diff --git a/archive-covid-19/06 May, 2023.html b/archive-covid-19/06 May, 2023.html new file mode 100644 index 0000000..5e9b0e6 --- /dev/null +++ b/archive-covid-19/06 May, 2023.html @@ -0,0 +1,196 @@ + +
+ + + ++Background: One of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as long COVID) which has emerged as a consequence of the SARS-CoV-2 epidemic. The World Health Organization (WHO) recognized long COVID as a distinct clinical entity in 2021. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. This has put a tremendous strain on still-overstretched healthcare systems around the world. Methods: In this study, our goal was to assess the plasma metabolome in a total of 108 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC-MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin concentrations were measured in long COVID patients by immunoenzymatic assay. Results: The comparison of paired COVID-19/post-COVID-19 samples revealed 53 metabolites that were statistically different (FDR < 0.05). Compared to controls, 29 metabolites remained dysregulated even after two years. Notably, glucose, kynurenine, and certain acylcarnitines continued to exhibit altered concentrations similar to the COVID-19 phase, while sphingomyelins and long saturated and monounsaturated LysoPCs, phenylalanine, butyric acid, and propionic acid levels normalized. Post-COVID-19 patients displayed a heterogeneous metabolic profile, with some showing no symptoms while others exhibiting a variable number of symptoms. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, sarcosine, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients. Conclusions: Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection. +
++Background: Vaccination against SARS-CoV-2 has been deployed in France since January 2021. Evidence was beginning to show that the most vulnerable populations were the most affected by COVID-19. Without specific action for different population subgroups, the inverse equity hypothesis postulates that people in the least deprived neighbourhoods will be the first to benefit. Methods: We performed a spatial analysis using primary data from the vaccination centre of the Avicenne Hospital in Bobigny (Seine-Saint-Denis, France) from January 8th to September 30th, 2021. We used secondary data to calculate the social deprivation index. We performed flow analysis, k-means aggregation, and mapping. Results: During the period, 32,712 people were vaccinated at the study centre. Vaccination flow to the hospital shows that people living in the least disadvantaged areas were the first to be vaccinated. The number of people immunized according to the level of social deprivation then scales out with slightly more access to the vaccination centre for the most advantaged. The furthest have travelled more than 100 kilometres, and more than 1h45 of transport time to get to this vaccination centre. Access times are, on average, 50 minutes in February to 30 minutes in May 2021. Conclusion: The study confirms the inverse equity hypothesis and shows that vaccination preparedness strategies must take equity issues into account. Public health interventions should be implemented according to proportionate universalism and use community health, health mediation, and outreach activities for more equity. +
++During viral infection the structure of host chromatin is modified. It is generally assumed that these chromatin modifications will affect variant-gene mapping, and therefore gene expression. What is not clear is how limitations imposed by host germline risk affect the expression changes that occur with infection induced chromatin remodelling. Critically, this lack of information extends to how germline variants associated with severe SARS-CoV-2 impact on tissue-specific gene expression changes in response to infection-induced chromatin conformation changes. Here we combined temporal chromatin conformation data from SARS-CoV-2 stimulated cells with a lung spatial-eQTL gene expression analysis to contextualise the functional effects and contributions of germline risk on the severe phenotypes observed in SARS-CoV-2. We identify changes in lung-specific SARS-CoV-2 risk variant-gene mapping across the infection time course. Our results provide evidence for infection-induced chromatin remodelling that impacts the regulation of genes associated with the severity of SARS-CoV-2 infection. The gene targets we identified are functionally involved in host chromatin modifications and maintenance and the expression of these genes is amplified by SARS-CoV-2-induced epigenetic remodelling. The effect of this remodelling includes transcriptional changes to gene targets such as SMARCA4, NCOR1, DNMT1, DNMT3a, DAXX, and PIAS4, all critical components of epigenetic control mechanisms and SARS-CoV-2 antiviral activity, along with several genes involved in surfactant metabolism. We show how severe-phenotype-associated eQTLs form and break in an infection time-course-dependent manner that mimics positive feedback loops connecting germline variation with the process of viral infection and replication. Our results provide a novel bridge between existing COVID-19 epigenetic research and demonstrate the critical role of epigenomics in understanding SARS-CoV-2-risk-associated gene regulation in the lung. +
++IMPORTANCE Several pharmacotherapies have been authorized to treat non-hospitalized persons with symptomatic COVID-19. Longitudinal information on their use is needed. OBJECTIVE To analyze trends and factors related to prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA). DESIGN, SETTINGS, AND PARTICIPANTS This cohort study evaluated non-hospitalized veterans in VHA care who tested positive for SARS-CoV-2 from January 2022 through January 2023, using VHA and linked Community Care and Medicare databases. EXPOSURES Demographic characteristics, regional and local systems of care including Veterans Integrated Services Networks (VISNs), underlying medical conditions, COVID-19 vaccination. MAIN OUTCOMES AND MEASURES Monthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab) was described. Multivariable logistic regression was used to identify factors independently associated with receipt of any versus no COVID-19 pharmacotherapy. RESULTS Among 285,710 veterans (median [IQR] age, 63.1 [49.9-73.7] years; 247,358 (86.6%) male; 28,444 (10%) Hispanic; 198,863 (72.7%) White; 61,269 (22.4%) Black) who tested positive for SARS-CoV-2 between January 2022 and January 2023, the proportion receiving any pharmacotherapy increased from 3.2% (3,285/102,343) in January 2022 to 23.9% (5,180/21,688) in August 2022, and declined slightly to 20.8% (2,194/10,551) by January 2023. Across VISNs, the range in proportion of test-positive patients who received nirmatrelvir-ritonavir or molnupiravir during January 2023 was 5.9 to 21.4% and 2.1 to 11.1%, respectively. Veterans receiving any treatment were more likely to be older (adjusted odds ratio [aOR], 1.18, 95% CI 1.14-1.22 for 65 to 74 versus 50 to 64 years; aOR 1.19, 95% CI 1.15-1.23 for 75 versus 50 to 64 years), have a higher Charlson Comorbidity Index (CCI) (aOR 1.52, 95% CI 1.44-1.59 for CCI ≥6 versus 0), and be vaccinated against COVID-19 (aOR 1.25, 95% CI 1.19-1.30 for primary versus no vaccination; aOR 1.47, 95% CI 1.42-1.53 for booster versus no vaccination). Compared with White veterans, Black veterans (aOR 1.06, 95% CI 1.02 to 1.09) were more likely to receive treatment, and compared with non-Hispanic veterans, Hispanic veterans (aOR 1.06, 95% CI 1.01-1.11) were more likely to receive treatment. CONCLUSIONS AND RELEVANCE Among veterans who tested positive for SARS-CoV-2 between January 2022 and January 2023, prescription of outpatient COVID-19 pharmacotherapies peaked in August 2022 and declined thereafter. There remain large regional differences in patterns of nirmatrelvir-ritonavir and molnupiravir use. +
++Wastewater is a discarded human by-product but analyzing it may help us understand the health of communities. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. We conducted a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Over 450 distinct pathogenic viruses were detected. Sequencing reads of established pathogens and emerging viruses correlated to clinical data sets. Viral communities were tightly organized by space and time. Finally, the most abundant human viruses yielded sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health. +
++Since emergence of the initial SARS-CoV-2 omicron BA.1, BA.2 and BA.5 variants, omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5 omicron. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants. +
++Turkey experienced substantial excess mortality in 2020 and 2021 related to the COVID-19 pandemic. Methods used to estimate excess mortality vary, making comparisons difficult. This study assessed the impact of the COVID-19 pandemic in Turkey, using the TURKSTAT data which became available on February 23, 2023. We applied a quasi-Poisson model to estimate excess mortality during 2020-2021, comparing excess mortality by time periods and socioeconomic factors (SEGE grades). During 2020-2021, Turkey experienced 72,886 excess deaths in 2020 (P-score 16.8%) and 125,540 in 2021 (P-score 28.5%). Excess all-cause mortality varied across SEGE levels, with notable social disparities in pandemic deaths as the highest rates were observed in SEGE 6, the lowest socioeconomic group. An additional 80 excess deaths per 100,000 people were recorded in 2020 and 143 in 2021. This study highlights the importance of a comprehensive approach to address the diverse impacts of the pandemic on health and well-being while considering socioeconomic disparities, and potential areas for improvement in data collection and reporting. +
