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<title>14 September, 2023</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Bayesian Framework for Moderated Mediation Using Covid-19-caused Natural Experiment: Modeling Home Advantage in Soccer</strong> -
<div>
Observational studies are being used more and more in psychology and medicine since they provide a wealth of data for real-world issues. Their biggest drawback is the lack of falsification due to the control mechanisms of control conditions being unavailable. However, the Covid-19 pandemic and the isolation policies related to it have provided an environment in which researchers can use natural experimental design to establish causal pathways in phenomena. Here we demonstrate how Covid-19-related changes can be used to investigate causal effects behind Home Advantage (HA), a robust phenomenon in which sport teams are more successful when they play in front of their fans. HA theories assume that the crowd support spurs home players to better performance and biases referees, and that these two factors in turn influence the result. Covid-19 has provided the perfect control condition for disentangling the causal links of the HA as sport teams have played at home but without the presence of fans. Using our newly developed Home Advantage Mediated (HAM) model, which considers all individual factors and their interrelations simultaneously instead of in isolation as was previously the case, we demonstrate how Covid-19 enables us to disentangle the processes behind the HA phenomenon. Besides throwing new (modeling) light on one of the most robust phenomena in sport, our paper also provides information about the practical implementation of mediation and moderated mediation mixed-effects models in the Bayesian framework. Similar implementations can be adapted in other medical and social science fields.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/vz7de/" target="_blank">Bayesian Framework for Moderated Mediation Using Covid-19-caused Natural Experiment: Modeling Home Advantage in Soccer</a>
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<li><strong>Revising Home Advantage in Sport – Home Advantage Mediation (HAM) Model</strong> -
<div>
Home Advantage (HA) is a robust phenomenon in which sport teams or individuals are more successful when they play in front of their fans. There are a number of causes of HA, but most theories assume that the crowd support spurs home players to better performance and biases referees, and that these two factors in turn influence the result. The interest in HA has grown during the Covid-19 pandemic as most competitions were taking place behind closed doors, a perfect control condition for disentangling the causal effects behind HA. Despite the presence of useful conceptual frameworks, most previous research has focused on investigating isolated individual factors. Here we review our newly developed Home Advantage Mediated (HAM) model, which considers all individual factors and their interrelations simultaneously. HAM assumes that the crowd effects are mediated through other relevant factors, such as referee bias and team performance. Most importantly, HAM can be formally expressed as a mediation model, a technique widely employed in social sciences for investigating causal pathways. We demonstrate how researchers can use HAM to model the HA in European football and how moderating variables, such as Covid-19 and absence of fans, can be incorporated in the model to disentangle the processes behind the HA phenomenon. Besides throwing new (modeling) light on one of the most robust phenomena in sport, we also provide information about practical implementation of mediation and moderated mediation models in the Bayesian framework. Similar implementations can be adapted for use in other sport science domains.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/c8tu3/" target="_blank">Revising Home Advantage in Sport – Home Advantage Mediation (HAM) Model</a>
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<li><strong>The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions</strong> -
<div>
The Covid-19 pandemic has significantly altered the way sporting events are observed. With the absence or limited presence of spectators in stadiums, the traditional advantage enjoyed by home teams has diminished considerably. This underscores the notion that the support of home fans can often be considered a key factor of the home advantage (HA) phenomenon, wherein teams perform better in front of their own supporters. However, the impact of reduced attendance on games with higher stakes, as opposed to low-stakes friendly matches, remains uncertain. In this study, we investigate the recently concluded European football championship (EURO 20), wherein several teams had the advantage of playing at home in high-stakes games with only one-third of the stadium capacity filled. Firstly, we demonstrate that the Covid-19 restrictions, leading to reduced fan attendance, resulted in a nearly 50% decrease in HA compared to the HA exhibited by the same teams during the qualification stage preceding EURO 20, even after accounting for team strength. Secondly, we show that while low-stakes friendly matches generally exhibit a smaller overall HA compared to high-stakes games, the absence of fans led to a similar reduction in HA during the low-stakes matches. Utilizing the recently developed Home Advantage Mediated (HAM) model (Bilalić et al., 2021, Scientific Reports, 21558), we were able to attribute the reduction in both high- and low-stakes games to poorer team performance, with no significant contribution from referee bias.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/d3xat/" target="_blank">The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions</a>
</div></li>
<li><strong>Home Advantage during the COVID-19 Pandemic in European football</strong> -
<div>
The home advantage (HA) is a robust phenomenon in soccer whereby the home team wins more games and scores more goals than the away team. One explanation is that the home crowd spurs on home team performance and causes the referee to unconsciously favour the home team. The Covid-19 pandemic provided a unique opportunity to assess this explanation for HA, as European soccer leagues played part of the 2019/2020 season with crowds present and concluded with crowds absent. Using multi-level modelling we compared team performance and referee decisions pre-Covid (crowd present) and post-Covid (crowd absent) across 9,528 games from 15 leagues in 11 countries. HA (goals scored and points gained) was significantly reduced post pandemic, which reflected the inferior performance of the home team. In addition, referees awarded significantly fewer sanctions against the away teams, and home teams created significantly fewer attacking opportunities when they played without fans.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/2gkht/" target="_blank">Home Advantage during the COVID-19 Pandemic in European football</a>
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<li><strong>Towards mitigating health inequity via machine learning: a nationwide cohort study to develop and validate ethnicity-specific models for prediction of cardiovascular disease risk in COVID-19 patients</strong> -
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Background Emerging data-driven technologies in healthcare, such as risk prediction models, hold great promise but also pose challenges regarding potential bias and exacerbation of existing health inequalities, which have been observed across diseases such as cardiovascular disease (CVD) and COVID-19. This study addresses the impact of ethnicity in risk prediction modelling for cardiovascular events following SARS-CoV-2 infection and explores the potential of ethnicity-specific models to mitigate disparities. Methods This retrospective cohort study utilises six linked datasets accessed through National Health Service (NHS) England9s Secure Data Environment (SDE) service for England, via the BHF Data Science Centre9s CVD-COVID-UK/COVID-IMPACT Consortium. Inclusion criteria were established, and demographic information, risk factors, and ethnicity categories were defined. Four feature selection methods (LASSO, Random Forest, XGBoost, QRISK) were employed and ethnicity-specific prediction models were trained and tested using logistic regression. Discrimination (AUROC) and calibration performance were assessed for different populations and ethnicity groups. Findings Several differences were observed in the models trained on the whole study cohort vs ethnicity-specific groups. At the feature selection stage, ethnicity-specific models yielded different selected features. AUROC discrimination measures showed consistent performance across most ethnicity groups, with QRISK-based models performing relatively poorly. Calibration performance exhibited variation across ethnicity groups and age categories. Ethnicity-specific models demonstrated the potential to enhance calibration performance for certain ethnic groups. Interpretation This research highlights the importance of considering ethnicity in risk prediction modelling to ensure equitable healthcare outcomes. Differences in selected features and asymmetric calibration across ethnicities underscore the necessity of tailored approaches. Ethnicity-specific models offer a pathway to addressing disparities and improving model performance. The study emphasises the role of data-driven technologies in either alleviating or exacerbating existing health inequalities. Keywords Prediction, machine learning, electronic health records, bias, ethnicity.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.13.23295489v1" target="_blank">Towards mitigating health inequity via machine learning: a nationwide cohort study to develop and validate ethnicity-specific models for prediction of cardiovascular disease risk in COVID-19 patients</a>
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<li><strong>Determinants of SARS-CoV-2 IgG response and decay in Canadian healthcare workers: a prospective cohort study.</strong> -
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Introduction Healthcare workers (HCWs) from an interprovincial Canadian cohort were asked to give serial blood samples to identify factors associated with anti-receptor binding domain (anti-RBD) IgG response to the SARS-CoV-2 virus. Methods Members of the HCW cohort donated blood samples four months after their first SARS-CoV-2 immunization and again at 7, 10 and 13 months. Date and type of immunizations and dates of SARS-CoV-2 infection were collected at each of four contacts, together with information on immunologically-compromising conditions and current therapies. Blood samples were analyzed centrally for anti-RBD IgG and anti-nucleocapsid IgG (Abbott Architect, Abbott Diagnostics). Records of immunization and SARS-CoV-2 testing from public health agencies were used to assess the impact of reporting errors on estimates from the random-effects multivariable model fitted to the data. Results 2752 of 4567 vaccinated cohort participants agreed to donate at least one blood sample. Modelling of anti-RBD IgG titer from 8903 samples showed an increase in IgG with each vaccine dose and with first infection. A decrease in IgG titer was found with the number of months since vaccination or infection, with the sharpest decline after the third dose. An immunization regime that included mRNA1273 (Moderna) resulted in higher anti-RBD IgG. Participants reporting multiple sclerosis, rheumatoid arthritis or taking selective immunosuppressants, tumor necrosis factor inhibitors, calcineurin inhibitors and antineoplastic agents had lower anti-RBD IgG. Supplementary analyses showed higher anti-RBD IgG in those reporting side-effects of vaccination, no relation of anti-RBD IgG to obesity and lower titers in women immunized early in pregnancy. Sensitivity analysis results suggested no important bias in the self-report data. Conclusion Creation of a prospective cohort was central to the credibility of results presented here. Serial serology assessments, with longitudinal analysis, provided effect estimates with enhanced accuracy and a clearer understanding of medical and other factors affecting response to vaccination.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.12.23295445v1" target="_blank">Determinants of SARS-CoV-2 IgG response and decay in Canadian healthcare workers: a prospective cohort study.</a>
</div></li>
<li><strong>Changes in stillbirths and child and youth mortality in 2020 and 2021 during the Covid-19 pandemic</strong> -
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Background: The COVID-19 pandemic9s impact on mortality, especially among the elderly, has been extensively studied. While COVID-19 rarely causes direct mortality in children and youth, the pandemic9s indirect effects might harm these age groups. Yet, its influence on stillbirths and mortality rates in neonates, infants, children, and youth remains poorly understood. This study examines disruptions in such trends across 95 countries in 2020 and 72 in 2021, providing the inaugural comprehensive analysis of COVID-199s effect on young mortality and stillbirths. Methods: We estimate expected mortality levels in a non-pandemic setting and calculate relative mortality changes (p-scores) by applying generalized linear models to data from civil registers and vital statistics systems (CRSV) and from the Health Management Information System (HMIS). We then use these estimates to analyze, for each age group, the distribution of country-specific mortality changes and the proportion of countries experiencing mortality deficits, no changes, and excess. Results: For most countries and territories, stillbirths and mortality at ages under 25 did not differ from expected levels in 2020 and 2021. However, when focusing on the countries that did show changes, more countries experienced mortality deficits than excess. The exception was stillbirths in both years and mortality among neonates and those aged 10-24 in 2021, where more countries had an excess rather than a deficit. Overall, a quarter of the countries examined experienced increases in stillbirths and young adult mortality (20-24). Conclusion: Despite global disruptions to essential services, stillbirths and youth mortality were as expected in most countries, defying expectations. However, this doesn9t dismiss hypotheses suggesting delayed adverse effects on the youngest that may require more time to be noticeable at the population level. Close and long-term monitoring of health and deaths among children and youth, particularly in low-income and lower-middle-income countries, is required to fully understand the lasting impacts of the COVID-19 pandemic.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.13.23295484v1" target="_blank">Changes in stillbirths and child and youth mortality in 2020 and 2021 during the Covid-19 pandemic</a>
