Safety and immunogenicity of heterologous and homologous inactivated and adenoviral-vectored COVID-19 vaccines in healthy adults -
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+In light of intermittent supply shortages of individual vaccines and evidence of rare but serious adverse events after vaccination, heterologous regimens for COVID-19 vaccines have gained significant interest. This study aims to assess the reactogenicity and immunogenicity of the heterologous adenoviral vector vaccine regimen (ChAdOx1-S, AstraZeneca; hereafter referred to as AZ) and the inactivated vaccine regimen (CoronaVac; hereafter referred to as CV) regimen in healthy Thai adults immunized between June and September 2021. Our study showed that adverse events following homologous CV-CV and AZ-AZ, and heterologous CV-AZ and AZ-CV combinations, were mild and well tolerated overall. Receptor-binding domain (RBD)-specific antibody responses and neutralizing activities against wild-type and variants of concern after two-dose vaccination were higher in the heterologous CV-AZ and homologous AZ-AZ groups compared to the CV- CV and AZ-CV groups. Conversely, the spike-specific IgA response was detected only in the CV-AZ group after two doses of vaccination. The total interferon gamma response was detected in both the CV-AZ and AZ-CV groups after the two-dose vaccination. Given the shorter completion time of two doses, heterologous CoronaVac followed by ChAdOx1-S can be considered as an alternative regimen to homologous efficacy-proven ChAdOx1-S in countries with circulating variants. Additional studies on the efficacy and durability of immune responses induced by heterologous vaccine regimens are warranted.
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Current state of COVID-19 knowledge, attitude, practices, and associated factors among Bangladeshi food handlers from various food industries. -
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+While people around the world are terrified of the global pandemic coronavirus disease 2019 (COVID-19) and are dying for a permanent solution, undertaking preventive safety measures are said to be the most effective way to stay away from it. Peoples adherences to these measures are broadly dependent on their knowledge, attitude, and practices (KAP). People working in the food industries must be extra cautious during this time because they are in close proximity to consumable items. The present study was designed to evaluate food handlers knowledge, attitude, and practices regarding COVID-19 in different food industries in Bangladesh. A number of 400 food handlers from 15 food industries took part in this online-based study. The information was collected from the participants through a questionnaire prepared in Google form. With a correct response rate of about 90% on average (knowledge 89.7%, attitude 93%, practices 88.2%), the participants showed an acceptable of KAP regarding COVID-19. Education and working experiences had a significant association with the total KAP scores (p < 0.05). The findings may assist public health professionals and practitioners in developing targeted strategies for implementing such studies in other industrial sectors and taking appropriate measures based on the KAP studies.
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Post‑COVID‑19 syndrome in outpatients: a cohort study -
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+Background After mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed. Objectives To characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors. Participants Outpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative). Design Monocentric cohort study with prospective phone interview between more than three months to ten months after initial visit to the emergency department and outpatient clinics. Main Measures Data of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey. Key results The study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID- positive and COVID-negative, respectively; p=0.020) and health care workers (67% versus 82%; p=0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p=0.006). Overall, 21% COVID-positive and 15% COVID-negative patients (p=0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio [or] 2.14, 95%CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16) and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms. Conclusions More than half of COVID-positive outpatients report persistent symptoms up to ten months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society.
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SARS-CoV-2 epidemic after social and economic reopening in three US states reveals shifts in age structure and clinical characteristics -
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+In the United States, state-level re-openings in spring 2020 presented an opportunity for the resurgence of SARS-CoV-2 transmission. One important question during this time was whether human contact and mixing patterns could increase gradually without increasing viral transmission, the rationale being that new mixing patterns would likely be associated with improved distancing, masking, and hygiene practices. A second key question to follow during this time was whether clinical characteristics of the epidemic would improve after the initial surge of cases. Here, we analyze age-structured case, hospitalization, and death time series from three states - Rhode Island, Massachusetts, and Pennsylvania - that had successful re-openings in May 2020 without summer waves of infection. Using a Bayesian inference framework on eleven daily data streams and flexible daily population contact parameters, we show that population- average mixing rates dropped by >50% during the lockdown period in March/April, and that the correlation between overall population mobility and transmission-capable mobility was broken in May as these states partially re-opened. We estimate the reporting rates (fraction of symptomatic cases reporting to health system) at 96.0% (RI), 72.1% (MA), and 75.5% (PA); in Rhode Island, when accounting for cases caught through general-population screening programs, the reporting rate estimate is 94.5%. We show that elderly individuals were less able to reduce contacts during the lockdown period when compared to younger individuals, leading to the outbreak being concentrated in elderly congregate settings despite the lockdown. Attack rate estimates through August 31 2020 are 6.4% (95% CI: 5.8% − 7.3%) of the total population infected for Rhode Island, 5.7% (95% CI: 5.0% − 6.8%) in Massachusetts, and 3.7% (95% CI: 3.1% − 4.5%) in Pennsylvania, with some validation available through published seroprevalence studies. Infection fatality rates (IFR) estimates are higher in our analysis (>2%) than previously reported values, likely resulting from the epidemics in these three states affecting the most vulnerable sub-populations, especially the most vulnerable of the ≥80 age group. We make several suggestions for enhancements to current data collection practices that could improve response efforts in winter.
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How did covid19 change our communities? Acompared analysis of meetup communitiesbefore and after the pandemic -
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+The year 2020 has been characterized by the outbreak of covid19. The spread of the disease has had a severe impact in many aspects of our lives that go beyond our health. From economical to psychological or social contexts, covid19 caused a halt in our daily activities and forced us to adapt or develop new habits. The following study uses data retrieved from 800 groups in the platform meetup.com to study and compare the impact of the coronavirus in the social life of two vibrant but culturally different cities such as Washington DC and Barcelona. Results suggest that though groups have been able to maintain their activity, mostly through complementing offline with online events, communities have become more fragmented in 2020. The results also suggest that the halt in activity along with the fragmentation has been higher in Barcelona where a very strict lockdown policy was implemented and that Washington DC has been more able to effectively switch to online events after the outbreak of the pandemic.
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One year after the outbreak – Involvement of scientists in the Covid-19 pandemic Findings from a Germany-wide study -
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+The Covid-19 pandemic initially led to high demands for scientific expertise, while at the same time scientific results, for example in the form of preprints, being widely and sometimes critically discussed in public almost as soon as they were published. It is an open question how Scientists react and adopt to the changed situation. With data from the (German) Scientists Survey, it is possible to map the scientists’ involvement in the pandemic - across academic positions and disciplines. Our results show that scientists from all disciplines are involved in corona-related research, have started or acquired projects and already published with relation to COVID-19. Social Sciences are even more involved than e.g. life science. Gender effects emerge I such a way that women actually less rapidly adopt to the new situation.
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Real-world evaluation of AI driven COVID-19 triage for emergency admissions: External validation & operational assessment of lab-free and high-throughput screening solutions -
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+Background Uncertainty in patients9 COVID-19 status contributes to treatment delays, nosocomial transmission, and operational pressures in hospitals. However, typical turnaround times for batch-processed laboratory PCR tests remain 12-24h. Although rapid antigen lateral flow testing (LFD) has been widely adopted in UK emergency care settings, sensitivity is limited. We recently demonstrated that AI-driven triage (CURIAL-1.0) allows high-throughput COVID-19 screening using clinical data routinely available within 1h of arrival to hospital. Here we aimed to determine operational and safety improvements over standard-care, performing external/prospective evaluation across four NHS trusts with updated algorithms optimised for generalisability and speed, and deploying a novel lab-free screening pathway in a UK emergency department. Methods We rationalised predictors in CURIAL-1.0 to optimise separately for generalisability and speed, developing CURIAL-Lab with vital signs and routine laboratory blood predictors (FBC, U&E, LFT, CRP) and CURIAL-Rapide with vital signs and FBC alone. Models were calibrated during training to 90% sensitivity and validated externally for unscheduled admissions to Portsmouth University Hospitals, University Hospitals Birmingham and Bedfordshire Hospitals NHS trusts, and prospectively during the second-wave of the UK COVID-19 epidemic at Oxford University Hospitals (OUH). Predictions were generated using first-performed blood tests and vital signs and compared against confirmatory viral nucleic acid testing. Next, we retrospectively evaluated a novel clinical pathway triaging patients to COVID-19-suspected clinical areas where either model prediction or LFD results were positive, comparing sensitivity and NPV with LFD results alone. Lastly, we deployed CURIAL-Rapide alongside an approved point-of- care FBC analyser (OLO; SightDiagnostics, Israel) to provide lab-free COVID-19 screening in the John Radcliffe Hospital9s Emergency Department (Oxford, UK), as trust-approved service improvement. Our primary improvement outcome was time-to-result availability; secondary outcomes were sensitivity, specificity, PPV, and NPV assessed against a PCR reference standard. We compared CURIAL-Rapide9s performance with clinician triage and LFD results within standard-care. Results 72,223 patients met eligibility criteria across external and prospective validation sites. Model performance was consistent across trusts (CURIAL-Lab: AUROCs range 0.858-0.881; CURIAL-Rapide 0.836-0.854), with highest sensitivity achieved at Portsmouth University Hospitals (CURIAL-Lab:84.1% [95% Wilson9s score CIs 82.5-85.7]; CURIAL-Rapide:83.5% [81.8 - 85.1]) at specificities of 71.3% (95% Wilson9s score CIs: 70.9 - 71.8) and 63.6% (63.1 - 64.1). For 3,207 patients receiving LFD-triage within routine care for OUH admissions between December 23, 2021 and March 6, 2021, a combined clinical pathway increased sensitivity from 56.9% for LFDs alone (95% CI 51.7-62.0) to 88.2% with CURIAL-Rapide (84.4-91.1; AUROC 0.919) and 85.6% with CURIAL-Lab (81.6-88.9; AUROC 0.925). 520 patients were prospectively enrolled for point-of-care FBC analysis between February 18, 2021 and May 10, 2021, of whom 436 received confirmatory PCR testing within routine care and 10 (2.3%) tested positive. Median time from patient arrival to availability of CURIAL-Rapide result was 45:00 min (32-64), 16 minutes (26.3%) sooner than LFD results (61:00 min, 37-99; log-rank p<0.0001), and 6:52 h (90.2%) sooner than PCR results (7:37 h, 6:05-15:39; p<0.0001). Sensitivity and specificity of CURIAL-Rapide were 87.5% (52.9-97.8) and 85.4% (81.3-88.7), therefore achieving high NPV (99.7%, 98.2-99.9). CURIAL-Rapide correctly excluded COVID-19 for 58.5% of negative patients who were triaged by a clinician to COVID-19-suspected (amber) areas. Impact CURIAL-Lab & CURIAL-Rapide are generalisable, high-throughput screening tests for COVID-19, rapidly excluding the illness with higher NPV than LFDs. CURIAL-Rapide can be used in combination with near-patient FBC analysis for rapid, lab-free screening, and may reduce the number of COVID-19-negative patients triaged to enhanced precautions (amber) clinical areas.
