diff --git a/archive-covid-19/08 May, 2023.html b/archive-covid-19/08 May, 2023.html new file mode 100644 index 0000000..30d6c54 --- /dev/null +++ b/archive-covid-19/08 May, 2023.html @@ -0,0 +1,194 @@ + +
+ + + ++Background. Regulatory approval of new over-the-counter tests for infectious agents such as SARS-CoV-2 has historically required that clinical trials include diverse groups of specific patient populations, making the approval process slow and expensive. Showing that populations do not differ in their viral loads—the key factor determining test performance—could expedite the evaluation of new tests. Methods. 46,726 RT-qPCR-positive SARS-CoV-2 viral loads were annotated with patient demographics and health status. Real-world performance of two commercially available antigen tests was evaluated over a wide range of viral loads. An open-access web portal was created allowing comparisons of viral-load distributions across patient groups and application of antigen-test performance characteristics to patient distributions to predict antigen-test performance on these groups. Findings. In several cases distributions were surprisingly similar where a difference was expected (e.g. smokers vs. non-smokers); in other cases there was a difference that was the opposite direction from expectations (e.g. higher in patients who identified as White vs. Black). Sensitivity and specificity of antigen tests for detecting contagiousness were similar across most groups. The portal is at https://arnaoutlab.org/coviral/. Conclusions. In silico analyses of large-scale, real-world clinical data repositories can serve as a timely evidence-based proxy for dedicated trials of antigen tests for specific populations. Free availability of richly annotated data facilitates large-scale hypothesis generation and testing. +
++Background: Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with a novel airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease. Methods: Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns. Results: Forty patients (32M:8F, age:22-98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury. Conclusions: The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established. +
++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. +
+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
Safety, Tolerability and Immunogenicity of Alveavax-v1.2, a BA.2/Omicron-optimized, DNA Vaccine for COVID-19 Prevention - Condition: Sars-CoV-2 Infection
Interventions: Drug: Alveavax-v1.2; Drug: Janssen Ad26.COV2.S
Sponsor: Alvea Holdings, LLC
Completed
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
COVID-19 Vaccination Detoxification in LDL-C - 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
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
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
Digital Multimodal Rehabilitation for People With Post-acute COVID-19 Syndrome. - Condition: Post-COVID Syndrome
Interventions: Behavioral: RehabCovid_Telematic; Behavioral: RehabCovid_ImmersiveVR; Behavioral: Control_Condition
Sponsors: Consorci Sanitari de Terrassa; University of Barcelona; Universitat de Girona; Unitat Assistencial i Preventiva de l’Esport- Centre d’Alt rendiment; Politecnic University of Catalonia; Corporación Fisiogestión
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
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
Critical role of TLR activation in viral replication, persistence, and pathogenicity of Theiler’s virus - Theiler’s murine encephalomyelitis virus (TMEV) establishes persistent viral infections in the central nervous system and induces chronic inflammatory demyelinating disease in susceptible mice. TMEV infects dendritic cells, macrophages, B cells, and glial cells. The state of TLR activation in the host plays a critical role in initial viral replication and persistence. The further activation of TLRs enhances viral replication and persistence, leading to the pathogenicity of TMEV-induced…
Increased inflammatory cytokines and oxidative stress enhanced antibody production in breast and prostate cancer patients with COVID-19 related depression - Cancer management is highly dependent on the immune status of the patient. During the COVID-19 pandemic, a large number of people suffered from anxiety and depression, especially cancer patients. The effect of depression on breast cancer (BC) and prostate cancer (PC) patients, during the pandemic has been analyzed in this study. Levels of proinflammatory cytokines (IFN-γ, TNF-α, and IL-6) and oxidative stress markers malondialdehyde (MDA) and carbonyl content (CC) were estimated in patients’…
“Super” SERPINs-A stabilizing force against fibrinolysis in thromboinflammatory conditions - The superfamily of serine protease inhibitors (SERPINs) are a class of inhibitors that utilise a dynamic conformational change to trap and inhibit their target enzymes. Their powerful nature lends itself well to regulation of complex physiological enzymatic cascades, such as the haemostatic, inflammatory and complement pathways. The SERPINs α2-antiplasmin, plasminogen-activator inhibitor-1, plasminogen-activator inhibitor-2, protease nexin-1, and C1-inhibitor play crucial inhibitory roles in…
A Developmental Pathway From Early Behavioral Inhibition to Young Adults’ Anxiety During the COVID-19 Pandemic - CONCLUSION: This study identifies a developmental pathway from toddlerhood BI to young adults’ elevated anxiety during the COVID-19 pandemic. Findings have implications for early identification of individuals at risk for dysregulated worry and the prevention of anxiety during stressful life events in young adulthood.Reprinted from J Am Acad Child Adolesc Psychiatry, 60, Zeytinoglu et al., A Developmental Pathway From Early Behavioral Inhibition to Young Adults’ Anxiety During the COVID-19…
Deficient Radiation Transcription Response in COVID-19 Patients - CONCLUSIONS: SARS-CoV-2 infection affects a DNA damage response that may modify radiation-induced health risks in exposed patients with COVID-19.
