bluuebunny/crossref_metadata_2025 huggingface dataset:
Suicide prevention by education and the moulding of attitudes
Authors: Titelman David , Wasserman Danuta
Published: February 2021

In this chapter, the challenge of influencing the attitudes towards suicide prevention in key individuals or gatekeepers, in mental health and suicide prevention, is addressed. Based on experiences from several training programmes, the importance of a psychological perspective on suicidality is seen as relevant even in population-based research and prevention. One focus in the discussion is on the distinction between having an immediate impact on conscious attitudes and the more difficult challenge of influencing less conscious, individual, and cultural ambivalent attitudes to suicide prevention. In light of the universal stigma of and taboo against the topic of suicide, the ability of prevention specialists to withhold judgement and reflect on their own emotional responses to self-destructiveness is considered as an aspect of a scientific attitude. In addition, an anthropological elucidation of mental ill-health and suicide is called for as a supplement to the biopsychosocial, stress-vulnerability paradigm in suicide-preventive training programmes.
Prevention of suicide due to charcoal burning
Authors: Chen Ying-Yeh , Wong Jacky , Yip Paul
Published: February 2021

Since the year 2000, suicide by combustion of barbecue charcoal in an enclosed space has become a common method of suicide in many East Asian countries. The spread of charcoal burning suicides was related to the pervasive media glamorization of the method to be a painless, peaceful, and effective way to end one’s life. Popularity of the internet accompanying its contagious effect further imposes challenges in suicide prevention, in particular, in the prevention of charcoal burning suicides. In areas where charcoal burning has already become a common method of suicide, effective strategies include working with the media to moderate the reporting of suicide news and creating barriers in the purchase of charcoal. In other areas where the method is still not widely known, muting the media reporting of this specific method of suicide to eliminate its ‘cognitive availability’ is key to prevent the seeding of charcoal burning suicides.
The American Foundation for Suicide Prevention (AFSP)
Authors: Gebbia Robert , Moutier Christine
Published: February 2021

In 1987, leading suicide researchers joined with families who had lost a loved one to suicide to form the American Foundation for Suicide Prevention (AFSP). It was established with the goal of advancing research necessary to understand and prevent suicide and has since evolved to include educating mental health professionals and the public about suicide prevention. Using scientific evidence to guide its prevention work, the AFSP aims to lower suicide rates, increase public and private resources available for suicide research and prevention, and develop and support programmes to assist survivors of suicide loss, through focuses that include advocacy and public policy. The work and influence of the AFSP on suicide prevention is presented here.
Evidence-based suicide prevention strategies during and after the COVID-19 pandemic
Authors: Wasserman Danuta , Carli Vladimir
Published: February 2021

Evidence has shown that during times of crises, suicide rates can decrease but tend to increase as the crisis alleviates. The consequences of the global COVID-19 pandemic, whether direct or indirect, will be far reaching. In this chapter the impact of the pandemic on the risk and protective factors of suicide, grouped according to the socio-ecological model at individual, relationship, community, and society levels, is described. To prevent unnecessary suicides, the effects of Covid-19 pandemic, on health care and public health suicide prevention strategies, and recommendations for implementation are presented.
The scope of psychiatric ethics
Authors: Bloch Sidney , Green Stephen A.
Published: February 2021

Ethical decision-making is no easy matter, as absolutes of right and wrong, good and bad, should and ought, and other evaluative terms are elusive. Both providing the best attainable care for the patient and conducting scientific research guided by lofty ethical principles are paramount. This chapter, an introduction to the fifth edition of Psychiatric Ethics, outlines how the book aims to promote the moral agency of psychiatrists and mental health professionals when relating to patients and their families, colleagues, professional associations, and other organizations, and the society in which they work. It summarizes theoretical frameworks used in ethical decision-making and the range of topics discussed in the other 24 chapters, and offers guidelines to mental health students and graduate clinicians about how to master the field of ethics in psychiatry.
Psychiatric ethics and the professions
Authors: Coady Margaret M.
Published: February 2021

The chapter provides a critical analysis of past understandings of the characteristics of professions. Many of these characteristics have lost meaning in the twenty-first century. High status has been diminished partly by professionals’ betrayal of the values they expound, but partly also by social factors such as rapid communication of information and changed understanding of the nature of knowledge, both of which have led to general scepticism about expertise. Professionals’ previous relative autonomy is challenged by government intervention and by the fact that more professionals are employed in large organizations where managers are the power centres. The chapter argues for a ‘new professionalism’ and takes two principles from the Code of Ethics of the Royal Australian and New Zealand College of Psychiatry to demonstrate how carefully deliberated codes of ethics can enunciate the particular values which the professions contribute in a well-functioning society.
Psychiatric genetics
Authors: Allan Charlotte L. , Farmer Anne , McGuffin Peter
Published: February 2021

