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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Patterns of within-host genetic diversity in SARS-CoV-2</strong> -
<div>
Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1,181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within and between host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.23.424229v1" target="_blank">Patterns of within-host genetic diversity in SARS-CoV-2</a>
</div></li>
<li><strong>Potent in vitro anti-SARS-CoV-2 activity by gallinamide A and analogues via inhibition of cathepsin L</strong> -
<div>
The emergence of SARS-CoV-2 in late 2019, and the subsequent COVID-19 pandemic, has led to substantial mortality, together with mass global disruption. There is an urgent need for novel antiviral drugs for therapeutic or prophylactic application. Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is recognized as a promising drug target. The marine natural product, gallinamide A and several synthetic analogues, were identified as potent inhibitors of cathepsin L activity with IC50 values in the picomolar range. Lead molecules possessed selectivity over cathepsin B and other related human cathepsin proteases and did not exhibit inhibitory activity against viral proteases Mpro and PLpro. We demonstrate that gallinamide A and two lead analogues potently inhibit SARS-CoV-2 infection in vitro, with EC50 values in the nanomolar range, thus further highlighting the potential of cathepsin L as a COVID-19 antiviral drug target.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.23.424111v1" target="_blank">Potent in vitro anti-SARS-CoV-2 activity by gallinamide A and analogues via inhibition of cathepsin L</a>
</div></li>
<li><strong>A SARS-CoV-2 spike binding DNA aptamer that inhibits pseudovirus infection in vitro by an RBD independent mechanism</strong> -
<div>
The receptor binding domain (RBD) of the spike glycoprotein of the coronavirus SARS-CoV-2 (CoV2-S) binds to the human angiotensin converting enzyme 2 (ACE2) representing the initial contact point for leveraging the infection cascade. We used an automated selection process and identified an aptamer that specifically interacts with CoV2-S. The aptamer does not bind to the RBD of CoV2-S and does not block the interaction of CoV2-S with ACE2. Notwithstanding, infection studies revealed potent and specific inhibition of pseudoviral infection by the aptamer. The present study opens up new vistas in developing SARS-CoV2 infection inhibitors, independent of blocking the ACE2 interaction of the virus and harnesses aptamers as potential drug candidates and tools to disentangle hitherto inaccessible infection modalities, which is of particular interest in light of the increasing number of escape mutants that are currently being reported.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.23.424171v1" target="_blank">A SARS-CoV-2 spike binding DNA aptamer that inhibits pseudovirus infection in vitro by an RBD independent mechanism</a>
</div></li>
<li><strong>SARS-CoV-2 infecting the inner ear results in potential hearing damage at the early stage or prognosis of COVID-19 in rodents</strong> -
<div>
Objectives: In order to find out the association between the sensorineural hearing loss and COVID-19, we detected the expression ACE2 and TMPRSS2 in the mouse the hamster. Design: Using the public data from NCBI and GISAID, we assessed the expression of ACE2 and TMPRSS2 at the transcriptomic, DNA, and protein levels of ACE2 in the brain, inner ear, and muscle from the golden Syrian hamster (Mesocricetus auratus) and mouse (Mus musculus). Results: We identified ACE2 and TMPRSS2 expressed at different level in the inner ear and brain at DNA and transcriptomic levels of both mouse and the hamster. The protein expression shows a similar pattern of the brain and inner ear, while the expression of ACE2 from the inner ear was relatively higher than it from the muscle. Conclusion: SARS-CoV-2 could infect the hearing system potentially and SSNHL could be a characteristic to detect asymptomatic patients of COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.23.423942v1" target="_blank">SARS-CoV-2 infecting the inner ear results in potential hearing damage at the early stage or prognosis of COVID-19 in rodents</a>
</div></li>
<li><strong>REAL-TIME MECHANISTIC BAYESIAN FORECASTS OF COVID-19 MORTALITY</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The COVID-19 pandemic emerged in late December 2019. In the first six months of the global outbreak, the US reported more cases and deaths than any other country in the world. Effective modeling of the course of the pandemic can help assist with public health resource planning, intervention efforts, and vaccine clinical trials. However, building applied forecasting models presents unique challenges during a pandemic. First, case data available to models in real-time represent a non-stationary fraction of the true case incidence due to changes in available diagnostic tests and test-seeking behavior. Second, interventions varied across time and geography leading to large changes in transmissibility over the course of the pandemic. We propose a mechanistic Bayesian model (MechBayes) that builds upon the classic compartmental susceptible-exposed-infected-recovered (SEIR) model to operationalize COVID-19 forecasting in real time. This framework includes non-parametric modeling of varying transmission rates, non-parametric modeling of case and death discrepancies due to testing and reporting issues, and a joint observation likelihood on new case counts and new deaths; it is implemented in a probabilistic programming language to automate the use of Bayesian reasoning for quantifying uncertainty in probabilistic forecasts. The model has been used to submit forecasts to the US Centers for Disease Control, through the COVID-19 Forecast Hub. We examine the performance relative to a baseline model as well as alternate models submitted to the Forecast Hub. Additionally, we include an ablation test of our extensions to the classic SEIR models. We demonstrate a significant gain in both point and probabilistic forecast scoring measures using MechBayes when compared to a baseline model. We show that MechBayes ranks as one of the top models out of those submitted to the COVID-19 Forecast Hub. Finally, we demonstrate that MechBayes performs significantly better than the classical SEIR model.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.22.20248736v2" target="_blank">REAL-TIME MECHANISTIC BAYESIAN FORECASTS OF COVID-19 MORTALITY</a>
</div></li>
<li><strong>Prioritizing Risk Groups for SARS-CoV-2 Vaccination "By the Numbers"</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background Given the limited supply of two COVID-19 vaccines, it will be important to choose which risk groups to prioritize for vaccination in order to get the most health benefits from that supply. Method In order to help decide how to get the maximum health yield from this limited supply, we implemented a logistic regression model to predict COVID-19 death risk by age, race, and sex and did the same to predict COVID-19 case risk. Results Our predictive model ranked all demographic groups by COVID-19 death risk. It was highly concentrated in some demographic groups, e.g. 85+ year old Black, Non-Hispanic patients suffered 1,953 deaths per 100,000. If we vaccinated the 17 demographic groups at highest COVID-19 death ranked by our logistic model, it would require only 3.7% of the vaccine supply needed to vaccinate all the United States, and yet prevent 47% of COVID-19 deaths. Nursing home residents had a higher COVID-19 death risk at 5,200 deaths/100,000, more than our highest demographic risk group. Risk of prison residents and health care workers (HCW) were lower than that of our demographic groups with the highest risks. We saw much less concentration of COVID-19 case risk in any demographic groups compared to the high concentration of COVID-19 death in some such groups. We should prioritize vaccinations with the goal of reducing deaths, not cases, while the vaccine supply is low. Conclusion SARS-CoV-2 vaccines protect against severe COVID-19 infection and thus against COVID-19 death per vaccine studies. Allocating at least some of the early vaccine supplies to high risk demographic groups could maximize lives saved. Our model, and the risk estimate it produced, could help states define their vaccine allocation rules.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.18.20248504v2" target="_blank">Prioritizing Risk Groups for SARS-CoV-2 Vaccination "By the Numbers"</a>
</div></li>
<li><strong>Investigating the origin of the Belgian second SARS-CoV-2 wave by using (pre)admission screening samples.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Belgium has been struggling with a second pandemic wave caused by SARS-CoV-2. Aim: The goal of this study was to estimate rates of carriership and viral loads in the general population in order to evaluate the dynamics leading to the second wave. Methods: Since the major Antwerp hospitals implemented extensive (pre-)admission SARS-CoV-2 screening of patients (eg. prior to elective surgery), they have gathered valuable information regarding the viral prevalence, incidence, and viral loads in the general population throughout the pandemic period. Prevalences and incidences were calculated and compared with available governmental data (numbers of positively tested and contacted cases). Major government coronavirus responses were taken into account. Results: The overall positivity rate of (pre)admission screenings was 1.3% (35.4% of positive cases carrying high viral loads). The highest prevalence of carriership was found in the elderly (2.6% for +80 y). 0-18 year-olds tested positive in 0.9% of cases. We estimated that, by extrapolation of cohort data, 20.3 % of the Antwerp population contracted the virus, whereas only 3.0 % was tested positive. In September, restriction measures were eased at a time when increased incidences were being observed. Conclusion: The estimation that only a small proportion of the positive cases (including cases with high viral loads) was detected and traced, in combination with a country-wide easing of restriction measures within a period of increasing incidences (and within an overall high base-line prevalence of the virus), were, in our opinion, the major drivers in the origin of the second pandemic wave.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.09.20246462v2" target="_blank">Investigating the origin of the Belgian second SARS-CoV-2 wave by using (pre)admission screening samples.</a>
</div></li>
<li><strong>Probability-based approaches for identifying low-titer antibody responses against SARS-CoV-2</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The levels of the antibody response against SARS-CoV-2 varies widely between individuals, which together with the decline of antibody responses over time, complicates the correct classification of seropositivity using conventional assay cut-offs. All subjects in a cohort of SARS-CoV-2 PCR+ individuals representing different disease severity categories (n=105), and a group of PCR+ hospital staff (n=33), developed IgG against pre-fusion-stabilized spike (S) trimers and 97% did against the receptor-binding domain (RBD). The levels differed by several orders of magnitude and associated with disease phenotype. Concomitant analysis of a cohort of healthy blood donors and pregnant women (n=1,000), representing individuals who had undergone milder infections, demonstrated highly variable IgG titers, including several that scored between the classical 3SD and 6SD cut-offs. Since the correct classification of seropositivity is critical for epidemiological estimates, we trained probabilistic algorithms to assign likelihood of past infection using anti-S and -RBD IgG data from PCR+ individuals and a large cohort of historical negative controls (n=595). Applied to blood donors and pregnant women, this probabilistic approach provided a more accurate way to interpret antibody titers spread over a large continuum offering a probability-based diagnosis. The methods described here are directly applicable to serological measurements following natural infection and vaccination.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.07.17.20155937v4" target="_blank">Probability-based approaches for identifying low-titer antibody responses against SARS-CoV-2</a>
</div></li>
<li><strong>ace2 expression is higher in intestines and liver while being tightly regulated in development and disease in zebrafish</strong> -
<div>
