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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>A human primary airway microphysiological system infected with SARS-CoV-2 distinguishes the treatment efficacy between nirmatrelvir and repurposed compounds fluvoxamine and amodiaquine</strong> -
<div>
The COVID-19 pandemic necessitated a rapid mobilization of resources toward the development of safe and efficacious vaccines and therapeutics. Finding effective treatments to stem the wave of infected individuals needing hospitalization and reduce the risk of adverse events was paramount. For scientists and healthcare professionals addressing this challenge, the need to rapidly identify medical countermeasures became urgent, and many compounds in clinical use for other indications were repurposed for COVID-19 clinical trials after preliminary preclinical data demonstrated antiviral activity against SARS-CoV-2. Two repurposed compounds, fluvoxamine and amodiaquine, showed efficacy in reducing SARS-CoV-2 viral loads in preclinical experiments, but ultimately failed in clinical trials, highlighting the need for improved predictive preclinical tools that can be rapidly deployed for events such as pandemic emerging infectious diseases. The PREDICT96-ALI platform is a high-throughput, high-fidelity microphysiological system (MPS) that recapitulates primary human tracheobronchial tissue and supports highly robust and reproducible viral titers of SARS-CoV-2 variants Delta and Omicron. When amodiaquine and fluvoxamine were tested in PREDICT96-ALI, neither compound demonstrated an antiviral response, consistent with clinical outcomes and in contrast with prior reports assessing the efficacy of these compounds in other human cell-based in vitro platforms. These results highlight the unique prognostic capability of the PREDICT96-ALI proximal airway MPS to assess the potential antiviral response of lead compounds.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.27.546790v1" target="_blank">A human primary airway microphysiological system infected with SARS-CoV-2 distinguishes the treatment efficacy between nirmatrelvir and repurposed compounds fluvoxamine and amodiaquine</a>
</div></li>
<li><strong>Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential</strong> -
<div>
Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (Mpro) inhibitor nirmatrelvir had increased efficacy in vivo against SARS-CoV-2 compared to each single agent. Altogether, our data supports the continuing clinical evaluation of GS-5245 in humans infected with COVID-19, including as part of a combination antiviral therapy, especially in populations with the most urgent need for more efficacious and durable interventions.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.27.546784v1" target="_blank">Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential</a>
</div></li>
<li><strong>Targeting Multiple Conserved T-Cell Epitopes for Protection against COVID-19 Moderate-Severe Disease by a Pan-Sarbecovirus Vaccine</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background Most of current approved vaccines, based on a Spike-only as single immunogen, fall short of producing a full-blown T-cell immunity. SARS-CoV-2 continues to evolve with ever-emergent higher-contagious mutants that may take a turn going beyond Omicron to bring about a new pandemic outbreak. New recombinant SARS-CoV-2 species could be man-made through genetic manipulation to infect systemically. Development of composition-innovated, pan-variant COVID-19 vaccines to prevent from hospitalization and severe disease, and to forestall the next pandemic catastrophe, is an urgent global objective. Methods and findings In a retrospective, e-questionnaire Observational Study, extended from a clinical Phase-2 trial conducted in Taiwan, during the prime time of Omicron outbreak dominated by BA.2 and BA.5 variants, we investigated the preventive effects against COVID-19 moderate-severe disease (hospitalization and ICU admission) by a pan-Sarbecovirus vaccine UB-612 that targets monomeric S1-RBD-focused subunit protein and five designer peptides comprising sequence-conserved, non-mutable helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from Spike (S2), Membrane (M) and Nucleocapsid (N) proteins. Per UB-612 vaccination, there were no hospitalization and ICU admission cases (0% rate, 6 months after Omicron outbreak) reported ≥14 months post-2nd dose of primary series, and ≥10 months post-booster (3rd dose), to which the potent memory cytotoxic CD8 T cell immunity may be the pivotal in control of the infection disease severity. Six months post-booster, the infection rate (asymptomatic and symptomatic mild) was only 1.2%, which increased to 27.8% observed ≥10 months post-booster. The notable protection effects are in good alignment with a preliminary Phase-3 heterologous booster trial report showing that UB-612 can serve as a competent booster substitute for other EUA-approved vaccine platforms to enhance their seroconversion rate and viral-neutralizing titer against Omicron BA.5. Conclusions UB-612, a universal multitope vaccine promoting full-blown T cell immunity, may work as a competent primer and booster for persons vulnerable to Sarbecovirus infection. Trial Registration. Clinical Trials.gov ID: NCT04773067.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.28.23291948v1" target="_blank">Targeting Multiple Conserved T-Cell Epitopes for Protection against COVID-19 Moderate-Severe Disease by a Pan-Sarbecovirus Vaccine</a>
</div></li>
<li><strong>Bayesian nowcasting with Laplacian-P-splines</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
During an epidemic, the daily number of reported infected cases, deaths or hospitalizations is often lower than the actual number due to reporting delays. Nowcasting aims to estimate the cases that have not yet been reported and combine it with the already reported cases to obtain an estimate of the daily cases. In this paper, we present a fast and flexible Bayesian approach to do nowcasting by combining P-splines and Laplace approximations. The main benefit of Laplacian-P-splines (LPS) is the flexibility and faster computation time compared to Markov chain Monte Carlo (MCMC) algorithms that are often used for Bayesian inference. In addition, it is natural to quantify the prediction uncertainty with LPS in the Bayesian framework, and hence prediction intervals are easily obtained. Model performance is assessed through simulations and the method is applied to COVID-19 mortality and incidence cases in Belgium.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.26.22279249v2" target="_blank">Bayesian nowcasting with Laplacian-P-splines</a>
</div></li>
<li><strong>COVID-19 Impact in Crohn Disease Patients Underwent Autologous Hematopoietic Stem Cell Transplantation</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
SARS COV 2 is the virus responsible for COVID-19, a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases. Crohn9s disease (CD) is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota. Patients who underwent Hematopoietic Stem cell Transplantation are considered at risk for COVID-19. The objective of this report was to describe for the first time the impact of COVID-19 in a group of 50 patients with Crohn9s Disease (CD, 28 females, and 22 male) with a mean age of 38 years, previously submitted to Autologous, non-myeloablative, Hematopoietic Stem Cell Transplantation (Auto HSCT) between 2013 and 2021. In this series, 19 patients were diagnosed with positive COVID-19. In two (2) patients there was a report of the occurrence of two infectious episodes. Parameters related to HSCT, such as time elapsed since the procedure, vaccination status, CD status before and after infection, and clinical manifestations resulting from COVID-19, were evaluated. Among the patients with COVID-19, in three, submitted to Auto HSCT less than six (6) months ago, there was a change in the CD status, and one of them, in addition to the CD symptoms, started to present thyroid impairment with positive anti-TPO. Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission. Nine patients reported late symptoms that may be related to COVID-19. There were no deaths, and the statistical evaluation of the series of COVID-19 patients after HSCT and those who did not present an infectious episode did not present significant data regarding the analyzed parameters. Despite the change in CD status in three patients and the presence of nine patients with late symptoms, we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD. Key Words: Inflammatory bowel disease, Crohn Disease, SARs COV 2, COVID - 19, Autologous Hematopoietic Stem Cell Transplantation, Stem Cell Therapy.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.22.23291610v1" target="_blank">COVID-19 Impact in Crohn Disease Patients Underwent Autologous Hematopoietic Stem Cell Transplantation</a>
</div></li>
<li><strong>SARS-CoV-2 testing in the Slovak Republic from March 2020 to September 2022 - summary of the pandemic trends</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The COVID-19 pandemic has been part of Slovakia since March 2020. Intensive laboratory testing ended in October 2022, when the number of tests dropped significantly, but the state of the pandemic continues to this day. For the management of COVID-19, it is important to find an indicator that can predict pandemic changes in the community. The average daily/weekly Ct value with a certain time delay can predict changes in the number of cases of SARS-CoV-2 infection, which can be a useful indicator for the healthcare system. The study analyzed the results of 1,420,572 RT-qPCR tests provided by one accredited laboratory during the ongoing pandemic in Slovakia from March 2020 to September 2022. The total positivity of the analyzed tests was 24.64%. The average Ct values found were the highest in the age group of 3-5 years, equal to the number 30.75; the lowest were in the age group &gt; 65 years, equal to the number 27. The average weekly Ct values ranged from 22.33 (pandemic wave week) to 30.12 (summer week). We have summarized the results of SARS-CoV-2 diagnostic testing in Slovakia with the scope defined by the rate and positivity of tests carried out at Medirex a.s. laboratories.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.26.23291891v1" target="_blank">SARS-CoV-2 testing in the Slovak Republic from March 2020 to September 2022 - summary of the pandemic trends</a>
</div></li>
<li><strong>Design and Analysis Heterogeneity in Observational Studies of COVID-19 Booster Effectiveness: A Review and Case Study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background Observational vaccine effectiveness (VE) studies based on real-world data are a crucial supplement to initial randomized clinical trials of Coronavirus Disease 2019 (COVID-19) vaccines. However, there exists substantial heterogeneity in study designs and statistical methods for estimating VE. The impact of such heterogeneity on VE estimates is not clear. Methods We conducted a two-step literature review of booster VE: a literature search for first or second monovalent boosters on January 1, 2023, and a rapid search for bivalent boosters on March 28, 2023. For each study identified, study design, methods, and VE estimates for infection, hospitalization, and/or death were extracted and summarized via forest plots. We then applied methods identified in the literature to a single dataset from Michigan Medicine (MM), providing a comparison of the impact of different statistical methodologies on the same dataset. Results We identified 53 studies estimating VE of the first booster, 16 for the second booster. Of these studies, 2 were case-control, 17 were test-negative, and 50 were cohort studies. Together, they included nearly 130 million people worldwide. VE for all outcomes was very high (around 90%) in earlier studies (i.e., in 2021), but became attenuated and more heterogeneous over time (around 40%-50% for infection, 60%-90% for hospitalization, and 50%-90% for death). VE compared to the previous dose was lower for the second booster (10-30% for infection, 30-60% against hospitalization, and 50-90% against death). We also identified 11 bivalent booster studies including over 20 million people. Early studies of the bivalent booster showed increased effectiveness compared to the monovalent booster (VE around 50-80% for hospitalization and death). Our primary analysis with MM data using a cohort design included 186,495 individuals overall (including 153,811 boosted and 32,684 with only a primary series vaccination), and a secondary test-negative design included 65,992 individuals tested for SARS-CoV-2. When different statistical designs and methods were applied to MM data, VE estimates for hospitalization and death were robust to analytic choices, with test-negative designs leading to narrower confidence intervals. Adjusting either for the propensity of getting boosted or directly adjusting for covariates reduced the heterogeneity across VE estimates for the infection outcome. Conclusion While the advantage of the second monovalent booster is not obvious from the literature review, the first monovalent booster and the bivalent booster appear to offer strong protection against severe COVID-19. Based on both the literature view and data analysis, VE analyses with a severe disease outcome (hospitalization, ICU admission, or death) appear to be more robust to design and analytic choices than an infection endpoint. Test-negative designs can extend to severe disease outcomes and may offer advantages in statistical efficiency when used properly.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.22.23291692v1" target="_blank">Design and Analysis Heterogeneity in Observational Studies of COVID-19 Booster Effectiveness: A Review and Case Study</a>
</div></li>
