bluuebunny/crossref_metadata_2025 huggingface dataset:
The ISM local to the runaway star WR16
Authors: Cichowolski S , Duronea N U , Suad L A , Reynoso E M , Noriega-Crespo A , Bronfman L
Published: April 2020

Massive stars leave their imprint on the interstellar medium as they radiate their energy and undergo episodes of mass ejection throughout their lives. In this paper, we analyse the case of the Wolf–Rayet star WR16 combining archival multiwavelength data with new molecular observations obtained with the Atacama Submillimeter Telescope Experiment (ASTE). Our results suggest that during the main-sequence phase, WR16 swept up the surrounding gas creating a molecular structure (which we call Component 1) which also contains very cold dust observed in the infrared band. In a subsequent stage of evolution, as an LBV, the star underwent mass eruptions that were later overrun by the fast winds of the current WR phase. The final result is the round nebula revealed by the optical and IR images, and the molecular clumps detected. We have also computed the peculiar velocity of WR16 using Gaia data and, accordingly, confirm it as a runaway star. We propose that several features observed in different wavelengths can be explained under a bow-shock scenario linked to the high velocity of WR16.
Fisher for complements: extracting cosmology and neutrino mass from the counts-in-cells PDF
Authors: Uhlemann Cora , Friedrich Oliver , Villaescusa-Navarro Francisco , Banerjee Arka , Codis Sandrine
Published: April 2020

We comprehensively analyse the cosmology dependence of counts-in-cells statistics. We focus on the shape of the one-point probability distribution function (PDF) of the matter density field at mildly non-linear scales. Based on large-deviation statistics, we parametrize the cosmology dependence of the matter PDF in terms of the linear power spectrum, the growth factor, the spherical collapse dynamics, and the non-linear variance. We extend our formalism to include massive neutrinos, finding that the total matter PDF is highly sensitive to the total neutrino mass Mν and can disentangle it from the clustering amplitude σ8. Using more than a million PDFs extracted from the Quijote simulations, we determine the response of the matter PDF to changing parameters in the νΛCDM model and successfully cross-validate the theoretical model and the simulation measurements. We present the first νΛCDM Fisher forecast for the matter PDF at multiple scales and redshifts, and its combination with the matter power spectrum. We establish that the matter PDF and the matter power spectrum are highly complementary at mildly non-linear scales. The matter PDF is particularly powerful for constraining the matter density Ωm, clustering amplitude σ8 and the total neutrino mass Mν. Adding the mildly non-linear matter PDF to the mildly non-linear matter power spectrum improves constraints on Ωm by a factor of 5 and σ8 by a factor of 2 when considering the three lowest redshifts. In our joint analysis of the matter PDF and matter power spectrum at three redshifts, the total neutrino mass is constrained to better than 0.01 eV with a total volume of 6 (Gpc h−1)3. We discuss how density-split statistics can be used to translate those encouraging results for the matter PDF into realistic observables in galaxy surveys.
The high-energy emission from HD 93129A near periastron
Authors: del Palacio S , García F , Altamirano D , Barbá R H , Bosch-Ramon V , Corcoran M , De Becker M , Hamaguchi K , Maíz Apellániz J , Munar Adrover P , Paredes J M , Romero G E , Sana H , Tavani M , ud-Doula A
Published: April 2020

We conducted an observational campaign towards one of the most massive and luminous colliding wind binaries in the Galaxy, HD 93129A, close to its periastron passage in 2018. During this time the source was predicted to be in its maximum of high-energy emission. Here we present our data analysis from the X-ray satellites Chandra and NuSTAR and the γ-ray satellite AGILE. High-energy emission coincident with HD 93129A was detected in the X-ray band up to ∼18 keV, whereas in the γ-ray band only upper limits were obtained. We interpret the derived fluxes using a non-thermal radiative model for the wind-collision region. We establish a conservative upper limit for the fraction of the wind kinetic power that is converted into relativistic electron acceleration, fNT,e < 0.02. In addition, we set a lower limit for the magnetic field in the wind-collision region as BWCR > 0.3 G. We also argue a putative interpretation of the emission from which we estimate fNT,e ≈ 0.006 and BWCR ≈ 0.5 G. We conclude that multiwavelength, dedicated observing campaigns during carefully selected epochs are a powerful tool for characterizing the relativistic particle content and magnetic field intensity in colliding wind binaries.
Games
Authors: Nguyen C. Thi
Published: April 2020

Games are a unique art form. Game designers don’t just create a world; they create who you will be in that world. They tell you what abilities to use and what goals to take on. In other words, games work in the medium of agency. This book explores what games have to teach us about our own rationality and agency. We have the capacity for a peculiar sort of motivational inversion. For some of us, winning is not the point. We take on an interest in winning temporarily, so that we can play the game. Thus, we are capable of taking on temporary and disposable ends. At the center of this book is a view about games as communicative artifacts. Games are a way of recording forms of agency; they are a library of agencies. And exploring that library can help us develop our own agency and autonomy. But this technology can also be used for art. Games can sculpt our practical activity, for the sake of the beauty of our own actions. Our struggles, in games, can be designed to fit our capacities. Games can present a harmonious world, where our abilities fit the task. Games are a kind of existential balm against the difficult and exhausting value clarity of the world. But this presents a special danger. Games can be a fantasy of value clarity, which can encourage us to oversimplify our enduring values.
Grief
Authors: Shneer David
Published: April 2020