Application of single-cell RNA sequencing on human testicular samples: a comprehensive review - So far there has been no comprehensive review using systematic literature search strategies to show the application of single-cell RNA sequencing (scRNA-seq) in the human testis of the whole life cycle (from embryos to aging males). Here, we summarized the application of scRNA-seq analyses on various human testicular biological samples. A systematic search was conducted in PubMed and Gene Expression Omnibus (GEO), focusing on English researches published after 2009. Articles related to GEO…
In silico study of potential SARS-CoV-2 antagonist from Clitoria ternatea - CONCLUSION: From these results, it was concluded that C. ternatea possess potential therapeutic properties against COVID-19.
Antiviral properties of trans-δ-viniferin derivatives against enveloped viruses - Over the last century, the number of epidemics caused by RNA viruses has increased and the current SARS-CoV-2 pandemic has taught us about the compelling need for ready-to-use broad-spectrum antivirals. In this scenario, natural products stand out as a major historical source of drugs. We analyzed the antiviral effect of 4 stilbene dimers [1 (trans-δ-viniferin); 2 (11’,13’-di-O-methyl-trans-δ-viniferin), 3 (11,13-di-O-methyl-trans-δ-viniferin); and 4…
Porcine epidemic diarrhea virus (PEDV) ORF3 protein inhibits cellular type I interferon signaling through down-regulating proteins expression in RLRs-mediated pathway - Porcine epidemic diarrhea virus (PEDV) is an entero-pathogenic coronavirus, which belongs to the genus Alphacoronavirus in the family Coronaviridae, causing lethal watery diarrhea in piglets. Previous studies have shown that PEDV has developed an antagonistic mechanism by which it evades the antiviral activities of interferon (IFN), such as the sole accessory protein open reading frame 3 (ORF3) being found to inhibit IFN-β promoter activities, but how this mechanism used by PEDV ORF3 inhibits…
Development and validation of an LC-MS/MS method for quantification of favipiravir in human plasma - Favipiravir (FVP) is a broad-spectrum antiviral that selectively inhibits viral RNA-dependent RNA polymerase, first trialled for the treatment of influenza infection. It has been shown to be effective against a number of RNA virus families including arenaviruses, flaviviruses and enteroviruses. Most recently, FVP has been investigated as a potential therapeutic for severe acute respiratory syndrome coronavirus 2 infection. A liquid chromatography tandem mass spectrometry method for the…
Evaluating the ability of some natural phenolic acids to target the main protease and AAK1 in SARS COV-2 - Researchers are constantly searching for drugs to combat the coronavirus pandemic caused by SARS-CoV-2, which has lasted for over two years. Natural compounds such as phenolic acids are being tested against Mpro and AAK1, which are key players in the SARS-CoV-2 life cycle. This research work aims to study the ability of a panel of natural phenolic acids to inhibit the virus’s multiplication directly through Mpro and indirectly by affecting the adaptor-associated protein kinase-1 (AAK1)….
Myeloperoxidase inhibition may protect against endothelial glycocalyx shedding induced by COVID-19 plasma - CONCLUSIONS: Neutrophil MPO may increase EG shedding in COVID-19, and inhibiting MPO activity may protect against EG degradation. Further research is needed to evaluate the utility of MPO inhibitors as potential therapeutics against severe COVID-19.
Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation - Severe COVID-19 is characterized by an increase in the number and changes in the function of innate immune cells including neutrophils. However, it is not known how the metabolome of immune cells changes in patients with COVID-19. To address these questions, we analyzed the metabolome of neutrophils from patients with severe or mild COVID-19 and healthy controls. We identified widespread dysregulation of neutrophil metabolism with disease progression including in amino acid, redox, and central…
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…
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 Uneventful Success of King Charles’s Coronation - The careful preparation with which every detail had been mapped out in advance is a prerequisite for military maneuvers. A comparable precision had been applied to the minutiae of peace. - link
Will Trump’s Crimes Matter on the Campaign Trail? - The former President has faced two impeachments and countless accusations of public and private wrongdoing. Yet his approval rating is pretty much unchanged. - link
An Eyewitness to Jordan Neely’s Death - “It’s shameful,” Johnny Grima, a formerly homeless man, who was aboard the train in which Neely was choked to death, said. “There’s no getting around it.” - link
+A new survey finds two-thirds of car dealers didn’t have a single electric vehicle for sale. +
++Electric cars and trucks are more popular than ever, and sales are growing, but if you want one, you’ll probably have a hard time finding an EV in stock near you. +
++Two-thirds of US car dealers surveyed in a new Sierra Club study, published Monday, didn’t have any battery electric or plug-in hybrids for sale in 2022, new or used. +
++“There are more dealerships that have electric vehicles since the last time we did this report [in 2019], but it’s still shockingly low,” said Katherine García, director of the Clean Transportation for All Campaign at the Sierra Club. +
++Transportation is the largest source of greenhouse gas emissions in the US, with passenger cars and trucks making up 57 percent of this share. So electrifying sedans, SUVs, and pickups is an essential component of the strategy for meeting climate change targets. The US has committed to cutting its total emissions in half from 2005 levels by 2030. Meanwhile, automakers like General Motors have committed to going all-electric, and there are looming bans on fossil fuel-powered cars in some of the largest car-buying states like California and New York. +
+ ++So what’s the holdup? +
++A big part of it is due to supply chain blockages, with shortfalls in semiconductor and battery production preventing manufacturers from making enough electrics to meet demand. Some of the largest carmakers in the world — Honda, Toyota, Stellantis — had few if any EVs and plug-in hybrid models at all for sale in North America last year. According to the Sierra Club survey, 44 percent of car dealers who didn’t have an EV on their lots would gladly sell them if they could get their hands on one. +
++“The larger bottleneck is with the manufacturers themselves,” García said. +
++But 45 percent of dealers without EVs said they wouldn’t sell them even if they were available. The structure of the car sales model can put dealers, manufacturers, and customers at odds since the economics of EVs can disrupt the business model for dealerships. It’s another critical choke point: If a dealer is resistant to stocking electric cars and trucks, a buyer might not have any nearby options for the specific EV they want since manufacturers grant dealers monopolies in a given area. +
++With the rise of all-electric carmakers like Tesla and Rivian, however, there’s a push for car companies to sell their vehicles directly to customers without the middleman. It’s forcing major auto companies and dealers to adapt and it will chart the route ahead for zero-emissions cars and trucks. +
++The EV buying experience varies a lot depending on what kind of car you’re looking for and where you are. Ninety percent of Mercedes-Benz dealers had an EV for sale compared to 11 percent of Honda retailers, according to the Sierra Club study. This includes used vehicles for sale that were made by another manufacturer. +
++Your best bet for finding an EV on the lot was in the southeastern US in states like Georgia and Florida, where 41 percent of dealers had an electric for sale. In Western states like California, Oregon, and Washington, only 27 percent of dealers had EVs in stock. This region also accounted for 45 percent of EV sales in the US, so the lower stock was likely due to more demand. +
+ ++Some manufacturers are racing to keep up while also coping with recalls. Dealers in turn are adjusting to these sporadic supplies, but also trying to accommodate how EVs are changing the way they do business. +
++All states have rules that encourage or require carmakers to sell vehicles to customers through dealerships. There are close to 17,000 franchise new car dealers in the US, and they sold 13.7 million light-duty vehicles last year, according to the National Automobile Dealers Association. +
++Originally, these regulations were designed to prevent a handful of major car companies from colluding across the country and fixing prices. Dealers also expanded the footprint of carmakers and gave buyers a local point of contact. They’re technically independent franchises, which means that they can set their own prices and incentives, but carmakers have a lot of leverage in how dealerships function. +