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A Time Series Analysis and Predictive Modeling of COVID-19 Impacts in the African American Community -
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+Background: Sometimes in 2019, there was an outbreak of coronavirus pandemic. Data shows that the virus has infected millions of people and claimed thousands of lives. Vaccination and other non-pharmacological interventions have brought a relief; however, COVID-19 left some indelible marks. This work focuses on a time series analysis and prediction of COVID-19 fatality rates in the Black community. Decision makers will find the work useful in building a robust architecture for a resilient pandemic preparedness and responsiveness against the next pandemic. Method: Our analysis of COVID-19 cases and deaths spans March 2020 to December 2020. Assuming there was no vaccine and other factors remained the same, we hypothesized that COVID-19 disproportionality would have continued. To test our hypothesis, COVID-19 forecasting cases and deaths models were built for the total population as well as the Black population. Holt and Holt-Winters exponential smoothing forecast methodologies were used for the forecast modeling. Forecasting accuracy was based on Mean Absolute Percentage Error (MAPE). Furthermore, we designed, developed, and evaluated a fatality rate predictive model for a Black county. Considering the number of ethnic groups in the USA, a Black county was defined as any county in the USA that at least 45% of its population are Blacks. Five learning algorithms were trained and evaluated. Dataset was a merger of datasets obtained from John Hopkins COVID-19 repository, US Census Bureau and US Center for Disease Control and Prevention. Results and Conclusion: Time series analysis shows that there exists a strong evidence of COVID-19 disproportionate impacts in the states investigated. Using 9 different criteria for performance comparison, our predictive modeling showed that decision tree model has a slight edge over other models. Our experiment suggests that Blacks and senior citizens with pre-existing condition living in Georgia State are the most vulnerable to COVID-19.
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Efficacy and safety of SOBERANA 02, a COVID-19 conjugate vaccine in heterologous three-dose combination -
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+Background: SOBERANA 02 is a COVID19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phase 1 and 2 clinical trials demonstrated its high immunogenicity, promoting neutralizing IgG and specific Tcell response. A third dose, of SOBERANA Plus (RBDdimer), further increased the specific anti RBD neutralizing antibodies. Methods: In a randomized, double-blind, placebo controlled, phase 3 trial (https://rpcec.sld.cu/trials/RPCEC00000354-En) we randomly assigned 44 031 participants, aged 19 to 80 years to three groups to receive a) two doses, SOBERANA 02, or b) two doses, SOBERANA 02 and a third dose, SOBERANA Plus, or c) placebo. Study endpoints are vaccine efficacy (VE) evaluated through confirmed symptomatic COVID-19 and safety. During the trial, the SARS CoV-2 isolates in Havana were 74.0 BETA;, shifting gradually to 100% DELTA; . Results: Two doses of SOBERANA 02 protected against symptomatic COVID-19: 43 cases in the two-dose group (14 371) vs. 155 in the placebo group (14 403), VE 71.0%, adjusted (CI 95%, 58.9 to 79.1). The heterologous three-dose combination increased the protection: 15 cases in the vaccine groups (13 833) vs. 155 in the placebo group (14 303), VE 92.4%, adjusted (CI 95%, 86.9 to 95.6%). For the two-dose schedule, VE against severe COVID-19 was 63.0% and for death, 59.0%; for the heterologous three-dose schedule, VE was 100% in both cases. Conclusions: This is the first phase-3 study of a three-dose, heterologous COVID-19 vaccine. Two doses of SOBERANA 02 were safe and attained efficacy of 71.0% in the adult population 19-80 y/o; incorporating SOBERANA Plus increased efficacy from 71.0 % to 92.4%.
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Shedding of Infectious SARS-CoV-2 Despite Vaccination -
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+The SARS-CoV-2 Delta variant is highly transmissible and contains mutations that confer partial immune escape. We compared RT-PCR cycle threshold (Ct) data from 699 test-positive anterior nasal swab specimens from fully vaccinated (n = 310) or unvaccinated (n=389) individuals. We observed low Ct values (<25) in 212 of 310 fully vaccinated (68%) and 246 of 389 (63%) unvaccinated individuals. Testing a subset of these low-Ct samples revealed infectious SARS- CoV-2 in 15 of 17 specimens (88%) from unvaccinated individuals and 37 of 39 (95%) from vaccinated people. To determine whether infectious virus titers differed in vaccinated and unvaccinated persons, we performed plaque assays on an additional set of 48 samples with Ct <25, finding no difference in infectious virus titer between groups.
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But Mouse, you are not alone: On some severe acute respiratory syndrome coronavirus 2 variants infecting mice -
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+In silico predictions combined with in vitro, in vivo and in situ observations collectively suggest that mouse adaptation of the SARS-CoV-2 virus requires an aromatic substitution in position 501 or position 498 (but not both) of the spike protein receptor binding domain. This effect could be enhanced by mutations in positions 417, 484, and 493 (especially K417N, E484K, Q493K and Q493R), and to a lesser extent by mutations in positions 486 and 499 (such as F486L and P499T). Such enhancements due to more favourable binding interactions with residues on the complementary angiotensin-converting enzyme 2 (ACE2) interface, are however, unlikely to sustain mouse infectivity on their own based on theoretical and experimental evidence to date. Our current understanding thus points to the Alpha, Beta and Gamma variants of concern infecting mice, while Delta and Delta Plus lack a similar biomolecular basis to do so. This paper identifies eleven countries (Brazil, Chile, Djibouti, Haiti, Malawi, Mozambique, Reunion, Suriname, Trinidad and Tobago, Uruguay and Venezuela) where targeted local field surveillance of mice is encouraged because they may have come in contact with humans who had the virus with adaptive mutation(s). It also provides a systematic methodology to analyze the potential for other animal reservoirs and their likely locations.
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LinearTurboFold: Linear-Time Global Prediction of Conserved Structures for RNA Homologs with Applications to SARS- CoV-2 -
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+The constant emergence of COVID-19 variants reduces the effectiveness of existing vaccines and test kits. Therefore, it is critical to identify conserved structures in SARS-CoV-2 genomes as potential targets for variant-proof diagnostics and therapeutics. However, the algorithms to predict these conserved structures, which simultaneously fold and align multiple RNA homologs, scale at best cubically with sequence length, and are thus infeasible for coronaviruses, which possess the longest genomes (~30,000 nt) among RNA viruses. As a result, existing efforts on modeling SARS-CoV-2 structures resort to single sequence folding as well as local folding methods with short window sizes, which inevitably neglect long-range interactions that are crucial in RNA functions. Here we present LinearTurboFold, an efficient algorithm for folding RNA homologs that scales linearly with sequence length, enabling unprecedented global structural analysis on SARS-CoV-2. Surprisingly, on a group of SARS-CoV-2 and SARS-related genomes, LinearTurboFold’s purely in silico prediction not only is close to experimentally-guided models for local structures, but also goes far beyond them by capturing the end-to-end pairs between 5’ and 3’ UTRs (~29,800 nt apart) that match perfectly with a purely experimental work. Furthermore, LinearTurboFold identifies novel conserved structures and conserved accessible regions as potential targets for designing efficient and mutation-insensitive small-molecule drugs, antisense oligonucleotides, siRNAs, CRISPR-Cas13 guide RNAs and RT-PCR primers. LinearTurboFold is a general technique that can also be applied to other RNA viruses and full-length genome studies, and will be a useful tool in fighting the current and future pandemics. Availability and implementation: Our source code is available at https://github.com/LinearFold/LinearTurboFold.
