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Maladaptive offspring emotion regulation has been identified as one pathway linking maternal and child psychological well-being in school-aged children. Whether such a pathway is present earlier in life still remains unclear. The present study investigated the role of preschoolers’ emotion reactivity and regulation in the association between maternal psychological distress and child internalizing and externalizing problems. Children’s emotion reactivity and regulation were assessed through both observed behavior and physiology. At 42 months of age, children (n = 251; 128 girls) completed a fear induction task during which their heart-rate variability was assessed and their behavior was monitored, and maternal self-reports on depressive mood and anxiety were collected. At 48 months mothers and fathers reported on their children’s internalizing and externalizing problems. Higher maternal depressive mood was associated with lower child fear-related reactivity and regulation, as indexed by heart-rate variability. The latter mediated the association between higher maternal depressive mood and higher preschoolers’ externalizing problems. Overall, our findings support the role of preschoolers’ emotion reactivity and regulation in the relationship between maternal psychological distress and children’s socio-emotional difficulties. This role may also depend on the discrete emotion to which children react or seek to regulate as, here, we only assessed fear-related reactivity and regulation.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with its impact on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behaviour and, therefore, the risk of contracting the virus.
We examined overlapping genetic underpinnings between major psychiatric disorders, personality traits and susceptibility to SARS-CoV-2 infection.
Linkage disequilibrium score regression was used to explore the genetic correlations of coronavirus disease 2019 (COVID-19) susceptibility with psychiatric disorders and personality traits based on data from the largest available respective genome-wide association studies (GWAS). In two cohorts (the PsyCourse (n = 1346) and the HeiDE (n = 3266) study), polygenic risk scores were used to analyse if a genetic association between, psychiatric disorders, personality traits and COVID-19 susceptibility exists in individual-level data.
We observed no significant genetic correlations of COVID-19 susceptibility with psychiatric disorders. For personality traits, there was a significant genetic correlation for COVID-19 susceptibility with extraversion (P = 1.47 × 10−5; genetic correlation 0.284). Yet, this was not reflected in individual-level data from the PsyCourse and HeiDE studies.
We identified no significant correlation between genetic risk factors for severe psychiatric disorders and genetic risk for COVID-19 susceptibility. Among the personality traits, extraversion showed evidence for a positive genetic association with COVID-19 susceptibility, in one but not in another setting. Overall, these findings highlight a complex contribution of genetic and non-genetic components in the interaction between COVID-19 susceptibility and personality traits or mental disorders.
Pneumatic launch systems for Unmanned Aerial Vehicles (UAVs), including mechanical and pneumatic systems, are complex and non-linear. They are subjected to system parameters during launch, which leads to difficulty in engineering research analysis. For example, the mismatch between the UAV parameters and the parameter design indices of the launch system as well as the unclear design indices of the launching speed and overload of UAVs have a great impact on launch safety. Considering this situation, some studies are presented in this paper. Taking the pneumatic launch system as a research object, a pneumatic launcher dynamic simulation model is built based on co-simulation considering the coupling characteristics of the mechanical structure and transmission system. Its accuracy was verified by laboratory test results. Based on this model, the paper shows the effects of the key parameters, including the mass of the UAV, cylinder volume, pressure and moment of inertia of the pulley block, on the performance of the dynamic characteristics of the launch process. Then, a method for matching the parameter characteristics between the UAV and launch system based on batch simulation is proposed. The set of matching parameter values of the UAV and launch system that satisfy the launch take-off safety criteria are calculated. Finally, the influence of the system parameters of the launch process on the launch performance was analysed in detail, and the design optimised. Meaningful conclusions were obtained. The analysis method and its results can provide a reference for engineering and theoretical research and development of pneumatic launch systems.
The objective of this study was to investigate changes in serum biomarkers of acute brain injury, including white matter and astrocyte injury during chronic foetal hypoxaemia. We have previously shown histopathological changes in myelination and neuronal density in fetuses with chronic foetal hypoxaemia at a level consistent with CHD.
Mid-gestation foetal sheep (110 ± 3 days gestation) were cannulated and attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile fluid environment mimicking the intrauterine environment. Fetuses were maintained with an oxygen delivery of 20–25 ml/kg/min (normoxemia) or 14–16 ml/kg/min (hypoxaemia). Myelin Basic Protein and Glial Fibrillary Acidic Protein serum levels in the two groups were assessed by ELISA at baseline and at 7, 14, and 21 days of support.