The development of psychiatric genetics as a scientific discipline has provided extraordinary changes in our ability to understand the causes of psychiatric illness. Yet, any research that delves into our genetic code and the fundamentals of what it is to be human is bound to be accompanied by vigorous ethical debate. This has certainly been the case for psychiatric genetics. We offer an overview of the development of the discipline and its associated controversies, and a consideration of recent advances in psychiatric genetics that continue to provide lively debate. Key ethical issues including those relating to eugenics, consent, confidentiality, commercialization and direct to consumer testing, prenatal testing, and clinical use of genetic testing are considered in the hope of ensuring that future developments are accompanied by a well-reasoned conversation that ensures that technological and scientific advances are used for patient benefit in its broadest sense.
Community psychiatry
Authors: Szmukler George
Published: February 2021

Ethical dilemmas in community psychiatry are not novel, but they present in sufficiently different guises to warrant reconsideration in a new context. The models of care and the social climate in which they have developed are reviewed, as well as the key ethical challenges that have emerged. These include concerns about privacy, confidentiality, coercive practices (the range of treatment pressures, ‘involuntary outpatient commitment’ or ‘community treatment orders’), and conflicts of duty to the patient versus others. Approaches to dealing with these issues are presented. These include increasing patients’ involvement in their care (e.g., ‘crisis cards’, ‘joint crisis plans’, and advance directives), clarifying grounds for coercive interventions in the health interests of the patient (e.g., a decision-making-capacity-based approach, the influence of the UN Convention on the Rights of Persons with Disabilities), and considerations concerning the risk of harm to others, including duties to carers.
Trauma and psychiatry
Authors: Robertson Michael , Walter Garry
Published: February 2021

Over the last decade, psychological trauma has re-emerged as a critical factor in psychiatric discourse. The ubiquity of traumatic stress, extending from the hidden ‘epidemic’ of violence within families to the vexed challenges posed by the chaotic geopolitical challenges since 9/11, has forced psychiatry to engage again with the area. This chapter examines the ethical challenges arising from the reformulation of posttraumatic stress disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, trauma-informed care in health systems, recent progress in the understanding of the psychobiology of traumatic stress, and how psychiatrists must position themselves in an increasingly illiberal society that often fails to protect the most vulnerable people.
Prevention of postpartum venous thromboembolism (VTE)
Authors: O’Doherty Roseann , Ní Ainle Fionnuala
Published: February 2021

Venous thromboembolism (VTE) is a leading cause of maternal mortality in developed countries. The baseline pregnancy-associated VTE (PA-VTE) risk is further increased by additional maternal, pregnancy, and delivery characteristics. In a recently developed risk prediction model for postpartum VTE, emergency caesarean section, stillbirth, postpartum haemorrhage, pre-eclampsia/eclampsia, infection, and medical comorbidities were the strongest VTE predictors. While the evidence base supporting optimal strategies for reducing the risk of postpartum VTE in general is weak, for women with prior VTE it appears that this risk may be reduced by up to 75% with low-molecular-weight heparin (LMWH). VTE prevention in women with more common VTE risk factors is a knowledge gap in 2020, with widely varying international guideline recommendations. However, there is no debate surrounding the requirement to perform systematic VTE risk assessment in pregnant and postpartum women.
Pregnancy and obstetric complications in women with autoimmune diseases
Authors: Ware Branch D.
Published: February 2021

For most women, pregnancy is suspected when the symptoms of early pregnancy develop—these include breast soreness or tenderness, fatigue, nausea, and missed menses. Human chorionic gonadotropin (hCG) is first detectable using sensitive tests in the urine and blood of pregnant women 8–10 days after conception (day 22–24 of a 28-day menstrual cycle). Concentrations of hCG rise rapidly in early pregnancy, peak at 9–10 weeks, and decline thereafter to a nadir at 20 weeks. Understanding embryo-foetal development and maternal physiological accommodation to pregnancy is required for the optimal management of pregnancy in women with autoimmune diseases. This chapter reviews the important developmental and physiologic aspects of normal pregnancy and both common and unique obstetric complications associated with selected rheumatic conditions.
Treatment of a Combined Pectoralis Major Tear, Anterior Labral Tear, and Humeral Avulsion of the Glenohumeral Ligament (HAGL) in an Active Duty Soldier
Authors: Wolfley Cortney N , DeFoor Mikalyn T , Antosh Ivan J , Parada Stephen A
Published: February 2021

Anterior glenohumeral instability is an increasingly common injury among young military servicemen. First-time dislocations occurring in combination with anterior labral tears and humeral avulsion of glenohumeral ligament lesions, although rare, significantly contribute to further shoulder dysfunction with recurrent instability and pain. Tears of the pectoralis major are also a type of injury more common in the military population, with operative management resulting in decreased strength. We present a unique case of a young, active duty male that sustains an anterior shoulder dislocation with a concomitant pectoralis major tendon rupture while bench press weight lifting in preparation for the Army Special Forces selection. To the best of our knowledge, this is the first case presented in the literature describing management of a simultaneous anterior shoulder dislocation, humeral avulsion of glenohumeral ligament lesion, and pectoralis major tendon rupture treated with a single operation. After aggressive rehabilitation, the patient was able to successfully pass Special Forces selection and has near full function of the operative shoulder with remarkable satisfaction scores.
Housing insecurity and sleep among welfare recipients in California
Authors: Bozick Robert , Troxel Wendy M , Karoly Lynn A
Published: February 2021

Study Objectives

To estimate the effect of housing insecurity on sleep duration and sleep quality.