Human Angiotensin I Converting Enzyme 2 (ACE2) that acts as a receptor for SARS-CoV-2 entry is highly expressed in human type II pneumocytes and enterocytes and similarly in other mammals and zebrafish (Danio rerio). The zebrafish genome has a highly conserved, one-to-one ortholog of ACE2, i.e., ace2, whose expression profile however has not yet been studied during development or in pathologies relevant to COVID-19. Herein, we identified significant development-, tissue- and gender-specific modulations in ace2 expression based on meta-analysis of zebrafish Affymetrix transcriptomics datasets (ndatasets=107, GPL1319 in GEO database). Co-expression network analysis of ace2 revealed distinct positively correlated (carboxypeptidase activity and fibrin clot formation), and negatively correlated (cilia biogenesis/transport and chromatin modifications) STRING network modules. Using additional transcriptomics datasets, we showed zebrafish embryos before 3 days post fertilization (dpf) exhibited low levels of ace2 that increased significantly until 4 dpf implicating a role for ace2 in organogenesis. Re-analysis of RNA-seq datasets from zebrafish adult tissues demonstrated ace2 was expressed highly in intestines, variably in liver, and at lower levels in other organs. In addition, zebrafish females and males showed significant dimorphism in their age-dependent expression of ace2, and between ovary and testis where the latter had higher levels. Moreover, we demonstrated ace2 expression was significantly modulated under different physiological and pathological conditions associated with development, diet, infection, and inflammation. Our findings implicate a novel translational role for zebrafish ace2 in differentiation and pathologies predominantly found in intestines and liver, in which the effects of SARS-CoV-2 could be detrimental.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.24.424209v1" target="_blank">ace2 expression is higher in intestines and liver while being tightly regulated in development and disease in zebrafish</a>
</div></li>
<li><strong>HLA-C* 04:01 is a Genetic Risk Allele for Severe Course of COVID-19</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing demand to identify predictors of severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors. We sought to evaluate this hypothesis by conducting an international multicenter study using HLA sequencing with subsequent independent validation. Methods We analyzed a total of 332 samples. First, we enrolled 233 patients in Germany, Spain, and Switzerland for HLA and whole exome sequencing. Furthermore, we validated our results in a public data set (United States, n=99). Patients older than 18 years presenting with COVID-19 were included, representing the full spectrum of the disease. HLA candidate alleles were identified in the derivation cohort (n=92) and tested in two independent validation cohorts (n=240). Results We identified HLA-C* 04:01 as a novel genetic predictor for severe clinical course in COVID-19. Carriers of HLA-C* 04:01 had twice the risk of intubation when infected with SARS-CoV-2 (hazard ratio 2.1, adjusted p-value=0.0036). Importantly, these findings were successfully replicated in an independent data set. Furthermore, our findings are biologically plausible, as HLA-C* 04:01 has fewer predicted bindings sites with relevant SARS-CoV-2 peptides as compared to other HLA alleles. Exome sequencing confirmed findings from HLA analysis. Conclusions HLA-C* 04:01 carriage is associated with a twofold increased risk of intubation in patients infected with SARS-CoV-2. Testing for HLA-C* 04:01 could have clinical implications to identify high-risk patients and individualize management.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.21.20248121v1" target="_blank">HLA-C* 04:01 is a Genetic Risk Allele for Severe Course of COVID-19</a>
</div></li>
<li><strong>Novel air sterilization process for clean air production and microbial spread limitation using protection devices</strong> -
<div>
The aim of this work is to develop and simulate a novel process based on sterilizing natural air by heating at high temperatures followed by a rapid cooling. The new sustainable process is called “Air Rapid Heating Rapid Cooling Sterilization” (ARHRCS). Thus, it can be used in Heating, Ventilation, and Air Conditioning (HVAC) system in hospitals to produce safe air, free of pathogenic airborne microbes including bacteria and viruses such as tuberculosis (TB) and coronavirus (SARS-CoV-2). A crown fixed on the head of the medical staff may be connected to the HVAC system to produce a constant flow of clean laminar air. Hence, this crown is capable of keeping airborne microorganisms at a safe distance from Health Care Workers (HCWs), avoiding any potential microbial infection. Accordingly, HCWs will be able to work in a more suitable and safe conditions, especially in high infection risk areas. Depending on its need, the newly developed process may be implemented in different other locations such as laboratories, malls, buildings and other crowded spaces. Further applications of this method may arise including its usage in the sterilization of recirculated air in biosafety cabinets and the development of a portable air sterilizing unit.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/gq9t8/" target="_blank">Novel air sterilization process for clean air production and microbial spread limitation using protection devices</a>
</div></li>
<li><strong>A Neanderthal OAS1 Isoform Protects Against COVID-19 Susceptibility and Severity: Results from Mendelian Randomization and Case-Control Studies</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Proteins detectable in peripheral blood may influence COVID-19 susceptibility or severity. However, understanding which circulating proteins are etiologically involved is difficult because their levels may be influenced by COVID-19 itself and are also subject to confounding factors. To identify circulating proteins influencing COVID-19 susceptibility and severity we undertook a large-scale two-sample Mendelian randomization (MR) study, since this study design can rapidly scan hundreds of circulating proteins and reduces bias due to reverse causation and confounding. We identified genetic determinants of 931 circulating proteins in 28,461 SARS-CoV-2 uninfected individuals, retaining only single nucleotide polymorphism near the gene encoding the circulating protein. We found that a standard deviation increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (N = 4,336 cases / 623,902 controls; OR = 0.54, P = 7x10-8), COVID-19 hospitalization (N = 6,406 / 902,088; OR = 0.61, P = 8x10-8) and COVID-19 susceptibility (N = 14,134 / 1,284,876; OR = 0.78, P = 8x10-6). Results were consistent in multiple sensitivity analyses. We then measured OAS1 levels in 504 patients with repeated plasma samples (N=1039) with different COVID-19 outcomes and found that increased OAS1 levels in a non-infectious state were associated with protection against very severe COVID-19, hospitalization and susceptibility. Further analyses suggested that a Neanderthal isoform of OAS1 affords this protection. Thus, evidence from MR and a case-control study supported a protective role for OAS1 in COVID-19 outcomes. Available medicines, such as phosphodiesterase-12 inhibitors, increase OAS1 and could be explored for their effect on COVID-19 susceptibility and severity.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.10.13.20212092v4" target="_blank">A Neanderthal OAS1 Isoform Protects Against COVID-19 Susceptibility and Severity: Results from Mendelian Randomization and Case-Control Studies</a>
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<li><strong>Aerosolized Hydrogen Peroxide Decontamination of N95 Respirators, with Fit-Testing and Virologic Confirmation of Suitability for Re-Use During the COVID-19 Pandemic</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In response to the current demand for N95 respirators by healthcare workers responding to the COVID-19 pandemic, we evaluated decontamination of N95 respirators using a low concentration aerosolized hydrogen peroxide (aHP) system. This system dispenses a consistent atomized spray of micron-sized, low concentration, hydrogen peroxide (H2O2) particles over a treatment cycle. Multiple N95 respirator models were subjected to ten or more cycles of respirator decontamination, and masks were periodically assessed for qualitative and quantitative fit testing to verify respirator integrity. In parallel, we assessed the ability of aHP treatment to inactivate multiple viruses absorbed onto masks, including phi6 bacteriophage, HSV-1, CVB3, and SARS-CoV-2. Given that SARS-CoV-2 is transmitted via expired respiratory droplets and aerosols, it is critical to address respirator safety for reuse. This study provided experimental validation of a suitable aHP treatment process that decontaminates the respirators while maintaining N95 function. After ten rounds of aHP treatment, respirators passed N95 filtration efficiency testing. Virus inactivation by aHP was comparable to the sterilization of commercial spore-based biological indicators. These data demonstrate that the aHP process is effective, on the basis of zero failure rate on fit-testing of respirators, effective decontamination of multiple virus species including SARS-CoV-2, successful sterilization of bacterial spores, and filtration efficiency maintained at or greater than 95%. Collectively, these studies support the use of specific aHP decontamination protocol that permits safe reuse of N95 respirators by healthcare providers.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.04.17.20068577v2" target="_blank">Aerosolized Hydrogen Peroxide Decontamination of N95 Respirators, with Fit-Testing and Virologic Confirmation of Suitability for Re-Use During the COVID-19 Pandemic</a>
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<li><strong>Shortcomings of SARS-CoV-2 genomic metadata</strong> -
<div>
Metadata is integral to data-driven association studies relevant to epidemiology, viral population dynamics and public health response. However, SARS-CoV-2 metadata quality remains inadequate. Here I exemplify this through a brief analysis of two metadata categories in the GISAID SARS-CoV-2 genomic database: “originating lab” and “submitting lab”. My analysis reveals a startling prevalence of spelling errors and inconsistent naming conventions, which together occur in an estimated ~9.8% and ~11.6% of “originating labs” and “submitting labs” respectively. In addition, I find numerous ambiguous lab names, such as “Biology Dpt” and “Hospital” which provide very little information with regard to the actual source of a sample and could easily associate with multiple sources worldwide. Importantly, all of these issues can impair the ability and accuracy of association studies by deceptively causing a group of samples to identify with multiple sources when they truly all identify with one source, or vice versa. GISAID’s “originating lab” and “submitting lab” categories are specifically relevant to identifying problematic sites in SARS-CoV-2 genomic data through lab association. Thus, I advocate that both data submitters and maintainers strive for a higher metadata quality standard now and in the future.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/pzcwv/" target="_blank">Shortcomings of SARS-CoV-2 genomic metadata</a>
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<li><strong>Substantial Impact of Post Vaccination Contacts on Cumulative Infections during Viral Epidemics</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<b>Background:</b> The start of 2021 will be marked by a global vaccination campaign against the novel coronavirus SARS-CoV-2. Formulating an optimal distribution strategy under social and economic constraints is challenging. Optimal distribution is additionally constrained by the potential emergence of vaccine resistance. Analogous to chronic low-dose antibiotic exposure, recently inoculated individuals who are not yet immune play an outsized role in the emergence of resistance. Classical epidemiological modelling is well suited to explore how the behavior of the inoculated population impacts the total number of infections over the entirety of an epidemic. <b>Methods:</b> A deterministic model of epidemic evolution is analyzed, with 7 compartments defined by their relationship to the emergence of vaccine-resistant mutants and representing three susceptible populations, three infected populations, and one recovered population. This minimally computationally intensive design enables simulation of epidemics across a broad parameter space. The results are used to identify conditions minimizing the cumulative number of infections. <b>Results:</b> When an escape variant is only modestly less infectious than the originating strain within a naive population, there exists an optimal rate of vaccine distribution. Exceeding this rate increases the cumulative number of infections due to vaccine escape. Analysis of the model also demonstrates that inoculated individuals play a major role in the mitigation or exacerbation of vaccine-resistant outbreaks. Modulating the rate of host-host contact for the inoculated population by less than an order of magnitude can alter the cumulative number of infections by more than 20%. <b>Conclusions:</b> Mathematical modeling shows that optimization of the vaccination rate and limiting post-vaccination contacts can affect the course of an epidemic. Given the relatively short window between inoculation and the acquisition of immunity, these results might merit consideration for an immediate, practical public health response.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.19.20248554v2" target="_blank">Substantial Impact of Post Vaccination Contacts on Cumulative Infections during Viral Epidemics</a>