++Vivek Astvansh, an assistant professor of marketing at Indiana University, explained that car dealers have three main functions: They sell cars and take trade-ins on behalf of the manufacturer, they provide loans to buyers, and they perform maintenance and repairs. +
++It turns out that parts and service can account for nearly half of a dealership’s profits. But EVs don’t need oil changes, spark plugs, or valve checks. “All else equal, an electric car has fewer mechanical parts than a gasoline or diesel car, which directly means that the revenue a car dealer makes from an electric car is much lower than what the dealer will make from a gas or diesel counterpart,” said Astvansh. +
++If there are any issues or recalls, many fixes for EVs can be applied over the air rather than going to a dealer. It’s a selling point for an EV buyer but a challenge for a dealer. “That is why they are hesitant to make a strong case for electric cars,” Astvansh said. +
++On the other hand, many people are buying EVs for the first time and they’re counting on dealers to teach them the ins and outs of charging, maximizing range, and taking advantage of government incentives. As cars have become less mechanical, they’ve become more computerized, creating a learning curve for first-time drivers who may not appreciate the importance of keeping their car’s software updated, for example. +
++“The foremost function that a dealer can provide is that of educating the buyers,” Astvansh said. “Customers cannot just use ChatGPT or Google and have all the information. They need to interact with a human being.” +
++But dealers have to make investments in their infrastructure to sell EVs. Ford has created an EV certification program for its dealers, which requires them to build fast chargers and train their staff to work on electrics. The top-tier certification can cost a dealership up to $1.2 million to achieve, but it gives them first crack at new EVs and allocates them more inventory. Ford said that more than half of Ford dealers in the US have signed on as the company aims to build its own EV charging network. +
+ ++“It’s good for Ford; it’s just that the initial investment is expensive,” said Devron Stevenson, general manager of Banister Ford of Marlow Heights in Maryland. Stevenson said his dealership is gearing up to install level 3 fast chargers this year that can top up an EV in minutes, but require dedicated grid connections and specialized electrical hardware. +
++Similarly, General Motors, the parent company of Chevrolet, is enacting standards for dealers. “For EVs, dealers must maintain the proper service tools, battery charging equipment, and training, as well as meeting customer experience standards,” said David Caldwell, a spokesperson for GM. “More than 90 percent of Chevrolet dealers are enrolled.” +
++But even if manufacturers build them and dealers sell them, the trickier question is whether enough people will buy electric cars and trucks to make this all worthwhile. With borrowing costs increasing, EVs are a tougher sell since on average they have a higher sticker price than their fossil fuel counterparts. Earlier this month, Ford announced a price cut of up to 8 percent on its Mustang Mach-E. For dealers, how much they invest in EV infrastructure now is a delicate balancing act. “It’s going to depend: How fast can we get them? Can we afford them? Does it make sense overall in the next 24 months? To me, it’s a bit of a toss-up,” Stevenson said. +
++Dealer franchise laws across the US benefit existing dealers but pose a problem for manufacturers that want to sell directly to their customers in some states. Tesla operates a factory in Texas, but the company can’t sell its cars to Texans directly. The cars have to be shipped out of the state before delivery to a Texas buyer. +
++Other EV-only carmakers like Rivian and Lucid also sell directly to consumers. This doesn’t factor into the Sierra Club’s calculations, so EVs are more accessible to more people than the number of cars on lots lets on. +
++EV companies say that this direct-to-consumer model lets them elide the haggling of traditional car dealers and avoid the costs of maintaining dealer lots and sales staff. Twenty-three states now allow direct sales for EV-only auto companies, though they they still face restrictions in many cases. Several more states are working on laws to make direct sales easier, either by relaxing rules or granting EV makers dealer licenses. +
+ ++Conventional automakers like Ford and Volkswagen have recently started to echo this, letting customers buy cars online and pick them up at a dealer rather than going through the sales process in person. +
++Yet even EVs need to have their tires rotated, and all-electric companies are rushing to build out service centers to handle maintenance and recalls, or leaning on traditional automakers. “How important is convenient local service to customers? Since 2021, Tesla owners have come to GM dealerships for service on more than 11,000 occasions,” Caldwell said. +
++He added that while EVs may not yet be available everywhere, the auto industry is making the largest and fastest technological change in its history. In 2020, electric cars and trucks accounted for 4.2 percent of new vehicle sales worldwide. In 2021, 8.3 percent. Last year, 14 percent. +
++“Two words: It’s happening,” Caldwell said. +
+New research suggests the party has room for improvement ahead of 2024. +