Based on overlapping 95% confidence intervals, there were no statistically significant differences in either Myelin Basic Protein or Glial Fibrillary Acidic Protein serum levels between the normoxemic and hypoxemic groups, at any time point. No statistically significant correlations were observed between oxygen delivery and levels of Myelin Basic Protein and Glial Fibrillary Acidic Protein.
Chronic foetal hypoxaemia during mid-gestation is not associated with elevated serum levels of acute white matter (Myelin Basic Protein) or astrocyte injury (Glial Fibrillary Acidic Protein), in this model. In conjunction with our previously reported findings, our data support the hypothesis that the brain dysmaturity with impaired myelination found in fetuses with chronic hypoxaemia is caused by disruption of normal developmental pathways rather than by direct cellular injury.
A study of 1,558 US households in June 2020 evaluated utilization of online grocery shopping during the COVID-19 pandemic, influences on utilization, and plans for future online grocery shopping. Nearly 55 percent of respondents shopped online in June 2020; 20 percent were first-timers. Cragg model estimates showed influences on online shopping likelihood and frequency included demographics, employment, and prior online shopping. Illness concerns increased likelihood, while food shortage concerns increased frequency of online shopping. A multinomial probit suggested 58 percent respondents planned to continue online grocery shopping regardless of pandemic conditions.
New Zealand has a strategy of eliminating SARS-CoV-2 that has resulted in a low incidence of reported coronavirus-19 disease (COVID-19). The aim of this study was to describe the spread of SARS-CoV-2 in New Zealand via a nationwide serosurvey of blood donors. Samples (n = 9806) were collected over a month-long period (3 December 2020–6 January 2021) from donors aged 16–88 years. The sample population was geographically spread, covering 16 of 20 district health board regions. A series of Spike-based immunoassays were utilised, and the serological testing algorithm was optimised for specificity given New Zealand is a low prevalence setting. Eighteen samples were seropositive for SARS-CoV-2 antibodies, six of which were retrospectively matched to previously confirmed COVID-19 cases. A further four were from donors that travelled to settings with a high risk of SARS-CoV-2 exposure, suggesting likely infection outside New Zealand. The remaining eight seropositive samples were from seven different district health regions for a true seroprevalence estimate, adjusted for test sensitivity and specificity, of 0.103% (95% confidence interval, 0.09–0.12%). The very low seroprevalence is consistent with limited undetected community transmission and provides robust, serological evidence to support New Zealand's successful elimination strategy for COVID-19.
Stratospheric airships are lighter-than-air vehicles that work at an altitude of 20km in the lower calm portion of the stratosphere. They can be used as real-time surveillance platforms for environment monitoring and civil communication. Solar energy is the ideal power choice for long-endurance stratospheric airships. Attitude control is important for airships so that they can point at a target for observation or adjust the attitude to improve the output performance of solar panels. Stratospheric airships have a large volume and semi-flexible structure. The typical actuators used are aerodynamic surfaces, vectored thrust and ballonets. However, not all these actuators can work well under special working conditions, such as low density and low speed. In this study, moving-mass control is introduced to stratospheric airships because its control efficiency is independent of airspeed and atmospheric density. A nonlinear feedback controller based on generalised inverse with a nonlinear mapping module is designed to implement moving-mass control. Such a new station keeping scheme with moving masses is proposed for airships with different working situations.
Abstract: Responsible supply chain is about ensuring that members of the supply chain act responsibly for the well-being of all people and Mother Earth. It involves both the environmental responsibility side and the social responsibility side. On top of this, responsibility also entails ensuring that products sold to consumers are authentic without having been adulterated, and that the processes throughout the supply chain are run in an ethical manner. Although interests in and concerns over responsibility by the general public, governments, and companies have continued to increase, the problems of controlling violations and noncompliance with responsibility standards remain daunting. This chapter uses a “sense” and “respond” lens to look at how such problems can be addressed. We describe some of the innovative ways that some leading companies have used to make progress.
The study aims to investigate attention deficit hyperactivity disorder (ADHD) symptoms, gastrointestinal (GI) symptoms, comorbid psychopathology and behaviour problems in children and adolescents with autism spectrum disorder (ASD).