In January 1942, Soviet photographers came upon a scene like none they had ever documented. That day, they took pictures of the first liberation of a German mass atrocity site, where an estimated seven thousand Jews and others were executed at a trench near Kerch on the Crimean peninsula. Dmitri Baltermants, a photojournalist working for the Soviet newspaper Izvestiia, took pictures that day that would have a long life in shaping the image of Nazi genocide in and against the Soviet Union. Presenting never-before-seen photographs, Grief: The Biography of a Holocaust Photograph shows how Baltermants used the image of a grieving woman to render this gruesome mass atrocity into a transcendentally human tragedy. David Shneer tells the story of how one photograph from the trench became much more widely known than the others, eventually being titled Grief. Baltermants turned this shocking atrocity photograph into a Cold War–era artistic meditation on the profundity and horror of war that today can be found in Holocaust archives as well as art museums and at art auctions. Although the journalist documented murdered Jews in other pictures he took at Kerch, in Grief there are likely no Jews among the dead or the living, save for the possible officer securing the site. Nonetheless, Shneer shows that this photograph must be seen as an iconic Holocaust photograph. Unlike emaciated camp survivors or barbed-wire fences, Shneer argues, the “Holocaust by bullets” in the Soviet Union makes Grief a quintessential Soviet image of Nazi genocide.
An ulcerated giant segmental hemangioma resulting in contracture of the left elbow
Authors: Leung Alexander K C , Leong Kin Fon , Lam Joseph M
Published: April 2020

The majority of infantile hemangiomas are benign and will resolve on their own. We report a 4-month-old infant with an ulcerated giant segmental infantile hemangioma involving the left upper limb who developed a contracture of the left elbow despite treatment with oral propranolol, proper wound care, and regular intense physiotherapy. To our knowledge, contracture resulting from an infantile hemangioma has not been reported previously.
Mechanism of Peripheral Nerve Stimulation in Chronic Pain
Authors: Lin Tiffany , Gargya Akshat , Singh Harmandeep , Sivanesan Eellan , Gulati Amitabh
Published: April 2020

Introduction

With the advancement of technology, peripheral nerve stimulation (PNS) has been increasingly used to treat various chronic pain conditions. Its origin is based on the gate control theory postulated by Wall and Melzack in 1965. However, the exact mechanism behind PNS’ analgesic effect is largely unknown. In this article, we performed a comprehensive literature review to overview the PNS mechanism of action.

Design

A comprehensive literature review on the mechanism of PNS in chronic pain.

Methods

Comprehensive review of the available literature on the mechanism of PNS in chronic pain. Data were derived from database searches of PubMed, Scopus, and the Cochrane Library and manual searches of bibliographies and known primary or review articles.

Results

Animal, human, and imaging studies have demonstrated the peripheral and central analgesic mechanisms of PNS by modulating the inflammatory pathways, the autonomic nervous system, the endogenous pain inhibition pathways, and involvement of the cortical and subcortical areas.

Conclusions

Peripheral nerve stimulation exhibits its neuromodulatory effect both peripherally and centrally. Further understanding of the mechanism of PNS can help guide stimulation approaches and parameters to optimize the use of PNS.
Information Bias in the Proxy Advisory Market
Authors: Ma Shichao , Xiong Yan
Published: April 2020

We study an information sale problem in which a monopolist proxy advisor sells recommendations to a firm’s shareholders for corporate voting. We find that even an unconflicted proxy advisor skews its recommendations based on its clients’ beliefs or preferences. A novel bias-quantity relationship affects firm value. Under some parameters, shareholders’ biased beliefs or preferences can lead shareholders to make more information purchases, which enhances their collective decision-making. Thus, firm value may increase despite the negative effects of biased proxy voting recommendations. JEL D82, G34, L15

Received: April 16, 2019; editorial decision March 25, 2020 by Editor Uday Rajan.
Femoral vein wall thickness measurement: A new diagnostic tool for Behçet’s disease
Authors: Alibaz-Oner Fatma , Ergelen Rabia , Yıldız Yasin , Aldag Mustafa , Yazici Ayten , Cefle Ayşe , Koç Ertan , Artım Esen Bahar , Mumcu Gonca , Ergun Tulin , Direskeneli Haner
Published: April 2020

Objectives

Diagnosing Behçet’s disease (BD) is a challenge, especially in countries with a low prevalence. Recently, venous wall thickness (VWT) in lower extremities has been shown to be increased in BD patients. In this study, we aimed to investigate the diagnostic performance of common femoral vein (CFV) thickness measurement in BD and whether it can be used as a diagnostic tool.

Methods

. Patients with BD (n = 152), ankylosing spondylitis (n = 27), systemic vasculitides (n = 23), venous insufficiency (n = 29), antiphospholipid syndrome (APS; n = 43), deep vein thrombosis due to non-inflammatory causes (n = 25) and healthy controls (n = 51) were included in the study. Bilateral CFV thickness was measured with ultrasonography by a radiologist blinded to cases.

Results

Bilateral CFV thickness was significantly increased in BD compared with all control groups (P < 0.001 for all). The area under the receiver operating characteristic curve for bilateral CFV thicknesses in all comparator groups was >0.95 for the cut-off value (0.5 mm). This cut-off value also performed well against all control groups with sensitivity rates >90%. The specificity rate was also >80% in all comparator groups except APS (positive predictive value: 79.2–76.5%, negative predictive value: 92–91.8% for right and left CFV, respectively).

