bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute appendicitis located within Amyand’s hernia—a complex case with concurrent acute cholecystitis
Authors: O’Connor Adam , John Fallon , Sabri Shariq
Published: October 2020

Amyand’s hernia is the presence of the vermiform appendix within an inguinal hernia sac. It is rare, and even rarer is the presence of acute appendicitis within the sac. It presents in a variety of different ways and often is only diagnosed intra-operatively. We present the case of a 90 year old male with extensive co-morbidities presenting with right upper quadrant pain, who on computed tomography scan of the abdomen, had acute cholecystitis alongside acute appendicitis within Amyand’s hernia. Ultimately given his co-morbidities, a conservative approach with prolonged antibiotic therapy was adopted, with a successful outcome. This case highlights that although classifications for treatment of Amyand’s hernia exist, careful clinical assessment is warranted in each case to ensure optimal outcome based upon individual circumstances.
Diagnostic accuracy of non-contact infrared thermometers and thermal scanners: a systematic review and meta-analysis
Authors: Aggarwal Nishant , Garg Mohil , Dwarakanathan Vignesh , Gautam Nitesh , Kumar Swasthi S , Jadon Ranveer Singh , Gupta Mohak , Ray Animesh
Published: October 2020

Infrared thermal screening, via the use of handheld non-contact infrared thermometers (NCITs) and thermal scanners, has been widely implemented all over the world. We performed a systematic review and meta-analysis to investigate its diagnostic accuracy for the detection of fever. We searched PubMed, Embase, the Cochrane Library, medRxiv, bioRxiv, ClinicalTrials.gov, COVID-19 Open Research Dataset, COVID-19 research database, Epistemonikos, EPPI-Centre, World Health Organization International Clinical Trials Registry Platform, Scopus and Web of Science databases for studies where a non-contact infrared device was used to detect fever against a reference standard of conventional thermometers. Forest plots and Hierarchical Summary Receiver Operating Characteristics curves were used to describe the pooled summary estimates of sensitivity, specificity and diagnostic odds ratio. From a total of 1063 results, 30 studies were included in the qualitative synthesis, of which 19 were included in the meta-analysis. The pooled sensitivity and specificity were 0.808 (95%CI 0.656–0.903) and 0.920 (95%CI 0.769–0.975), respectively, for the NCITs (using forehead as the site of measurement), and 0.818 (95%CI 0.758–0.866) and 0.923 (95%CI 0.823–0.969), respectively, for thermal scanners. The sensitivity of NCITs increased on use of rectal temperature as the reference. The sensitivity of thermal scanners decreased in a disease outbreak/pandemic setting. Changes approaching statistical significance were also observed on the exclusion of neonates from the analysis. Thermal screening had a low positive predictive value, especially at the initial stage of an outbreak, whereas the negative predictive value (NPV) continued to be high even at later stages. Thermal screening has reasonable diagnostic accuracy in the detection of fever, although it may vary with changes in subject characteristics, setting, index test and the reference standard used. Thermal screening has a good NPV even during a pandemic. The policymakers must take into consideration the factors surrounding the screening strategy while forming ad-hoc guidelines.
The influence of line opacity treatment in stella on supernova light curves
Authors: Kozyreva Alexandra , Shingles Luke , Mironov Alexey , Baklanov Petr , Blinnikov Sergey
Published: October 2020

We systematically explore the effect of the treatment of line opacity on supernova light curves. We find that it is important to consider line opacity for both scattering and absorption (i.e. thermalization, which mimics the effect of fluorescence). We explore the impact of the degree of thermalization on three major types of supernovae: Type Ia, Type II-peculiar, and Type II-plateau. For this we use the radiative transfer code stella and analyse broad-band light curves in the context of simulations done with the spectral synthesis code artis and in the context of a few examples of observed supernovae of each type. We found that the plausible range for the ratio between absorption and scattering in the radiation hydrodynamics code stella is (0.8–1):(0.2–0), i.e. the recommended thermalization parameter is 0.9.
Helicity in the large-scale Galactic magnetic field
Authors: West J L , Henriksen R N , Ferrière K , Woodfinden A , Jaffe T , Gaensler B M , Irwin J A
Published: October 2020

We search for observational signatures of magnetic helicity in data from all-sky radio polarization surveys of the Milky Way Galaxy. Such a detection would help confirm the dynamo origin of the field and may provide new observational constraints for its shape. We compare our observational results to simulated observations for both a simple helical field, and for a more complex field that comes from a solution to the dynamo equation. Our simulated observations show that the large-scale helicity of a magnetic field is reflected in the large-scale structure of the fractional polarization derived from the observed synchrotron radiation and Faraday depth of the diffuse Galactic synchrotron emission. Comparing the models with the observations provides evidence for the presence of a quadrupolar magnetic field with a vertical component that is pointing away from the observer in both hemispheres of the Milky Way Galaxy. Since there is no reason to believe that the Galactic magnetic field is unusual when compared to other galaxies, this result provides further support for the dynamo origin of large-scale magnetic fields in galaxies.
The completed SDSS-IV extended baryon oscillation spectroscopic survey: geometry and growth from the anisotropic void–galaxy correlation function in the luminous red galaxy sample
Authors: Nadathur Seshadri , Woodfinden Alex , Percival Will J , Aubert Marie , Bautista Julian , Dawson Kyle , Escoffier Stéphanie , Fromenteau Sebastien , Gil-Marín Héctor , Rich James , Ross Ashley J , Rossi Graziano , Magaña Mariana Vargas , Brownstein Joel R , Schneider Donald P
Published: October 2020