Methods

Using longitudinal data from a sample of 1,046 welfare recipients in the state of California followed from 2015–2016 through 2017–2018, we regressed self-reported measures of sleep duration and sleep quality recorded in 2017–2018 on experiences of housing insecurity in the prior year. We applied propensity score weights to attenuate potential bias from an array of observed covariates, including sleep duration and sleep quality measured prior to experiences with housing insecurity.

Results

Sample members who were unable to make their rent/mortgage payments slept on average 22 fewer minutes a night and had lower quality sleep than those who were able to make their rent/mortgage payments. Sample members who were forced to move because of an inability to make rent/mortgage payments slept on average 32 fewer minutes a night and had lower quality sleep than those who were not forced to move.

Conclusions

By compromising sleep health, housing insecurity represents a distinct form of stress in the lives of economically-disadvantaged adults, which could also contribute to other health disparities.
Is complex fault zone behaviour a reflection of rheological heterogeneity?
Authors: Fagereng Å. , Beall A.
Published: February 2021

Fault slip speeds range from steady plate boundary creep through to earthquake slip. Geological descriptions of faults range from localized displacement on one or more discrete planes, through to distributed shearing flow in tabular zones of finite thickness, indicating a large range of possible strain rates in natural faults. We review geological observations and analyse numerical models of two-phase shear zones to discuss the degree and distribution of fault zone heterogeneity and effects on active fault slip style. There must be certain conditions that produce earthquakes, creep and slip at intermediate velocities. Because intermediate slip styles occur over large ranges in temperature, the controlling conditions must be effects of fault properties and/or other dynamic variables. We suggest that the ratio of bulk driving stress to frictional yield strength, and viscosity contrasts within the fault zone, are critical factors. While earthquake nucleation requires the frictional yield to be reached, steady viscous flow requires conditions far from the frictional yield. Intermediate slip speeds may arise when driving stress is sufficient to nucleate local frictional failure by stress amplification, or local frictional yield is lowered by fluid pressure, but such failure is spatially limited by surrounding shear zone stress heterogeneity.

This article is part of a discussion meeting issue ‘Understanding earthquakes using the geological record’.
Antigen-specific tolerization in human autoimmunity: Inhibition of interferon-beta1a anti-drug antibodies in multiple sclerosis
Authors: Marta Monica , Baker David , Creeke Paul , Pryce Gareth , Gnanapavan Sharmilee , Giovannoni Gavin
Published: February 2021

Background

Antigen-specific tolerance in auto-immune diseases is the goal for effective treatment with minimal side-effects. Whilst this is achievable in animal models, notably via intravenous delivery of the model-specific autoantigen following transient CD4 T cell depletion, specific multiple sclerosis autoantigens remain unproven. However, anti-drug antibodies to human therapeutic proteins represent a model human autoimmune condition, which may be used to examine immune-tolerance induction. Some people with MS (PwMS) on interferon-beta1a (IFNβ1a) develop neutralizing antibodies to IFNβ1a that do not disappear in repeated tests over years.

Methods

One PwMS was recruited, as part of a planned phase IIa trial (n=15), who had developed neutralizing antibodies to subcutaneous IFNβ1a. Mitoxantrone (12mg/m2) was administered as a lymphocyte depleting agent followed by four days of (88μg/day + three 132μg/day) intravenous IFNβ1a. Subcutaneous IFNβ1a three times a week was maintained during follow-up. IFNβ1a neutralizing antibody responses in serum were measured during treatment and three-monthly for 12 months.

Findings

One participant was recruited and, within 6 months of tolerization, the neutralizing antibodies were undetectable. The tolerization treatment was well tolerated. However, the study was terminated after the first enrolment, on ethical grounds, as treatment alternatives became available and the potential risks of mitoxantrone use increased.

Interpretation

The data suggest that it may be possible to induce antigen-specific tolerance by providing tolerogenic antigen following transient immune depletion. Further studies are warranted.

Funding

The study was supported by an unrestricted research grant from Merck-Serono.
PCR assay to enhance global surveillance for SARS-CoV-2 variants of concern
Authors: Vogels Chantal B.F. , Breban Mallery I. , Alpert Tara , Petrone Mary E. , Watkins Anne E. , Ott Isabel M. , de Jesus Jaqueline Goes , Claro Ingra Morales , Magalhães Ferreira Giulia , Crispim Myuki A.E. ,   Brazil-UK CADDE Genomic Network, Singh Lavanya , Tegally Houriiyah , Anyaneji Ugochukwu J. ,   NGS-SA, Hodcroft Emma B. , Mason Christopher E. , Khullar Gaurav , Metti Jessica , Dudley Joel T. , MacKay Matthew J. , Nash Megan , Wang Jianhui , Liu Chen , Hui Pei , Murphy Steven , Neal Caleb , Laszlo Eva , Landry Marie L. , Muyombwe Anthony , Downing Randy , Razeq Jafar , de Oliveira Tulio , Faria Nuno R. , Sabino Ester C. , Neher Richard A. , Fauver Joseph R. , Grubaugh Nathan D.
Published: February 2021

