We propose a simple SIR model in order to investigate the impact of various confinement strategies on a most virulent epidemic. Our approach is motivated by the current COVID-19 pandemic. The main hypothesis is the existence of two populations of susceptible persons, one which obeys confinement and for which the infection rate does not exceed 1, and a population which, being non confined for various imperatives, can be substantially more infective. The model, initially formulated as a differential system, is discretised following a specific procedure, the discrete system serving as an integrator for the differential one. Our model is calibrated so as to correspond to what is observed in the COVID-19 epidemic. Several conclusions can be reached, despite the very simple structure of our model. First, it is not possible to pinpoint the genesis of the epidemic by just analysing data from when the epidemic is in full swing. It may well turn out that the epidemic has reached a sizeable part of the world months before it became noticeable. Concerning the confinement scenarios, a universal feature of all our simulations is that relaxing the lockdown constraints leads to a rekindling of the epidemic. Thus we sought the conditions for the second epidemic peak to be lower than the first one. This is possible in all the scenarios considered (abrupt, progressive or stepwise exit) but typically a progressive exit can start earlier than an abrupt one. However, by the time the progressive exit is complete, the overall confinement times are not too different. From our results, the most promising strategy is that of a stepwise exit. And in fact its implementation could be quite feasible, with the major part of the population (minus the fragile groups) exiting simultaneously but obeying rigorous distancing constraints.

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has been declared a pandemic by WHO. The clinical manifestation and disease progression in COVID-19 patients varies from minimal symptoms to severe respiratory issues with multiple organ failure. Understanding the mechanism of SARS-CoV-2 interaction with host cells will provide key insights into the effective molecular targets for the development of novel therapeutics. Recent studies have identified virus-mediated phosphorylation or activation of some major signaling pathways, such as ERK1/2, JNK, p38, PI3K/AKT and NF-κB signaling, that potentially elicit the cytokine storm that serves as a major cause of tissue injuries. Several studies highlight the aggressive inflammatory response particularly 'cytokine storm' in SARS-CoV-2 patients. A depiction of host molecular dynamics triggered by SARS-CoV-2 in the form of a network of signaling molecules will be helpful for COVID-19 research. Therefore, we developed the signaling pathway map of SARS-CoV-2 infection using data mined from the recently published literature. This integrated signaling pathway map of SARS-CoV-2 consists of 326 proteins and 73 reactions. These include information pertaining to 1,629 molecular association events, 30 enzyme catalysis events, 43 activation/inhibition events, and 8,531 gene regulation events. The pathway map is publicly available through WikiPathways: https://www.wikipathways.org/index.php/Pathway:WP5115 .

Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) classically present with ventricular arrhythmias and less commonly heart failure. ARVC is an inherited cardiomyopathy and generally based on a variant of desmosomal genes. Recently, the association between myocardial inflammation and ARVC has been a matter of great concern. We encountered a patient with ARVC who had a desmoglein-2 mutation with advanced right ventricular failure accompanying a preserved left ventricular function. Concomitant right ventricular myocarditis was detected four years after the diagnosis of ARVC. ARVC and myocarditis might have a deep pathophysiological association, at least in some cases.

One striking characteristic of certain herpesviruses is their ability to induce rapid and widespread RNA decay in order to gain access to host resources. This phenotype is induced by viral endoribonucleases, including SOX in Kaposi's sarcoma-associated herpesvirus (KSHV), muSOX in murine gammaherpesvirus 68 (MHV68), BGLF5 in Epstein-Barr virus (EBV), and vhs in herpes simplex virus 1 (HSV-1). Here, we performed comparative transcriptome sequencing (RNA-seq) upon expression of these herpesviral endonucleases in order to characterize their effect on the host transcriptome. Consistent with previous reports, we found that approximately two-thirds of transcripts were downregulated in cells expressing any of these viral endonucleases. Among the transcripts spared from degradation, we uncovered a cluster of transcripts that systematically escaped degradation from all tested endonucleases. Among these escapees, we identified C19ORF66 and reveal that this transcript is protected from degradation by its 3' untranslated region (UTR). We then show that C19ORF66 is a potent KSHV restriction factor by impeding early viral gene expression, suggesting that its ability to escape viral cleavage may be an important component of the host response to viral infection. Collectively, our comparative approach is a powerful tool to pinpoint key regulators of the viral-host interplay and led us to uncover a novel KSHV regulator.IMPORTANCE Viruses are master regulators of the host gene expression machinery. This is crucial to promote viral infection and to dampen host immune responses. Many viruses, including herpesviruses, express RNases that reduce host gene expression through widespread mRNA decay. However, it emerged that some mRNAs escape this fate, although it has been difficult to determine whether these escaping transcripts benefit viral infection or instead participate in an antiviral mechanism. To tackle this question, we compared the effect of the herpesviral RNases on the human transcriptome and identified a cluster of transcripts consistently escaping degradation from all tested endonucleases. Among the protected mRNAs, we identified the transcript C19ORF66 and showed that it restricts Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Collectively, these results provide a framework to explore how the control of RNA fate in the context of viral-induced widespread mRNA degradation may influence the outcome of viral infection.