Conclusion

Increased CFV thickness is a distinctive feature of BD and is rarely present in healthy and diseased controls, except APS. Our results suggest that CFV thickness measurement with ultrasonography, a non-invasive radiological modality, can be a diagnostic tool for BD with sensitivity and the specificity rates higher than 80% for the cut-off value ≥0.5 mm.
Changes in Local Network Activity Approximated by Reverse Spike-Triggered Local Field Potentials Predict the Focus of Attention
Authors: Sharafeldin Abdelrahman , Mock Vanessa L , Meisenhelter Stephen , Hembrook-Short Jacqueline R , Briggs Farran
Published: April 2020

The effects of visual spatial attention on neuronal firing rates have been well characterized for neurons throughout the visual processing hierarchy. Interestingly, the mechanisms by which attention generates more or fewer spikes in response to a visual stimulus remain unknown. One possibility is that attention boosts the likelihood that synaptic inputs to a neuron result in spikes. We performed a novel analysis to measure local field potentials (LFPs) just prior to spikes, or reverse spike-triggered LFP “wavelets,” for neurons recorded in primary visual cortex (V1) of monkeys performing a contrast change detection task requiring covert shifts in visual spatial attention. We used dimensionality reduction to define LFP wavelet shapes with single numerical values, and we found that LFP wavelet shape changes correlated with changes in neuronal firing rate. We then tested whether a simple classifier could predict monkeys’ focus of attention from LFP wavelet shape. LFP wavelet shapes sampled in discrete windows were predictive of the locus of attention for some neuronal types. These findings suggest that LFP wavelets are a useful proxy for local network activity influencing spike generation, and changes in LFP wavelet shape are predictive of the focus of attention.
In Utero Infection with Coxsackievirus-B is Associated with Congenital Pulmonary Atresia
Authors: Sharma Vipul , Goessling Lisa S. , Brar Anoop K. , Eghtesady Pirooz
Published: April 2020

The research for this study was undertaken to examine association between perinatal infection with Coxsackievirus B (CVB) and congenital heart defects (CHD). Suggestive, although inconclusive, data exists of an association between CVB infection during pregnancy and CHD. We present data from a clinical study showing that CVB infection in early pregnancy induces heart defects. In a prospective study of 123 pregnant women with pregnancies affected with CHD we found circulating CVB IgG and IgM in the serum. A significant number of the women were positive for CVB antibodies; 30.9% for IgG and 6.5% for IgM. Our data demonstrates not only an association of CVB with CHD in pregnant women but this is the first report showing significant association between in-utero CVB infection and Pulmonary Atresia (PA) and HLHS (AA/MS variant). Elevated levels of IgG were seen in 55.5% of women carrying babies with PA and 60% of women carrying babies with HLHS (AA/MS), with p-values of 0.01 and 0.03 respectively. To determine specific CVB serotypes involved, neutralizing antibody titers to CVB1, CVB3, and CVB4 were analyzed on samples with positive IgG/IgM levels, and showed a possible association between CVB4 and CHD in the cohort. Our study has broad implications for the future understanding and potential management of CHD as well as introduces a new avenue of research for cardiac defects.
Healthcare worker mask reuse in a global pandemic: Using idle resources to create an inexpensive, scalable, and accessible UV system for N95 sterilization
Authors: Gilbert Rachel M. , Donzanti Michael J. , Minahan Daniel J. , Shirazi Jasmine , Hatem Christine L. , Hayward-Piatkovskyi Brielle , Dang Allyson M. , Nelson Katherine M. , Bothi Kimberly L. , Gleghorn Jason P.
Published: April 2020

As the current COVID-19 pandemic illustrates, not all hospitals and other facilities are equipped with enough personal protective equipment to meet the demand in a crisis. Healthcare workers around the world utilize N95 masks to protect themselves and their patients, yet during this global pandemic they are forced to re-wear what is intended to be single-use masks. This poses significant risk to these healthcare workers along with the populations they are trying to protect. Ultraviolet germicidal irradiation (UVGI) has been validated previously as a way to effectively sterilize these masks between use, however, not all facilities have access to the high cost commercial UV-C lamp sterilization equipment. However, UV-C bulbs are sitting idle in biosafety cabinets (BSCs) at universities and research facilities around the globe that have been shuttered to slow the spread of COVID-19. These bulbs may also be available in existing medical centers where infectious diseases are commonly treated. Therefore, we have developed a method to modify existing light fixtures, or create custom light fixtures compatible with new or existing common UV-C bulbs. This system is scalable and can be created for less than 50 US dollars, on site, at the point of need, and leverages resources that are currently untapped and sitting unused in public and private research facilities. The freely-accessible design can be easily modified for use around the world. Hospitals can obtain this potentially life-saving UVGI resource with minimal funds, via collaboration between research facilities to obtain the UV-C meters and limited availability UVGI bulbs. While mask reuse is not ideal, we must do what we can in emergency situations to protect our frontline healthcare workers and the communities they serve.
Evidence-Based, Cost-Effective Interventions To Suppress The COVID-19 Pandemic: A Systematic Review
Authors: Juneau Carl-Etienne , Pueyo Tomas , Bell Matt , Gee Genevieve , Collazzo Pablo , Potvin Louise
Published: April 2020

Background

In an unparalleled global response, during the COVID-19 pandemic, 90 countries asked 3.9 billion people to stay home. Yet some countries avoided lockdowns and focused on other strategies, like contact tracing and case isolation. How effective and cost-effective are these strategies? We aimed to provide a comprehensive summary of the evidence on pandemic control, with a focus on cost-effectiveness.

