bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Modeling of COVID-19 Case Growth Highlights Evolving Demographic Risk Factors in Tennessee and Georgia
Authors: Gray Jamieson D. , Harris Coleman R. , Wylezinski Lukasz S. , Spurlock Charles F.
Published: February 2021

The COVID-19 pandemic has exposed the need to understand the unique risk drivers that contribute to uneven morbidity and mortality in US communities. Addressing the community-specific social determinants of health that correlate with spread of SARS-CoV-2 provides an opportunity for targeted public health intervention to promote greater resilience to viral respiratory infections in the future.

Our work combined publicly available COVID-19 statistics with county-level social determinants of health information. Machine learning models were trained to predict COVID-19 case growth and understand the unique social, physical and environmental risk factors associated with higher rates of SARS-CoV-2 infection in Tennessee and Georgia counties. Model accuracy was assessed comparing predicted case counts to actual positive case counts in each county. The predictive models achieved a mean r-squared (R2) of 0.998 in both states with accuracy above 90% for all time points examined. Using these models, we tracked the social determinants of health, with a specific focus on demographics, that were strongly associated with COVID-19 case growth in Tennessee and Georgia counties. The demographic results point to dynamic racial trends in both states over time and varying, localized patterns of risk among counties within the same state.

Identifying the specific risk factors tied to COVID-19 case growth can assist public health officials and policymakers target regional interventions to mitigate the burden of future outbreaks and minimize long-term consequences including emergence or exacerbation of chronic diseases that are a direct consequence of infection.
SARS-CoV-2 seropositivity after infection and antibody response to mRNA-based vaccination
Authors: Ciccone Emily J. , Zhu Deanna R. , Ajeen Rawan , K. Lodge Evans , Shook-Sa Bonnie E. , Boyce Ross M. , Aiello Allison E. ,   COVID HCP Study Team
Published: February 2021

The effect of SARS-CoV-2 infection on response to mRNA-based SARS-CoV-2 vaccines is not well-described. We assessed longitudinal SARS-CoV-2-specific antibody responses pre- and post-vaccination among individuals with and without prior infection. The antibody response to the first vaccine dose was almost two-fold higher in individuals who were seropositive before vaccination compared to those who were seronegative, suggesting that prior infection primes the immune response to the first dose of mRNA-based vaccine.
Modafinil for Wakefulness in the Critical Care Units: A Literature Review and Case Series including COVID-19 Patients at a Tertiary Care Saudi Hospital
Authors: Amer Marwa , Bawazeer Mohammed , Butt Abid Shahzad , Dahhan Talal I. , Kseibi Eiad , Jamil Mouhamad Ghyath
Published: February 2021

Cognitive improvement after critical illness is complex. Neuro-stimulants are used to speed up physical and mental processes through the increase in arousal, and wakefulness. In this case series, we reviewed the literature and described the effect of modafinil for wakefulness in a cohort of adult patients admitted to our COVID and non-COVID intensive care unit (ICU) between January 2017 and June 2020. A total of 8 patients included; 3 admitted to COVID-19, 4 surgical, and 1 transplant ICU. Obstructive sleep apnea was noted in 2 (25%), 2 patients (25 %) had an initial neuroimaging that showed hemorrhagic stroke, and 1 (12.5%) showed ischemic stroke with hemorrhagic transformation. Modafinil 100-200 mg daily was started for a median duration of 4 days and the median initiation time in relation to ICU admission was 11 (IQR 9-17) days. Glasgow coma Scale improvement was noted on 5 patients (62.5%). The median duration of mechanical ventilation was 17.5 (IQR 15-31.75) days, and the median ICU stay was 28.5 (IQR 20.25-48) days. All-cause mortality rate was 25 % at 28 days and 62.5 % at 90 days. Modafinil prevented tracheostomy in 1 COVID-19 patient. No significant adverse drug reactions were documented. In our case series, we described our experience for modafinil use for wakefulness in ICU ventilated patients including COVID-19 patients. Based on our observations, the known effects of modafinil, and its safety profile, it holds the potential to facilitate recovery from cognitive impairment. Larger studies are warranted to fully evaluate its role for this indication.
Detection and quantification of enteric pathogens in aerosols near open wastewater canals in cities with poor sanitation
Authors: Ginn Olivia , Rocha-Melogno Lucas , Bivins Aaron , Lowry Sarah , Cardelino Maria , Nichols Dennis , Tripathi Sachchida Nand , Soria Freddy , Andrade Marcos , Bergin Mike , Deshusses Marc A. , Brown Joe
Published: February 2021

Urban sanitation infrastructure is inadequate in many low-income countries, leading to the presence of highly concentrated, uncontained fecal waste streams in densely populated areas. Combined with mechanisms of aerosolization, airborne transport of enteric microbes and their genetic material is possible in such settings but remains poorly characterized. We detected and quantified enteric pathogen-associated gene targets in aerosol samples near open wastewater canals (OWCs) or wastewater-impacted surface waters and control sites in La Paz, Bolivia; Kanpur, India; and Atlanta, USA via multiplex reverse-transcription qPCR (37 targets) and ddPCR (13 targets). We detected a wide range of enteric targets, some not previously reported in extramural urban aerosols, with more frequent detections of all enteric targets at higher densities in La Paz and Kanpur near OWCs. We report density estimates ranging up to 4.7 × 102 gc per m3air across all targets including heat stabile enterotoxigenic E. coli, C. jejuni, enteroinvasive E. coli/Shigella spp., Salmonella spp., norovirus, and Cryptosporidium spp. An estimated 25%, 76%, and 0% of samples containing positive pathogen detects were accompanied by culturable E. coli in La Paz, Kanpur, and Atlanta, respectively, suggesting potential for viability of enteric microbes at the point of sampling. Airborne transmission of enteric pathogens merits further investigation in cities with poor sanitation.