With the emergence of SARS-CoV-2 variants that may increase transmissibility and/or cause escape from immune responses1–3, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant first detected in the UK4,5 could be serendipitously detected by the ThermoFisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike Δ69-70, would cause a “spike gene target failure” (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern that lack spike Δ69-70, such as B.1.351 (also 501Y.V2) detected in South Africa6 and P.1 (also 501Y.V3) recently detected in Brazil7. We identified a deletion in the ORF1a gene (ORF1a Δ3675-3677) in all three variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675-3677 as the primary target and spike Δ69-70 to differentiate, we designed and validated an open source PCR assay to detect SARS-CoV-2 variants of concern8. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence spread of B.1.1.7, B.1.351, and P.1.
Age significantly influences the sensitivity of SARS-CoV-2 rapid antibody assays
Authors: Irwin Natalie , Murray Lyle , Ozynski Benjamin , Richards Guy A , Paget Graham , Venturas Jacqueline , Kalla Ismail , Diana Nina , Mahomed Adam , Zamparini Jarrod
Published: February 2021

BACKGROUND

Point of care serological assays are a promising tool in COVID-19 diagnostics but do have limitations. This study evaluated the sensitivity of five rapid antibody assays and explored factors influencing their sensitivity to detect SARS-CoV-2-specific IgG and IgM antibodies.

METHODS

Finger-prick blood samples from 102 participants, within two to six weeks of PCR-confirmed COVID-19 diagnosis, were tested for IgG and IgM on five rapid serological assays. The assay sensitivities were compared, and patient factors evaluated in order to investigate potential associations with assay sensitivity.

RESULTS

Sensitivity ranged from 36% to 69% for IgG and 13% to 67% for IgM. Age was the only factor significantly influencing the likelihood of a detectable IgG or IgM response. Individuals aged 40 years and older had an increased likelihood of a detectable IgG or IgM antibody response by rapid antibody assay.

CONCLUSION

Rapid serological assays demonstrate significant variability when used in a real-world clinical context. There may be limitations in their use for COVID-19 diagnosis amongst the young.
Pharmacometabolomics Identifies Candidate Predictor Metabolites of an L-carnitine Treatment Mortality Benefit in Septic Shock
Authors: Puskarich Michael A. , Jennaro Theodore S. , Gillies Christopher E. , Evans Charles R. , Karnovsky Alla , McHugh Cora E. , Flott Thomas L. , Jones Alan E. , Stringer Kathleen A.
Published: February 2021

Background

Sepsis-induced metabolic dysfunction contributes to organ failure and death. L-carnitine has shown promise for septic shock, but a recent study demonstrated a non-significant reduction in mortality.

Methods

A pharmacometabolomics study of patients (n=250) in a Phase II trial of L-carnitine to identify metabolic profiles predictive of a 90-day mortality benefit from L-carnitine. The independent predictive value of each pre-treatment metabolite concentration, adjusted for L-carnitine dose, on 90-day mortality was determined by logistic regression. A grid-search analysis maximizing the Z-statistic from a binomial proportion test identified specific metabolite threshold levels that discriminated L-carnitine responsive patients. Threshold concentrations were further assessed by hazard-ratio and Kaplan-Meier estimate.

Findings

Accounting for L-carnitine treatment and dose, 11 1H-NMR metabolites and 12 acylcarnitines were independent predictors of 90-day mortality. Based on the grid-search analysis numerous acylcarnitines and valine were identified as candidate metabolites of drug response. Acetylcarnitine emerged as highly viable for the prediction of an L-carnitine mortality benefit due to its abundance and biological relevance. Using its most statistically significant threshold concentration, patients with acetylcarnitine ≥35µM were less likely to die at 90 days if treated with L-carnitine (18 g) versus placebo (p=0.01 by log rank test).

Interpretation

Metabolomics identified independent predictors of 90-day sepsis mortality. Our proof-of-concept approach shows how pharmacometabolomics may be useful for tackling the heterogeneity of sepsis and informing clinical trial design. Also, metabolomics can help understand mechanisms of sepsis heterogeneity and variable drug response, since sepsis induces alterations in numerous metabolite concentrations.
Resource Allocation for Different Types of Vaccines against COVID-19: Tradeoffs and Synergies between Efficacy and Reach
Authors: Kim Daniel , Pekgün Pelin , Yildirim İnci , Keskinocak Pınar
Published: February 2021

Objective

Vaccine shortage and supply-chain challenges have caused limited access by many resource-limited countries during the COVID-19 pandemic. One of the primary decisions for a vaccine-ordering decision-maker is how to allocate the limited resources between different types of vaccines effectively. We studied the tradeoff between efficacy and reach of the two vaccine types that become available at different times.

Methods

We extended a Susceptible-Infected-Recovered-Deceased (SIR-D) model with vaccination, ran extensive simulations with different settings, and compared the level of infection attack rate (IAR) under different reach ratios between two vaccine types under different resource allocation decisions.

Results

We found that when there were limited resources, allocating resources to a vaccine with high efficacy that became available earlier than a vaccine with lower efficacy did not always lead to a lower IAR, particularly if the former could vaccinate less than 42.5% of the population (with the selected study parameters) who could have received the latter. Sensitivity analyses showed that this result stayed robust under different study parameters.