++Democrats know that Republican attacks on abortion rights will be central to their efforts to reelect Joe Biden and regain full control of Congress in 2024. +
++And for good reason — Democrats won competitive midterm races last fall while running on protecting reproductive freedom. Last month, in another high-stakes election in Wisconsin, the judicial candidate who staunchly supported abortion rights beat her anti-abortion opponent by 11 points. +
++Polls conducted over the last few months indicate that abortion remains top of mind for voters, who seem to have grown even more supportive of abortion rights than they were before the Dobbs v. Jackson decision overturned the constitutional right to an abortion last June. +
++“I don’t think Democrats have fully processed that this country is now 10 to 15 percent more pro-choice than it was before Dobbs in state after state and national data,” pollster Celinda Lake said recently. +
++But there is one worrying sign for Democrats in the polling data. Over the past two weeks, for example, two new national polls and data from three focus groups conducted in swing states (Ohio, North Carolina, and Michigan) indicated that significant numbers of independent voters remain confused and skeptical about where Republicans and Democrats stand on protecting abortion rights. The upside for Democrats is they may have substantial room to grow with these voters. +
++One survey, conducted in mid-April by Marist Poll in partnership with NPR and PBS NewsHour, found 38 percent of independent voters think neither Democrats nor Republicans handle the abortion issue well, compared to just 10 percent of Democratic voters and 21 percent of Republican voters who felt the same. And when the progressive polling group Navigator asked voters in April what they thought came closest to the Democratic Party’s position on abortion, 34 percent of independents said they didn’t know enough to say, compared to just 9 percent of Democrats and 11 percent of Republicans. +
++These gaps are significant, as most US adults self-identify as independent voters — 41 percent, according to Gallup, compared to 28 percent of adults who ID as Republican and 28 percent as Democrat. “Since 2009, independent identification has grown and reached levels not seen before,” Gallup reported this year. +
++The surveys come as some abortion rights activists continue to raise frustrations with the president for what they see as his lackluster support for keeping abortion legal. While the Biden administration has done much to defend abortion rights since the Supreme Court issued its ruling last summer, the president himself has struggled to talk about abortion, relying largely on surrogates and euphemisms like “protect women’s health care” and “a woman’s right to choose.” In Biden’s recently released reelection launch video, he did not say “abortion” himself — though a woman was featured holding an “abortion is healthcare” protest sign. In February, Biden used the word “abortion” explicitly for the first time in a State of the Union address, though many activists were still upset he devoted just four sentences to the topic, and almost an hour into his speech. “It was, to be blunt, offensive,” feminist writer Jessica Valenti said after. +
++The Biden administration did not return a request for comment. +
++Bryan Bennett, a pollster with Navigator, said independents broadly report pro-choice attitudes, so the two new surveys suggest Biden and Democrats “have a real opportunity to talk more and crystallize” where they stand on abortion. +
++Bennett noted that among independent women, the gaps were even higher, with 43 percent in their latest survey saying they weren’t sure what Democrats’ position on abortion was. “Focusing on that, and trying to reach that 34 percent of independents who don’t have a position, represents a real chance to drive that [pro-abortion rights] advantage,” he said. +
++A majority of independent voters back abortion rights, though public opinion research indicates there may be some notable differences between their views and those of self-identified Democrats. For example, while a post-Dobbs Navigator survey found 84 percent of Democrats identified as “pro-choice,” the pollsters found just 54 percent of independents did. Thirty percent of independents in the same survey identified as “pro-life,” compared to 11 percent of Democrats. +
++Heading into the 2022 midterms, pollsters found abortion rights to be a significantly motivating issue for independent voters, though again less motivating than for Democrats. A quarter of independents told Navigator the Dobbs decision made them “much more motivated” to vote in November, compared to 56 percent of Democrats. And 41 percent of independents told KFF the decision made them “more motivated” to vote, compared to 64 percent of Democrats. A Wall Street Journal poll found 9 percent of independents ranked the Supreme Court ruling as the top issue among five choices motivating them to vote, compared with 77 percent of Democrats. +
++In days immediately following the midterms, NARAL Pro-Choice America led exit surveys of voters in battleground states and found that while Democrats ranked abortion a top priority for Congress and the White House, independents did not. +
++Still, independents definitely reported broad pro-choice attitudes in NARAL’s exit survey, with 54 percent saying they’d be less likely to support Republicans if they tried to pass more abortion bans, and 74 percent of independents said women and their doctors should make decisions about abortion, not politicians. +