Methods

Following PRISMA systematic review guidelines, MEDLINE (1946 to April week 2, 2020) and Embase (1974 to April 17, 2020) were searched using a range of terms related to pandemic control. Articles reporting on the effectiveness or cost-effectiveness of at least one intervention were included and grouped into higher-quality evidence (randomized trials) and lower-quality evidence (other study designs).

Results

We found 1,653 papers; 62 were included. Higher-quality evidence was only available to support the effectiveness of hand washing and face masks. Modelling studies indicated that these measures are highly cost-effective. For other interventions, lower-quality evidence suggested that: (1) the most cost-effective interventions are swift contact tracing and case isolation, surveillance networks, protective equipment for healthcare workers, and early vaccination (when available); (2) home quarantines and stockpiling antivirals are less cost-effective; (3) social distancing measures like workplace and school closures are effective but costly, making them the least cost-effective options; (4) combinations are more cost-effective than single interventions; (5) interventions are more cost-effective when adopted early and for severe viruses like SARS-CoV-2. For H1N1 influenza, contact tracing was estimated to be 4,363 times more cost-effective than school closures ($2,260 vs. $9,860,000 per death prevented).

Conclusions

A cautious interpretation of the evidence suggests that for COVID-19: (1) social distancing is effective but costly, especially when adopted late and (2) adopting as early as possible a combination of interventions that includes hand washing, face masks, ample protective equipment for healthcare workers, and swift contact tracing and case isolation is likely to be the most cost-effective strategy.

Funding

LP holds the Canada Research Chair in Community Approaches and Health Inequalities (CRC 950232541). This funding source had no role in the design, conduct, or reporting of the study.
The production and clinical implications of SARS-CoV-2 antibodies
Authors: Hu Qianfang , Cui Xiaoping , Liu Xinzhu , Peng Bin , Jiang Jinyue , Wang Xiaohui , Li Yan , Hu Wenhui , Ao Zhi , Duan Jun , Wang Xue , Zhu Linxiao , Wu Guicheng , Guo Shuliang
Published: April 2020

Background

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), a novel betacoronavirus, has caused an outburst of pneumonia cases in Wuhan, China. We report the production of specific IgM and IgG antibodies after the infection of SARS-CoV-2 and its implication for the diagnosis, pathology and the course of the disease as well as the recurrence of positive nucleic acid tests after discharge.

Methods

Test results for SARS-CoV-2 IgM and IgG antibodies of 221 confirmed COVID-19 patients were retrospectively examined, and their clinical data were collected and analyzed based on various subgroups. SARS-CoV-2 IgM and IgG antibodies were determined with the chemiluminescence method.

Findings

The concentration (S/CO) of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, with a median of 17.38 (IQR 4.39-36.4) for IgM and 5.59 (IQR 0.73-13.65) for IgG. Detection rates reached highest on day 16-18 and day 19-21 for IgM and IgG, which were 73.6% and 98.6%, respectively, with significantly higher concentration of IgG in critically ill patients than in those with mild to moderate disease (P=0.027). The concentration of the antibodies on day 16-21 is not correlated with the course or outcome of the disease (Spearman r < 0.20, P > 0.05). Nasopharyngeal swabs revealed positive SARS-CoV-2 RNA in up to 52.7% of recovered patients after discharge, whose IgG proved to be significantly lower than that of those with negative RNA results (P = 0.009). IgG and IgM were tested twice within 14 days after discharge with a 7-day interval, and the second testing of these antibodies displayed a decrease in concentration of 21.2% (IQR, 11.2%,34.48%) for IgG and 23.05% (IQR, −27.96%,46.13%) for IgM, without statistical significance between the patients with re-detectable positive RNA results and those with negative RNA results after discharge. However, those with positive results experienced a count decrease in lymphocyte subsets.

Interpretation

The concentration of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, and antibody testing on day 16-21 is associated with increased detection rates, but the antibody concentration does not affect the course and outcome of the infection. Recovering patients with re-detectable positive SARS-CoV-2 RNA displayed lower concentration of IgG, but the downward trend of IgG during recovery indicated its limited duration of protection, and the protective effect of IgG remains to be investigated.