Conclusions

Our results showed that a vaccine with lower resource requirements (wider reach) can significantly contribute to reducing IAR, even if it becomes available later in the pandemic, compared to a higher efficacy vaccine that becomes available earlier but requires more resources. Limited resource in vaccine distribution is significant challenge in many parts of the world that needs to be addressed to improve the global access to life-saving vaccines. Understanding the tradeoffs between efficacy and reach is critical for resource allocation decisions between different vaccine types for improving health outcomes.
TIME TO LUNG VOLUME STABILITY AFTER PRESSURE CHANGE DURING HIGH-FREQUENCY OSCILLATORY VENTILATION
Authors: Tingay David G , Kiraly Nicholas , Mills John F , Dargaville Peter A
Published: February 2021

Objectives

Clinicians have little guidance on the time needed before assessing the effect of a mean airway pressure (PAW) change during high-frequency oscillatory ventilation (HFOV). We aimed to determine 1) time to stable lung volume after a PAW change during HFOV and, 2) the relationship between time to volume stability and the volume state of the lung.

Methods

Continuous lung volume measurements (respiratory inductive plethysmography) after 1-2 cmH2O PAW changes made every 10 minutes during an open lung strategy (n=13 infants) were analysed with a bi-exponential model. Time to stable lung volume (extrapolated to maximum 3600s) was calculated if the model R2 was >0.6.

Results

196 PAW changes were made, with no volume change in 33 (17%) occurrences. 125 volume signals met modelling criteria for inclusion; median (IQR) R2 0.96 (0.91, 0.98). The time to stable lung volume was 1131 (718, 1959)s (PAW increases) and 647 (439, 1309)s (PAW decreases), with only 17 (14%) occurring within 10 minutes and time to stability being longer when the lung was atelectatic.

Conclusions

During HFOV, the time to stable lung volume after a PAW change is variable, often requires more than 10 minutes and is dependent on the preceding volume state.

Impact Statement

In infants without preterm respiratory distress syndrome the time to achieve lung volume stability after a PAW change during HFOV is usually greater than 10 minutes.

The volume state of the lung at the time of PAW change influences the time required to achieve a stable new lung volume; being shorter when the lung is well recruited and longer when the lung is already atelectatic.

Clinicians should be aware that it may require least 10 minutes before assessing the clinical response to a change in PAW during HFOV
Metastatic risk stratification of leiomyosarcoma patients using transcription- and replication-associated chromosomal instability mechanisms
Authors: Benhaddou Ataaillah , Gaston Laetitia , Pérot Gaëlle , Desplat Nelly , Leroy Laura , Guellec Sophie Le , Haddou Mohamed Ben , Rochaix Philippe , Valentin Thibaud , Ferron Gwenaël , Chevreau Christine , Bui Binh , Stoeckle Eberhard , Cesne Axel Le , Piperno-Neumann Sophie , Colin Françoise , Firmin Nelly , De Pinieux Gonzague , Coindre Jean-Michel , Blay Jean-Yves , Chibon Frédéric
Published: February 2021

Leiomyosarcoma (LMS) is an aggressive smooth muscle cancer with few therapeutic options. LMSs show a high level of genomic instability (GI) and the mechanisms underlying their oncogenic processes are poorly understood. While the level of GI influences treatment efficacy and resistance, an accurate measure of it is lacking. Current measures of GI are based on counts of specific structural variation (SV) and mutational signatures. Here, we present a holistic approach to measuring GI based on the quantification of the steady-state equilibrium between DNA damage and repair as assessed by the residual breakpoints (BP) remaining after repair, irrespective of SV type. We use the notion of Hscore, a BP “hotspotness” magnitude scale, to measure the propensity of genomic structural or functional DNA elements to break more than expected by chance. We then derived new measures of transcription- and replication-associated GI that we call iTRAC (Transcription-Associated Chromosomal instability index (iTRAC) and iRACIN (Replication-Associated Chromosomal INstability index). We show that iTRAC and iRACIN are predictive of metastatic relapse in LMS and that they may be combined to form a new classifier called MAGIC (Mixed transcription-and replication-Associated Genomic Instability Classifier). MAGIC outperforms the gold standards FNCLCC and CINSARC in stratifying metastatic risk in LMS. Furthermore, iTRAC stratifies chemotherapeutic response in LMS. We finally show that this approach is applicable to other cancers.
Differential Cytokine Signatures of SARS-CoV-2 and Influenza Infection Highlight Key Differences in Pathobiology
Authors: Karaba Andrew H. , Zhou Weiqiang , Hsieh Leon L. , Figueroa Alexis , Massaccesi Guido , Rothman Richard E. , Fenstermacher Katherine Z.J. , Sauer Lauren , Shaw-Saliba Kathryn , Blair Paul W. , Leung Sherry , Wesson Russell , Alachkar Nada , El-Diwany Ramy , Ji Hongkai , Cox Andrea L.
Published: February 2021

Background

Several inflammatory cytokines are upregulated in severe COVID-19. We compared cytokines in COVID-19 versus influenza in order to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease.

Methods

Thirty-seven cytokines and chemokines were measured in plasma from 145 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was utilized to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was utilized to identify cytokines that mediate the effect of BMI on disease severity.