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Scrutiny of human lung infection by SARS-CoV-2 and associated human immune responses in humanized mice -
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+There is an urgent need for animal models of COVID-19 to study immunopathogenesis and test therapeutic intervenes. In this study we showed that NSG mice engrafted with human lung (HL) tissue (NSG-L) could be infected efficiently by SARS-CoV-2, and that live virus capable of infecting Vero cells was found in the HL grafts and multiple organs from infected NSG-L mice. RNA-seq examination identified a series of differentially expressed genes, which are enriched in viral defense responses, chemotaxis, interferon stimulation, and pulmonary fibrosis between HL grafts from infected and control NSG-L mice. Furthermore, when infecting humanized mice with human immune system (HIS) and autologous HL grafts (HISL mice), the mice had bodyweight loss and hemorrhage and immune cell infiltration in HL grafts, which were not observed in immunodeficient NSG-L mice, indicating the development of anti-viral immune responses in these mice. In support of this possibility, the infected HISL mice showed bodyweight recovery and lack of detectable live virus at the later time. These results demonstrate that NSG-L and HISL mice are susceptible to SARS-CoV-2 infection, offering a useful in vivo model for studying SARS-CoV-2 infection and the associated immune response and immunopathology, and testing anti-SARS-CoV-2 therapies.
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SARS-CoV-2 infection in free-ranging white-tailed deer (Odocoileus virginianus) -
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+Human-to-animal spillover of SARS-CoV-2 virus has occurred in a wide range of animals, but thus far, the establishment of a new natural animal reservoir has not been detected. Here, we detected SARS-CoV-2 virus using rRT-PCR in 129 out of 360 (35.8%) free-ranging white-tailed deer (Odocoileus virginianus) from northeast Ohio (USA) sampled between January-March 2021. Deer in 6 locations were infected with at least 3 lineages of SARS-CoV-2 (B.1.2, B.1.596, B.1.582). The B.1.2 viruses, dominant in Ohio at the time, spilled over multiple times into deer populations in different locations. Deer-to-deer transmission may have occurred in three locations. The establishment of a natural reservoir of SARS-CoV-2 in white-tailed deer could facilitate divergent evolutionary trajectories and future spillback to humans, further complicating long-term COVID-19 control strategies.
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Optimising the quarantining and response sequence towards SARS-CoV-2 outbreaks on board cargo vessels -
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+The Coronavirus Disease (COVID-19) pandemic has brought significant impact onto the maritime activities worldwide, including disruption to global trade and supply chains. The ability to predict the evolution and duration of a COVID-19 outbreak on cargo vessels would inform a more nuanced response to the event and provide a more precise return-to-trade date. A SEIQ(H)R (Susceptibility-Exposed-Infected-Quarantine-(Hospitalisation)-Removed/Recovered) model is developed and fit-tested to simulate the transmission dynamics of COVID-19 on board cargo vessels of up to 60 crew. Due to specific living and working circumstances on board cargo vessels, instead of utilising the reproduction number, we consider the crew members from the same country to quantify the transmission of the disease. The performance of the model is verified using case studies based on data collected during COVID-19 outbreaks on three cargo vessels in Western Australia during 2020. The convergence between simulation results and the data verifies the performance of the model. The simulations show that the model can forecast the time taken for the transmission dynamics on each vessel to reach their equilibriums, providing informed predictions on the evolution of the outbreak, including hospitalisation rates and duration. The ability to model the evolution of an outbreak, both in duration and severity, is essential to predict outcomes and to plan for the best response strategy. At the same time, if offers a higher degree of certainty regarding the return to trade, which in turn is of significant importance to multiple stakeholders.
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BREATHE: Virtual Self-management for Long COVID-19 - Condition: COVID-19 Intervention: Other: BREATHE Sponsor:
+University of Calgary Not yet recruiting
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COVID-19 Study of Pharmacokinetics, Safety, Tolerability, and Efficacy of Intravenous Anti-Spike(s) SARS-CoV-2 Monoclonal Antibodies (Casirivimab+Imdevimab) for the Treatment of Pediatric Patients Hospitalized Due to COVID-19 - Condition: COVID-19 Intervention: Drug: casirivimab+imdevimab Sponsor:
+Regeneron Pharmaceuticals Not yet recruiting
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JINZHEN for Treatment of Mild to Moderate COVID-19 - Condition: COVID-19 Interventions: Drug: JINZHEN Granules for Oral Solution; Drug: Placebo Sponsor: Lianyungang Kanion Group, Ltd. Not yet recruiting
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Hypertonic Saline Nasal Irrigation and Gargling (HSNIG) for Suspected COVID-19 in Pakistan - Condition: COVID-19 Intervention: Other: Hypertonic Saline Nasal Irrigation and Gargles (HSNIG) Sponsors: The Allergy and Asthma Institute, Pakistan; University of Edinburgh Recruiting
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Clinical Validation of Breath Analyser Tests for Diagnosis of COVID-19. - Condition: COVID-19 Intervention: Diagnostic Test: Breath Sample analysis Sponsor: Tera Group Recruiting
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Immunogenicity And Safety of COVID-19 Vaccine , Inactivated Co -Administration With EV71 Vaccine (Vero Cell) - Condition: COVID-19 Intervention: Biological: Experimental Group Sponsor:
+Sinovac Biotech Co., Ltd Not yet recruiting
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A Study to Evaluate Safety & Immunogenicity of SARS-CoV-2 DNA Vaccine Delivered Intramuscularly Followed by Electroporation for COVID-19 - Condition: Covid19 Interventions: Biological: SARS-CoV-2 DNA Vaccine; Biological: Matching placebo Sponsors: The University of Hong Kong; Immuno Cure 3 Limited Not yet recruiting
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Phase 1 Trial of ChAd68 and Ad5 Adenovirus COVID-19 Vaccines Delivered by Aerosol - Conditions: COVID-19; SARS-CoV2 Infection Interventions: Biological: Ad5-triCoV/Mac; Biological: ChAd-triCoV/Mac Sponsors: McMaster University; Canadian Institutes of Health Research (CIHR) Not yet recruiting
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Homeopathic Treatment of Post-acute COVID-19 Syndrome - Condition: Post-acute Covid-19 Syndrome Interventions: Drug: Homeopathic Medication; Other: Placebo Sponsors: Southwest College of Naturopathic Medicine; Samueli Institute for Information Biology Recruiting
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Effect of PBM on Functional Capacity and Fatigability in Post Covid-19 Elderly - Condition: Post Covid-19 Elderly Interventions: Radiation: photobiomodulation; Other: placebo intervention by photobiomodulation device Sponsor: Cairo University Recruiting
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Effectiveness of Interactive Voice Response for COVID-19 Vaccination Training in the Democratic Republic of the Congo - Conditions: COVID-19 Vaccine Knowledge; COVID-19 Vaccine Beliefs and Behaviors Interventions: Behavioral: COVID-19 Vaccine IVR Training; Behavioral: Control Condition Sponsors:
+Stanford University; Viamo Not yet recruiting
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Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) Booster Study - Condition: COVID-19 Pandemic Interventions: Biological: Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01); Biological: Blank Preparation of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) Sponsor: Livzon Pharmaceutical Group Inc. Not yet recruiting
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Home-based Brain Stimulation Treatment for Post-acute Sequelae of COVID-19 (PASC) - Condition: Post-Acute Sequelae of COVID-19 Interventions: Device: Active tDCS; Device: Sham tDCS Sponsor: Massachusetts General Hospital Not yet recruiting
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The Effect Of Music On Compliance Of Patients İn COVİD-19 Intensive Care Unit With CPAP Device - Conditions: COVID-19; COVID-19 Acute Respiratory Distress Syndrome Intervention: Device: Listening to music with a bluetooth headset to patients receiving CPAP support Sponsors: SÜMEYYE BİLGİLİ; Ataturk University Recruiting
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Ad26.COV2.S as a Heterologous Booster in Adults After Single- or Two-Dose of Inactivated COVID-19 Vaccine - Condition: SARS-CoV-2 Infection Interventions: Biological: Full dose of Ad26.COV2.; Biological: Half dose of Ad26.COV2. Sponsors: Mahidol University; National Vaccine Institute, Thailand; International Vaccine Institute; Janssen Pharmaceuticals Not yet recruiting
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From PubMed
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Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion - SARS-CoV-2 enters the intestine by the spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors in enterocyte apical membranes, leading to diarrhea in some patients. Early treatment of COVID-19-associated diarrhea could relieve symptoms and limit viral spread within the gastrointestinal (GI) tract. Diosmectite, an aluminomagnesium silicate adsorbent clay with antidiarrheal effects, is recommended in some COVID-19 management protocols. In rotavirus models, diosmectite prevents…
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Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferrets - Remdesivir is an antiviral approved for COVID-19 treatment, but its wider use is limited by intravenous delivery. An orally bioavailable remdesivir analog may boost therapeutic benefit by facilitating early administration to non- hospitalized patients. This study characterizes the anti-SARS-CoV-2 efficacy of GS-621763, an oral prodrug of remdesivir parent nucleoside GS-441524. Both GS-621763 and GS-441524 inhibit SARS-CoV-2, including variants of concern (VOC) in cell culture and human airway…
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alpha-Ketoglutarate Inhibits Thrombosis and Inflammation by Prolyl Hydroxylase-2 Mediated Inactivation of Phospho- Akt - BACKGROUND: Phospho-Akt1 (pAkt1) undergoes prolyl hydroxylation at Pro125 and Pro313 by the prolyl hydroxylase-2 (PHD2) in a reaction decarboxylating α-ketoglutarate (αKG). We investigated whether the αKG supplementation could inhibit Akt- mediated activation of platelets and monocytes, in vitro as well as in vivo, by augmenting PHD2 activity.