We present an analysis of the anisotropic redshift-space void–galaxy correlation in configuration space using the Sloan Digital Sky Survey extended Baryon Oscillation Spectroscopic Survey (eBOSS) Data Release 16 luminous red galaxy (LRG) sample. This sample consists of LRGs between redshifts 0.6 and 1.0, combined with the high redshift z > 0.6 tail of the Baryon Oscillation Spectroscopic Survey Data Release 12 CMASS sample. We use a reconstruction method to undo redshift-space distortion (RSD) effects from the galaxy field before applying a watershed void-finding algorithm to remove bias from the void selection. We then perform a joint fit to the multipole moments of the correlation function for the growth rate fσ8 and the geometrical distance ratio DM/DH, finding $f\sigma _8(z_\rm {eff})=0.356\pm 0.079$ and $D_M/D_H(z_\rm {eff})=0.868\pm 0.017$ at the effective redshift $z_\rm {eff}=0.69$ of the sample. The posterior parameter degeneracies are orthogonal to those from galaxy clustering analyses applied to the same data, and the constraint achieved on DM/DH is significantly tighter. In combination with the consensus galaxy BAO and full-shape analyses of the same sample, we obtain fσ8 = 0.447 ± 0.039, DM/rd = 17.48 ± 0.23, and DH/rd = 20.10 ± 0.34. These values are in good agreement with the ΛCDM model predictions and represent reductions in the uncertainties of $13{{\ \rm per\ cent}}$, $23{{\ \rm per\ cent}}$, and $28{{\ \rm per\ cent}}$, respectively, compared to the combined results from galaxy clustering, or an overall reduction of 55 per cent in the allowed volume of parameter space.
Magnetic quadri-dipolar stars rotating in vacuum
Authors: Pétri J
Published: October 2020

Main-sequence stars and compact objects such as white dwarfs and neutron stars are usually embedded in magnetic fields that strongly deviate from a pure dipole located right at the stellar centre. An off-centred dipole can sometimes better adjust existing data and offer a simple geometric picture to include multipolar fields. However, such configurations are usually to restrictive, limiting multipolar components to strength less than the underlying dipole. In this paper, we consider the most general lowest order multipolar combination given by a dipole and a quadrupole magnetic field association in vacuum. Following the general formalism for multipolar field computations, we derive the full electromagnetic field outside a rotating quadridipole. Exact analytical expressions for the Poynting flux and the electromagnetic kick are given. Such geometry is useful to study the magnetosphere of neutron stars for which more and more compelling observations reveals hints for at least quadridipolar fields. We also show that for sufficiently high quadrupole components at the stellar surface, the electromagnetic kick imprinted to a neutron star can reach thousands of km s−1 for a millisecond period at birth.
Doppler profiles of the interacting contact binary W Corvi
Authors: Eaton Joel A , Odell Andrew P , Nitschelm Christian
Published: October 2020

We use spectra from 2011 and 2012 to investigate the distribution of local effective temperature and non-orbital velocity over the surface of the common envelope of this peculiar contact binary. There seems to be a hot surface flow from the more massive to the less massive (secondary) component, possibly equatorial, which extends roughly one quarter-way around both sides of that secondary star, corresponding to the hotspot postulated to explain the star’s light-curve peculiarities. This feature is clear in the shape of the profiles of metallic lines, but it shows up in H α/H β profiles, as well. The profiles imply small flow velocities in contrast to those detected in some A-type W UMa systems, less than a few km s−1 for the primary but indeterminate for the secondary. We also classify the star’s spectrum (G1-2 V) and present more radial velocities confirming the Ruciński–Lu radial-velocity solution.
The 2019 Hong Kong Protests: A Role for Historical Sociology
Authors: Newburn Tim
Published: October 2020

This article responds to Stott et al.’s ‘Patterns of disorder in the 2019 protests in Hong Kong’. In that paper, they offer a social psychological analysis of the Hong Kong events and, in so doing, draw upon the ‘Elaborated Social Identity Model’, and deploy it as the basis for understanding the escalating tensions and violence that occurred through 2019. This model has a number of positive features, not least that it foregrounds rationality and the organized and purposive nature of collective conduct while also paying careful attention to the wider context in which identity within large groups is formed and reformed. The aim in this article is simply to point to the importance of situating such an account within a wider historical sociology, in particular, considering the longer-term ‘life-cycle’ of riot and violent protest. Utilizing Sewell’s notion of ‘events’, the article seeks to point to the ways in which such signal phenomena may be considered to have laid the foundations for at least elements of what occurred subsequently. Such an approach provides a basis within which the growth of Hong Kong’s localism may be situated, as well as offering a longer-term context for understanding the rapidly shifting position occupied by Hong Kong’s police.
‘Race’ and Resistance to Policing Before the ‘Windrush Years’: The Colonial Defence Committee and the Liverpool ‘Race Riots’ of 1948
Authors: Fevre Christopher
Published: October 2020