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<li><strong>Infectious touching: Has COVID-19 changed our perceptions of social touch? A neural and behavioral study</strong> -
<div>
Social touch is essential for reducing stress, improving mood and fostering a sense of social connectedness. Stimuli related to social touch are generally perceived as positive. Nevertheless, the social restrictions imposed by the COVID-19 pandemic may have changed the way human beings perceive and react to social touch. Indeed, the social distancing imposed by the pandemic may have had long term effects on human perceptions of social touch. In the current study, we examined how perceptions of interpersonal touch in social interactions were affected by the COVID-19 pandemic. Specifically, we compared behavioral and neural responses to observed social touch between two groups: pre- and post-COVID-19. Participants in both groups rated the pleasantness of photos of social touch between humans, nonsocial touch between inanimate objects or non-touch photos of either two humans or inanimate objects. We hypothesized that social touch in the post-COVID-19 group would induce hypervigilance due to the risk of infection. In line with our predictions, we found behavioral changes in perceptions of social touch among participants in this group, who rated photos with touch as less pleasant than did participants in the pre-COVID-19 group. Participants in the post-COVID-19 group also rated photos with humans as less pleasant than did participants in the pre-COVID-19 group. Additionally, EEG analysis revealed neural changes in the ERP components associated with hypervigilance: P1 and LPP. Contrary to pre-COVID-19 measures showing more positive P1 amplitudes for touch than for non-touch photos, after COVID-19 no differences in P1 amplitudes were found between touch and non-touch photos. Furthermore, after COVID-19 the P1 amplitudes for human and inanimate photos in the touch condition were similar, a pattern that did not emerge prior to COVID-19. These findings suggest that COVID-19 had a surprising impact on human perceptions of social touch, such that observing nonsocial touch evoked more positive emotions than observing human touch. Further, these findings may reflect shifts in attention or changes in the salience of touch-related information due to the altered circumstances brought about by the pandemic. Overall, our results indicate that COVID-19 has modified human perceptions of social touch, providing evidence that the pandemic has affected individuals' perceptual and evaluative processes and highlighting the importance of considering social and environmental factors in understanding subjective experiences.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.12.557330v1" target="_blank">Infectious touching: Has COVID-19 changed our perceptions of social touch? A neural and behavioral study</a>
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<li><strong>Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus</strong> -
<div>
Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad ACE2 usage and that RBD mutations further expand receptor promiscuity and enable human ACE2 utilization. We determined a cryoEM structure of the PRD-0038 RBD bound to R. alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryoEM and monoclonal antibody reactivity revealed its distinct antigenicity relative to SARS-CoV-2 and identified PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicited greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared to SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.12.557371v1" target="_blank">Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus</a>
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<li><strong>Circulation of SARS-CoV-2 and co-infection with Plasmodium falciparum in Equatorial Guinea</strong> -
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The impact of COVID-19 in Africa has been a big concern since the beginning of the pandemic. However, low incidence of COVID-19 case severity and mortality has been reported in many African countries, although data are highly heterogeneous and, in some regions, like Sub-Saharan Africa, very scarce. Many of these regions are also the cradle of endemic infectious diseases like malaria. The aim of this study was to determine the prevalence of SARS-CoV-2, the diversity and origin of circulating variants as well as the frequency of co-infections with malaria in Equatorial Guinea. For this purpose, we conducted antigen diagnostic tests for SARS-CoV-2, and microscopy examinations for malaria of 1,556 volunteers at six health centres in Bioko and Bata from June to October 2021. Nasopharyngeal swab samples were also taken for molecular detection of SARS-CoV-2 by RT-qPCR and whole genome viral sequencing. We report 3.0% of SARS-CoV-2 and 24.4% of malaria prevalence over the sampling in Equatorial Guinea. SARS-CoV-2 cases were found at a similar frequency in all age groups, whereas the age groups most frequently affected by malaria were children (36.8% [95% CI 30.9-42.7]) and teenagers (34.7% [95% CI 29.5-39.9]). We found six cases of confirmed co-infection of malaria and SARS-CoV-2 distributed among all age groups, representing a 0.4% frequency of co-infection in the whole sampled population. Interestingly, the majority of malaria and SARS-CoV-2 co-infections were mild. We obtained the genome sequences of 43 SARS-CoV-2 isolates, most of which belong to the lineage Delta (AY.43) and that according to our pandemic-scale phylogenies were introduced from Europe in multiple occasions (7 transmission groups and 17 unique introductions). This study is relevant in providing first-time estimates of the actual prevalence of SARS-CoV-2 in this malaria-endemic country, with the identification of circulating variants, their origin, and the occurrence of SARS-CoV-2 and malaria co-infection.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.12.23295464v1" target="_blank">Circulation of SARS-CoV-2 and co-infection with Plasmodium falciparum in Equatorial Guinea</a>
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<li><strong>The Impact of the UK COVID-19 Lockdown on the Screening, Diagnostics and Incidence of Breast, Colorectal, Lung and Prostate Cancer in the UK: a Population-Based Cohort Study</strong> -
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Objectives: This study aimed to assess the impact of the COVID-19 lockdown on the screening and diagnosis of breast, colorectal, lung, and prostate cancer. The study also investigated whether the rates returned to pre-pandemic levels by December 2021. Design: Cohort study. Setting: Electronic health records from UK primary care Clinical Practice Research Datalink (CPRD) GOLD database. Participants: The study included individuals registered with CPRD GOLD between January 2017 and December 2021, with at least 365 days of prior observation. Main outcome measures: The study focused on screening, diagnostic tests, referrals and diagnoses of first-ever breast, colorectal, lung, and prostate cancer. Incidence rates (IR) were stratified by age, sex and region, and incidence rate ratios (IRR) were calculated to compare rates during and after lockdown with the reference period before lockdown. Forecasted rates were estimated using negative binomial regression models. Results: Among 5,191,650 eligible participants, the initial lockdown resulted in reduced screening and diagnostic tests for all cancers, which remained dramatically reduced across the whole observation period for almost all tests investigated. For cancer incidence rates, there were significant IRR reductions in breast (0.69), colorectal (0.74), and prostate (0.71) cancers. However, the reduction in lung cancer incidence (0.92) was non-significant. Extrapolating to the entire UK population, an estimated 18,000 breast, 13,000 colorectal, 10,000 lung, and 21,000 prostate cancer diagnoses were missed from March 2020 to December 2021. Conclusion: The national COVID-19 lockdown in the UK had a substantial impact on cancer screening, diagnostic tests, referrals and diagnoses. Although incidence rates started to recover after the lockdown, they remained significantly lower than pre-pandemic levels for breast and prostate cancers and associated tests. Delays in diagnosis are likely to have adverse consequences on cancer stage, treatment initiation, mortality rates, and years of life lost. Urgent strategies are needed to identify undiagnosed cases and address the long-term implications of delayed diagnoses.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.21.23292937v3" target="_blank">The Impact of the UK COVID-19 Lockdown on the Screening, Diagnostics and Incidence of Breast, Colorectal, Lung and Prostate Cancer in the UK: a Population-Based Cohort Study</a>
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<li><strong>MEGA: Machine Learning-Enhanced Graph Analytics for Infodemic Risk Management</strong> -
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The COVID-19 pandemic brought not only global devastation but also an unprecedented infodemic of false or misleading information that spread rapidly through online social networks. Network analysis plays a crucial role in the science of fact-checking by modeling and learning the risk of infodemics through statistical processes and computation on mega-sized graphs. This paper proposes MEGA, <i>M</i>achine Learning-<i>E</i>nhanced <i>G</i>raph <i>A</i>nalytics, a framework that combines feature engineering and graph neural networks to enhance the efficiency of learning performance involving massive graphs. Infodemic risk analysis is a unique application of the MEGA framework, which involves detecting spambots by counting triangle motifs and identifying influential spreaders by computing the distance centrality. The MEGA framework is evaluated using the COVID-19 pandemic Twitter dataset, demonstrating superior computational efficiency and classification accuracy.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.10.24.20215061v7" target="_blank">MEGA: Machine Learning-Enhanced Graph Analytics for Infodemic Risk Management</a>
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<li><strong>A hematopoietic stem cell subset that retains memory of prior inflammatory stress accumulates in aging and clonal hematopoiesis</strong> -
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Hematopoietic stem cells (HSC) must persist through a lifetime of infections to ensure life-long blood production, but whether molecular adaptations following inflammatory stress recovery in HSC are linked to aging and clonal hematopoiesis (CH) are unclear. Here, we performed single cell (sc) Multiomics on human HSC isolated from a xenograft inflammation-recovery model. Two transcriptionally and epigenetically distinct HSC subsets expressing canonical HSC programs were identified. Only one showed scATACseq and scRNAseq changes after recovery from TNF or lipopolysaccharide treatment. This inflammatory memory HSC (HSC-iM) program is enriched in memory T cells and HSC from recovered COVID-19 patients. Importantly, HSC-iM accumulates with age and with CH. Overall, a human HSC subset that retains memory of prior inflammatory stress has implications towards HSC fitness and leukemia transformation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.11.557271v1" target="_blank">A hematopoietic stem cell subset that retains memory of prior inflammatory stress accumulates in aging and clonal hematopoiesis</a>
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<li><strong>Effect of Higher-Dose Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial</strong> -
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Background: The impact of fluvoxamine in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) remains uncertain. Our objective was to assess the effectiveness of fluvoxamine 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Methods: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were age &gt;=30 years with confirmed SARS-CoV-2 infection and &gt;=2 acute COVID-19 symptoms for &lt;=7 days. Participants were randomized to receive fluvoxamine 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days or to placebo. The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID clinical progression scale; and difference in mean time unwell. Results: Among participants who were randomized and received study drug, the median age was 50 years (IQR 40-60), 66% were female, 45% identified as Hispanic/Latino, and 77% reported &gt;=2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09; P(efficacy) = 0.4]). Additionally, unadjusted, median time to sustained recovery was 10 days (95% CI 10-11) in both the intervention and placebo group. No deaths were reported. Thirty-five participants reported healthcare utilization events (a priori defined as death, hospitalization, emergency department/urgent care visit); 14 in the fluvoxamine group compared with 21 in the placebo group (HR 0.69; 95% CrI 0.27-1.21; P(efficacy)=0.86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo). Conclusions: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov (NCT04885530).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.12.23295424v1" target="_blank">Effect of Higher-Dose Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial</a>
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<li><strong>Contributions of human ACE2 and TMPRSS2 in determining host-pathogen interaction in COVID-19</strong> -