Funding

Chongqing Education Board, Chongqing Science and Technology Bureau, Famous teacher project of Chongqing talent plan
Modest effects of contact reduction measures on the reproduction number of SARS-CoV-2 in the most affected European countries and the US
Authors: Ensser Armin , Überla Pia , Überla Klaus
Published: April 2020

Population density, behaviour and cultural habits strongly influence the spread of pathogens. Consequently, key epidemiological parameters may vary from country to country. Many estimates of SARS-CoV-2 and COVID-19 strongly depend on testing frequency and case definitions. The fatal cases due to SARS-CoV2 could be a more reliable parameter, since missing of deaths is less likely. We analysed the dynamics of new infection and death cases to estimate the daily reproduction numbers (Rt) and the effectiveness of control measures in the most affected European Countries and the US. In summary, calculating Rt based on the daily number of deaths as well as of new infections may lead to more reliable estimates than those based on infection cases alone, as death based Rt are expected to be less susceptible to testing bias or limited capacities.
Detection of Nucleocapsid Antibody to SARS-CoV-2 is More Sensitive than Antibody to Spike Protein in COVID-19 Patients
Authors: Burbelo Peter D. , Riedo Francis X. , Morishima Chihiro , Rawlings Stephen , Smith Davey , Das Sanchita , Strich Jeffrey R. , Chertow Daniel S. , Davey Richard T. , Cohen Jeffrey I.
Published: April 2020

Background

SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), is associated with respiratory-related morbidity and mortality. Assays to detect virus-specific antibodies are important to understand the prevalence of infection and the course of the immune response.

Methodology

Quantitative measurements of plasma or serum antibodies by luciferase immunoprecipitation assay systems (LIPS) to the nucleocapsid and spike proteins were analyzed in 100 cross-sectional or longitudinal samples from SARS-CoV-2-infected patients. A subset of samples was tested with and without heat inactivation.

Results

Fifteen or more days after symptom onset, antibodies against SARS-CoV-2 nucleocapsid protein showed 100% sensitivity and 100% specificity, while antibodies to spike protein were detected with 91% sensitivity and 100% specificity. Neither antibody levels nor the rate of seropositivity were significantly reduced by heat inactivation of samples. Analysis of daily samples from six patients with COVID-19 showed anti-nucleocapsid and spike antibodies appearing between day 8 to day 14 after initial symptoms. Immunocompromised patients generally had a delayed antibody response to SARS-CoV-2 compared to immunocompetent patients.

Conclusions

Antibody to the nucleocapsid protein of SARS-CoV-2 is more sensitive than spike protein antibody for detecting early infection. Analyzing heat-inactivated samples by LIPS is a safe and sensitive method for detecting SARS-CoV-2 antibodies.
Climatic factors influence COVID-19 outbreak as revealed by worldwide mortality
Authors: Quilodrán Claudio S. , Currat Mathias , Montoya-Burgos Juan I.
Published: April 2020

The COVID-19 outbreak is triggering a global crisis that is challenging governments, health systems and the scientific community worldwide1. A central question in the COVID-19 pandemic is whether climatic factors modulate its progression. This information is key to epidemiologists and healthcare decision-makers for improving their management plans2. Previous attempts to assess the impact of climatic parameters have yielded ambiguous results, either because they were using geographically or temporally restricted data, or because they were comparing infection rates across countries, which were measured differently depending on local screening strategies. In March 2020, the spread of COVID-19 dramatically increased the number of countries recording deaths3, providing an opportunity to use mortality rate, which is measured more homogeneously across countries than infection rates, as a descriptor of the COVID-19 outbreak over a large latitudinal range. Here, using data recorded in 208 territories from 88 countries, we show that mortality rate is negatively influenced by warmer air temperature and positively affected by higher relative humidity. Each additional Celsius degree decreases mortality rate by ∼4%, while a 1% increase in relative humidity raises mortality rate by ∼2%. Temperature is positively correlated with UV-index, for which one unit of increase results in a ∼15% decrease in the mortality rate. We also show that other factors contribute to the dynamics of the COVID-19 outbreak, such as the proportion of vulnerable age classes in the population, access to a non-overwhelmed health system, as well as governmental travel restrictions for controlling the spread of the disease. All of them are critical factors impacting the mortality rate of COVID-19. The influence of climatic factors is a warning to all southern hemisphere countries where winter is coming soon. Northern hemisphere countries should also be warned that climatic factors alone will likely not be sufficient to contain the disease.
Estimated surge in hospitalization and intensive care due to the novel coronavirus pandemic in the Greater Toronto Area, Canada: a mathematical modeling study with application at two local area hospitals
Authors: Mishra Sharmistha , Wang Linwei , Ma Huiting , Yiu Kristy CY , Paterson J. Michael , Kim Eliane , Schull Michael J , Pequegnat Victoria , Lee Anthea , Ishiguro Lisa , Coomes Eric , Chan Adrienne , Downing Mark , Landsman David , Straus Sharon , Muller Matthew
Published: April 2020

Background

A hospital-level pandemic response involves anticipating local surge in healthcare needs.

Methods

We developed a mechanistic transmission model to simulate a range of scenarios of COVID-19 spread in the Greater Toronto Area. We estimated healthcare needs against 2019 daily admissions using healthcare administrative data, and applied outputs to hospital-specific data on catchment, capacity, and baseline non-COVID admissions to estimate potential surge by day 90 at two hospitals (St. Michael’s Hospital [SMH] and St. Joseph’s Health Centre [SJHC]). We examined fast/large, default, and slow/small epidemics, wherein the default scenario (R0 2.4) resembled the early trajectory in the GTA.

Results

Without further interventions, even a slow/small epidemic exceeded the city’s daily ICU capacity for patients without COVID-19. In a pessimistic default scenario, for SMH and SJHC to remain below their non-ICU bed capacity, they would need to reduce non-COVID inpatient care by 70% and 58% respectively. SMH would need to create 86 new ICU beds, while SJHC would need to reduce its ICU beds for non-COVID care by 72%. Uncertainty in local epidemiological features was more influential than uncertainty in clinical severity. If physical distancing reduces contacts by 20%, maximizing the diagnostic capacity or syndromic diagnoses at the community-level could avoid a surge at each hospital.