<li><strong>The effect of residential aged care facility COVID-19 lockdowns on resident mortality</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Aims This perspective is exploring the effect of residential aged care facility COVID-19 lockdowns on resident mortality. Relevance People living in residential aged care facilities (RACFs) are at increased risk of COVID-19 infection and death. In Australia, COVID-19 infections in RACF residents represented seven percent of recorded infections and the case fatality rate (CFR) was 33%. RACFs were categorised as high-risk settings for COVID-19 and a number of measures to reduce the risk of acquiring COVID-19 were implemented at the National and State and Territory levels, such as strict infection control, monitoring, testing, vaccination and increased clinical capacity. Methods All COVID-19 infections and deaths in the 12-months from 15 October 2021 to 14 October 2022 for the cohort of residents living in an Australian RACF (except Western Australia) at the beginning of this period were analysed. Key points Lockdowns of RACFs were successful in substantially reducing the number of COVID-19 infections and deaths in RACF residents. This was largely because the infection and mortality rates of COVID-19 were high in 2020 and 2021. The findings of this study could be used to evaluate and inform national and local states and territory guidelines on the management of COVID-19 in RACFs.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.26.23291907v1" target="_blank">The effect of residential aged care facility COVID-19 lockdowns on resident mortality</a>
</div></li>
<li><strong>Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Molnupiravir, an antiviral medication that has been widely used against SARS-CoV-2, acts by inducing mutations in the virus genome during replication. Most random mutations are likely to be deleterious to the virus, and many will be lethal, and so molnupiravir-induced elevated mutation rates reduce viral load. However, if some patients treated with molnupiravir do not fully clear SARS-CoV-2 infections, there could be the potential for onward transmission of molnupiravir-mutated viruses. Here we show that SARS-CoV-2 sequencing databases contain extensive evidence of molnupiravir mutagenesis. Using a systematic approach, we find that a specific class of long phylogenetic branches, distinguished by a high proportion of G-to-A and C-to-T mutations, appear almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age-groups with widespread usage of the drug. We identify a mutational spectrum, with preferred nucleotide contexts, from viruses in patients known to have been treated with molnupiravir and show that its signature matches that seen in these long branches, in some cases with onwards transmission of molnupiravir-derived lineages. Finally, we analyse treatment records to confirm the association between these high G-to-A branches and the use of molnupiravir.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.26.23284998v3" target="_blank">Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases</a>
</div></li>
<li><strong>Prevalence, knowledge, causes, and practices of self-medication during the COVID-19 pandemic in Bangladesh: A cross-sectional survey</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: During the COVID-19 pandemic, self-medication (SM) has become a critical element in the healthcare system. SM can ease the burden on hospitals and medical resources by treating minor illnesses. However, inappropriate SM practices can lead to adverse drug reactions, drug resistance, and incorrect diagnoses, resulting in poor health outcomes. Methods: To evaluate the prevalence, knowledge, causes, and practices of SM among the Bangladeshi population during the COVID-19 outbreak, a cross-sectional survey with structured questionnaires was conducted in Chittagong from March to May 2022. The survey included 265 participants, with an average age of 35.09 years, and a multiple-choice questionnaire was used to gather information. Results: The study found that 64.15% of respondents had sufficient knowledge of SM, while 35.8% had insufficient knowledge. The primary reasons for SM during the pandemic were the influence of friends/family (90.74%), fear of infection or contact with COVID-19 cases (73.15%), and fear of quarantine or self-isolation (72.22%). Analgesics/pain relievers (84%) were the most commonly used drugs for SM for COVID-19 prevention and treatment. Antiulcerants/anti acid (42%), Vitamin C and Multivitamin (42%), and Antibiotics (32%) were also frequently used. Conclusion: This study suggests that SM is prevalent among Chittagong City residents, particularly those with less than a tertiary education. The study highlights the importance of building awareness about SM practices and taking necessary steps to control them.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.27.23291974v1" target="_blank">Prevalence, knowledge, causes, and practices of self-medication during the COVID-19 pandemic in Bangladesh: A cross-sectional survey</a>
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<li><strong>What works and for whom in treating depression in older adults in deprived communities in Brazil: Findings from a causal mediation analyses of the PROACTIVE trial that overlapped with the COVID-19 pandemic</strong> -
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Background: The PROACTIVE trial was a task-shared, collaborative care, psychosocial intervention that was highly effective at improving recovery from depression in older adults in Brazil that overlapped with the COVID-19 pandemic. Here we investigate mediators of the interventions effectiveness. Methods: Causal mediation analysis using interventional indirect effects, decomposed the total effect of PROACTIVE on recovery from depression (PHQ-9 less than 10), into multiple indirect effects including: dose of intervention (number of sessions and number of activities completed); social support measured through Luben Social Network Scale; perceived loneliness through the three-item UCLA questionnaire; conditions associated with frailty; and extra sessions offered to participants who did not respond to the intervention. Findings: Of the interventions total effect (difference in probability of recovery from depression between the intervention and control arms 0.211 [bias-corrected 95% CI: 0.139, 0.274]): 14% was mediated through improved conditions associated with frailty 0.030 [0.003, 0.065]); 6% through reduced loneliness (0.013 [0.001, 0.028]); and 20% through attending extra sessions for participants who did not respond to the intervention (0.042 [0.007, 0.105]). Interpretation: Our findings emphasise the importance of a home-based intervention to improve depression outcomes where participants are encouraged to self-select activities to mitigate against loneliness and are referred to primary care to manage health issues relating to frailty. Importantly, our findings suggest that offering extra sessions to participants who did not respond to the intervention shows promise in ensuring a sustained recovery from depression.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.26.23291868v1" target="_blank">What works and for whom in treating depression in older adults in deprived communities in Brazil: Findings from a causal mediation analyses of the PROACTIVE trial that overlapped with the COVID-19 pandemic</a>
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<li><strong>The Role of VSL#3 in the Treatment of Fatigue and Other Symptoms in Long Covid-19 Syndrome: a Randomized, Double-blind, Placebo-controlled Pilot Study (DELong#3)</strong> -
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Long COVID, also known as Post-acute COVID-19 Syndrome (PACS), is a chronic condition affecting individuals who have recovered from acute COVID-19. It is currently estimated that around 65 million people worldwide suffer from Long COVID. It is characterized by a range of symptoms, including fatigue, exertion intolerance, neurocognitive and sensory impairment, sleep disturbance, myalgia/arthralgia, and dysautonomia. Among them fatigue has emerged as a burdensome and pervasive issue, significantly impacting the quality of life and daily functioning of Long COVID patients. Alterations in the composition of the intestinal microbiota has been reported in COVID-19 patients. Dysbiosis persists even after several months of recovery from acute SARS-CoV-2 infection. Based on this evidence, we carried out a phase 3, randomized, double-blind, placebo-controlled trial aimed at evaluating the efficacy of VSL#3, a consortium of probiotic bacterial strains, in reducing fatigue and improving various aspects of patients9 well-being in patients with Long COVID syndrome.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.28.23291986v1" target="_blank">The Role of VSL#3 in the Treatment of Fatigue and Other Symptoms in Long Covid-19 Syndrome: a Randomized, Double-blind, Placebo-controlled Pilot Study (DELong#3)</a>
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<li><strong>Examining the inter-relationships between social isolation and loneliness and their correlates among older British adults before and during the COVID-19 lockdown: evidence from four British longitudinal studies</strong> -
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Background and Objectives: Unprecedented social restrictions during the COVID-19 pandemic have provided a new lens for considering the inter-relationship between social isolation and loneliness in later life. We present these inter-relationships before and during the COVID-19 restrictions and investigate to what extent demographic, socio-economic, and health factors associated with such experiences differed during the pandemic. Research Design and Method: We used data from four British longitudinal population-based studies (1946 MRC NSHD, 1958 NCDS, 1970 BCS, and ELSA). Rates, co-occurrences, and correlates of social isolation and loneliness are presented prior to and during the early stage of the COVID-19 pandemic and the inter-relationships between these experiences are elucidated in both periods. Results: Across the four studies, pre-pandemic proportions reporting social isolation ranged from 15 to 54%, with higher rates in older ages (e.g., 32% of 70-79 and 54% of those over 80). During the pandemic, the percentage of older people reporting both social isolation and loneliness and isolation only slightly increased. The inter-relationship between social isolation and loneliness did not change. Associations between socio-demographic and health characteristics and social isolation and loneliness also remained consistent, with greater burden among those with greater economic precarity (females, non-homeowners, unemployed, illness and greater financial stress). Discussion and Implications: There were already large inequalities in experiences of social isolation and loneliness and the pandemic had a small impact on worsening these inequalities. The concepts of loneliness and social isolation are not transferable and clarity is needed in how they are conceptualised, operationalised, and interpreted.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.27.23291947v1" target="_blank">Examining the inter-relationships between social isolation and loneliness and their correlates among older British adults before and during the COVID-19 lockdown: evidence from four British longitudinal studies</a>
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<li><strong>Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq</strong> -
<div>
Genomic and proteomic screens have identified numerous host factors of SARS-CoV-2, but efficient delineation of their molecular roles during infection remains a challenge. Here we use Perturb-seq, combining genetic perturbations with a single-cell readout, to investigate how inactivation of host factors changes the course of SARS-CoV-2 infection and the host response in human lung epithelial cells. Our high-dimensional data resolve complex phenotypes such as shifts in the stages of infection and modulations of the interferon response. However, only a small percentage of host factors showed such phenotypes upon perturbation. We further identified the NF-{kappa}B inhibitor I{kappa}B (NFKBIA), as well as the translation factors EIF4E2 and EIF4H as strong host dependency factors acting early in infection. Overall, our study provides massively parallel functional characterization of host factors of SARS-CoV-2 and quantitatively defines their roles both in virus-infected and bystander cells.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.15.500120v2" target="_blank">Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq</a>
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<li><strong>mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization in children aged 6 months to 5 years</strong> -