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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is an emerging global public health crisis. Angiotensin converting enzyme 2 (ACE2) and trans-membrane protease serine 2 (TMPRSS2) are the two major host factors that contribute to the virulence of SARS-CoV-2 and pathogenesis of coronavirus disease-19 (COVID-19). Animal to human transmission of SARS-CoV-2 is considered as a rare event that necessarily required strong evolutionary adaptations. Till date no other human cellular receptors were identified beside ACE2 for SARS-CoV-2 entry inside the human cell. Proteolytic cleavage of viral spike (S)-protein and ACE2 by TMPRSS2 began the entire host-pathogen interaction initiated with the physical binding of ACE2 to S-protein. SARS-CoV-2 S-protein binds to ACE2 with much higher affinity and stability than that of SARS-CoV’s. Molecular interactions between ACE2-S and TMMPRSS2-S are crucial and preciously mediated by specific residues. Structural stability, binding affinity and level of expression of these three interacting proteins are key susceptibility factors for COVID-19. Specific protein-protein interactions (PPI) are being identified that explains uniqueness of SARS-CoV-2 infection. Amino acid substitutions due to naturally occurring genetic polymorphisms potentially alter these PPIs and poses further clinical heterogeneity of COVID-19. Repurposing of several phytochemicals and approved drugs against ACE2, TMPRSS2 and S-protein have been proposed that could inhibit PPI between them. We have also identified some novel lead phytochemicals present in Azadirachta indica and Aloe barbadensis which could be utilized for further in vitro and in vivo anti-COVID-19 drug discovery. Uncovering details of ACE2-S and TMPRSS2-S interactions would further contribute in the future research on COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/evuby/" target="_blank">Contributions of human ACE2 and TMPRSS2 in determining host-pathogen interaction in COVID-19</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: hAd5-S-Fusion+N-ETSD;   Biological: Placebo (0.9% (w/v) saline)<br/><b>Sponsor</b>:   ImmunityBio, Inc.<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</strong> - <b>Conditions</b>:   Immunosuppression;   COVID-19<br/><b>Intervention</b>:   Biological: NVX-CoV2372<br/><b>Sponsors</b>:   University of Wisconsin, Madison;   Novavax<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations</strong> - <b>Conditions</b>:   Influenza;   COVID-19<br/><b>Interventions</b>:   Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster);   Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster);   Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)<br/><b>Sponsors</b>:   Duke University;   Centers for Disease Control and Prevention;   Arizona State University;   University Hospitals Cleveland Medical Center;   University of Pittsburgh;   Washington University School of Medicine;   Valleywise Health;   VA Northeast Ohio Health Care;   Senders Pediatrics<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents</strong> - <b>Conditions</b>:   Vaccine-Preventable Diseases;   COVID-19 Pandemic;   Health-Related Behavior;   Health Knowledge, Attitudes, Practice;   Narration<br/><b>Interventions</b>:   Behavioral: Baseline surveys;   Behavioral: Digital Storytelling Intervention;   Behavioral: Information Control Intervention<br/><b>Sponsors</b>:   Arizona State University;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia</strong> - <b>Condition</b>:   Bronchoalveolar Lavage<br/><b>Intervention</b>:   Procedure: Bronchoalveolar Lavage<br/><b>Sponsors</b>:   Mohamed Abd Elmoniem Mohamed;   Marwa Salah Abdelrazek Ghanem;   Mohammad Khairy El-Badrawy;   Tamer Ali Elhadidy;   Dalia Abdellateif Abdelghany<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203)</strong> - <b>Conditions</b>:   COVID-19 Infection;   COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>:   Biological: LEM-mR203;   Biological: Placebo<br/><b>Sponsor</b>:   Lemonex<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults</strong> - <b>Condition</b>:   SARS-CoV-2 Infection<br/><b>Intervention</b>:   Biological: B/HPIV3/S-6P<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   Johns Hopkins Bloomberg School of Public Health;   National Institutes of Health (NIH)<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Determine the Tolerability of Intranasal LMN-301</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: LMN-301<br/><b>Sponsor</b>:   Lumen Bioscience, Inc.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effect of Cognitive Behavioral Therapy on Post-Traumatic Stress Symptoms in Nursing Students</strong> - <b>Condition</b>:   Trauma and Stressor Related Disorders<br/><b>Intervention</b>:   Other: Cognitive Behavioral Therapy Group<br/><b>Sponsor</b>:   Necmettin Erbakan University<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long COVID Immune Profiling</strong> - <b>Conditions</b>:   Long COVID;   POTS - Postural Orthostatic Tachycardia Syndrome;   Autonomic Dysfunction<br/><b>Interventions</b>:   Diagnostic Test: IL-6;   Diagnostic Test: cytokines (IL-17, and IFN-ɣ);   Behavioral: Compass 31<br/><b>Sponsors</b>:   Vanderbilt University Medical Center;   American Heart Association<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Healthy Microbiome, Healthy Mind</strong> - <b>Conditions</b>:   Critical Illness;   COVID-19;   PICS;   Cognitive Impairment;   Mental Health Impairment;   Weakness, Muscle;   Dysbiosis<br/><b>Intervention</b>:   Behavioral: Fermented Food Diet<br/><b>Sponsor</b>:   Mayo Clinic<br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Association between levels of IgG antibodies from vaccines and Omicron symptomatic infection among children and adolescents in China</strong> - CONCLUSION: The risk of developing a symptomatic infection can be predicted independently by tertiles of IgG antibodies to wild-type SARS-CoV-2 antigens. High IgG levels can inhibit viral replication, vastly reduce the risk of symptomatic infections and promote a virus-negative conversion, especially when IgG quantitative detection was ≥3.44 S/CO, a potential threshold for protection and booster strategy in the future. More data and research are needed in the future to validate the predictive…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of essential genes associated with SARS-CoV-2 infection as potential drug target candidates with machine learning algorithms</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the fast discovery of effective treatments to fight this worldwide concern. Several genes associated with the SARS-CoV-2, which are essential for its functionality, pathogenesis, and survival, have been identified. These genes, which play crucial roles in SARS-CoV-2 infection, are considered potential therapeutic targets. Developing drugs against these essential genes to inhibit their regular functions could be a good approach…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets</strong> - The virus life cycle depends on host-virus protein-protein interactions, which often involve a disordered protein region binding to a folded protein domain. Here, we used proteomic peptide phage display (ProP-PD) to identify peptides from the intrinsically disordered regions of the human proteome that bind to folded protein domains encoded by the SARS-CoV-2 genome. Eleven folded domains of SARS-CoV-2 proteins were found to bind 281 peptides from human proteins, and affinities of 31 interactions…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Broadly neutralizing antibodies derived from the earliest COVID-19 convalescents protect mice from SARS-CoV-2 variants challenge</strong> - Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Suramin inhibits SARS-CoV-2 nucleocapsid phosphoprotein genome packaging function</strong> - The coronavirus disease 2019 (COVID-19) pandemic is fading, however its etiologic agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues posing - despite the availability of licensed vaccines - a global health threat, due to the potential emergence of vaccine-resistant SARS-CoV-2 variants. This makes the development of new drugs against COVID-19 a persistent urgency and sets as research priority the validation of novel therapeutic targets within the SARS-CoV-2 proteome….</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhalable dry powder containing remdesivir and disulfiram: Preparation and in vitro characterization</strong> - The respiratory tract, as the first and most afflicted target of many viruses such as SARS-CoV-2, seems to be the logical choice for delivering antiviral agents against this and other respiratory viruses. A combination of remdesivir and disulfiram, targeting two different steps in the viral replication cycle, has showed synergistic activity against SARS-CoV-2 in-vitro. In this study, we have developed an inhalable dry powder containing a combination of remdesivir and disulfiram utilizing the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MICROVASCULAR ENDOTHELIAL ACTIVATION/DYSFUNCTION AND DYSREGULATION OF THE ANGIOPOIETIN-TIE2 SYSTEM IN THE PATHOGENESIS OF LIFE-THREATENING INFECTIONS</strong> - Microvascular endothelial activation/dysfunction has emerged as an important mechanistic pathophysiological process in the development of morbidity and mortality in life-threatening infections. The angiopoietin-Tie2 system plays an integral role in the regulation of microvascular endothelial integrity. Angiopoietin-1 (Ang-1), produced by platelets and pericytes, is the cognate agonistic ligand for Tie2, promoting endothelial quiescence and inhibiting microvascular leak. Angiopoietin-2 (Ang-2),…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Prime editor-mediated functional reshaping of <em>ACE2</em> prevents the entry of multiple human coronaviruses, including SARS-CoV-2 variants</strong> - The spike protein of SARS-CoV-2 hijacks the host angiotensin converting enzyme 2 (ACE2) to meditate its entry and is the primary target for vaccine development. Nevertheless, SARS-CoV-2 keeps evolving and the latest Omicron subvariants BQ.1 and XBB have gained exceptional immune evasion potential through mutations in their spike proteins, leading to sharply reduced efficacy of current spike-focused vaccines and therapeutics. Compared with the fast-evolving spike protein, targeting host ACE2…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting host calcium channels and viroporins: a promising strategy for SARS-CoV-2 therapy</strong> - Despite passing the pandemic phase of the COVID-19, researchers are still investigating various drugs. Previous evidence suggests that blocking the calcium channels may be a suitable treatment option. Ca^(2+) is required to enhance the fusion process of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also, some important inflammatory factors during SARS-CoV-2 infection are dependent on Ca^(2+) level. On the other hand, viroporins have emerged as attractive targets for antiviral…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19</strong> - Previously, we and others have shown that SARS-CoV-2 spike-specific IgG antibodies play a major role in disease severity in COVID-19 by triggering macrophage hyperactivation, disrupting endothelial barrier integrity, and inducing thrombus formation. This hyperinflammation is dependent on high levels of anti-spike IgG with aberrant Fc tail glycosylation, leading to Fcγ receptor hyperactivation. For development of immune-regulatory therapeutics, drug specificity is crucial to counteract excessive…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of the BNT162b2 Vaccine Coadministered with Seasonal Inactivated Influenza Vaccine in Adults</strong> - CONCLUSIONS: BNT162b2 coadministered with SIIV elicited immune responses that were noninferior to those elicited by BNT162b2 alone and SIIV alone, and BNT162b2 had an acceptable safety profile when coadministered with SIIV. The results of this study support the coadministration of BNT162b2 and SIIV in adults.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Farnesoid X receptor enhances epithelial ACE2 expression and inhibits viral-induced IL-6 secretion: implications for intestinal symptoms of SARS-CoV-2</strong> - CONCLUSION: By virtue of its ability to modulate epithelial ACE2 expression and inhibit virus-mediated pro-inflammatory cytokine release, FXR represents a promising target for development of new approaches to prevent intestinal manifestations of SARS-CoV-2.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting spike glycans to inhibit SARS-CoV2 viral entry</strong> - SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PARP12 is required to repress the replication of a Mac1 mutant coronavirus in a cell- and tissue-specific manner</strong> - ADP-ribosyltransferases (ARTs) mediate the transfer of ADP-ribose from NAD^(+) to protein or nucleic acid substrates. This modification can be removed by several different types of proteins, including macrodomains. Several ARTs, also known as PARPs, are stimulated by interferon indicating ADP-ribosylation is an important aspect of the innate immune response. All coronaviruses (CoVs) encode for a highly conserved macrodomain (Mac1) that is critical for CoVs to replicate and cause disease,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and safety evaluation of Azvudine in the prospective treatment of COVID-19 based on four phase III clinical trials</strong> - Azvudine (FNC) is a synthetic nucleoside analog used to treat adult patients living with human immunodeficiency virus-1 (HIV-1) infection with high viral load. After phosphorylation, Azvudine inhibits RNA-dependent RNA polymerase, leading to the discontinuation of RNA chain synthesis in viruses. In addition, Azvudine is the first dual-target nucleoside oral drug worldwide to simultaneously target reverse transcriptase and viral infectivity factors in the treatment of HIV infection. On 9 August…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How a Culture War Over Race Engulfed a School District</strong> - After a ten-year-old took her own life, residents battled over whether her death was a tragic but isolated incident, or caused by a pattern of racist bullying. - <a href="https://www.newyorker.com/news/us-journal/how-a-culture-war-over-race-engulfed-a-school-district">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The U.A.W. Strike Threat Poses a Tricky Political Challenge for Biden</strong> - As the negotiating deadline approaches, the issues at stake go beyond wages and benefits to whether the union’s members will benefit or suffer from the transition to electric vehicles. - <a href="https://www.newyorker.com/news/our-columnists/the-uaw-strike-threat-poses-a-tricky-political-challenge-for-biden">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Real Stakes of the Google Antitrust Trial</strong> - The case, centering on Google’s dominance in the search-engine industry, will have implications that ripple throughout the tech world, and beyond. - <a href="https://www.newyorker.com/news/daily-comment/the-real-stakes-of-the-google-antitrust-trial">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Elvis Impersonator’s Summer of Extreme-Weather Weddings</strong> - Bob McArthur has lived in Las Vegas for only a year and a half, but has worked through the wettest monsoon in decades, a rare tropical storm, and the city’s hottest month ever. - <a href="https://www.newyorker.com/news/dispatch/an-elvis-impersonators-summer-of-extreme-weather-weddings">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Secret Life and Anonymous Death of the Most Prolific War-Crimes Investigator in History</strong> - When Mustafa died, in the earthquakes in Turkey, his work in Syria had assisted in the prosecutions of numerous figures in Bashar al-Assad’s regime. - <a href="https://www.newyorker.com/news/a-reporter-at-large/the-secret-life-and-anonymous-death-of-the-most-prolific-war-crimes-investigator-in-history">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>What happened to the family doctor?</strong> -