Interpretation

As distribution of the city’s surge varies across hospitals over time, efforts are needed to plan and redistribute ICU care to where demand is expected. Hospital-level surge is based on community-level transmission, with community-level strategies key to mitigating each hospital’s surge.
A model-based evaluation of the efficacy of COVID-19 social distancing, testing and hospital triage policies
Authors: McCombs Audrey , Kadelka Claus
Published: April 2020

We present a stochastic compartmental network model of SARS-CoV-2 and COVID-19 exploring the effects of policy choices in three domains: social distancing, hospital triaging, and testing. We distinguished between high-risk and low-risk members of the population, and modeled differences in social interactions due to context, risk level, infection status, and testing status. The model incorporates many of the currently important characteristics of the disease, including overcapacity in the healthcare system and uncertainties surrounding the proportion and transmission potential of asymptomatic cases. We compared current policy guidelines from public health agencies with alternative options, and investigated the effects of policy decisions on the overall proportion of COVID-19-related deaths. Our results support current policies to contain the outbreak but also suggest possible refinements, including emphasizing the need to reduce public, random contacts more than private contacts, and testing low-risk symptomatic individuals before high-risk symptomatic individuals. Our model furthermore points to interactions among the three policy domains; the efficacy of a particular policy choice depends on other implemented policies. Finally, our results provide an explanation for why societies like Germany, with lower average rates of social contact, are more successful at containing the outbreak than highly social societies such as Italy, despite the implementation of similar policy measures.
Genetic evidence for protective effects of smoking and drinking behavior on Parkinson’s disease: A Mendelian Randomization study
Authors: Domínguez-Baleón Carmen , Ong Jue-Sheng , Scherzer Clemens R. , Rentería Miguel E. , Dong Xianjun
Published: April 2020

Background

Observational studies have identified correlations between environmental and lifestyle factors and Parkinson’s disease (PD). However, the causal direction of many of these relationships remains unclear.

Objective

To infer causal relationships between smoking and alcohol intake and PD.

Methods

We use a two-sample Mendelian randomization (MR) experimental design to infer causal relationships between smoking (initiation, age of initiation, heaviness, and cessation) and alcohol (drinks per week) consumption as exposure variables and PD as the health outcome. We also conduct sensitivity analyses, including testing for pleiotropic effects MR-Egger and MR-PRESSO, and multivariable MR to jointly model the effects of drinking and smoking behavior on PD risk.

Results

Both alcohol intake (OR = 0.69; 95% CI 0.56-0.86; p=0.001). and smoking cessation (comparing current vs. former smokers) (IVW OR = 0.39; 95% CI 0.22 to 0.69; p=0.001) were causally associated with a reduced risk of PD. In addition, our multivariable MR results provide additional assurance that the causal association between drinks per week and PD is unlikely due to confounding by smoking behavior.

Conclusion

Our findings support the role of smoking as a protective factor against PD, but only when comparing current vs. former smokers. Increased alcohol intake also had a protective effect over PD risk, and the alcohol dehydrogenase 1B (ADH1B) locus is a candidate for further investigating the mechanisms underlying this association.
Copy Number Variation at 16p11.2 Imparts Transcriptional Alterations in Neural Development in an hiPSC-derived Model of Corticogenesis
Authors: Roth Julien G. , Muench Kristin L. , Asokan Aditya , Mallett Victoria M. , Gai Hui , Verma Yogendra , Weber Stephen , Charlton Carol , Fowler Jonas L. , Loh Kyle M. , Dolmetsch Ricardo E. , Palmer Theo D.
Published: April 2020

Microdeletions and microduplications of the 16p11.2 chromosomal locus are associated with syndromic neurodevelopmental disorders and reciprocal physiological conditions such as macro/microcephaly and high/low body mass index. To facilitate cellular and molecular investigations of these phenotypes, 65 clones of human induced pluripotent stem cells (hiPSCs) were generated from 13 individuals with 16p11.2 copy number variations (CNVs). Cortical neural progenitor cells derived from these hiPSCs were profiled using RNA-Seq, which identified alterations in radial glial gene expression that precede morphological abnormalities reported at later neurodevelopmental stages. Moreover, a customizable bioinformatic strategy for the detection of random integration and expression of reprogramming vectors was developed and leveraged towards identifying a subset of “footprint”-free hiPSC clones that are available by request from the Simons Foundation Autism Research Initiative. This publicly available resource of 65 human hiPSC clones can serve as a powerful medium for probing the etiology of developmental disorders associated with 16p11.2 CNVs.
Self-reported symptoms of covid-19 including symptoms most predictive of SARS-CoV-2 infection, are heritable
Authors: Williams Frances MK , Freidin Maxim B , Mangino Massimo , Couvreur Simon , Visconti Alessia , Bowyer Ruth CE , Le Roy Caroline I , Falchi Mario , Sudre Carole , Davies Richard , Hammond Christopher , Menni Cristina , Steves Claire J , Spector Tim D
Published: April 2020

Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n=2633) completing the C-19 Covid symptom tracker app allowed classical twin studies of covid-19 symptoms including predicted covid-19, a symptom-based algorithm predicting true infection derived in app users tested for SARS-CoV-2. We found heritability for fever = 41 (95% confidence intervals 12-70)%; anosmia 47 (27-67)%; delirium 49 (24-75)%; and predicted covid-19 gave heritability = 50 (29-70)%.
Cellular expression and functional roles of all 26 neurotransmitter GPCRs in theC. elegansegg-laying circuit
Authors: Fernandez Robert W. , Wei Kimberly , Wang Erin Y. , Mikalauskaite Deimante , Olson Andrew , Pepper Judy , Christie Nakeirah , Kim Seongseop , Koelle Michael R.
Published: April 2020

Maps of the synapses made and neurotransmitters released by all neurons in model systems such asC. eleganshave left still unresolved how neural circuits integrate and respond to neurotransmitter signals. Using the egg-laying circuit ofC. elegansas a model, we mapped which cells express each of the 26 neurotransmitter G protein coupled receptors (GPCRs) of this organism and also genetically analyzed the functions of all 26 GPCRs. We found that individual neurons express many distinct receptors, epithelial cells often express neurotransmitter receptors, and receptors are often positioned to receive extrasynaptic signals. The egg-laying circuit appears to use redundancy and compensation to achieve functional robustness, as receptor knockouts reveal few defects; however, increasing receptor signaling through overexpression more efficiently reveals receptor functions. This map of neurotransmitter GPCR expression and function in the egg-laying circuit provides a model for understanding GPCR signaling in other neural circuits.
Early detection of daylengths with a feedforward circuit coregulated by circadian and diurnal cycles
Authors: Panchy Nicholas , von Arnim Albrecht G. , Hong Tian
Published: April 2020

Light-entrained circadian clocks confer rhythmic dynamics of cellular and molecular activities to animals and plants. These intrinsic clocks allow stable anticipations to light-dark (diel) cycles. Many genes in the model plantArabidopsis thalianaare regulated by diel cycles via pathways independent of the clock, suggesting that the integration of circadian and light signals is important for the fitness of plants. Previous studies of light-clock signal integrations have focused on moderate phase adjustment of the two signals. However, dynamical features of integrations across a broad range of phases remain elusive. We recently found that phosphorylation of RIBOSOMAL PROTEIN OF THE SMALL SUBUNIT 6 (RPS6 or eS6), a ubiquitous post-translational modification across kingdoms, is influenced by the circadian clock and the light-dark (diel) cycle in an opposite manner. In order to understand this striking phenomenon and its underlying information processing capabilities, we built a mathematical model for the eS6-P control circuit. We found that the dynamics of eS6-P can be explained by a feedforward circuit with inputs from both circadian and diel cycles. Furthermore, the early-day response of this circuit with dual rhythmic inputs is sensitive to the changes in daylength, including both transient and gradual changes observed in realistic light intervals across a year, due to weather and seasons. By analyzing published gene expression data, we found that the dynamics produced by the eS6-P control circuit can be observed in the expression profiles of a large number of genes. Our work provides mechanistic insights into the complex dynamics of a ribosomal protein, and it proposes a previously underappreciated function of the circadian clock which not only prepares organisms for normal diel cycles but also helps to detect both transient and seasonal changes with a predictive power.
Ras Inhibitor CAPRI Enables Neutrophils to Chemotax Through a Higher-Concentration Range of Gradients
Authors: Xu Xuehua , Wen Xi , Moosa Amer , Bhimani Smit , Jin Tian
Published: April 2020

Neutrophils sense and migrate through an enormous range of chemoattractant gradients through adaptation. Here, we reveal that, in human neutrophils, Calcium-promoted Ras inactivator (CAPRI) locally controls the GPCR-stimulated Ras adaptation. Human neutrophils lacking CAPRI (caprikd) exhibit chemoattractant-induced non-adaptive Ras activation; significantly increased phosphorylation of AKT, GSK3α/3β, and cofilin; and excessive actin polymerization.caprikdcells display defective chemotaxis in response to high-concentration gradients but exhibit improved chemotaxis in low- or subsensitive-concentration gradients of various chemoattractants as a result of their enhanced sensitivity. Taken together, our data reveal that CAPRI controls GPCR activation-mediated Ras adaptation and lowers the sensitivity of human neutrophils so that they are able to chemotax through a higher concentration range of chemoattractant gradients.

Significance Statement

Neutrophils provide first-line host defense by migrating through chemoattractant gradients to the sites of inflammation. Inappropriate recruitment and mis-regulated activation of neutrophils contribute to tissue damage and cause autoimmune and inflammatory disease. One fascinating feature of chemotactic neutrophils is their ability to migrate through an enormous concentration range of chemoattractant gradients (10−9∼ 10−5M) through “adaptation,” in which cells no longer respond to the present stimuli, but remain sensitive to stronger stimuli. The inhibitory mechanism largely remains elusive, although many molecules of the excitatory signaling pathway have been identified. Our study reveals, for the first time, that the inhibitory component, CAPRI, is essential for both the sensitivity and the GPCR-mediated adaptation of human neutrophils.
Hepatocyte-specific deletion of XBP1 sensitizes mice to liver injury through hyperactivation of IRE1α
Authors: Duwaerts Caroline C. , Siao Kevin , Soon Russell K. , Her Chris , Iwawaki Takao , Kohno Kenji , Mattis Aras N. , Maher Jacquelyn J.
Published: April 2020