SYNOPSIS

We detected and quantified molecular targets associated with important enteric pathogens in outdoor aerosols in cities with poor sanitation to assess the potential role of the aeromicrobiological pathway in enteric infection transmission in such settings.
Using DNA to predict behaviour problems from preschool to adulthood
Authors: Gidziela Agnieszka , Rimfeld Kaili , Malanchini Margherita , Allegrini Andrea G. , McMillan Andrew , Selzam Saskia , Ronald Angelica , Viding Essi , von Stumm Sophie , Eley Thalia C. , Plomin Robert
Published: February 2021

Background

One goal of the DNA revolution is to predict problems in order to prevent them. We tested here if the prediction of behaviour problems from genome-wide polygenic scores (GPS) can be improved by creating composites across ages and across raters and by using a multi-GPS approach that includes GPS for adult psychiatric disorders as well as for childhood behaviour problems.

Method

Our sample included 3,065 genotyped unrelated individuals from the Twins Early Development Study who were assessed longitudinally for hyperactivity, conduct, emotional problems and peer problems as rated by parents, teachers and children themselves. GPS created from 15 genome-wide association studies were used separately and jointly to test the prediction of behaviour problems composites (general behaviour problems, externalizing and internalizing) across ages (from age 2 to age 21) and across raters in penalized regression models. Based on the regression weights, we created multi-trait GPS reflecting the best prediction of behaviour problems. We compared GPS prediction to twin heritability using the same sample and measures.

Results

Multi-GPS prediction of behaviour problems increased from less than 2% of the variance for observed traits to up to 6% for cross-age and cross-rater composites. Twin study estimates of heritability mirrored patterns of multi-GPS prediction as they increased from less than 40% to up to 83%.

Conclusions

The ability of GPS to predict behaviour problems can be improved by using multiple GPS, cross-age composites and cross-rater composites, although the effect sizes remain modest, up to 6%. Our results can be used in any genotyped sample to create multi-trait GPS predictors of behaviour problems that will be more predictive than polygenic scores based on a single age, rater or GPS.

Key points

Genome-wide polygenic scores (GPS) can be used to predict behaviour problems in childhood, but the effect sizes are generally less than 3.5%.

DNA-based prediction models of achieve greater accuracy if holistic approaches are employed, that is cross-trait, longitudinal and trans-situational approaches.

The prediction of childhood behaviour problems can be improved by using multiple GPS to predict composites that aggregate behaviour problems across ages and across raters.

Our results yield weights that can be applied to GPS in any study to create multi-trait GPS predictors of behaviour problems based on cross-age and cross-rater composites.

As compared to individuals in the lowest multi-trait GPS decile, nearly three times as many individuals in the highest internalizing multi-trait GPS decile were diagnosed with anxiety disorder and 25% more individuals in the highest general behaviour problems and externalizing multi-trait GPS deciles have taken medication for mental health.
The Effect of NFL and NCAA Football Games on the Spread of COVID-19 in the United States: An Empirical Analysis
Authors: Toumi Asmae , Zhao Haoruo , Chhatwal Jagpreet , Linas Benjamin P. , Ayer Turgay
Published: February 2021

Importance

In 2020 and early 2021, the National Football League (NFL) and National Collegiate Athletic Association (NCAA) had opted to host games in stadiums across the country. The in-person attendance of games has varied with time and from county to county. There is currently no evidence on whether limited in-person attendance of games has caused a substantial increase in coronavirus disease 2019 (COVID-19) cases.

Objective

To assess whether NFL and NCAA football games with limited in-person attendance have contributed to a substantial increase in COVID-19 cases in the counties they were held.

Design

In this time-series cross-sectional study, we matched every county hosting game(s) with in-person attendance (treated) in 2020 and 2021 with a county that has an identical game history for up to 14 days (control). We employed a standard matching method to further refine this matched set so that the treated and matched control counties have similar population size, non-pharmaceutical intervention(s) in place, and COVID-19 trends. We assessed the effect of hosting games with in-person attendance using a difference-in-difference estimator.

Setting

U.S. counties.

Participants

U.S. counties hosting NFL and/or NCAA games.

Exposure

Hosting NFL and/or NCAA games.

Main outcomes and measures

Estimating the impact of NFL and NCAA games with in-person attendance on new, reported COVID-19 cases per 100,000 residents at the county-level up to 14 days post-game.

Results

The matching algorithm returned 361 matching sets of counties. The effect of in-person attendance at NFL and NCAA games on community COVID-19 spread is not significant as it did not surpass 5 new daily cases of COVID-19 per 100,000 residents on average.