++When asked about the Marist/NPR survey finding high levels of distrust among independents for both Democrats and Republicans, Angela Vasquez-Giroux, NARAL’s vice president of research, noted that many voters support abortion access because they distrust politicians generally. “Voters don’t want politicians involved in their personal freedoms and personal medical decisions,” she told Vox. +
++In late April, Navigator hosted three focus groups with women voters to learn more about how abortion issues continue to motivate Americans politically. The participants in Ohio and North Carolina were suburban women who identified as either weak Democrats, independents, or weak Republicans; the participants in Michigan were women of color who identified as either strong Democrats, weak Democrats, or independents. +
++Each group had between seven and nine participants, and all had previously stated they either support the right to abortion or do not believe the government should prevent access to abortion even if they are personally against it. While these are tiny samples, researchers say the qualitative data from a focus group helps clarify voter beliefs and signals questions to more rigorously study in the future. +
++Vox reviewed video footage and transcripts from the three focus groups and found in each some women who support abortion rights had significant trouble identifying Democrats’ and Republicans’ stances on abortion. +
++“I think Democrats are pro-life and Republicans are against it,” said one participant in Ohio, when asked what Democrats and Republicans believe on abortion. +
++In Michigan, a woman was asked how the two parties differ on abortion and how she would describe each party’s position. +
++“I’m not sure,” the woman answered. “I really haven’t basically heard anything about which party is leaning toward it and which one isn’t.” When the focus group moderator pressed her to guess, she answered: “If I had to guess, I would say Democrat would probably be against it and Republican probably would be for it.” +
++In North Carolina, a participant said she wasn’t sure where the parties stand on abortion and had been surprised Roe v. Wade was overturned under a Democrat. +
++“Okay, but did Joe Biden have a say in whether or not it was overturned?” the focus group moderator asked. +
++“No, but he helped get the Supreme judges where they are.” The moderator then informed the woman that the most recent judges came in under Donald Trump. +
++Confusion among independents has been reflected in some other polling data. For example, in a survey conducted in the two weeks after Dobbs, 23 percent of independents said they don’t know if abortion rights were at risk in their state, compared to just 5 percent of Democrats who said the same. Likewise, while a majority of independents said in the same survey they would support a nationwide law that protects the right of a woman to have an abortion, 18 percent of independents said they weren’t sure either way, suggesting there might be more need to clarify for voters what that means. +
++One Democratic pollster, speaking on background, said the data about independents was great to have and provides “actionable information” for campaigns ahead of 2024. +
++Other leaders have been more hesitant to suggest Democrats could benefit from new tactics to target pro-choice independents — saying the recent election results in Democrats’ favor speak for themselves. +
++“Time and time again, whether it was the 2022 midterms, ballot initiatives, or special elections in Virginia and Wisconsin, voters continue to prove that they will support the candidate who will protect their reproductive freedom,” said Jenny Lawson, the vice president of organizing and electoral campaigns at Planned Parenthood Action Fund. “The data is clear and we have the receipts: Anti-abortion politicians are on the losing side of the issue.” +
++Vasquez-Giroux of NARAL also defended Biden’s rhetoric. “I think the president is doing a pretty good job of being clear about where he stands, and [regarding] the reelection video — taking one example out is not fully representative,” she said. “And you do have [Vice President] Kamala Harris out on the road talking about abortion. It should be clear where the administration stands.” +
+How much trouble you think we’re in depends on how pragmatic — and tethered to reality — you think each side is. +
++Amid a rapidly approaching debt ceiling deadline and a continued standoff between Democrats and Republicans, it may be hard to see how this crisis ends. +
++Republicans believe (correctly) that holding the debt ceiling hostage gives them more leverage to win spending cuts from Biden. Democrats believe (correctly) that this is dangerous and irresponsible behavior that risks economic devastation, and that rewarding it with policy concessions would lead to more such behavior. +
++Just how much trouble you think we’re in depends on just how pragmatic — and tethered to reality — you think each side is. +
++The question about Republicans is pretty simple: Are the adults in charge? +
++Put it another way: Is the party controlled by extremists willing to burn down the country’s credit rating if they can’t force Democrats into unthinkable concessions? Or are they taking a tough negotiating position but likely to agree to some reasonable compromise with Democrats in the end? +
++There’s a question about Democrats too: Will they conclude that they probably do have to give up something to free the hostage? +