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Harnessing stress granule formation by small molecules to inhibit the cellular replication of SARS-CoV-2 - We identified small-molecule enhancers of cellular stress granules by observing molecular crowding of proteins and RNAs in a time-dependent manner. Hit molecules sensitized the IRF3-mediated antiviral mechanism in the presence of poly(I:C) and inhibited the replication of SARS-CoV-2 by inducing stress granule formation. Thus, modulating multimolecular crowding can be a promising strategy against SARS-CoV-2.
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New tale on LianHuaQingWen: IL6R/IL6/IL6ST complex is a potential target for COVID-19 treatment - LianHuaQingWen (LHQW) improves clinical symptoms and alleviates the severity of COVID-19, but the mechanism is unclear. This study aimed to investigate the potential molecular targets and mechanisms of LHQW in treating COVID-19 using a network pharmacology-based approach and molecular docking analysis. The main active ingredients, therapeutic targets of LHQW, and the pathogenic targets of COVID-19 were screened using the TCMSP, UniProt, STRING, and GeneCards databases. According to the…
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Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L - Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is a promising drug target for novel antivirals against SARS-CoV-2. The marine natural product gallinamide A and several synthetic analogues were identified as potent inhibitors of cathepsin L with IC(50) values in the picomolar range. Lead molecules possessed selectivity over other cathepsins and alternative host proteases involved in viral entry. Gallinamide A directly interacted with cathepsin L in cells…
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Dasabuvir Inhibits Human Norovirus Infection in Human Intestinal Enteroids - Human noroviruses (HuNoVs) are acute viral gastroenteritis pathogens that affect all age groups, yet no approved vaccines and drugs to treat HuNoV infection are available. In this study, we screened an antiviral compound library to identify compound(s) showing anti-HuNoV activity using a human intestinal enteroid (HIE) culture system in which HuNoVs are able to replicate reproducibly. Dasabuvir (DSB), which has been developed as an anti-hepatitis C virus agent, was found to inhibit HuNoV…
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Microbial based natural compounds as potential inhibitors for SARS-CoV-2 Papain-like protease (PLpro): a molecular docking and dynamic simulation study - COVID-19 (Coronavirus disease of 2019) pandemic is one of the largest health threats the planet has faced in recent decades. Efforts are being continuously made to design a viable drug or a vaccine. Several natural and synthetic molecules are under study for their potency to inhibit viral replication. In order to emphasize the importance of microbial-based natural components in antiviral drug discovery, an attempt has been made through this study to find potential inhibitors for SARS-CoV-2…
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Rapid inactivation of SARS-CoV-2 with LED irradiation of visible spectrum wavelengths - Difficulty in controlling SARS-CoV-2 transmission made the ability to inactivate viruses in aerosols and fomites to be an important and attractive risk reduction measure. Evidence that light frequencies have the ability to inhibit microorganisms has already been reported by many studies which, however, focused on ultraviolet (UV) wavelengths, which are known to induce potential injury in humans. In the present study, the effect on suspensions of SARS-CoV-2 of a Light Emitting Diode (LED) device…
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Broad spectrum antiviral nucleosides-Our best hope for the future - The current focus for many researchers has turned to the development of therapeutics that have the potential for serving as broad-spectrum inhibitors that can target numerous viruses, both within a particular family, as well as to span across multiple viral families. This will allow us to build an arsenal of therapeutics that could be used for the next outbreak. In that regard, nucleosides have served as the cornerstone for antiviral therapy for many decades. As detailed herein, many nucleosides…
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Protease Inhibitors as Promising Weapons against COVID-19: Focus on Repurposing of Drugs used to Treat HIV and HCV Infections - As a part of the efforts to quickly develop pharmaceutical treatments for COVID-19 through repurposing existing drugs, some researchers around the world have combined the recently released crystal structure of SARS-CoV-2 M^(pro) in complex with a covalently bonded inhibitor with virtual screening procedures employing molecular docking approaches. In this context, protease inhibitors (PIs) clinically available and currently used to treat infectious diseases, particularly viral ones, are relevant…
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Antivirals for Coexistence with COVID-19: Brief Review for General Physicians - In order to end the coronavirus disease 2019 (COVID-19) pandemic that has lasted for nearly two years, it is most necessary to introduce antiviral drugs specific to COVID-19 along with the establishment of herd immunity by vaccination. Candidates currently being studied include nucleoside analogues that inhibit replication, protease inhibitors, and entry blockers. Not only the virus itself, but also the host protein that the virus uses in its pathogenesis is the target of treatment. Although the…
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Interferon-Lambda Intranasal Protection and Differential Sex Pathology in a Murine Model of SARS-CoV-2 Infection - Outbreaks of emerging viral pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a major medical challenge. There is a pressing need for antivirals that can be rapidly deployed to curb infection and dissemination. We determined the efficacy of interferon lambda-1 (IFN-λ) as a broad-spectrum antiviral agent to inhibit SARS-CoV-2 infection and reduce pathology in a mouse model of disease. IFN-λ significantly limited SARS-CoV-2 production in primary human bronchial…
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Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2 - COVID-19 is a global health emergency that causes serious concerns. A global effort is underway to identify drugs for the treatment of COVID-19. One possible solution to the present problem is to develop drugs that can inhibit SARS-CoV-2 main protease (M^(pro)), a coronavirus protein that been considered as one among many drug targets. In this work, lactoferrin from Bos taurus L. was in silico hydrolyzed. The bioactivity, water solubility, and ADMET properties of the generated peptides were…
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Untapping host-targeting cross-protective efficacy of anticoagulants against SARS-CoV-2 - Responding quickly to emerging respiratory viruses, such as SARS-CoV-2 the causative agent of coronavirus disease 2019 (COVID-19) pandemic, is essential to stop uncontrolled spread of these pathogens and mitigate their socio-economic impact globally. This can be achieved through drug repurposing, which tackles inherent time- and resource-consuming processes associated with conventional drug discovery and development. In this review, we examine key preclinical and clinical therapeutic and…
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From Patent Search
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Anti-SARS-CoV-2 antibodies and uses thereof I - - link
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Anti-SARS-CoV-2 antibodies and uses thereof II - - link
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휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수물 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 약 90% 이며, 건강한 성인이면, 육각수 물은 약 62% 이며, COVID-19 환자, 사고의 부상, 17만개의 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수 물을 평소보다 많이 흡수 하면서 동반 산소부족 상태가 되며, 육각수물 보충 없이 산소 호흡기를 사용하면 심각한 후유증이 발병 할 수 있다.