Conclusions and relevance

This time-series, cross-sectional matching study with a difference-in-differences design did not find an increase in COVID-19 cases per 100,000 residents in the counties where NFL and NCAA games were held with in-person attendance. Our study suggests that NFL and NCAA football games hosted with limited in-person attendance do not cause a significant increase in local COVID-19 cases.

Key points

Question

Did NFL and NCAA football games with limited in-person attendance cause a substantia increase in coronavirus disease 2019 (COVID-19) cases in the U.S. counties where the games were held?

Findings

This time-series, cross-sectional study of U.S. counties with NFL and NCAA football games used matching and difference-in-differences design to estimate the effect of games with limited in-person attendance on county-level COVID-19 spread. Our study does not find an increase in county-level COVID-19 cases per 100,000 residents due to NFL and NCAA football games held with limited in-person attendance.

Meaning

This study suggests that NFL and NCAA games held with limited in-person attendance do not cause an increase in COVID-19 cases in the counties they are held.
Genetic Connection to Drug-Induced Liver Injury (DILI) Through Statistical Learning Methods
Authors: Moore Roland , McEuen Kristin
Published: February 2021

Drug-Induced Liver Injury (DILI) is one of the major causes of drug development failure or drug withdrawal from the market after development. Therefore, investigating factors associated with DILI is of paramount importance. Environmental factors that contribute to DILI have been investigated and are, by and large, known. However, recent genomic studies have indicated that genetic diversity can lead to inter-individual differences in drug response. Consequently, it has become necessary to also investigate how genetic factors contribute to the development of DILI in the presence of environmental factors. Thus, our aim is to find appropriate statistical methods to investigate gene-gene and/or gene-environment interactions that are associated with DILI. This is an initial study that only explores statistical learning methods to find gen-gene interactions (epistasis). We introduce Multifactor Dimensionality Reduction (MDR), Random Forest (plus logistic regression), and Multivariate Adaptive Regression Splines (MARS), as the few potential methodological approaches that we found. Next, we attempt to improve the MARS method by combining it with a variable selection method.
Altered immunity to microbiota, B cell activation and depleted γδ / resident memory T cells in colorectal cancer
Authors: Noble Alistair , Pring Edward T , Durant Lydia , Man Ripple , Dilke Stella M , Hoyles Lesley , James Steve A , Carding Simon R , Jenkins John T , Knight Stella C
Published: February 2021

We sought methods of rectifying microbiota:immune dysregulation as a route to prophylaxis and improved immunotherapy of colorectal cancer (CRC). CRC develops in gut epithelium, accompanied by low level inflammatory signaling, intestinal microbial dysbiosis and immune dysfunction. We examined populations of intraepithelial lymphocytes in non-affected colonic mucosa of CRC and healthy donors and circulating immune memory to commensal bacterial species and yeasts. Colonic tissue in CRC was significantly depleted of γδ T cells and resident memory T cells, populations with a regulatory CD39-expressing phenotype. T cell memory responses to a panel of commensals were distinct in CRC, while B cell memory responses to several bacteria/yeast were significantly increased, accompanied by increased proportions of effector memory B cells, transitional B cells and plasmablasts in blood. IgA responses to mucosal microbes were unchanged. Our data describe a novel immune signature with similarities to and differences from that of inflammatory bowel disease. They implicate B cell dysregulation as a potential contributor to parainflammation and identify pathways of weakened barrier function and tumor surveillance in CRC-susceptible individuals.
CREBRF missense variant rs373863828 has both direct and indirect effects on type 2 diabetes and fasting glucose in Polynesians living in Samoa and Aotearoa New Zealand
Authors: Russell Emily M. , Carlson Jenna C. , Krishnan Mohanraj , Hawley Nicola L. , Sun Guangyun , Cheng Hong , Naseri Take , Sefuiva Reupena Muagututi‘a , Viali Satupa‘itea , Tuitele John , Major Tanya J. , Miljkovic Iva , Merriman Tony R. , Deka Ranjan , Weeks Daniel E. , McGarvey Stephen T. , Minster Ryan L.
Published: February 2021

Objective

The minor allele of rs373863828 in CREBRF is associated with higher BMI, lower fasting glucose, and lower odds of type 2 diabetes. We examined the associations between BMI and rs373863828 on type 2 diabetes and fasting glucose with a large sample of adult Polynesians from Samoa, American Samoa and Aotearoa New Zealand and estimated direct and indirect (via BMI) effects of rs373863828 on type 2 diabetes and fasting glucose.

Research Design and Methods

We regressed type 2 diabetes and fasting glucose on BMI and rs373863828 stratified by obesity, regressed type 2 diabetes and fasting glucose on BMI stratified by rs373863828 genotype, and assessed the effects of rs373863828 on type 2 diabetes and fasting glucose with path analysis.

Results

Association of BMI with fasting glucose was greater in those without obesity than in those with obesity. We did not observe evidence of differences by genotype. In the path analysis, the minor allele has direct negative and indirect positive effects on type 2 diabetes risk and fasting glucose, with the indirect effect mediated through a direct positive effect on BMI.