++BACKGROUND Eye diseases worldwide, including within the United States, are underdiagnosed and undertreated1. A multitude of factors contribute to this deficiency in eye care including, but not limited to, availability of specialists, transportation and mobility barriers, financial burden, lack of education, and poor patient-physician communication and understanding2,3,4. Teleophthalmology, a paradigm of care delivery in which ocular images are interpreted remotely by an eye specialist, has increased in interest since the COVID-19 pandemic, may offer improved access to necessary eye care5. The need for improved access through teleophthalmology is particularly critical for diabetic retinopathy (DR), the leading cause of new cases of blindness among adults aged 20 to 60 affecting more than 100 million patients worldwide6,7. DR arises when elevated levels of blood sugar resulting from either type 1 or 2 diabetes mellitus damage the blood vessels that supply oxygen and nutrients to the retina, the light-sensing part of the eye. The risk of developing DR is directly related to the length of time that a patient has diabetes and usually does not appear for approximately five years after a type 1 diabetes diagnosis, although it may already be present when type 2 diabetes is diagnosed8. In the absence of glycemic control and/or ophthalmic treatment, the disease may progress through three stages of non-proliferative retinopathy (mild, moderate, severe) before proliferative retinopathy develops. Diabetic macular edema can occur with any stage of retinopathy. If DR is diagnosed early, vision loss may be mitigated or prevented9. An annual fundus examination to screen for DR is critical, however, only about half of all patients with diabetes receive proper screening and less than 40% of patients with a high risk of vision loss ever undergo treatment10,11. In 2010, primary care providers (PCPs) delivered clinical care to approximately 90% of individuals with type 2 diabetes, and the proportion has increased over time12. The importance of primary care practitioners ensuring that their diabetic patients receive recommended eye care is reflected in the Healthcare Effectiveness Data and Information Set (HEDIS). This comprehensive set of quality performance measures across six domains of care guide the primary care of chronic medical conditions like diabetes mellitus and includes assessment of whether a diabetic patient receives diabetic eye screening at least every two years13. Attainment of these quality measures is increasingly important for health-system quality ratings and value-based reimbursement models. Practices are increasingly turning to teleophthalmology programs to aid in this goal of care5,14. Traditionally, DR is diagnosed by an eye specialist via an annual in-person fundoscopic examination. However, with appropriate training, non-ophthalmic clinicians and clinical personnel are able to use a fundus camera to take retinal photos that can then be evaluated by an ophthalmologist typically via a store-and-forward model. DR can be determined with high sensitivity and specificity from fundus photography, and a referral for further ophthalmic evaluation or treatment is made for those patients with retinopathy15. Primary care-based teleophthalmology programs have improved the accessibility and cost-effectiveness of DR screening in both rural and urban settings worldwide and are currently being applied to DR screening more commonly than any other ocular pathology16, 17,18. The ongoing COVID-19 pandemic has exacerbated existing barriers and increased the likelihood of ophthalmic appointment postponement or cancellation rendering teleophthalmology services even more critical to DR screening programs19, 20. The prevalence of diabetes in California is more than 40% above the United States national average21. As a means to improve the ophthalmic health of our patients, the Stanford Teleophthalmology Automated Testing and Universal Screening (STATUS) program was developed as a multi-site teleophthalmology DR screening collaboration between the Byers Eye Institute of Stanford (BEIS) and five affiliated primary care clinics throughout the San Francisco Bay Area. The program was initiated two to six months (depending on the site) prior to the onset of the COVID-19 pandemic in the United States and continued to provide remote eye examinations to patients throughout 2020 and 2021. The goal of the program was to evaluate whether the use of teleophthalmology could increase the percentage of patients screened for DR in collaboration with regional primary care clinics. Here, we examine the ability of the 18-month teleophthalmology program to improve and maintain access to DR eye care prior to and during the COVID-19 pandemic. METHODS Clinic Sites Non-mydriatic fundus cameras were deployed at an academic-affiliated primary care site in Santa Clara, CA in September 2019, and in four additional affiliated primary care sites in Los Gatos, Oakland, Hayward, and Pleasanton, CA beginning in February 2020. The primary care sites ranged from 20 miles (25-minute drive) to 42 miles (45-minute drive) away from the BEIS. Store-and-forward teleophthalmology screening for diabetic retinopathy continued at all five locations throughout the study period which ended April 2021. In order to determine whether the teleophthalmology program impacted the adherence rate to annual diabetic eye exams, HEDIS measures at two primary care sites (Pinole, CA and San Pablo, CA) in the same healthcare system that did not deploy the teleophthalmology system were also assessed. The study was approved by the Institutional Review Board at Stanford University. Patient Image Collection and Assessment Patients 18 years or older with type 1 or type 2 diabetes mellitus without a prior DR diagnosis or a DR exam in the past 12 months were offered the opportunity to have fundus photographs taken at the end of their primary care visit. Fundus imaging was performed by a trained medical assistant using the CenterVue DRS fundus camera (Hillrom Inc., Chicago, IL) at the Santa Clara primary clinic site and the TopCon NW400 fundus camera (Welch Allyn Inc., Skaneateles Falls, NY) at the Los Gatos, Oakland, Hayward, and Pleasanton primary care clinics. If medical assistants deemed the image quality to be poor, they repeated image acquisition and did so up to 4 times. The fundus images were forwarded to vitreoretinal specialists at BEIS who evaluated the images within one week. These fundus images were classified as ungradable (such as when opacity, blurring, or decentration impaired visualization of the fundus), or gradable if quality was sufficient for grading of DR. Images of adequate quality had a DR grade assigned in accordance with the International Clinical Diabetic Retinopathy Disease Severity Scale with moderate and severe categories combined on teleophthalmology evaluation (no diabetic retinopathy/mild non-proliferative diabetic retinopathy/moderate to severe non-proliferative diabetic retinopathy/proliferative diabetic retinopathy)22. Patient images were also assessed for the presence of macular edema or other fundus abnormalities. Patients with images of insufficient quality from one or both eyes were recommended to have the images retaken or present for an in-person eye examination. Diagnosis and stage of DR was determined by the eye with more advanced retinopathy. Those with referral-warranted disease were referred for an in-person exam at BEIS or their local ophthalmologist. A subset of patients (N=26) voluntarily presented for a second teleophthalmology screening one year after their first examination. Patient Data Patient files containing information on labs, orders, clinical notes, and patient information were retrieved from The STAnford Research Repository (STARR), an institutional resource for working with clinical data for research purposes. Data was managed and analyzed using Python (version 3.9.0) with Pandas (version 1.3.0). Patients who underwent fundus imaging without a documented assessment by BEIS specialists were excluded (N = 23). For all patients who were seen at BEIS after a referral for in-person examination, data was manually collected from the electronic health record. For analyses comparing patients prior to and during the COVID-19 pandemic, March 16th, 2020, was used as the start of the pandemic since on that date legal stay-at-home orders were announced in Alameda, Contra Costa, Marin, San Francisco, San Mateo, and Santa Clara counties. Longitudinal HEDIS data were only available for three of the teleophthalmology primary care sites and the two non-teleophthalmology comparison sites; two teleophthalmology primary care sites did not have structured HEDIS data available for analysis. +
++Dynamic distribution shifts caused by evolving diseases and demographic changes require domain-incremental adaptation of clinical deep learning models. However, this process of adaptation is often accompanied by catastrophic forgetting, and even the most sophisticated methods are not good enough for clinical applications. This paper studies incremental learning from the perspective of mode connections, that is, the low-loss paths connecting the minimisers of neural architectures (modes or trained weights) in the parameter space. The paper argues for learning the low-loss paths originating from an existing mode and exploring the learned paths to find an acceptable mode for the new domain. The learned paths, and hence the new domain mode, are a function of the existing mode. As a result, unlike traditional incremental learning, the proposed approach is able to exploit information from a deployed model without changing its weights. Pre-COVID and COVID-19 data collected in Oxford University hospitals are used as a case study to demonstrate the need for domain-incremental learning and the advantages of the proposed approach. +
++Background Healthcare workers (HCWs) have experienced high rates of COVID-19 morbidity and mortality. We estimated COVID-19 two-dose primary series and monovalent booster vaccine effectiveness (VE) against symptomatic SARS-CoV-2 Omicron (BA.1 and BA.2) infection among HCWs in three Albanian hospitals during January-May 2022. Methods Study participants completed weekly symptom questionnaires, underwent PCR testing when symptomatic, and provided quarterly blood samples for serology. We estimated VE using Cox regression models (1-hazard ratio), with vaccination status as the time-varying exposure and unvaccinated HCWs as the reference group, adjusting for potential confounders: age, sex, prior SARS-CoV-2 infection (detected by PCR, rapid-antigen test or serology), and household size. Results At the start of the analysis period, 76% of 1,462 HCWs had received a primary series, 10% had received a booster dose, and 9% were unvaccinated; 1,307 (89%) HCWs had evidence of prior infection. Overall, 86% of primary series and 98% of booster doses received were BNT162b2. The median time interval from the second dose and the booster dose to the start of the analysis period was 289 days (IQR:210-292) and 30 days (IQR:22-46), respectively. VE against symptomatic PCR-confirmed infection was 34% (95%CI: -36;68) for the primary series and 88% (95%CI: 38;98) for the booster. Conclusions Among Albanian HCWs, most of whom had been previously infected, COVID-19 booster dose offered improved VE during a period of Omicron BA.1 and BA.2 circulation. Our findings support promoting booster dose uptake among Albanian HCWs, which, as of January 2023, was only 20%. +