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Importance: Data on mRNA-1273 (Moderna) vaccine effectiveness in children aged 6 months to 5 years are limited. Objective: To assess mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization among children aged 6 months to 5 years. Design, Setting, and Participants: A test-negative study using linked health administrative data in Ontario, Canada. Participants included symptomatic children aged 6 months to 5 years who were tested by RT-PCR. Exposures: mRNA-1273 vaccination. Main Outcomes and Measures: Symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization. Results: We included 3467 test-negative controls and 572 test-positive cases. Receipt of mRNA-1273 was associated with reduced symptomatic SARS-CoV-2 infection (VE=90%; 95%CI: 53, 99%) and COVID-19-related hospitalization (VE=82%; 95%CI: 4, 99%) ≥7 days after the second dose. Conclusions and Relevance: Our findings suggest mRNA-1273 vaccine effectiveness is initially strong against symptomatic SARS-CoV-2 infection and hospitalization in children aged 6 months to 5 years. Further research is needed to understand long-term effectiveness and the need for booster doses.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.27.23291933v1" target="_blank">mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization in children aged 6 months to 5 years</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>Probiotic and Colchicine in COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Colchicine 0.5 MG;   Dietary Supplement: Probiotic Formula;   Other: Standard protocol<br/><b>Sponsor</b>:   Ain Shams University<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Influence of Manual Diaphragm Release on Pulmonary Functions in Women With COVID-19</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Interventions</b>:   Other: manual therapy;   Other: breathing exercise and prone position alone<br/><b>Sponsor</b>:   Cairo University<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Evaluating SHEN26 Capsule in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: SHEN26 capsule;   Drug: SHEN26 placebo<br/><b>Sponsor</b>:   Shenzhen Kexing Pharmaceutical Co., Ltd.<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 Clinical Trial of Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) in Booster Vaccination</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) (WSK-V101C);   Biological: Recombinant COVID-19 vaccine(Sf9 Cell) (WSK-V101)<br/><b>Sponsor</b>:   WestVac Biopharma Co., Ltd.<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 Phase Ⅲ Clinical Trial of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell) in Booster Vaccination</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: High dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell);   Biological: Low dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell);   Biological: control group;   Biological: Placebo group<br/><b>Sponsor</b>:   WestVac Biopharma Co., Ltd.<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>Impact Of Sensory Re-Education Paradigm On Sensation And Quality Of Life In Patients Post-Covid 19 Polyneuropathy</strong> - <b>Condition</b>:   Post-COVID-19 Syndrome<br/><b>Interventions</b>:   Other: sensory re-education training;   Other: traditional treatment<br/><b>Sponsor</b>:   Cairo University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comprehensive Imaging Exam of Convalesced COVID-19 Patients</strong> - <b>Conditions</b>:   COVID-19;   COVID Long-Haul<br/><b>Interventions</b>:   Other: Magnetic Resonance Imaging;   Other: Ultra-High Resolution Computed Tomography (CT) Scan<br/><b>Sponsors</b>:   Johns Hopkins University;   Canon Medical Systems, USA<br/><b>Enrolling by invitation</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>UNAIR Inactivated COVID-19 Vaccine as Heterologue Booster (Immunobridging Study)</strong> - <b>Conditions</b>:   COVID-19 Pandemic;   COVID-19 Vaccines<br/><b>Interventions</b>:   Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg;   Biological: CoronaVac Biofarma COVID-1 9 Vaccine 3 µg<br/><b>Sponsors</b>:   Dr. Soetomo General Hospital;   Indonesia-MoH;   Universitas Airlangga;   Biotis Pharmaceuticals, Indonesia<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 Investigate the Safety, Immunogenicity of Bivalent mRNA Vaccine RQ3027 and RQ3025 as a Booster Dose in Healthy Adults</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: RQ3013;   Biological: RQ3025;   Biological: RQ3027<br/><b>Sponsors</b>:   Affiliated Hospital of Yunnan University;   Yunnan University;   Kunming Medical University<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety and Efficacy of COVID-19 Convalescent Plasma (CCP) Transfusion to Prevent COVID-19 in Adult Recipients Following Hematopoietic Stem Cell Transplantation</strong> - <b>Conditions</b>:   COVID-19;   Hematopoietic Stem Cell Transplantation<br/><b>Intervention</b>:   Biological: COVID Convalescent Plasma<br/><b>Sponsor</b>:   Institute of Hematology &amp; Blood Diseases Hospital<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>Evaluating the Efficacy of Remdesivir for Long COVID Following a Confirmed COVID-19 Infection.</strong> - <b>Conditions</b>:   SARS-CoV-2 Infection;   COVID-19<br/><b>Intervention</b>:   Drug: Remdesivir<br/><b>Sponsors</b>:   University of Derby;   University of Exeter;   Peninsula Clinical Trials Unit;   University Hospitals of Derby and Burton NHS Foundation Trust<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>Immunogenicity and Safety Study of SARS-CoV-2 DNA Vaccine (ICCOV)</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: SARS-CoV-2 DNA Vaccine (ICCOV)<br/><b>Sponsors</b>:   Immuno Cure 3 Limited;   The University of Hong Kong<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>The Effect of Smart Sensor Combined With APP for Individualized Precise Exercise Training in Long Covid-19</strong> - <b>Conditions</b>:   Coronavirus Disease;   COVID-19;   Long Covid-19;   Telerehabilitation<br/><b>Interventions</b>:   Device: KNEESUP smart knee assistive device + KNEESUP care APP;   Device: KNEESUP care APP;   Behavioral: Healthy consulation<br/><b>Sponsor</b>:   Shang-Lin Chiang<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>Open Label Extension of Efgartigimod in Adults With Post-COVID-19 POTS</strong> - <b>Condition</b>:   Post-COVID Postural Orthostatic Tachycardia Syndrome Postural Orthostatic Tachycardia Syndrome<br/><b>Intervention</b>:   Drug: Efgartigimod<br/><b>Sponsors</b>:   argenx;   Iqvia Pty Ltd<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>Digital Interventions to Understand and Mitigate Stress Response</strong> - <b>Conditions</b>:   Distress, Emotional;   Stress Response Among Nursing Professionals During the COVID-19;   Stress Reaction; Acute<br/><b>Intervention</b>:   Behavioral: Digital Intervention Group<br/><b>Sponsors</b>:   Unity Health Toronto;   Toronto Metropolitan University;   University of Toronto;   University of Ontario Institute of Technology;   Boston University;   University of Ottawa;   Western University, Canada;   Centre for Addiction and Mental Health<br/><b>Recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Novel Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial</strong> - CONCLUSIONS: rNAPc2 treatment in hospitalized patients with COVID-19 was well tolerated without excess bleeding or serious adverse events but did not significantly reduce D-dimer more than heparin at day 8.</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>Endotyping of IgE-mediated polyethylene glycol and/or polysorbate 80 allergy</strong> - CONCLUSION: PEG and PS80 cross-reactivity is determined by IgE recognizing short PEG motifs, whilst PS80 mono-allergy is PEG-independent. PS80 skin test positivity in PEG allergics was associated with a severe and persistent phenotype, higher serum PEG-specific IgE levels and enhanced BAT reactivity. Spherical PEG-exposure via LNP enhances BAT sensitivity through increased avidity. All PEG and/or PS80 excipient allergic patients can safely receive SARS-CoV-2 vaccines.</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>Hindered visibility improvement despite marked reduction in anthropogenic emissions in a megacity of southwestern China: An interplay between enhanced secondary inorganics formation and hygroscopic growth at prevailing high RH conditions</strong> - The PM(2.5)-bound visibility improvement remains challenging in China despite vigorous control on anthropogenic emissions in recent years. One critical issue could exist in the distinct physicochemical properties especially of secondary aerosol components. Taken the COVID-19 lockdown as an extreme case, we focus on the relationship between visibility, emission cuts, and secondary formation of inorganics with changing optical and hygroscopic behaviors in Chongqing, a representative city…</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>Anthracyclines inhibit SARS-CoV-2 infection</strong> - Vaccines and drugs are two effective medical interventions to mitigate SARS-CoV-2 infection. Three SARS-CoV-2 inhibitors, remdesivir, paxlovid, and molnupiravir, have been approved for treating COVID-19 patients, but more are needed, because each drug has its limitation of usage and SARS-CoV-2 constantly develops drug resistance mutations. In addition, SARS-CoV-2 drugs have the potential to be repurposed to inhibit new human coronaviruses, thus help to prepare for future coronavirus outbreaks….</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>Statins: Beneficial Effects in Treatment of COVID-19</strong> - The recent viral disease COVID-19 has attracted much attention. The disease is caused by SARS-CoV-19 virus which has different variants and mutations. The mortality rate of SARS-CoV-19 is high and efforts to establish proper therapeutic solutions are still ongoing. Inflammation plays a substantial part in the pathogenesis of this disease causing mainly lung tissue destruction and eventually death. Therefore, anti-inflammatory drugs or treatments that can inhibit inflammation are important…</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>mLST8 is essential for coronavirus replication and regulates its replication through the mTORC1 pathway</strong> - Coronaviruses (CoVs), which pose a serious threat to human and animal health worldwide, need to hijack host factors to complete their replicative cycles. However, the current study of host factors involved in CoV replication remains unknown. Here, we identified a novel host factor, mammalian lethal with sec-13 protein 8 (mLST8), which is a common subunit of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), and is critical for CoV replication. Inhibitor and knockout (KO) experiments revealed…</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>Validity of Rapid Antibody Testing for COVID-19 Vaccine in Homeless People</strong> - (1) Background: There is a paucity of data regarding the validity of rapid antibody testing for SARS-CoV-2 vaccine response in homeless people worldwide. The objective of this study was to evaluate a rapid SARS-CoV-2 IgM/IgG antibody detection kit as a qualitative screen for vaccination in homeless people. (2) Methods: This study included 430 homeless people and 120 facility workers who had received one of BNT162b2, mRNA-1273, AZD1222/ChAdOx1, or JNJ-78436735/AD26.COV2.5 vaccines. They were…</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>Correlation between Clinical Characteristics and Antibody Levels in COVID-19 Convalescent Plasma Donor Candidates</strong> - COVID-19 convalescent plasma (CCP) with high neutralizing antibodies has been suggested in preventing disease progression in COVID-19. In this study, we investigated the relationship between clinical donor characteristics and neutralizing anti-SARS-CoV-2 antibodies in CCP donors. COVID-19 convalescent plasma donors were included into the study. Clinical parameters were recorded and anti-SARS-CoV-2 antibody levels (Spike Trimer, Receptor Binding Domain (RBD), S1, S2 and nucleocapsid protein) as…</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>Anticoronavirus Evaluation of Antimicrobial Diterpenoids: Application of New Ferruginol Analogues</strong> - The abietane diterpene (+)-ferruginol (1), like other natural and semisynthetic abietanes, is distinguished for its interesting pharmacological properties such as antimicrobial activity, including antiviral. In this study, selected C18-functionalized semisynthetic abietanes prepared from the commercially available (+)-dehydroabietylamine or methyl dehydroabietate were tested in vitro against human coronavirus 229E (HCoV-229E). As a result, a new ferruginol analogue caused a relevant reduction in…</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>Molnupiravir Inhibits Porcine Epidemic Diarrhea Virus Infection In Vitro</strong> - Porcine epidemic diarrhea virus (PEDV) is a swine coronavirus that is highly infectious and prone to variation. Vaccines derived from traditional PEDV strains provide less protection against PEDV-variant strains. Furthermore; there is a complex diversity of sequences among various PEDV-variant strains. Therefore; there is an urgent need to develop alternative antiviral strategies to defend against PEDV. Molnupiravir is a nucleotide analogue that could replace natural nucleosides to restrain…</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>SARS-CoV-2 Structural Proteins Modulated Blood-Testis Barrier-Related Proteins through Autophagy in the Primary Sertoli Cells</strong> - The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disrupts the blood-testis barrier (BTB), resulting in alterations in spermatogenesis. However, whether BTB-related proteins (such as ZO-1, claudin11, N-cadherin, and CX43) are targeted by SARS-CoV-2 remains to be clarified. BTB is a physical barrier between the blood vessels and the seminiferous tubules of the animal testis, and it is one of the tightest blood-tissue barriers in the mammalian body. In this study, we investigated…</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>Complement Activation-Independent Attenuation of SARS-CoV-2 Infection by C1q and C4b-Binding Protein</strong> - The complement system is a key component of the innate immune response to viruses and proinflammatory events. Exaggerated complement activation has been attributed to the induction of a cytokine storm in severe SARS-CoV-2 infection. However, there is also an argument for the protective role of complement proteins, given their local synthesis or activation at the site of viral infection. This study investigated the complement activation-independent role of C1q and C4b-binding protein (C4BP)…</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>BNT162b2 Vaccination after SARS-CoV-2 Infection Changes the Dynamics of Total and Neutralizing Antibodies against SARS-CoV-2: A 6-Month Prospective Cohort Study</strong> - This study aimed to analyze the dynamics, duration, and production of total and neutralizing antibodies induced by the BNT162b2 vaccine and the possible effect of gender and prior SARS-CoV-2 infection on the generation of these antibodies. Total antibodies were quantified via chemiluminescent microparticle immunoassay (CMIA), and neutralizing antibodies were quantified using the cPass SARS-CoV-2 kit. Individuals with a history of COVID-19 produced twice as many antibodies than vaccinated…</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>Intranasal Single-Replication Influenza Vector Induces Cross-Reactive Serum and Mucosal Antibodies against SARS-CoV-2 Variants</strong> - Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death, but remain inefficient at inhibiting initial infection and transmission. Despite updated booster formulations, breakthrough infections and reinfections from emerging SARS-CoV-2 variants are common. Intranasal vaccination to elicit mucosal immunity at the site of infection can improve the performance of respiratory virus vaccines. We developed SARS-CoV-2 M2SR, a dual SARS-CoV-2 and influenza vaccine…</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 Glycoprotein S1 Mediated by NLRP3 Inflammasome Machinery and the Cytokine Releases in A549 Lung Epithelial Cells by Nanocurcumin</strong> - Chronic inflammation and tissue damage can result from uncontrolled inflammation during SARS-CoV-2 or COVID-19 infections, leading to post-acute COVID conditions or long COVID. Curcumin, found in turmeric, has potent anti-inflammatory properties but limited effectiveness. This study developed nanocurcumin, a curcumin nanoparticle, to enhance its physical and chemical stability and investigate its in vitro anti-inflammatory properties upon CoV2-SP induction in lung epithelial cells. Nanocurcumin…</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>The Supreme Court Declines to Dismantle Democracy</strong> - The Court has consigned the independent-state-legislature theory to the “dustbin of history.” But, even as the electoral system remains intact, it’s worth reckoning with its fragility. - <a href="https://www.newyorker.com/news/daily-comment/the-supreme-court-declines-to-dismantle-democracy">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What Prigozhin’s Half-Baked “Coup” Could Mean for Putin’s Rule</strong> - Although the immediate threat of revolt has been extinguished, the episode may embolden future challengers to Russia’s status quo. - <a href="https://www.newyorker.com/news/q-and-a/what-prigozhins-half-baked-coup-could-mean-for-putins-rule">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Does It Matter That Neil Gorsuch Is Committed to Native American Rights?</strong> - The Justice doesn’t just join with the liberals on the bench when it comes to tribal rights; he often seems to lead them. - <a href="https://www.newyorker.com/news/daily-comment/does-it-matter-that-neil-gorsuch-is-committed-to-native-american-rights">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why Donald Trump Was So Mad at Mark Milley That He Confessed to a Crime</strong> - The backstory on the tape that could get the ex-President convicted in the classified-documents case. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/why-donald-trump-was-so-mad-at-mark-milley-that-he-confessed-to-a-crime">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Joe Biden Tries to Change the Narrative on the Economy</strong> - The President gave a speech touting his economic record, which is stronger than he has been given credit for. - <a href="https://www.newyorker.com/news/our-columnists/joe-biden-tries-to-change-the-narrative-on-the-economy">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Can you trust a Harvard dishonesty researcher?</strong> -
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<img alt="A photo of a river in the foreground, with kayakers and a bridge. In the backround is a clock tower and buildings of Harvard University campus." src="https://cdn.vox-cdn.com/thumbor/wwCknKzZZOWoWhKfTcLpDOfudNU=/406x0:6955x4912/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72411904/1404549205.0.jpg"/>
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Sergi Reboredo/VW Pics/Universal Images Group via Getty Images
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The hard problem of faked data in science.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r2Lakk">
Francesca Gino is a Harvard Business School professor who studies, among other things, dishonesty. How often do people lie and cheat when they think they can get away with it? How can people be prompted to lie or cheat less often?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mB87Zq">
Those are some great questions. But it’s been a rough few years for the field of dishonesty studies because<strong> </strong>it has turned out that several of the researchers were, well, <a href="https://datacolada.org/109">making up their data</a>. The result<em> </em>is<em> </em>a fascinating insight into dishonesty, if not the one that the authors intended.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ilimH5">
This story starts with a<a href="https://www.pnas.org/doi/abs/10.1073/pnas.1209746109"> 2012 paper </a>about academic dishonesty co-authored by Gino. The paper claimed that if you ask people to sign an honesty commitment before doing a project they have the opportunity to cheat on, they’re much less likely to cheat compared to if they sign the honesty pledge at the end of the experiment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CP8dYf">
“Signing before — rather than after — the opportunity to cheat makes ethics salient when they are needed most and significantly reduces dishonesty,” the paper claimed. It featured three different experiments: two in a lab setting and one field experiment with reporting odometer mileage when applying for car insurance.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zfFuBd">
In 2021, that paper was retracted when it turned out the data from the third experiment — the one about the car insurance — didn’t add up. Other researchers tried to replicate the paper’s eye-popping results and ran into a bunch of inconsistencies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JbdrB7">
The spotlight then quickly fell on one of the paper’s authors, Dan Ariely, a behavioral economist at Duke University and the author of <em>The Honest Truth About Dishonesty</em>. Ariely <a href="https://openmkt.org/blog/2022/dan-ariely-claims-authorship-order-shields-him-from-blame-speculates-that-a-low-level-envelope-stuffer-committed-the-fraud/">admitted</a><strong> </strong>that he <a href="https://openmkt.org/blog/2021/conflicts-between-dan-arielys-statement-and-footnote-14-datacolada-98/">“mislabeled” some data</a> but denied that he deliberately falsified anything, proposing it may have been falsified by the insurance company he partnered with. But records show that he was the last to modify the spreadsheet in which the falsified data appeared.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8dZnsv">
That seemed to be the end of it. With the paper more than a decade old, it’d be hard to reach any definitive conclusions about what exactly happened. But it turns out that it was only the beginning. In a report published last week, a team of independent investigators laid out their evidence that there was actually a lot more fraud in the academic dishonesty world than that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="c11EcR">
“In 2021, we and a team of anonymous researchers examined a number of studies co-authored by Gino, because we had concerns that they contained fraudulent data,” the <a href="https://datacolada.org/109">new report begins</a>. “We discovered evidence of fraud in papers spanning over a decade, including papers published quite recently (in 2020).”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Uj8y2b">
Gino has <a href="https://www.npr.org/2023/06/26/1184289296/harvard-professor-dishonesty-francesca-gino">been placed</a> on administrative leave at Harvard Business School, and Harvard has requested that three more papers be retracted. In a <a href="https://www.linkedin.com/feed/update/urn:li:activity:7078154339113914368/">statement on LinkedIn</a>, Gino said: “As I continue to evaluate these allegations and assess my options, I am limited into what I can say publicly. I want to assure you that I take them seriously and they will be addressed.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="d2E6Ld">
I highly recommend the <a href="https://datacolada.org/110">series of blog posts </a>in which the report authors explain, paper by paper, how they detected the cheating. Some impressive work went into proving not just that the data must have been tampered with, but that the tampering was deliberate. The investigators used Microsoft Excel’s version control features to demonstrate that the initial versions of the data looked quite different and that someone went in and changed the numbers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uTNlVI">
Take that 2012 study I mentioned above. The third experiment, the insurance fraud one, had data that appeared fabricated. But when researchers looked more closely, so did the first and second experiments. Gino was entirely responsible for data collection for the first experiment and is the one suspected of having a hand in its fabrication. But she had nothing to do with the data collection for the third experiment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mPtEs9">
This, of course, means that it looks like that single 2012 paper on dishonesty had <em>two different people </em>fabricate data in order to get a publishable result.
</p>
<h3 id="iDqMjS">
What we’ve learned about dishonesty
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Bwb5AV">
There’s a lot of discussion about the pressure to publish in academia and how it can lead to bad statistical practices aimed at fishing for a good p-value, or pumping up a result as much more impactful and important to the field than it really is.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8QGY52">
There’s less discussion of actual straight-up fraud, even though it’s disturbingly common and can have a huge impact on our understanding of a subject. Early in the Covid-19 pandemic, bad claims about treatments popped up <a href="https://www.vox.com/future-perfect/22776428/ivermectin-science-publication-research-fraud">thanks to fraudulent studies</a> and then took lots of good research to disprove.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HpK5jZ">
The problem is that our peer review process isn’t very well suited to looking for outright, purposeful fabrication. We can reduce many kinds of scientific malpractice by preregistering studies, being willing to publish null results, looking out for irresponsibly testing lots of hypotheses without appropriate statistical corrections, and so on. But that does nothing against someone who just switches data points from the control group to the experimental group in an Excel spreadsheet, which is what it appears Gino did.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3pF9HQ">
That’s not to say that frauds can’t be caught. One huge thing that I hear about from experts every single time I cover a scientific fraud case: Publishing the data is the way the fraud gets detected. It’s not that hard to manipulate some numbers, but it’s hard to do it without a trace. Many of the fraud cases highlighted by the team investigating Gino are downright clumsy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZGp9Yl">
Some journals now enforce an expectation that you publish your data when you publish your research. Some academics hesitate — it takes a lot of work to build a dataset, and they may want to write more papers using the same data and not be scooped by other researchers — but I think the pros of a policy about data publishing strongly outweigh the cons. It’s bad for everyone when fraudulent science gets published. It’s an injustice to scientists who are really doing the work but can’t manufacture such clean and eye-popping results. In cases like Covid-19, it resulted in research funding being badly directed and people taking medications that couldn’t help them.
</p></li>
<li><strong>Amazon, Walmart, and the price we pay for low prices</strong> -
<figure>
<img alt="Amazon boxes and a Walmart sign with some dollar signs." src="https://cdn.vox-cdn.com/thumbor/SD2IOA2eAJDZeAnYaaQ0EfE2i_k=/240x0:1680x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72411867/V2_Vox_TheBigSqueeze_WalmartAmazon.0.jpg"/>
<figcaption>
Amazon and Walmart are in a race to make everything cheaper, faster, and … worse. | Paige Vickers/Vox; Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Amazon and Walmart are a little bit evil and make us a little bit evil, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4Zs24u">
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="s17nTW">
It’s <a href="https://www.vox.com/amazon">Amazon</a>’s world, and we’re just living in it. Or Walmart’s. Or really, actually, both.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yOWtdn">
Many Americans like to think of themselves as conscientious consumers — as the types of people who shop their values, support small businesses, and generally try to do the right thing when they buy. We also all live in reality, where people are busy, our funds are limited, and convenience is really nice. Many of us <em>know </em>that buying shampoo at the local pharmacy would be the better option, but it’s 20 minutes away, and what if, once we get there, it’s locked up? So we place an order on Amazon and move on. We’re well aware we could go to any number of stores for a new bath mat and holiday decorations and back-to-school gear, but we also know we get them all at Walmart for less. We appreciate that; we just don’t appreciate thinking about how little they pay their employees.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xdsP7o">
Amazon and Walmart are fixtures of commerce in the United States today, retail behemoths that have a stronghold on what consumers buy, online and off. We have played a key role in helping them get there, often neglecting to weigh the trade-offs we make when we resort to them when we shop.