<figure>
<img alt="A doctor’s bag is surrounded by family photos." src="https://cdn.vox-cdn.com/thumbor/dIUuatqAmAr5tgjGShB7FvHmbpY=/298x0:1738x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72520935/Doctor_MinHeo.0.png"/>
<figcaption>
Min Heo for Vox
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Primary care is the foundation of American medicine — and it’s withering.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BHNieZ">
Soon after Dr. Gerard Weigel moved his family to Somerset, Kentucky, in the mid-1960s, he found himself not only the town’s only primary care doctor but the only doctor of any kind — the cardiologist, endocrinologist, and pulmonologist for each patient at his practice.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4TndrA">
In a 1967 Mercury Monterey — ”It looked just like Steve McGarrett’s car on <em>Hawaii Five-O</em>,” his son, Dr. Joseph Weigel, recalls — his father would drive around the town of 10,000 to see patients at their homes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aMgh0N">
“My father was an old-school general internist,” Joseph Weigel told me. “He was literally ‘the man’ here for all of those years.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YsG394">
Four of the eight Weigel children went into medicine, and Joseph, the oldest, decided to become a generalist like his dad, who is now 96. After graduating from medical school, Joseph Weigel started practicing in Somerset in the 1980s.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mIegnA">
At first, his career was based on relationships with patients, just like his dad’s. He felt he knew everything about them: their medical history, whether they had lost a job recently, if they had gone through a divorce. Early in his career, if one of his patients was admitted to the hospital, Weigel would follow them there. He would work in the critical care unit and sometimes even do surgical procedures, such as placing temporary pacemakers, because there was no other clinician around who could do it. Once his patients had been discharged, they would come back to his office. He would see the person through every step of their care.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5Jhd82">
But those patient-doctor relationships Weigel remembers have become a relic in the modern American <a href="https://www.vox.com/health-care">health care</a> system.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uAUZ7k">
Sam, Weigel’s son, remembers going out in public as a kid with his dad and they would often run into one of his dad’s patients. The respect they would show was one of the reasons Sam wanted to go into medicine. He, too, is now a doctor, the third generation in the family. But he works at the local hospital, where he sometimes treats a patient for a few days for an acute illness and then never sees them again.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WsR4sY">
“He has a completely different lifestyle, a completely different way of practicing medicine than either my father or I ever did,” Joseph Weigel said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZxnHHt">
Sam doesn’t envy the early mornings and late nights that Joseph would have to work back in those days to maintain his practice; his dad would come home from work and pop dinner in the microwave at 8 pm because he missed the family meal. But Sam recognizes he has missed out on something. “I haven’t had that same experience,” he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nz44JN">
Today, primary care is being squeezed from all sides. Long-standing patient-doctor relationships, once the foundation of medical treatment, are becoming less common: The number of Americans who say their source of medical care is a personal physician <a href="https://www.aafp.org/pubs/afp/issues/2015/1215/p1053.html">has been steadily declining</a>. That is especially true for younger patients: As of 2018, <a href="https://kffhealthnews.org/news/spurred-by-convenience-millennials-often-spurn-the-family-doctor-model/">nearly half</a> of adults under 30 said they did not have a primary care doctor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="l24CXr">
Many opt instead for the convenience offered by urgent care clinics, clinics in retail stores, and even their local emergency room.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WpDWEv">
The once-dominant model of an independent practitioner who ran their own practice, an entrepreneur as much as a physician, is less and less feasible. The overhead is prohibitive. Hospital systems and other corporate entities have absorbed <a href="https://www.medpagetoday.com/practicemanagement/practicemanagement/92451">the majority of America’s primary care workforce</a>. The field is becoming less attractive to aspiring doctors, who can <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388019/">make more money in another specialty</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5nUlhJ">
Patients are paying the price for America’s failure to invest in primary care. Clinical evidence <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/1468-0009.12638">indicates</a> that when patients have a steady primary care relationship, they tend to be healthier and live longer. But it is too hard for too many Americans to find and keep a primary care doc. By <a href="https://www.nachc.org/resource/closing-the-primary-care-gap-how-community-health-centers-can-address-the-nations-primary-care-crisis/">one recent estimate</a>, 100 million Americans face some kind of barrier (physical or financial) to accessing primary care. One in four Americans <a href="https://www.graham-center.org/content/dam/rgc/documents/publications-reports/reports/pcc-evidence-report-2022.pdf">doesn’t have a regular source of health care</a>, a share that has been steadily growing since 2000.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="c96vMH">
In the face of those headwinds, some primary care practices are trying to recapture what has been lost, to re-engage their patients and communities so that they might enjoy the benefits of having a long-term relationship with one physician. Some of these experiments rely on new technologies (such as for virtual visits) and on new business models (such as direct primary care practices and concierge-style clinics).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MKJRrF">
In one sense, primary care is trying to find a modern version of the kind of more personal medicine the elder Drs. Weigel practiced. Doctors say they are doing more home visits, holding later office hours, and setting up clinics in schools and workplaces. They are trying anything to meet their patients where they are, to salvage that core tenet of medical care Weigel and others fear is disappearing.
</p>
<h3 id="7LKkCB">
Why fewer and fewer Americans have a primary care doctor
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="G6CUxx">
Primary care doctors are intended to be patients’ first contact point with the health care system, the practice where people receive regular physicals, basic medical tests and treatment for mild illnesses, and are referred out to other doctors if their problems are serious.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="11Uh26">
These long-term relationships of mutual trust between doctors and patients are part of the foundation of American medicine. In the 1800s, the profession was in competition with home-based care and unscientific healers. It distinguished itself over time through professionalization, but also because doctors established their authority by settling down in a community, caring for patients’ medical needs for years. Paul Starr, in his acclaimed history <em>The Social Transformation of American Medicine</em>, quoted contemporary reports of patients in the 1840s and 1850s who would wait for hours at their doctor’s home until he returned from another call.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Tcclv2">
That image of the do-it-all primary care physician persisted for generations, well into living memory. Dr. Dominic Mack, a doctor for more than 30 years and the director of the National Center for Primary Care at the Morehouse School of Medicine, described growing up in Augusta, Georgia, where a handful of primary care doctors cared for most of the Black population. They admitted patients to the hospital and called in prescriptions. They would even deliver babies and perform general surgery.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Nx64vH">
“That one doctor retained the knowledge of your health throughout the system,” Mack told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Eyokqe">
In the early 1980s, three-quarters of US doctors <a href="https://c-hit.org/2021/04/07/can-independent-primary-care-doctors-survive-dominance-of-hospital-health-systems/">still owned</a> their own practice. But over the ensuing decades, that share would steadily drop. The push to control costs in the ’80s and ’90s led hospitals to start buying up more independent practices. Managed care — the idea that a single patient’s needs across the health system should be overseen in a more comprehensive way — made integrating physicians into a larger health system the logical move. Even as the craze for HMOs faded, doctors found it increasingly difficult to operate their own practices in competition with the growing hospital systems. Joining a larger system became more attractive, and hospitals were willing to put a lot of money down to get their foot in the primary care field.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eJP0yk">
Today, for the first time, fewer than half of doctors own their own practices. Doctors under 40 are <a href="https://www.ama-assn.org/system/files/2021-05/2020-prp-physician-practice-arrangements.pdf">much more likely</a> to work for somebody else than their older counterparts.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="la1cCU">
It’s not just the business side of primary care that is changing. Patients’ expectations are evolving, too. Even in the 1990s, Americans would often face <a href="https://www.aafp.org/pubs/fpm/issues/2000/0900/p45.html">much longer wait times</a> than they do now. But today’s patients no longer have the patience to wait for the doctor to see them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pO13rA">
A survey of physician staffing firms <a href="https://www.merritthawkins.com/physician-appointment-wait-times-up-from-2017/">observed</a> that wait times for primary care have actually dropped from a high of more than four weeks in 2017 to about three weeks in 2022. But that improvement was not really a sign that it was easier for patients to get an appointment. Instead, analysts at Merritt Hawkins wrote that “a growing number of patients are accessing primary care through urgent care centers, retail clinics, and telemedicine.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7CUUbn">
“What is unique about current times is the changes in patients’ expectations with immediacy of access to doctors. I don’t want to be on hold for 10 to 15 minutes. I don’t want to wait months for an appointment,” Ishani Ganguli, assistant professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, said. “It makes sense we as consumers and patients want that from our primary care.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lTOIVg">
So patients have sought out alternative options, prioritizing their convenience over the continuity that is increasingly hard to find.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NfXYFM">
Urgent care clinics have been around since the 1970s, but they have enjoyed a boom in the past decade. In 2014, there were<a href="https://enablecomp.com/2022/01/25/the-motivation-behind-the-proliferation-of-urgent-care-sites/"> about 6,400 urgent care clinics</a> in the US; that number had grown to<a href="https://www.cnn.com/2023/01/28/business/urgent-care-centers-growth-health-care/index.html"> more than 11,000 as of early 2023</a>. CVS and Walgreens have established in-store clinics built on a similar premise: You may not see the same doctor every time, but you can see a doctor quickly. Walmart began to adopt the same model in 2019, and the company plans to<a href="https://corporate.walmart.com/newsroom/2023/03/02/walmart-health-nearly-doubles-in-size-with-launch-into-two-new-states-in-2024"> double its health care footprint</a> by the end of 2024. Dollar General, which recently <a href="https://www.cnbc.com/2021/07/07/dollar-general-hires-chief-medical-officer-boosts-health-care-items.html">hired a chief medical office</a>r, appears to be on the same path.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HPB6JZ">
“We’re living in an era when people don’t have a relationship with a bank teller or hardware store,” said Dr. Yul Ejnes, who practices in Rhode Island and is the former chair of the American Board of Internal Medicine’s board of directors. Consumers expect service “24/7/365 … Health care has evolved in that way. People want what they want when they want it.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fWZl0t">
But something may be lost under the new model. Research has consistently found that a long-term relationship with a doctor leads to better health results. <a href="https://drive.google.com/file/d/1HzpEUqQTkpxm0gY6PLu54uUjA1zLi8Am/view">One recent analysis</a>, published in April of this year, found that when patients lose their longtime primary care doctor, the number of emergency department visits and hospital admissions increases, as does their mortality rate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iDGdfK">
“These effects were magnified if that relationship was longer in the first place. That really does align well with prior studies and clinical experience,” Ganguli told me. “A patient you meet for the first time may not believe you for good reason: They don’t know you. But over time, you build that relationship, that same advice carries a lot more weight.”