In this study, we aimed to investigate psychological well-being, depression, and stress among healthcare professionals and non-healthcare professionals in Turkey. An online questionnaire was prepared and shared with participants using social networking sites. Participants were 546 healthcare professionals (females = 313) and 445 non-healthcare professionals (females = 333), aged between 20 and 67 years. All participants completed measures of Depression Anxiety and Stress Scale-21 and Psychological Well-Being Scale. The results showed no significant difference in the scores of psychological well-being, depression and stress of healthcare professionals and non-healthcare professionals. However, the psychological well-being of healthcare professionals and stress varied in terms of age, gender, marital status, job descriptions, and ways of working in clinic. Women, non-physician healthcare professionals, young and single people and those who worked in COVID-19 service and stayed at least one week away from their families during the pandemic were found to have poor mental well-being. Psychological well-being was significantly and negatively correlated with depression and anxiety. Our findings indicate that healthcare professionals who are at the frontline of the fight against the COVID-19, and nurses, women, single person and those who are away from their family for more than a week during the pandemic are at greater risk.

Using new panel data from a representative survey of households in the six largest euro area economies, the paper estimates the impact of the Covid-19 crisis on consumption. The panel provides, each month, household-specific indicators of the concern about finances due to Covid-19 from the first peak of the pandemic until October 2020. The results show that this concern causes a significant reduction in non-durable consumption. The paper also explores the potential impact on consumption of government interventions and of another wave of Covid-19, using household-level consumption adjustments to scenarios that involve positive and negative income shocks. Fears of the financial consequences of the pandemic induce a significant reduction in the marginal propensity to consume, an effect consistent with models of precautionary saving and liquidity constraints. The results are robust to endogeneity concerns through use of panel fixed effects and partial identification methods, which account also for time-varying unobservable variables, and provide informative identification regions of the average treatment effect of the concern for Covid-19 under weak assumptions.

The human TMPRSS2 gene is pathogenetically implicated in both coronaviral lung infection and prostate cancer, suggesting its potential as a drug target in both contexts. SARS-COV-2 spike polypeptides are primed by the host transmembrane TMPRSS2 protease, triggering virus fusion with epithelial cell membranes followed by an endocytotic internalisation process that bypasses normal endosomal activation of cathepsin-mediated innate immunity; viral co-opting of TMPRSS2 thus favors microbial survivability by attenuating host inflammatory responses. In contrast, most early hormone-dependent prostate cancers express TMPRSS2:ERG fusion genes arising from deletions that eliminate the TMPRSS2 coding region while juxtaposing its androgen-inducible promoter and the open reading frame of ERG, upregulating pro-inflammatory ERG while functionally disabling TMPRSS2. Moreover, inflammatory oxidative DNA damage selects for TMPRSS2:ERG-fused cancers, whereas patients treated with antiinflammatory drugs develop fewer of these fusion-dependent tumors. These findings imply that TMPRSS2 protects the prostate by enabling endosomal bypass of pathogens which could otherwise trigger inflammation-induced DNA damage that predisposes to TMPRSS2:ERG fusions. Hence, the high oncogenic selectability of TMPRSS2:ERG fusions may reflect a unique pro-inflammatory synergy between androgenic ERG gain-of-function and fusogenic TMPRSS2 loss-of-function, cautioning against the use of TMPRSS2-inhibitory drugs to prevent or treat early prostate cancer.

This report is an account of the authors' experiences as organizers of WiML's "Un-Workshop" event at ICML 2020. Un-workshops focus on participant-driven structured discussions on a pre-selected topic. For clarity, this event was different from the "WiML Workshop", which is usually co-located with NeurIPS. In this manuscript, organizers, share their experiences with the hope that it will help future organizers to host a successful virtual event under similar conditions. Women in Machine Learning (WiML)'s mission is creating connections within a small community of women working in machine learning, in order to encourage mentorship, networking, and interchange of ideas and increase the impact of women in the community.