Conclusions

There may be a stronger effect of BMI on fasting glucose in Polynesians without obesity than in those with obesity. Carrying the rs373863828 minor allele does not decouple higher BMI from odds of type 2 diabetes. Given the current cost of genotyping compared to the accessibility of measuring BMI, including rs373863828 as a clinical predictor of type 2 diabetes may not be indicated.
Size and duration of COVID-19 clusters go along with a high SARS-CoV-2 viral load : a spatio-temporal investigation in Vaud state, Switzerland
Authors: Ladoy Anaïs , Opota Onya , Carron Pierre-Nicolas , Guessous Idris , Vuilleumier Séverine , Joost Stéphane , Greub Gilbert
Published: February 2021

To understand the geographical and temporal spread of SARS-CoV-2 during the first wave of infection documented in the canton of Vaud, Switzerland, we analysed clusters of positive cases using the precise place of residence of 33’651 individuals tested (RT-PCR) between January 10 and June 30, 2020. We identified both space-time (SaTScan) and transmission (MST-DBSCAN) clusters; we estimated their duration, their transmission behavior (emergence, growth, reduction, etc.) and relative risk. For each cluster, we computed the within number of individuals, their median age and viral load.

Among 1’684 space-time clusters identified, 457 (27.1%) were significant (p ≤ 0.05), i.e. harboring a higher relative risk of infection, as compared to other regions. They lasted a median of 11 days (IQR 7-13) and included a median of 12 individuals per cluster (IQR 5-20). The majority of significant clusters (n=260; 56.9 %) had at least one person with an extremely high viral load (above 1 billion copies/ml). Those clusters were considerably larger (median of 17 infected individuals, p < 0.001) than clusters with subjects showing a viral load lower than 1 million copies/ml (median of 3 infected individuals). The highest viral loads were found in clusters with the lowest average age, while clusters with the highest average age had low to middle viral load. Interestingly, in 20 significant clusters the viral load of three first cases were all below 100’000 copies/ml suggesting that subjects with less than 100’000 copies/ml may still have been contagious. Noteworthy, the dynamics of transmission clusters made it possible to identify three diffusion zones, which mainly differentiated rural from urban areas, the latter being more prone to last and spread in a new nearby clusters.

The use of geographic information is key for public health decision makers to mitigate the spread of the virus. This study suggests that early localization of clusters help implementing targeted protective measures limiting the spread of the SARS-CoV-2 virus.
Associations of Race/Ethnicity and Other Demographic and Socioeconomic Factors with Vaccine Initiation and Intention During the COVID-19 Pandemic in the United States
Authors: Kim Daniel
Published: February 2021

Background

To date, there has been limited data available to understand the associations between race/ethnicity and socioeconomic and related characteristics with novel coronavirus disease (COVID-19) vaccine initiation and planned vaccination in the United States.

Methods

To better characterize COVID-19 vaccinations nationally, we leveraged large cross-sectional surveys conducted between January and March 2021 with relatively complete race/ethnicity and socioeconomic data and nationally-representative of U.S. households to estimate trends in levels of COVID-19 vaccine initiation and vaccine intention. We further used survey data from January and March 2021 in adults aged 18-85 years to analyze the associations between race/ethnicity, education, pre-pandemic household income, and financial hardship during the pandemic and the adjusted odds of: 1) receipt of ≥1 dose of a COVID-19 vaccine; and 2) among those unvaccinated, the definite intention to receive a vaccine, controlling for other demographic and socioeconomic factors.

Results

We observed persistent disparities in vaccine initiation for non-Hispanic Blacks, Hispanics, and non-Hispanic multiracial persons, and in vaccine intention for Blacks and multiracial persons, compared to non-Hispanic Whites and non-Hispanic Asians. In late March 2021, the prevalence estimates of Hispanics and Blacks receiving a vaccine were 12 percentage points and 8 percentage points lower than for Whites, respectively. Moreover, both education and income levels exhibited positive dose-response relationships with vaccine initiation (P for trend≤01 and <.001, respectively). Substantial financial hardship was linked to 35-44% lower odds of vaccination (P<.001). The most common reasons for vaccine hesitancy were concerns about side effects and safety, with evidence of higher levels of concerns about vaccine safety among Blacks vs. Whites.

Conclusions

In this large, nationally-representative study with relatively complete race/ethnicity and socioeconomic data, we find that being Black non-Hispanic and having the least education and income were each independently associated with a markedly lower likelihood of definitely planning to get vaccinated or having been vaccinated. In the ensuing months of the pandemic, addressing the persevering racial/ethnic and socioeconomic inequities in vaccination due to differential access and vaccine hesitancy is essential to mitigate the pandemic’s higher risks of infection and adverse health outcomes in Hispanic, Black, and socioeconomically-disadvantaged communities.
SEIR Filter: A Stochastic Model of Epidemics
Authors: Šmíd Martin , Berec Luděk , Kuběna Aleš Antonín , Levínský René , Trnka Jan , Tuček Vít , Zajíček Milan
Published: February 2021

There are many epidemiological models at hand to cope with the present pandemic; it is, however, difficult to calibrate these models when data are noisy, partial or observed only indirectly. It is also difficult to distinguish relevant data from noise, and to distinguish the impact of individual determinants of the epidemic.