</p>
<h3 id="QhBZJV">
How primary care doctors are trying to reinvigorate their practices
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Viart6">
In some ways, the problems facing primary care are not new. Ejnes remembers being at a policy meeting in the mid-1990s when one of the agenda items was about a troublesome demographic: young adult men who had health insurance but who were not establishing relationships with primary care docs. The Washington Post <a href="https://www.washingtonpost.com/wellness/2023/04/17/mens-health-longevity-gap/">reported</a> on the same trend earlier this year.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jub55P">
But the problems are going to get worse as fewer doctors in training elect to practice primary care and more family physicians reach retirement age. Right now, according to a report from <a href="https://www.milbank.org/wp-content/uploads/2023/02/Milbank-Baseline-Scorecard_final_V2.pdf">the Milbank Memorial Fund</a>, 1 in 3 US doctors practices primary care, but among young doctors two years into their career, the share is only one in five. The Association of American Medical Colleges <a href="https://www.aamc.org/media/54681/download?attachment">projects</a> the country will be short as many as 48,000 primary care doctors by 2034.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4zh2wa">
The traditional fee-for-service model for financing medical care — in which doctors are paid based on how many appointments they have and how many tests they order — also contributed to primary care’s deterioration. Doctors have been rewarded for seeing as many patients as possible in a given day, not taking more time to establish closer relationships with them. Insurers and health systems have been slow to adopt so-called “value-based payments,” which could reward primary care’s contribution to patients’ long-term health.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Qu24jg">
Doctors characterize the new mode of health care as “industrial” or, as Ejnes put it, “transactional.” Thirty years ago, Ejnes told me, “it was just you and the patient in the exam room.” But today, “a dozen other people are there in spirit” — a performance evaluation team monitoring how the patient is faring with managing their diabetes, a billing team that decides how to code every service, an insurer that wants all this documentation in order to cover drugs or tests.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kpJHom">
As they feel intimacy with patients slipping away, doctors are turning to technology that promises to provide convenience: telemedicine, widely adopted during and after the pandemic, and new business models, particularly direct primary care and concierge-like clinics, that could eliminate some of the perverse incentives created by volume-based payments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ei1Td6">
For both primary and concierge care, patients pay a flat fee — a retainer of sorts — to establish a relationship with a doctor. In direct primary care, the doctor will typically make house calls for both check-ups and sick visits. That model has been growing quickly, with <a href="https://www.dpcare.org/about">an estimated 1,600 practices</a> across the United States, but still serves a small percentage of the population, about 300,000 patients. With concierge clinics, the best known of which is probably <a href="https://www.vox.com/amazon">Amazon</a>-owned One Medical (though it sometimes disavows the “concierge” label), patients can not only access their personal doctor on demand, they may also be enrolled in <a href="https://www.vox.com/health">wellness</a> programs and other perks the clinic offers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ypprwf">
Both models mean doctors are no longer dependent entirely on the number of services they provide. They have a steady source of income from patients’ membership fees. Ejnes noted that direct primary care was not as financially affected during the first few months of the pandemic, whereas regular independent practices saw a huge drop in patient visits and <a href="https://www.vox.com/2020/4/27/21231528/coronavirus-covid-19-primary-care-doctors-crisis">some were threatened with closure as a result</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NF6TSu">
Based on his conversations with colleagues, doctors at a regular clinic might have as many as 1,500 patients on their rolls; those in direct primary care or concierge care may carry only 500. The model gives physicians the leeway to give their patients the more personal touch without jeopardizing their livelihood.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tu8cEq">
“We have to understand, patients don’t necessarily want what we’ve been selling,” Ejnes said. “We can still offer the same good we would have offered 30 or 40 years ago, but in a contemporary way.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HdqcR5">
These ventures aren’t a cure-all. If every primary care doctor suddenly cut their patient roster in half, the shortages already in existence would get worse. And these clinics have often catered to upper-middle-class professionals living in cities, not marginalized communities where medical access is most constrained.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yNgaK7">
Even at more conventional practices, though, doctors are experimenting. What unites these disparate efforts to reinvigorate the field is, ironically, a return to the basics.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dhdnkg">
Dr. Oswaldo Bacani and Dr. Jennifer Bacani McKenney, father and daughter, are part of a practice in Fredonia, Kansas, that is taking an all-of-the-above approach to connecting with their patients.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dtJ2tn">
Bacani came to the US from the Philippines and settled down in Fredonia for what was supposed to be a one-year trial after his medical residency. But he and his wife liked the town so they stayed; they’ve now lived there for 45 years. At first, he was one of the do-it-all doctors, performing surgeries at the local hospital in the morning and seeing his primary care patients in the afternoon. But over time, he focused more on the latter. McKenney says she remembers watching cartoons in the back office of his primary care practice, watching the patients come and go.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2Xjv9s">
“The thing I always remembered is watching Dad interact with his patients. You could see it was personal,” she told me. “They would hug. They would laugh.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="t4diV8">
He would come home with pies his patients had made him. One time, a patient paid for surgery with a goat. The kids named it Peaches, after its favorite food.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="59YcP9">
“I’d see the way his patients loved him, the way they came up to him,” McKenney, who works with her father now at the hospital where she was born, said. “I never remember not wanting to be a doctor.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OkoDPr">
Even in their small town, where interpersonal relationships may come more naturally, they have noticed some disengagement from patients. Some people in Fredonia became more skeptical of medical experts after the Covid-19 pandemic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PBxpRA">
So their practice is reaching out to the community. They have started setting up flu shot clinics on-site at local businesses. They have considered contracting with local companies to act as a direct primary care provider for their employees. The practice has also set up a clinic at a local school so that students and teachers wouldn’t have to leave and come sit in their waiting room if they need care for something minor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fXdEk4">
Those attempts to bridge the patient’s desire for convenience while maintaining a long-term relationship with one practice could help arrest primary care’s decline. Ganguli told me she has begun holding office hours until 7 pm at least once a week, so it’s easier for people to come in after work, and she has seen employer-driven efforts to provide primary care up close after one Boston-area hospital <a href="http://ambulatory.healthdesign.org/clinic-design/clinic-examples/ambulatory-practice-future-apf">set up an on-site clinic for its employees</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rPI75z">
Ejnes, whose practice was recently acquired by a larger health system, said he and his colleagues have set up an after-hours co-op of sorts: They take turns being on call after regular business hours. Maybe the patient won’t see their own doctor, but they’ll at least see someone who knows their doctor. (It is a similar concept to the co-ops that are prevalent in the Netherlands, <a href="https://www.vox.com/policy-and-politics/2020/1/17/21046874/netherlands-universal-health-insurance-private">which Vox profiled a few years ago</a>.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yWgXZV">
This is what the new MO in primary care looks like. Meet the patients where they are. Lure them back with the kind of convenience that had prompted them to seek other options in the first place.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GbO5Ro">
“We’re not waiting for them to show up,” McKenney said.
</p></li>
<li><strong>How Israel’s court became so controversial</strong> -
<figure>
<img alt="A woman illuminated in red holding an Israeli flag outside the Supreme Court building." src="https://cdn.vox-cdn.com/thumbor/cIbBy0-p21q5UPjnCK65X5aZ07I=/407x0:4768x3271/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72645971/1659530657.0.jpg"/>
<figcaption>
An Israeli demonstrator holds up a flare outside the Supreme Court in Jerusalem, during a protest against Israeli Prime Minister Benjamin Netanyahu’s government plan to overhaul the judicial system on September 11, 2023. | Ilia Yefimovich/Picture Alliance/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The history behind Israel’s democratic crisis, explained.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HUATlr">
The Israeli Supreme Court is currently hearing arguments in a landmark case about itself.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JB83G6">
At issue is the first law passed in Prime Minister Benjamin Netanyahu’s judicial overhaul package — a new limitation on the court’s ability to overturn decisions made by Netanyahu and his cabinet it finds “extremely unreasonable.” This may sound like a small technocratic dispute, but in fact, the <a href="https://www.vox.com/2023/7/24/23805532/israel-judicial-overhaul-reasonableness">fundamental nature and even survival of Israeli democracy is at stake</a>. There’s a reason Netanyahu’s overhaul has spawned <a href="https://www.vox.com/2023/7/24/23805532/israel-judicial-overhaul-reasonableness">the largest protest in Israeli history</a>: The attack on the court is seen, by millions of Israelis, as an attack on Israeli democracy itself.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="id__l70znpt4cw">
“Absolute power corrupts absolutely, and while this government may not abuse its power, when the power is there, it will be used,” Aner Helman, the lawyer representing <a href="https://www.vox.com/israel">Israel</a>’s attorney general, said in Tuesday’s hearing while arguing the new law should be overturned. Helman’s argument was notable not only for its seriousness, but also for the fact that he is a government attorney who typically defends its policies in court.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0bR0VC">
To understand how the judiciary became <em>the</em> policy issue in Israeli politics, one potent enough to turn core state institutions against each other, you need to understand a series of profound and overlapping tensions in Israeli Jewish society — divisions between the religious and the secular, between the right wing and the center left, and between Netanyahu and the country’s traditional political establishment. All of these tensions are connected to perhaps the central philosophical question of Israeli politics: What does Israel’s core legal identity as a “Jewish and democratic” state mean?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LErBKs">
For years, it seemed possible that this fundamental issue could be worked out within the confines of the existing political and legal system. But the rise of the Israeli far right in the past two decades, and Netanyahu’s fateful decision to join ranks with them, pushed things well outside “normal” political parameters. The court is the last institutional bulwark standing in the way of a series of far-right initiatives on everything from the Palestinian conflict to the role of religion in public life. The far right wants to smash through this guardrail, and has the votes in the Knesset (Israeli parliament) to do so.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ywyHq3">
Many specific developments in Israeli politics, ranging from controversial Supreme Court rulings to Netanyahu’s trial on corruption charges, came together to make the attack on the court possible. A democratic “perfect storm” created a unique opportunity for the right to permanently resolve the central dilemma of Israeli politics on their terms — and galvanized those committed to alternative visions of Israel to fight for a court they see as their last best hope.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="92PX4G">
This week’s case, then, is not just about a specific judicial power. It is part of a bigger fight over whether the right will be allowed to continue redefining the Israeli state along illiberal and anti-democratic lines — and whether the Supreme Court is willing to risk a constitutional crisis to stop them.