Parents of 147 children and adolescents with ASD aged 6–18 years completed the Conners 3 Parent-Short Form, Gastrointestinal Symptom Inventory, Behavior Problems Inventory-Short Form and Autism Spectrum Disorder-Comorbid for Children.
Fifty-six per cent of children and adolescents had a comorbid diagnosis of ADHD, yet over 70% presented with clinically significant ADHD symptoms. Forty per cent of participants received a diagnosis of ADHD before ASD and 25.6% received a diagnosis of ASD first. Relationships were found between ADHD symptoms and comorbid psychopathology, GI symptoms, and behaviour problems.
The outcomes suggest that ADHD is being underestimated as a comorbid disorder of ASD. This may have implications on treatment and interventions for children and adolescents who have a diagnosis of both ASD and ADHD.
Sleep problems are common among children with autism spectrum disorder (ASD) and can have a negative impact on the child’s behaviour and daytime functioning. The current pilot study examined objective measurements of child and parent sleep as factors associated with the stress, anxiety, depressive symptoms, social support and quality of life of parents of children with ASD.
Participants were nine children with ASD and their parents (nine mothers and three fathers). Participants wore an actigraph for 7 consecutive days and nights. Measures of sleep habits and quality were used to ascertain child and parent sleep. Measures of parenting stress, anxiety, depressive symptoms, quality of life and social support were collated.
Results indicated the emergence of high parental stress, anxiety and depressive symptoms. Significant correlations were observed between parent depressive symptoms, and both subjective sleep quality and child sleep disruptions.
The present study found that parental well-being is affected by child sleep problems.
Emergency Medical Services (EMS) providers are trained to place endotracheal tubes (ETTs) in the prehospital setting when indicated. Endotracheal tube cuffs are traditionally inflated with 10cc of air to provide adequate seal against the tracheal lumen. There is literature suggesting that many ETTs are inflated well beyond the accepted safe pressures of 20-30cmH2O, leading to potential complications including ischemia, necrosis, scarring, and stenosis of the tracheal wall. Currently, EMS providers do not routinely check ETT cuff pressures. It was hypothesized that the average ETT cuff pressure of patients arriving at the study site who were intubated by EMS exceeds the safe pressure range of 20-30cmH2O.
While ETT cuff inflation is necessary to close the respiratory system, thus preventing air leaks and aspiration, there is evidence to suggest that over-inflated ETT cuffs can cause long-term complications. The purpose of this study is to characterize the cuff pressures of ETTs placed by EMS providers.
This project was a single center, prospective observational study. Endotracheal tube cuff pressures were measured and recorded for adult patients intubated by EMS providers prior to arrival at a large, urban, tertiary care center over a nine-month period. All data were collected by respiratory therapists utilizing a cuff pressure measurement device which had a detectable range of 0-100cmH2O and was designed as a syringe. Results including basic patient demographics, cuff pressure, tube size, and EMS service were recorded.
In total, 45 measurements from six EMS services were included with ETT sizes ranging from 6.5-8.0mm. Mean patient age was 52.2 years (67.7% male). Mean cuff pressure was 81.8cmH2O with a range of 15 to 100 and a median of 100. The mode was 100cmH2O; 40 out of 45 (88.9%) cuff pressures were above 30cmH2O. Linear regression showed no correlation between age and ETT cuff pressure or between ETT size and cuff pressure. Two-tailed T tests did not show a significant difference in the mean cuff pressure between female versus male patients.
An overwhelming majority of prehospital intubations are associated with elevated cuff pressures, and cuff pressure monitoring education is indicated to address this phenomenon.
Case identification is an ongoing issue for the COVID-19 epidemic, in particular for outpatient care where physicians must decide which patients to prioritise for further testing. This paper reports tools to classify patients based on symptom profiles based on 236 severe acute respiratory syndrome coronavirus 2 positive cases and 564 controls, accounting for the time course of illness using generalised multivariate logistic regression. Significant symptoms included abdominal pain, cough, diarrhoea, fever, headache, muscle ache, runny nose, sore throat, temperature between 37.5 and 37.9 °C and temperature above 38 °C, but their importance varied by day of illness at assessment. With a high percentile threshold for specificity at 0.95, the baseline model had reasonable sensitivity at 0.67. To further evaluate accuracy of model predictions, leave-one-out cross-validation confirmed high classification accuracy with an area under the receiver operating characteristic curve of 0.92. For the baseline model, sensitivity decreased to 0.56. External validation datasets reported similar result. Our study provides a tool to discern COVID-19 patients from controls using symptoms and day from illness onset with good predictive performance. It could be considered as a framework to complement laboratory testing in order to differentiate COVID-19 from other patients presenting with acute symptoms in outpatient care.