++That is: Will Biden climb down from his “no negotiations” position soon? Or are too many in the party truly dug into the position that any debt ceiling negotiations are immoral and dangerous, clinging to the hope that Republicans will cave with no concessions? (Many liberal commentators hope Biden will take the debt limit off the table entirely by using his executive power in some way, but administration officials have publicly dismissed such ideas.) +
++The debt ceiling discourse is a bit confusing because it isn’t just about the debt ceiling. As my colleague Dylan Matthews recently explained, what Republicans actually want to negotiate over is government spending levels. And Democrats will definitely have to deal with the GOP-controlled House to get government funding bills passed through Congress — if they don’t, the government shuts down after September 30. That would be true even if there was no debt ceiling fight at all. +
++President Biden’s current position is that he is happy to negotiate with Republicans on government spending, but not on the debt ceiling. That may be hair-splitting. The question is whether he will demand the debt ceiling be taken off the table entirely before spending talks begin. If he doesn’t, then negotiations are on, and the real question is whether the two sides can find a mutually acceptable compromise on spending. +
++Only then will we learn whether the adults are in fact in charge of the GOP. +
++If you talk privately to informed, reasonable people on this topic, they see a pretty plausible outcome where a spending deal could be reached. +
++It starts with a number. The centerpiece of negotiations will be how much the government should allot to discretionary spending, a category of spending that excludes entitlement programs like Social Security, Medicare, Medicaid, and certain other mandatory spending allotments. +
++Biden’s budget plan proposed $1.695 trillion in discretionary spending for fiscal year 2024. The bill that House Republicans just passed proposed $1.471 trillion. +
++To state the extremely obvious, a final deal would fall somewhere in between those numbers. (For comparison, last year’s level was $1.6 trillion.) +
++Of course, Democrats argue that Republicans’ number is appallingly low. David Reich of the Center on Budget and Policy Priorities writes that, if defense and veterans’ programs are protected from cuts (as Republicans want), the GOP bill would end up cutting the rest of discretionary spending by 33 percent in 2024 — a massive cut. +
++Democrats will not agree to anything remotely this extreme, so Republicans will have to move up their number quite a bit. But the GOP likely won’t accept much — if any — discretionary spending increases over last year’s level. They’ll also likely be adamantly opposed to any tax increases. +
++There’s also the question of future years’ spending levels. The last big debt ceiling deal, in 2011, set spending caps lasting 10 years. The House GOP bill proposes doing that again, with only 1 percent increases in discretionary spending each year. +
++That would seem to mean enormous cuts lasting far into the future, since that wouldn’t keep up with inflation or population growth — though it’s unclear future Congresses would abide by these spending caps (they were regularly overridden over the last decade). Democrats will likely push for a shorter timespan with bigger spending increases, though it may be in both parties interest to cut a deal that would last past the 2024 election. +
++The House GOP bill also included several policy changes Democrats really do not like. The bill would roll back Biden’s increased IRS funding, block his student loan relief program, repeal the clean energy tax breaks passed in the Inflation Reduction Act, add work requirements for many Medicaid and SNAP beneficiaries, boost fossil fuel production via permitting reform, and rescind unspent Covid-19 relief money. +
++Most of those ideas seem dead on arrival. Perhaps Democrats could stomach very limited or scaled-back concessions on some of them, but the GOP shouldn’t expect much. One big exception is permitting reform — there has been interest from Democrats in striking a bipartisan deal there, though it’s unclear whether it will be ready by the debt ceiling deadline. +
++But the feasible deal would likely mainly center on setting discretionary spending somewhere close to the current level — forgoing most or all of the typical yearly increase — in a way that lets Republicans argue they won serious cuts and lets Democrats argue they avoided devastating cuts. (Depending on where you set the baseline, whether you adjust for inflation and population growth, and what happens with defense versus non-defense funding, it would likely be possible to argue it both ways.) +
++The biggest question is whether enough House Republicans will be able to recognize a realistic and reasonable compromise, or whether they’ll just keep fantasizing about driving an unrealistically hard bargain where they force Democrats to give in on topics where Democrats are adamantly against giving in. +
++During the last GOP House majority, which lasted from 2011 to 2018, we repeatedly saw a dynamic where GOP leaders would try to cut a spending deal with Democrats, and hardline conservatives would recoil, arguing it wasn’t good enough. And even when leaders like Speaker John Boehner put out their own plan with the intention of unifying the party, they’d often fail to get the votes for it. +