</p>
<h3 id="kAXBXK">
The conflicts at the heart of Israeli identity
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HgZvVx">
Israel does not have a formal constitution. Instead, it has what are called “Basic Laws” — laws that create a kind of constitution-lite amendable by a simple majority vote in the Knesset. The current crisis stems from <a href="https://www.vox.com/2023/7/24/23805532/israel-judicial-overhaul-reasonableness">a new Basic Law</a>, passed this June, that eliminates courts’ power to overturn decisions by Israel’s cabinet or its ministers that they find to be “extremely unreasonable” — meaning decisions that the government can’t prove were made according to some <a href="https://en.idi.org.il/articles/50104">basic standards of fair and just policymaking</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lJv9ny">
Such a standard for judicial review might seem overbroad in the United States. But it’s actually <a href="https://www.nytimes.com/article/israel-judicial-overhaul-vote.html">relatively common internationally</a>, and Israel in particular has a need for it given that it has no constitution, no federal system, and no separation of executive and legislative powers. The courts are basically the only check on decisions made by the elected government — and the current government, a far-right coalition led by Prime Minister Benjamin Netanyahu, is trying to weaken the judiciary’s powers and pack the courts with ideologically friendly jurists.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BhzJFv">
At issue in this week’s case, in part, is whether the court can do something it’s never done before: overturn a new Basic Law on grounds that it conflicts with <em>other </em>Basic Laws. The issue is not just whether this one change to the law is defensible. It’s an existential question of how the basic contours of the Israeli political system are to work.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ENFptF">
To understand just why the stakes have gotten so high, it’s necessary to dwell on the definition of the state as both “Jewish and democratic” — which is not only a guiding vision for the state but also an identity legally inscribed in the Basic Laws.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Kl43wr">
The idea, at least in theory, is that Israel is supposed to be at once a distinctly Jewish state and a democratic state founded on liberal ideas of equality and human rights.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uPhH97">
“Compatibility between the democratic and Jewish-Zionist character of the state is a cornerstone in the ideology of all Zionist political parties in Israel and the opinion of the overwhelming majority of the Jews,” the <a href="https://www.jstor.org/stable/30246820">Israeli sociologist Sammy Smooha argued in the late 1990s</a> (while noting that “from this Jewish consensus, ultra-nationalists dissent.”)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RxIg6Z">
In practice, Smooha argues, there are obvious tensions between these two prongs of its self-identity — ones inherent to the “Jewish and democratic” concept itself and thus evident since the state’s creation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hHZUWZ">
One of Israel’s foundational aims is to serve as a homeland for Jews around the world and a refuge for those facing persecution. As such, Israeli immigration policy allows for Jews anywhere to move to Israel and become a citizen. But the same immigration rights are not extended to anyone who isn’t Jewish. Ethnoreligious discrimination is, by design, a central part of Israeli immigration law.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DBEWmI">
It gets thornier. The question of what it means to be a “Jewish” state is contested, to put it mildly. Religious extremists believe the government should be based on halakah (Jewish law), while staunch secularists believe the Israeli state should play no role at all at in strictly religious matters. Most Israeli Jews <a href="https://en.idi.org.il/media/19697/the-israeli-democracy-index-2022.pdf">fall somewhere along that spectrum</a>, leading to bitter fights on a series of specific policy questions (like whether public transportation should be open on Shabbat).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JYeLpA">
There’s also the critical question of non-Jewish citizens.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="si9CiU">
After the Israeli War of Independence, the Arab Palestinian population that remained inside its borders were granted citizenship but put under martial law — a not-very-democratic legal arrangement that remained in place until 1966. Today, Arab citizens make up around 20 percent of the population, and are subject to <a href="https://www.cfr.org/backgrounder/what-know-about-arab-citizens-israel">frequent discrimination</a> in areas like <a href="https://www.haaretz.com/israel-news/business/real-estate/2023-04-11/ty-article/.premium/dont-call-it-a-housing-crisis-the-discriminatory-plight-of-israeli-arabs/00000187-526f-dde0-afb7-7e7f62cc0000">housing</a> and <a href="https://www.bbc.com/news/world-middle-east-58183954">policing</a>. And that’s to say nothing of the authoritarian military occupation that noncitizen Palestinians live under in the West Bank.
</p>
<figure class="e-image">
<img alt="Protest against government’s indifference on the increase in crime rates in Israel" src="https://cdn.vox-cdn.com/thumbor/w7OvObu8gOhnjX3w8UZ24YM60no=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24918891/1581702086.jpg"/> <cite>Mostafa Alkharouf/Anadolu Agency/Getty Images</cite>
<figcaption>
A protest march against the government’s indifference on the increase in crime rates among Palestinian citizens of Israel at Habima Square in Tel Aviv, Israel, on August 6, 2023.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6PWjWY">
For this reason, Smooha argues that Israel is a very particular kind of democracy: an “ethnic democracy” that “combines the extension of civil and political rights to individuals and some collective rights to minorities with institutionalization of majority control over the state.” Such a state is split between the “democratic principle,” which prioritizes “equal rights and equal treatment of all,” and the “ethnic principle,” which prioritizes “fashioning a homogenous nation-state and privileging the ethnic majority.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Q7c8F2">
Managing this tension is difficult both philosophically and legally. There will always be specific cases that push the limits of what the laws, Basic or otherwise, have set as legal standards for managing Israel’s dual identity.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="czBuCC">
This means Israel’s courts are, by necessity, regularly called upon to make judgments about the most fundamental issues surrounding the nature of Israeli state and society. While courts in every country make controversial decisions, few face the kind of existential questions about the country’s survival and purpose that Israel’s do.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="02ifLu">
As a result, the court’s judgments were bound to attract anger from the losing side in major cases — ones that might lead them to attack the institution itself. In fact, that’s been happening since the state’s earliest days.
</p>
<h3 id="Fqfpjy">
The long history of struggle over the courts
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="crWrGL">
In a 2021 paper <a href="https://tcf.org/content/report/assault-israels-judiciary/">on the history of political conflict over the court system</a>, Israeli scholar Dahlia Scheindlin finds an almost immediate post-independence conflict between secular and ultra-Orthodox Israelis about the proper role of the judiciary — to the point where Israel’s leading rabbis actually boycotted the opening ceremonies for the Supreme Court in 1948.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AHumcf">
“For certain groups in society, there has never even been full agreement over the role and authority of civil law versus religious law. In turn, the institutions of justice have been flashpoints of tension from the earliest years of statehood — and none more than the Supreme Court,” Scheindlin finds.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7zUdsB">
After Israel seized the West Bank and Gaza Strip in the 1967 Six-Day War, the country was faced with a whole new set of legal questions surroundings its military occupation of those lands. These, too, implicated fundamental questions of Israeli identity. What lands, exactly, should constitute its final borders? Should biblical descriptions of ancient Jewish land have any authority over present-day policy? And how could Israel be a democracy of any kind when it ruled over a Palestinian population who would never be permitted the rights of citizens?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="US9oFJ">
The settlement enterprise — a campaign by religious nationalist Israelis to establish towns designed to cement control over Palestinian land, aided and abetted by the government — forced the court to weigh in on these weighty disputes. Typically, the court deferred to the the settlers, especially when the government claimed that establishing settlements in a particular area was a matter of national security.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="w7RPqa">
But in 1979, the court ruled that a new settlement called Elon Moreh could not be justified on any legal grounds, security or otherwise. It ordered that the settlement be moved. The settlers were furious, with their spokespeople <a href="https://www.haaretz.co.il/opinions/2018-11-27/ty-article-opinion/.premium/0000017f-eaae-d0f7-a9ff-eeef31240000">almost immediately</a> calling for political war on the legal system.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vPXggb">
“We must create a team of jurists for whom the matter of settlements is close to their hearts, in order to solve legal problems and prevent mishaps,” one said. “If democracy begins to interfere with the building of a Jewish state, we must give up democracy,” said another.
</p>
<figure class="e-image">
<img alt="(FILE) Right-Wing Israelis Establish First West Bank Settlements" src="https://cdn.vox-cdn.com/thumbor/QbprQ-foUHULaAq0hajFdvrSZaQ=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24918898/53023408.jpg"/> <cite>Chanania Herman/GPO/Getty Images</cite>
<figcaption>
An Israeli soldier on guard duty outside mobile homes at the settlement of Elon Moreh on November 21, 1979.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KFMzWq">
The political resentment of both groups, the ultra-Orthodox and the settlers, became supercharged in the 1990s — the decade where it seemed most likely that the Israeli state might settle on a more liberal answer to the Jewish/democratic tension.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dx8s5n">
In 1992, the Knesset enacted two new Basic Laws that significantly expanded the scope of Israeli protections of individual rights. Protections for “human dignity” and “liberty,” specifically included “to embed the values of the State of Israel as a Jewish and democratic state in a basic law,” created significant grounds for courts to declare legislation at odds with the Basic Law.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VVtnJY">
Supreme Court Justice Aharon Barak declared this to be a “<a href="https://openyls.law.yale.edu/bitstream/handle/20.500.13051/3114/A_Constitutional_Revolution_Israel_s_Basic_Laws.pdf">constitutional revolution</a>.” In the following years, the court would rule that the the new Basic Laws included a fundamental right to equality for all Israelis, an idea that struck at the heart of both the ultra-Orthodox and settler visions for the state. A state that protects equality cannot privilege one ethnoreligious group in the institutionalized way these groups believed it should.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mYGnfU">
Not coincidentally, this constitutional revolution happened at the same time as the Oslo peace process with the Palestinians. The agreements, which set up the Palestinian Authority as a temporary self-rule mechanism until a final peace agreement could be reached, threatened to destroy the settlement enterprise altogether.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yN2KpF">
It hasn’t played out that way: The occupation of Palestinian land is now so entrenched that leading <a href="https://www.btselem.org/publications/fulltext/202101_this_is_apartheid">human</a> <a href="https://www.amnesty.org/en/latest/campaigns/2022/02/israels-system-of-apartheid/">rights</a> <a href="https://www.hrw.org/news/2021/07/19/israeli-apartheid-threshold-crossed?gclid=CjwKCAjwu4WoBhBkEiwAojNdXu4gUW0ZbBMQgI-v_vf5ywQxInrnyHBMWAqvFYCAP04z8XX-zEd53RoCOSkQAvD_BwE">groups</a> have described the situation as a form of apartheid. But at the time, the Israeli state seemed on the verge of moving its “ethnic democracy” in a more liberal direction: one in which the power of religion over private life was minimized, and Jewish supremacy from the river to the sea foreclosed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="smVeNj">
The court, being a central agent of this overall change, was obviously a major target of its enemies’ anger at this development. The question is not why they wanted to weaken the court, but whether they’d ever be strong enough to do it.