Short stature may reflect health in early life and be an enduring disability. How birth weight, gender, household, elementary schooling and diet play a role in associations between stature and overall school competence (OSC) have been assessed.
The 2001–2002 Nutrition and Health Survey in Taiwan (NAHSIT) for elementary schoolchildren (n 2274, 52·1 % boys) was linked to birth records. It provided sociodemographic, dietary quality, body compositional and school performance (as Scale for Assessing Emotional Disturbance, SAED; OSC as an SAED subscale) data. Lower birth weight was ≤15th percentile: 2850 g for boys and 2700 g for girls, and stature as z-scores for Taiwanese. Multivariable linear regression was used for relationships between OSC and stature. Trends in OSC by stature and school grade were assessed.
The 2001–2002 NAHSIT for elementary schoolchildren.
Totally, 2274 schoolchildren aged 6–13 years.
Compared to normal height (−2< height for age z-score (HAZ) <2), shorter girls (HAZ ≤ −2) had a lower OSC (8·87 v. 10·5, P < 0·05) and taller girls (HAZ ≥ 2) had a better OSC (12·3 v. 10·5, P < 0·001). Maternal education and household income each contributed more than 5 % of OSC variance. OSC and HAZ among girls were positively associated and emotional disturbance negatively associated. Shortness-associated lower OSC underwent remediation with advancing school grade. Stature and OSC were not evidently related in boys.
Shorter stature can compromise OSC among school girls. The major determinants in shorter girls are less household income and limited parental education.
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) led to a significant disease burden and disruptions in health systems. We describe the epidemiology and transmission characteristics of early coronavirus disease 2019 (COVID-19) cases in Bavaria, Germany. Cases were reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections, reported from 20 January−19 March 2020. The incubation period was estimated using travel history and date of symptom onset. To estimate the serial interval, we identified pairs of index and secondary cases. By 19 March, 3546 cases were reported. A large proportion was exposed abroad (38%), causing further local transmission. Median incubation period of 256 cases with exposure abroad was 3.8 days (95%CI: 3.5–4.2). For 95% of infected individuals, symptom onset occurred within 10.3 days (95%CI: 9.1–11.8) after exposure. The median serial interval, using 53 pairs, was 3.5 days (95%CI: 3.0–4.2; mean: 3.9, s.d.: 2.2). Travellers returning to Germany had an important influence on the spread of SARS-CoV-2 infections in Bavaria in early 2020. Especially in times of low incidence, public health agencies should identify holiday destinations, and areas with ongoing local transmission, to monitor potential importation of SARS-CoV-2 infections. Travellers returning from areas with ongoing community transmission should be advised to quarantine to prevent re-introductions of COVID-19.
ABSTRACT IMPACT: Screening the effect of thousands of non-coding genetic variants will help identify variants important in the etiology of diseases OBJECTIVES/GOALS: Massively parallel reporter assays (MPRAs) can experimentally evaluate the impact of genetic variants on gene expression. In this study, our objective was to systematically evaluate the functional activity of 3’-UTR SNPs associated with neurological disorders and use those results to help understand their contributions to disease etiology. METHODS/STUDY POPULATION: To choose variants to evaluate with the MPRA, we first gathered SNPs from the GWAS Catalog that were associated with any neurological disorder trait with p-value < 10-5. For each SNP, we identified the region that was in linkage disequilibrium (r2 > 0.8) and retrieved all the common 3’-UTR SNPs (allele-frequency > 0.05) within that region. We used an MPRA to measure the impact of these 3’-UTR variants in SH-SY5Y neuroblastoma cells and a microglial cell line. These results were then used to train a deep-learning model to predict the impact of variants and identify features that contribute to the predictions. RESULTS/ANTICIPATED RESULTS: Of the 13,515 3’-UTR SNPs tested, 400 and 657 significantly impacted gene expression in SH-SY5Y and microglia, respectively. Of the 84 SNPs significantly impacted in both cells, the direction of impact was the same in 81. The direction of eQTL in GTEx tissues agreed with the assay SNP effect in SH-SY5Y cells but not microglial cells. The deep-learning model predicted sequence activity level correlated with the experimental activity level (Spearman’s corr = 0.45). The deep-learning model identified several predictive motifs similar to motifs of RNA-binding proteins. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study demonstrates that MPRAs can be used to evaluate the effect of non-coding variants, and the results can be used to train a machine learning model and interpret its predictions. Together, these can help identify causal variants and further understand the etiology of diseases.