</p>
<aside id="9WstXv">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lWAqro">
The two companies are fierce competitors, and the competition between them has led to a race to the bottom on pricing, speed, and ruthlessness in an effort for one to come out on top. Their rivalry — and its implications — is the topic of the recently released <a href="https://www.harpercollins.com/products/winner-sells-all-jason-del-rey"><em>Winner Sells All: Amazon, Walmart, and the Battle for Our Wallets</em></a><em> </em>by veteran business reporter (and my former Vox colleague) Jason Del Rey.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="auYKgb">
I recently spoke with Del Rey about the grip Amazon and Walmart have on the American <a href="https://www.vox.com/economy">economy</a>, the trade-offs they (and, ultimately, we) make for them to run their businesses, and what, if anything, poses a threat to these companies. We also got into how Amazon has managed to take over from Walmart as the Bad Guy in retail — even though nobody’s really a hero here.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gf1oR1">
<em>This conversation has been edited for length and clarity.</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JkUlJU">
<strong>How much of a hold do Amazon and Walmart have on us, as consumers? Like, are there any legitimate competitors?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hnqweT">
They have a huge hold on us. What Amazon has done over the years with Prime is a profound change that, by now, goes overlooked. It makes it so a lot of us feel like we can order one product at a time from this magic screen, and that it’s sustainable for business in this country and for the world that it will arrive that day or tomorrow. And that’s the way shopping is today. The effect of Amazon Prime on shopping habits just can’t be overstated enough.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VufWFv">
What Walmart’s done, and they’re not the only ones, is they’ve drilled home the idea that what we should value above all else is the lowest possible cost for a good. There are plenty of reasons why tens of millions of people base their shopping on that — they have no choice. But my fear is just within the rivalry that there’s a constant race to the bottom that might be good for each of us in the short term, but long-term poses a whole slew of problems.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5McprZ">
<strong>It feels to me that part of the story is that these two companies have sort of out-terribled each other over the years to try to compete, constantly undercutting one another and competitors to be faster and cheaper. Do you think that’s a fair assessment?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="X1NSYh">
Listen, I can understand how that can be the view, and there are many times in my reporting history on them that that’s how I felt. If I take a step back, I look at it with a little more nuance.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3RGwyn">
They have each had, at different times and to different levels, negative impacts on small businesses and working-class people in this country, and they deserve to continue to have scrutiny placed on them for that. It may very well take government intervention to quote-unquote “fix” some of those issues. Putting that aside, it’s hard for me to look at events like the pandemic and the role each of them played in different ways in helping large masses of people get by on a day-to-day basis and think it’s all bad.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7Y9kLP">
Now, why were they in that position to be almost utilities in the first place? A lot of competition has gone away over the years. Is that government’s fault? Do we wish there were better people leading these companies that took a different path? There are a bunch of different answers.
</p>
<div class="c-float-right">
<aside id="YfcyA2">
<q>“They have played the role of doing what this country has rewarded big corporations for doing in the last few decades, and that’s showing growth at all costs”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DsoYdu">
They have played the role of doing what this country has rewarded big corporations for doing in the last few decades, and that’s showing growth at all costs. Everything else is an afterthought.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ThIRrU">
<strong>Is it possible to compete with Amazon and Walmart in the current landscape?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ewyqcY">
If you’re going head-on at them in industries or categories that are core to their business, it has been very difficult to compete with them at scale. You can carve off customers on the fringes, but if you’re talking about building a multibillion-dollar business doing something that they do well or they care about, it has been next to impossible. There are a few exceptions. I think about Chewy in the pet product category. I don’t know what Chewy’s market cap is today, but it’s a considerable-sized business that has found success.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="imwfID">
In decades past, if you went head-to-head, Amazon and Walmart were going to eventually crush you or buy you.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uxpqeH">
<strong>So really, really hard to try to compete, even with </strong><a href="https://www.vox.com/recode/22836368/amazon-antitrust-ftc-marketplace"><strong>possible antitrust action</strong></a><strong> from government regulators swirling around them?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RHVveD">
In the future, I think a lot of it will depend on whether there is some type of government intervention. I’m mainly talking about Amazon here, because the days of Walmart being at risk of any antitrust scrutiny feel like they’re gone — much to the frustration of Amazon leadership.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BNk6rv">
They have both failed a decent amount when it comes to them trying to enter a new space that has successful incumbents.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WeBkRt">
<strong>Like what?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vgFgA4">
Health care is one space they’ve both had challenges in. Amazon’s trying to buy their way in with their <a href="https://www.cnbc.com/2023/02/22/amazon-closes-deal-to-buy-primary-care-provider-one-medical.html">acquisition of One Medical</a> [a primary care provider].
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N8mxlr">
Amazon’s physical retail initiatives, including buying Whole Foods, have largely been, for them, huge disappointments. When I talk to former Amazonians, as they call themselves, they think of themselves as technologists. They just get bored as hell working on physical retail, and I think that showed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9P0DIW">
<strong>So maybe you can compete with them in things that they’re bad at, or at something else in the future we don’t see yet.</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sfdtAW">
You can look at the apparel and accessories space, companies like <a href="https://www.vox.com/the-goods/22573682/shein-future-of-fast-fashion-explained">Shein</a> and Temu; those companies are growing very quickly and have extremely low prices. I’m sure Amazon’s paying attention as they once did <a href="https://www.vox.com/the-goods/2019/6/17/18679107/wish-shopping-app">with Wish.com</a>, but I’m skeptical about the long-term sustainability of those businesses and those models.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U6xj6N">
I hope there’s a company that doesn’t exist today or isn’t getting attention, and in 10, 20 years from now, we are talking about them in this space. Walmart and Amazon are just so entrenched, especially in their combined size in online retail. Even with the slowdown in the last year or two, it’s hard to see real threats to them — unless it’s a company coming from a different angle, maybe a Shopify in software or a <a href="https://www.vox.com/tiktok">TikTok</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="s413jS">
<strong>Walmart was the original Big Bad in terms of taking out competitors, killing off local retailers, underpaying workers, etc. And then Amazon came along and their positions kind of shifted, at least reputationally. What’s changed?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lgEIjv">
In the early 2000s, Walmart leadership, including their CEO, essentially made nice with some of their biggest critics — on the environmental front, with critical journalists. It was self-serving, yes, but they went out and took the time to actually meet with and listen to critics, and I think that actually worked for them. Whether that was them really changing their business for moral or good reasons at the time, undertaking some environmental or green initiatives, or whether it was all about PR, it kind of worked.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B1WFGo">
Amazon has never accepted or had the self-awareness of “maybe these people who say bad things about us have a point.” Folks who have been at the company in recent years talk about this extreme lack of self-awareness that they’re not just a startup out to do good anymore and that when they make decisions, whether it’s labor decisions or partner decisions with the small businesses that sell on their marketplace, these tiny tweaks have massive impacts. All the way up to the top of the company, they have a hard time accepting criticism. They are largely thin-skinned and think they’re misunderstood. It definitely has an effect in Washington, DC, and it makes a lot of critics dig in their heels.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YVTMeZ">
<strong>So Amazon’s just kind of bad at the PR part at this point?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WmNpK9">
Amazon is Walmart 2.0 or 3.0. Walmart, on the fringes, has made some changes to better satisfy some critics, but at their core, there’s a lot of similar, justified criticisms of them that Amazon mostly takes the brunt of.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hp0XCz">
One big difference, as smart Amazon critics lay out, is Amazon is doing so much in so many different ways across the internet, essentially laying the pipes and then putting up the tollbooth so that their power feels much more dangerous and harder to break. I think that’s why you see in DC and in antitrust circles the infrastructure they’re trying to control from AWS [Amazon Web Services, their cloud computing service] to the advertising platform to all the other fees they charge to their partners. It makes them seem like a different type of danger to competition.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qSBu8E">
Having <a href="https://www.vox.com/jeff-bezos">Jeff Bezos</a> as the world’s richest man for a long time only hurt them as well, which is ironic when you consider what the Walton family’s combined wealth is.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WFVRHC">
I wouldn’t understate or undersell how much Jeff Bezos putting himself into <a href="https://www.vox.com/media">the media</a> over the last three or four years has hurt the company in that it has brought more overall attention to him and his wealth.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uaBZ25">
I’m sure [Amazon CEO] <a href="https://www.vox.com/andy-jassy">Andy Jassy</a> would love to sit down with you and make the case that Walmart should get a lot more scrutiny. But it does feel, despite their longstanding <a href="https://www.vox.com/unions">union</a> beliefs, like they’ve escaped their darkest days of criticisms. I wouldn’t say they’re beloved, but they’re not viewed as poorly as Amazon is in some circles.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nbbLRi">
<strong>Right. Walmart is no longer the boogeyman. </strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SO6k22">
One more thing: There are a lot of people who have issues with Amazon, but I’m no longer surprised how many people do love the company, or love the service. I don’t know if your readers do, or I think a lot of them won’t admit it, but they do.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dPSCk8">
<strong>Well, that’s always the thing. You see the media and certain critics saying everybody hates Big Tech, Amazon’s evil. And then you look at brand favorability, and Amazon is one of the most popular brands in the country. It’s a good service. </strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9G3801">
I think it’s gotten worse, but yeah.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="b7cXg2">
<strong>How do you think about some of the trade-offs both of these companies make — and have consumers make — in order to get people stuff fast and at super-low prices? What does that mean for how they pay and treat their employees so consumers can have low-priced convenience?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OZW0dy">
There are some really shitty trade-offs. I used to think each of us is to blame for those trade-offs, and I kind of feel that way sometimes, but there are all these reasons why these companies were allowed to become as entrenched and as hard to compete with as they are. Is it the average person’s fault, day to day, doing what they think is the most convenient thing for their lives?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p8gChV">
In our house, we are customers of Amazon, of Walmart, of Target and Trader Joe’s and the local coffee shops and restaurants. On a personal level, we try to think about whether we actually need that thing the next day or two days later. Sometimes, it feels like yes, and we’ll still place that order with that service. We’ve gotten better about taking other paths when we don’t. But these companies have convinced us that we need everything within one or two days.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZGCaT4">
Jet.com, an e-commerce company that briefly existed as an independent company [before being acquired by Walmart], had this idea that they would kick you back some savings if you waited a little longer. That would take some costs out of the logistics part of the business, and oh, by the way, maybe that’s a little better for employees and the environment, too. I wanted to believe all of that could work because it seemed the direction we were heading was a really bad one for everyone except the executives, but that model ended up not working for a variety of reasons.
</p>
<div class="c-float-right">
<aside id="WTeODB">
<q>“A lot of people are addicted to convenience”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a4POBp">
I’m hopeful there’s a world where we can turn back the clock, but I think a lot of people are addicted to convenience and have convinced themselves it saves time that they use in better ways. Instead, we’re fucking scrolling TikTok.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="knJ7YA">
We’re headed in a direction where there’s absolutely <a href="https://www.vox.com/recode/2022/9/27/23373588/amazon-warehouse-robots-manipulation-picker-stower">more automation</a> going into these businesses. Walmart and Amazon will make the argument that workers are not going away, we are making their lives and work better and taking away the worst work. But there are also really negative consequences when you add automation to the work, such as quotas for workers being increased.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZkQckx">
I’m really hoping there are entrepreneurs out there who can somehow convince us that we don’t need things the same day or the next day, or there’s a sustainable business model to really make a go at a new type of service. It may be just too late, which is dark and depressing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jwy931">
<strong>Once these companies offer one-day shipping or two-day shipping or whatever, doesn’t everybody else have to in order to even try to compete or keep up? </strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6U9cFX">
The ripple effects of everyone else following them are real. For someone to choose a different path or a different way, it has to be a very, very young company that is sort of naive and has nothing to lose because they only have three employees. That seems, to me, to be just about it.