Between 31 July and 2 August 1948, Liverpool experienced three nights of racial violence on a scale not witnessed since the end of the First World War. Despite being initiated by white rioters, the so-called ‘race riots’ of 1948 were more significant in terms of the relationship between the police and Liverpool’s black population. Previous studies have sought to understand why and what happened during the riots; however, there has been little analysis of the aftermath. This article looks specifically at how black people responded to the ‘race riots’ in 1948 and argues that this episode led to a period of heightened political activity at a local and national level centred around the issue of policing. It focusses on the Colonial Defence Committee (CDC) that was formed immediately after the riots to organize the legal defence of individuals believed to have been wrongfully arrested. In its structure and organizational methods, the CDC represented a prototype of the defence committees that became a hallmark of black political opposition to policing during the 1970s and 1980s. Examining the aftermath of the Liverpool ‘race riots’ in 1948, thus, offers new perspectives on the historical development of black political resistance to policing in twentieth-century Britain. On the one hand, it reveals a longer history of struggle against racially discriminatory policing, which predates the ‘Windrush years’ migration of the 1950s and early 1960s. It also highlights the historical continuities in the way that black resistance to policing manifested itself over the twentieth century.
Phylogeographic Approaches to Characterize the Emergence of Plant Pathogens
Authors: Rasmussen David A. , Grünwald Niklaus J.
Published: October 2020

Phylogeography combines geographic information with phylogenetic and population genomic approaches to infer the evolutionary history of a species or population in a geographic context. This approach has been instrumental in understanding the emergence, spread, and evolution of a range of plant pathogens. In particular, phylogeography can address questions about where a pathogen originated, whether it is native or introduced, and when and how often introductions occurred. We review the theory, methods, and approaches underpinning phylogeographic inference and highlight applications providing novel insights into the emergence and spread of select pathogens. We hope that this review will be useful in assessing the power, pitfalls, and opportunities presented by various phylogeographic approaches.
Serum Responses of Children With Kawasaki Disease Against Severe Acute Respiratory Syndrome Coronavirus 2 Proteins
Authors: Chang Arthur J. , Croix Michael , Kenney Patrick , Baron Sarah , Hicar Mark D.
Published: October 2020

With recent reports showing clinical and laboratory overlap of multisystem inflammatory syndrome in children and Kawasaki disease (KD), we addressed the hypothesis that cross coronavirus humoral immunity leads to a parallel postinfectious phenomenon explaining similar pathologic findings in KD and multisystem inflammatory syndrome in children. We demonstrated no cross-reactivity in children with KD but observed some nonspecific interactions postintravenous immunoglobulin infusion.
Is a Fundamental Design Change for Gastrointestinal Endoscopes Required?
Authors: Holtmann Gerald J. , Huelsen Alexander , Shah Ayesha , Hourigan Luke F. , Morrison Mark
Published: October 2020

Since the first fiberoptic instruments, gastrointestinal endoscopy has shaped the field of gastroenterology and is now a key diagnostic and therapeutic tool. Compared with the initial fiberoptic endoscopes state-of-the-art optical chips (or charge-coupled device technology) allowed a quantum leap in image quality. Despite these advances, gastrointestinal endoscopy is far from being perfect. The diagnostic yield (eg, for adenoma detection rates) is highly operator dependent and there is still the need for sedation or even anesthesia to address discomfort during the procedure. Despite highly standardized cleaning and high-level disinfection the reuse of contemporary (and difficult to clean) endoscopes with multiple channels exposes patients to the risk of transmission of infections. Artificial intelligence and pattern recognition should eliminate interindividual variability including polyp detection rates, self-propelled, and (potentially remotely controlled) scopes with a soft shaft could reduce the discomfort during procedures and abolish the need for sedation and anesthesia altogether and single-use designs should eliminate the risk of patient-to-patient transmission of infections. While these innovations are feasible and could be implemented rapidly utilizing available technology, they require a paradigm shift affecting all levels of the value chain from the supplier of the instruments to the end-users. Some may negate the need for a paradigm shift, but it is evident that a major redesign of the endoscopic equipment is overdue to fully utilize novel technologies and most importantly ensure the best possible outcomes for patients.
Longitudinal Course of Depressive, Anxiety, and Posttraumatic Stress Disorder Symptoms After Heart Surgery: A Meta-Analysis of 94 Studies
Authors: Rosson Stella , Monaco Francesco , Miola Alessandro , Cascino Giammarco , Stubbs Brendon , Correll Christoph U. , Firth Joseph , Ermis Cagatay , Perrotti Andrea , Marciello Francesca , Carvalho Andrè F. , Brunoni Andre R. , Fusar-Poli Paolo , Fornaro Michele , Gentile Giovanni , Granziol Umberto , Pigato Giorgio , Favaro Angela , Solmi Marco
Published: October 2020

Objective

This study aimed to analyze the longitudinal course of depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms in patients with cardiac disease after heart surgery (HS).