Results

IL-18, IL-1β, IL-6, and TNF-α were significantly increased in COVID-19 versus influenza patients while GM-CSF, IFN-γ, IFN-λ1, IL-10, IL-15, and MCP-2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF-α were elevated in severe COVID-19, but not severe influenza. Random forest analysis identified high IL-6 and low IFN-λ1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity.

Conclusions

These findings point to activation of fundamentally different innate immune pathways in SARS-CoV-2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.

Severe COVID-19 is marked by dysregulated inflammation and is associated with elevated BMI. By comparing cytokines and chemokines in patients with either COVID-19 or influenza, we identified distinct inflammatory pathways and a cytokine mediator of the effect of BMI.
Hot days and Covid-19 – unusual heat stress for nursing professions in Germany
Authors: Jegodka Yvette , Lagally Lena , Mertes Hanna , Deering Katharina , Schoierer Julia , Buchberger Barbara , Bose-O’Reilly Stephan
Published: February 2021

Objectives

Our aim was to identify whether working during hot days alongside with Covid-19 related personal protective equipment causes heat stress for nursing professionals in Germany.

Methods

Using an online survey, we assessed the impact of hot weather on nursing staff performing in personal protective equipment. A random selection of nursing staff from hospitals, nursing homes and outpatient care participated in the survey.

Results

Out of 428 participants, 6.3% were between 16 and 25 years old, 22.8% between 26 and 35 years, 21.9% between 36 and 45 years, 30.5% between 45 and 55 years, 18.2% between 56 and 65 years, and 0.3% were older than 65 years. Out of all participants, 18.2% were male and 82.5% female. The results of the survey showed that 48.3% had more than 20 years of experience in nursing and 46.2% cardiac, pulmonary, or other pre-existing conditions. Work was found exhaustive while working in PPE by 96.5% of the participants, and 93% complained of worse breathing. We found out that 85.8% reported difficulties to focus. Many workplaces turned out to lack adequate heat protection, with distinct differences concerning the amount of prophylactic and heat mitigating measures across institutions.

Conclusions

Our results clearly show that employers must make more of an effort to provide adequate heat protection for their nursing staff. In order to secure the public health care, there is a need for action, especially in the case of previous conditions of caregivers.

What is already known about this subject?

►

Working in personal protective equipment is often needed during pandemics, to protect nurses, doctors and staff from an infection.

►

However, the equipment can also hamper efficiency and productivity of healthcare workers and lead to personal discomfort, for example, during heat waves.

What are the new findings?

►

According to our study, nurses and nursing assistants in Germany are often older than 45 years and, in many cases, suffer from pre-existing conditions, which exacerbate the problems with personal protective equipment during periods of hot temperatures.

►

Many healthcare institutions do not offer adequate ways to mitigate heat stress for their staff.

How might this impact on policy or clinical practice in the foreseeable future?

►

The results from this study can inform policy makers and clinical practitioners to modify their protocols to include better protective measures during extreme heat or other adverse environmental conditions.
Impact of public sentiments on the transmission of COVID-19 across a geographical gradient
Authors: Agusto Folashade B. , Numfor Eric , Srinivasan Karthik , Iboi Enahoro , Fulk Alexander , Saint Onge Jarron M. , Peterson Townsend
Published: February 2021

COVID-19 is a respiratory disease caused by a recently discovered, novel coronavirus, SARS-COV2. The disease has led to over 81 million confirmed cases of COVID-19, with close to 2 million deaths. In the current social climate, the risk of COVID-19 infection is driven by individual and public perception of risk and sentiments. A number of factors influences public perception, including an individual’s belief system, prior knowledge about a disease and information about a disease. In this paper, we develop a model for COVID-19 using a system of ordinary differential equations following the natural history of the infection. The model uniquely incorporates social behavioral aspects such as quarantine and quarantine violation. The model is further driven by people’s sentiments (positive and negative) which accounts for the influence of disinformation. People’s sentiments were obtained by parsing through and analyzing COVID-19 related tweets from Twitter, a social media platform across six countries. Our results show that our model incorporating public sentiments is able to capture the trend in the trajectory of the epidemic curve of the reported cases. Furthermore, our results show that positive public sentiments reduce disease burden in the community. Our results also show that quarantine violation and early discharge of the infected population amplifies the disease burden on the community. Hence, it is important to account for public sentiment and individual social behavior in epidemic models developed to study diseases like COVID-19.
Standardization of a flow cytometry SARS-CoV-2 serologic test
Authors: Simard Carl , Richard Jonathan , Bazin Renée , Finzi Andrés , Trépanier Patrick
Published: February 2021

The SARS-CoV-2 virus is the causing agent of the coronavirus disease 2019 (COVID-19) pandemic which is responsible for millions of deaths worldwide. The development of the humoral response to the virus has been the subject of intensive research and development. A flow cytometry-based assay using native full-length SARS-CoV-2 Spike protein expressed in 293T cells was recently proposed as a complementary seropositivity determination assay.

