with long-term drying after c. 7.7 Ma. Times of dry conditions are largely associated with weaker chemical alteration measured by K/Rb and reduced coarse clastic flux, constrained by Si/Al and Zr/Al. A temporary phase of increased humidity from 6.3 to 5.95 Ma shows a reversal to stronger weathering and erosion. Wetter conditions can result in both more and less alteration due to the nonlinear relationship between weathering rates, precipitation and sediment transport times. Trends in relative aridity do not follow existing palaeoceanographic records and are not apparently linked to changes in Tibetan or Himalayan elevation, but more closely correlate with global cooling. An apparent opposing trend in the humidity evolution in the Indus compared to southern China, as tracked by spectrally estimated hematite/goethite, likely reflects differences in the topography in the Indus compared to the Pearl River drainage basins, as well as the generally wetter climate in southern China.
The aim of the 25 and Up (25Up) study was to assess a wide range of psychological and behavioral risk factors behind mental illness in a large cohort of Australian twins and their non-twin siblings. Participants had already been studied longitudinally from the age of 12 and most recently in the 19Up study (mean age = 26.1 years, SD = 4.1, range = 20–39). This subsequent wave follows up these twins several years later in life (mean age = 29.7 years, SD = 2.2, range = 22–44). The resulting data set enables additional detailed investigations of genetic pathways underlying psychiatric illnesses in the Brisbane Longitudinal Twin Study (BLTS). Data were collected between 2016 and 2018 from 2540 twins and their non-twin siblings (59% female, including 341 monozygotic complete twin-pairs, 415 dizygotic complete pairs and 1028 non-twin siblings and singletons). Participants were from South-East Queensland, Australia, and the sample was of predominantly European ancestry. The 25Up study collected information on 20 different mental disorders, including depression, anxiety, substance use, psychosis, bipolar and attention-deficit hyper-activity disorder, as well as general demographic information such as occupation, education level, number of children, self-perceived IQ and household environment. In this article, we describe the prevalence, comorbidities and age of onset for all 20 examined disorders. The 25Up study also assessed general and physical health, including physical activity, sleep patterns, eating behaviors, baldness, acne, migraines and allergies, as well as psychosocial items such as suicidality, perceived stress, loneliness, aggression, sleep–wake cycle, sexual identity and preferences, technology and internet use, traumatic life events, gambling and cyberbullying. In addition, 25Up assessed female health traits such as morning sickness, breastfeeding and endometriosis. Furthermore, given that the 25Up study is an extension of previous BLTS studies, 86% of participants have already been genotyped. This rich resource will enable the assessment of epidemiological risk factors, as well as the heritability and genetic correlations of mental conditions.
Background: Observational studies have reported an association between childhood obesity and a higher risk of multiple sclerosis (MS). However, the difficulties to fully account for confounding and long recall periods make causal inference from these studies challenging. The objective of this study was to assess the contribution of childhood obesity to the development of MS through Mendelian randomization, which uses genetic associations to minimize the risk of confounding. Methods: We selected 23 independent genetic variants strongly associated with childhood body mass index (BMI) in a genome-wide association study (GWAS) which included 47,541 children. The corresponding effects of these variants on risk of MS were obtained from a GWAS of 14,802 MS cases and 26,703 controls. Standard two-sample Mendelian randomization methods were performed, with additional sensitivity analyses to assess the likelihood of bias from genetic pleiotropy. Results: The inverse-variance weighted MR analysis revealed that one standard deviation increase in childhood BMI increased odds of MS by 26% (odds ratio=1.26, 95% confidence interval 1.10-1.45, p=0.001). There was no significant heterogeneity across the individual estimates. Sensitivity analyses were consistent with the main findings and provided no evidence of pleiotropy. Conclusions: This study provides genetic support of a role for increased childhood BMI in the development of MS.