bluuebunny/crossref_metadata_2025 huggingface dataset:
A pseudo-anelastic model for stress softening in liquid crystal elastomers
Authors: Angela Mihai L. , Goriely Alain
Published: November 2020

Liquid crystal elastomers exhibit stress softening with residual strain under cyclic loads. Here, we model this phenomenon by generalizing the classical pseudo-elastic formulation of the Mullins effect in rubber. Specifically, we modify the neoclassical strain-energy density of liquid crystal elastomers, depending on the deformation and the nematic director, by incorporating two continuous variables that account for stress softening and the associated set strain. As the material behaviour is governed by different forms of the strain-energy density on loading and unloading, the model is referred to as pseudo-anelastic. We then analyse qualitatively the mechanical responses of the material under cyclic uniaxial tension, which is easier to reproduce in practice, and further specialize the model in order to calibrate its parameters to recent experimental data at different temperatures. The excellent agreement between the numerical and experimental results confirms the suitability of our approach. Since the pseudo-energy function is controlled by the strain-energy density for the primary deformation, it is valid also for materials under multiaxial loads. Our study is relevant to mechanical damping applications and serves as a motivation for further experimental tests.
Extreme dissipation and intermittency in turbulence at very high Reynolds numbers
Authors: Elsinga Gerrit E. , Ishihara Takashi , Hunt Julian C. R.
Published: November 2020

Extreme dissipation events in turbulent flows are rare, but they can be orders of magnitude stronger than the mean dissipation rate. Despite its importance in many small-scale physical processes, there is presently no accurate theory or model for predicting the extrema as a function of the Reynolds number. Here, we introduce a new model for the dissipation probability density function (PDF) based on the concept of significant shear layers, which are thin regions of elevated local mean dissipation. At very high Reynolds numbers, these significant shear layers develop layered substructures. The flow domain is divided into the different layer regions and a background region, each with their own PDF of dissipation. The volume-weighted regional PDFs are combined to obtain the overall PDF, which is subsequently used to determine the dissipation variance and maximum. The model yields Reynolds number scalings for the dissipation maximum and variance, which are in agreement with the available data. Moreover, the power law scaling exponent is found to increase gradually with the Reynolds numbers, which is also consistent with the data. The increasing exponent is shown to have profound implications for turbulence at atmospheric and astrophysical Reynolds numbers. The present results strongly suggest that intermittent significant shear layer structures are key to understanding and quantifying the dissipation extremes, and, more generally, extreme velocity gradients.
Trophic cascades alter eco-evolutionary dynamics and body size evolution
Authors: Luhring Thomas M. , DeLong John P.
Published: November 2020

Trait evolution in predator–prey systems can feed back to the dynamics of interacting species as well as cascade to impact the dynamics of indirectly linked species (eco-evolutionary trophic cascades; EETCs). A key mediator of trophic cascades is body mass, as it both strongly influences and evolves in response to predator–prey interactions. Here, we use Gillespie eco-evolutionary models to explore EETCs resulting from top predator loss and mediated by body mass evolution. Our four-trophic-level food chain model uses allometric scaling to link body mass to different functions (ecological pleiotropy) and is realistically parameterized from the FORAGE database to mimic the parameter space of a typical freshwater system. To track real-time changes in selective pressures, we also calculated fitness gradients for each trophic level. As predicted, top predator loss generated alternating shifts in abundance across trophic levels, and, depending on the nature and strength in changes to fitness gradients, also altered trajectories of body mass evolution. Although more distantly linked, changes in the abundance of top predators still affected the eco-evolutionary dynamics of the basal producers, in part because of their relatively short generation times. Overall, our results suggest that impacts on top predators can set off transient EETCs with the potential for widespread indirect impacts on food webs.
Parasite infection disrupts escape behaviours in fish shoals
Authors: Demandt Nicolle , Praetz Marit , Kurvers Ralf H. J. M. , Krause Jens , Kurtz Joachim , Scharsack Jörn P.
Published: November 2020

Many prey species have evolved collective responses to avoid predation. They rapidly transfer information about potential predators to trigger and coordinate escape waves. Predation avoidance behaviour is often manipulated by trophically transmitted parasites, to facilitate their transmission to the next host. We hypothesized that the presence of infected, behaviourally altered individuals might disturb the spread of escape waves. We used the tapewormSchistocephalus solidus, which increases risk-taking behaviour and decreases social responsiveness of its host, the three-spined stickleback, to test this hypothesis. Three subgroups of sticklebacks were placed next to one another in separate compartments with shelter. The middle subgroup contained either uninfected or infected sticklebacks. We confronted an outer subgroup with an artificial bird strike and studied how the escape response spread through the subgroups. With uninfected sticklebacks in the middle, escape waves spread rapidly through the entire shoal and fish remained in shelter thereafter. With infected sticklebacks in the middle, the escape wave was disrupted and uninfected fish rarely used the shelter. Infected individuals can disrupt the transmission of flight responses, thereby not only increasing their own predation risk but also that of their uninfected shoal members. Our study uncovers a potentially far-reaching fitness consequence of grouping with infected individuals.
Famine-related mortality in early life and accelerated life histories in nineteenth-century Belgium
Authors: Pink Katharina E. , Quinlan Robert J. , Hin Saskia
Published: November 2020