X-box binding protein-1 (XBP1) is a transcription factor that plays a central role in controlling cellular responses to endoplasmic reticulum (ER) stress. Under stress conditions, the transcriptionally active form of XBP1 is generated by unique splicing ofXbp1mRNA by the ER-resident protein inositol-requiring enzyme-1 (IRE1α). Genetic deletion of XBP1 has multiple consequences: some resulting from the loss of the transcription factor per se, and others related to compensatory upstream activation of IRE1α. The objective of the current study was to investigate the effects of XBP1 deletion in adult mouse liver and determine to what extent they are direct or indirect. XBP1 was deleted specifically from hepatocytes in adultXbp1fl/flmice using AAV8-Transthyretin-Cre (Xbp1Δhep).Xbp1Δhepmice exhibited no liver disease at baseline, but developed acute biochemical and histologic liver injury in response to a dietary challenge with fructose for 4 wk. Fructose-mediated liver injury inXbp1Δhepmice coincided with heightened IRE1α activity, as demonstrated by cJun phosphorylation and regulated IRE1α -dependent RNA decay (RIDD). Activation of eIF2α was also evident, with associated up-regulation of the pro-apoptotic molecules CHOP, BIM and PUMA. To determine whether the adverse consequences of liver-specific XBP1 deletion were due to XBP1 loss or heightened IRE1α activity, we repeated a fructose challenge in mice with liver-specific deletion of both XBP1 and IRE1α (Xbp1Δhep;IRE1αΔhep).Xbp1Δhep;IRE1αΔhepmice were protected from fructose-mediated liver injury and failed to exhibit any of the signs of ER stress seen in mice lacking XBP1 alone. The protective effect of IRE1α deletion persisted even with long-term exposure to fructose.Xbp1Δhepmice developed liver fibrosis at 16 wk, butXbp1Δhep;IRE1αΔhepmice did not. Overall, the results indicate that the deleterious effects of hepatocyte-specific XBP1 deletion are due primarily to hyperactivation of IRE1α. They support further exploration of IRE1α as a contributor to acute and chronic liver diseases.
The conservation of a core virome inAedesmosquitoes across different developmental stages and continents
Authors: Shi Chenyan , Zhao Lu , Atoni Evans , Zeng Weifeng , Hu Xiaomin , Matthijnssens Jelle , Yuan Zhiming , Xia Han
Published: April 2020

Mosquitoes belonging to the genusAedescan efficiently transmit many pathogenic arboviruses, placing a great burden on public health worldwide. In addition, they also carry a number of insect specific viruses (ISVs), and it was recently suggested that some of these ISVs might form a stable species-specific “core virome” in mosquito populations. However, little is known about such a core virome in laboratory colonies and if it is present across different developmental stages. In this study, we compared the viromes in eggs, larvae, pupae and adults ofAedes albopictusmosquitoes collected from the field as well as from a lab colony. The virome in lab-derivedAe. albopictusis very stable across all stages, consistent with a vertical transmission route of these viruses, forming a “vertically transmitted core virome”. The different stages of field collectedAe. albopictusmosquitoes also contains this stable vertically transmitted core virome as well as another set of viruses shared by mosquitoes across different stages, which might be an “environment derived core virome”. Both these vertically and environmentally transmitted core viromes inAe. albopictusdeserve more attention with respect to their effects on vector competence for important medically relevant arboviruses. To further study this core set of ISVs, we screened 46 publically available SRA viral metagenomic dataset of mosquitoes belonging to the genusAedes. Some of the identified core ISVs are identified in the majority of SRAs. In addition, a novel virus, Aedes phasmavirus, is found to be distantly related to Yongsan bunyavirus 1, and the genomes of the core virus Phasi Charoen-like phasivirus is highly prevalent in the majority of the tested samples, with nucleotide identities ranging from 94% to 99%. Finally, Guadeloupe mosquito virus, and some related viruses formed three separated phylogenetic clades. How these core ISVs influence the biology of mosquito host, arboviruses infection and evolution deserve to be further explored.
Agro-industrialisation and financial intermediation in Nigeria
Authors: Adeleye Ngozi , Osabuohien Evans , Asongu Simplice
Published: April 2020

Purpose

The study aims to analyse the role of finance in the agro-industrialisation nexus in Nigeria using annual data on manufacturing value added, agricultural value added and volume of finance availed to the agricultural sector from 1981 to 2015.

Design/methodology/approach

To establish the presence of a long-run relationship, the error correction model and bounds cointegration techniques are employed. Likewise, the model is augmented to test whether the associated relationship between industrial output and agricultural output depends on access to finance by farmers with the inclusion of an interaction term.

Findings

Some salient contributions to the literature are as follows: agriculture and finance are strong and positive predictors of industrialisation in the long run; in the short run, past realisations of industrial output and finance have significant asymmetric effects on industrial output; the explanatory power of agriculture decreases with the growth of the financial system; and the long-run results validate the role of finance in the agro-industrialisation nexus.

Originality/value

Given these findings, achieving growth in the agricultural sector that will induce desired industrialisation should be prioritised by the government through agencies such as the central bank, financial intermediaries and other stakeholders with a view to making agricultural financing a major concern for sustainable domestic consumption and industrial growth.