</p>
<div class="c-float-right">
<aside id="8zl0gW">
<q>“What you do with Amazon is actually not shopping it’s buying”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HQSVVh">
What you do with Amazon is actually not shopping; it’s buying. Largely, it’s a very transactional relationship that people have with it. Every so often, there’s an Amazon dress or Amazon whatever, but usually, you’re being sent to the site for some very specific reason. You’re transacting, you’re fulfilling some desire or need. But the idea that you’re browsing or enjoying yourself or window shopping or getting some kind of entertainment value is something they’ve been terrible at. And they’ve tried for years. They’re best at selling stuff that lends itself to transactions and not shopping.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="h08C2i">
Is there a competitor that upends them by taking the shopping approach? I don’t know. When the stuff we buy most frequently, like groceries or consumer goods or clothing basics, is stuff you don’t need to do much browsing to feel good about your buying decision.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XWyg19">
<strong>I’ve never thought about it, but it does feel like every time it’s the holiday season I wind up on Amazon looking for stuff to buy and within two minutes am like okay, this is pointless, I can’t do anything, and log off. </strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gzONIG">
The site is not a fun one to move around on, and it doesn’t look all that different from 15 years ago, but they still feel so entrenched that it’s reflex or comfort just to turn to them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xwDmzr">
<strong>If we think that Amazon and Walmart do have too much control, what’s the biggest threat to them? Unions? Government regulation? Is there a threat at all?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="P3gbkH">
On the Amazon side, they are at this inflection point with layoffs and cost-cutting and a pullback in some areas where they were heavily investing, such as Alexa. Morale is not good there. It feels, in some corners, like a boring, mature company. One big risk to them is bigness and moving slower than they have in their early years, when really their biggest advantage was speed. They were able to roll stuff out and test it for a variety of reasons. Wall Street gave them a long leash, so they didn’t have to worry about profitability. Their bigness is a threat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3GNwis">
On unionization, I’m more skeptical today than I was a year ago that there’s a real, sustainable drive that’s going to make a difference in working conditions there. Maybe if the Teamsters make up more ground than they have to date, they could make a difference, but I’m skeptical of that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jbMCv3">
I, like a lot of people, am waiting for this long-rumored FTC antitrust lawsuit to drop [separate from the <a href="https://www.vox.com/technology/2023/6/21/23768370/ftc-amazon-prime-dark-patterns">Prime cancellation lawsuit</a> that the Federal Trade Commission recently filed], and that could have an impact. But it also could be a five- to seven-year process. How much ground they gain in five to seven years as a technology company of their size, I don’t know; it in some ways seems like a hopeless fight. I look at Amazon and think the biggest threat to themselves today really is themselves.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VLMNJe">
With Walmart, it has taken so much effort and time for them to get to a place where their online services are not awful. They are more committed than they have ever been to try to meet shoppers where they want to be met, when they want to be met, with the products they want to buy, but man, it’s taken a long time and a lot of money. The CEO told me it’s gotten better, but he’s still dissatisfied.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="R0fYLf">
There was a time where Amazon was a real existential threat to Walmart because of how much Walmart was ignoring them, but now it just feels like perhaps they’ll stay in this position of a much smaller number two in e-commerce and kind of be content with that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qT3AyH">
Walmart stores, especially as they try to convert them, finally, into mini warehouses and <a href="https://www.vox.com/robots">robot</a> headquarters, are not going away. That’s still where so much of their business is done that they’re going to do okay for themselves for a while.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rZwT9S">
<strong>So, for now, we’re just stuck with Amazon and Walmart and being a little complicit in the meantime?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8zpkF9">
These are complicated companies with complicated impacts. I’d love to say there’s a world where someone upends them because they are big and bad and do a lot of harmful things to partners and employees, but I’ve accepted that they’re not going anywhere and we’ve got to make do with them and then hope on the fringes competitors can gnaw away. Maybe, if they are in fact breaking the law, they can be forced to change the way they do business, but I’m not holding out much hope on any of that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5G5qzT">
<em>We live in a world that’s constantly trying to sucker us and trick us, where we’re always surrounded by scams big and small. It can feel impossible to navigate. Every two weeks, join Emily Stewart to look at all the little ways our economic systems control and manipulate the average person. Welcome to </em><a href="https://www.vox.com/the-big-squeeze"><em>The Big Squeeze</em></a><em>.</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NF25sR">
<a href="http://vox.com/big-squeeze-newsletter"><em>Sign up to get this column in your inbox</em></a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fEmYHz">
<em>Have ideas for a future column or thoughts on this one? Email </em><a href="mailto:emily.stewart@vox.com"><em>emily.stewart@vox.com</em></a>.
</p></li>
<li><strong>AI is supposedly the new nuclear weapons — but how similar are they, really?</strong> -
<figure>
<img alt="Two Air Force officers, a man and a woman, are at computer stations for a launch control inspection in 2018." src="https://cdn.vox-cdn.com/thumbor/dTFnYWbHEkEYwV1ZPYga7KVH7ig=/0x0:6549x4912/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72411857/1230576984.0.jpg"/>
<figcaption>
Air Force officers manning the computers at a launch control center in Great Falls, Montana, capable of launching intercontinental ballistic missiles. Could the computers become more dangerous than the missiles? | Lido Vizzutti for The Washington Post via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
What the history of nuclear arms can — and can’t — tell us about the future of AI.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ceho2a">
If you spend enough time reading about artificial intelligence, you’re bound to encounter one specific analogy: nuclear weapons. Like nukes, the argument goes, AI is a cutting-edge technology that emerged with unnerving rapidity and comes with serious and difficult to predict risks that society is ill-equipped to handle.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="57CAjk">
The heads of AI labs OpenAI, Anthropic, and Google DeepMind, as well as researchers like Geoffrey Hinton and Yoshua Bengio and prominent figures like Bill Gates, <a href="https://www.safe.ai/statement-on-ai-risk">signed an open letter</a> in May making the analogy explicitly, stating: “Mitigating the risk of extinction from AI should be a global priority alongside other societal-scale risks such as pandemics and nuclear war.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r3yjp6">
<em>Oppenheimer </em>director Christopher Nolan, by contrast, <a href="https://www.wired.com/story/christopher-nolan-oppenheimer-ai-apocalypse/">doesn’t think AI and nukes are very similar</a>. <em>The Making of the Atomic Bomb</em> author Richard Rhodes thinks there are <a href="https://www.dwarkeshpatel.com/p/richard-rhodes#details:~:text=I%20don%27t%20think%20there%27s%20much%20question%20that%20AI%20is%20going%20to%20be%20at%20least%20as%20transformative%20as%20nuclear%20weapons%20and%20nuclear%20energy.">important parallels</a>. The New York Times ran a quiz asking people <a href="https://www.nytimes.com/2023/06/10/upshot/artificial-intelligence-nuclear-weapons-quiz.html">if they could distinguish quotes about nuclear weapons from quotes about AI</a>. Some policy experts are calling for a <a href="https://www.politico.com/news/magazine/2023/05/08/manhattan-project-for-ai-safety-00095779">Manhattan Project for AI</a>, just to make the analogy super-concrete. Anecdotally, I know tons of people working on AI policy who’ve been reading Rhodes’s book for inspiration. I recently saw a copy on a coffee table at Anthropic’s offices, when I was visiting there for a reporting trip.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="y4pLLt">
It’s easy to understand why people grasp for analogies like this. AI is a new, bewildering technology that many experts believe is extremely dangerous, and we want conceptual tools to help us wrap our heads around it and think about its consequences. But the analogy is crude at best, and there are important differences between the technologies that will prove vital in thinking about how to regulate AI to ensure it’s deployed safely, without bias against marginalized groups and with protections against misuse by bad actors.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6CvcQX">
Here’s an incomplete list of ways in which the two technologies seem similar — and different.
</p>
<h3 id="RCO7M4">
Similarity: extremely rapid scientific progress
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OlAij3">
In December 1938, the chemists Otto Hahn and Fritz Strassmann found that if they bombarded the radioactive element uranium with neutrons, <a href="https://www.google.com/books/edition/The_Making_of_the_Atomic_Bomb/aSgFMMNQ6G4C?hl=en&amp;gbpv=1&amp;pg=PA251&amp;printsec=frontcover">they got what looked like barium</a>, an element much smaller than uranium. It was a baffling observation — radioactive elements had to that point only been known to emit small particles and transmute to slightly smaller elements — but by <a href="https://www.google.com/books/edition/The_Making_of_the_Atomic_Bomb/aSgFMMNQ6G4C?hl=en&amp;gbpv=1&amp;pg=PA260&amp;printsec=frontcover">Christmas Eve</a>, their collaborators, the physicists Lise Meitner and Otto Frisch, had come up with an explanation: the neutrons had split the uranium atoms, creating solid barium and krypton gas. Frisch called the process “fission.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nIJeu8">
On July 16, 1945, after billions of dollars of investment and the equivalent of <a href="https://www.americanscientist.org/article/from-treasury-vault-to-the-manhattan-project">67 million hours of labor</a> from workers and scientists including Frisch, the US military detonated the Trinity device, the first nuclear weapon ever deployed, using the process that Frisch and Meitner had only theorized less than seven years earlier.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TbaH0U">
Few scientific fields have seen a theoretical discovery translated into an immensely important practical technology quite that quickly. But AI might come close. Artificial intelligence as a field was <a href="https://sitn.hms.harvard.edu/flash/2017/history-artificial-intelligence/">born in the 1950s</a>, but modern “deep learning” techniques in AI, which process data through several layers of “neurons” to form artificial “neural networks,” only took off with the <a href="https://www.economist.com/special-report/2016/06/23/from-not-working-to-neural-networking">realization around 2009</a> that specialized chips called graphics processing units (GPUs) could train such networks much more efficiently than standard central processing units (CPUs) on computers. Soon thereafter, <a href="https://people.idsia.ch/~juergen/DanNet-triggers-deep-CNN-revolution-2011.html">deep learning models</a> began <a href="https://proceedings.neurips.cc/paper_files/paper/2012/file/c399862d3b9d6b76c8436e924a68c45b-Paper.pdf">winning tournaments</a> testing their ability to categorize images. The same techniques proved able to <a href="https://www.deepmind.com/blog/alphago-zero-starting-from-scratch">beat world champions at Go</a> and <a href="https://www.vox.com/future-perfect/2019/1/24/18196177/ai-artificial-intelligence-google-deepmind-starcraft-game">StarCraft</a> and produce models like GPT-4 or Stable Diffusion that produce incredibly compelling text and image outputs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j8SqLM">
Progress in deep learning appears to be roughly exponential, because the computing resources and data applied to it seem to be steadily growing. The <a href="https://gwern.net/note/scaling">field of model scaling</a> estimates what happens to AI models as the data, computing power, and number of parameters available to them are expanded. A team at the Chinese tech giant Baidu demonstrated this in an <a href="https://arxiv.org/abs/1712.00409">empirical paper in 2017</a>, finding that “loss” (the measured error of a model, compared to known true results, on various tasks) decays at an exponential rate as the model’s size grows, and subsequent research from <a href="https://arxiv.org/abs/2001.08361">OpenAI</a> and <a href="https://arxiv.org/abs/2203.15556">DeepMind</a> has reached similar findings.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TSURKA">
All of which is to say: much as nuclear fission developed astonishingly quickly, advanced deep learning models and their capabilities appear to be improving at a similarly startling pace.
</p>
<h3 id="gPvGWh">
Similarity: potential for mass harm
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qJKaR8">
I presume I do not need to explain how nuclear weapons, let alone the thermonuclear weapons that make up modern arsenals, can cause mass harm on a scale we’ve never before experienced. The same potential for AI requires somewhat more exposition.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dbL93n">
Many scholars have demonstrated that existing machine learning systems adopted for purposes like <a href="https://www.wired.com/story/excerpt-from-automating-inequality/">flagging parents for Child Protective Services</a> often <a href="https://www.npr.org/transcripts/929204946">recapitulate biases from their training data</a>. As these models grow and are adopted for more and more purposes, and as we grow increasingly dependent on them, these kinds of biases will prove more and more consequential.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KpzDeN">
There is also substantial misuse potential for sufficiently complex AI systems. In an April paper, <a href="https://arxiv.org/abs/2304.05332">researchers at Carnegie Mellon</a> were able to stitch together large language models into a system that, when instructed to make chlorine gas, could figure out the right chemical compound and instruct a “cloud laboratory” (an online service where chemists can conduct real, physical chemistry experiments remotely) to synthesize it. It appeared capable of synthesizing VX or sarin gas (as well as methamphetamine) and only declined due to built-in safety controls that model developers could easily disable. Similar techniques could be used to <a href="https://www.vox.com/future-perfect/2023/6/21/23768810/artificial-intelligence-pandemic-biotechnology-synthetic-biology-biorisk-dna-synthesis">develop bioweapons</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lcNqqi">
Much of the information needed to make chemical or biological weapons is available publicly now, and has been for some time — but it requires specialists to understand and act on that information. The difference between a world where laypeople with access to a large language model can build a dangerous bioweapon, and a world where only specialists can, is somewhat akin to the difference between a country like the US where large-capacity semiautomatic guns <a href="https://www.vox.com/policy-and-politics/2015/12/4/9850572/gun-control-us-japan-switzerland-uk-canada">are widely available</a> and a country like the UK where access to such weapons is <a href="https://www.theguardian.com/uk-news/2021/aug/13/what-are-rules-firearms-licences-uk">strictly controlled</a>. The vastly increased access to these guns has left the US a country with <a href="https://www.vox.com/2015/10/1/18000444/gun-crime-us-foreign-countries#:~:text=Gun%20homicides%20are%20considerably%20more,Global%20Burden%20of%20Disease%20study.">vastly higher gun crime</a>. LLMs could, without sufficient controls, lead to a world where the lone wolves who currently kill through mass shootings in the US instead use bioweapons with the potential to kill thousands or even millions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wXYWRm">
Is that as bad as nuclear weapons? Probably not. For that level of harm you need <a href="https://www.lesswrong.com/posts/pRkFkzwKZ2zfa3R6H/without-specific-countermeasures-the-easiest-path-to">AI takeover scenarios</a> which are necessarily much more speculative and harder to reason about, as they require AIs vastly more powerful than anything that exists today. But the harms from things like algorithmic bias and bioweapons are more immediate, more concrete, and still large enough to demand a lot of attention.