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육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수 물을 62% ~ 80% 이상, 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link
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휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 90% 이며, 육각수물은 약 62% 이며, COVID-19, 사고 부상, 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수물을 평소보다 많이 흡수하면서 산소부족 상태가 되며, 육각수 보충 없이 산소호흡기를 사용하면 심각한 후유증이 발병 할 수 있다 육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수물을 62% ~ 80% 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link
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用于检测新冠病毒的配对抗体及其应用 - 本发明涉及一种用于检测新冠病毒的配对抗体及其应用，其包括第一检测抗体和第二检测抗体；第一检测抗体具有如SEQ ID NO:1~3所示的轻链互补决定区，以及如SEQ ID NO:4~6所示的重链互补决定区，第二检测抗体具有如SEQ ID NO:7~9所示的轻链互补决定区，以及如SEQ ID NO:10~12所示的重链互补决定区。本发明筛选得到具有上述互补决定区序列的配对抗体，其识别N蛋白的不同表位，且由于两种抗体识别的是N蛋白非核酸结合区域，不会受核酸负电荷干扰，对核酸抗原表现出了兼容性，具有较好的稳定性，同时上述配对抗体具有较高的亲和力，病毒N蛋白检测灵敏度高。 - link
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抗KL-6双特异性抗体及基因、重组载体、药物、试剂盒 - 本发明公开了抗KL‑6双特异性抗体或其变体、或其功能性片段，所述抗KL‑6双特异性抗体或其变体、或其功能性片段包括抗PTS域和抗SEA域，所述抗PTS域的重链可变区的CDR1、CDR2和CDR3分别具有SEQ ID NO.1~3所示的氨基酸序列。本发明还提供了基因、重组载体、药物、试剂盒。本发明的抗KL‑6双特异性抗体或其变体、或其功能性片段用于与KL‑6蛋白特异性结合，基因、重组载体用于抗KL‑6双特异性抗体的制备，药物用于治疗KL‑6蛋白引起的相关疾病，试剂盒用于KL‑6蛋白的定量检测。 - link
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基于决策树模型与逻辑回归模型组合的感染筛查方法 - 本发明公开了一种基于决策树模型与逻辑回归模型组合的感染筛查方法，其检测操作方便，可提高感染筛查准确性，该方法基于生命体征监护仪实现，生命体征监护仪与远程数据服务平台通信连接，远程数据服务平台依据临床数据进行感染筛查，该方法包括：通过生命体征监护仪检测获取用户临床数据，将临床数据随机划分为训练集、测试集，将训练集均分为两份：训练集A、训练集B，基于训练集A构建决策树模型，同时，对训练集A进行特征选择，将关键特征向量作为已构建的决策树模型的输入，获取新构造特征向量，基于组合特征向量，构造逻辑回归模型，基于决策树模型和逻辑回归模型组合，对测试集进行预测分类，获取分类结果。 - link
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病毒中和抗体与非中和抗体联合检测方法、检测卡及应用 - 一种病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用，通过病毒受体结合蛋白夹心法原理检测中和抗体，其为通过提前设置病毒受体结合蛋白和能阻断中和抗体与其结合的作为配体的蛋白所形成的复合物，将靶向受体蛋白的非中和抗体提前捕获，保证后续通过夹心法检测中和抗体的特异性。解决了现有技术中中和抗体检测灵敏度低、特异性差以及不能区分中和抗体与非中和抗体的问题，提供了一种简便、快速、灵敏度高、特异性高的病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用。 - link
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扩增△500-532的SARS-CoV-2 Nsp1基因的引物对及其检测方法 - 本发明公开了一种扩增Δ500‑532的SARS‑CoV‑2 Nsp1基因的引物对及其检测方法。引物对的具体序列如SEQ ID NO.1和SEQ ID NO.2所示，其检测方法为：采用引物对对SARS‑CoV‑2 Nsp1基因进行PCR，对PCR产物进行变性退火后，加入T7EI内切酶孵育，再进行PCR扩增，并判断是否存在Δ500‑532的SARS‑CoV‑2 Nsp1基因。本发明可简便快捷的区分出SARS‑CoV‑2 Nsp1基因突变型和野生型。 - link
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多肽及其在新型冠状病毒检测中的应用 - 本发明涉及生物医学领域，具体而言，涉及一种多肽及其在新型冠状病毒检测中的应用。所述多肽包括如下部分：S——Linker——N——avi‑tag。通过经过优化的刚性linker序列把S蛋白和N蛋白串联起来，使得这两个蛋白即具备相对独立的空间构象，又增加了许多优势表位，很大程度上提高了灵敏度和信号值；此外，融合蛋白引入Avi‑tag，使得重组蛋白可以通过固定的位点被固相化，降低包被过程所带来的空间位阻的影响。由此，该多肽能够达到很高的灵敏度和特异性，并且不易发生漏检。 - link
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+Daily-Dose
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Biden and Trump Both Lost This Week - Reading the portents of the off-year elections. - link
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The Meta Narrative: What We’ve Learned from the Facebook Papers - Thousands of documents uncovered by Frances Haugen reveal, among other things, how employees of Facebook—or Meta, as it’s now known—talk when they think that no one is listening. - link
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Is This the Worst Place to Be Poor and Charged with a Federal Crime? - The Southern District of Georgia does remarkably little to provide for indigent defendants. - link
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Why Was the New Jersey Gubernatorial Race So Close? - A pollster for Governor Phil Murphy explains how Republicans nearly pulled off an upset in the Garden State. - link
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The Book That Taught Me What Translation Was - In its attention to substitution, Domenico Starnone’s “Trust” embodies the joy of moving words from one language to another. - link
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From Vox
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What proposed SALT changes could mean for your next tax bill -
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+Rep. Josh Gottheimer (D-NJ) speaks with reporters on the steps of the US Capitol on Thursday, November 4, 2021, in Washington, DC. | Kent Nishimura / Los Angeles Times via Getty Images
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+The Build Back Better Act could include an increased cap for the state and local tax deduction.
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+As negotiations over the Build Back Better Act (BBB) move forward, the state and local tax deduction, or SALT, has emerged as the latest intraparty bargaining chip in Democrats’ efforts to pass the $1.75 trillion social spending package.
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+Specifically, Democrats in states with high state and local taxes like California, New York, and New Jersey are backing a proposal to raise the cap on the amount of state and local taxes individuals can deduct from their federal income taxes from $10,000 to $72,500.
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+The SALT deduction is a way for people, especially in states where income, sales, and property taxes are high, to escape double-paying on taxes that they’ve paid for the services provided by states and localities — things like education, health care, and transportation. Before 2017, taxpayers who itemized their returns could claim an unlimited dollar amount as a SALT deduction; subsequently, a Republican Congress passed the Tax Cuts and Jobs Act, or TCJA, limiting the eligible SALT deduction to $10,000 per year.
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+Imposing that cap primarily affected high earners in blue states and allowed the government to raise more money from taxes, though it was offset at the time by sweeping tax cuts in the same Republican bill. Now, the push to raise the cap is a way to get more Democrats — particularly moderates and the aforementioned legislators from high-tax states with high earners — on board with the broader reconciliation bill.
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+But given that the existing SALT cap aligns with the general progressive belief that the highest earners should pay more in taxes to fund investments like the BBB, Democratic support for raising it can be confusing. Here’s why some Democrats want to see the SALT cap lifted anyway, what that would mean for tax policy in the US — and how it could affect ordinary American taxpayers:
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+How will a higher cap on the SALT deduction affect me?
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+If the SALT cap changes currently being discussed for the reconciliation bill go through, whether or not they’ll affect your tax bill depends on your income, where you live, and other specifics, like property ownership.
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+As Vox’s Emily Stewart explained in April, people can choose to deduct some expenses from their taxable income.
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+As Stewart writes:
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+When people file their taxes, they can deduct certain expenses to make their taxable incomes lower. A lot of people just take the “standard deduction” and lop off a flat amount. Others, however, choose to itemize their deductions, so they can subtract things like charitable deductions and medical expenses. Generally, taxpayers choose whichever avenue will be more beneficial for them — as in, whichever will leave them with less income to be taxed.
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+The types of expenses people can choose to deduct — income or sales tax, property tax, medical expenses, and charitable donations, for example — won’t change. The amount they are able to deduct because of those state and local taxes, however, could.
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+Much like the 2017 deduction cap impacted higher earners — typically those earning more than $100,000 — by effectively increasing the amount of annual income subject to federal taxes, an increase in the deduction cap would primarily benefit those same higher earners.
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+Furthermore, higher earners are more likely to own property and thus pay property taxes in their state and locality — another expense people can choose to deduct from their taxable income.
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+According to the Tax Policy Center, a joint project from the Urban Institute and the Brookings Institution, “sixteen percent of tax filers with income between $20,000 and $50,000 claimed the SALT deduction in 2017, compared to 76 percent for tax filers with income between $100,000 and $200,000 and over 90 percent of tax filers with income above $200,000.”
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+High earners in places with high taxes — primarily blue states like California, New York, and New Jersey — are more likely to be able to claim the SALT deduction in order to reduce their taxable income.
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+What are the specific proposed changes to SALT, and who supports them?
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+In the most basic terms, the proposed changes to the SALT deductionwould increasethe deduction cap from $10,000 to $72,500 per year, with the raised cap set to expire January 1, 2032.
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+According to Roll Call, the new $72,500 cap would also be retroactive to the start of the year.
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+Legislators in favor of lifting the SALT deduction cap include Reps. Tom Suozzi (D-NY), Mikie Sherrill (D-NJ), and Josh Gottheimer (D-NJ) — all of whom represent districts with lots of high-earning individuals paying high taxes. But high-profile progressives, like Rep. Katie Porter (D-CA), are also in favor — in fact, Porter, whose district in California had a median household income of $115,427 and median property value of $794,400 in 2019, has been a driving force behind raising the SALT cap.
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+In September, Porter defended her position on the Pod Save America podcast, arguing that keeping the current SALT cap or eliminating the deduction altogether would mean taxpayers would essentially be double-paying some taxes.
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+“No American with the same income level, the same earning power, the same salary, should owe more federal taxes just because of where they live,” Porter said.
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+The SALT deduction described above is the version currently in place in the most recent House version of the Build Back Better Act — but it’s not the only plan. Sens. Bernie Sanders (I-VT) and Bob Menendez (D-NJ) have proposed an alternate plan — one which would keep the $10,000 cap in place, but only for taxpayers making more than about $400,000 to $550,000, depending on estimates from the nonpartisan Joint Committee on Taxation. For taxpayers who make less than that, there would be no SALT cap.