In mathematical statistics, the tools to handle all of these phenomena exist; however, they are seldom used for epidemiological models. The goal of this paper is to start filling this gap by proposing a general stochastic epidemiological model, which we call SEIR Filter.

Technically our model is a heterogeneous partially observable vector autoregression model, in which we are able to express closed form formulas for the distribution of compartments and observations, so both maximum likelihood and least square estimators are analytically tractable. We give conditions for vanishing, explosion and stationary behaviour of the epidemic and we are able to express a closed form formula for reproduction number.

Finally, we present several examples of the model’s application. We construct an estimate age-cohort model of the COVID-19 pandemic in the Czech Republic. To demonstrate the strengths of the model, we employ it to analyse and compare three vaccination scenarios.
Relationship Between Depression, Prefrontal Creatine and Gray Matter Volume
Authors: Faulkner Paul , Paioni Susanna Lucini , Kozhuharova Petya , Orlov Natasza , Lythgoe David J. , Daniju Yusuf , Morgenroth Elenor , Barker Holly , Allen Paul
Published: February 2021

Background

Depression and low mood are leading contributors to disability worldwide. Research indicates that clinical depression may be associated with low creatine concentrations in the brain and low prefrontal gray matter volume. Because sub-clinical depression also contributes to difficulties in day-to-day life, understanding the neural mechanisms of depressive symptoms in all individuals, even at a sub-clinical level, may aid public health.

Methods

Eighty-four young adult participants completed the Depression, Anxiety and Stress Scale (DASS) to quantify severity of depression, anxiety and stress, and underwent 1H-Magnetic Resonance Spectroscopy of the medial prefrontal cortex and structural MRI to determine whole-brain gray matter volume.

Results/Outcomes

DASS depression scores were negatively associated with A) concentrations of creatine (but not other metabolites) in the prefrontal cortex, and B) with gray matter volume in the right superior medial frontal gyrus. Medial prefrontal creatine concentrations and right superior medial frontal gray matter volume were positively correlated. DASS anxiety and DASS stress scores were not related to prefrontal metabolite concentrations or whole-brain gray matter volume.

Conclusions/Interpretations

This study provides preliminary evidence from a representative group of individuals who exhibit a range of depression levels, that prefrontal creatine and gray matter volume are negatively associated with depression. While future research is needed to fully understand this relationship, these results provide support for previous findings which indicate that increasing creatine concentrations in the prefrontal cortex may improve mood and wellbeing.

Declaration of Interest/Funding

This research was partly funded by a British Academy/Leverhulme Trust Research Grant, awarded to PA.
A Normative Database of A-Scan Data Using the Heidelberg Spectralis Spectral Domain Optical Coherence Tomography Machine
Authors: Meyer Joos , Karri Roshan , Danesh-Meyer Helen , Drummond Kate , Symons Andrew
Published: February 2021

Purpose

Develop the first normative database of macular and circumpapillary scans with reference values at the level of the A-scan using the Heidelberg Spectralis Optical Coherence Tomography (OCT) machine.

Methods

This study is a retrospective cross sectional analysis of macular and circumpapillary OCT scans of healthy individuals. All participants had a full ophthalmic examination, including best corrected visual acuity, intraocular pressure, biomicroscopy, posterior segment examination and OCT scan. The volume and thickness of each of the nine Early Treatment Diabetic Retinopathy zones at the macula were analysed for the total retinal thickness, retinal nerve fibre layer (RNFL), ganglion cell layer (GCL) and inner plexiform layer (IPL). The thickness of the circumpapillary RNFL was analysed at the disc. De-identified A-scans were extracted from the OCT machine as separate tab-separated text file and made available according to the data sharing statement.

Results

Two-hundred eyes from 144 participants were included of which 98 (49%) were female. The mean age (SD) was 48.52 (17.52). Participants were evenly distributed across four age groups and represented nine broad ethnic groups in proportions comparable to the local distribution. All the macular scans were 20° x 20° (5.9 mm x 5.9 mm), with a total scan density between 12,800 and 49,152 A-scans. The peripapillary scans were all 12° (3.5 mm), at a scan density of 768 A-scans. The mean retinal, GCL and IPL volumes were significantly greater in males than females. Age and total retinal volume (r = –0.2561), GCL volume (– 0.2911) and IPL volume (–0.3194) were negatively correlated. No significant correlation was found between the RNFL and age.

Conclusion

This study provides a normative database of macular and circumpapillary scans with reference values at the level of the A-scan using the Heidelberg Spectralis Optical Coherence Tomography (OCT) machine.
Evidence of increasing recorded diagnosis of autism spectrum disorders in Wales, UK – an e-cohort study
Authors: Underwood Jack F G , DelPozo-Banos Marcos , Frizzati Aura , John Ann , Hall Jeremy
Published: February 2021

Estimates place the prevalence of autism spectrum disorders (autism) at around 1% in the population. New services for adult diagnosis have been set up in Wales, UK, at a time of rising awareness of the spectrum of autism experiences, however no studies have examined adult autism prevalence in Wales. In this study we use an anonymised e-cohort comprised of healthcare record data to produce all-age estimates of prevalence and incidence of recorded autism for the years 2001-2016. We found the overall prevalence rate of autism in healthcare records was 0.51%. The number of new-recorded cases of autism increased from 0.188 per 1000 person-years in 2001 to 0.644 per 1000 person-years in 2016. The estimate of 0.51% prevalence in the population is lower than suggested by population survey and cohort studies study methodologies, but comparable to other administrative record study estimates. Rates of new incident diagnoses of autism saw a >150% increase in the years 2008-2016, with a trend towards more diagnoses in those over 35 and an eightfold increase in diagnoses in women from 2000-2016. Our study suggests that while the number of people being diagnosed with autism is increasing, many are still unrecognised by healthcare services.