Methods

We conducted a systematic review and random-effects meta-analysis of cohort studies in patients undergoing HS, measuring anxiety, depressive, and PTSD symptoms before and at least 30 days thereafter. Subgroup and meta-regression analyses, investigation of publication bias, and quality assessment were undertaken.

Results

We included 94 studies relating to 15,561 patients. HS included coronary artery bypass graft surgery, valve replacement, implantable cardioverter-defibrillator placement, left ventricular assist device placement, heart transplantation, and other types of HS. Across studies, symptoms of depression (g = 0.32; 95% confidence interval [CI] = 0.25 to 0.39; p < .001) and anxiety improved after HS (g = 0.52; 95% CI = 0.43 to 0.62; p < .001), whereas PTSD symptoms worsened (g = −0.42; 95% CI = −0.80 to −0.04; p = .032). The reduction of depression and anxiety levels was more pronounced for patients with underlying coronary artery disease and heart failure and persisted for 1 year after HS, whereas the increase in PTSD symptoms returned to baseline after 6 months. Depression improvement was inversely associated with older age, diabetes, hypertension, and dyslipidemia and positively with baseline heart failure. No additional clinical or demographic variables were associated with the course of anxiety symptoms. Quality of included studies was low overall. Publication bias was nonsignificant.

Conclusions

Depressive and anxiety symptoms improve for 1 year after HS, whereas PTSD symptoms might worsen. Older patients and those with metabolic comorbidities, valve disease, or ventricular arrhythmias are at higher risk for continued depressive and anxiety symptoms and should be monitored closely.
Lymphocyte Immunosuppression and Dysfunction Contributing to Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS)
Authors: Bergmann Christian B. , Beckmann Nadine , Salyer Christen E. , Crisologo Peter A. , Nomellini Vanessa , Caldwell Charles C.
Published: October 2020

Persistent Inflammation, Immune Suppression, and Catabolism Syndrome (PICS) is a disease state affecting patients who have a prolonged recovery after the acute phase of a large inflammatory insult. Trauma and sepsis are two pathologies after which such an insult evolves. In this review, we will focus on the key clinical determinants of PICS: Immunosuppression and cellular dysfunction. Currently, relevant immunosuppressive functions have been attributed to both innate and adaptive immune cells. However, there are significant gaps in our knowledge, as for trauma and sepsis the immunosuppressive functions of these cells have mostly been described in acute phase of inflammation so far, and their clinical relevance for the development of prolonged immunosuppression is mostly unknown. It is suggested that the initial immune imbalance determines the development of PCIS. Additionally, it remains unclear what distinguishes the onset of immune dysfunction in trauma and sepsis and how this drives immunosuppression in these cells. In this review, we will discuss how regulatory T cells (Tregs), innate lymphoid cells, natural killer T cells (NKT cells), TCR-a CD4− CD8− double-negative T cells (DN T cells), and B cells can contribute to the development of post-traumatic and septic immunosuppression. Altogether, we seek to fill a gap in the understanding of the contribution of lymphocyte immunosuppression and dysfunction to the development of chronic immune disbalance. Further, we will provide an overview of promising diagnostic and therapeutic interventions, whose potential to overcome the detrimental immunosuppression after trauma and sepsis is currently being tested.
An improved and readily available version of Bst DNA Polymerase for LAMP, and applications to COVID-19 diagnostics
Authors: Maranhao Andre , Bhadra Sanchita , Paik Inyup , Walker David , Ellington Andrew D.
Published: October 2020

Despite the fact that strand-displacing activity is of great utility for a variety of applications, including isothermal amplification assays, there are relatively few strand-displacing DNA polymerases. In particular, the thermotolerant DNA polymerase from Geobacillus stearothermophilus (previously Bacillus stearothermophilus), Bst DNA polymerase (Bst DNAP), is used in a variety of assays, including loop-mediated isothermal amplification. However, despite its wide use, its properties remain open to improvement, as has been demonstrated by a variety of engineering efforts, including the identification of point mutations that impact its robustness, strand-displacement capabilities, and nascent reverse transcriptase activity.

Interestingly, a strategy that has been commonly used to alter the capabilities of DNA polymerases, the addition of additional DNA- or RNA-binding domains, has yet to be applied to Bst DNAP. To this end, we now show that by adding fusion domains the performance of Bst DNAP in isothermal amplification assays, including its nascent RT activity, can be greatly improved. The impact of these improvements on the development of LAMP assays for the detection of SARS-CoV-2 is fully explored.
Evaluating the Efficacy of COVID-19 Vaccines
Authors: Lin Dan-Yu , Zeng Donglin , Mehrotra Devan V. , Corey Lawrence , Gilbert Peter B.
Published: October 2020

A large number of studies are being conducted to evaluate the efficacy and safety of candidate vaccines against novel coronavirus disease-2019 (COVID-19). Most Phase 3 trials have adopted virologically confirmed symptomatic COVID-19 disease as the primary efficacy endpoint, although laboratory-confirmed SARS-CoV-2 is also of interest. In addition, it is important to evaluate the effect of vaccination on disease severity. To provide a full picture of vaccine efficacy and make efficient use of available data, we propose using SARS-CoV-2 infection, symptomatic COVID-19, and severe COVID-19 as dual or triple primary endpoints. We demonstrate the advantages of this strategy through realistic simulation studies. Finally, we show how this approach can provide rigorous interim monitoring of the trials and efficient assessment of the durability of vaccine efficacy.