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+Senate Majority Leader Chuck Schumer has proposed his own idea, which would completely do away with the SALT cap for the next five years and shift back to the $10,000 cap in 2026.
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+When did the SALT deduction change?
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+The SALT deduction been a part of tax policy since before the federal income tax was created in 1913, and apart from some minor changes in the 1960s and 1970s, it hadn’t changed significantly until the 2017 overhaul through the TCJA.
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+Whereas the 1964 and 1978 changes to the law addressed what could be deducted, the TCJA addressed how much could be deducted.
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+Taken on its own, the 2017 cap — which was set to expire in 2025 — looks like progressive tax policy. But it was enacted by a Republican Congress to make up for a revenue shortfall caused by cutting the marginal tax rate for the highest earners from 39.6 percent to 37 percent and corporate tax rates from 35 percent to 21 percent — hence the “tax cuts” part of the bill. Overall, according to the Tax Policy Center, the Congressional Budget Office predicted at the time that the Republican tax bill would increase the federal deficit by almost $1.9 trillion over its first decade.
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+Will the SALT changes actually become law?
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+The proposed SALT changes — either the current House version or the alternate Senate plans — are by no means a sure thing yet. As part of the BBB, an increase to the current SALT cap still has a long road ahead.
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+Specifically, as Vox’s Li Zhou explained Friday, the reconciliation bill still needs to pass the House — which at this point likely won’t happen until mid-November at the earliest — before moving to the Senate and then back to the House for (potential) final passage. In both chambers, unified Democratic support is crucial — with a 50-seat Senate majority decided by Vice President Kamala Harris in her role as president of the Senate, the party has no margin for error in one chamber, and only a few votes to spare in the closely divided House.
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+SALT, however, could help with that. Lifting the current SALT cap has been a key priority for Gottheimer, who leads the small group of moderate House Democrats who have thus far resisted voting for BBB without a Congressional Budget Office score, and the inclusion of SALT changes in the House bill could prove important in shoring up his support for reconciliation.
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+“We’re confident that with this [SALT relief] agreement, we can move forward on this crucially important package and we will continue working to ensure that this tax cut gets signed into law to deliver this relief to our constituents as soon as possible,” Gottheimer said in a Friday statement with Sherrill and Suozzi.
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Can the Iran nuclear deal be saved? -
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+A boy carries an Iranian flag at a rally celebrating the 41st anniversary of the Islamic Revolution in Tehran, in February 2020. | Vahid Salemi/AP
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+Talks are set to resume at the end of the month, but the challenges to reaching an agreement are still immense.
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+At the Group of 20 summit, the United States and its allies said they were “convinced that it is possible” to bring everyone back into compliance with the Iran nuclear deal.
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+It was the latest attempt from Western governments to salvage the agreement, formally known as the Joint Comprehensive Plan of Action (JCPOA). And now, at least, there’s a date to maybe start making that happen: November 29, when talks will resume in Vienna.
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+Signed in 2015 by Iran, the United States and the rest of the P5+1 countries (China, Russia, United Kingdom, France, and Germany), the JCPOA set limits on Iran’s nuclear program such that the country wouldn’t be able to create a nuclear weapon for the duration of the deal. Tehran agreed to allow independent international inspectors to verify it was complying with the terms (like limits on uranium enrichment and centrifuges.) In exchange, the other signatories relieved global economic sanctions put on Iran for its nuclear activities, which had pushed Iran’s economy to the brink.
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+The negotiating will restart later this month. The goal of any talks is to get both sides to climb down — Iran to stop doing things like creating nuclear fuel in fast, next- generation centrifuges; the US to peel back sanctions, like those on Iran’s energy sector and anyone who trades with it — and reach what the diplomats and negotiators like to call “mutual compliance.”
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+And Tehran may want one more thing that might be extraordinarily difficult to deliver: a guarantee that it won’t all go away if another guy — or the same guy again — becomes US president.
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+Reviving the JCPOA is going to face tough odds. Iran has signaled it’s coming back to the table, so that’s something. The remarks at the G-20, on the part of the Europeans and the US, are also a nice show of unity. But those are tiny Band-Aids on the badly broken political trust between Washington and Tehran.
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+The Iran deal’s current state-of-play
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+The United States’s goal is to “quickly reach and implement an understanding on a mutual return to compliance” to the JCPOA, as State Department spokesperson Ned Price said this week. On Thursday, Price said that will put Iran’s nuclear program “back in the box that it was in for several years after the deal was implemented in 2016.”
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+Critics of the Iran nuclear deal often lambasted the agreement because it failed to address Iran’s other malign activities, like its ballistic missile program and its interference by and support for proxy forces in the region. When it comes to “lengthening and strengthening the deal,” the US has said it wants to get everyone back into that mutual compliance first — so the JCPOA will deal, as it did before, with just Iran’s nuclear activities. Some experts think a restoration of the JCPOA will be a starting point for more cooperation, or at the very least a victory for nonproliferation, while Iran’s regional adventures get dealt with in other forums. But the Biden administration is continuing to sanction Iran for things, including a recent batch related to its drone program, a sign the US still keeping up the pressure.
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+For Iran, it may have dilly-dallied on coming back to negotiations to try to build its leverage by continuing to push its nuclear program along. The United States, meanwhile, has exhausted a lot of its leverage. It has throttled Iran with sanctions (though, again, it’s still adding to them), and despite Secretary of State Antony Blinken saying last weekend that “every option is on the table,” it seems unlikely the administration has an appetite for more military intervention in the region. And while the sanctions are crushing Iran, the country is withstanding the pressure to a degree.
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+ Evan Vucci/AP
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+President Joe Biden speaks with Secretary of State Antony Blinken during the G-20 leaders’ summit in Rome, on October 31.
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+If leverage is the goal, then the big question ahead of any new talks is what, exactly, Iran might want. “There’s an assumption that this [Raisi] administration is going to take a maximalist approach to the negotiations,” said Esfandyar Batmanghelidj, visiting fellow at the European Council on Foreign Relations (ECFR).
+
+
+That “maximalist” approach is a bit of a nice way of saying Tehran could makea demand that is a nonstarter for the United States, something like pushing for more sanctions relief beyond that involving its nuclear program, or by calling for the US to offer economic support or a sanctions reprieve first.
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+Iran will likely argue that the United States is the one that blew the deal up, and Tehran stayed in compliance for a year, so it’s up to the US to prove they’re acting in good faith. But that line is a bit tired now that Iran has definitely breached the agreement, too. “Both sides are now very far away from compliance with the deal. So it does make sense for both sides to incrementally take steps to return to the deal,” said Samuel Hickey, a research analyst at the Center for Arms Control and Non-Proliferation, a nonpartisan nonprofit dedicated to eliminating the threat of nuclear weapons.
+
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+Even if Iran doesn’t go full maximalist, exactly what sanctions relief will look like, and how it will work, will be a big part of making these negotiations work. Alex Vatanka, director of the Middle East Institute’s Iran program, said that in 2015, the sanctions relief the JCPOA promised didn’t fully deliver for Iran. “What they discovered in reality was that the threat of American penalty still loomed large and was hanging over their heads. On paper, they could trade with the world,” he said. “In reality companies, and many countries, still kept a distance from Iran.” Iran’s Supreme Leader Ayatollah Ali Khamenei has said the same: Iran wants sanctions relief not only on paper, but “in practice.”
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+ Michael Nagle/Bloomberg via Getty Images
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+Iranian President Ebrahim Raisi called for an end to US sanctions against Iran in a pre- recorded video at the United Nations General Assembly in New York, on September 21.
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+
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+That first demand may be further complicated by a second: some sort of guarantee that this deal can withstand US domestic political shifts. Opposition to the Iran deal persists, especially among Republicans; as Sen. Ted Cruz recently tweeted of the Iran deal: “it is a 100% certainty that any future Republican president will tear it up.” This issue of US credibility is a real challenge, as it’s not something the US can easily deliver on, even if the Biden administration would like to do so. So the threat of American penalties still looms.
+
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+This also works in Iran’s favor, as it can use it as a cudgel in any talks. As Iran’s foreign ministry spokesperson replied to Cruz’s tweet: “Onus is on @POTUS to convince int’l community—incl all JCPOA participants—that his signature means something.”
+
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+Seyed Hossein Mousavian, a former Iranian diplomat and Middle East security and nuclear policy specialist at Princeton University’s Program on Science and Global Security, said Iran could deliver by curtailing its nuclear program, but when it comes to assurances that the US won’t renege, “the US delegation cannot give any assurance.”
+
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+All of that is going to be difficult to overcome. Experts said the US and its European partners may have to offer speedy relief from sanctions, but also find a mechanism to reassure the rest of the world and financial institutions that it’s truly okay to do business with Iran. Vatanka said the “silver bullet” would be American buy-in, including by US businesses, which would be an important signal when it came to the “in practice” part.