Lay Abstract

Autism spectrum disorders (autism) are thought to be relatively common, with analyses estimating 1% in the population could meet diagnostic criteria. New services for adult diagnosis have been set up in Wales, UK, however no studies have examined for the proportion of adults with autism in Wales. In this study we take anonymised healthcare record data from more than 3.6 million people to produce a national estimate of recorded autism diagnoses. We found the overall prevalence rate of autism in healthcare records was 0.51%. The number of new-recorded cases of autism increased from 0.188 per 1000 person-years in 2001 to 0.644 per 1000 person-years in 2016. The estimate of 0.51% prevalence in the population is lower than suggested by population survey and cohort studies, but comparable to other administrative records. From 2001-2016 the number of autism services for adults has increased, and autism is more widely known in society, while concurrently in healthcare records there was a >150% increase autism diagnoses in the years 2008-2016. An increasing number of diagnoses were amongst women and those aged over 35. Our study suggests that while the number of people being diagnosed with autism is increasing, many are still unrecognised by healthcare services.
Structural differences between healthy subjects and patients with schizophrenia and schizoaffective disorder: A graph and control theoretical perspective
Authors: Dimulescu Cristiana , Gareayaghi Serdar , Kamp Fabian , Fromm Sophie , Obermayer Klaus , Metzner Christoph
Published: February 2021

The coordinated, dynamical interactions of large-scale networks give rise to cognitive function. Recent advances in network neuroscience have suggested that the anatomical organization of such networks puts a fundamental constraint on the dynamical landscape of the brain. Consequently, changes in large-scale brain activity have been hypothesized to underlie many neurological and psychiatric disorders. Specifically, evidence has emerged that large-scale dysconnectivity might play a crucial role in the pathophysiology of schizophrenia. To investigate potential differences in graph and control theoretic measures between patients with schizophrenia (SCZ), patients with schizoaffective disorder (SCZaff) and matched healthy controls (HC), we use structural MRI data. More specifically, we first calculate seven graph measures of integration, segregation, centrality and resilience and test for group differences. Second, we extend our analysis beyond these traditional measures and employ a simplified noise-free linear discrete-time and time-invariant network model to calculate two complementary measures of controllability. Average controllability identifies brain areas that can guide brain activity into different, easily reachable states with little input energy. Modal controllability on the other hand, characterizes regions that can push the brain into difficult-to-reach states, i.e. states that require substantial input energy. We identified differences in standard network and controllability measures for both patient groups compared to HCs. Specifically, we found a strong reduction of betweenness centrality for both patient groups and a strong reduction in average controllability for the SCZ group again in comparison to the HC group. Our findings of network level deficits might help to explain the many cognitive deficits associated with these disorders.
Assessment of knowledge, attitude and practices among Accredited Social Health Activists (ASHAs) towards COVID-19: a descriptive cross-sectional study in Tripura, India
Authors: Chowdhury Purvita , Baidya Subrata , Paul Debosmita , Debbarma Pinki , Kalita Biraj , Karmakar Sanjoy
Published: February 2021

With the surge in COVID-19 cases, community healthcare workers (CHW) remain pivotal for proper dissemination of awareness of disease transmission and infection control measures among the communities in low- and middle-income countries. In this context, lack of adequate knowledge and appropriate attitude among the CHW can directly influence the COVID-19 management programme. Therefore, the present study was designed to assess the knowledge, attitude and practices towards COVID-19 among the CHW of India known as Accredited Social Health Activists (ASHAs). A descriptive cross-sectional was conducted in the state of Tripura, Northeast India, among ASHAs with 14-, 4- and 3-item self-administered questionnaire for knowledge, attitude and practice. Around 61.2% of participants had the mean correct answer rate and the mean score of knowledge was 8.57± 2.25 (±SD). As per Bloom’s cut-off, it was observed that only 10% of the ASHAs had adequate knowledge, 30.9% showed positive attitude and 88% adhered to the good practices. It was observed that the indigenous ASHAs were 1.79 times more likely to adhere to the good practice of wearing masks during filed visits in the community (OR: 1.791, 95% CI: 1.059-3.028, p=0.030). Multinomial regression analysis showed that practice was significantly associated with fear of getting infected during service and the community’s fearfulness of ASHAs spreading the disease. Urgent addressing of the provisions of support, guidance and training of grassroot level healthcare workers in rural tough terrains can ensure robust output from the existing community healthcare workers in future pandemic-like emergencies.
Harnessing recombinase polymerase amplification for rapid detection of SARS-CoV-2 in resource-limited settings
Authors: Cherkaoui Dounia , Huang Da , Miller Benjamin S. , McKendry Rachel A.
Published: February 2021

The COVID-19 pandemic has challenged testing capacity worldwide. The mass testing needed to stop the spread of the virus requires new molecular diagnostic tests that are faster and with reduced equipment requirement, but as sensitive as the current gold standard protocols based on polymerase chain reaction.