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</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating Safety, Pharmacokinetics and Clinical Benefit of Silmitasertib (CX-4945) in Subjects With Moderate COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Drug: Silmitasertib;   Drug: SOC<br/><b>Sponsor</b>:   Chris Recknor, MD<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of the Efficacy of High Doses of Methylprednisolone in SARS-CoV2 ( COVID-19) Pneumonia Patients</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Drug: Methylprednisolone, Placebo<br/><b>Sponsor</b>:   Azienda Unità Sanitaria Locale Reggio Emilia<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Changes in Viral Load in COVID-19 After Probiotics</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Dietary Supplement: Dietary supplementation in patients with covid disease admitted to hospital<br/><b>Sponsors</b>:   Hospital de Sagunto;   Biopolis S.L.;   Laboratorios Heel España<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Ivermectin for Treatment and Prophylaxis of COVID-19 Pandemic</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Drug: Ivermectin;   Drug: Hydroxychloroquine;   Behavioral: personal protective Measures<br/><b>Sponsor</b>:   Benha University<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Drug: Dalcetrapib;   Other: Placebo<br/><b>Sponsors</b>:   DalCor Pharmaceuticals;   The Montreal Health Innovations Coordinating Center (MHICC);   Covance<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 3 Inhaled Novaferon Study in Hospitalized Patients With Moderate to Severe COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: Novaferon;   Biological: Placebo<br/><b>Sponsor</b>:   Genova Inc.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>suPAR-Guided Anakinra Treatment for Management of Severe Respiratory Failure by COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Drug: Anakinra;   Drug: Placebo<br/><b>Sponsor</b>:   Hellenic Institute for the Study of Sepsis<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of High-dose Vitamin C Combined With Chinese Medicine Against Coronavirus Pneumonia (COVID-19)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C;   Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose;   Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment<br/><b>Sponsor</b>:   Xi'an International Medical Center Hospital<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on Safety and Clinical Efficacy of AZVUDINE in COVID-19 Patients (SARS-CoV-2 Infected)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: AZVUDINE;   Drug: AZVUDINE placebo<br/><b>Sponsors</b>:   HRH Holdngs Limited;   GALZU INSTITUTE OF RESEARCH, TEACHING, SCIENCE AND APPLIED TECHNOLOGY, Brazil;   SANTA CASA DE MISERICORDIA DE CAMPOS HOSPITAL (SCMCH), Brazil;   UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating the Impact of EnteraGam In People With COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Dietary Supplement: Bovine Plasma-Derived Immunoglobulin Concentrate;   Other: Standard of care<br/><b>Sponsors</b>:   Entera Health, Inc;   Lemus Buhils, SL;   Clinical Research Unit, IMIM (Hospital del Mar Medical Research Institute)<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Remdesivir and Tociluzumab for the Management of Severe COVID-19: A Randomized Controlled Trial</strong> - <b>Conditions</b>:   Covid19;   Covid-19 ARDS<br/><b>Interventions</b>:   Drug: Remdesivir;   Drug: Tocilizumab<br/><b>Sponsors</b>:   M Abdur Rahim Medical College and Hospital;   First affiliated Hospital of Xi'an Jiaoting University<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhaled Ivermectin and COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Ivermectin Powder<br/><b>Sponsor</b>:   Mansoura University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AZD1222 Vaccine in Combination With rAd26-S, Recombinant Adenovirus Type 26 Component of Gam-COVID-Vac Vaccine, for the Prevention of COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: AZD1222;   Biological: rAd26-S<br/><b>Sponsors</b>:   AstraZeneca;   R-Pharm<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-COVID19 AKS-452 - ACT Study</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Biological: AKS-452<br/><b>Sponsors</b>:   University Medical Center Groningen;   Akston Biosciences Corporation<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mushroom-based Product for COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: FoTv<br/><b>Sponsors</b>:   Gordon Saxe;   University of California, Los Angeles;   University of California, Irvine<br/><b>Recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Tocilizumab in COVID-19 patients: a cohort study</strong> - CONCLUSIONS: Majority of patients demonstrated clinical improvement and were successfully discharged alive from the hospital after receiving tocilizumab. We observed a rebound effect with CRP, which may suggest the need for higher or subsequent doses to adequately manage cytokine storm. Based on our findings, we believe that tocilizumab may have a role in the early treatment of COVID-19, however larger randomized controlled studies are needed to confirm this.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Gallium maltolate has in vitro antiviral activity against SARS-CoV-2 and is a potential treatment for COVID-19</strong> - CONCLUSION: The in vitro activity of GaM against SARS-CoV-2, together with GaM's known anti-inflammatory activity, provide justification for testing GaM in COVID-19 patients.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform</strong> - BACKGROUND: Hydroxychloroquine has been shown to inhibit entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into epithelial cells in vitro, but clinical studies found no evidence of reduced mortality when treating patients with COVID-19. We aimed to evaluate the effectiveness of hydroxychloroquine for prevention of COVID-19 mortality, as opposed to treatment for the disease.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of FDA approved drugs and nucleoside analogues as potential SARS-CoV-2 A1pp domain inhibitor: An in silico study</strong> - Coronaviruses are known to infect respiratory tract and intestine. These viruses possess highly conserved viral macro domain A1pp having adenosine diphosphate (ADP)-ribose binding and phosphatase activity sites. A1pp inhibits adenosine diphosphate (ADP)-ribosylation in the host and promotes viral infection and pathogenesis. We performed in silico screening of FDA approved drugs and nucleoside analogue library against the recently reported crystal structure of SARS-CoV-2 A1pp domain. Docking...</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA</strong> - Self-amplifying RNA (saRNA) is a cutting-edge platform for both nucleic acid vaccines and therapeutics. saRNA is self-adjuvanting, as it activates types I and III interferon (IFN), which enhances the immunogenicity of RNA vaccines but can also lead to inhibition of translation. In this study, we screened a library of saRNA constructs with cis-encoded innate inhibiting proteins (IIPs) and determined the effect on protein expression and immunogenicity. We observed that the PIV-5 V and Middle East...</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structure-Based Screening to Discover New Inhibitors for Papain-like Proteinase of SARS-CoV-2: An In Silico Study</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expresses a multifunctional papain-like proteinase (PLpro), which mediates the processing of the viral replicase polyprotein. Inhibition of PLpro has been shown to suppress the viral replication. This study aimed to explore new anti-PLpro candidates by applying virtual screening based on GRL0617, a known PLpro inhibitor of SARS coronavirus (SARS-CoV). The three-dimensional (3D) structure of SARS-CoV-2 PLpro was built by homology...</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A ligand selection strategy identifies chemical probes targeting the proteases of SARS-CoV-2</strong> - Activity-based probes are valuable tools for chemical biology. However, finding probes that specifically target the active site of an enzyme remains a challenging task. Here we present a ligand selection strategy that allows to rapidly tailor electrophilic probes to a target of choice and showcase its application for the two cysteine proteases of SARS-CoV-2 as proof of concept. The resulting probes were specific for the active site labelling of 3CL pro and PL pro with sufficient selectivity in a...</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Spiky nanostructures for virus inhibition and infection prevention</strong> - The outbreak of a novel highly infectious virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has aroused people's concern about public health. The lack of ready-to-use vaccines and therapeutics makes the fight with these pathogens extremely difficult. To this point, rationally designed virus entry inhibitors that block the viral interaction with its receptor can be novel strategies to prevent virus infection. For ideal inhibition of the virus, the virus-inhibitor interaction...</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The SARS-CoV-2 RNA-protein interactome in infected human cells</strong> - Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome...</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension</strong> - The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to &gt;200 countries posing a global public health concern. Patients with comorbidity, such as hypertension suffer more severe infection with elevated mortality. The development of effective antiviral drugs is in urgent need to treat COVID-19 patients. Here, we report that calcium channel blockers (CCBs), a type of antihypertensive drug that is widely used in clinics,...</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus</strong> - CONCLUSION: The results showed that INAE alleviated IAV induced ALI in mice. The mechanisms of INAE were associated with its anti-influenza, anti-inflammatory and anti-oxidation properties. Indigo Naturalis might have clinical potential to treat ALI induced by IAV.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Action of dipeptidyl peptidase-4 inhibitors on SARS-CoV-2 main protease</strong> - In a recent publication in this journal Eleftheriou et al. proposed inhibitors of dipeptidyl peptidase-4 (DPP-4) to be functional inhibitors of the main protease (M pro ) of SARS-CoV-2. Their predictions prompted the authors to suggest linagliptin, a DPP-4 inhibitor and approved anti-diabetes drug, as a repurposed drug candidate against the ongoing COVID-19 pandemic. We used an enzymatic assay measuring inhibition of M pro catalytic activity in the presence of four different commercially...</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>"Silent hypoxaemia in COVID-19 patients"</strong> - The clinical presentation of COVID-19 due to infection with SARS-CoV-2 is highly variable with the majority of patients having mild symptoms while others develop severe respiratory failure. The reason for this variability is unclear but is in critical need of investigation. Some COVID-19 patients have been labeled with 'happy hypoxia,' in which patient complaints of dyspnoea and observable signs of respiratory distress are reported to be absent. Based on ongoing debate, we highlight key...</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Recognition of Plausible Therapeutic Agents to Combat COVID-19: An Omics Data Based Combined Approach</strong> - Coronavirus disease-2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has become an immense threat to global public health. In this study, more than 67,000 reference sequences including a complete genome sequence of SARS-CoV-2 isolate performed by us and several in silico techniques were merged to propose prospective therapeutics. Through meticulous analysis, several conserved and therapeutically suitable regions of SARS-CoV-2 such as RNA-dependent RNA...</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Understanding the immunopathogenesis of COVID-19: Its implication for therapeutic strategy</strong> - Although 80% of individuals infected with the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) recover without antiviral treatments, the other 20% progress to severe forms of pulmonary disease, suggesting that the host's immune response to the virus could influence the outcome of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects alveolar epithelial type 2 cells expressing angiotensin-converting enzyme 2, and these infected epithelial cells recruit dendritic cells, neutrophils...</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Covid 19 - Chewing Gum</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313269181">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313300659">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19</strong> - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN313339294">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251184">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251182">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>"AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2."</strong> - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN312324209">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>제2형 중증급성호흡기증후군 코로나바이러스 감염 질환의 예방 또는 치료용 조성물</strong> - 본 발명은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염; 및 글루카곤 수용체 작용제(glucagon receptor agonist), 위 억제 펩타이드(gastric inhibitory peptide, GIP), 글루카곤-유사 펩타이드 1(glucagon-like peptide 1, GLP-1) 및 글루카곤 수용체/위 억제 펩타이드/글루카곤-유사 펩타이드 1(Glucagon/GIP/GLP-1) 삼중 완전 작용제(glucagon receptors, gastric inhibitory peptide and glucagon-like peptide 1 (Glucagon/GIP/GLP-1) triple full agonist)로 이루어진 군으로부터 선택된 1종 이상;을 포함하는 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물을 제공한다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR313434044">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Haptens, hapten conjugates, compositions thereof and method for their preparation and use</strong> - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU311608060">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 RBD共轭纳米颗粒疫苗</strong> - 本发明涉及免疫医学领域，具体而言，涉及一种SARS‑CoV‑2 RBD共轭纳米颗粒疫苗。