++Background: Patients with ischemic stroke and concomitant coronavirus 2019 (COVID-19) infection have worse outcomes than those without this infection. However, research on the impact of COVID-19 infection on outcomes following hemorrhagic stroke remains limited. We aim to study whether concomitant COVID-19 infection leads to worse outcomes in spontaneous intracerebral hemorrhage (ICH).<break><break>Design: We conducted an observational study using data from Get With The Guidelines Stroke, an ongoing, multi-center, nationwide quality assurance registry. <break><break>Methods: We implemented a two-stage design: first, we compared outcomes of ICH patients with and without COVID-19 infection admitted during the pandemic (from March 2020 to February 2021). Second, we compared the same outcomes between ICH patients admitted before (March 2019 to February 2020) and during (March 2020 and February 2021) the pandemic. Main outcomes were poor functional outcome (defined as a modified Rankin Scale of 4 to 6 [mRS] at discharge), mortality and discharge to skilled nursing facility (SNF) or hospice. <break><break>Results: The first stage included 60,091 COVID-19-negative and 1,326 COVID-19-positive ICH patients. In multivariable analyses, ICH patients with versus without COVID-19 infection had 68% higher odds of poor outcome (OR 1.68, 95%CI 1.41-2.01), 51% higher odds of mortality (OR 1.51, CI 1.33-1.71) and 66% higher odds of being discharged to a SNF/hospice (OR 1.66, 95%CI 1.43-1.93). The second stage included 62,743 pre-pandemic and 64,681 intra-pandemic ICH cases. In multivariable analyses, ICH patients admitted during versus before the COVID-19 pandemic had a 10% higher odds of poor outcome (OR 1.10, 95%CI 1.07-1.14), 5% higher mortality (OR 1.05, 95%CI 1.02-1.08) and no significant difference in the risk of being discharged to SNF/hospice (OR 0.93, 95%CI 0.90-0.95). <break><break>Conclusions: The pathophysiology of the COVID-19 infection and changes in healthcare delivery during the pandemic played a role in worsening outcomes in this patient population. Further research is needed to identify these factors and understand their effect on the long-term outcome. +
++Knowledge is limited as to how prior SARS-CoV-2 infection influences cellular and humoral immunity after booster-vaccination with bivalent BA.4/5-adapted mRNA-vaccines, and whether vaccine-induced immunity correlates with subsequent infection. In this observational study, individuals with prior infection (n=64) showed higher vaccine-induced anti-spike IgG antibodies and neutralizing titers, but the relative increase was significantly higher in non-infected individuals (n=63). In general, both groups showed higher neutralizing activity towards the parental strain than towards Omicron subvariants BA.1, BA.2 and BA.5. In contrast, CD4 or CD8 T-cell levels towards spike from the parental strain and the Omicron subvariants, and cytokine expression profiles were similar irrespective of prior infection. Breakthrough infections occurred more frequently among previously non-infected individuals, who had significantly lower vaccine-induced spike-specific neutralizing activity and CD4 T-cell levels. Thus, the magnitude of vaccine-induced neutralizing activity and specific CD4 T-cells after bivalent vaccination may serve as a correlate for protection in previously non-infected individuals. +
++Background: The COVID-19 pandemic has been characterized by ongoing evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with concomitant variation in viral transmissibility and morbidity. Within specific timeframes and geographic areas, multiple SARS-CoV-2 variants have coexisted in the human population, each characterized by distinct biologic and clinical features, such as varying susceptibility to neutralizing monoclonal antibodies (nMAbs), a major frontline treatment. As part of an observational real-world data study of the effectiveness of nMAbs for treatment of COVID-19, SARS-CoV-2 viral samples were obtained from patients under treatment, generating paired clinical and genomics data. This paper describes the processing pipeline and findings from the genomics portion of this combined data set. Methods: SARS-CoV-2 sequences were generated from 14,796 diagnostic samples from four large U.S. health systems between July 2020 and March 2022. Among nMAbs-treated patients, samples were collected on the same day as, or prior to, treatment with nMAbs. Thus, these samples represent a snapshot of SARS-CoV-2 variants circulating in the respective patient groups, as opposed to variants that arose in response to specific treatments. Health systems collected viral samples and performed library creation and sequencing according to local protocols, using tiled ARTIC amplicon primers. FASTQ files were submitted to a study data platform and processed through a common pipeline. This pipeline enabled a unified approach to quality control, assembly, and production of genomics features for downstream analysis. Results: Alpha and pre-Alpha SARS-CoV-2 lineages were predominant in the data set prior to June 2021. From June 2021 through November 2021, Delta was the dominant variant. Beginning in December 2021, Omicron was dominant. A variety of mutations associated with decreased nMAbs binding to the spike protein in vitro were detected, including lineage-defining mutations and non-lineage-defining mutations such as E340A, G446V, and S494P. Distinct patterns of sequence gaps and ambiguous base calls were associated with distinct variants. Conclusions: The distribution of SARS-CoV-2 variants, per WHO nomenclature, across epochs in this data set matched concurrent CDC genomic surveillance results across the U.S. Detection of putative nMAbs escape mutations within clinical samples was consistent with FDA decisions to amend EUAs as variants emerged. This genomics data set provides an opportunity to examine associations between SARS-CoV-2 genomic variation and clinical outcomes in the associated EHR data set. The expansion of real-world data sets such as this to study the relationship between viral sequence and treatment outcomes could provide the foundation for future efforts to achieve near-real-time understanding of clinical outcomes related to genomic variation over time, and evidence to update treatment decisions more rapidly and to greater effect during ongoing and future pandemics. +
+Long COVID-19 Syndrome Lifestyle Intervention Study - Condition: Long COVID-19 Syndrome
Intervention: Dietary Supplement: Low carbohydrate diet intervention
Sponsor: University of Southern California
Not yet recruiting
Working Towards Empowered Community-driven Approaches to Increase Vaccination and Preventive Care Engagement - Condition: COVID-19
Interventions: Other: mHealth Outreach; Other: Care Coordination
Sponsors: University of California, San Diego; San Ysidro Health Center
Not yet recruiting
A Coping and Resilience Intervention for Adolescents - Condition: COVID-19 Pandemic
Interventions: Behavioral: Coping and Resilience Intervention for Adolescents; Other: Printing materials of Coping and Resilience Intervention for Adolescents
Sponsor: Taipei Medical University
Enrolling by invitation
Effectiveness of Modified Diaphragmatic Training for Gastroesophageal Reflux Disease Post Covid-19 - Conditions: GERD; Post COVID-19 Condition; Diaphragm Issues
Interventions: Other: modified diaphragmatic training; Other: standard diaphragmatic training
Sponsor: Indonesia University
Completed
The Safety, Tolerability and Pharmacokinetics Study of RAY1216 in Healthy Adult Participants - Condition: COVID-19 (Coronavirus Disease 2019)
Interventions: Drug: RAY1216 dose 1; Drug: RAY1216 dose 2; Drug: RAY1216 dose 3; Drug: RAY1216 dose 4 &ritonavir Drug: RAY1216 dose 5; Drug: RAY1216 dose 6; Drug: RAY1216 dose 7; Drug: RAY1216 dose 8; Drug: RAY1216 dose 9; Drug: RAY1216 dose 10
Sponsor: Guangdong Raynovent Biotech Co., Ltd
Completed
COVID-19 Vaccination Detoxification - Conditions: COVID-19 Stress Syndrome; COVID-19 Vaccine Adverse Reaction; COVID-19-Associated Thromboembolism; COVID-19 Post-Intensive Care Syndrome; COVID-19-Associated Stroke; COVID-19 Respiratory Infection
Intervention: Combination Product: Atorvastatin Calcium Tablets
Sponsor: Yang I. Pachankis
Active, not recruiting
A Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558 - Condition: COVID-19
Interventions: Drug: ALG-097558; Drug: Placebo; Drug: Midazolam; Drug: Itraconazole; Drug: Carbamazepine; Drug: ALG-097558 in solution formulation; Drug: ALG-097558 in tablet formulation
Sponsor: Aligos Therapeutics
Not yet recruiting
Computerized Training of Attention and Working Memory in Post COVID-19 Patients With Cognitive Complaints - Conditions: COVID-19; Cognitive Impairment; Cognition Disorder; Memory Disorders; Attention Deficit; Memory Impairment; Memory Loss; Attention Impaired
Intervention: Device: RehaCom
Sponsor: Erasmus Medical Center
Not yet recruiting
Immunoadsorption Study Mainz in Adults With Post-COVID Syndrome - Conditions: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition
Interventions: Device: Immunoadsorption; Device: Sham-apheresis
Sponsor: University Medical Center Mainz
Recruiting
Digital Mental Health Care for COVID-19 High-Risk Populations - Phase 2 - Conditions: Stigma, Social; Help-Seeking Behavior
Interventions: Other: Adjusted Content Intervention; Other: Non-Adjusted Intervention Video
Sponsors: Research Foundation for Mental Hygiene, Inc.; Columbia University
Not yet recruiting
A Study of mRNA-based Influenza and SARS-CoV-2 (COVID-19) Multi-component Vaccines in Healthy Adults - Conditions: SARS-CoV-2; Influenza
Interventions: Biological: Fluarix; Biological: mRNA-1083.1; Biological: mRNA-1083.2; Biological: mRNA-1083.3; Biological: mRNA-1010.4; Biological: mRNA-1283.222; Biological: mRNA-1273.222; Biological: mRNA-1010; Biological: Fluzone HD
Sponsor: ModernaTX, Inc.