We developed a fast (25-35 minutes) molecular test using reverse transcription recombinase polymerase amplification for simultaneous detection of two conserved regions of the virus, targeting the E and RdRP genes. The diagnostic platform offers two complementary detection methods: real-time fluorescence or visual dipstick.

The analytical sensitivity of the test by real-time fluorescence was 9.5 (95% CI: 7.0-18) RNA copies per reaction for the E gene and 17 (95% CI: 11-93) RNA copies per reaction for the RdRP gene. The analytical sensitivity for the dipstick readout was 130 (95% CI: 82-500) RNA copies per reaction. The assay showed high specificity with both detection methods when tested against common seasonal coronaviruses, SARS-CoV and MERS-CoV model samples. The dipstick readout demonstrated potential for point-of-care testing, with simple or equipment-free incubation methods and a user-friendly prototype smartphone application was proposed with data capture and connectivity.

This ultrasensitive molecular test offers valuable advantages with a swift time-to-result and it requires minimal laboratory equipment compared to current gold standard assays. These features render this diagnostic platform more suitable for decentralised molecular testing.
Estimating the Failure Risk of Quarantine Systems for Preventing COVID-19 Outbreaks in Australia and New Zealand
Authors: Grout Leah , Katar Ameera , Ouakrim Driss Ait , Summers Jennifer A. , Kvalsvig Amanda , Baker Michael G. , Blakely Tony , Wilson Nick
Published: February 2021

Objectives

To identify COVID-19 outbreaks and border control failures associated with quarantine systems in Australia and New Zealand and to estimate the failure risks.

Design, setting, participants

Observational epidemiological study of travellers transiting quarantine in Australia and New Zealand up to 15 June 2021.

Main outcome measures

The incidence of COVID-19 related failures arising from quarantine, and the failure risk for those transiting quarantine, estimated both per 100,000 travellers and per 1000 SARS-CoV-2 positive cases.

Results

Australia and New Zealand had 32 COVID-19 related failures arising from quarantine systems up to 15 June 2021 (22 and 10, respectively). One resultant outbreak involved an estimated 800 deaths and quarantine failures instigated nine lockdowns. The failure risk for those transiting quarantine was estimated at 5.0 failures per 100,000 travellers and 6.1 failures (95%CI: 4.0 to 8.3) per 1000 SARS-CoV-2 positive cases. The latter risk was two-fold higher in New Zealand compared with Australia. The full vaccination of frontline border workers could likely have prevented a number of quarantine system failures.

Conclusions

Quarantine system failures can be costly in terms of lives and economic impacts such as lockdowns. Ongoing improvements or alternatives to hotel-based quarantine are required.
Early pandemic molecular diversity of SARS-CoV-2 in children
Authors: Moustafa Ahmed M. , Otto William , Gai Xiaowu , Pandey Utsav , Ryutov Alex , Bootwalla Moiz , Maglinte Dennis T , Shen Lishuang , Ruble David , Ostrow Dejerianne , Gerber Jeffrey S. , Bard Jennifer Dien , Harris Rebecca M. , Planet Paul J.
Published: February 2021

Background

In the US, community circulation of the SARS-CoV-2 virus likely began in February 2020 after mostly travel-related cases. Children’s Hospital of Philadelphia began testing on 3/9/2020 for pediatric and adult patients, and for all admitted patients on 4/1/2020, allowing an early glimpse into the local molecular epidemiology of the virus.

Methods

We obtained 169 SARS-CoV-2 samples (83 from patients <21 years old) from March through May and produced whole genome sequences. We used genotyping tools to track variants over time and to test for possible genotype associated clinical presentations and outcomes in children.

Results

Our analysis uncovered 13 major lineages that changed in relative abundance as cases peaked in mid-April in Philadelphia. We detected at least 6 introductions of distinct viral variants into the population. As a group, children had more diverse virus genotypes than the adults tested. No strong differences in clinical variables were associated with genotypes.

Conclusions

Whole genome analysis revealed unexpected diversity, and distinct circulating viral variants within the initial peak of cases in Philadelphia. Most introductions appeared to be local from nearby states. Although limited by sample size, we found no evidence that different genotypes had different clinical impacts in children in this study.

Using sequencing and a novel technique for quantifying SARS-CoV-2 diversity, we investigated 169 SARS-CoV-2 genomes (83 <21 years old). This analysis revealed unexpected diversity especially in children. No clear differences in clinical presentation were associated with the different virus lineages.
Comprehensive lipidomics reveals reduced hepatic lipid turnover in NAFLD during alcohol intoxication
Authors: Israelsen Mads , Kim Min , Suvitaival Tommi , Stæhr Madsen Bjørn , Hansen Camilla Dalby , Torp Nikolaj , Trost Kajetan , Thiele Maja , Hansen Torben , Legido-Quigley Cristina , Krag Aleksander
Published: February 2021

Background & Aims

In experimental models, alcohol induces acute changes in lipid metabolism that cause hepatocyte lipoapoptosis and inflammation. Here we study human hepatic lipid turnover during controlled alcohol intoxication.