To increase statistical power and meet vaccine success criteria, we propose to evaluate the efficacy of COVID-19 vaccines by using the dual or triple primary endpoints of SARS-CoV-2 infection, symptomatic COVID-19, and severe COVID-19.
The revolution will be hard to evaluate: How co-occurring policy changes affect research on the health effects of social policies
Authors: Matthay Ellicott C. , Hagan Erin , Joshi Spruha , Tan May Lynn , Vlahov David , Adler Nancy , Maria Glymour M.
Published: October 2020

Extensive empirical health research leverages variation in the timing and location of policy changes as quasi-experiments. Multiple social policies may be adopted simultaneously in the same locations, creating co-occurrence which must be addressed analytically for valid inferences. The pervasiveness and consequences of co-occurring policies have received limited attention. We analyzed a systematic sample of 13 social policy databases covering diverse domains including poverty, paid family leave, and tobacco. We quantified policy co-occurrence in each database as the fraction of variation in each policy measure across different jurisdictions and times that could be explained by co-variation with other policies (R2). We used simulations to estimate the ratio of the variance of effect estimates under the observed policy co-occurrence to variance if policies were independent. Policy co-occurrence ranged from very high for state-level cannabis policies to low for country-level sexual minority rights policies. For 65% of policies, greater than 90% of the place-time variation was explained by other policies. Policy co-occurrence increased the variance of effect estimates by a median of 57-fold. Co-occurring policies are common and pose a major methodological challenge to rigorously evaluating health effects of individual social policies. When uncontrolled, co-occurring policies confound one another, and when controlled, resulting positivity violations may substantially inflate the variance of estimated effects. Tools to enhance validity and precision for evaluating co-occurring policies are needed.
How motivational signals disrupt metacognitive signals in the human VMPFC
Authors: Hoven Monja , Brunner Gina , de Boer Nina , Goudriaan Anneke , Denys Damiaan , van Holst Ruth , Luigjes Judy , Lebreton Mael
Published: October 2020

A growing body of evidence suggests that, during decision-making, BOLD signal in the VMPFC correlates both with motivational variables – such as incentives and expected values – and metacognitive variables – such as confidence judgments, which reflect the subjective probability of being correct. At the behavioral level, we recently demonstrated that the value of monetary stakes bias confidence judgments, with gain (respectively loss) prospects increasing (respectively decreasing) confidence judgments, even for similar levels of difficulty and performance. If and how this value-confidence interaction is also reflected in VMPFC signals remains unknown. Here, we used an incentivized perceptual decision-making task that dissociates key decision-making variables, thereby allowing to test several hypotheses about the role of the VMPFC in the incentive-confidence interaction. While initial analyses seemingly indicate that VMPFC combines incentives and confidence to form an expected value signal, we falsified this conclusion with a meticulous dissection of qualitative activation patterns. Rather, our results show that strong VMPFC confidence signals observed in trials with gain prospects are disrupted in trials with no – or negative (loss) monetary prospects. Deciphering how decision variables are represented and interact at finer scales (population codes, individual neurons) seems necessary to better understand biased (meta)cognition.
PREDICTIONS FOR EUROPE FOR THE COVID-19 PANDEMIC AFTER LOCKDOWN WAS LIFTED USING AN SIR MODEL
Authors: Patwardhan Jay
Published: October 2020

Abstract

I analyze a simplified SIR model developed from a paper written by Gyan Bhanot and Charles de Lisi in May of 2020 to find the successes and limitations of their predictions. In particular, I study the predicted cases and deaths fitted to data from March and its potential application to data in September. The data is observed to fit the model as predicted until around 150 days after December 31, 2019, after which many countries lift their lockdowns and begin to reopen. A plateau in cases followed by an increase approximately 1.5 months after is also observed. In terms of deaths, the data fits the shape of the model, but the model mostly underestimates the death toll after around 160 days. An analysis of the residuals is provided to locate the precise date of the departure of each country from its accepted data estimates and test each data point to its predicted value using a Z-test to determine whether each observation can fit the given model. The observed behavior is matched to policy measures taken in each country to attach an explanation to these observations. I notice that an international reopening results in a sharp increase in cases, and aim to plot this new growth in cases and predict when the pandemic will end for each country.
Monitoring for COVID-19 by universal testing in a homeless shelter in Germany: a prospective feasibility cohort study
Authors: Lindner Andreas K. , Sarma Navina , Rust Luise Marie , Hellmund Theresa , Krasovski-Nikiforovs Svetlana , Wintel Mia , Klaes Sarah M. , Hoerig Merle , Monert Sophia , Schwarzer Rolf , Edelmann Anke , Martinez Gabriela Equihua , Mockenhaupt Frank P. , Kurth Tobias , Seybold Joachim
Published: October 2020

Background

Living conditions in homeless shelters may facilitate the transmission of COVID-19. Social determinants and pre-existing health conditions place homeless people at increased risk of severe disease. Described outbreaks in homeless shelters resulted in high proportions of infected residents and staff members. In addition to other infection prevention strategies, regular shelter-wide (universal) testing for COVID-19 may be valuable, depending on the level of community transmission and when resources permit.