Density-dependent and extrinsic mortality are predicted to accelerate reproductive maturation. The first 5 years of life is a proposed sensitive period for life-history regulation. This study examines the ways in which local mortality during this sensitive period was related to subsequent marriage timing in nineteenth-century Belgium (nwomen = 11 892;nmen = 14 140). Local mortality during the sensitive period was inversely associated with age at first marriage for men and women controlling for literacy, occupational status, population growth and migration. Cox regression indicated decreased time to marriage for women (HR = 1.661, 95% CI: 1.542–1.789) and men (HR = 1.327, 95% CI: 1.238–1.422) from high mortality municipalities. Rising population growth rates were associated with earlier marriage for men and women. Migration in general was associated with later marriage for men and women. Consistent with life-history predictions, harsh ecological conditions during early life such as famine coincided with earlier marriage.
Comparative genomics of wild-type and laboratory-evolved biofilm-overproducing Deinococcus metallilatus strains
Authors: Park Chulwoo , Shin Bora , Kim Wonjae , Cheong Hoon , Park Soyoon , Park Woojun
Published: November 2020

Deinococcus metallilatus

MA1002 was exposed to ultraviolet radiation to generate mutants with enhanced biofilm production. Two strains (nos 5 and 6) were then selected based on their high biofilm formation, as well as their possession of higher concentrations of extracellular matrix components (eDNA, protein and saccharides) than the wild-type (WT). Genomic sequencing revealed the presence of large genome deletions in a secondary chromosome in the mutants. Expression analyses of the WT and mutant strains indicated the upregulation of genes associated with exopolysaccharide synthesis and stress response. The mutant strains showed high mortality in glucose-supplemented (TYG) medium; however, cell death and biofilm formation were not increased in mutant cells grown under acetate- or glyoxylate-added media, suggesting that metabolic toxicity during glucose metabolism induced a high rate of cell death but improved biofilm formation in mutant strains. In damaged cells, eDNAs contributed to the enhanced biofilm formation of

D. metallilatus

.
Role of ivermectin in the prevention of COVID-19 infection among healthcare workers in India: A matched case-control study
Authors: Behera Priyamadhaba , Patro Binod Kumar , Singh Arvind Kumar , Chandanshive Pradnya Dilip , S.R. Ravi Kumar , Pradhan Somen Kumar , Pentapati Siva Santosh Kumar , Batmanabane Gitanjali , Padhy Biswa Mohan , Bal Shakti , Singh Sudipta Ranjan , Mohanty Rashmi Ranjan
Published: November 2020

Background

Ivermectin is one among several potential drugs explored for its therapeutic and preventive role in COVID-19 infection. The study was aimed to explore the association between ivermectin prophylaxis and development of COVID-19 infection among healthcare workers.

Methods

A hospital-based matched case-control study was conducted among healthcare workers of AIIMS Bhubaneswar, India, from September to October 2020. Profession, gender, age and date of diagnosis were matched for 186 case-control pairs. Cases and controls were healthcare workers who tested positive and negative, respectively, for COVID-19 by RT-PCR. Exposure was defined as the intake of ivermectin and/or hydroxychloroquine and/or vitamin-C and/or other prophylaxis for COVID-19. Data collection and entry was done in Epicollect5, and analysis was performed using STATA version 13. Conditional logistic regression models were used to describe the associated factors for COVID-19 infection.

Results

Ivermectin prophylaxis was taken by 77 controls and 38 cases. Two-dose ivermectin prophylaxis (0.27, 95% CI, 0.15-0.51) was associated with 73% reduction of COVID-19 infection among healthcare workers for the following one month, those who were involved in physical activity (3.06 95% CI, 1.18-7.93) for more than an hour/day were more likely to contract COVID-19 infection. Type of household, COVID duty, single-dose ivermectin prophylaxis, vitamin-C prophylaxis and hydroxychloroquine prophylaxis were not associated with COVID-19 infection.

Conclusion

Two-dose ivermectin prophylaxis at a dose of 300 μg/kg with a gap of 72 hours was associated 73% reduction of COVID-19 infection among healthcare workers for the following one-month. Further research is required before its large scale use.
Attitudes and beliefs about family and domestic violence in Australian faith-based communities: A qualitative study
Authors: Truong Mandy , Sharif Mienah , Olsen Anna , Pasalich Dave , Calabria Bianca , Priest Naomi
Published: November 2020

Family and domestic violence (FDV) is a major public health and social issue that is associated with a range of physical, mental and behavioural health outcomes. Religion and faith are powerful and influential in shaping the lives of many individuals and societies, in addition to the social practices, norms and structures that are significant in understanding and responding to FDV. This qualitative study aims to deepen understanding of the influence of religious beliefs and values on attitudes and beliefs of FDV among culturally diverse faith communities in Australia. Interviews and focus groups were conducted with 64 participants from a diverse range of cultural and religious backgrounds which included faith leaders, community members and FDV sector workers. Six main themes were identified describing attitudes, beliefs and knowledge about FDV: 1) Faith and religion do not condone violence; 2) Awareness of FDV is increasing, yet remains often poorly understood; 3) FDV is still a taboo topic; 4) Denial and defensiveness about FDV persist; 5) Patience, endurance and forgiveness is often prioritised over safety; 6) Gender roles and norms founded on religious beliefs and interpretations underpin many FDV understandings and responses. These findings demonstrate the tensions between expressions of faith and attitudes to women and FDV. Further exploration of these issues within specific faith communities, as well as how to support and engage with these communities in increasing understandings of FDV and developing effective responses, is needed in the Australian context.
Infections after routine syndesmotic screw removal – a retrospective quality study
Authors: Øverby Thomas Aleksander , Jakobsen Rune B.
Published: November 2020

Background

Infections after routine removal of syndesmotic screws are an unwanted complication.