The aim of our study was to further develop the flow cytometry assay for potential use as a confirmatory test and to standardize its parameters and results for reliable inter-laboratory use. We have optimized the protocol, established the Receiving Operating Characteristic (ROC) curve and tested reproducibility using pre-COVID plasma samples and convalescent, SARS-CoV-2 individual plasma samples.

The flow-based assay was simplified and standardized by cultivating the 293T cells in suspension and expressing results in Mean Equivalent Soluble Fluorochrome (MESF) using an internal antibody positive control. The ROC curve was determined with an area under the curve (AUC) of 0.996 and the assay specificity and sensitivity were established at 100% and 97.7% respectively. Reproducibility was good as determined on multiple cytometers, on different days, and with data acquisition as far as 72h post-staining. The optimized and standardized assay could be used as a high throughput confirmation confirmatory assay in flow cytometry laboratories involved in serological testing.
Sensitive extraction-free SARS-CoV-2 RNA virus detection using a novel RNA preparation method
Authors: Guan Bin , Frank Karen M. , Maldonado José O. , Beach Margaret , Pelayo Eileen , Warner Blake M. , Hufnagel Robert B.
Published: February 2021

Current conventional detection of SARS-CoV-2 involves collection of a patient sample with a nasopharyngeal swab, storage of the swab during transport in a viral transport medium, extraction of RNA, and quantitative reverse transcription PCR (RT-qPCR). We developed a simplified and novel preparation method using a Chelex resin that obviates RNA extraction during viral testing. Direct detection RT-qPCR and digital-droplet PCR was compared to the current conventional method with RNA extraction for simulated samples and patient specimens. The heat-treatment in the presence of Chelex markedly improved detection sensitivity as compared to heat alone, and lack of RNA extraction shortens the overall diagnostic workflow. Furthermore, the initial sample heating step inactivates SARS-CoV-2 infectivity, thus improving workflow safety. This fast RNA preparation and detection method is versatile for a variety of samples, safe for testing personnel, and suitable for standard clinical collection and testing on high throughput platforms.
COVID-19 Prevention Beliefs and Practices in College Students
Authors: Cassimatis Caitlyn , Kreitner Liga , Njai Abdoulie , Leary Emily , Gray Aaron
Published: February 2021

Background

As college students in the United States return to university campuses, it is important to understand their beliefs and practices on coronavirus disease 2019 (COVID-19) prevention.

Purpose

To assess beliefs and practices regarding COVID-19 prevention among college students in the United States

Methods

An online, self-administered survey was developed that collected information on COVID-19 preventative practice and beliefs. Survey responses were collected between July 13, 2020 and July 31, 2020.

Results

A total of 4,834 college students participated in the survey with a response rate of 22.9%. Compared to males, more female college students practiced COVID-19 preventative measures, includingalwayswearing masks or face coverings in public (52% vs. 44%, p<0.001) andalwaysoroftenobserving social distancing (70% vs. 63%, p<0.001). In contrast to students from larger population areas, fewer college students from rural areas reported practicing prevention measures, such asalwayswearing a mask (24% rural v. 45% towns vs. 55% cities, p<0.001) andalwayssocial distancing (20% rural vs. 21% towns vs. 29% cities, p<0.001). Additionally, more students from rural areas have becomemuch lessworried about personally contracting COVID-19 over the last 3 months when compared to students from towns and cities (21% vs. 16% vs. 11%, p<0.001). Fewer white college students compared to other racial groups thought it wasvery importantto wear masks (55% white vs. 76% Black vs. 82% Asian vs. 63% American Indian or Alaskan native (AIAN) & Native Hawaiian or Other Pacific Islander (NHOPI), p<0.001) andvery importantto practice social distancing (29% white vs. 50% Black vs. 53% Asian vs. 36% AIAN/NHOPI, p <0.001). Compared to Non-Hispanic students, more Hispanic students thought it wasvery importantto practice preventative measures, including wearing a mask (71% vs. 58%, p<0.001), social distancing (37% vs. 32%, p=0.017), and good hand hygiene (77% vs. 67%, p=0.013).

Conclusion

COVID-19 prevention beliefs and practices differ between sexes, the size of town one lives, race, and ethnicity. In general, female students followed Center for Disease Control and Prevention (CDC) COVID-19 prevention guidelines more closely than male students. Students who reside in areas of larger populations have more strict COVID-19 prevention beliefs and practices than students from areas with smaller populations. Asian and Black/African American students adhered closer to CDC COVID-19 prevention guidelines and had stronger beliefs for infection prevention measures than white or AIAN/NHOPI students. Hispanic/Latino students were more stringent in COVID-19 prevention beliefs and practices than non-Hispanic/Latino students.
Identification of B.1.346 lineage of SARS-CoV-2 in Japan: Genomic evidence of re-entry of Clade 20C
Authors: Abe Kodai , Shimura Takako , Takenouchi Toshiki , Iwasaki Yuka W. , Ishizu Hirotsugu , Uwamino Yoshifumi , Uno Shunsuke , Gotoh Jun , Tachikawa Natsuo , Takeuchi Yuriko , Katayama Junpei , Nozaki Hiroyuki , Fujii Susumu , Seki Shikou , Nakamura Morio , Uda Kazuhiro , Misumi Takahiko , Ishihara Jun , Yamada Kenichiro , Kanai Toshio , Murai Shinji , Araki Kazuhiro , Ebihara Tamotsu , Shiomi Haruhiko , Hasegawa Naoki , Kitagawa Yuko , Amagai Masayuki , Suematsu Makoto , Kosaki Kenjiro
Published: February 2021

Objectives

Whole SARS-CoV-2 genome sequencing from COVID-19 patients is useful for infection control and regional trends evaluation. We report a lineage data collected from hospitals in the Kanto region of Japan.