Methods

This was a prospective feasibility cohort study to evaluate universal testing for COVID-19 at a homeless shelter with 106 beds in Berlin, Germany. Co-researchers were recruited from the shelter staff. A PCR analysis of saliva or self-collected nasal/oral swab was performed weekly over a period of 3 weeks in July 2020. Acceptability and implementation barriers were analyzed by process evaluation using mixed methods including evaluation sheets, focus group discussion and a structured questionnaire.

Results

Ninety-three out of 124 (75%) residents were approached to participate in the study. Fifty-one out of the 93 residents (54.8%) gave written informed consent. High retention rates (88.9% – 93.6%) of a weekly respiratory specimen were reached, but repeated collection attempts, as well as assistance were required. A self-collected nasal/oral swab was considered easier and more hygienic to collect than a saliva specimen. No resident was tested positive. Language barriers were the main reason for non-participation. Flexibility of sample collection schedules, the use of video and audio materials, and concise written information were the main recommendations of the co-researchers for future implementation.

Conclusion

Voluntary universal testing for COVID-19 is feasible in homeless shelters. Universal testing of high-risk facilities will require flexible approaches, considering the level of the community transmission, the available resources, and the local recommendations. Lack of human resources and laboratory capacity may be a major barrier for implementation of universal testing, requiring adapted approaches compared to standard individual testing. Assisted self-collection of specimens and barrier free communication may facilitate implementation in homeless shelters. Program planning must consider homeless people’s needs and life situation, and guarantee confidentiality and autonomy.
WORLDWIDE CASE FATALITY RATIO OF COVID-19 OVER TIME
Authors: Chaubal Rohan , Kannan Sadhana , Khattry Navin , Gupta Sudeep
Published: October 2020

Background

The case fatality ratio (CFR) of coronavirus disease 2019 (COVID-19) has been reported to be variable among different countries and regions but few analyses have tracked this ratio worldwide over time.

Methods

The primary objective was to assess the time-course evolution of CFR of COVID-19 in all countries with available data and secondary objective was to evaluate associations between country-wise CFR and country-level health, human development, demographic and economic parameters. Day-wise data of COVID-19 cases and deaths for each country was extracted from a public repository and countries with at least 1000 cases on cutoff date were clustered by unsupervised k-means on the basis of deaths per 100000 population (DP100K). Day-wise CFR (cumulative deaths divided by cumulative cases, multiplied by 100) for each country and cluster (country group) was plotted as time-series and country-level parameters were tested for association with CFR using weighted multiple linear regression.

Results

On September 24, 2020 there were 32140504 cumulative COVID-19 cases and 981792 deaths reported from 184 countries for a worldwide CFR of 3.06 % (95%CI 3.05 -3.07). Unsupervised k-means clustering in 157 countries with at least 1000 reported cases resulted in Clusters (country groups) A, B, C, D and E with centroid DP100K and CFR of 0.100 and 2.51 (95% CI 2.42-2.61), 0.503 and 2.28 (95% CI 2.23-2.33), 1.816 and 1.73 (95% CI 1.71-1.75), 7.395 and 1.76 (95% CI 1.75-1.76), and 36.303 and 3.82 (95% CI 3.82-3.83), respectively. In a log-log analysis DP100K and CFR were significantly positively correlated (R=0.3570, p<0.001) with each other. All country groups and majority of included countries showed a pattern of gradually increasing CFR from the beginning of pandemic, followed by a plateau and then a steady decline in CFR. Among 10 country-level parameters, GDP per capita (β=-0.483, p=0.000), hospital beds per population (β=-0.372, p<0.001), mortality from air pollution (β=-0.487, p=0.003) and population density (β=-0.570, p< 0.000) were significantly negatively associated while maternal mortality ratio (β=0.431, p=0.000) and age (β=0.635, p<0.000) were positively associated with CFR.