该疫苗包含免疫原性复合物，所述免疫原性复合物包含：a）与SpyCatcher融合表达的载体蛋白自组装得到的纳米颗粒载体；b）与SpyTag融合表达的SARS‑CoV‑2病毒的RBD抗原；所述载体蛋白选自Ferritin、mi3和I53‑50；所述载体蛋白与所述抗原之间通过SpyCatcher‑SpyTag共价连接。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN313355625">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Устройство электронного контроля и дистанционного управления аппарата искусственной вентиляции легких</strong> - Полезная модель относится к медицинской технике, а именно к устройствам для воздействия на дыхательную систему пациента смесью различных газов, в частности, к устройствам для проведения искусственной вентиляции легких (ИВЛ). Технический результат предлагаемой полезной модели заключается в решении технической проблемы, состоящей в необходимости расширения арсенала технических средств, предназначенных для электронного контроля и управления ИВЛ, путем реализации возможности дистанционного управления аппаратами ИВЛ в медицинских учреждениях, не оборудованных кабельными вычислительными сетями. Указанный технический результат достигается благодаря тому, что в известное устройство электронного контроля и дистанционного управления аппарата ИВЛ, содержащее центральный микроконтроллер, а также программно-аппаратные средства управления функциями доставки воздушной смеси пациенту и многоуровневой тревожной сигнализации об отклонениях от нормативных условий и технических неполадках в аппарате ИВЛ, введены связанные друг с другом микроконтроллер связи и дистанционного управления и радиомодем, выполненный с возможностью связи с точками доступа радиканальной сети, при этом центральный микроконтроллер устройства выполнен с дополнительными входом/выходом, которые связаны с управляющими выходом/входом микроконтроллера связи и дистанционного управления, а, в зависимости от типа применяемой в медицинском учреждении радиоканальной сети связи и передачи данных, радиомодем может быть выполнен в виде интерфейсного аудиомодуля Bluetooth 4.0 BLE, приемопередающего модуля Wi-Fi либо устройства "малого радиуса действия", работающего по технологии LoRa на нелицензируемых частотах мегагерцового диапазона, например, в диапазоне 868 МГц. 3 з.п. ф-лы, 1 ил. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=RU313244211">link</a></p></li>
</ul>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can Wall Street’s Heaviest Hitter Step Up to the Plate on Climate Change?</strong> - More significant than BlackRock executives’s pledges is the firm’s continued inclusion of fossil-fuel companies in its index funds. - <a href="https://www.newyorker.com/news/annals-of-a-warming-planet/can-wall-streets-heaviest-hitter-step-up-to-the-plate-on-climate-change">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Trump Directs His Wrecking Ball at the COVID-19 Relief Bill and Mitch McConnell</strong> - After a week spent largely out of the public eye, the President reappeared with a flurry of pardons and an attack on the House Speaker’s coronavirus relief bill. - <a href="https://www.newyorker.com/news/our-columnists/trump-directs-his-wrecking-ball-at-the-covid-19-relief-bill-and-mitch-mcconnell">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Georgia Trump Fans Say the Last Election Was a Sham. Will They Vote in This One?</strong> - Kelly Loeffler and David Perdue are trying to placate the President and run for the Senate at the same time. - <a href="https://www.newyorker.com/news/us-journal/georgia-trump-fans-say-the-2020-election-was-a-sham-will-they-vote-in-this-one">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>As the Vaccine Arrives, Death and Denial Rage in a California Coronavirus Epicenter</strong> - In the San Joaquin Valley, medical professionals fear that many in the public still fail to grasp the dangers of COVID-19. - <a href="https://www.newyorker.com/science/medical-dispatch/as-the-vaccine-arrives-death-and-denial-rage-in-a-california-coronavirus-epicenter">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The New COVID-19 Relief Package Is Flawed But Essential</strong> - If Congress had done nothing, the U.S. would soon face a humanitarian disaster as well as an economic one. - <a href="https://www.newyorker.com/news/our-columnists/the-new-covid-19-relief-package-is-flawed-but-essential">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study: Smoking bans saved countless lives — could they have increased drunk driving?</strong> -
<figure>
<img alt="A hand holding a cellphone and two cigarettes." src="https://cdn.vox-cdn.com/thumbor/cRacN1HZgDr6fjqzlK7v617P3zo=/270x0:2731x1846/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/68578020/GettyImages_992611410.0.jpg"/>
<figcaption>
John J. Kim/Getty Images
</figcaption>
</figure></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
New research finds potential unintended consequences from “one of the greatest public health successes of the past 25 years.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ew216b">
Alcohol has <a href="https://www.vox.com/future-perfect/2020/1/13/21058864/alcohol-deaths-study">really bad health consequences</a>, and the US doesn’t take that seriously enough. While America may have taken smoking more seriously, it continues to kill nearly half a million people every year. Alcohol-related deaths number almost 100,000 annually.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7WQymv">
A new <a href="https://annemburton.com/pages/working_papers/Burton_JMP.pdf#page=68&amp;zoom=100,96,86">job market paper</a> by Anne Burton, an economics PhD candidate at Cornell University, looked into how smoking bans at bars and restaurants affected alcohol consumption, violent crime, and fatal drunk-driving crashes. Her most notable finding was a 4 percent increase in fatal drunk-driving crashes associated with the implementation of these bans in areas with high levels of smoking. If accurate, this would be a significant harm policymakers need to consider when designing other policies that attempt to curb the use of harmful substances.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7CO0DC">
While smoking bans indoors have become pretty ubiquitous,<strong> </strong>this research may have new relevance as states begin liberalizing marijuana laws and cracking down on e-cigarettes and vaping. Policymakers have to determine if tamping down or easing up on drug restrictions affects the use of other potentially dangerous substances. If legalizing marijuana has the unintended consequence of increasing cigarette usage or cracking down on e-cigarettes pushes those consumers to smoke cigarettes more, that’s a big problem. Burton’s research looks to see if a policy that worked to stop smoking actually could have led people to drink more and led to measurable increases in drunk driving fatalities.
</p>
<figure class="e-image">
<pre><code> &lt;img alt=" " src="https://cdn.vox-cdn.com/thumbor/bRuqWhX8jXdJc14e-fVCJPa8PG8=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22176228/GettyImages_1215179164.jpg" /&gt;
&lt;cite&gt;Apu Gomes/Getty Images&lt;/cite&gt;
&lt;figcaption&gt;Illustrating the potential complementary nature of some drugs, a woman who was released from jail because of the coronavirus pandemic, smokes a pipe loaded with methamphetamine, while her boyfriend smokes a cigarette next to the 110 Freeway in Los Angeles on May 25, 2020.&lt;/figcaption&gt;</code></pre>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nn7XW1">
But first — from one drinker to another (<a href="https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/alcohol-facts-and-statistics">probably</a>) — why drinking and smoking are actually very, very bad and why we should care if more of it happens:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="812CUx">
From 1999 to 2017, a <a href="https://www.nih.gov/news-events/news-releases/alcohol-related-deaths-increasing-united-states">study</a> by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) tracked nearly a million alcohol-related deaths in the United States. In a 2010 National Bureau of Economic Research <a href="https://www.nber.org/system/files/working_papers/w15828/w15828.pdf">paper</a>, researchers systematically reviewed the existing evidence linking alcohol and violent crimes and concluded that the “extensively documented correlations” between alcohol and crime represent “‘true’ causal effects of alcohol use on crime commission.” That’s a big deal. That means the researchers believe it’s not just an association and that some other factor is making people both drink heavily and commit crimes — it’s that alcohol is a big factor in whether some crimes even happen at all.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7s9YEg">
“The number one substance that is involved in arrests and incarceration is alcohol in the United States,” Keith Humphreys, a drug policy expert and professor of psychiatry at Stanford University, told me. “In terms of the damage — people think of illegal drugs as the drivers of the criminal justice system, [but] none of them come close to alcohol.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jr9d5P">
However, as a country, we’ve been overwhelmingly focused on regulating other drugs. My colleague German Lopez wrote a piece titled <a href="https://www.vox.com/2015/6/15/8774233/alcohol-dangerous">“Imagine if the media covered alcohol like other drugs.”</a> Here’s my favorite excerpt:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ER38vi">
What’s worse, public use of this drug has become widely accepted in some circles. In New Orleans, several men and women in their 20s and 30s shouted that they’re going to get “wasted” — a slang term for coming under the effects of alcohol. Some have even turned drinking alcohol into a game that involves ping pong balls and cups. One popular holiday, St. Patrick’s Day, appears to <a href="http://www.vox.com/2016/3/17/11250046/st-patricks-day-google-doodle"><strong>celebrate</strong></a> the dangerous drug...
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="h5gho6">
No other drug comes close to the staggering fatalities of these two. Illicit fentanyl, which has consumed widespread media attention due to the opioid epidemic in the past few years, was linked to fewer than 30,000 overdose deaths in 2017. And marijuana — another drug that federal law enforcement officials have warned is dangerous — reportedly caused zero overdose deaths in the past few thousand years.
</p>
</blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BADI1Q">
Cigarettes are also extremely bad for health — though we’ve done more as a country to combat their use. They remain the <a href="https://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/effects_cig_smoking/index.htm">leading cause of preventable death</a> in the US, killing more than 480,000 people every year. The Centers for Disease Control and Prevention <a href="https://www.cdc.gov/tobacco/basic_information/health_effects/index.htm#:~:text=Smoking%20causes%20cancer%2C%20heart%20disease,immune%20system%2C%20including%20rheumatoid%20arthritis.">adds</a> that “for every person who dies because of smoking, at least 30 people live with a serious smoking-related illness.”
</p>
<h3 id="gS8dZr">
Do more people drive drunk after smoking bans are implemented?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jdp5L3">
Burton wasn’t the first to study smoking bans and their relationship with alcohol consumption as well as events associated with drinking like drunk driving and violent crime.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wpgEWt">
Economists Scott Adams and Chad Cotti of the University of Wisconsin Milwaukee and UW Oshkosh, respectively, looked into the relationship between smoking bans and drunk driving between 2000 and 2005. They began their <a href="https://www.researchgate.net/publication/222817797_Drunk_Driving_after_the_Passage_of_Smoking_Bans_in_Bars">study</a> by noting that “the expected effect of smoking bans on drunk driving is ambiguous” since smokers might choose to go out less, lowering the number of people drinking in total. However, their research indicates that “fatal accidents involving a drunk driver increase by about 13 percent” following the implementation of a smoking ban — an astonishing finding.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SklnGB">
Adams and Cotti looked into what might be happening here, and after reviewing case studies they settled on two theories. The first is “cross-border shopping,” where smokers are willing to drive farther to go to a bar in a neighboring jurisdiction that allows smoking, thereby increasing the number of miles driven after drinking. One example they point to is Minneapolis and St. Paul, Minnesota, which is one large metropolitan area split into two counties. Hennepin County, where Minneapolis is, enacted a smoking ban in 2005, after which there was a 12 percent increase in fatal accidents in Ramsey County, which contains St. Paul.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XtH8SS">
The second theory is that bars are differentiating themselves within jurisdictions with smoking bans by providing outdoor seating or by not enforcing the ban, and that is leading smokers to drive more as well.