</p>
<h3 id="qgsjx7">
Difference: one is a military technology, one is a general-purpose technology
</h3>
<figure class="e-image">
<img alt="In a black-and-white photo, a group of men stand around a pile of ash and melted, twisted metal, on a cracked desert landscape." src="https://cdn.vox-cdn.com/thumbor/7oXkv5sk-voh9COqg1UL4b4Ku8I=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24758587/615305238.jpg"/> <cite>Corbis via Getty Images</cite>
<figcaption>
Robert Oppenheimer, Gen. Leslie Groves, and other Manhattan Project team members examine the wreckage of the Trinity bomb demonstration.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="L2zz4u">
I do not use nuclear weapons in my everyday life, and unless you’re in a very specific job in one of a handful of militaries, you probably don’t either. Nuclear fission has affected our everyday lives through nuclear energy, which provides <a href="https://ourworldindata.org/nuclear-energy#what-share-of-primary-energy-comes-from-nuclear">some 4 percent of the world’s energy</a>, but due to its limited adoption, that technology hasn’t exactly transformed our lives either.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qu2nk3">
We don’t know with any specificity how AI will affect the world, and anyone who tells you what’s about to happen in much detail and with a great deal of confidence is probably grifting you. But we have reason to think that AI will be a <a href="https://openai.com/research/gpts-are-gpts">general-purpose technology</a>: something like electricity or telegraphy or the internet that broadly changes the way businesses across sectors and nations operate, as opposed to an innovation that makes a dent in one specific sector (as nuclear fission did in the energy sector and in military and geopolitical strategy).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GgfCxf">
Producing text quickly, as large language models do, is a pretty widely useful service for everything from marketing to technical writing to internal memo composition to lawyering (assuming <a href="https://fortune.com/2023/06/23/lawyers-fined-filing-chatgpt-hallucinations-in-court/">you know the tech’s limits</a>) to, unfortunately, disinformation and propaganda. Using AI to improve services like Siri and Alexa so they function more like a personal assistant, and can intelligently plan your schedule and respond to emails, would help in many jobs. McKinsey <a href="https://www.mckinsey.com/capabilities/mckinsey-digital/our-insights/the-economic-potential-of-generative-ai-the-next-productivity-frontier#key-insights">recently projected</a> that generative AI’s impact on productivity could eventually add as much as $4.4 trillion to the global economy — more than the annual GDP of the UK. Again, take these estimates with a large grain of salt, but the point that the technology will be broadly important to a range of jobs and sectors is sound.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LbxuQu">
Banning nuclear fission would probably be a bad idea — nuclear power is a very useful technology — but humans have other sources of energy. Banning advanced AI, by contrast, is clearly not viable, given how broadly useful it could be even with the major threats it poses.
</p>
<h3 id="NVlfyL">
Similarity: uranium and chips
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5vI7FG">
When the theoretical physicist Niels Bohr first theorized in 1939 that uranium fission was due to one specific isotope of the element (uranium-235), he thought this meant that a nuclear weapon would be wholly impractical. U235 is <a href="https://world-nuclear.org/information-library/nuclear-fuel-cycle/conversion-enrichment-and-fabrication/uranium-enrichment.aspx">much rarer</a> than the dominant uranium-238 isotope, and separating the two was, and remains, an incredibly costly endeavor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VtwLVN">
Separating enough U235 for a bomb, Bohr said at the time, “<a href="https://www.google.com/books/edition/The_Making_of_the_Atomic_Bomb/aSgFMMNQ6G4C?hl=en&amp;gbpv=1&amp;pg=PA294&amp;printsec=frontcover">can never be done unless you turn the United States into one huge factory</a>.” A few years later, after visiting Los Alamos and witnessing the scale of industrial effort required to make working bombs, which at its peak <a href="https://www.energy.gov/lm/manhattan-project-background-information-and-preservation-work#:~:text=At%20its%20peak%2C%20the%20project,the%20Manhattan%20Project%20is%20immense.">employed 130,000 workers</a>, he <a href="https://gwern.net/doc/radiance/1962-teller-thelegacyofhiroshima.pdf#page=213">quipped to fellow physicist Ed Teller</a>, “You see, I told you it couldn’t be done without turning the whole country into a factory. You have done just that.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NveYmL">
Separating out uranium in <a href="https://ahf.nuclearmuseum.org/ahf/location/oak-ridge-tn/">Oak Ridge, Tennessee</a>, was indeed a massive undertaking, as was the parallel effort in <a href="https://www.nps.gov/mapr/hanford.htm">Hanford, Washington</a>, to produce plutonium (the Hiroshima bomb used the former, the Trinity and Nagasaki bombs the latter). That gave arms control efforts something tangible to grasp onto. You could not make nuclear weapons without producing large quantities of plutonium or enriched uranium, and it’s pretty hard to hide that you’re producing large quantities of those materials.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ahNdfp">
A useful analogy can be made between efforts to control access to uranium and efforts to control access to the optimized computer chips necessary to do modern deep learning. While AI research involves many intangible factors that are difficult to quantify — the workforce skill needed to build models, the capabilities of the models themselves — the actual chips used to train models are <a href="https://asteriskmag.com/issues/03/how-we-can-regulate-ai">trackable</a>. They are built in a handful of fabrication plants (“fabs”). Government agencies can monitor when labs are purchasing tens or hundreds of thousands of these chips, and could <a href="https://arxiv.org/abs/2303.11341">even mandate firmware on the chips that logs certain AI training activity</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nfPMMT">
That’s led some analysts to <a href="https://arxiv.org/abs/2304.04123">suggest that an arms control framework for AI could look like that for nuclear weapons</a> — with chips taking the place of uranium and plutonium. This might be more difficult for various reasons, from the huge amount of international cooperation required (including between China and Taiwan) to the libertarian culture of Silicon Valley pushing against imprinting tracking info on every chip. But it’s a useful parallel nonetheless.
</p>
<h3 id="Jj4Cio">
Similarity: arms race dynamics
</h3>
<figure class="e-image">
<img alt="Lloyd Austin, a tall Black man in a black suit and blue tie, speaks to an audience out of view, in front of a screen showing a National Security Commission on AI logo." src="https://cdn.vox-cdn.com/thumbor/YmfL7Yqg0OERlcYpSdX101XejSk=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24759023/1328571814.jpg"/> <cite>Kevin Dietsch/Getty Images</cite>
<figcaption>
Secretary of Defense Lloyd Austin delivers remarks at the 2021 National Security Commission on Artificial Intelligence summit in Washington, DC. National security leaders like Austin are increasingly active in AI policy, fueling fears of an arms race.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bYcdoL">
As <a href="http://publ.royalacademy.dk/backend/web/uploads/2019-10-28/AFL%205/AFL%205/SP_132_00_00_1986_6188/SP_132_21_00_1986_6210.pdf#page=6">early as 1944</a>, Niels Bohr was holding meetings with Franklin Roosevelt and Winston Churchill and urging them in the strongest terms to tell Joseph Stalin about the atomic bomb project. If he found out through espionage, Bohr argued, the result would be distrust between the Allied powers after World War II concluded, potentially resulting in an arms race between the US/UK and the Soviet Union and a period of grave geopolitical danger as rival camps accumulated mass nuclear arsenals. Churchill thought this was absurd and <a href="https://ahf.nuclearmuseum.org/ahf/key-documents/hyde-park-aide-memoire/">signed a pledge with Roosevelt not to tell Stalin</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AJO22Q">
The postwar arms race between the US and the Soviet Union proceeded much as Bohr predicted, with Churchill’s nation as an afterthought.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="k3rQwb">
The historical context behind AI’s development now is much less fraught; the US is not currently in an alliance of convenience with a regime it despises and expects to enter geopolitical competition with as soon as a massive world war concludes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qe3xIb">
But the arms race dynamics that Bohr prophesied are already emerging in relation to AI and US-Chinese relations. Tech figures, particularly ex-Google CEO Eric Schmidt, have been <a href="https://ainowinstitute.org/publication/tracking-the-us-and-china-ai-arms-race">invoking the need for the US to take the lead on AI development</a> lest China pull ahead. National security adviser Jake Sullivan said in a speech last year that the US must maintain <a href="https://www.nbcnews.com/tech/innovation/chatgpt-intensified-fears-us-china-ai-arms-race-rcna71804">“as large of a lead as possible” in AI</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0yJ9Yj">
As my colleague <a href="https://www.vox.com/the-highlight/23621198/artificial-intelligence-chatgpt-openai-existential-risk-china-ai-safety-technology">Sigal Samuel has written</a>, this belief might rest on misconceptions that <a href="https://www.foreignaffairs.com/china/illusion-chinas-ai-prowess-regulation">being “first” on AI matters more than how one uses the technology</a>, or that China will leave its AI sector unregulated, when it’s <a href="https://twitter.com/hlntnr/status/1664656621790691329">already imposing regulations</a>. Arms races, though, can be self-fulfilling: if enough actors on each side think they’re in an arms race, eventually they’re in an arms race.
</p>
<h3 id="BaiaSP">
Difference: AI technology is much easier to copy
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lg6sax">
The vast majority of nations have declined to develop nukes, including many wealthy nations that easily have the resources to build them. Partially this limited proliferation is due to the fact that building nuclear weapons is fundamentally hard and expensive.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IQIpcL">
The International Campaign to Abolish Nuclear Weapons estimates that ultra-poor North Korea spent <a href="https://www.icanw.org/wasted_2022_global_nuclear_weapons_spending">$589 million on its nuclear program in 2022</a> alone, implying it has spent many billions over the decades the program has developed, Most countries do not want to invest those kinds of resources to develop a weapon they will likely never use. Most terrorist groups lack the resources to build such a weapon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pJoiHa">
AI is difficult and costly to train — but relative to nukes, much easier to piggyback off of and copy once some company or government has built a model. Take <a href="https://lmsys.org/blog/2023-03-30-vicuna/">Vicuna</a>, a recent language model built off of the <a href="https://ai.facebook.com/blog/large-language-model-llama-meta-ai/">LLaMA model</a> released by Meta (Facebook’s parent company), whose internal details were leaked to the public and are widely available. Vicuna was trained using about 70,000 conversations that real users had with ChatGPT which, when used to “fine tune” LLaMA, produced a much more accurate and useful model. According to its creators, training Vicuna cost $300, and they argue its output rivals that of ChatGPT and its underlying models (GPT-3.5 and GPT-4).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3UND97">
There are <a href="https://www.interconnects.ai/p/openai-google-llm-moats">lots of nuances here that I’m glossing over</a>. But the capability gap between hobbyist and mega-corporation is simply much smaller in AI than it is in nukes. A team of hobbyists trying to develop a nuclear weapon would have a much easier job than the Manhattan Project did, simply because they can benefit from everything the latter, and every nuclear project since, has learned. But they simply could not build a working nuclear device. People with minimal resources can build and customize advanced AI systems, even if not cutting-edge ones, and will likely continue to be able to do so.