</p>
<h3 id="2TStux">
The court’s perfect storm
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7uvmQc">
The 21st century has, broadly speaking, marked the decline of the Israeli left and the rise of its far right.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fxqXrI">
The Oslo peace process failed, devolving into the bloodshed of the second intifada in the early 2000s. When Israel withdrew from Gaza in 2005, dismantling and evacuating Jewish settlements, the result was the Strip’s conquest by the militant Hamas faction. Israelis soured on the feasibility of a negotiated settlement with the Palestinians — and the political left that had long championed peace accords. Through it all, Israel expanded West Bank settlements and deepened the occupation, in ways that <a href="https://www.vox.com/policy-and-politics/2020/2/27/21075868/israeli-democracy-war-netanyahu">necessarily degraded the quality of its democracy</a> inside its legally recognized borders.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="okSL67">
As the left lost influence, Israeli politics lurched to the right. Netanyahu, the leader of the historically center-right Likud party, ruled the country between 2009 and 2021 — at the helm of coalition governments that, over time, became increasingly dependent on settler and ultra-Orthodox parties. This manifested in an increasingly hostile policy approach toward the courts.
</p>
<figure class="e-image">
<img alt="Netanyahu embraces and shakes hands with Ben-Gvir." src="https://cdn.vox-cdn.com/thumbor/78U9p8mj6XbLtIavW3YUjXWchpI=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24918906/1257512457.jpg"/> <cite>Gil Cohen-Magen/AFP/Getty Images</cite>
<figcaption>
Israeli Prime Minister Benjamin Netanyahu, left, greets National Security Minister Itamar Ben-Gvir, from the extremist Jewish Power party, in May 2023.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZVPZ5J">
From 2015 to 2019, Netayahu’s justice minister — a Knesset member named Ayelet Shaked from a far-right settler party — made a series of efforts to try to bring the courts to heel. She worked hard to politicize Israel’s nonpartisan process for appointing judges, bragging about getting<a href="https://www.timesofisrael.com/justice-minister-high-court-no-longer-a-branch-of-left-wing-meretz-party/"> a record number of conservatives on the bench</a>. She stripped the high court of its jurisdiction over West Bank land issues, handing it to a Jerusalem circuit more friendly to the interests of settlers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iWZzC0">
By the time she left the Justice Ministry, she claimed to have “broken” the vision of the judiciary championed <a href="https://www.haaretz.com/israel-news/2019-01-08/ty-article/.premium/israeli-justice-chief-i-broke-the-old-conception-of-the-justice-system/0000017f-e962-dc91-a17f-fdef8e4f0000">by Aharon Barak</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0DychO">
But this wasn’t enough for the settler radicals Shaked represented. Their aim was not merely to weaken the court, but to eliminate it as a potential threat to their enterprise and ethnonationalist vision of what a “Jewish and democratic” state means. In particular, the settler parties viewed the court’s remaining power to block the seizure of private Palestinian land as a significant barrier <a href="https://www.washingtoninstitute.org/policy-analysis/israel-expands-settlements-smotrich-increases-his-authority">to building up settlements in places that would make the foundation of a Palestinian state maximally difficult</a>. For the settlers to accomplish their dream of Jewish supremacy from the river to the sea, the judiciary needs to be fully brought to heel.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qH07Fu">
In this campaign, both the ultra-Orthodox and Netanyahu became willing allies — for their own reasons.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YBSLZV">
In the past decade, the courts have issued a series of rulings on issues like<a href="https://www.washingtonpost.com/world/2021/07/11/israel-lgbtq-surrogate-parents/"> same-sex parenting</a>, <a href="https://www.nytimes.com/2021/03/01/world/middleeast/israel-jewish-converts-citizenship.html">non-Orthodox Jewish conversion</a>, and (most importantly) <a href="https://www.nytimes.com/2017/09/12/world/middleeast/israel-ultra-orthodox-military.html">mandatory military service</a> that have infuriated the ultra-Orthodox. Reining in the court, in their mind, is necessary not only to preserve their particular vision of a religious Jewish state but also to protect their community from outside secular influence.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qdPmnP">
Netanyahu’s interest is less ideological and more practical: He is currently <a href="https://www.vox.com/policy-and-politics/23301390/trump-investigation-mar-a-lago-search-netanyahu">being tried on charges related to alleged corrupt and anti-democratic behavior</a>. The more the prime minister and his allies control the judiciary, the easier it will be for him to use his position to stay in power and out of jail. He aimed, in short, to weaken the democratic character of the Israeli state in order to protect himself from legal accountability.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jL1saf">
These three factions — the pro-settlement parties, Netanyahu’s Likud, and the ultra-Orthodox — do not always agree on everything. But they each have every reason to put an assault on the powers of the judiciary first. And when they won the November 2022 election, returning Netanyahu to the top post after a mere year in opposition, that’s exactly what happened. The new government’s first big act was to introduce an omnibus bill containing a series of reforms designed to bring the court system to heel.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a8rV4m">
In theory, there was nothing the opposition could do to stop them. The coalition had a Knesset majority, which was all they needed to amend Basic Laws. But the public reaction to their proposed power grab was astonishingly negative, going merely beyond <a href="https://www.reuters.com/world/middle-east/israels-netanyahu-down-polls-over-judicial-reform-2023-07-26/">bad poll numbers</a>. The proposals so spooked Israelis on the center and the left, who had counted on the courts to check Netanyahu’s extreme-right government, that they turned out to protest in record numbers.
</p>
<figure class="e-image">
<img alt="Protests continue against Israel’s controversial judicial reform" src="https://cdn.vox-cdn.com/thumbor/bnkDBuc1eq_OEdrZgTjEz1e6O_4=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24918913/1659527328.jpg"/> <cite>Stringer/Anadolu Agency via Getty Images</cite>
<figcaption>
An aerial view shows people during a Jerusalem demonstration against the government’s judicial reform on September 11, 2023.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7pIqhT">
Throughout 2023, Israeli cities have seen weekly mass protests against the judicial overhaul — the largest social movement in the country’s history. These protests were disruptive enough to scare the government into backing down from first version of the judicial overhaul, which would have imposed a series of major curbs on court power all at once. But the court overhaul was too important for the government to abandon; it was, after all, the glue binding together its three major factions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UaaFzw">
So instead, the government chose to enact its overhaul piecemeal: doing one component at a time, a tactic for deliberately eroding a democracy that political scientists call “<a href="https://en.idi.org.il/articles/50283">salami slicing</a>.” The reasonableness bill was the first cut of the meat log; everyone expects there to be more coming soon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6RDIoF">
This showdown over the courts, then, is really a showdown between fundamentally incompatible visions of what it means to be Jewish and democratic — a crystallized struggle over the kind of country that Israel is to be. No wonder it’s dividing Israelis starkly: It could very well decide their collective future.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1ujLi6">
</p></li>
<li><strong>Lead poisoning could be killing more people than HIV, malaria, and car accidents combined</strong> -
<figure>
<img alt="A thin, dark-skinned infant with an oxygen tube wrapped around their face and a blanket covering their body lies on a bed as their mother, in a dark red dress and black headscarf, sits looking on. " src="https://cdn.vox-cdn.com/thumbor/IPgsXcLrp52eLOYh2Dw_S2qvCpw=/374x0:6347x4480/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72645940/1193579475.0.jpg"/>
<figcaption>
A mother and child at a Médecins Sans Frontières clinic in Anka, Nigeria, the site of a major lead poisoning outbreak in 2019. | Kola Sulaimon/AFP via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
However bad you think lead poisoning is for the world, it’s worse.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Emwqyv">
Everyone knows <a href="https://www.vox.com/future-perfect/22834666/lead-exposure-poisoning-developing-countries">lead is bad for you</a>. We’ve known this for a very long time: in the first century BCE, the <a href="https://www.jstor.org/stable/504874">Roman architect Vitruvius</a> warned against using lead in pipes, observing the “pallid color” of plumbers forced to work with it. We know <a href="https://arefiles.ucdavis.edu/uploads/filer_public/d6/2d/d62d46a3-8558-48a7-bbdc-1c9183b47482/hollingsworth_rudik.pdf">leaded gasoline leads to premature death</a> in the elderly, that high lead exposure can <a href="https://jamanetwork.com/journals/jama/fullarticle/2613157">substantially reduce IQ</a>, and that there is likely a relationship between <a href="https://www.manhattan-institute.org/verbruggen-lead-and-crime-review-evidence">lead exposure in children and high rates of crime later on</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j4W75C">
Yet lead is still everywhere — especially in poorer countries. <a href="https://www.pureearth.org/our-projects/global-lead-program/">Pure Earth</a>, the largest nonprofit working on lead contamination internationally, recently conducted a <a href="https://www.pureearth.org/rapid-market-screening-program/">massive survey of products</a> in 25 low and middle-income countries, from Peru to Nigeria to India to the Philippines, to test for lead levels in household goods. In their sample they found high levels of lead in 52 percent of metal and 45 percent of ceramic foodware (a category including dishes, utensils, pots and pans), as well as 41 percent of house paints and 13 percent of toys.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Aarkxx">
This has major consequences. A <a href="https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(23)00166-3/fulltext">new paper in <em>Lancet Planetary Health</em></a>, authored by economist Bjorn Larsen and Ernesto Sánchez-Triana, World Bank’s global lead for pollution management, tries to quantify the scale of the lead problem globally.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uDQeBm">
The authors estimate that some 5.5 million people die prematurely due to lead exposure every year, and that the problem as a whole imposes a social cost of $6 trillion a year. That equals 6.9 percent of total world GDP.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xzTLvr">
These are massive numbers, and it’s worth putting them into context: 5.5 million deaths from lead in 2019 exceeds the <a href="https://ourworldindata.org/grapher/annual-number-of-deaths-by-cause">number of people who died that year</a> from car accidents (1.2 million), tuberculosis (1.18 million), HIV/AIDS (863,837), suicide (759,028), and malaria (643,381) <em>combined</em>. If accurate, the figure means that a little under <a href="https://ourworldindata.org/births-and-deaths#how-many-people-die-each-year">one in 10 deaths globally can be traced to lead</a>. Meanwhile, a social cost of 6.9 percent of global GDP exceeds a <a href="https://documents.worldbank.org/en/publication/documents-reports/documentdetail/455211643691938459/the-global-health-cost-of-pm-2-5-air-pollution-a-case-for-action-beyond-2021">recent World Bank estimate of the social cost of air pollution</a>, which added up to 6.1 percent of GDP.