Methods

We included all patients treated with syndesmotic screw with routine removal in a five-year period and extracted information regarding fracture characteristics and patient characteristics. Infections were classified as superficial or deep incisional.

Results

1246 patients with ankle fractures were treated surgically in the study period. 343 had routine removals of the syndesmotic screw. We identified 6 cases with infection (1.7%) developing after routine syndesmotic screw removal.

Conclusions

We found a low infection rate but when infections did occur, they frequently required surgical revision(s) and long-time antibiotic treatment.
COVID-19 Pandemic Among Immigrant Latinx Farmworker and Non-farmworker Families: A Rural-Urban Comparison of Economic, Educational, Healthcare, and Immigration Concerns
Authors: Quandt Sara A. , LaMonto Natalie J. , Mora Dana C. , Talton Jennifer W. , Laurienti Paul J. , Arcury Thomas A.
Published: November 2020

COVID-19 has highlighted social and health injustices in the US. Structural inequalities have increased the likelihood of immigrants contracting COVID-19, by being essential workers and through poverty that forces this population to continue working. Rural and urban immigrant families may face different concerns. Using a telephone survey in May 2020 of 105 Latinx families in an existing study, quantitative and qualitative data were gathered on work and household economics, childcare and education, healthcare, and community climate. Analyses show that, although rural and urban groups experienced substantial economic effects, impacts were more acute for urban families. Rural workers reported fewer workplace protective measures for COVID-19. For both groups, fear and worry, particularly about finances and children, dominated reports of their situations with numerous reports of experiencing stress and anxiety. The experience of the pandemic is interpreted as an example of contextual vulnerability of a population already experiencing structural violence through social injustice.
Racial and Ethnic Disparities in Health of Adults in the United States: A 20-Year National Health Interview Survey Analysis, 1999-2018
Authors: Mahajan Shiwani , Caraballo César , Lu Yuan , Massey Dorothy , Murugiah Karthik , Annapureddy Amarnath R. , Roy Brita , Riley Carley , Onuma Oyere , Nunez-Smith Marcella , Valero-Elizondo Javier , Forman Howard P. , Nasir Khurram , Herrin Jeph , Krumholz Harlan M.
Published: November 2020

Importance

Thirty-five years ago, the Heckler Report described health disparities among minority populations in the US. Since then, policies have been implemented to address these disparities. However, a recent evaluation of progress towards improving the health and health equity among US adults is lacking.

Objectives

To evaluate racial/ethnic disparities in the physical and mental health of US adults over the last 2 decades.

Design

Cross-sectional.

Setting

National Health Interview Survey data, years 1999–2018.

Participants

Adults aged 18–85 years.

Exposure

Race/ethnicity subgroups (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic).

Main outcome and measures

Proportion of adults reporting poor/fair health status, severe psychological distress, functional limitation, and insufficient sleep. We also estimated the gap between non-Hispanic White and the other subgroups for these four outcomes.

Results

We included 596,355 adults (mean age 46 years, 51.8% women), of which 69.7%, 13.8%, 11.8% and 4.7% identified as non-Hispanic White, Hispanic, non-Hispanic Black, and non-Hispanic Asian, respectively. Between 1999 and 2018, Black individuals fared worse on most measures of health, with 18.7% (95% CI 17.1–20.4) and 41.1% (95% CI 38.7–43.5) reporting poor/fair health and insufficient sleep in 2018 compared with 11.1% (95% CI 10.5– 11.7) and 31.2% (95% CI 30.3–32.1) among White individuals. Notably, between 1999–2018, there was no significant decrease in the gap in poor/fair health status between White individuals and Black (−0.07% per year, 95% CI −0.16–0.01) and Hispanic (−0.03% per year, 95% CI −0.07– 0.02) individuals, and an increase in the gap in sleep between White individuals and Black (+0.2% per year, 95% CI 0.1–0.4) and Hispanic (+0.3% per year, 95% CI 0.1–0.4) individuals. Additionally, there was no significant decrease in adults reporting poor/fair health status and an increase in adults reporting severe psychological distress, functional limitation, and insufficient sleep.

Conclusions and Relevance

The marked racial/ethnic disparities in health of US adults have not improved over the last 20 years. Moreover, the self-perceived health of US adults worsened during this time. These findings highlight the need to re-examine the initiatives seeking to promote health equity and improve health.
Aerosol and bioaerosol particle size and dynamics from defective sanitary plumbing systems
Authors: Gormley Michael , Aspray Thomas J , Kelly David A
Published: November 2020

Aerosols are readily transported on airstreams through building sanitary plumbing and sewer systems and those containing microbial pathogens (known as bioaerosols) are recognised as contributors to infection spread within buildings. When a defect occurs in the sanitary plumbing system that affects the system integrity, a cross-transmission route is created that can enable the emission of bioaerosols from the system into the building. These emission occurrences are characterised as short-burst events (typically < 1 minute in duration) which makes them difficult to detect and predict. The characterisation of these emission events is the focus of this research.