+
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+Batmanghelidj, at ECFR, said Western governments got a “crash course” from the failures of JCPOA implementation and attempts to mitigate Trump’s unilateral sanctions. And that may, counterintuitively, help negotiations. (European countries tried to set up a workaround to Trump’s sanctions, but it didn’t really do much.) The US and other countries can be prepared for pitfalls they weren’t before, and potentially could come up with ways to try to make the sanctions relief more robust and more durable.
+
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+Still, there are no guarantees for what might happen in 2024. Some experts think it may still be in Iran’s interest to take even a temporary break from sanctions, and then use that time to prepare in case another Iran-deal skeptic ends up in the White House and sanctions are reimposed.
+
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+That may be in Iran’s interest, but Iran itself might not see it that way. “Iran is in the driver’s seat,’’ said Afshon Ostovar, an Iran expert at the Naval Postgraduate School. Iran doesn’t really seem all that interested in returning to the deal, or even in getting sanctions relief.
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+“They’ve found a way to skirt sanctions, at least to the extent that they can stay afloat and manage the crisis that sanctions imposed upon the country,” he said. Meanwhile, they haven’t had to sacrifice or compromise in any other way; strategically, or militarily, or in terms of foreign policy,” Ostovar said.
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+Iran has withstood the “maximum pressure” campaign, even if it has compounded the economic pain for Iran and its people. The country may try to see if it can stall a little bit longer, while continuing to advance its interests and regional ambitions, and the nuclear program that Europeans and the US still really want to scale back.
+
+
+And if that’s the case, these November talks might not deliver that so-called “mutual compliance” with the JCPOA that the parties are saying they want.
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+
America can’t fix policing without fixing the country’s gun problem -
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+Amanda Northrop/Vox
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+America’s tremendous number of firearms makes it much harder to reform policing.
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+I started reporting this article with a simple question: What would it look like to build a better police department from the ground up?
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+Police in the US, after all, are more likely to shoot and kill someone than their peers around the developed world, and disproportionately the victims are Black Americans. Meanwhile, serious crimes are often unsolved — with almost half of murders in 2020 going uncleared.
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+So I asked a dozen experts, focused on criminal justice, what could be done about this to build better police departments. They gave me a lot of different answers, with a consensus on more accountability, a greater focus on crime prevention and more serious offenses over minor ones, and support for non- police efforts to address root causes of crime, among other ideas.
+
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+But they consistently gave the same caveat: America’s gun problem. The US has the most civilian-owned firearms in the world, with more than one gun in circulation for every person. A bevy of research has linked greater gun ownership to more deadly violence in the US — and, America, relatedly, has the highest murder rate out of the world’s developed countries.
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+For police, the huge number of guns in America also means that every single call is treated as if someone involved could be armed — and that an otherwise nonviolent wellness check, mental health call, or traffic stop could turn into a deadly encounter. US law generally allows police to use force because they merely perceive a threat, and the many firearms in civilian hands give police officers a reason to believe they’re in danger.
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+“It’s Schrödinger’s gun: It’s always there, but it’s not there until you see it,” Michael Sierra-Arévalo, a sociologist at the University of Texas Austin, told me. “That cost is borne by two parties: It’s borne by the public, when police make mistakes, and it’s borne by police themselves, when they’re attacked by firearms.”
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+
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+Of course, other factors play a role in how US police behave. Racism, at the individual and systemic level, is a real force throughout much of American society. Racial disparities in all aspects of American life, from health to the economy, can translate to higher crime rates in minority communities, where police are subsequently deployed in greater force. And since the 1970s and ’80s, US policymaking has trended toward a “tough on crime” approach that encourages police to act very aggressively.
+
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+But guns act as a ratchet in policing. Firearms make every call to the police more risky, but also make officers and the public perceive every situation as inherently more risky. This helps explain not just how cops themselves behave but why police are involved in so many different calls to begin with, from murders to wellness checks. Armed officials ended up in charge of so many areas of society in part because the US has more guns and sees more deadly violence than its peers.
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+This complicates any effort to reduce the role of the police in American society. One of the more popular proposals today is to get the police out of mental health crises, replacing the cops called about people in crisis with special teams that take a softer, more public health–minded approach.
+
+
+But the vast number of firearms makes it more likely these calls could escalate, endangering a member of the response team and potentially requiring armed backup. Eugene, Oregon’s vaunted CAHOOTS program, for example, has reportedly diverted 5 to 8 percent of dispatch calls away from the police by deploying unarmed, health-oriented staff to crisis situations. But as the Eugene Police Department explains, sometimes officers have to be deployed along with CAHOOTS, or even beforehand, to secure a possibly dangerous scene.
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+Reducing the footprint of police isn’t impossible. But the abundance of guns places limits on how far these reforms can go. To put it another way, there’s a choice that America, as a whole, and its leaders have to make: Do something about all of the guns in circulation, or limit the scope of police reform.
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+ Michael M. Santiago/Getty Images
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+People gather at the “Stand Up Against Gun Violence” rally at Bronx Borough Hall on July 19 in New York City. Families affected by gun violence were joined by violence interrupter groups, community leaders, and elected officials for a press conference and rally calling for an end to gun violence in their communities.
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+
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+Guns complicate any efforts to reform police
+
+
+The US has more civilian-owned firearms than any country on Earth. There are about 120 guns for every 100 people, according to 2018 data from the Small Arms Survey. Yemen, in second place, has about 53 guns per 100 people. Canada has about 35 per 100, England and Wales — where police are often unarmed — have nearly five per 100, and Japan has fewer than one per 100.
+
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+A long line of research has connected more guns to more gun violence, including police shootings. The issue is not that America has more crime or violence than other developed countries, but that guns make it much easier for an event to escalate from a merely criminal offense to a deadly encounter. For police, this reality makes them more guarded, and, potentially, more likely to shoot unnecessarily.
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+“Police officers are being asked to make these often very subtle decisions in situations in which they legitimately feel their life is really threatened,” Emily Owens, a University of California Irvine economist focused on crime and policing, told me. “The prevalence of firearms in the United States doesn’t help that situation, certainly.”
+
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+To be sure, other factors besides guns, from personal views to systemic issues, contribute to those subtle decisions officers make as well. There are reforms that could be tried even within the context of Americans’ massive stockpile of firearms. But guns act as a constant force in the background, drawing boundaries around how far reforms can go and how well they can work.
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+As one example, the abundance of guns complicates a key concept in many police reform proposals: a higher bar for getting officers involved at all.
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+American law enforcement respond to a lot of calls that don’t involve violence or even conflict between people. One recent study in Police Quarterly found the top three calls across nine departments were about traffic, public disturbances (like noise violations, graffiti, fireworks, and public urination), or suspicious people and activities; just 7.2 percent were about violence or involved some kind of conflict between different people. The hope is that police, as armed and possibly violent state actors who can escalate a situation themselves, could be removed from the many lower-level calls.
+
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+“If police are going to be the armed emergency first responder, what do you want these people with guns to do?” Tracey Meares, the founding director of the Justice Collaboratory at Yale Law School, said. “There are people whose dogs poop in my front yard, and there’s a law against that. Do I think it’s a good idea to call a person with a gun to deal with that? No, I don’t. Just like I don’t think it’s a good idea for a person with a gun to deal with a noise complaint. I can come up with a whole bunch of other examples.”
+
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+But the number of guns among the civilian population raises the chances any given call in America will turn into violence, either by a police officer or by a civilian on the scene. In the UK or Japan, anyone responding to a mental health call — police or otherwise — can safely assume a gun won’t be present; in the US, that’s far from a sure bet.
+
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+The potential risk of a hypothetical gun is further complicated by the unpredictable nature of policing. Temple University criminologist Jerry Ratcliffe analyzed 911 calls in Philadelphia for a study in Crime Science. He found that calls for one thing can often turn into an entirely different matter — those about crime often turn out to be mental health cases or “sick assists” (such as helping a person who’s physically ill), and wellness checks sometimes turn out to be violent crimes or missing persons situations.
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+Jerry Ratcliffe/Crime Science
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+On the left, the chart shows what calls for service in Philadelphia were originally about. On the right, the chart shows what the calls actually ended up being.
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+
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+Even if someone thinks that they might be going into a relatively safe call, it could turn out that’s not the case. Add in the risk presented by America’s guns, and you may have a very volatile, potentially dangerous situation. “You don’t know what you’re getting,” Ratcliffe told me. “You don’t know for sure it’s a nonviolent call when you turn up.”
+
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+Most police calls are resolved safely without any serious incident. As New York City Police Department analyst John Hall noted, “just one in every 6,959 [traffic] stops results in an assault on an officer … an officer sustaining serious injury or death from a traffic stop is even rarer.” Still, each cop can respond to multiple calls while on duty — and each call carries a roll of the dice that ends in a dangerous encounter. As Hall put it, “Over the course of a career, these stops add up.”
+
+
+The officers responding to these calls are also planning for the worst, not the ideal. If there’s a decent chance that someone will encounter a gun at a call — especially if something has already happened to a colleague — officers will tend to be more guarded.
+
+
+This doesn’t excuse criminal acts or horrifying, avoidable mistakes by police officers. Other factors can drive up the risk of violence at any given call, from racial profiling to insufficient housing to poor mental health systems.