Recruiting
Efficacy of an Smartphone App Intervention Based on Self-compassion for Mental Health Among University Students - Condition: Mental Health Issue
Interventions: Behavioral: mHealth Intervention Based on Self-Compassion; Behavioral: Psychoeducation Intervention
Sponsors: Federal University of Health Science of Porto Alegre; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Not yet recruiting
Obesity, Insulin Resistance, and PASC: Persistent SARS-CoV-2 - Conditions: Long COVID; Insulin Resistance; Insulin Sensitivity
Interventions: Procedure: Adipose Tissue Biopsy; Diagnostic Test: Steady State Plasma Glucose (SSPG) Test
Sponsor: Stanford University
Not yet recruiting
Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients - Drug repurposing requires distinguishing established drug class targets from novel molecule-specific mechanisms and rapidly derisking their therapeutic potential in a time-critical manner, particularly in a pandemic scenario. In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. However, it is unknown if different statins exhibit consistent function or may have varying…
The anti-inflammatory and antiviral properties of anionic pulmonary surfactant phospholipids - The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse and the innate immune system in the lung. Pulmonary surfactant is a lipoprotein complex consisting of 90% phospholipids and 10% protein, by weight. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), exist at very high concentrations in the extracellular alveolar…
Prenol, but Not Vitamin C, of Fruit Binds to SARS-CoV-2 Spike S1 to Inhibit Viral Entry: Implications for COVID-19 - Fruit consumption may be beneficial for fighting infection. Although vitamin C is the celebrity component of fruit, its role in COVID-19 is unclear. Because spike S1 of SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) on host cells to enter the cell and initiate COVID-19, using an α-screen-based assay, we screened vitamin C and other components of fruit for inhibiting the interaction between spike S1 and ACE2. We found that prenol, but neither vitamin C nor other major components of…
Orthogonal dual reporter-based gain-of-signal assay for probing SARS-CoV-2 3CL protease activity in living cells: inhibitor identification and mutation investigation - The main protease (3-chymotrypsin-like protease, 3CLpro) of SARS-CoV-2 has become a focus of anti-coronavirus research. Despite efforts, drug development targeting 3CLpro has been hampered by limitations in the currently available activity assays. Additionally, the emergence of 3CLpro mutations in circulating SARS-CoV-2 variants has raised concerns about potential resistance. Both emphasize the need for a more reliable, sensitive, and facile 3CLpro assay. Here, we report an orthogonal dual…
SARS-CoV-2 N Protein Triggers Acute Lung Injury via Modulating Macrophage Activation and Infiltration in in vitro and in vivo - CONCLUSION: SARS-CoV-2 and its N protein but not S protein induced acute lung injury and systemic inflammation, which was closely related to macrophage activation, infiltration and release cytokines.
Biogenic silver nanoparticles eradicate of Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA) isolated from the sputum of COVID-19 patients - In recent investigations, secondary bacterial infections were found to be strongly related to mortality in COVID-19 patients. In addition, Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA) bacteria played an important role in the series of bacterial infections that accompany infection in COVID-19. The objective of the present study was to investigate the ability of biosynthesized silver nanoparticles from strawberries (Fragaria ananassa L.) leaf extract without a…
Immunogenicity and reactogenicity of heterologous prime-boost vaccination with inactivated COVID-19 and ChAdOx1 nCoV-19 (AZD1222) vaccines, a quasi-experimental study - The global supply of COVID-19 vaccines has been limited, and concerns have arisen about vaccine supply chain disruptions in developing countries. Heterologous prime-boost vaccination, which involves using different vaccines for the first and second doses, has been proposed to enhance the immune response. We aimed to compare the immunogenicity and safety of a heterologous prime-boost vaccination using an inactivated COVID-19 vaccine and AZD1222 vaccine with that of a homologous vaccination using…
Proton Pump Inhibitors, Kidney Damage, and Mortality: An Updated Narrative Review - Since their approval by the Food and Drug Administration (FDA) in 1989, proton pump inhibitors (PPIs) have become one of the most highly utilized drugs in the United States, assuming a position as one of the top 10 most prescribed medications in the country. The purpose of PPIs is to limit the amount of gastric acid secreted by the parietal cells via irreversible inhibition of the H+/K+-ATPase pump, therefore maintaining an elevated gastric acid pH of greater than 4 for 15-21 h. Even though PPIs…
New Ways to Protect the Host from SARS-CoV-2? Lung Microbiome Metabolites Inhibit STAT3 and Modulate the Immunological Network - COVID-19 caused by the SARS-CoV-2 infection is a systemic disease that affects multiple organs, biological pathways, and cell types. A systems biology approach would benefit the study of COVID-19 in the pandemic as well as the endemic state. Notably, patients with COVID-19 have dysbiosis of lung microbiota whose functional relevance to the host is largely unknown. We carried out a systems biology investigation of the impact of lung microbiome-derived metabolites on host immune system during…
A Multicenter Randomized Controlled Trial To Evaluate the Efficacy and Safety of Nelfinavir in Patients with Mild COVID-19 - Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of nelfinavir in patients with SARS-CoV-2 infection. We included unvaccinated asymptomatic or mildly symptomatic adult patients who tested positive for SARS-CoV-2 infection within 3 days before enrollment. The patients were…
In silico evaluation of some commercially available terpenoids as spike glycoprotein of SARS-CoV-2 - inhibitors using molecular dynamic approach - Coronavirus, an extremely contagious infections disease had a harmful effect on the world’s population. It is a family of enveloped, single-stranded, positive-strand RNA viruses of Nidovirales order belongs to coroviridae family. At present, worldwide several lakhs of deaths and several billions of infections have been reported. Hence, the focus of the present study was to assess the SARS-CoV-2 enzyme inhibitory potential of certain commercially available terpenoids using Lamarckian genetic…
Infection routes, invasion mechanisms, and drug inhibition pathways of human coronaviruses on the nervous system - So far, numerous studies have reported on how coronaviruses affect the human nervous system. However, these studies mainly focused on the impact of a single coronavirus on the nervous system, and failed to fully report the invasion mechanisms and the rules of symptoms of the seven human coronaviruses. This research can assist medical professionals in identifying the regularity of coronavirus invasion into the nervous system by examining the impacts of human coronaviruses on the nervous system….
High-breathable, antimicrobial and water-repellent face mask for breath monitoring - Face masks with multiple functionalities and exceptional durability have attracted increasing interests during the COVID-19 pandemic. How to integrate the antibacterial property, comfortability during long-time wearing, and breath monitoring capability together on a face mask is still challenging. Here we developed a kind of face mask that assembles the particles-free water-repellent fabric, antibacterial fabric, and hidden breath monitoring device together, resulting in the highly breathable,…
Non-neutralizing antibodies to SARS-Cov-2-related linear epitopes induce psychotic-like behavior in mice - OBJECTIVE: An increasing number of studies have reported that numerous patients with coronavirus disease 2019 (COVID-19) and vaccinated individuals have developed central nervous system (CNS) symptoms, and that most of the antibodies in their sera have no virus-neutralizing ability. We tested the hypothesis that non-neutralizing anti-S1-111 IgG induced by the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could negatively affect the CNS.