Two methods were used to characterise bioaerosol emission events in a full scale test rig: (i) an Aerodynamic Particle Sizer (APS) for particle size distribution and concentrations; and (ii) a slit-to-agar sampler to enumerate the ingress of a viable tracer microorganism (Pseudomonas putida). The APS data confirmed that most particles (> 99.5%) were <5 μm and were therefore considered aerosols. Particles generated within the sanitary plumbing system as a result of a toilet flush leads to emissions into the building during system defect conditions with an equivalence of someone talking loudly for over 6 and a half minutes. There were no particles detected of a size > 11μm anywhere in the system. Particle count was influenced by flush volume, but it was not possible to determine if there was any direct influence from airflow rate. Typical emissions resulting from a 6 litre flush were in the range of 280 – 400 particles per second at a concentration of typically 9 to 12 number per cm3 and a total particle count in the region of 3,000 to 4,000 particles, whereas the peak emissions from a 1.2 litre flush was 60 - 80 particles per second at a concentration of 2.4 to 3 number per cm3 and a total particle count in the region of 886 to 1045 particles. The reduction in particles is in direct proportion to the reduction in flush volume. The slit-to-agar sampler was able to provide viable time course CFU data and confirmed the origin of the particles to be the tracer microorganism flushed into the system. The time course data also has characteristics consistent with the unsteady nature of a toilet flush.
MODELLING PRESYMPTOMATIC INFECTIOUSNESS IN COVID-19
Authors: Cheng Russell , Dye Christopher , Dagpunar John , Williams Brian
Published: November 2020

This paper considers SEPIR, the extension of an existing parametric SEIR continuous simulation compartment model. Both models can be fitted to real data as they include parameters that can simply be estimated from the data. However SEPIR deploys an additional presymptomatic (also called asymptomatic) infectious stage that is not included in SEIR but which is known to exist in COVID-19. This stage is also parametrised and so can be fitted to data. Both SEPIR and the existing SEIR model assume a homogeneous mixing population, an idealisation that is unrealistic in practice when dynamically varying control strategies are deployed against virus. This means that if either model is to represent more than just a single period in the behaviour of the epidemic, then the parameters of the model will have to be time dependent. This issue is also discussed in this paper.
Development of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob disease
Authors: Nihat Akin , Mok Tze How , Odd Hans , Thompson Andrew , Caine Diana , McNiven Kirsty , O’Donnell Veronica , Tesfamichael Selam , Rudge Peter , Collinge John , Mead Simon
Published: November 2020

Objective

Sporadic Creutzfeldt-Jakob disease (sCJD) causes rapidly-progressive dementia and complex abnormalities of motor systems with striking phenotypic heterogeneity, but no tools are available for the clinician to determine disease severity from bedside cognitive and neurological assessments. We used a robust statistical methodology and routinely-collected examination data to develop and validate short clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sCJD.

Methods

We undertook a retrospective analysis of clinical examination data from the prospective National Prion Monitoring Cohort study, October 2008 – December 2016. Rasch analysis was used to iteratively construct interval scales measuring composite cognitive and motor dysfunction from pooled bedside neurological and cognitive examination tests.

A longitudinal clinical examination dataset was constructed from a total of 528 patients with sCJD, comprising 1030 Motor Scale and 757 Cognitive Scale scores, over 130 patient-years of study, and used to demonstrate scale utility.

Results

The Rasch-derived Motor Scale consists of 8 items, including examination items reliant on pyramidal, extrapyramidal and cerebellar systems. The Cognitive Scale comprises 6 items, and includes measures of executive function, language, visual perception and memory. Both scales are unidimensional, perform consistently regardless of age or gender and have excellent inter-rater reliability. Each scale can be completed in a few minutes at the bedside, as part of a normal neurocognitive examination. Several uses of the scales, in measuring longitudinal change, prognosis, and phenotypic heterogeneity are illustrated.

Interpretation

These two novel scales measuring motor and cognitive dysfunction in sCJD should prove useful to objectively measure phenotypic and clinical change in future clinical trials and for patient stratification. This statistical approach can help to overcome obstacles to assessing clinical change in rapidly-progressive, multisystem conditions with limited longitudinal follow-up.
Mobile Monitoring of Mood (MoMo-Mood) Pilot: A Longitudinal, Multi-Sensor Digital Phenotyping Study of Patients with Major Depressive Disorder and Healthy Controls
Authors: Triana Ana María , Martikkala Annasofia , Baryshnikov Ilya , Heikkilä Roope , Alakörkkö Tuomas , Darst Richard K. , Ekelund Jesper , Isometsä Erkki , Aledavood Talayeh
Published: November 2020

Mental disorders are a major global cause of morbidity and mortality. The surge in adoption of smartphones and other wearable devices has made it possible to use the data generated by them for clinical purposes. In particular, in psychiatry, detailed and high-resolution information on patient’s state, mood, and behavior can significantly improve the assessment, diagnosis and the treatment of patients. However, there is long path to turn the raw data created by these sensors, to information and insights that can be applied in clinical practice.