+
+
+But guns are the one uniquely American factor that can escalate a police call.
+
+
+Addressing the root causes of crime means addressing guns
+
+
+Ideally, policing in the US would look very different. Several experts pointed to the principles laid out by Sir Robert Peel, who established the London Metropolitan Police Force in 1829, emphasizing crime prevention, rather than reaction to crime, and efforts to build public support. They called for evidence-based police training, stronger accountability measures, more use of research-backed crime prevention strategies, and greater focus on violence and interpersonal conflicts, leaving lower-level offenses and incidents to unarmed officials when possible.
+
+
+Some activists have gone further, with calls to “defund the police” and redirect savings to other programs that address root causes of crime, such as poverty, mental health care, and housing.
+
+
+But guns are also a root cause of violence, and not addressing it makes police reform approaches less likely to succeed as intended. What happens, for instance, when staff members of an unarmed team tasked with responding to nonviolent calls get shot? Do they ask for police escorts or backup — diminishing the purpose of the reform? Do they ask to be armed — also defeating the purpose of the reform?
+
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+University of Missouri St. Louis criminologist Richard Rosenfeld said that the latter has happened before: Probation and parole officers frequently started out unarmed but over time have armed themselves because, in their view, “they were endangered by their armed clients.”
+
+
+That doesn’t mean other reforms aren’t worth trying, experts said. But they are likely to be limited in scope and reach by the reality of guns in America.
+
+
+In some cases, police reform may even conflict with the task of addressing root causes — making it less likely the reform can succeed on all fronts. For example, a lot of attention has gone to police’s involvement in routine traffic stops, with Philadelphia recently banning officers from stopping drivers for low-level offenses.
+
+
+But it turns out traffic stops are also a big source of the guns police take off the streets. Hall’s analysis for the Manhattan Institute found 42.3 percent of the NYPD’s gun arrests in 2020 were during vehicle stops. Many of these calls can start over a broken taillight or reckless driving, only for the officer to discover an illegal firearm. And, unfortunately, it’s really hard for officers to know which stops will go in this direction; you can’t tell who’s carrying a gun simply by looking at the vehicle or driver.
+
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+It also may not be that police’s footprint in US society — and all the costs that brings — are taking up resources from better solutions, but that police are necessary because US society has failed to address root causes of crime and violence first. As University of Pennsylvania criminologist Aaron Chalfin told me, “The police are the residual claimants on all the stuff that no one else is willing or able to deal with. We put them in that position.”
+
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+In the case of guns, police are frequently needed because a country awash with firearms requires some sort of armed presence to keep people safe. Only once that abundance of guns is reduced can the police safely retreat.
+
+
+ Jon Cherry/Bloomberg via Getty Images
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+Handguns for sale at Knob Creek Gun Range in West Point, Kentucky, on July 22.
+
+
+
+Stricter gun laws could help. A 2016 review of 130 studies in 10 countries, published in Epidemiologic Reviews, found legal restrictions on owning and purchasing guns tended to be followed by a drop in gun violence — a strong indicator that reducing access to guns can save lives. In the US, there’s particular evidence for requiring a license to purchase and own a firearm. But for political and cultural reasons, America has resisted new, serious national measures for decades, letting firearm purchases continue with few if any checks.
+
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+This has contributed to the dynamic of police acting as American society’s backup solution, which is what has saddled officers with so much responsibility to begin with. It’s not that cops wanted more duties. In my years of reporting on this issue, many officers have told me the opposite: that they were called to fill in — by lawmakers and the public — when society had already failed.
+
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+To describe these extra duties, police officers “use different terms — nonsense, bullshit, whatever they want to call it,” Sierra-Arévalo, the sociologist, said. “That’s a consistent thing: They don’t think they should be going to a lot of these things.”
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+America’s tremendous number of guns is at the center of all of this, exacerbating many of the country’s problems by adding a higher risk that any situation can escalate into deadly violence. Once this problem is seen, it’s hard to unsee; it makes it clear why police are responding to so much of the “nonsense” and “bullshit” in the first place.
+
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+Doing something about the guns may be the only hope of truly altering that reality — and allowing more police reform.
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+
+
From The Hindu: Sports
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T20 World Cup | Short break after IPL would have helped, says outgoing bowling coach Bharat Arun - “May be a short break between IPL and World Cup could have done a lot of good for these boys”
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ICC Twenty20 World Cup | Afghanistan post 124/8 against New Zealand - Afghanistan needs to restrict New Zealand below 124 for India to have a chance to qualify for the semis
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T20 World Cup 2022 | West Indies, Sri Lanka to play in qualifying round; Bangladesh, Afghanistan earn direct entry - The automatic qualifiers for the Super 12 stage next year were determined to be the winner and runner-up of the ongoing T20 World Cup, alongside the next six highest ranking teams
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Grand Swiss chess: Harika draws with Paehtz, in joint third place - Indian chess ace Dronavalli Harika could not break through the defences of lower-rated German Elisabeth Paehtz in the 10th round to slip to joint thi
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Mexican Grand Prix | Bottas takes pole as Mercedes goes 1-2 in qualifying - Verstappen leads Hamilton by 12 points with five races to go in Formula One’s best driver duel in years
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From The Hindu: National News
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Faizabad Junction now Ayodhya Cantt: Mixed reactions from historians, locals on station renaming - The BJP government in U.P. had earlier renamed Allahabad as Prayagraj and Mughalsarai Railway Junction to Pandit Deen Dayal Upadhyay Junction in 2018
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ISRO to set up a space museum and space centre in Kanniyakumari - Indian Space Research Organisation (ISRO) will set up a Space Museum and Space Centre in Kanniyakumari at a cost of ₹ 100 crore.Information Technology
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BJP national executive meeting | Party’s best yet to come: Nadda - Very few parallels in Indian politics to party’s growth in Bengal, says BJP president J.P. Nadda
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Chennai Rains | Flights continue to take off and land at Chennai airport with some minor delays - Though water from Chembarambakkam lake is being released, for now, the water levels have not risen to alarming levels.
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Maharashtra fisherman killed in firing by Pakistan maritime troop off Gujarat coast: Police - The body of the deceased fisherman, Sridhar Ramesh Chamre, was brought to Okha port
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From BBC: Europe
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Three seriously injured in knife attack on train in Germany - A 27-year-old Syrian man is arrested after the attack on a high-speed train in Bavaria.
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Palma de Mallorca: Fleeing passengers shut down busy Spanish airport - Palma de Mallorca Airport closes for four hours after 21 people run from a plane across the tarmac.
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Russian diplomat found dead outside Berlin embassy - Reports of last month’s death have only just emerged and suggest the man fell from an upper floor.
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Brexit: ‘Serious consequences’ if Article 16 triggered, warns EU - EC Vice-President Maros Sefcovic says the move would lead to instability in Northern Ireland.
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Camels escape circus and wander Madrid streets - Eight camels and a llama were found, with managers blaming their escape on animal rights activists.
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From Ars Technica
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Eleven tries to adjust to SoCal life in underwhelming Stranger Things S4 teaser - There are surfer dudes, roller rinks, mean girls, and some pretty disastrous haircuts - link
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Here are the best “early Black Friday” deals we’re seeing this weekend [Updated] - Dealmaster has new lows on Amazon tablets, AirPods Max, gaming chairs, and more. - link
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Tagalong robots follow you to learn where you go - Burro makes carts that help growers of trees and vineyards with harvests. - link
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These parents built a school app. Then the city called the cops - Official app was a disaster, so knowledgeable parents built an open source alternative. - link
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It’s time to delete carbon from the atmosphere. But how? - It’s not enough to drastically slash emissions—we need more carbon capture. - link
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From Jokes Subreddit
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+
James Bond walks into a bar -
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+He looks around, and takes a seat neat to a very attractive women.
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+He gives her a quick glance, then causally looks at his watch for a moment.
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+The women notices this and asks, “Is your date running late?”
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+“No”, he replies, “Q has just given me this state- of-the-art watch. I was just testing it.”
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+The intrigued women says “A state-of-the-art watch? Whats so special about it?”
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+
+Bond explains “It uses alpha waves to talk to me telepathically”.
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+The lady says “Whats it telling you now?”
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+“Well, it says you are not wearing any panties.”
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+The women giggles and replies, “Well , it must be broken because I am wearing panties”
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Two men are playing golf when one realizes he’s left his jacket at the last tee -
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+He goes back to get it, stops halfway and turns back. “What’s up?” asks his mate. “Well, you see those two women at the tee. One’s my wife, and she’s playing with my mistress.” His mate laughs and says, “No worries, I’ll go get it for you.” He stops halfway, comes back, looks at his mate and says “Small world.”
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+cdn.com/uploads/chorus_asset/file/22986074/AP21304606902438.jpg)
Evan Vucci/AP/cdn.vox-
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Michael Nagle/Bloomberg via Getty Images
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+cdn.com/uploads/chorus_asset/file/22980154/GettyImages_1329591596.jpg)
Michael M. Santiago/Getty Images
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Jon Cherry/Bloomberg via Getty Images
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