</p>
<hr class="p-entry-hr" id="bc1g2z"/>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7ZPr67">
One expert I spoke to when thinking about this piece said bluntly that “analogies are the worst form of reasoning.” He has a point: one of my own takeaways from considering this particular analogy is that it’s tempting in part because it gives you a lot more historical material to work with. We know a <em>lot</em> about how nuclear weapons were developed and deployed. We know very <em>little</em> about how the future development and regulation of AI is likely to proceed. So it’s easier to drone on about nukes than it is to try to think through future AI dynamics, because I have more history to draw upon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n19uhk">
Given that, my main takeaway is that glib “AI=nukes” analogies are probably a waste … but more granular comparisons of particular processes, like the arms race dynamics between the US and Soviets in the 1940s and the US and China today, can possibly be fruitful. And those comparisons point in a similar direction. The best way to handle a new, powerful, dangerous technology is through broad international cooperation. The right approach isn’t to lie back and just let scientists and engineers transform our world without outside input.
</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>France’s highest administrative court says the soccer federation can ban headscarves in matches</strong> - The Council of State issued its ruling after a collective of headscarf-wearing soccer players called “Les Hijabeuses” campaigned against the ban.</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>ARCHERY | Abhishek Verma’s scintillating form a good omen ahead of big ticket events</strong> - The experienced compound archer, armed with a positive mindset and a new bow set, secured his third individual gold medal recently in Colombia</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>Isnt She Beautiful, Gimmler, Adbhut and Fast Rain please</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>Indian hockey hires mental trainer Paddy Upton for Men’s Asian Champions Trophy</strong> - Upton was part of the staff en route to Indian cricket team’s 2011 World Cup triumph</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>Rajasthan Royals set to offer Jos Buttler lucrative multi-year contract</strong> - “It is understood that the offer to Buttler is yet to be formally tabled, and its unclear whether the T20 World Cup winning captain intends to accept the deal,” a British newspaper reported</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>One killed as ‘rioters’ open unprovoked firing in Manipur’s Kangpokpi</strong> - While the local army unit tweeted that “unconfirmed reports” indicated some casualties in the incident, official sources said one body had been recovered from the area and a few others could be seen lying on the ground</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>Here are the big stories from Karnataka today</strong> - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated and written by Nalme Nachiyar.</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>Religious fervour, charity mark Bakrid in Telangana</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>Kerala scales up Gulf campaign to promote monsoon tourism</strong> - As a prelude, Kerala Tourism showcased a wide range of its products and themes in Dubai last month during the 30th edition of Arabian Travel Market</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>Rosemala to welcome visitors from July 1</strong> -</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What we know about killing of Paris teen… in 55 seconds</strong> - The BBC’s Hugh Schofield investigates at the scene where police shot dead 17-year-old Nahel.</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 shooting: Who was Nahel M, shot by police in Nanterre?</strong> - He was learning to be an electrician and played rugby league but died at a police check near Paris.</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>Paris shooting: Why French government backed family so fast</strong> - President Macron angered French police unions by criticising the shooting of a 17-year-old boy.</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>‘Mum was sent to Ireland, shamed and had to give me up’</strong> - A woman sent from Britain to Ireland as a baby speaks about repatriations of unmarried Irish mothers.</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>Ukraine war: Countdown has begun to end of Putin, say Kyiv officials</strong> - Senior officials suggest the Russian leader cannot survive a catastrophic loss of authority.</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>Speed matters: How Ethernet went from 3Mbps to 100Gbps… and beyond</strong> - One of the biggest computing inventions of all time, courtesy of Xerox PARC. - <a href="https://arstechnica.com/?p=1950755">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>US public wants climate change dealt with, but doesn’t like the options</strong> - People want both action and to keep using fossil fuels. - <a href="https://arstechnica.com/?p=1950878">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Brave aims to curb practice of websites that port scan visitors</strong> - Brave will allow users to choose which sites can access local network resources. - <a href="https://arstechnica.com/?p=1950882">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>NANOGrav hears “hum” of gravitational wave background, louder than expected</strong> - Exotic stars called millisecond pulsars serve as celestial metronomes. - <a href="https://arstechnica.com/?p=1950301">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Medical waste company sues health system over hidden human torso</strong> - The suit also alleges deceit, staged photos, and hidden hazardous waste. - <a href="https://arstechnica.com/?p=1950825">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>Forging A Return To Productive Conversation: An Open Letter to Reddit</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
To All Whom It May Concern,
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
For fifteen years, <a href="https://www.reddit.com/r/Jokes">/r/Jokes</a> has been one of Reddit’s most-popular communities. That time hasn’t been without its difficulties, but for the most part, we’ve all gotten along (with each other and with administrators). Members of our team fondly remember Moderator Roadshows, visits to Reddit’s headquarters, Reddit Secret Santa, April Fools’ Day events, regional meetups, and many more uplifting moments. We’ve watched this platform grow by leaps and bounds, and although we haven’t been completely happy about every change that we’ve witnessed, we’ve always done our best to work with Reddit at finding ways to adapt, compromise, and move forward.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
This process has occasionally been preceded by some exceptionally public debate, however.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
On June 12th, 2023, <a href="https://www.reddit.com/r/Jokes">/r/Jokes</a> joined thousands of other subreddits in protesting the planned changes to Reddit’s API; changes which – despite being immediately evident to only a minority of Redditors – threatened to worsen the site for everyone. By June 16th, 2023, that demonstration had evolved to represent a wider (and growing) array of concerns, many of which arose in response to <a href="https://www.washingtonpost.com/technology/2023/06/16/reddit-ceo-blackout-moderators-steve-huffman/">Reddit’s statements to journalists</a>. Today (June 26th, 2023), we are hopeful that users and administrators alike can make a return to the productive dialogue that has served us in the past.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
We acknowledge that Reddit has placed itself in a situation that makes adjusting its current API roadmap impossible.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
However, we have the following requests:
</p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Commit to exploring ways by which third-party applications can make an affordable return.
</li>
<li>
Commit to providing moderation tools and <a href="https://www.reddit.com/r/Blind/comments/14ds81l/rblinds_meetings_with_reddit_and_the_current/">accessibility options</a> (on Old Reddit, New Reddit, and mobile platforms) which match or exceed the functionality and utility of third-party applications.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Commit to prioritizing a significant reduction in spam, misinformation, bigotry, and illegal content on Reddit.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Guarantee that any future developments which may impact moderators, contributors, or stakeholders will be announced no less than one fiscal quarter before they are scheduled to go into effect.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Work together with longstanding moderators to establish a reasonable roadmap and deadline for accomplishing all of the above.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Affirm that efforts meant to keep Reddit accountable to its commitments and deadlines will hereafter not be met with insults, threats, removals, or hostility.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Publicly affirm all of the above by way of updating Reddit’s User Agreement and Reddit’s Moderator Code of Conduct to include reasonable expectations and requirements for administrators’ behavior.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Implement and fill a senior-level role (with decision-making and policy-shaping power) of “Moderator Advocate” at Reddit, with a required qualification for the position being robust experience as a volunteer Reddit moderator.
</li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Reddit is unique amongst social-media sites in that its lifeblood – its multitude of moderators and contributors – consists entirely of volunteers. We populate and curate the platform’s many communities, thereby providing a welcoming and engaging environment for all of its visitors. We receive little in the way of thanks for these efforts, but we frequently endure abuse, threats, attacks, and exposure to truly reprehensible media. Historically, we have trusted that Reddit’s administrators have the best interests of the platform and its users (be they moderators, contributors, participants, or lurkers) at heart; that while Reddit may be a for-profit company, it nonetheless recognizes and appreciates the value that Redditors provide.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
That trust has been all but entirely eroded… but we hope that together, we can begin to rebuild it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In simplest terms, Reddit, we implore you: <strong>Remember the human</strong>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
We look forward to your response by Thursday, June 29th, 2023.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
There’s also just <a href="https://i.imgur.com/xLmTxcR.jpg">one other thing</a>.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/JokeSentinel"> /u/JokeSentinel </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/14jn9rg/forging_a_return_to_productive_conversation_an/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/14jn9rg/forging_a_return_to_productive_conversation_an/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man is sitting on a flight from NYC to London</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He feels a little cold, so he asks the cabin attendant for a blanket. The cabin crew completely ignores him. On the seat next to him is no other than a parrot. The parrot screams “get me a scotch on the rocks you stupid cunt”. Not a moment passes and the parrot gets a nice glass of whiskey. The man asks for a blanket again only to be ignored. “Hey, old cow” yells the parrot “where’s my snacks?” Peanuts, cashews and salted almonds find themselves immediately on the parrot’s tray. The man gives up “I’m freezing you stupid bitch. What the hell do I need to do to get a fuckin’ blanket on this shit of a flight?!” The flight attendant says something into a comm system and a big man comes, opens the door at 37,000ft and throws both the man and the parrot out of the plane. On the way down, the parrot takes a good look at the man and says: “you know something? You’re pretty brave for someone with no wings”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/kfiri"> /u/kfiri </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/14lyz7d/a_man_is_sitting_on_a_flight_from_nyc_to_london/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/14lyz7d/a_man_is_sitting_on_a_flight_from_nyc_to_london/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man goes down to a ranch to look at a horse</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The rancher brings out a beautiful mare.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Can I see her teeth?” The man asks nicely.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Sure thing!” Says the rancher and opens her lips to show off her perfect teeth.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Bautiful! Can I see her tail and hooves?” The man asks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“By all means, partner!” Replied the rancher and turns her around to show her expertly manicured back left hoof and braided tail.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Lovely!” The man exclaimed “Now, can I see her twat?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“WHAT?!” Asked the rancher sharply.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Her twat, sir.” The man said again “Can I see her twat?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The rancher gets furious, grabs the man by the neck, lifts the horses tail, shoves the man’s face into the mare’s rear and shouts “Get a good look pervert!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I dont know why you did that!” Huffed the man exasperated, “All I <em>weawy</em> wanted was to see her <em>wun</em>!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/headexpl0dy"> /u/headexpl0dy </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/14lsc8q/a_man_goes_down_to_a_ranch_to_look_at_a_horse/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/14lsc8q/a_man_goes_down_to_a_ranch_to_look_at_a_horse/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Women say they like a man who is “funny” and “spontaneous”</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
But you knock on their bedroom window at midnight wearing a clown costume and suddenly it’s all screaming and throwing things and police sirens.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Gil-Gandel"> /u/Gil-Gandel </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/14lxsdh/women_say_they_like_a_man_who_is_funny_and/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/14lxsdh/women_say_they_like_a_man_who_is_funny_and/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What’s one thing you shouldn’t say at your boss’s funeral?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Who’s thinking outside the box now, Kyle?
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Dirt_Empty"> /u/Dirt_Empty </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/14l8pav/whats_one_thing_you_shouldnt_say_at_your_bosss/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/14l8pav/whats_one_thing_you_shouldnt_say_at_your_bosss/">[comments]</a></span></p></li>
</ul>
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