</p>
<div class="p-fullbleed-block">
<figure class="e-image">
<pre><code> &lt;img alt=" " src="https://cdn.vox-cdn.com/thumbor/npdhTkSJNLX3nG9y0NuQ38wCmz0=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22176284/GettyImages_1180048075.jpg" /&gt;
&lt;cite&gt;Robert Alexander/Getty Images&lt;/cite&gt;
&lt;figcaption&gt;A “No Smoking” sign on the side of a brick building in downtown Nashville, Tennessee.&lt;/figcaption&gt;</code></pre>
</figure>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mTAKqj">
Burton’s study, which builds on this research, looked at smoking bans in bars and restaurants from 2004 to 2012. She pulled from the Behavioral Risk Factor Surveillance System (BRFSS) and the Nielsen Consumer Panel to measure alcohol consumption and the location of alcohol consumption by smoking status. She turned to the Uniform Crime Reports (UCR) for information on alcohol-related crimes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Em8sIo">
Burton found no statistically significant effect from the bans on whether people remained smokers or on violent crime. However, she did find that for those who drink, the bans increased how much they drank and that in high-prevalence smoking areas, there was a 4 percent increase in fatal drunk-driving crashes but only among high-prevalence smokers. Among all subjects, there was no increase in accidents. This means in the other subgroups, there were slight decreases or no effect on drunk driving. However, Burton told me the 4 percent finding among high-prevalence smokers was the only statistically significant finding.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XaKzOa">
Burton inferred that the 4 percent observed increase in drinking was likely happening at bars and restaurants because there was no effect or a slight decline in alcohol purchased for home consumption. She said she isn’t very concerned about the increase in drinking observed in her study — it amounts to about one drink a month, and there was no evidence that people were all of a sudden binge drinking or engaging in especially dangerous drinking behavior.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ltnT6H">
But there are concerns with the drunk driving findings, which other researchers have pointed out.
</p>
<h3 id="B7n9Vw">
Drunk driving may not be affected by smoking bans, and if it is, it’s fixable
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3ZEZcA">
Before I get into the arguments against Adams, Cotti, and Burton’s findings, I want to make something clear: At the end of the day, the documented health benefits to smoking bans like reductions in secondhand smoke exposure largely outweigh any of the costs, like a small increase in drunk driving in some places. Additionally, there are simple ways to eliminate potential increases in drunk driving.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="c3fvne">
Following the release of Adams and Cotti’s research (which originally showed an association between smoking bans and fatal drunk driving accidents), several researchers dove into the question in order to test their findings.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gzbH2Q">
<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558754/">NIAAA-funded research in 2013</a> examined the effect of New York’s and California’s statewide bar and restaurant smoking bans on “alcohol-related car crash fatalities” and found no association. They tested Adams and Cotti’s hypothesis about jurisdiction shopping by looking at communities along the Pennsylvania-New York border but found no effect on drunk driving accidents.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="y2HLWG">
Andrew Hyland, chair of the department of health behavior at Roswell Park Comprehensive Cancer Center who was one of the authors of the 2013 paper, told me that the biggest concern his team had with Adams and Cotti’s findings was that their research did not include counties where they found zero drunk driving fatalities, which could have biased their observed effect upward.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3tc6ZH">
“Zero events is a very important piece of information,” Hyland told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AWWOGd">
Importantly, Hyland’s research only looked at statewide bans. That means it doesn’t rule out the most plausible jurisdiction-shopping story: one where a city has banned smoking but the state has not, so it’s easy to find a bar just a few miles away that lets people indulge in both vices.
</p>
<div class="c-float-right c-float-hang">
<figure class="e-image">
<pre><code> &lt;img alt=" " src="https://cdn.vox-cdn.com/thumbor/F7bA5305DmMNAXQGzj7MhLARIkM=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22176123/Screen_Shot_2020_12_16_at_3.23.50_PM.png" /&gt;
&lt;cite&gt;Anne Burton&lt;/cite&gt;
&lt;figcaption&gt;Figure 5 in Burton’s paper “The Impact of Smoking Bans in Bars and Restaurants on Alcohol Consumption, Smoking, and Alcohol-Related Externalities,” published November 13, 2020.&lt;/figcaption&gt;</code></pre>
</figure>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vUsMTx">
As statewide smoking bans have proliferated over the years, this jurisdiction-shopping effect is becoming less plausible, highlighting an easy way to eliminate this concern — passing statewide bans everywhere.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GsDf5P">
Looking to Burton’s research, concerns with her findings can be boiled down to measurement error and whether she was actually able to isolate the effect of smoking bans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dTSlfH">
Self-reported measures of alcohol and cigarette consumption can be unreliable. First, because of something called “social desirability bias,” people will often say what reflects better on them rather than the truth. In this case, smokers ashamed of the habit might report fewer cigarettes smoked than is true; heavy drinkers could do the same with their alcohol intake.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0IG5kp">
Second, there’s the issue of “recall bias” — it’s actually just really hard to remember exact numbers when it comes to things like this.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7k7iGl">
“If you add up all the alcohol that Americans say that they drink, you come to the conclusion that roughly half of all alcohol is poured down the drain, because nobody claims it. ... That means people aren’t very good at reporting their drinking,” Humphreys told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jjP3yJ">
For tobacco use, researchers have been able to corroborate survey data with biomarkers (which can’t lie to pollsters). But for alcohol, this type of analysis isn’t possible.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GGg8pw">
“She’s trying to do the best that she can with the data that she has available,” Hyland said of Burton’s research. “The question is, is that sufficient to make a statement that smoke-free policies are causing a 4 percent increase in [drunk driving] fatalities.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aOhIhH">
Burton defends her use of survey data here by saying that even though there could be errors in self-reporting, those errors are likely uncorrelated with the implementation of a smoking ban. She believes the implementation of a smoking ban shouldn’t affect how people respond to survey questions about their alcohol consumption and thus the change between those two points in time should still show the effect of smoke-free policies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RDv6Vd">
Measurement error could also exist in Burton’s reliance on data from the BRFSS and Nielsen. These sources provide data at the individual and household level, respectively. In order to compare county-by-county numbers, Burton used provided “weights” to extrapolate the given information. But the problem is, neither of these data sets is designed to be representative at the county level. So her county-by-county data could be fuzzy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OLrCH6">
As with most research, the biggest problem is trying to isolate the cause of the effect being studied. Aren’t jurisdictions that implement smoking bans likely to have implemented other public health measures around the same time?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kGKc0P">
Burton controls for a few of these, like state blood alcohol concentration limits for driving under the influence and whether the state has a cigarette tax, but says in the future she hopes to go further and include workplace smoking bans and other anti-smoking measures that could be driving the results she finds here.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hkDPpT">
Notably, Burton did not control for the cost of alcohol or taxes on alcohol in her results. This is troubling since these have a well-documented effects on demand and could be confounding her results.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NgskGA">
“I don’t think that small increases in alcohol consumption by themselves are a bad thing,” Burton told me. “The biggest concern is trying to compare the protective effects from secondhand smoke exposure, particularly for bar and restaurant workers ... against the cost of those potential increases in drunk driving fatalities.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="agzMYj">
She’s right — and luckily, the small increase in drinking and the ambiguous effect on drunk driving she found are far outweighed by the benefits of smoke-free laws.
</p>
<div class="c-float-left c-float-hang">
<figure class="e-image">
<pre><code> &lt;img alt=" " src="https://cdn.vox-cdn.com/thumbor/boyJsDJdgdYPAdEYoPVbc252oUY=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22176294/GettyImages_1192557497.jpg" /&gt;
&lt;cite&gt;Andrew Lichtenstein/Getty Images&lt;/cite&gt;
&lt;figcaption&gt;A woman smokes at Sophie’s, a neighborhood bar, in January 1995 in the Lower East Side, New York City, eight years before the city would ban the practice.&lt;/figcaption&gt;</code></pre>
</figure>
</div>
<h3 id="hqQeOs">
Smoking bans are good, actually
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9BstWb">
“Smoke-free policies in worksites and hospitality venues have been one of the greatest public health successes of the last 25 years,” Hyland told Vox.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="T2n2b7">
While there is still some debate around the potential increase in drunk driving, there is a vast, peer-reviewed, scientific literature around the harms of secondhand smoke inhalation, and around the massive health benefits associated with the sharp decline in smoking in part due to smoke-free policies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FlEtFH">
We know that smoking bans have been <a href="https://pubmed.ncbi.nlm.nih.gov/11527773/">effective</a> at <a href="https://pubmed.ncbi.nlm.nih.gov/17637596/">reducing secondhand smoke exposure</a>. Bans in restaurants, bars, and other hospitality establishments have the added benefit of ensuring that workers are not forced to carry the health costs against their will simply due to their place of employment. Bans have also been effective at reducing <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660989/">smoking</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558754/">“reducing opportunities to smoke, changing smoking norms, and reducing smoking rates.” </a>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cje7AP">
Smoking and exposure to secondhand smoke increases the risk of cardiovascular disease, pulmonary disease, cancer, and death. <a href="https://pubmed.ncbi.nlm.nih.gov/17293735/">Research</a> has shown that heart attack admissions “rapidly declined” after the implementation of 100 percent smoke-free laws.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="P8GnhB">
All of this to say that if there was in fact a small increase in fatal drunk driving accidents as a result of these bans, the bans were still worth it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pFeHUq">
It can seem callous to think about policy in these terms, but it cannot be understated how much anti-smoking policies have improved health and general well-being. And that benefit far outweighs the potential that there could be some small increase in drunk driving fatalities. Especially since that risk could be curbed with other anti-drunk driving measures and by universalizing anti-smoking laws at bars, restaurants, and other hospitality establishments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="96GaLn">
“Reading this paper makes me more confident in the value of smoke-free laws,” said Humphreys. “Because what it shows is there is no effect on violence, there is no effect on drunk driving ... and the claimed increases in drinking amount to a teaspoon of wine a day. So even if I believed that we could measure the alcohol consumption that accurately in big panel studies, which I don’t, I don’t care.”