ABSTRACT IMPACT: Urine tumor DNA non-invasively detects minimal residual disease and infers tumor mutational burden in locally advanced bladder cancer prior to radical cystectomy, which may potentially enable the selection of patients for bladder-sparing treatment or facilitate personalized adjuvant immunotherapy. OBJECTIVES/GOALS: Standard-of-care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy. The inability to assess minimal residual disease (MRD) non-invasively limits our ability to offer bladder-sparing treatment. We sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis. METHODS/STUDY POPULATION: We applied uCAPP-Seq, a targeted sequencing method for detecting utDNA, to urine cell-free DNA samples acquired on the day of radical cystectomy from 42 patients with bladder cancer. utDNA variant-calling was performed non-invasively without prior tumor mutational knowledge. The overall utDNA level for each patient was represented by the non-silent mutation with the highest variant allele fraction after removing germline variants. Urine was similarly analyzed from 15 healthy adults. Tumor mutational burden (TMB) was inferred from the number of non-silent mutations detected in urine cell-free DNA by applying a linear relationship derived from TCGA whole exome sequencing of 409 MIBC tumors. RESULTS/ANTICIPATED RESULTS: utDNA levels were significantly higher in patients with residual disease detected in their surgical pathology compared to those who achieved a pathologic complete response (P = 0.002). Using an optimal utDNA threshold to define MRD detection, positive utDNA MRD significantly predicted the absence of pathologic complete response with a sensitivity of 81% and specificity of 81%. Positive utDNA MRD also portended significantly worse progression-free survival (HR = 7.4; P = 0.03) compared to negative utDNA MRD. Furthermore, we applied a linear relationship (Pearson r = 0.84; P < 0.0001) to identify patients with high inferred TMB who may have been candidates for early immune checkpoint blockade. DISCUSSION/SIGNIFICANCE OF FINDINGS: utDNA MRD analysis prior to surgery correlated significantly with pathologic response and progression-free survival, which may help select patients for bladder-sparing treatment. utDNA can also non-invasively infer TMB, which could facilitate personalized adjuvant therapy for patients in the future.
It is uncertain if long-term levels of low-density lipoprotein-cholesterol (LDL-C) affect cognition in middle age. We examined the association of LDL-C levels over 25 years with cognitive function in a prospective cohort of black and white US adults.
Lipids were measured at baseline (1985–1986; age: 18–30 years) and at serial examinations conducted over 25 years. Time-averaged cumulative LDL-C was calculated using the area under the curve for 3,328 participants with ≥3 LDL-C measurements and a cognitive function assessment. Cognitive function was assessed at the Year 25 examination with the Digit Symbol Substitution Test [DSST], Rey Auditory Visual Learning Test [RAVLT], and Stroop Test. A brain magnetic resonance imaging (MRI) sub-study (N = 707) was also completed at Year 25 to assess abnormal white matter tissue volume (AWMV) and gray matter cerebral blood flow volume (GM-CBFV) as secondary outcomes.
There were 15.6%, 32.9%, 28.9%, and 22.6% participants with time-averaged cumulative LDL-C <100 mg/dL, 101–129 mg/dL, 130–159 mg/dL, and ≥160 mg/dL, respectively. Standardized differences in all cognitive function test scores ranged from 0.16 SD lower to 0.09 SD higher across time-averaged LDL-C categories in comparison to those with LDL-C < 100 mg/dL. After covariate adjustment, participants with higher versus lower time-averaged LDL-C had a lower RAVLT score (p-trend = 0.02) but no differences were present for DSST, Stroop Test, AWMV, or GM-CBFV.
Cumulative LDL-C was associated with small differences in memory, as assessed by RAVLT scores, but not other cognitive or brain MRI measures over 25 years of follow-up.