Conclusions

The CFR of COVID-19 has gradually increased over time in majority of countries at various stages of the pandemic, followed by a plateau and a steady decline. Population level COVID-19 mortality burden and CFR are significantly positively associated with each other.
Regulation of theACE2locus in human airways cells
Authors: Lee Hye Kyung , Jung Olive , Hennighausen Lothar
Published: October 2020

The angiotensin-converting enzyme 2 (ACE2) receptor is the gateway for SARS-CoV-2 to airway epithelium1,2and the strong inflammatory response after viral infection is a hallmark in COVID-19 patients. Deciphering the regulation of the ACE2 gene is paramount for understanding the cell tropism of SARS-CoV-2 infection. Here we identify candidate regulatory elements in theACE2locus in human primary airway cells and lung tissue. Activating histone and promoter marks and Pol II loading characterize the intronicdACE2and define novel candidate enhancers distal to the genuineACE2promoter and within additional introns.dACE2, and to a lesser extentACE2, RNA levels increased in primary bronchial cells treated with interferons and this induction was mitigated by Janus kinase (JAK) inhibitors that are used therapeutically in COVID-19 patients. Our analyses provide insight into regulatory elements governing theACE2locus and highlight that JAK inhibitors are suitable tools to suppress interferon-activated genetic programs in bronchial cells.
Power Analysis for Stepped Wedge Trials with Two Treatments
Authors: Sundin Phillip T , Crespi Catherine M
Published: October 2020

Abstract

Stepped wedge designs (SWDs) are designs for cluster randomized trials that feature staggered, unidirectional cross-over, typically from a control to a treatment condition. Existing literature on statistical power for SWDs primarily focuses on designs with a single treatment. However, SWDs with multiple treatments are being proposed and conducted. We present a linear mixed model for a SWD with two treatments, with and without an interaction between them. We derive closed form solutions for the standard errors of the treatment effect coefficients for such models along with power calculation methods. We consider repeated cross-sectional designs as well as open and closed cohort designs and different random effect structures. Design features are examined to determine their impact on power for main treatment and interaction effects.
Pre-school childcare and inequalities in child development
Authors: Green Michael J , Pearce Anna , Parkes Alison , Robertson Elaine , Katikireddi S Vittal
Published: October 2020

Centre-based childcare may benefit pre-school children and alleviate inequalities in early childhood development, but evidence on socio-emotional and physical health outcomes is limited. Data were from the UK Millennium Cohort Study (n=14,376). Inverse-probability weighting was used to estimate confounder-adjusted population-average effects of centre and non-centre-based childcare (compared to parental care only) between ages 26-31 months on (age 3): internalising and externalising symptoms, pro-social behaviour, independence, emotional dysregulation, vocabulary, school readiness, and body mass index. To assess impacts on inequalities, controlled direct effects of low parental education and lone parenthood on all outcomes were estimated under two hypothetical scenarios: 1) universal take-up of centre-based childcare; and 2) parental care only. On average, non-centre based childcare improved vocabulary and centre-based care improved school readiness, with little evidence of other benefits. However, socio-economic inequalities were observed for all outcomes and were attenuated in scenario 1 (universal take-up). For example, inequalities in externalising symptoms (according to low parental education) were reduced from a confounder-adjusted standard deviation difference of 7.8 (95% confidence intervals: 6.7, 8.8), to 1.7 (0.6, 2.7). Inequalities by parental education in scenario 2 (parental care only) were wider than in scenario 1 for externalising symptoms (at 3.4 (2.4, 4.4)), and for emotional dysregulation and school readiness. Inequalities by lone parenthood, which were smaller, fell in scenario 1, and fell further in scenario 2. Universal access to centre-based pre-school care may alleviate inequalities, while restricted access (e.g. during lockdown for a pandemic such as Covid-19) may widen some inequalities in socioemotional and cognitive development.
Evaluating the Effect of Prebiotics on the Gut Microbiome Profile and β-cell Function in Youth with Newly-Diagnosed Type 1 Diabetes: Protocol of a Randomized Controlled Trial
Authors: Ismail Heba M. , Spall Maria , Evans-Molina Carmella , DiMeglio Linda A.
Published: October 2020

Introduction

Data show that disturbances in the gut microbiota play a role in glucose homeostasis, type 1 diabetes (T1D) risk and progression. The prebiotic high amylose maize starch (HAMS) alters the gut microbiome profile and metabolites favorably with an increase in bacteria producing short chain fatty acids (SCFAs) that have significant anti-inflammatory effects. HAMS also improves glycemia, insulin sensitivity and secretion in healthy non-diabetic adults. Additionally, a recent study testing an acetylated and butyrylated form of HAMS (HAMS-AB) that further increases SCFA production prevented T1D in a rodent model without adverse safety effects. The overall objective of this human study will be to assess how daily HAMS-AB consumption impacts the gut microbiome profile, SCFA production, β-cell heath, function and glycemia as well as immune responses in newly-diagnosed T1D youth.

Methods and Analysis

We hypothesize that HAMS-AB intake will improve the gut microbiome profile, increase SCFA production, improve β-cell health, function and glycemia as well as modulate the immune system. We describe here a pilot, randomized crossover trial of HAMS-AB in 12 newly-diagnosed T1D youth with residual β-cell function. In Aim 1, we will determine the effect of HAMS-AB on the gut microbiome profile and SCFA production; in Aim 2, we will determine the effect of HAMS-AB on β-cell health, function and glycemia; and in Aim 3, we will determine the peripheral blood effect of HAMS-AB on frequency, phenotype and function of specific T cell markers. We anticipate beneficial effects from a simple, inexpensive, and safe dietary approach.