</p>
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<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How we can encourage people to wear masks — for others’ sake</strong> -
<figure>
<img alt="A person wearing a face mask at a Trump campaign rally." src="https://cdn.vox-cdn.com/thumbor/hGGTXCOJK-ApRHKAeBrQ0mWwQ4c=/175x0:4858x3512/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/68577910/1283270840.0.jpg"/>
<figcaption>
So far, many leaders, including the president, have not communicated that wearing a mask is a benevolent — or even a patriotic — act. Doing this could help more people start wearing them, my research suggests. | Ben Hasty/MediaNews Group/Reading Eagle via Getty Images
</figcaption>
</figure></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
My research shows that people think highly of others who conform to rules out of benevolence, which is a good way to sell mask-wearing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B55n5Z">
Governors, mayors, and public health officials are sounding the alarm about rising levels of <a href="https://www.vox.com/coronavirus-covid19">Covid-19</a> across every part of the country. The disease is surging, the death toll is soaring, and it’s clear that some states need more restrictive measures to control the spread.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Wq45Fi">
What continues to frustrate so many leaders is that nine months into this pandemic, science and data have painted a clear path for how to beat the virus and reduce transmission. But the disappointing and deadly truth is that in many cases, it’s difficult to get Americans to follow the rules.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NaiaZU">
Boosted by a president who celebrates breaking rules and deliberately defies science and time-tested norms of civility, millions of Americans have been flagrantly flouting simple requests to wear masks in public, to refrain from congregating in large groups, or to limit their unnecessary travel. With the rule-makers themselves <a href="https://www.nytimes.com/2020/12/01/us/politics/white-house-holiday-parties.html">publicly disregarding</a> the recommendations of experts and scientists of their own administration, rule-breaking Americans have quickly followed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="q0YjzS">
As it happens, the US loves rule breakers; the ethos of breaking with tradition is in our country’s DNA. New Hampshire’s state motto is <a href="https://www.nbcnews.com/news/us-news/new-hampshire-restaurant-shuts-its-doors-rather-enforce-mask-mandate-n1244319">“Live Free or Die,”</a> <a href="https://www.washingtonpost.com/health/arizonas-rugged-individualism-poses-barrier-to-mask-rules/2020/07/19/20de0d4e-c9d1-11ea-99b0-8426e26d203b_story.html">Western states like Arizona</a> famously celebrate rugged individualism, the country’s founders are revered as rebels who defied a demanding government, and even a reality TV star could be elected president.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="g8ArVv">
But in a pandemic, what public health officials are pleading for is a little more conformity. Flattening the curve requires Americans to all take fairly uniform actions — wearing masks, not gathering — for the betterment of the whole of society. It isn’t a time to bristle at being “told what to do.” President-elect Joe Biden has already signaled that he intends, unlike President Trump, to follow the science and issue a national <a href="https://www.cnn.com/2020/12/03/politics/biden-harris-interview-covid-mask/index.html">100-day mask-wearing campaign</a>. While we wait for the months-long rollout of a vaccine to hundreds of millions of Americans, people must fall in line with this and other public health recommendations if there’s to be any hope of beating the virus. But will they?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YvZCkY">
While it may seem unlikely that Biden and public health officials can really encourage many more Americans to follow rules, there are ways to bring Americans together to support conformity. This, in turn, could help get Americans through the last several months of the pandemic with tens of thousands of fewer lives lost.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tVwPK8">
It’s important to think carefully about the message, because there’s more than one type of conformity. The type we think about most often — self-focused conformity — describes actions taken to fit in with a group. (These can be conspicuous inactions, too, such as some Trump supporters refusing to wear masks.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4XlWYB">
But my <a href="https://journals.sagepub.com/doi/10.1177/0146167220963702">research</a> with collaborator Matthew Wice, assistant professor of psychology at SUNY New Paltz, looks at others-focused conformity, what we call “benevolent conformity,” and shows how following norms or rules can benefit others.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9mMXY0">
In one study, we asked more than 300 participants to think back to a time when they saw someone conform to their group. Some participants were asked to think about an instance when someone conformed because they wanted others to like them. Others were asked to think about a time when someone conformed for others’ sake. We then asked all of our participants to report what they thought about this person whose public behavior differed from their privately held beliefs. Did this person have a strong moral character? Were they competent people? Were they kind and friendly?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YGAqIq">
While participants in our research scoffed at conformity when it was perceived as selfish, they respected and appreciated benevolent conformity, seeing it as courageous and praiseworthy. Our experiments showed that Americans found people who conform to protect others’ feelings or to maintain group harmony to be warmer, more competent, and more authentic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qPutgm">
This is a key lesson for Biden and for governors who seek to enforce conformity to help protect people from a deadly virus. They should emphasize that sometimes conformity takes courage. This point should be made loud and clear: In the battle against Covid-19, the courageous and commendable thing to do is to put other people first.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7j99Kr">
So when presented with the idea that following Covid-19 safety measures is “<a href="https://www.vox.com/the-goods/21356150/american-men-wont-wear-masks-covid-19">weak</a>” or “un-American,” public health experts should flip this argument on its head: emphasize the benefits of people’s helpful actions. Wherever possible, leaders must employ the benevolent conformity Americans seem to gravitate toward and respect.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RUj9HR">
Emphasizing a <a href="https://vanbavellab.hosting.nyu.edu/documents/VanBavel.etal.2020.NHB.pdf">strong sense of shared identity</a> can remind Americans that the real reason for adhering to safety measures is not just to fit in, but also to protect the group to which they belong. When adhering to simple safety measures can save tens of thousands of American lives, wearing a mask is not an act of blind obedience, it is an act of patriotism. As vaccines begin to be deployed (with vaccine <a href="https://www.vox.com/recode/22174135/covid-19-vaccine-pfizer-celebrities-influencer-marketing">hesitancy still high</a>) and the pandemic reaching new heights, this kind of messaging will be increasingly urgent to get us back on track.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BlWLOY">
Our research makes one thing clear: Americans love rule breakers, but they also hold a special place in their heart for benevolent, other-focused rule followers. If 2020 has shown us anything, it’s that sometimes, we need to conform for others’ sake.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="inwysq">
<em>Shai Davidai is assistant professor in the management division of Columbia Business School with expertise in the psychology of judgment and decision-making, economic inequality and social mobility, social comparisons, and zero-sum thinking. A social psychologist, his research examines people’s everyday judgments of themselves, other people, and society as a whole.</em>
</p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Christmas Carol, explained by a 5-year-old</strong> -
<figure>
<img alt="The Muppet Christmas Carol." src="https://cdn.vox-cdn.com/thumbor/hTrVSfMgnAEGh4PWKhxr_AQASpI=/0x576:3132x2925/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/68577798/muppetchristmascarol.0.jpg"/>
<figcaption>
Michael Caine gathers with the Muppets for a very festive Christmas. | Disney/Jim Henson Studios
</figcaption>
</figure></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The critic at large (40) and critic at small (5) talk Mickey’s Christmas Carol and The Muppet Christmas Carol.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hzx7E8">
<a href="https://www.gutenberg.org/files/46/46-h/46-h.htm"><em>A Christmas Carol</em></a>, Charles Dickens’s beloved novella about a miserly old man and the three ghosts who visit to teach him about the spirit of Christmas, is one of my favorite stories ever written.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NCRAwA">
I’ve loved it since I was a child obsessed with <em>Mickey’s Christmas Carol, </em>the 1983 animated short starring beloved Disney characters in the major roles. Nominated for an Oscar, <em>Mickey’s Christmas Carol</em> proved a boon to the studio’s animation division at a time when it was flailing. It also became a regular feature of Christmas TV for much of my childhood, turning up every year to retell its familiar tale.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mezECM">
What surprised me to learn as a kid was that there have been many adaptations of <em>A Christmas Carol</em>, across all manner of genres and styles and characters. If there’s a beloved troupe of characters, the odds are good that they’ve taken a crack at <em>A Christmas Carol</em> at one point or another. Mr. Magoo has played Scrooge. Fred Flintstone has played Scrooge. Yosemite Sam has played Scrooge. And, of course, Scrooge McDuck has played Scrooge, opposite Mickey Mouse’s Bob Cratchit. I loved this story, so I consumed as many versions as I could.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Au8uNw">
My childhood also saw the release of a different adaptation of this story that has stood the test of time: the 1992 film <em>The Muppet Christmas Carol</em>, with Kermit the Frog as Bob Cratchit, Statler and Waldorf as Jacob and Robert Marley, and the very human Michael Caine as Scrooge (in one of the renowned thespian’s best performances). A bit of a box office and critical disappointment at its release, <em>The Muppet Christmas Carol</em> has gone on to become a holiday classic for many.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KnRRnq">
But I wondered what a child of today might make of both <em>Mickey’s</em> and <em>Muppet Christmas Carol</em>, and fortunately for me, I just happen to know Vox’s esteemed critic at small, Eliza, who is 5 and 5/12. (I doubt the copy desk will let me put that in the headline. Sorry, Eliza, for mis-aging you.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yNlPf8">
Eliza and I sat down to talk about just what makes <em>A Christmas Carol</em> so timeless and what makes an adaptation of the story successful.
</p>
<h3 id="L1853X">
Emily and Eliza on adaptation choices
</h3>
<figure class="e-image">
<pre><code> &lt;img alt="Scrooge gives the Cratchit children gifts in Mickey’s Christmas Carol." src="https://cdn.vox-cdn.com/thumbor/3CD4lYeAPDCb-blR7oCFTjc3Xbk=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22193903/Screen_Shot_2020_12_23_at_12.19.32_PM.png" /&gt;
&lt;cite&gt;Disney&lt;/cite&gt;
&lt;figcaption&gt;The Cratchit children and Scrooge celebrate a Christmas together.&lt;/figcaption&gt;</code></pre>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1C1xew">
<strong>Emily: </strong>When you’ve watched <a href="https://www.vox.com/2014/12/23/7439089/christmas-carol-best-adaptation">as many adaptations of <em>A Christmas Carol</em> as I have</a>, you start to spot small, telling differences among them. Which story elements from the original work do screenwriters choose to prioritize over others? And which story elements do they leave out entirely?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="d3XnlM">
Even a book as slim as <em>A Christmas Carol</em> can’t be adapted with 100 percent faithfulness, and any given screenwriter must make choices about whether to underline the ghost story, the good Christmas cheer, the story of an old man’s regret, Dickens’s social conscience, or the occasional stabs at dry humor. There are a bunch of possible takes hiding within this one tale, and each is as valid as the last.
</p>
<aside id="SZEEuq">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qX3NTo">
<em>Mickey’s Christmas Carol</em> mostly chooses to make Dickens come to Disney, rather than sending Disney to Dickens. The special borrows the familiar story elements and sends them through the Disney prism, so that, say, Goofy is playing the ghost of Jacob Marley, while Jiminy Cricket plays the Ghost of Christmas Past. At the center is Alan Young as Scrooge McDuck, and his performance is the special’s greatest asset. (Young had first played Scrooge McDuck in a <a href="http://www.mousevinyl.com/content/dickens-christmas-carol-disneyland-records">1974 children’s record version of <em>A Christmas Carol</em></a> that was largely adapted for <em>Mickey’s Christmas Carol</em>.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O8rb2r">
The special’s tone lurches all over the place, something that is not helped by its 25-minute runtime. It’s surprising it comes together at all — there’s no way the slapstick of Goofy should work with the creepiness of Marley’s ghost, but it kinda does — but it’s always hampered by being a Disney production first and a Dickens adaptation second. In the end, it suggests that the moral of this story is mostly “Be nice to other people, okay?” which is a good lesson to impart but not really the focus of the novella.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mE4i9D">
<em>The Muppet Christmas Carol</em> is altogether stronger. It doesn’t force the Muppet characters into roles they wouldn’t fit particularly well, so that Michael Caine’s work as Scrooge can have the weight it requires. (He’s one of the <a href="https://www.vox.com/culture/2016/12/21/14020014/scrooges-ranked-best-scrooge-christmas-carol">best Scrooges ever</a>.) But it does allow, say, Fozzie Bear to step in as Fezziwig — or should I say Fozziwig — which is exactly the sort of tiny, comedic cameo where one of the sillier Muppets can be very funny.