A novel coronavirus (SARS-CoV2) has caused a major outbreak in humans around the globe, and it became a severe threat to human healthcare than all other infectious diseases. Researchers were urged to discover and test various approaches to control and prevent such a deadly disease. Considering the emergency and necessity, we screened reported antiviral compounds present in the traditional Indian medicinal plants for the inhibition of SARS-CoV2 main protease. In this study, we used molecular docking to screen 41 reported antiviral compounds that exist in Indian medicinal plants and shown amentoflavone from the plant Torreyanucifera with a higher docking score. Furthermore, we performed a 40 ns atomic molecular dynamics simulation and free binding energy calculations to explore the stability of the top five proteinCligand complexes. Through the article, we insist that the amentoflavone, hypericin and Torvoside H from the traditional Indian medicinal plants may be used as a potential inhibitor of SARS-CoV2 main protease and further biochemical experiments could shed light on understanding the mechanism of inhibition by these plant-derived antiviral compounds. Communicated by Ramaswamy H. Sarma

The outbreak of COVID-19 has caused serious epidemic events in China and other countries. With the rapid spread of COVID-19, it is urgent to explore the pathogenesis of this novel coronavirus. However, the foundational research of COVID-19 is very weak. Although angiotensin converting enzyme 2 (ACE2) is the reported receptor of SARS-CoV-2, information about SARS-CoV-2 invading airway epithelial cells is very limited. Based on the analysis of the Human Protein Atlas database, we compared the virus-related receptors of epithelial-derived cells from different organs and found potential key molecules in the local microenvironment for SARS-CoV-2 entering airway epithelial cells. In addition, we found that these proteins were associated with virus reactive proteins in host airway epithelial cells, which may promote the activation of the immune system and the release of inflammatory factors. Our findings provide a new research direction for understanding the potential microenvironment required by SARS-CoV-2 infection in airway epithelial, which may assist in the discovery of potential drug targets against SARS-CoV-2 infection.

The heft of non-bank financial intermediaries (NBFIs) in the financial system has grown significantly after the Great Financial Crisis of 2008. This paper reviews structural shifts in intermediation and how NBFIs have shaped the demand and supply of liquidity in financial markets. We then lay out a framework for the key channels of systemic risk propagation in the presence of NBFIs, emphasising the central role of leverage fluctuations through changes in margins. The debt capacity of an investor is increasing in the debt capacity of other investors in the system, so that leverage enables greater leverage, and spikes in margins can lead to system-wide deleveraging. In our framework, deleveraging and dash for cash scenarios (as during the Covid-19 crisis) emerge as two sides of the same coin, rather than being two distinct channels of stress propagation. These findings have implications for the design of NBFI regulations and of central bank backstops.

Background: The asymptomatic proportion is a critical epidemiological characteristic that modulates the pandemic potential of emerging respiratory virus, which may vary depending on the nature of the disease source, population characteristics, source-host interaction, and environmental factors. Methods: We developed a simple likelihood-based framework to estimate the instantaneous asymptomatic proportion of infectious diseases. Taking the COVID-19 epidemics in Hong Kong as a case study, we applied the estimation framework to estimate the reported asymptomatic proportion (rAP) using the publicly available surveillance data. We divided the time series of daily cases into four stages of epidemics in Hong Kong by examining the persistency of the epidemic and compared the rAPs of imported cases and local cases at different stages. Results: As of July 31, 2020, there were two intermittent epidemics in Hong Kong. The first one was dominated by imported cases, accounting for 63.2% of the total cases, and the second one was dominated by local cases, accounting for 86.5% of the total cases. The rAP was estimated at 23.1% (95% CI: 10.8-39.7%) from January 23 to July 31, and the rAPs were estimated at 22.6% (95% CI: 11.1-38.9%) among local cases and 38.7% (95% CI: 9.0-72.0%) among imported cases. Our results showed that the rAPs of local cases were not significantly different between the two epidemics, but increased gradually during the first epidemic period. In contrast, the rAPs of imported cases in the latter epidemic period were significantly higher than that in the previous epidemic period. Conclusion: Hong Kong has a high rAP of imported COVID-19 cases and should continue to strengthen the detection and isolation of imported individuals to prevent the resurgence of the disease.