</p>
<h3 id="eeAeRt">
Digging into the cost of lead
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fQVHHP">
These massive numbers may seem more plausible when you consider just how prevalent serious lead exposure is in developing countries.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5qLh8a">
A <a href="https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(20)30278-3/fulltext">2021 evidence review</a> led by environmental scientist Bret Ericson reviewed blood lead surveys in 34 nations, which together account for <a href="https://docs.google.com/spreadsheets/d/1uST1PWOCCKfwLpj2oQccKv7gR5K5gHQYpdNHBcw3hyk/edit?usp=sharing">over two-thirds of the world’s population</a>. Overall, those studies estimated that 48.5 percent of children had high lead levels (defined as above 5 micrograms per deciliter, or µg/dL). Levels of exposure varied greatly, with surveys in a few countries (like Tanzania) not finding any children with blood lead levels above 5 µg/dL, and other countries (like Pakistan) showing huge majorities with levels that high. (Of course, it’s possible that limitations in these surveys underestimate lead exposure in some countries.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oyQHBH">
We can identify a number of possible sources of these high lead levels. Historically, the major driver was lead in gasoline, but in 2021 the last country on Earth still using lead for that purpose (Algeria) <a href="https://www.vox.com/future-perfect/22650920/leaded-gasoline-eradicated-public-health">phased it out</a>. Lead is widely used in car batteries, plane fuel, and the consumer goods that Pure Earth surveyed in its report, but which source is most important in contributing to poisoning in children is still unclear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="irloH4">
For one thing, we know surprisingly little about how lead in, say, a plate translates into lead in the system of a human eating off that plate. The Pure Earth study included a test of some aluminum cookware, wherein it boiled acetic acid (the main ingredient in vinegar) in them for two hours, and then tested the liquid for lead. Fifty-two percent of the pots had leached an amount of lead above the World Health Organization guideline level for drinking water. That suggests that food cooked in such pots would contain lead, which would then poison children who drink it. But much more research is needed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V7a4s7">
Indeed, “more research is needed” is a decent summary for the whole state of lead research. The <em>Lancet Planetary Health</em> study finding that lead kills 5.5 million people a year relied on lead poisoning estimates from the <a href="https://www.healthdata.org/research-analysis/gbd">Global Burden of Disease study</a>, which sometimes produces its numbers not based on surveys of actual people, but on other data (like the share of population in urban areas, and the year that leaded gasoline was phased out) that is in turn predictive of lead exposure.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iTr9HQ">
Further, the <em>Lancet</em> study estimates deaths caused by lead-induced cardiovascular disease based on studies of the US, estimating the effect of lead on cardiovascular disease rates. Air pollution expert Roy Harrison told the news agency AFP that applying such findings to the whole world is “<a href="https://medicalxpress.com/news/2023-09-poisoning-death-iq-loss-thought.html">a huge jump of faith</a>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2xf61r">
That said, any errors could go in both directions. The actual surveys that Ericson and coauthors compiled of blood lead levels showed that the problem was <em>worse </em>than the Global Burden of Disease data suggested. It might be that lead is a greater risk factor for cardiovascular disease in poor countries than in the US, because there are more medical resources to counter the negative effects of lead in the US. All of that could mean the new study actually underestimates the damage lead is doing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sh0iVy">
The only way to have a stronger sense of the scale of the problem is to invest more in understanding it. A <a href="https://rethinkpriorities.org/publications/global-lead-exposure-report">2021 report</a> found that nonprofits spend, at most, $10 million a year addressing lead exposure in developing countries, with much of that money coming from governments. For comparison, global efforts to fight HIV/AIDS, which, if this new report is to be believed, kills about one-fifth as many people globally as lead does, got <a href="https://www.kff.org/global-health-policy/press-release/in-2022-donor-governments-spent-us8-2-billion-on-efforts-to-fight-hiv-aids-globally/#:~:text=The%20U.S.%20continues%20to%20be,%25%2C%20US%24191%20million).">$8.2 billion in government funding</a> in 2022 alone.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n0cY88">
The point here is not that we’re spending too much on HIV/AIDS — we may still be spending too little there too. But we’re spending far<em> </em>too little on understanding and tackling lead exposure, when it could be a problem of similar or greater magnitude. It’s among the most neglected problems in global health, and one where a substantial investment could go a long way.
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Asia Cup 2023 | Pakistan opt to bat against Sri Lanka in Super 4 match</strong> - The toss was delayed due to inclement weather and the contest has been reduced to 45-overs per-side affair. The winner will face India in the final of the Asia Cup on Sunday.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hall Of Grace and Raffaello show out</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Diamond And Pearls and Danny’s Girl impress</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What did Muttiah Muralitharan say to umpire Darrell Hair years after the chucking controversy?</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Asia Cup 2023 | Rain delays toss in Sri Lanka-Pakistan virtual semifinal clash</strong> - The winner of this match will be facing India in the Asia Cup 2023 finals on September 17, 2023.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Government further cuts stock limit on wheat traders, wholesalers &amp; big chain retailers amid uptick in prices</strong> - The stock limit has been reduced to 2,000 tonnes as the government found there is an “an uptick in the wheat prices on the NCDEX by 4% to Rs. 2,550 per quintal in the past one month”</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Programme to distribute menstrual cups inaugurated in Chennai</strong> - Under the ‘Thinkal’ project, envisaged to distribute menstrual cups to 1,500 women, launched by South Chennai MP Thamizhachi Thangapandian</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bihar boat capsized: 12, including six children, go missing</strong> - The boat was said to be carrying over 30 people, including several school going children, overturned mid-stream in river Bagmati at Madhupur Patti ghat in Muzaffarpur district</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ahead of festive season, Nepal to import 20,000 MT sugar from India</strong> - Nepal’s domestic demand for sugar stands at 3,00,000 MT.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>‘Emergency era mindset’ is alive in INDIA parties, says Nadda</strong> - Reacting to the INDIA bloc move to draw up a list of TV anchors to boycott, the BJP chief said that the Opposition alliance was only interested in “bashing Sanatan Sanskriti” and “bullying the media”</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Russian air defence system destroyed in Crimea, Ukraine says</strong> - A Ukrainian official tells the BBC the air defence system was destroyed in a cruise missile attack.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rogue Russian pilot tried to shoot down RAF aircraft in 2022</strong> - The pilot fired two missiles - the first missed rather than malfunctioned, as was claimed at the time.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>France sets out plan to ban disposable vapes</strong> - France joins several other European countries that are trying to stop children using e-cigarettes.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Isa Balado: Man arrested after touching Spanish reporter during live broadcast</strong> - Isa Balado was interrupted during a live broadcast when a man appeared to touch her bottom.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UK and Irish nationals ill after Bordeaux sardines</strong> - Multiple people need hospital treatment after contracting botulism at a restaurant in the city.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>With 0-days hitting Chrome, iOS, and dozens more this month, is no software safe?</strong> - With 70 zero-days uncovered so far this year, 2023 is on track to set a new record. - <a href="https://arstechnica.com/?p=1968268">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Even more Google layoffs: This time it’s “significant” cuts to recruiting</strong> - Google plans to slow down hiring, and that means fewer recruiters. - <a href="https://arstechnica.com/?p=1968202">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AI can now generate CD-quality music from text, and it’s only getting better</strong> - Musicians: Speak now or forever hold your beats. - <a href="https://arstechnica.com/?p=1968056">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dealmaster: Coffee gear, iPhone 15 accessory discounts, and more</strong> - We have the usual tech stuff and some extras for making the day-to-day easier. - <a href="https://arstechnica.com/?p=1968070">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Calif. passes strongest right-to-repair bill yet, requiring 7 years of parts</strong> - Repair shops must disclose if they’re using “non-authorized” parts. - <a href="https://arstechnica.com/?p=1968123">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A duck walks into a tavern and orders a beer.</strong> - <!-- SC_OFF --></p>
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The bartender thinks “Wow, a talking duck,” and pours him a beer.
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The bartender asks “I don’t think I’ve seen you in here before. Do you live in the neighborhood?”
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The duck says “No, I live across town. I’m a drywaller, and I’m working the office renovation across the street. I just dropped in for a beer before going home for the day.”
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The bartender, while trying to imagine how a duck handles drywall, asks “Well, how is that drywall job treating you?”
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The duck says “Well, as you know, this isn’t a union town. The pay isn’t that great, but it pays the rent and keeps me in duck food. I get along with the other trades, so I guess it’s O.K.”
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The bartender says "I have a friend who runs a circus. Would you like to talk to him about a gig with the circus?
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The duck said “That’s ridiculous. What would a circus want with drywall?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/BobT21"> /u/BobT21 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16i4aeq/a_duck_walks_into_a_tavern_and_orders_a_beer/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16i4aeq/a_duck_walks_into_a_tavern_and_orders_a_beer/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The other night I was invited out for a night with “the girls.” I told my husband that I would be home by midnight. “I promise!” Well, the hours passed and the margaritas went down way too easy. Around 3 a.m., a bit blitzed, I headed for home.</strong> - <!-- SC_OFF --></p>
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Just as I got in the door, the cuckoo clock in the hall started up and cuckooed 3 times. Quickly realizing my husband would probably wake up, I cuckooed another 9 times. I was really proud of myself for coming up with such a quick-witted solution (even when totally smashed), in order to escape a possible conflict with him. The next morning my husband asked me what time I got in, and I told him midnight. He didn’t seem disturbed at all. (Whew! Got away with that one!). Then he said, “We need a new cuckoo clock.” When I asked him why, he said, “Well, last night our clock cuckooed 3 times, then said,”Oh, crap," cuckooed 4 more times, cleared its throat, cuckooed another 3 times, giggled, cuckooed twice more, and then tripped over the cat and farted."
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16hk7js/the_other_night_i_was_invited_out_for_a_night/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16hk7js/the_other_night_i_was_invited_out_for_a_night/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What’s the difference between kinky and perverted?</strong> - <!-- SC_OFF --></p>
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Kinky is when you tickle your girlfriend with a feather, perverted is when you use the whole bird.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/TheQuietKid22"> /u/TheQuietKid22 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16ibn9f/whats_the_difference_between_kinky_and_perverted/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16ibn9f/whats_the_difference_between_kinky_and_perverted/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Escapee……..</strong> - <!-- SC_OFF --></p>
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A man escapes from prison where he has been for 15 years.
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He breaks into a house to look for money and guns and finds a young couple in bed.
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He orders the guy out of bed and ties him to a chair, while tying the girl to the bed he gets on top of her, kisses her neck, then gets up and goes into the bathroom.
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While he’s in there, the husband tells his wife: "Listen, this guy’s an escaped convict, look at his clothes! He probably spent lots of time in jail and hasn’t seen a woman in years.
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I saw how he kissed your neck. If he wants s*x, don’t resist, don’t complain, do whatever he tells you. Satisfy him no matter how much he nauseates you.
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This guy is probably very dangerous. If he gets angry, he’ll k*ll us. Be strong, honey. I love you."
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To which his wife responds: “He wasn’t kissing my neck. He was whispering in my ear. He told me he was gay, thought you were cute, and asked me if we had any vaseline. I told him it was in the bathroom. Be strong honey. I love you too!”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MercyReign"> /u/MercyReign </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16i4pzm/escapee/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16i4pzm/escapee/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Naked Cowboy</strong> - <!-- SC_OFF --></p>
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The Sheriff in a small town walks out in the street and sees a blond cowboy coming down the walk with nothing on but his cowboy hat, gun, and his boots, so he arrests him for indecent exposure.<br/> As he is locking him up, he asks “Why in the world are you dressed like this?“<br/> The Cowboy says, “Well it’s like this Sheriff… I was in the bar down the road and this pretty little red head asks me to go out to her motor home with her. So I did. We go inside and she pulls off her top and asks me to pull off my shirt . so I did. Then she pulls off her skirt and asks me to pull off my pants…so I did. Then she pulls off her panties and asks me to pull off my shorts… so I did. Then she gets on the bed and looks at me kind of sexy and says, ‘Now go to town, cowboy..’ and here I am.”<br/> Son of a Gun, Blond men do exist.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/BJnME17"> /u/BJnME17 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16hr04p/the_naked_cowboy/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16hr04p/the_naked_cowboy/">[comments]</a></span></p></li>
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