</p>
<aside id="rLWROT">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="166f4J">
<em>The Muppet Christmas Carol</em> finds a great middle ground between the book and the Muppets, right down to having Gonzo (as Charles Dickens) recite chunks of text from the book directly to viewers (with Rizzo the Rat on hand to provide comic relief). It’s not my favorite adaptation of this story, but it’s darn close.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eu3VAC">
Eliza, what did you see as the chief adaptation choices made by these two specials?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SnRbgU">
<strong>Eliza: </strong><em>The Muppet Christmas Carol</em> looked like Sesame Street, and <em>Mickey’s Christmas Carol</em> was a cartoon. The Spirit of Yet to Come in <em>Mickey’s Christmas Carol</em> had eyes [in its hood]. <em>The Muppet Christmas Carol</em> one didn’t have eyes and was gray with lines. The <em>Mickey’s Christmas Carol</em> one was brown. Plus, when the <em>Mickey’s Christmas Carol</em> spirit threw Scrooge in fire, he said, “SCROOOOOOOOOGE!” and the other one was way more quiet.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IpA7Id">
Oh! I was going to ask something about <em>Mickey’s Christmas Carol.</em> Why did the Spirit of the Future drop Donald Duck, who was playing Scrooge, in fire?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pwIXxs">
<strong>Emily: </strong>[desperately trying not to explain hell to a child] Well, uh, it was to show he had been bad. And if he stayed bad, he would go and get burned up.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LchYdh">
<strong>Eliza: </strong>[looking very concerned] Oh.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gWjVXz">
<strong>Emily: </strong>But that’s only if you’re bad. [disconcertingly long pause] He was pretty bad. Wait. Donald Duck doesn’t play Scrooge in <em>Mickey’s Christmas Carol</em>! He plays Scrooge’s nephew, Fred.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WBeiDx">
<strong>Eliza: </strong>No, that’s a smaller girl duck.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TmxSbi">
<strong>Emily: </strong>All right.
</p>
<h3 id="1v52U8">
Emily and Eliza on Ebenezer Scrooge
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7GmqKS">
<strong>Emily: </strong>Few characters in English literature are as memorable as Ebenezer Scrooge, who (if nothing else) shows off Dickens’s skill for naming characters with exactly the right series of syllables, such that you instantly understand who they are.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cgsKtM">
Hundreds, if not thousands, of people have played Scrooge over the years. It’s impossible to get an exact count, since stage adaptations of <em>A Christmas Carol</em> remain staples of regional theaters and the like. But <a href="https://en.wikipedia.org/wiki/Ebenezer_Scrooge#Portrayals_in_notable_adaptations">the list of “notable performances”</a> on Scrooge’s Wikipedia page is formidable, with seemingly every actor over 40 with a patrician air and stentorian bluster having taken a crack at the part. Why just this year, <a href="https://www.oldvictheatre.com/whats-on/2020/old-vic-in-camera/a-christmas-carol-5"><em>The Walking Dead</em>’s Andrew Lincoln</a> played Scrooge from the stage of London’s Old Vic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="liMG0g">
Scrooge has become such an immortal character because he somehow speaks to our worst and best selves. There are days when we want to say “humbug” to the world and days when we’re so full of good feeling that we could pop. We want to believe that it’s not too late to change our ways, and Christmas often brings out a fond feeling for our fellow human beings.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HPjyae">
Eliza, did you like Scrooge?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="g1ApOX">
<strong>Eliza: </strong>I didn’t like him at first, but then I liked him!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZoOYCM">
<strong>Emily: </strong>What didn’t you like about him?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="T5xbvX">
<strong>Eliza: </strong>[excited] The movie is kind of like the Grinch!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZqqBSX">
<strong>Emily: </strong>Eliza! A deliberate comparison between two disparate works! That’s the backbone of much critical analysis!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pyd4TE">
<strong>Eliza: </strong>The Grinch didn’t like Christmas. But what’s different about the two movies is that the Grinch stole Christmas, and Scrooge doesn’t do that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Dl0eE0">
<strong>Emily: </strong>Yeah, you’re right.<strong> </strong>Scrooge doesn’t have that level of ambition.
</p>
<h3 id="GiszJY">
Emily and Eliza on the many ghosts of Christmas
</h3>
<div id="tBQAJB">
<div style="width: 100%; height: 0; padding-bottom: 56.25%;">
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XisC8Z">
<strong>Emily: </strong>Broadly speaking, <em>A Christmas Carol</em> fits into a <a href="https://www.smithsonianmag.com/smart-news/why-do-ghost-stories-go-christmas-180961547/">longstanding tradition</a> of telling ghost stories during the Christmas season. Indeed, there are spooky Christmas stories stretching back to medieval times, and ghosts popping up at such a festive time of year were one of the handful of Christmas traditions hanging on in Dickens’s day.
</p>
<aside id="6XfQZp">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yEaoA5">
In 1843, when Dickens published <em>A Christmas Carol</em>, Christmas was often treated as just another day, with few people even getting time off work — that’s why Bob Cratchit asks if he can have the day off. So <em>A Christmas Carol</em> is an attempt to reinstate Christmas as an important holiday on both a plot level (the characters are taught to keep Christmas every day of the year) and a more metatextual level (a Christmas ghost story would have seemed properly festive to Dickens’s readers).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Hxwe45">
But forget all that heady nonsense. I just love <em>ghosts</em>. What about you, Eliza? Who were your favorite Christmas spirits?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bAJzZx">
<strong>Eliza: </strong>The Spirit of Christmas Present in <em>Mickey’s Christmas Carol</em>. He opens the roof of a house, and the person inside goes “EEEEEK!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9KRY9X">
<strong>Emily</strong>: I like when he goes right up next to the window, and his eye’s really big.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dK0Ups">
<strong>Eliza: </strong>And I like Jacob and Robert Marley from <em>Muppet Christmas Carol</em>! My favorite song is “Marley and Marley.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PUDjKy">
<strong>Emily: </strong>Great song. A real bop. Which one of the ghosts would you want to be?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1WMfI7">
<strong>Eliza: </strong>I would want to be the Spirit of Christmas Past. Too bad I couldn’t fly for real into the past! I would go back in time to all the Christmases and get all the [Lego] Advent calendars that we’ve done. We’ve done three, and four when we’ve finished this one. I’ll get all the other boxes that have been thrown away, and I’ll bring them home to the present.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="d5ZVCI">
<strong>Emily: </strong>I think the ghosts are cool. I wish I could meet the ghosts.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OcU7aE">
<strong>Eliza: </strong>Me too! It’s too bad that all the people in the world can’t be the ghosts. If everybody wanted to, they could be the ghosts, but if one person or two or maybe 100 didn’t want to, they could just not be it. [pause] I wish I could just go through the screen, so we could talk and interview in person.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8z0b6v">
<strong>Emily: </strong>I’d like that! I’ll have to come visit when all of this is over!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kcDIZj">
<strong>Eliza: </strong>Then you could meet my whole family!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GfxEGY">
<strong>Emily: </strong>Well, I’ve met your mom and your dad, and I met you when you were a baby.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="43vAMp">
<strong>Eliza</strong>: Yeah, but you haven’t met my grandpa and grandma! And you’re in luck! I’ve got <em>two</em> grandpas and grandmas.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nzRVI8">
<strong>Emily: </strong>I don’t have any grandpas or grandmas anymore.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HC7gi5">
<strong>Eliza: </strong>Why?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YazraV">
<strong>Emily: </strong>[aggressively backpedals]
</p>
<h3 id="MEA5cX">
Emily and Eliza (and Nora) on quills
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="crLlFO">
[Eliza’s younger sister, Nora, the critic at tiny who is 2 and 3/4, enters the room.]
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VChHSl">
<strong>Eliza: </strong>Nora! You should ask your question!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eqD37Z">
[Nora approaches and whispers something in Eliza’s ear.]