Here, we introduce the MoMo-Mood Pilot: a study created to investigate the feasibility of using smartphones and wearables as data collection tools from subjects suffering from major depressive disorder. We collect data from 14 patients and 22 controls in two phases (active and passive). We demonstrate the feasibility of monitoring patients with several devices over short periods and passively monitoring them over long periods of time with minimal disruption in their daily activities. We identify and describe a series of challenges in this process.

The MoMo-Mood pilot study is an encouraging step in the process of determining the effectiveness of using wearables for quantifying the behavior and the state of psychiatric patients with high temporal resolution, which can lead to their potential adoption in clinical practice.
Performance characteristics of a rapid SARS-CoV-2 antigen detection assay at a public plaza testing site in San Francisco
Authors: Pilarowski Genay , Lebel Paul , Sunshine Sara , Liu Jamin , Crawford Emily , Marquez Carina , Rubio Luis , Chamie Gabriel , Martinez Jackie , Peng James , Black Douglas , Wu Wesley , Pak John , Laurie Matthew T. , Jones Diane , Miller Steve , Jacobo Jon , Rojas Susana , Rojas Susy , Nakamura Robert , Tulier-Laiwa Valerie , Petersen Maya , Havlir Diane V. ,   The CLIAHUB Consortium, DeRisi Joseph
Published: November 2020

We evaluated the performance of the Abbott BinaxNOW™ Covid-19 rapid antigen test to detect virus among persons, regardless of symptoms, at a public plaza site of ongoing community transmission. Titration with cultured clinical SARS-CoV-2 yielded a human observable threshold between 1.6×104-4.3×104viral RNA copies (cycle threshold (Ct) of 30.3-28.8 in this assay). Among 878 subjects tested, 3% (26/878) were positive by RT-PCR, of which 15/26 had a Ct<30, indicating high viral load. 40% (6/15) of Ct<30 were asymptomatic. Using this Ct<30 threshold for Binax-CoV2 evaluation, the sensitivity of the Binax-CoV2 was 93.3% (14/15), 95% CI: 68.1-99.8%, and the specificity was 99.9% (855/856), 95% CI: 99.4-99.9%.
Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease
Authors: AlQahtani Manaf , Abdulrahman Abdulkarim , Almadani Abdulrahman , Alali Salman Yousif , Al Zamrooni Alaa Mahmood , Hejab Amal Hamza , Conroy Ronán M , Wasif Pearl , Atkin Stephen L , Otoom Sameer , Abduljalil Manal
Published: November 2020

Background

Convalescent plasma (CP) therapy in COVID-19 disease has been suggested to improve clinical outcome in severe disease. This pilot study was designed to inform the design of a definitive phase 3 clinical trial.

Methods

This was a prospective, interventional and randomized open label pilot trial involving 40 patients with COVID-19 who were requiring oxygen therapy and who had radiological evidence of pneumonia. Twenty COVID-19 patients received two 200ml transfusions of convalescent patient CP over 24 hours were compared with 20 patients who received routine care alone. The primary outcome was the requirement for ventilation. The secondary outcomes were white blood cell count, lactate dehydrogenase (LDH), C-reactive protein (CRP), Troponin, Ferritin, D-Dimer, procalcitonin, mortality rate at 28 days.

Results

The CP group were a higher risk group with higher ferritin levels (p<0.05) though respiratory indices did not differ. The primary outcome measure – ventilation – was required in 6 controls and 4 patients on CP (risk ratio 0.67 95% CI 0.22 – 2.0, p=0.72); mean time on ventilation was 10.5 days in the control against 8.2 days in patients on CP (p=0.81). There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm.

Conclusion

There were no significant differences in the primary or secondary outcome measures between CP and standard therapy though fewer patients required ventilation and for a shorter period of time. The study showed that CP therapy appears to be safe and it is feasible to perform a definitive phase 3 clinical trial using this study protocol.
Understanding COVID-19 testing pathways in English care homes to identify the role of point-of-care testing: an interview-based process mapping study
Authors: Micocci Massimo , Gordon Adam L , Allen A. Joy , Hicks Timothy , Kierkegaard Patrick , McLister Anna , Walne Simon , Buckle Peter
Published: November 2020

Introduction

Care home residents are at high risk of dying from COVID-19. Regular testing producing rapid and reliable results is important in this population because infections spread quickly and presentations are often atypical or asymptomatic. This study evaluated current testing pathways in care homes to explore the role of point-of-care tests (POCTs).

Methods

Ten staff from eight care homes, purposively sampled to reflect care organisational attributes that influence outbreak severity, underwent a semi-structured remote videoconference interview. Transcripts were analysed using process mapping tools and framework analysis focussing on perceptions about, gaps within, and needs arising from, current pathways.