Furin as a therapeutic target in cystic fibrosis airways disease - Clinical management of cystic fibrosis (CF) has been greatly improved by the development of small molecule modulators of the CF transmembrane conductance regulator (CFTR). These drugs help to address some of the basic genetic defects of CFTR; however, no suitable CFTR modulators exist for 10% of people with CF (PWCF). An alternative, mutation-agnostic therapeutic approach is therefore still required. In CF airways, elevated levels of the proprotein convertase furin contribute to the…
Jordan Neely’s Death and a Critical Moment in the Homelessness Crisis - After the homeless young man was killed on the subway, there has been a rare flash of national attention on the issue. Can the outrage be harnessed for actual change? - link
How a Cuban American Illustrator Sees This Country Today - Edel Rodriguez’s new exhibition, “Apocalypso,” reflects on democracy under threat in the nation that welcomed him in his childhood. - link
The Siege of Wounded Knee Was Not an End but a Beginning - Fifty years ago, the Oglala Sioux Civil Rights Organization invited the American Indian Movement to Pine Ridge and reignited a resistance that has never gone away. - link
In the Post-Roe Era, Letting Pregnant Patients Get Sicker—by Design - Fearing legal repercussions, doctors in Texas say they are risking grave patient harm to comply with new abortion restrictions. - link
Jonah Peretti Has Regrets About BuzzFeed News - The site’s founder and C.E.O. valued fun and experimentation on the Internet, but never found a way to make “free journalism purpose-built for social media” profitable. - link
+Is AI going to kill us? Or take our jobs? Or is the whole thing overhyped? Depends on who you ask. +
++At this point, you have tried ChatGPT. Even Joe Biden has tried ChatGPT, and this week, his administration made a big show of inviting AI leaders like Microsoft CEO Satya Nadella and OpenAI CEO Sam Altman to the White House to discuss ways they could make “responsible AI.” +
++But maybe, just maybe, you are still fuzzy on some very basics about AI — like, how does this stuff work, is it magic, and will it kill us all? — but don’t want to admit to that. +
++No worries. We have you covered: We’ve spent much of the spring talking to people working in AI, investing in AI, trying to build businesses in AI — as well as people who think the current AI boom is overblown or maybe dangerously misguided. We made a podcast series about the whole thing, which you can listen to over at Recode Media. +
++But we’ve also pulled out a sampling of insightful — and oftentimes conflicting — answers we got to some of these very basic questions. They’re questions that the White House and everyone else needs to figure out soon, since AI isn’t going away. +
++Read on — and don’t worry, we won’t tell anyone that you’re confused. We’re all confused. +
++Kevin Scott, chief technology officer, Microsoft: I was a 12-year-old when the PC revolution was happening. I was in grad school when the internet revolution happened. I was running a mobile startup right at the very beginning of the mobile revolution, which coincided with this massive shift to cloud computing. This feels to me very much like those three things. +
++Dror Berman, co-founder, Innovation Endeavors: Mobile was an interesting time because it provided a new form factor that allowed you to carry a computer with you. I think we are now standing in a completely different time: We’ve now been introduced to a foundational intelligence block that has become available to us, one that basically can lean on all the publicly available knowledge that humanity has extracted and documented. It allows us to retrieve all this information in a way that wasn’t possible in the past. +
++Gary Marcus, entrepreneur; emeritus professor of psychology and neural science at NYU: I mean, it’s absolutely interesting. I would not want to argue against that for a moment. I think of it as a dress rehearsal for artificial general intelligence, which we will get to someday. +
++But right now we have a trade-off. There are some positives about these systems. You can use them to write things for you. And there are some negatives. This technology can be used, for example, to spread misinformation, and to do that at a scale that we’ve never seen before — which may be dangerous, might undermine democracy. +
++And I would say that these systems aren’t very controllable. They’re powerful, they’re reckless, but they don’t necessarily do what we want. Ultimately, there’s going to be a question, “Okay, we can build a demo here. Can we build a product that we can actually use? And what is that product?” +
++I think in some places people will adopt this stuff. And they’ll be perfectly happy with the output. In other places, there’s a real problem. +
++James Manyika, SVP of technology and society, Google: You’re trying to make sure the outputs are not toxic. In our case, we do a lot of generative adversarial testing of these systems. In fact, when you use Bard, for example, the output that you get when you type in a prompt is not necessarily the first thing that Bard came up with. +
++We’re running 15, 16 different types of the same prompt to look at those outputs and pre-assess them for safety, for things like toxicity. And now we don’t always get every single one of them, but we’re getting a lot of it already. +
++One of the bigger questions that we are going to have to face, by the way — and this is a question about us, not about the technology, it’s about us as a society — is how do we think about what we value? How do we think about what counts as toxicity? So that’s why we try to involve and engage with communities to understand those. We try to involve ethicists and social scientists to research those questions and understand those, but those are really questions for us as society. +
++Emily M. Bender, professor of linguistics, University of Washington: People talk about democratizing AI, and I always find that really frustrating because what they’re referring to is putting this technology in the hands of many, many people — which is not the same thing as giving everybody a say in how it’s developed. +
++I think the best way forward is cooperation, basically. You have sensible regulation coming from the outside so that the companies are held accountable. And then you’ve got the tech ethics workers on the inside helping the companies actually meet the regulation and meet the spirit of the regulation. +
++And to make all that happen, we need broad literacy in the population so that people can ask for what’s needed from their elected representatives. So that the elected representatives are hopefully literate in all of this. +
++Scott: We’ve spent from 2017 until today rigorously building a responsible AI practice. You just can’t release an AI to the public without a rigorous set of rules that define sensitive uses, and where you have a harms framework. You have to be transparent with the public about what your approach to responsible AI is. +
++Marcus: Dirigibles were really popular in the 1920s and 1930s. Until we had the Hindenburg. Everybody thought that all these people doing heavier-than-air flight were wasting their time. They were like, “Look at our dirigibles. They scale a lot faster. We built a small one. Now we built a bigger one. Now we built a much bigger one. It’s all working great.” +
++So, you know, sometimes you scale the wrong thing. In my view, we’re scaling the wrong thing right now. We’re scaling a technology that is inherently unstable. +
++It’s unreliable and untruthful. We’re making it faster and have more coverage, but it’s still unreliable, still not truthful. And for many applications that’s a problem. There are some for which it’s not right. +
++ChatGPT’s sweet spot has always been making surrealist prose. It is now better at making surrealist prose than it was before. If that’s your use case, it’s fine, I have no problem with it. But if your use case is something where there’s a cost of error, where you do need to be truthful and trustworthy, then that is a problem. +
++Scott: It is absolutely useful to be thinking about these scenarios. It’s more useful to think about them grounded in where the technology actually is, and what the next step is, and the step beyond that. +
++I think we’re still many steps away from the things that people worry about. There are people who disagree with me on that assertion. They think there’s gonna be some uncontrollable, emergent behavior that happens. +
++And we’re careful enough about that, where we have research teams thinking about the possibility of these emergent scenarios. But the thing that you would really have to have in order for some of the weird things to happen that people are concerned about is real autonomy — a system that could participate in its own development and have that feedback loop where you could get to some superhumanly fast rate of improvement. And that’s not the way the systems work right now. Not the ones that we are building. +
++Bender: We already have WebMD. We already have databases where you can go from symptoms to possible diagnoses, so you know what to look for. +
++There are plenty of people who need medical advice, medical treatment, who can’t afford it, and that is a societal failure. And similarly, there are plenty of people who need legal advice and legal services who can’t afford it. Those are real problems, but throwing synthetic text into those situations is not a solution to those problems. +
++If anything, it’s gonna exacerbate the inequalities that we see in our society. And to say, people who can pay get the real thing; people who can’t pay, well, here, good luck. You know: Shake the magic eight ball that will tell you something that seems relevant and give it a try. +
++Manyika: Yes, it does have a place. If I’m trying to explore as a research question, how do I come to understand those diseases? If I’m trying to get medical help for myself, I wouldn’t go to these generative systems. I go to a doctor or I go to something where I know there’s reliable factual information. +
++Scott: I think it just depends on the actual delivery mechanism. You absolutely don’t want a world where all you have is some substandard piece of software and no access to a real doctor. But I have a concierge doctor, for instance. I interact with my concierge doctor mostly by email. And that’s actually a great user experience. It’s phenomenal. It saves me so much time, and I’m able to get access to a whole bunch of things that my busy schedule wouldn’t let me have access to otherwise. +