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Guedrh">
<strong>Eliza: </strong>Ask her!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JGnkMc">
<strong>Nora: </strong>You can’t write with a leaf!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2ENnZq">
<strong>Eliza: </strong>A leaf? Oh, a feather! Mickey and Donald Duck paint with a quill. She wants to know why they do that?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="J9CIEI">
<strong>Emily: </strong>Well, they’re just writing with them. They’re not painting. People would take feathers and make the tips really sharp. Then they would dip them in little ink pots and write things down. But now we have pens, and those are just a lot easier to use.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tv9V9f">
<strong>Eliza: </strong>My drawing desk has a little circle to put a bottle of ink in, and then you can put a pen in it. It’s George’s desk. He lived in our house before we did.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V81Gwh">
<strong>Emily: </strong>Does that answer your question, Nora?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TuTUdP">
<strong>Nora: </strong>[stares]
</p>
<h3 id="M5ww2S">
Emily and Eliza on <em>A Christmas Carol</em>’s enduring appeal
</h3>
<div id="rqzylM">
<div style="width: 100%; height: 0; padding-bottom: 56.25%;">
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FadEAt">
<strong>Emily: </strong><em>A Christmas Carol </em>is one of the <a href="https://www.vox.com/2014/12/28/7450079/a-christmas-carol">most successful books ever written</a>. Almost everyone alive knows some version of this story, and there are plenty of adaptations that have nothing to do with Christmas at all. (See also: McConaughey, Matthew, in <em>Ghosts of Girlfriends Past</em>.) Dickens’s story is beautifully structured, appropriately festive, and just the right amount of creepy. It’s no wonder so many filmmakers have tried their hand at adapting it, though many have failed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WXWgBu">
Eliza, why do you think this story has endured so long?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OegxBj">
<strong>Eliza: </strong>Because it’s about Christmas.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0pGtdd">
<strong>Emily: </strong>I like the way it’s about looking at your life and seeing the things that should and could be better and using Christmas as a way to make your life better and be a better person. But I also like the ghosts. I wish I could meet the ghosts.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="chAuUV">
<strong>Eliza: </strong>Me too!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lUIH4x">
<strong>Emily: </strong>I’m gonna ask you the question I always ask you: Who is the character you are the most similar to?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mF8vz4">
<strong>Eliza: </strong>I don’t know.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3tYQJZ">
<strong>Emily: </strong>I think you’re the most similar to that little bunny who carries the turkey in <em>The</em> <em>Muppet Christmas Carol</em>, because you’re nice and you like to help. Who’s your mom most similar to?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="umNp06">
<strong>Eliza: </strong>Maybe the bunny?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FTJp0w">
<strong>Emily: </strong>I think I’m most similar to one of the Cratchits, because I have to work and work for a boss who doesn’t appreciate me, and all the ink gets frozen —
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KbwFKI">
<strong>Jen, Eliza’s mom and Emily’s boss, offended and eavesdropping from outside the room: </strong>WHOAAAAAAAAA!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yztTp4">
<strong>Eliza: </strong>Mom, you’re in the middle of the bunny and Scrooge.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dXe85X">
<strong>Jen:</strong> That’s a good answer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vlhXmh">
<strong>Emily: </strong>Your mom is nothing like Scrooge, Eliza. Not even a little bit.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z3LE4e">
<strong>Eliza: </strong>I know who’s like Scrooge!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wxJuFz">
<strong>Emily:</strong> Who?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nD3lyl">
<strong>Eliza: </strong>Donald Trump!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9kwXzy">
<strong>Emily: </strong>Wow. Eliza with the hot takes. I hope he’s visited by three ghosts this Christmas, who convince him to change his ways.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6jGpNk">
<strong>Eliza: </strong>Me too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="feYHgX">
<strong>Correction: </strong>This article originally said <em>A Christmas Carol</em> was published in 1863. It was published in 1843. We have corrected the error.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="R3XLEF">
</p>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Apologised to Virat after that run out, he was okay about it: Rahane</strong> - Ajinkya Rahane on Friday said he had apologised to Virat Kohli after his horrible mix-up with him led to the India captain''s game-changing run out</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>‘Boxing day’: Hour of reckoning for Rahane as new-look India eye equaliser</strong> - A couple of forced and an equal number of tactical changes was always on cards for the visitors as they take on Tim Paine’s confident men.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Australia’s Tim Paine calls for Sydney ‘sacrifice’, invites broadcast staff to join them in bio-secure bubble</strong> - Cricket Australia said Melbourne has been placed on standby to host the third Test between India and Australia if Sydney's COVID-19 situation renders it "untenable"</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Australia vs India | Indians get to grips with tackling Aussie menace</strong> - Hands-on support from coaching staff as team undergoes intense training</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Compensatory package if season is curtailed</strong> - The domestic cricket fraternity will heave a sigh of relief after the BCCI’s AGM on Thursday agreed to work out a compensatory package should the dome</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Amarinder asks farmers not to disrupt State’s telecom services</strong> - The CM urged them to exercise the same restraint that they had been showing over the past several months and said that telecom connectivity had become even more critical for people amid the COVID-19 pandemic.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CBI books case against Haryana firm, others for cheating banks</strong> - Audit revealed alleged diversion of funds to related parties</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Five NSS volunteers from AU to take part in Republic Day parade</strong> - Five students from NSS, Andhra University, have been selected to take part in Republic Day 2021 parade. Vice-Chancellor P.V.G.D Prasad Reddy congratul</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dry run for COVID-19 vaccine rollout in 4 States next week: Govt.</strong> - Andhra Pradesh, Assam, Gujarat, Punjab to pilot process in two districts</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mamata Banerjee government destroying West Bengal; stopping Central benefits for State farmers: PM Modi</strong> - In an apparent attack on Left parties, Mr. Modi said, “Parties which are missing APMC-mandis nowadays, repeatedly forget that there are no APMC-mandis in Kerala. And these people never agitate in Kerala.”</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Brexit: EU diplomats get trade deal briefing</strong> - The BBC has seen the 1,246-page document, which includes about 800 pages of annexes and footnotes.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pope urges coronavirus vaccine access for all</strong> - "We cannot erect walls" to its availability, he says, in his first online Christmas Day message.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Notre-Dame: Choir sings inside cathedral for first time since fire</strong> - Singers perform inside the Paris cathedral for the first time since the April 2019 fire.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ivry Gitlis: Celebrated Israeli virtuoso violinist dies at 98</strong> - Described as one of the modern greats of classical music, he was a hugely charismatic figure.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Alexei Navalny ally Lyubov Sobol 'held after raid'</strong> - Lyubov Sobol had earlier turned up at the home of an agent Alexei Navalny says helped poison him.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>2020’s 20 most-commented stories</strong> - Yesterday we brought you the most popular stories of 2020. These are the most talked-about. - <a href="https://arstechnica.com/?p=1731551">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nikola stock craters after cancellation of major garbage truck order</strong> - Nikola has been on the defensive since fraud allegations surfaced in September. - <a href="https://arstechnica.com/?p=1731952">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Poignant The Midnight Sky wrestles with whether humankind is worth saving</strong> - George Clooney directed and stars in adaptation of the Lily Brooks-Dalton novel - <a href="https://arstechnica.com/?p=1730954">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>2020’s 20 most-read stories on Ars Technica</strong> - It's our annual rundown of the most-read stories. - <a href="https://arstechnica.com/?p=1731253">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Google develops an AI that can learn both chess and Pac-Man</strong> - MuZero handles both rules-based and open-ended games. - <a href="https://arstechnica.com/?p=1731895">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><strong>One Christmas morning, a cop on horseback is sitting at a traffic light and next to him is a little girl on her brand-new bike.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The cop says to the young girl, "Nice bike you got there sweetheart. Did Santa bring that to you?"
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Yes, he did,” she replied sweetly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
With a smile on his face, the cop says "Well, next year, tell Santa to put a taillight on that bike,” and he proceeds to hand the girl a $20 ticket.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Before the cop rides off she says "By the way, that's a nice horse you got there. Did Santa bring that to you?"
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Playing along the cop says, "Yeah, he sure did.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well, next year, tell Santa the dick goes underneath the horse, not on top.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/nothinlefttochoose"> /u/nothinlefttochoose </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/kjquhl/one_christmas_morning_a_cop_on_horseback_is/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/kjquhl/one_christmas_morning_a_cop_on_horseback_is/">[comments]</a></span></p></li>
<li><strong>In college, I was refused membership in all the fraternities because I was circumcised.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Apparently you need to be a complete dick.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/porichoygupto"> /u/porichoygupto </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/kjfib1/in_college_i_was_refused_membership_in_all_the/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/kjfib1/in_college_i_was_refused_membership_in_all_the/">[comments]</a></span></p></li>
<li><strong>As an Aussie, Americans are always asking me where in Australia there <em>isn’t</em> something trying to kill you...</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“School” is my answer
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/PerilousPeril"> /u/PerilousPeril </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/kjtwae/as_an_aussie_americans_are_always_asking_me_where/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/kjtwae/as_an_aussie_americans_are_always_asking_me_where/">[comments]</a></span></p></li>
<li><strong>(A tad NSFW) A friend got really mad at me for smelling his sister’s underwear.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I don’t know if it’s because she was still wearing them, or because the whole family was there. Either way, it made the rest of the funeral very awkward.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/vatufaire"> /u/vatufaire </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/kjsuj3/a_tad_nsfw_a_friend_got_really_mad_at_me_for/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/kjsuj3/a_tad_nsfw_a_friend_got_really_mad_at_me_for/">[comments]</a></span></p></li>
<li><strong>My son is 2934 days old today.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He was born on 12/12/12.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
 
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Edit: it's 12/12/12 for the non-Americans.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/RayInRed"> /u/RayInRed </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/kjdxvf/my_son_is_2934_days_old_today/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/kjdxvf/my_son_is_2934_days_old_today/">[comments]</a></span></p></li>
</ul>
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href="./archive-daily-dose/19 November, 2020.html">19 November, 2020</a></li><li><a href="./archive-daily-dose/18 November, 2020.html">18 November, 2020</a></li><li><a href="./archive-daily-dose/17 November, 2020.html">17 November, 2020</a></li><li><a href="./archive-daily-dose/16 November, 2020.html">16 November, 2020</a></li><li><a href="./archive-daily-dose/15 November, 2020.html">15 November, 2020</a></li><li><a href="./archive-daily-dose/14 November, 2020.html">14 November, 2020</a></li><li><a href="./archive-daily-dose/13 November, 2020.html">13 November, 2020</a></li><li><a href="./archive-daily-dose/12 November, 2020.html">12 November, 2020</a></li><li><a href="./archive-daily-dose/11 November, 2020.html">11 November, 2020</a></li> <ul id="daily-dose-list"><li><a href="./archive-daily-dose/25 December, 2020.html">25 December, 2020</a></li><li><a href="./archive-daily-dose/24 December, 2020.html">24 December, 2020</a></li><li><a href="./archive-daily-dose/23 December, 2020.html">23 December, 2020</a></li><li><a href="./archive-daily-dose/22 December, 2020.html">22 December, 2020</a></li><li><a href="./archive-daily-dose/21 December, 2020.html">21 December, 2020</a></li><li><a href="./archive-daily-dose/20 December, 2020.html">20 December, 2020</a></li><li><a href="./archive-daily-dose/19 December, 2020.html">19 December, 2020</a></li><li><a href="./archive-daily-dose/18 December, 2020.html">18 December, 2020</a></li><li><a href="./archive-daily-dose/17 December, 2020.html">17 December, 2020</a></li><li><a href="./archive-daily-dose/16 December, 2020.html">16 December, 2020</a></li><li><a href="./archive-daily-dose/15 December, 2020.html">15 December, 2020</a></li><li><a href="./archive-daily-dose/14 December, 2020.html">14 December, 2020</a></li><li><a href="./archive-daily-dose/13 December, 2020.html">13 December, 2020</a></li><li><a href="./archive-daily-dose/12 December, 2020.html">12 December, 2020</a></li><li><a href="./archive-daily-dose/11 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href="./archive-daily-dose/29 November, 2020.html">29 November, 2020</a></li><li><a href="./archive-daily-dose/28 November, 2020.html">28 November, 2020</a></li><li><a href="./archive-daily-dose/27 November, 2020.html">27 November, 2020</a></li><li><a href="./archive-daily-dose/26 November, 2020.html">26 November, 2020</a></li><li><a href="./archive-daily-dose/25 November, 2020.html">25 November, 2020</a></li><li><a href="./archive-daily-dose/24 November, 2020.html">24 November, 2020</a></li><li><a href="./archive-daily-dose/23 November, 2020.html">23 November, 2020</a></li><li><a href="./archive-daily-dose/22 November, 2020.html">22 November, 2020</a></li><li><a href="./archive-daily-dose/21 November, 2020.html">21 November, 2020</a></li><li><a href="./archive-daily-dose/20 November, 2020.html">20 November, 2020</a></li><li><a href="./archive-daily-dose/19 November, 2020.html">19 November, 2020</a></li><li><a href="./archive-daily-dose/18 November, 2020.html">18 November, 2020</a></li><li><a href="./archive-daily-dose/17 November, 2020.html">17 November, 2020</a></li><li><a href="./archive-daily-dose/16 November, 2020.html">16 November, 2020</a></li><li><a href="./archive-daily-dose/15 November, 2020.html">15 November, 2020</a></li><li><a href="./archive-daily-dose/14 November, 2020.html">14 November, 2020</a></li><li><a href="./archive-daily-dose/13 November, 2020.html">13 November, 2020</a></li><li><a href="./archive-daily-dose/12 November, 2020.html">12 November, 2020</a></li><li><a href="./archive-daily-dose/11 November, 2020.html">11 November, 2020</a></li>
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<h2 id="covid-19">Covid-19</h2> <h2 id="covid-19">Covid-19</h2>
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