Background and AimsDescribed during World War II, continuous spinal anesthesia (CSA) enables continuous administration of intrathecal drugs, offering several anesthetic options versus single shot technique, although underutilised.Here we present 4 cases of CSA performed for patients undergoing urgent upper abdominal and lower extremity orthopedic surgery during the COVID-19 pandemic. Our patients were ranked between 90C100 years old with ASA score IV, in which we highlight the presence of ischemic heart disease and chronic obstructive pulmonary disease.MethodsInvasive hemodynamic measurement was performed before CSA technique. Given the lack of microcatheter-over-the-needle kits in our center, we performed the technique using Perifix? Complete Set C B Braun, with full aseptic technique. The 18G Tuohy needle was introduced via a midline approach until CSF was encountered. The 20G catheter was then introduced 3cm into the subarachnoid space. In all situations we opted for the administration of sufentanil 0.0025 mg plus subsequent aliquots of hyperbaric bupivacaine 0.125%, guided by sensory assessment of block level.ResultsAll surgeries were successfully concluded with minimal haemodynamic variation and avoidance of mechanical invasive ventilation. Patients were admitted in the PACU, where spinal catheters were removed, and continued their recovery at the speciality yard. No complications were observed, particularly post-dural puncture headache, neurologic or infectious events.ConclusionsCSA is a useful anesthetic technique with a low failure rate. Its best role is likely to be in high-risk surgical patients, as it can provide excellent blockade conditions, with small doses of LA and little haemodynamic variation frequently seen with single shot techniques.

In recent years, nitrate plays an increasingly important role in haze pollution and strict emission control seems ineffective in reducing nitrate pollution in China. In this study, observations of gaseous and particulate pollutants during the COVID-19 lockdown, as well as numerical modelling were integrated to explore the underlying causes of the nonlinear response of nitrate mitigation to nitric oxides (NO(x)) reduction. We found that, due to less NO(x) titration effect and the transition of ozone (O(3)) formation regime caused by NO(x) emissions reduction, a significant increase of O(3) (by 69%) was observed during the lockdown period, leading to higher atmospheric oxidizing capacity and facilitating the conversion from NO(x) to oxidation products like nitric acid (HNO(3)). It is proven by the fact that 26C61% reduction of NO(x) emissions only lowered surface HNO(3) by 2C3% in Hebi and Nanjing, eastern China. In addition, ammonia concentration in Hebi and Nanjing increased by 10% and 40% during the lockdown, respectively. Model results suggested that the increasing ammonia can promote the gas-particle partition and thus enhance the nitrate formation by up to 20%. The enhanced atmospheric oxidizing capacity together with increasing ammonia availability jointly promotes the nitrate formation, thereby partly offsetting the drop of NO(x). This work sheds more lights on the side effects of a sharp NO(x) reduction and highlights the importance of a coordinated control strategy.

Most of the studies investigating the relationship between socioeconomic status and the occurrence of COVID-19 have limitations due to their ecological design. To investigate the relationship between socioeconomic status and individual-level risk of developing COVID-19, we conducted a population-based, age and gender matched, case-control study in a district of Istanbul. The case group was defined as all confirmed COVID-19 cases (n=232) in the district in a week of August 2020. The control group was matched with cases in terms of age and gender and selected randomly from the directory of the same primary care provider in the district in a 1:1 ratio. The socioeconomic status was measured by the Turkish Socioeconomic Status Index which considers its three dimensions: education, occupation, and income. 168 cases (72.4% response) and 168 controls are included in the study. The mean socioeconomic status score is 70.287.09 for cases and 69.257.46 for controls (p=0.201). 15.2% (n=25) of cases and 22.4% (n=37) of controls is in lower socioeconomic status group (p=0.091). The analysis did not reveal a statistically significant difference between study groups. Socioeconomic status may not a significant predictor of COVID-19 occurrence at the individual-level. The disease seems to be a common threat to all individuals.

For tourism to be considered sustainable, the industry needs to be transparent in measuring, monitoring and reporting all emissions to actively contribute to the decarbonisation of the economy. The purpose of this study was to identify to what level tourism decarbonisation has been discussed, assessed, and planned for globally. For this study, a content analysis of national tourism plans was implemented to identify if the carbon footprint of tourism has been assessed, establish a unified approach to measure tourism emissions and determine what level of tourism decarbonisation strategies are currently in place. The findings in this study identified that the carbon footprint of tourism has not been assessed globally, lacks serious discussion and planning for tourism decarbonisation. Crucially, baseline data for tourism emissions are not available, as a result, tourism policymakers cannot monitor and manage the level of decarbonisation in tourism. Furthermore, a unified approach to measure tourism emissions needs to be agreed upon to ensure that each country measures the same criteria. Consequently, allowing policymakers to compare international tourism emissions and establish if tourism is actively transitioning towards a low-carbon industry. Climate change is a significant crisis facing humanity, and until now, this research has not been completed.