++So for years I’ve thought, wouldn’t it be fantastic for everyone to have the same thing? An expert medical guru that you can go to that can help you navigate a very complicated system of insurance companies and medical providers and whatnot. Having something that can help you deal with the complexity, I think, is a good thing. +
++Marcus: If it’s medical misinformation, you might actually kill someone. That’s actually the domain where I’m most worried about erroneous information from search engines +
++Now people do search for medical stuff all the time, and these systems are not going to understand drug interactions. They’re probably not going to understand particular people’s circumstances, and I suspect that there will actually be some pretty bad advice. +
++We understand from a technical perspective why these systems hallucinate. And I can tell you that they will hallucinate in the medical domain. Then the question is: What becomes of that? What’s the cost of error? How widespread is that? How do users respond? We don’t know all those answers yet. +
++Berman: I think society will need to adapt. A lot of those systems are very, very powerful and allow us to do things that we never thought would be possible. By the way, we don’t yet understand what is fully possible. We don’t also fully understand how some of those systems work. +
++I think some people will lose jobs. Some people will adjust and get new jobs. We have a company called Canvas that is developing a new type of robot for the construction industry and actually working with the union to train the workforce to use this kind of robot. +
++And a lot of those jobs that a lot of technologies replace are not necessarily the jobs that a lot of people want to do anyway. So I think that we are going to see a lot of new capabilities that will allow us to train people to do much more exciting jobs as well. +
++Manyika: If you look at most of the research on AI’s impact on work, if I were to summarize it in a phrase, I’d say it’s jobs gained, jobs lost, and jobs changed. +
++All three things will happen because there are some occupations where a number of the tasks involved in those occupations will probably decline. But there are also new occupations that will grow. So there’s going to be a whole set of jobs gained and created as a result of this incredible set of innovations. But I think the bigger effect, quite frankly — what most people will feel — is the jobs changed aspect of this. +
+What is the debt ceiling? What happens if the US breaches it? And other questions you were too embarrassed to ask. +
++This spring, Congress finds itself standing at a familiar precipice. Once again, if lawmakers don’t agree to suspend or raise the debt ceiling, the federal government risks defaulting on its loans, which would likely cause a massive economic crisis. To add to this urgency, Treasury Secretary Janet Yellen recently announced that a default could happen as early as June 1. +
++At issue is not whether the debt ceiling — a legal cap on how much the US can borrow — should be raised, but how. Democrats, led by President Joe Biden, insist that Congress pass a “clean” debt ceiling increase that does not include any trade-offs to guarantee its passage. House Republicans, meanwhile, are eager to pass spending cuts in exchange for approving any debt ceiling increase, with some saying they’re unwilling to compromise on this point. +
++This standoff has led to concerns that the US could come dangerously close to actually defaulting, which it came within 72 hours of doing in 2011. +
++The reason Congress continues to land in the same place is that raising or suspending the debt ceiling, much like funding the government, is something it must address on a regular basis. Because it’s must-pass legislation and requires the backing of both chambers, the party that’s out of power in the White House or in the minority in Congress has often used this measure as leverage to extract policy concessions or send a political message. +
++Republicans are attempting to do just that this time around, pushing significant spending cuts in the Limit, Save Grow Act, which is their opening bid to negotiations. At this point, Biden has been unwilling to consider such tradeoffs, though the two sides are scheduled to meet at the White House next week to discuss potential options. +
++For years, the US has been in a dangerous cycle in which the minority party tries to squeeze every concession it can out of the process, debt ceiling negotiations go down to the wire, and any miscalculation on the part of lawmakers could tip the US toward default. Thus far, this year hasn’t proven any different. +
++The first thing to know about the debt ceiling is that, as the name implies, it has something to do with the national debt. +
++Congress passes spending bills and tax laws; the revenues from those taxes pay for the spending, but often there’s not enough — and the US Treasury has to borrow money to make up the difference. +
++Year after year of doing this has brought us the national debt, currently at more than $31 trillion. This debt has been accrued under both parties: During the Trump administration, the national debt rose roughly $7.8 trillion, and under the Biden administration so far, it’s gone up about $3.7 trillion. +
++The debt ceiling is simply the cap on how much the US can borrow — from banks, investors, foreign countries, etc. — to help pay for the spending Congress has enacted. +
++As Vox’s Dylan Matthews has explained, the United States is unique in having a debt limit that lawmakers need to suspend or raise every few years. Were the US to “hit” its debt ceiling, it would effectively mean that it couldn’t pay any of its bills. +
++A debt limit was first established in 1917 in order to “make it easier to finance mobilization efforts in World War I,” per the Brookings Institution. Before that, Congress had to issue bonds every time it needed to borrow money, which proved unwieldy. Setting a debt ceiling enabled the US government to take on debt to more quickly and efficiently finance the military. +
++But the debt ceiling doesn’t automatically adjust for inflation or a growing economy, so it has needed to be raised over time. Since the 1960s, Congress has raised the debt limit more than 70 times; 20 of those times have been in the last 23 years. And as the present situation suggests, it has become increasingly used as leverage in budget negotiations during periods when government is split between Republicans and Democrats. —Li Zhou +
++Technically, the US already hit the debt ceiling in January, and the Treasury Department has been employing accounting tactics known as “extraordinary measures” to buy some more time. That’s basically a fancy term for accounting gymnastics that buy the government more time before it truly runs out of money. +
++But as Yellen said in her letter, the Treasury Department is running out of such moves — and the so-called “X-date” might be as early as June 1. —Li Zhou +
+ ++The US has never knowingly and purposefully breached the debt ceiling before. Depending on how you define “default,” it may have defaulted in the past, but in bizarre situations that bear no resemblance to the current moment (one was the aftermath of the War of 1812). —Dylan Matthews +
++Once we breach the debt ceiling, the federal government will not be able to pay its bills, or for things like Social Security checks, payroll for service members and other federal employees, and Medicare reimbursements. Interest payments on past debt could go unpaid, which would mean the US government would default on its debts. In 2011, the Federal Reserve and Treasury Department planned on prioritizing interest payments, acknowledging that they would miss payments of other things like Social Security checks, veterans’ benefits, etc. +
++The US would almost certainly enter a recession, probably a quite severe one, and the whole world could face a massive financial crisis. Beth Ann Bovino, chief US economist at Standard and Poor’s, was hardly alone in 2017 when she predicted that “the impact of a default by the U.S. government on its debts would be worse than the collapse of Lehman Brothers in 2008.” — Dylan Matthews +
++While there are concerns that this year’s standoff could be the most dangerous yet, political threats about the debt ceiling have been around for a long time. +
++In the 1950s, Republican President Dwight D. Eisenhower navigated standoffs with Democratic members of Congress about increasing the debt ceiling. Much as Republicans do today, Senate Democrats argued that the federal government should focus on reducing its expenditures rather than raising the debt cap. By withholding their support for a higher ceiling, lawmakers forced the administration to consider serious spending cuts. +
++Since then, the debt ceiling has been weaponized by members of both parties. Republicans, for instance, like to point out that Biden was among the senators who opposed raising the debt limit in 2006 when Republicans had congressional control. (Then-Sen. Barack Obama also voted no on raising the debt ceiling.) +
++But the US was never actually in danger of default in that instance — Democrats didn’t filibuster the final vote on the debt limit year. +
++Experts say the debt ceiling fight in 2011 was a turning point in that regard, with some lawmakers actually seeming open to a possible default. That year, Republicans balked on increasing the debt limit and refused to do so until President Obama agreed to key spending cuts, some of which they ultimately secured. The US got so close to default that year that it led Standard & Poor’s to downgrade the country’s credit rating, a move that prompted stocks to drop at the time. +
++“I’d definitely say 2011 was a step forward in how aggressively the debt ceiling was weaponized to secure partisan policy goals,” Josh Bivens, the director of research at the Economic Policy Institute, previously told Vox. “I’d say 1995 was also important; [House Speaker Newt] Gingrich threatened this but didn’t take it as far as the GOP did in 2011.” +
++In the years since, Republicans have become more aggressive in holding debt ceiling increases hostage to either elicit a policy demand or send a message. According to data analysis Aaron Blake did for the Washington Post, that pattern is noticeable across administrations, with Republicans much more likely to rail against the debt ceiling increase if a Democrat president is in charge, and Democrats doing the same to a lesser degree: +
++++In the 10 debt ceiling votes under a Republican administration, an average of 65 percent of House Republicans and 74 percent of Senate Republicans voted in favor of adjusting or suspending it. But in Democratic administrations, those numbers decline to 24 percent and 20 percent, respectively. +