Results

Four main steps were identified in testing: infection prevention, preparatory steps, swabbing procedure, and management of residents. Infection prevention was particularly challenging for mobile residents with cognitive impairment. Swabbing and preparatory steps were resource-intensive, requiring additional staff resource. Swabbing required flexibility and staff who were familiar to the resident. Frequent approaches to residents were needed to ensure they would participate at a suitable time. After-test management varied between sites. Several homes reported deviating from government guidance to take more cautious approaches, which they perceived to be more robust.

Conclusion

Swab-based testing is organisationally complex and resource-intensive in care homes. It needs to be flexible to meet the needs of residents and provide care homes with rapid information to support care decisions. POCT could help address gaps but the complexity of the setting means that each technology must be evaluated in context before widespread adoption in care homes.

Key-points

Testing for COVID-19 in care homes is complex and requires reconfiguration of staffing and environment.

Isolation and testing procedures are challenged when providing person-centred care to people with dementia.

Point-of-care testing results could give care homes greater flexibility to test in person-centred ways.

There was evidence that care home staff interpret testing guidance, rather than follow it verbatim.

Each POCT must be evaluated in the context of care homes to understand its effect on care home processes.
Vascular Thrombosis in COVID-19: A Potential Association with Antiphospholipid Antibodies
Authors: Kallapur Aneesh S , Yen Eric Y , Singh Ram Raj
Published: November 2020

Background

Vascular thrombosis is common in patients with coronavirus disease 2019 (COVID-19). Etiologies underlying this complication are unclear.

Purpose

To determine the prevalence of antiphospholipid (aPL), including lupus anticoagulant, anti-cardiolipin and anti-β2-glycoprotein-1 antibodies, and its possible association with thrombotic manifestations of COVID-19.

Data Sources

We searched MEDLINE indexed journals on September 24, 2020 using the tool LitCovid and the pre-print server medRxIV.

Study Selection

Original investigations (cross-sectional studies, cohort studies, case series, and research letters) on COVID-19 and thrombosis were included.

Data Extraction

Data were independently extracted, and compiled into spreadsheets based on the PRISMA principles.

Data Synthesis

Hospitalized patients with COVID-19 showed a higher prevalence of lupus anticoagulant compared to non-COVID-19 patients. Temporally, lupus anticoagulant was generally positive early in the course of illness, whereas anti-cardiolipin and anti-β2-glycoprotein-1 antibodies appeared to emerge later in the disease. Some patients who were aPL-negative at an early time-point after disease onset became aPL-positive at a later time-point. Lupus anticoagulant was independently associated with thrombosis in 60 COVID-19 patients in New York had who had 32 thrombotic events (8 arterial and 24 venous). In 88 patients in Wuhan, who had more than 20 each of arterial and venous thrombotic events, medium/high positivity for multiple aPL was significantly associated with arterial thrombosis. However, the association of aPL with thrombosis was not evident in reports that had an overall lower number of or predominantly venous thrombotic events. Analysis of pooled patients revealed that aPL were significantly more frequent in COVID-19 patients with stroke than stroke patients in the general population. Furthermore, injection of IgG aPL fractions from COVID-19 patients into mice accelerated venous thrombosis.

Limitation

Limited data and paucity of prospective studies.

Conclusion

The aPL are prevalent in patients with COVID-19 and their presence is associated with thrombosis. Importantly, these antibodies may be a key mechanism of thrombosis in COVID-19. Follow-up studies are required to understand the relationship between aPL and the spectrum of vascular thrombosis during and after infection with SARS-CoV-2.

Primary Funding Source

None.
The CCR5-delta32 variant might explain part of the association between COVID-19 and the chemokine-receptor gene cluster
Authors: Gómez Juan , Cuesta-Llavona Elías , Albaiceta Guillermo M. , García-Clemente Marta , López-Larrea Carlos , Amado-Rodríguez Laura , López-Alonso Inés , Hermida Tamara , EnrÍquez Ana I. , Gil Helena , Alonso Belén , Iglesias Sara , Suarez-Alvarez Beatriz , Alvarez Victoria , Coto Eliecer
Published: November 2020

A polymorphism in the LZTFL1 gene located in the chemokine-receptor gene cluster (chromosome 3p) has been associated with the risk of developing COVID-19. The chemokine receptor-5 (CCR5) maps to this region, and the common 32 bp deletion variant (Δ32) has been associated with the extent of inflammatory disease and the outcome in several viral diseases. Several studies have also suggested that the pharmacological targeting of CCR5 could reduce the impact of SARS-CoV-2 infection and the severity of COVID-19. We sought to investigate whether this polymorphism was associated with the risk of moderate-severe COVID-19.