Ethics and Dissemination

The Institutional Review Board at Indiana University approved the study protocol. The findings of this trial will be submitted to a peer-reviewed pediatric journal. Abstracts will be submitted to relevant national and international conferences.

Trial registration number

NCT04114357; Pre-results.

Article Summary

Strengths and limitations of this study

The study design (randomized controlled trial, RCT) is the most robust methodology to assess the effectiveness of therapeutic interventions.

The findings of this RCT, whether positive or negative, will contribute to the formulation of further recommendations on the use of high amylose maize starch that has been acetylated and butyrylated for improving beta-cell function in children with newly diagnosed type 1 diabetes (T1D).
Functional interpretation ofATAD3Avariants in neuro-mitochondrial phenotypes
Authors: Yap Zheng Yie , Park YoHan , Wortmann Saskia B. , Gunning Adam C. , Lee Sukyoung , Duraine Lita , Wilichowski Ekkehard , Wilson Kate , Mayr Johannes A. , Wagner Matias , Li Hong , Kini Usha , Black Emily Davis , Lupski James R. , Ellard Sian , Westphal Dominik S. , Harel Tamar , Yoon Wan Hee
Published: October 2020

Background

The ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) inATAD3Alead to neurological syndromes in humans.

Objective

To expand the mutational spectrum ofATAD3Avariants and to provide functional interpretation of missense alleles in trans to deletion alleles.

Methods

Exome sequencing was used to identify single nucleotide variants (SNVs) and copy number variants (CNVs) inATAD3Ain individuals with neurological and mitochondrial phenotypes. A Drosophila Atad3A Gal4 trap null allele was generated using CRISPR-Cas9 genome editing technology to aid interpretation of variants.

Results

We report 13 individuals from 8 unrelated families with biallelicATAD3Avariants. Four of the identified missense variants, p.(Leu77Val), p.(Phe50Leu), p.(Arg170Trp), p.(Gly236Val), were inherited in trans to loss-of-function alleles. A fifth missense variant, p.(Arg327Pro), was homozygous. Affected individuals exhibited findings previously associated withATAD3Apathogenic variation, including developmental delay, hypotonia, congenital cataracts, hypertrophic cardiomyopathy, and cerebellar atrophy. Drosophila studies indicated that Phe50Leu, Gly236Val, and Arg327Pro are severe loss-of-function alleles leading to early developmental lethality and neurogenesis defects, whereas Leu77Val and Arg170Trp are partial loss of function alleles that cause progressive locomotion defects. Moreover, Leu77Val and Arg170Trp expression leads to an increase in autophagy and mitophagy in adult muscles.

Conclusion

Our findings expand the allelic spectrum of ATAD3A variants, and exemplify the use of a functional assay in Drosophila to aid variant interpretation.
Bayesian segmentation of spatially resolved transcriptomics data
Authors: Petukhov Viktor , Soldatov Ruslan A. , Khodosevich Konstantin , Kharchenko Peter V.
Published: October 2020

Spatial transcriptomics is an emerging stack of technologies, which adds spatial dimension to conventional single-cell RNA-sequencing. New protocols, based onin situsequencing or multiplexed RNA fluorescentin situhybridization register positions of single molecules in fixed tissue slices. Analysis of such data at the level of individual cells, however, requires accurate identification of cell boundaries. While many existing methods are able to approximate cell center positions using nuclei stains, current protocols do not report robust signal on the cell membranes, making accurate cell segmentation a key barrier for downstream analysis and interpretation of the data. To address this challenge, we developed a tool for Bayesian Segmentation of Spatial Transcriptomics Data (Baysor), which optimizes segmentation considering the likelihood of transcriptional composition, size and shape of the cell. The Bayesian approach can take into account nuclear or cytoplasm staining, however can also perform segmentation based on the detected transcripts alone. We show that Baysor segmentation can in some cases nearly double the number of the identified cells, while reducing contamination. Importantly, we demonstrate that Baysor performs well on data acquired using five different spatially-resolved protocols, making it a useful general tool for analysis of high-resolution spatial data.
A potential role for reinforcement learning in speech production
Authors: Parrell Benjamin
Published: October 2020

Reinforcement learning, the ability to change motor behavior based on external reward, has been suggested to play a critical role in early stages of speech motor development and is widely used in clinical rehabilitation for speech motor disorders. However, no current evidence exists that demonstrates the capability of reinforcement to drive changes in human speech behavior. Speech provides a unique test of the universality of reinforcement learning across motor domains: speech is a complex, high-dimensional motor task whose goals do not specify a task to be performed in the environment but ultimately must be self-generated by each speaker such that they are understood by those around them. Across four experiments, we examine whether reinforcement learning alone is sufficient to drive changes in speech behavior and parametrically test two features known to affect reinforcement learning in reaching: how informative the reinforcement signal is as well as the availability of sensory feedback about the outcomes of one’s motor behavior. We show that learning does occur and is more likely when participants receive auditory feedback that gives an implicit target for production, even though they do not explicitly imitate that target. Contrary to results from upper limb control, masking feedback about movement outcomes has no effect on speech learning. Together, our results suggest a potential role for reinforcement learning in speech but that it likely operates differently than in other motor domains.