++Under Democratic presidents, an average of 86 percent of House Democrats and 98 percent of Senate Democrats voted for debt ceiling increases. Under Republican presidents, those numbers drop to 51 percent and 58 percent, respectively. +
+
+The willingness to filibuster the debt ceiling, experts say, is also a sign of how partisan many legislative fights have become — even ones where the entire US economy hangs in the balance. —Li Zhou +
++A president acting on his own to unilaterally raise the debt ceiling is untested and would be controversial. That said, a few ideas have been floated on how the Biden administration can act if Congress won’t. +
++It’s strange but true: As blogger Carlos Mucha pointed out back in 2010, an existing law gives the US treasury secretary the power to issue platinum coins of any value she wishes. +
++The intention of the original 1997 law was about making it easier to produce platinum coins for the international coin collector market, but in 2011, Mucha revived the idea in the context of that year’s debt ceiling standoff. The treasury secretary could issue, say, a platinum coin worth $2 trillion, deposit it into the Treasury’s account at the Fed, and use those funds to sustain the government until the debt ceiling is raised. +
++The Obama administration found the idea too unserious there to use, but the legal case for minting the coin is as solid as platinum. Just ask debt ceiling hardliner Sen. Mike Lee (R-UT), who was sufficiently concerned about the option to introduce legislation to close the platinum coin loophole. The plain text of the 1997 law clearly allows the treasury secretary to do this, and Jerome Powell, the Fed chair who in a past career was an expert on the debt ceiling and its dangers, is arguably legally required to accept the coin as a deposit. (For what it’s worth, Powell has all but thrown cold water on this idea.) +
++Some legal scholars have argued that Section 4 of the 14th Amendment, which specifies that “the validity of the public debt of the United States, authorized by law … shall not be questioned,” renders the debt ceiling unconstitutional, as it threatens the validity of the US’s public debts by creating the possibility of default. The New York Times’s Jim Tankersley reports that the White House has been seriously debating the idea in recent weeks. +
++This is hardly a consensus position among constitutional law experts, but if Biden were to declare he was ignoring the debt ceiling because it’s unconstitutional, it’s not clear that anyone would have legal standing to sue him and challenge the decision. +
++That helped encourage a number of political actors, from then-House Minority Leader Nancy Pelosi to former President Bill Clinton, to urge Obama to invoke the 14th Amendment during his debt ceiling showdowns. Obama declined repeatedly, arguing in 2013 that “if you start having a situation in which there’s legal controversy about the US Treasury’s authority to issue debt, the damage will have been done, even if that were constitutional, because people wouldn’t be sure.” +
++University of Florida law professor Neil Buchanan and Cornell law professor Michael Dorf have, in a series of papers, proposed a way out of the debt ceiling that’s related to but distinct from the 14th Amendment option. +
++Buchanan and Dorf note that Congress, by setting spending and tax policy as well as a debt limit, has given the president three mandates: to spend the amount Congress authorizes, to tax the amount Congress authorizes, and to issue as much debt as Congress authorizes. When the debt ceiling is breached, it becomes impossible for the president to obey all three of these legal requirements. +
++Prioritizing spending on certain activities and cutting it elsewhere (as the Treasury planned to do in 2011) usurps Congress’s spending power by cutting spending unilaterally. Raising taxes without congressional authority would usurp Congress’s taxing power. And ignoring the debt ceiling would usurp Congress’s power to set debt limits. +
++The last option — respecting Congress’s taxing and spending powers while ignoring its debt limit — is the “least unconstitutional” option, Buchanan and Dorf argue. This judgment would no doubt be challenged in court, but it’s arguably less dramatic than the president unilaterally declaring the debt ceiling a violation of the 14th Amendment. (This may be my favorite of the options here.) +
++Steven Schwarcz, a professor at Duke Law and an expert on capital markets, has proposed getting around the debt ceiling by having the Treasury Department create a “special-purpose entity” to issue new securities, distinct from traditional Treasury bonds, that can pay for government expenditures. Because they’re not Treasury bonds, these securities would not be subject to the debt limit. +
++This may seem bizarre, but Schwarcz got the idea from state and municipal finance in the US; many states raise most of their debt with special-purpose entities, rather than by directly issuing bonds, often so they can get around their own state debt limits. —Dylan Matthews +
++The 2011 Budget Control Act was the result of that year’s debt ceiling standoff. +
++It included $917 billion in direct spending cuts, mostly implemented by capping “discretionary” spending, which includes defense programs and everything else the government does that isn’t a mandatory entitlement program like Social Security, food stamps, or veterans’ benefits. +
+ ++The bill then mandated another $1.2 trillion in deficit reduction to be determined through a congressional committee (colloquially called “the supercommittee”). If the supercommittee failed to put together a package slashing $1.2 trillion through tax hikes or spending cuts, indiscriminate spending cuts would ensue through forced decreases in the caps on defense and non-defense discretionary spending. +
++The across-the-board cuts included as a backup were never meant to take effect. But the supercommittee failed, forcing those spending cuts. +
++According to the Committee for a Responsible Federal Budget’s Marc Goldwein, the Budget Control Act resulted in $1.2 trillion or so in overall deficit reduction. +
++What did this all mean? +
++The Center on Budget and Policy Priorities’ David Reich co-authored a category-by-category report and found that, between 2010 and 2021, every single category of non-defense discretionary spending besides veterans’ programs saw declines after adjusting for inflation and population growth. +
++Economic security, health care, and scientific research programs were close to stagnant, falling by 4 percent or less. But funding for environmental protection and parks fell by 15 percent; general government operations by 26 percent; education and job training by 14 percent; and diplomacy and foreign aid by 19 percent. +
++A study from the American Association for the Advancement of Science found that aggregate research and development spending from the federal government was $200 billion lower due to the Budget Control Act; health research from the National Institutes of Health and the VA fell by over $7 billion a year relative to previous historical trends, while the National Science Foundation got almost $2 billion a year less. +
++This was all bad news for people interacting with government programs. The two biggest social assistance agencies in the US are the Social Security Administration (which administers old-age and disability payments) and the IRS, which administers tax credits that are crucial for reducing poverty. Adjusted for inflation, funding for the agencies fell by 13 and 19 percent between 2010 and 2021, respectively. —Dylan Matthews +
++The US government doesn’t have to work this way. +
++Congress could pass legislation doing away with the debt ceiling, and the president has options to ignore it as well, though they’d likely prompt legal challenges. As mentioned above, the president could invoke the 14th Amendment and ignore the debt limit, or Congress could approve an increase to the debt cap that’s so high it basically nullifies the ceiling. +
++Abolishing the debt limit altogether would prevent either party from using this process as political leverage. Doing so would greatly reduce the uncertainty that comes around every time there’s a deadline like this and prevent significant market volatility that results. +
++“There are zero downsides to getting rid of the debt ceiling,” said Bivens from the Economic Policy Institute. +
++Other economic experts note that eliminating the debt ceiling could take away an opportunity for Congress to debate fiscal policy. But many feel like that’s a moot point, given debt ceiling standoffs are rarely about any specific spending anymore, but rather about weakening the party in power. +
++Rather than do away with the debt limit altogether, some experts have proposed options like giving the president the ability to propose a suspension that Congress would need to override if it disagreed, making it tougher for legislators to jam up that process. A proposal that Shai Akabas of the Bipartisan Policy Center supports would pair this proposal with a mandatory debate on fiscal policy to force Congress to confront spending issues. +
++It’s unlikely there’s enough political will to make any of these changes happen. Instead, it seems as though lawmakers are comfortable getting right up to the brink — and running the risk of a default again and again. —Li Zhou +
++There’s significant uncertainty in how things could play out from here. +
++Biden has repeatedly emphasized that he’s not interested in negotiating on the debt ceiling and that he’d back separate talks on the budget and annual spending. Republicans, meanwhile, have tried to put forth their own position via recent legislation that lays out serious social spending cuts and rolls back Democratic policies like funding for the IRS and clean energy tax credits. That proposal is a non-starter for both the Senate and the White House. +
++The shadow of the 2011 debt ceiling crisis and the deal that ended it looms over today’s standoff. At the time, Democrats felt burned by Republicans after trying to negotiate and the GOP felt like they were able to secure significant wins by using the debt ceiling as a cudgel. +
++There are some off-ramps that lawmakers are eyeing. In one case, House Democrats are preparing to force a vote on a measure raising the debt ceiling by using a tool known as a discharge petition, which requires a simple majority — or 218 House members — to support it. To do so, the 213-member Democratic caucus would need the backing of five moderate Republicans — support that’s unlikely at the moment. +