++When Kevin McCarthy struggled for days to lock down enough hardline GOP votes to become Speaker of the House in January, it looked like we could be heading for a repeat of that dynamic — utter Republican disarray, with anti-spending hardliners so far out on a limb that it would be impossible for McCarthy to get anything through the chamber. +
++Yet McCarthy has managed to keep both the House and Senate GOP almost entirely united around his strategy so far. The House GOP passed his plan last week, and Senate Republicans are deferring to him — arguing that Biden needs to come to the table and cut a deal. +
++The anti-spending faction is, for now, on the team, and so are the moderates. (That’s why House Democrats’ hope to force a “clean” debt limit increase via a discharge petition is likely doomed — they’d need Republican moderates to join them, but those moderates haven’t split from McCarthy.) +
++But how will the Freedom Caucus types react when a deal inevitably falls far short of conservatives’ wildest dreams? Will McCarthy manage to bring them along and convince them it’s the best they could have gotten, or will they revolt and use procedural tactics to try to oust him from the speakership? +
++That’s where we again return to the question of who’s really in charge of the GOP. If the reasonable people are in charge and this is just a hardball negotiation with the goal of getting to yes in the end, then we’ll avoid disaster. If ideology, enmity, and wishful thinking about total victory carry the day, we won’t. Place your bets. +
World Test Championship | Ishan Kishan named as KL Rahul’s replacement for India’s final against Australia - Ruturaj Gaikwad, Mukesh Kumar and Suryakumar Yadav have been named as stand-by players
Messi back in training with PSG - Messi, who apologised to PSG and his teammates on Friday, was left out of the squad for their 3-1 win at second-bottom Troyes on Sunday
IPL 2023 | Have worked on improving my strike-rate: RCB skipper Du Plessis - RCB are currently fifth in the table with 10 points from 10 games
Hockey India names 20-member women’s team for Australia tour, Savita to lead - The tour will be part of the team’s preparations ahead of the all-important Hangzhou Asian Games
IPL 2023 | Samad was desperate to show his worth to team: Badani - Badani revealed Samad was gutted after the loss to KKR
Appachu Ranjan of BJP eyes fourth win in Madikeri by projecting rival as outsider - Mr Ranjan is from the Kodava community. He has been elected from the Vokkaliga Gowda-dominated constituency since 2008
Illegal houseboat operations thrive in Alappuzha - Many houseboats operate without mandatory licences, registration, insurance, and pollution certificates, and employing unlicensed crew
10 Indians arrested in Nepal for illegally acquiring citizenship cards - The Indian nationals were found to have obtained the Nepali citizenship certificates on different dates from the district administration offices
Envoy visit to Hyderabad celebrates Australia’s ties with Telangana - The High Commissioner will meet IT Minister KTR
Union Minister Jitendra Singh reviews status of creation of Science Media Communication Cell - He also reviewed preparations for the National Technology Day to be observed on May 11
Ukraine war: ‘Mad panic’ as Russia evacuates town near Zaporizhzhia plant - UN watchdog warns of “threat of a severe nuclear accident” at the Zaporizhzhia plant in Ukraine.
Yevgeny Prigozhin: Wagner boss ‘promised ammunition’ after retreat threat - Yevgeny Prigozhin seemingly U-turns on his threat to withdraw from the Ukrainian city of Bakhmut.
Zakhar Prilepin: Russian pro-war writer defiant after car bomb attack - Zakhar Prilepin said he had been driving and the bomb had been under the passenger seat.
BBC unveils Bike Bureau for green broadcasting - Two BBC journalists have spent the last few years building a mobile broadcast studio and office on two wheels.
Silvio Berlusconi: Italy ex-PM appears by video after serious illness - The 86-year-old is still in hospital after suffering from a lung infection linked to his leukaemia.
Yet another problem with recycling: It spews microplastics - One recycling facility emits as much as 3 million pounds of microplastics a year. - link
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
Why did Han Solo cry during his steak dinner? -
++Because it was Chewie. +
+ submitted by /u/Hawt_Mayun
[link] [comments]
My daughter came home today and said “Dad, I’d like you to meet my new boyfriend Mike.” -
++“Are you kidding me?!” I said, “What the fuck are you doing with this ugly loser? Don’t scrape the barrel, you can do much better than this.” +
++“Dad!!” my daughter screamed, “Mike is lovely!” +
++“I know.” I replied “I was talking to him.” +
+ submitted by /u/PaytheDevil
[link] [comments]
Americans In Canada -
++An American couple is driving through Canada and stops at a gas station to fuel up. +
++As the man goes into the station to pay, his wife calls out to him, “Ask them where we are!” So the husband walks in, pays, and asks, “By the way, where are we?” +
++To which the attendant answers, “Saskatoon, Saskatchewan.” +
++The man goes back to his car and the wife asks, “Where are we?” +
++“He doesn’t speak English” replies the husband. +
+ submitted by /u/pash5050
[link] [comments]
Vegans will be the first to invent intergalactic travel -
++Imagine living in the Milky Way +
+ submitted by /u/Significant-Glove232
[link] [comments]
What do baking and BDSM have in common? -
++They both involve lots of beating and whipping +
+ submitted by /u/tjmaxal
[link] [comments]