Antibiotic resistance is exuberantly becoming a deleterious health problem world-wide. Seeking innovative approaches is necessary in order to circumvent such a hazard. An unconventional fill-in to antibiotics is bacteriophage. Bacteriophages are viruses capable of pervading bacterial cells and disrupting their natural activity, ultimately resulting in their defeat. In this article, we will run-through the historical record of bacteriophage and its correlation with bacteria. We will also delineate the potential of bacteriophage as a therapeutic antibacterial agent, its supremacy over antibiotics in multiple aspects and the challenges that could arise on the way to its utilization in reality. Pharmacodynamics, pharmacokinetics and genetic engineering of bacteriophages and its proteins will be briefly discussed as well. In addition, we will highlight some of the in-use applications of bacteriophages, and set an outlook for their future ones. We will also overview some of the miscellaneous abilities of these tiny viruses in several fields other than the clinical one. This is an attempt to encourage tackling a long-forgotten hive. Perhaps, one day, the smallest of the creatures would be of the greatest help.

New York City (NYC) has emerged as one of the epicenters of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. To identify the early transmission events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus that causes coronavirus disease 2019 (COVID-19) in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV-2 genomes indicates multiple, independent, but isolated introductions mainly from Europe and other parts of the United States. Moreover, we found evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.

Background: The COVID-19 pandemic has caused unprecedented changes in the lives of 1.6 billion children and adolescents. First non-representative studies from China, India, Brazil, the US, Spain, Italy, and Germany pointed to a negative mental health impact. The current study is the first nationwide representative study to investigate the impact of the COVID-19 pandemic on health-related quality of life (HRQoL) and mental health of children and adolescents in Germany from the perspective of children themselves.Methods: A representative online survey was conducted among n = 1,586 families with 7- to 17-year-old children and adolescents between May 26 and June 10. The survey included internationally established and validated instruments for measuring HRQoL (KIDSCREEN-10), mental health problems (SDQ), anxiety (SCARED), and depression (CES-DC). Results were compared with data from the nationwide, longitudinal, representative BELLA cohort study (n = 1,556) conducted in Germany before the pandemic.Results: Two-thirds of the children and adolescents reported being highly burdened by the COVID-19 pandemic. They experienced significantly lower HRQoL (40.2% vs. 15.3%), more mental health problems (17.8% vs. 9.9%) and higher anxiety levels (24.1% vs. 14.9%) than before the pandemic. Children with low socioeconomic status, migration background and limited living space were affected significantly more.Discussion: Health promotion and prevention strategies need to be implemented to maintain childrens and adolescents mental health, improve their HRQoL, and mitigate the burden caused by COVID-19, particularly for children who are most at risk.

INTRODUCTION With the onset of Coronavirus disease (COVID-19), primary care has swiftly transitioned from face-to-face to virtual care, yet it remains largely unknown how this has impacted the quality and safety of care. We aim to evaluate patient use of virtual primary care models during COVID-19, including change in uptake, perceived impact on the quality and safety of care and willingness of future use. METHODOLOGY An online cross-sectional survey was administered to the public across the United Kingdom, Sweden, Italy and Germany. McNemar tests were conducted to test pre- and post-pandemic differences in uptake for each technology. One-way analysis of variance was conducted to examine patient experience ratings and perceived impacts on healthcare quality and safety across demographic characteristics. RESULTS Respondents (n = 6326) reported an increased use of telephone consultations ( + 6.3%, p < .001), patient-initiated services ( + 1.5%, n = 98, p < 0.001), video consultations ( + 1.4%, p < .001), remote triage ( + 1.3, p < 0.001) and secure messaging systems ( + 0.9%, p = .019). Experience rates using virtual care technologies were higher for men (2.4 1.0 vs. 2.3 0.9, p < .001), those with higher literacy (2.8 1.0 vs. 2.3 0.9, p < .001), and participants from Germany (2.5 0.9, p < .001). Healthcare timeliness and efficiency were the dimensions most often reported as being positively impacted by virtual technologies (60.2%, n = 2793 and 55.7%, n = 2,401, respectively), followed by effectiveness (46.5%, n = 1802), safety (45.5%, n = 1822), patient-centredness (45.2%, n = 45.2) and equity (42.9%, n = 1726). Interest in future use was highest for telephone consultations (55.9%), patient-initiated digital services (56.1%), secure messaging systems (43.4%), online triage (35.1%), video consultations (37.0%) and chat consultations (30.1%), although significant variation was observed between countries and patient characteristics. DISCUSSION Future work must examine the drivers and determinants of positive experiences using remote care to co-create a supportive environment that ensures equitable adoption and use. Comparative analysis between countries and health systems offers the opportunity for policymakers to learn from best practices internationally.