++Additionally, lawmakers could try to approve a short-term suspension that gives both sides more time to wrangle negotiations, though Senate Majority Leader Chuck Schumer has suggested he favors a longer-term two-year solution. Schumer also said that Senate Democrats would wait until after the White House meeting on May 9 to determine how they intend to move forward. +
++The question is still whether either side will blink. Negotiators from the 2011 debt ceiling crisis previously told Vox that it’s possible Democrats will have to offer Republicans some type of concession so that GOP members can claim they got something out of the talks. “Everybody needs something to save face,” Brian Riedl, a former economic policy staffer for Sen. Rob Portman (R-OH), said. —Li Zhou +
++
+Camilla chose not to wear the Queen Mother’s crown, but its ill-gotten jewel is still worth talking about. +
++When King Charles III and Queen Camilla are officially crowned at Westminster Abbey on Saturday, the Duchess of Sussex won’t be the only thing missing. +
++The controversy-stirring Kohinoor diamond — the 105-carat sparkler at the center of the violet crown Camilla was expected to wear — won’t make an appearance. The royals have good reason to want to keep the gem out of Saturday’s coronation festivities. The crown jewel of the crown jewels is widely considered an ill-gotten spoil of Britain’s colonial conquests, and calls for the British to return the stone to India have grown increasingly loud since the death of Queen Elizabeth II last year. (The current Indian government, under Narendra Modi, has vacillated on whether it wants the diamond back, but many others do.) The British have yet to heed them. +
++Flashing the Kohinoor (also sometimes spelled Koh-i-noor) might have attracted the wrong sort of attention, but attempting to simply hide away a colonial past doesn’t work when it comes to the royals: With the death of the queen last year came a massive reassessment of the symbolism of British royalty and the moral and cultural wrongs of colonialism it has perpetrated and continues to condone explicitly and implicitly, particularly by keeping plundered artifacts. Even in trying to avoid one controversy, they’ve stepped into another one. The Cullinan diamonds, chipped off a massive diamond taken from South African mines, will be part of the coronation, and sure enough, South Africans want those back, too. +
++The Kohinoor landed in British hands in the 1840s, when the colonial British East India Company wrested it, and other property and land, from an Indian boy-king — a Sikh emperor who was just 10 or 11 at the time — in the cruelest of ways. The British imprisoned his mother, leaving him no choice but to turn over the gem. +
++It was no accident: Vox has reported that the British plundered an estimated $45 trillion (in today’s currency) from India during its reign. It took art, artifacts, property, and lives. The Kohinoor, found in a mine in what is today the city of Hyderabad, had a storied history, having been set in the bejeweled throne of Shah Jahan (of Taj Mahal fame) and plundered by the Afghans at some point (the Kohinoor is also claimed by Afghanistan). The British had been angling for the famed stone for years, simply waiting for the right mark. They found it in a prepubescent boy. +
++The British have been hanging on to the stone — even slicing away at it until it shined and glittered in a way that appealed to distinctly Western tastes — ever since. After making an appearance as a brooch worn by Queen Victoria, it eventually landed on the purple-flecked crown of the Queen Mother. +
++Objects snatched up in the age of empire, as well as during the Nazi regime, have become cultural hot potatoes in recent years: Under pressure from other governments to return what is rightfully theirs, museums in the US and Europe have begun sending back (also known as repatriating) Nigeria’s Benin Bronzes, the Italian Orpheus and the Sirens, and Cambodia’s Khmer art, among other antiquities. +
++But the British remain unapologetic holdouts, arguing to Greece that the Elgin Marbles were gainfully acquired, having been stripped from the Parthenon with permission from the Ottomans (colonizers themselves). Egyptians have lobbied for the return of the Rosetta Stone, which has sat in the collection of the British Museum since 1802. No dice there, either. +
++The words of Rudyard Kipling’s “The White Man’s Burden” come to mind when trying to understand why the British don’t want to return precious artifacts to countries that would like to have parts of their culture back. The country’s actions suggest it doesn’t believe a poor brown nation is a capable steward of its own people or its own rich culture. +
++The British, for all we can figure, loved empire, and still do today. The Kohinoor diamond has long been “a symbol of potency rather than beauty,” Anita Anand, who with historian William Dalrymple wrote the definitive book on the Kohinoor, told Smithsonian Magazine. The Kohinoor will stay with the British for at least a while longer; they’ve already made plans to display it late this month at the Tower of London, as a “symbol of conquest.” +
++That an effectively looted jewel is set in a crown is highly symbolic — symbolic of the British Empire’s legacy of bloody conquest, of subjugating brown and Black people, and of having made off with the artifacts that help carry on a culture. Simply hiding it away on coronation day doesn’t change that. +
IPL 2023 | Mumbai Indians manage only 139/8 against Chennai Super Kings - Skipper Rohit Sharma (0) failed to score for the second game in a row.
India’s Bindyarani Devi wins silver at Asian Championships - The Commonwealth Games silver medallist had a total effort of 194 kg (83 kg+111 kg) in the non-olympic 55 kg category
Data | Run-fest IPL 2023: Highest run-rate, most sixes and boundaries per game across all seasons - Rule changes and team tactics have made “power hitting” a mainstay of T20 cricket
Babar Azam leads Pakistan to big win over NZ and No. 1 ODI ranking - The most lopsided win of the series lifted Pakistan to No. 1 in the ICC ODI rankings
Messi apologises to PSG for Saudi trip - French media reported that Messi was suspended for two weeks after an unauthorised trip to Saudi Arabia when he was supposed to train with the squad
Panchayat sarpanches demand Finance Commission funds, stage protest in Guntur -
Shivamogga: Prohibitory orders on counting day -
Government doing all it can to contain Manipur trouble: Kiren Rijiju - The Union Home Minister himself was monitoring the situation and taking all necessary steps, Mr. Rijiju told reporters at the sideline of an event
Do you want to rent a house when you grow up? -
Karnataka CM promises inquiry into audio clip threatening Kharge family - The threat was allegedly made by Manikanth Rathod, the BJP candidate from Chittapur in Kalaburagi district
Ukraine war: Russia accused of using phosphorus bombs in Bakhmut - Rights groups warn the chemical is “notorious for the severity of the injuries it causes”.
Yevgeny Prigozhin: Wagner Group boss says he will pull fighters out of Bakhmut - Yevgeny Prigozhin poses among dead mercenaries, blaming defence officials for lack of ammunition.
Serbian mass shootings: President vows crackdown on gun ownership - The president’s promise comes after two mass shootings within 48 hours killed 17 people.
Who was behind the Kremlin drone attack? - The BBC’s Russia editor Steve Rosenberg examines the theories about the Moscow explosion.
What it’s like inside Russia 14 months after Ukraine invasion - At first glance things may seem normal - until you look closer, says the BBC’s Steve Rosenberg.
The long-awaited mission that could transform our understanding of Mars - Next-gen gear on delayed Martian rover may help answer the question of life on Mars. - link
President Biden meets with AI CEOs at the White House amid ethical criticism - “A room full of the dudes who gave us the issues & fired us for talking about the risks.” - link
Apple Arcade still exists, adds 20 new games—and some of them sound neat - The mobile gaming service seemed to lose momentum—Apple wants to regain it. - link
Brydge is done making Apple gear, leaving preorders unfilled, employees stiffed - Lots went wrong at Brydge, but trying to work inside Apple’s market was brutal. - link
Microsoft and AMD are reportedly teaming up to combat Nvidia’s AI dominance - Microsoft’s Azure platform currently uses “tens of thousands” of Nvidia GPUs. - link
Imagine if Americans switched from pounds to kilograms overnight. -
++There would be mass confusion. +
+ submitted by /u/castle_03
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Prince Charles & the hooker -
++Prince Charles and the Hooker. +
++Prince Charles decided to take up walking every day. At the same street corner he passed a hooker standing there every day. He learned to brace himself as he approached her for what was almost certain to follow. +
++“One hundred and fifty pounds!” she’d shout. +
++“No! Five pounds!” He said from the side of his mouth, just to shut her up. +
++This ritual between him and the hooker became a daily occurrence. +
++She’d yell, “One hundred and fifty pounds!” He’d yell back, “Five pounds!” +
++One day, Camilla decided to accompany her husband. +
++As the couple neared the hooker’s corner, Prince Charles realised she’d bark her £150 offer and Camilla would wonder what he’d really been doing on all his past outings. +
++He figured he’d better have a good explanation for his wife. +
++As they neared the hooker’s corner he became even more apprehensive than usual. +
++Sure enough, there she stood. He tried to avoid eye contact as she watched the pair pass. +
++Then, the hooker yelled: +
++“See what you get for five pounds, you tight bastard !” +
+ submitted by /u/zentribes
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My date asked me to undress her with words. -
++I told her she has a spider in her bra. +
+ submitted by /u/PixelatedNPC
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I ran into my wife’s ex. -
++He smarmily asked, “How do you like that used pussy?” +
++I told him, “It ain’t too bad once you get past the used part.” +
+ submitted by /u/ADHD_Panda
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I just spent $600 on a limousine rental, and I just found out that doesn’t include a driver. -
++Spent all that money and I have nothing to chauffeur it. +
+ submitted by /u/PejaBob
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