We genotyped 294 patients who required hospitalization due to COVID-19 (85 were severe cases) and 460 controls. We found a significantly lower frequency of CCR5-Δ32 among the COVID-19 patients (0.10 vs 0.18 in controls; p=0.002, OR=0.48, 95%CI=0.29-0.76). The difference was mainly due to the reduced frequency of CCR5-Δ32 carriers in the severe, significantly lower than in the non-severe patients (p=0.036). Of note, we did not find deletion-homozygotes among the patients compared to 1% among controls. We also confirmed the association between a LZTFL1 variant and COVID-19. Our study points to CCR5 as a promising target for treatment of COVID-19, but requires validation in additional large cohorts. In confirmed by others, the genetic analysis of CCR5-variants (such as Δ32) might help to identify patients with a higher susceptibility to severe COVID-19.
Sharing ventilators in the Covid-19 pandemics. A bench study
Authors: Guérin Claude , Cour Martin , Stevic Neven , Degivry Florian , L’Her Erwan , Louis Bruno , Argaud Laurent
Published: November 2020

COVID-19 pandemics sets the healthcare system to a shortage of ventilators. We aimed at assessing tidal volume (VT) delivery and air recirculation during expiration when one ventilator is divided into 2 patients. The study was performed in a research laboratory in a medical ICU of a University hospital. An ICU-dedicated (V500) and a lower-level ventilator (Elisée 350) were attached to two test-lungs (QuickLung) through a dedicated flow-splitter. A 50 mL/cmH2O Compliance (C) and 5 cmH2O/L/s Resistance (R) were set in both A and B lungs (step1), C50R20 in A / C20R20 in B (step 2), C20R20 in A / C10R20 in B (step 3), and C50R20 in A / C20R5 in B (step 4). Each ventilator was set in volume and pressure control mode to deliver 0.8L VT. We assessed VT from a pneumotachograph placed immediately before each lung, rebreathed volume, and expiratory resistance (circuit and valve). Values are median (1st-3rd quartiles) and compared between ventilators by non-parametric tests. Between Elisée 350 and V500 in volume control VT in A/B patients were 0.381/0.387 vs. 0.412/0.433L in step 1, 0.501/0.270 vs. 0.492/0.370L in step 2, 0.509/0.237 vs. 0.496/0.332L in step 3, and 0.496/0.281 vs. 0.480/0.329L in step 4. In pressure control the corresponding values were 0.373/0.336 vs. 0.430/0.414L, 0.416/0.185/0.322/0.234L, 0.193/0.108 vs. 0.176/0.092L and 0.422/0.201 vs. 0.481/0.329L, respectively (P<0.001 between ventilators at each step for each volume). Rebreathed air volume ranged between 0.7 to 37.8 ml and negatively correlated with expiratory resistance in steps 2 and 3. The lower-level ventilator performed closely to the ICU-dedicated ventilator. Due to dependence of VT to C pressure control should be used to maintain adequate VT at least in one patient when C and/or R changes abruptly and monitoring of VT should be done carefully. Increasing expiratory resistance should reduce rebreathed volume.
Encoding of facial features by single neurons in the human amygdala and hippocampus
Authors: Cao Runnan , Li Xin , Brandmeir Nicholas J. , Wang Shuo
Published: November 2020

The human amygdala and hippocampus play a key role in face processing. However, it has been unknown how the neurons in the human amygdala and hippocampus encode facial feature information and directs eye movements to salient facial features such as the eyes and mouth. In this study, we identified a population of neurons that differentiated fixations on the eyes vs. mouth. The response of these feature-selective neurons was not dependent on fixation order, and eye-preferring and mouth-preferring neurons were not of different neuronal types. We found another population of neurons that differentiated saccades to the eyes vs. mouth. Population decoding confirmed our results and further revealed the temporal dynamics of face feature coding. Interestingly, we found that the amygdala and hippocampus played a different role in encoding face features. Lastly, we revealed two functional roles of feature-selective neurons that they encoded the salient region for face recognition and they encoded perceived social trait judgment. Together, we revealed and characterized a new class of neurons that encoded facial features. These neurons may play an important role in social perception and recognition of faces.
Heritable environments: bias due to conditioning on a collider in models with polygenic scores
Authors: Akimova Evelina T. , Breen Richard , Brazel David M. , Mills Melinda C.
Published: November 2020

The application of polygenic scores has transformed our ability to investigate whether and how genetic and environmental factors jointly contribute to the variation of complex traits. Modelling the complex interplay between genes and environment, however, raises serious methodological challenges. Here we illustrate the largely unrecognised impact of gene-environment dependencies on the identification of the effects of genes and their variation across environments. We show that controlling for heritable covariates in regression models that include polygenic scores as independent variables introduces endogenous selection bias when one or more of these covariates depends on unmeasured factors that also affect the outcome. This results in the problem of conditioning on a collider, which in turn leads to spurious associations and effect sizes. Using graphical and simulation methods we demonstrate that the degree of bias depends on the strength of the gene-covariate correlation and of hidden heterogeneity linking covariates with outcomes, regardless of whether the main analytic focus is mediation, confounding, or gene × covariate (commonly gene × environment) interactions. We offer potential solutions, highlighting the importance of causal inference. We also urge further caution when fitting and interpreting models with polygenic scores and non-exogenous environments or phenotypes and demonstrate how spurious associations are likely to arise, advancing our understanding of such results.
Cortical representation of pain by stable dedicated neurons and dynamic ensembles
Authors: Acuña Mario A. , Kasanetz Fernando , De Luna Paolo , Nevian Thomas
Published: November 2020