Methods

We performed whole genome sequencing in specimens of 198 COVID-19 patients at 13 collaborating hospitals in the Kanto region. Phylogenetic analysis and fingerprinting of the nucleotide substitutions underwent to differentiate and classify the viral lineages.

Results

More than 90% of the strains belonged to Clade 20B and two lineages (B.1.1.284 and B.1.1.214) have been detected predominantly in the Kanto region. However, one sample from a COVID-19 patient in November 2020, belonged to the B.1.346 lineage of Clade 20C, which has been prevalent in western United States. The patient had no history of overseas travel and no contact with anyone who had travelled abroad, suggesting that this strain appeared likely to have been imported from western United States, across the strict quarantine barrier.

Conclusion

B.1.1.284 and B.1.1.214 have been identified predominantly in the Kanto region and B.1.346 of clade 20C in one patient was probably imported from western United States. These results illustrate that a decentralized network of hospitals can be significantly advantageous for monitoring regional molecular epidemiologic trends.

Highlights

· Whole SARS-CoV-2 genome sequencing is useful for infection control

· B.1.1.284 and B.1.1.214 have been identified predominantly in the Kanto region

· B.1.346 of Clade 20C was detected in one COVID-19 patient in November

· Molecular genomic data sharing provides benefits to public health against COVID-19
Antisense therapy in a new rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment
Authors: Hagemann Tracy L. , Powers Berit , Lin Ni-Hsuan , Mohamed Ahmed F. , Dague Katerina L. , Hannah Seth C. , Mazur Curt , Rigo Frank , Feany Mel B. , Perng Ming-Der , Berman Robert F. , Messing Albee
Published: February 2021

Alexander disease (AxD) is a devastating leukodystrophy caused by gain of function mutations inGFAP, and the only available treatments are supportive. Recent advances in antisense oligonucleotide (ASO) therapy have demonstrated that transcript targeting can be a successful strategy for human neurodegenerative diseases amenable to this approach. We have previously used mouse models of AxD to show thatGfap-targeted ASO suppresses protein accumulation and reverses pathology; however, the mice have a mild phenotype with no apparent leukodystrophy or overt clinical features and are therefore limited for assessing functional outcomes. In this report we introduce a new rat model of AxD that exhibits hallmark pathology with GFAP aggregation in the form of Rosenthal fibers, widespread astrogliosis, and white matter deficits. These animals develop normally during the first postnatal weeks but fail to thrive after weaning and develop severe motor deficits as they mature, with approximately 15 % dying of unknown cause between 6 to 12 weeks of age. In this model, a single treatment withGfap-targeted ASO provides long lasting suppression, reverses GFAP pathology, and depending on age of treatment, prevents or mitigates white matter deficits and motor impairment. This is the first report of an animal model of AxD with myelin pathology and motor impairment, recapitulating prominent features of the human disease. We use this model to show that ASO therapy has the potential to not only prevent but also reverse many aspects of disease.
Rest-fMRI Based Comparison Study between Autism Spectrum Disorder and Typically Control Using Graph Frequency Bands
Authors: Jafadideh Alireza Talesh , Mohammadzadeh Asl Babak
Published: February 2021

Graph signal processing is a subset of signal processing enabling the analysis of functional magnetic resonance imaging (fMRI) data in brain topological domain. One of the most important and highly interested tool of GSP is graph Fourier transform (GFT) by which brain signals can be analyzed in different graph frequency bands. In this paper, the resting-state fMRI (rfMRI) data is analyzed using GFT tool in order to discover new knowledge about the autism spectrum disorder (ASD) and find features discriminating between ASD and typically control (TC) subjects. For ASD group, the signal concentration in both low and high frequency bands is decreased by increasing the age in most of the brain well-known networks. The ASD in comparison to TC shows less intention for changing the signal concentration level when the level is very low or very high. In graph low frequency band, increasing the age is along with increasing the segregation and integration of brain ROIs respectively for ASD and TC. Also, in this band, the brain ROIs integration of ASD is more than TC. By increasing the age, the auditory network of ASD subjects shows increasing segregation and integration in graph low and high frequency bands, respectively. The reduced segregation of default mode network in ASD is happened in graph middle and higher frequency bands. The functional connectivity analysis between low and high frequency signals shows that some of the high frequency ROIs have connections with all low frequency ROIs so that the most of these connections are dramatically and significantly different between ASD and TC. By analyzing the local vertex frequency spectrum (LVFS) of ASD and TC at different states, it is seen these groups show contradictory behaviors with respect to each other in brain default mode network in two states. The results of different scenarios at different graph frequency bands demonstrate that using functional and structural data together can provide powerful tool for recognizing the ASD or even other brain disorders.