Methods

We studied 39 participants with three distinct hepatic phenotypes: alcohol-related liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and healthy controls. Alcohol was administrated via nasogastric tube over 30 minutes. Hepatic and systemic venous blood were sampled simultaneously at three time points: baseline, 60 and 180 min after alcohol intervention. Liver biopsies were sampled 240 minutes after alcohol intervention. We used ultra-high-performance liquid chromatograph mass spectrometry to measure levels of more than 250 lipid species from the blood and liver samples.

Results

After alcohol intervention, the levels of blood free fatty acid (FFA) and lysophosphatidylcholine (LPC) decreased while triglyceride (TG) increased. FFA was the only lipid class to decrease in NAFLD after alcohol intervention, while LPC and FFA decreased and TG increased after intervention in ALD and healthy controls. Fatty acid chain uptake preference in FFAs and LPCs were oleic acid, linoleic acid, arachidonic acid, and docosahexaenoic acid. Hepatic venous blood FFA and LPC levels were lower when compared to systemic venous blood levels throughout the intervention. After alcohol intoxication, liver lipidome in ALD was similar to that in NAFLD.

Conclusions

Alcohol intoxication induces rapid changes in circulating lipids including hepatic turnaround from FFA and LPC, potentially leading to lipoapoptosis and steatohepatitis. TG clearance was suppressed in NAFLD, possibly explaining why alcohol and NAFLD are synergistic risk factors for disease progression. These effects may be central to the pathogenesis of ALD.
Is Google Trends a useful tool for tracking mental and social distress during a public health emergency? A time-series analysis
Authors: Knipe Duleeka , Gunnell David , Evans Hannah , John Ann , Fancourt Daisy
Published: February 2021

Background

Google Trends data are increasingly used by researchers as an indicator of population mental health, but few studies have investigated the validity of this approach.

Methods

Relative search volumes (RSV) for the topics depression, anxiety, self-harm, suicide, suicidal ideation, loneliness, and abuse were obtained from Google Trends. We used graphical and time-series approaches to compare daily trends in searches for these topics against population measures of these outcomes recorded using validated scales (PHQ-9; GAD-7; UCLA-3) in a weekly survey (n=∼70,000) of the impact COVID-19 on psychological and social experiences in the UK population (12/03/2020 to 21/08/ 2020).

Results

Self-reported levels of depression, anxiety, suicidal ideation, self-harm, loneliness and abuse decreased during the period studied. There was no evidence of an association between self-reported anxiety, self-harm, abuse and RSV on Google Trends. Trends in reported depression symptoms and suicidal ideation declined over the study period, whereas Google topic RSV increased (p=0.03 and p=0.04 respectively). There was some evidence that suicidal ideation searches preceded reported self-harm (p=0.05), but graphical evidence suggested this was an inverse association. However, there was statistical and graphical evidence that self-report and Google searches for loneliness (p<0.001) tracked one another.

Limitations

No age/sex breakdown of Google Trends data are available. Survey respondents were not representative of the UK population and no pre-pandemic data were available.

Conclusion

Google Trends data do not appear to be a useful indicator of changing levels of population mental health during a public health emergency, but may have some value as an indicator of loneliness.
Seasonal influenza vaccine hesitancy profiles and determinants among Chinese children’s guardians and the elderly
Authors: Wei Zheng , Sun Xiu , Yang Yingying , Zhan Siyi , Fu Chuanxi
Published: February 2021

Background

Seasonal influenza imposes a significant clinical and economic burden, yet vaccine coverage remains low in China due to possible influenza vaccine hesitancy (IVH) and practical issues. We sought to investigate IVH and its determinants among children’s guardians and the elderly for better understanding of the situation and for future intervention.

Methods

IVH scales for the guardians and elderly were designed. We then performed two cross-sectional studies to identify the profiles and determinants of IVH using stratified cluster random sampling in an eastern China province in 2019.

Results

Of the 1,564 guardians and 522 elders, 43.2% (95% confidence interval: 40.4–46.0%) of guardians and 33.5% of elders (95% confidence interval: 29.5–37.6%) had IVH, whereas 31.3% of the guardians and 5.5% of the elderly had Influenza vaccine demand. The scales were well structured (KMO: 0.736 and 0.682; Cronbach’s α: 0.638 and 0.611). ‘From rural area’ (Odds ratio: 1.36), ‘don’t know government recommendation for flu vaccination’ (1.39), ‘don’t know flu vaccine is vaccinated annually’ (1.93), ‘family members (0.22), friends and neighbors had positive attitude toward flu vaccine’(0.58) were related factors of the guardians’ IVH. ‘Aged 70–79 years’ (0.46), ‘had flu before’ (0.35) and ‘once had been vaccinated’ (0.42) were related to the elderly’s IVH.

Conclusion

Poor awareness of influenza and vaccination, relatives’ negative/positive attitude, lack of government recommendations, anxiety about vaccine quality, and practical issues such as short supply are related to IVH in China. Precision education aiming hesitancy in wider groups are anticipated to increase vaccine confidence and coverage in influenza-vulnerable groups.