The perception of pain arises from distributed brain activity triggered by noxious stimuli. However, which patterns of activity make nociception distinct from other salient sensory experiences is still unknown. Usingin vivochronic two-photon calcium imaging in slightly anaesthetized mice, we identified a nociception-specific representation in the anterior cingulate cortex (ACC), that is attained by a core of neurons that code for a generalized concept of the pain experience. The overall ensemble activity allowed for an efficient discrimination of the sensory space, despite a drift in single-neuron sensory tuning over time. Following sciatic nerve lesion, the representation of nociceptive stimuli was impaired as a consequence of innocuous stimuli expanded into the nociception-specific ensemble, leading to a dysfunctional discrimination of sensory events in the ACC. Thus, the hallmark of chronic pain at the cortical neuronal network level is an impairment of pattern separation and classification identifying a circuit mechanism for altered pain processing in the brain.
The meadow jumping mouse genome and transcriptome suggest mechanisms of hibernation
Authors: Cong Qian , Brem Ethan A. , Zhang Jing , Alföldi Jessica , Johnson Jeremy , Karlsson Elinor K. , Lindblad-Toh Kerstin , Malaney Jason L. , Israelsen William J.
Published: November 2020

Hibernating mammals exhibit medically relevant phenotypes, but the genetic basis of hibernation remains poorly understood. Using the meadow jumping mouse (Zapus hudsonius), we investigated the genetic underpinnings of hibernation by uniting experimental and comparative genomic approaches. We assembled aZ. hudsoniusgenome and identified widespread expression changes during hibernation in genes important for circadian rhythm, membrane fluidity, and cell cycle arrest. Tissue-specific gene expression changes during torpor encompassed Wnt signaling in the brain and structural and transport functions in the kidney brush border. Using genomes from the closely relatedZapus oregonus(previously classified asZ. princeps) and leveraging a panel of hibernating and non-hibernating rodents, we found selective pressure on genes involved in feeding behavior, metabolism, and cell biological processes potentially important for function at low body temperature. Leptin stands out with elevated conservation in hibernating rodents, implying a role for this metabolic hormone in triggering fattening and hibernation. These findings illustrate that mammalian hibernation requires adaptation at all levels of organismal form and function and lay the groundwork for future study of hibernation phenotypes.
Properties of genes encoding transfer RNAs as integration sites for genomic islands and prophages inKlebsiella pneumoniae
Authors: Berríos-Pastén Camilo , Acevedo Rodolfo , Arros Patricio , Varas Macarena A. , Wyres Kelly L. , Lam Margaret M. C. , Holt Kathryn E. , Lagos Rosalba , Marcoleta Andrés E.
Published: November 2020

The evolution of traits including antibiotic resistance, virulence, and increased fitness inKlebsiella pneumoniaeand related species has been linked to the acquisition of mobile genetic elements through horizontal transfer. Among them, genomic islands (GIs) preferentially integrating at genes encoding tRNAs and the tmRNA (t(m)DNAs) would be significant in promoting chromosomal diversity. Here, we studied the whole set of t(m)DNAs present in 66Klebsiellachromosomes, investigating their usage as integration sites and the properties of the integrated GIs. A total of 5,624 t(m)DNAs were classified based on their sequence conservation, genomic context, and prevalence. 161 different GIs and prophages were found at these sites, hosting 3,540 gene families including various related to virulence and drug resistance. Phylogenetic analyses supported the acquisition of several of these elements through horizontal gene transfer, likely mediated by a highly diverse set of encoded integrases targeting specific t(m)DNAs and sublocations inside them. Only a subset of the t(m)DNAs had integrated GIs and even identical tDNA copies showed dissimilar usage frequencies, suggesting that the genomic context would influence the integration site selection. This usage bias, likely towards avoiding disruption of polycistronic transcriptional units, would be conserved across Gammaproteobacteria. The systematic comparison of the t(m)DNAs across different strains allowed us to discover an unprecedented number ofK. pneumoniaeGIs and prophages and to raise important questions and clues regarding the fundamental properties of t(m)DNAs as targets for the integration of mobile genetic elements and drivers of bacterial genome evolution and pathogen emergence.
Successive waves in pandemic infections: physical diffusion theory and data comparisons
Authors: Duffey Romney B
Published: November 2020

We establish the principal that the prediction, timing and magnitude of second and more distinct waves of infection can be based on the well - known physics and assumptions of classical diffusion theory. This model is fundamentally different from the commonly used SEIR and R0 fitting methods. Driven by data, we seek a working approximation for the observed orders of magnitude for the timing and rate of second and more waves. The dynamic results and characteristics are compared to the data and enable predictions of timescales and maximum expected rates where diffusive effects dominate.

The important point is this simple physical model allows understanding of the dominant processes, provides prediction estimates, and is based the solutions derived from existing, consistent and well-known physical principles. The medical system and health policy implications of such inexorable diffusive spread are that any NPI and other countermeasures deployed for and after the rapid first peak must recognize that large residual infection waves will then likely occur.
Novel incursion of a highly pathogenic avian influenza subtype H5N8 virus in the Netherlands, October 2020
Authors: Beerens Nancy , Heutink Rene , Harders Frank , Roose Marit , Pritz-Verschuren Sylvia B.E. , Germeraad Evelien A. , Engelsma Marc
Published: November 2020

The HPAI H5N8 virus detected in mute swans in the Netherlands in October 2020 shares a common ancestor with clade 2.3.4.4b viruses last detected in Egypt in 2018-2019 and has a similar genetic composition. The virus is not directly related to European H5N8 viruses detected in first half of 2020.