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+ + + ++Introduction: Self-medication is a serious public health concern globally and is more prevalent in underserved populations, especially in resource limited settings. The lack of effective treatment for COVID-19 and poor access to healthcare were drivers of self-medication. We investigated the prevalence and associated factors with self-medication for COVID-19 among slum dwellers in a Ugandan slum. Methods and materials: We conducted a cross-sectional study using randomly selected respondents from slums in Jinja city, Uganda. Households were proportionately selected from the slums and one participant with confirmed or self-reported COVID-19 during 2021 was recruited. Poisson regression with robust standard errors was used to determine the crude (CPR) and adjusted prevalence ratios (APR) (95% CI) of factors associated with self-medication. Variables were selected apriori and backward elimination approach used to fit the final multivariate model in which variables with a P≤ 0.05 were included. Results: Overall, 517 respondents were recruited, median age (years) was 31 (26-40), and 59% were male. The prevalence of self-medication for COVID-19 was 87.23% (451/517), 95% CI: [84.00%-90.00%] and 56% knew that self-medication was dangerous. Age≥50 years, compared to 20-29 years [APR: 1.12, 95% CI:1.05, 1.20], being female [APR: 1.07, 95% CI: 1.02, 1.13], minor [APR: 1.62, 95% CI: 1.25, 2.11], and severe symptoms [APR: 1.51, 95% CI: 1.16, 1.96], access to internet [APR: 1.13, 95% CI: 1.07, 1.20]. Having medical insurance [APR: 0.63, 95% CI: 0.46, 0.87] and awareness about laws against self-medication [APR: 0.89, 95% CI: 0.81, 0.97] were associated with a lower risk of self-medication. Conclusion: The prevalence of self-medication in slum dwellers in Uganda was high despite high awareness about its dangers. Self-medication was common in those with severe symptoms and those access to internet. There is need to control infodemia and improve health insurance cover in informal settlements within Uganda. +
++Omicron BA.2.86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the first isolation of the live BA.2.86 subvariant from a diagnostic swab collected in South Africa which we tested for escape from neutralizing antibodies and viral replication properties in cell culture. BA.2.86 did not have significantly more escape than Omicron XBB.1.5 from neutralizing immunity elicited by infection of Omicron subvariants ranging from BA.1 to XBB, either by infection alone or as breakthrough infection in vaccinated individuals. Neutralization escape was present relative to earlier strains: BA.2.86 showed extensive escape both relative to ancestral virus in sera from pre-Omicron vaccinated individuals and relative to Omicron BA.1 in sera from Omicron BA.1 infected individuals. We did not observe substantial differences in viral properties in cell culture relative to XBB.1.5. Both BA.2.86 and XBB.1.5 produced infection foci of similar size, had similar cytopathic effect (both lower than ancestral SARS-CoV-2), and had similar replication dynamics. We also investigated the relationship of BA.2.86 to BA.2 sequences and found that the closest were BA.2 samples from Southern Africa circulating in early 2022. These observations suggest that BA.2.86 is more closely related to sequences from Southern Africa than other regions and so may have evolved there, and that evolution led to escape from neutralizing antibodies similar in scale to recently circulating strains of SARS-CoV-2. +
++Since its emergence in 1968, influenza A H3N2 has caused yearly epidemics in temperate regions. While infection confers immunity against antigenically similar strains, new antigenically distinct strains that evade existing immunity regularly emerge (9antigenic drift9). Immunity at the individual level is complex, depending on an individual9s lifetime infection history. An individual9s first infection with influenza typically elicits the greatest response with subsequent infections eliciting progressively reduced responses (9antigenic seniority9). The combined effect of individual-level immune responses and antigenic drift on the epidemiological dynamics of influenza are not well understood. Here we develop an integrated modelling framework of influenza transmission, immunity, and antigenic drift to show how individual-level exposure, and the build-up of population level immunity, shape the long-term epidemiological dynamics of H3N2. Including antigenic seniority in the model, we observe that following an initial decline after the pandemic year, the average annual attack rate increases over the next 80 years, before reaching an equilibrium, with greater increases in older age-groups. Our analyses suggest that the average attack rate of H3N2 is still in a growth phase. Further increases, particularly in the elderly, may be expected in coming decades, driving an increase in healthcare demand due to H3N2 infections. We anticipate our findings and methodological developments will be applicable to other antigenically variable pathogens. This includes the recent pandemic pathogens influenza A H1N1pdm09, circulating since 2009, and SARS-CoV-2, circulating since 2019. Our findings highlight that following the short-term reduction in attack rates after a pandemic, if there is any degree of antigenic seniority then a resurgence in attack rates should be expected over the longer-term. Designing and implementing studies to assess the dynamics of immunity for H1N1pdm09, SARS-CoV-2, and other antigenically variable pathogens may help anticipate any long-term rises in infection and health burden. +
++Linking clinical biomarkers and lung pathology still is necessary to understand COVID-19 pathogenesis and the basis of progression to lethal outcomes. Resolving these knowledge gaps enables optimal treatment approaches of severe COVID-19. We present an integrated analysis of longitudinal clinical parameters, blood biomarkers and lung pathology in COVID-19 patients from the Brazilian Amazon. We identified core signatures differentiating severe recovered patients and fatal cases with distinct disease trajectories. Progression to early death was characterized by rapid and intense endothelial and myeloid activation, presence of thrombi, mostly driven by SARS-CoV-2 + macrophages. Progression to late death was associated with systemic cytotoxicity, interferon and Th17 signatures and fibrosis, apoptosis, and abundant SARS-CoV-2 + epithelial cells in the lung. Progression to recovery was associated with pro-lymphogenic and Th2-mediated responses. Integration of antemortem clinical and blood biomarkers with post-mortem lung-specific signatures defined predictors of disease progression, identifying potential targets for more precise and effective treatments. +
++Background: Immunocompromised patients with COVID-19 have higher morbidity and mortality than general population. Some authors have successfully used antiviral combination, but never in the early phase of the infection. Methods: Retrospective cohort study to describe efficacy and safety of the combination of 2 antivirals, with or without a mAb, both in early (within 10 days from symptoms) and in later phase (after 10 days) of SARS-CoV-2 infection in immunocompromised patients admitted to our facility. Results: We treated 11 patients (7 in early phase and 4 in later phase of COVID-19) with 10 days of intravenous remdesivir plus 5 days of oral nirmatelvir/ritonavir, also combined with sotrovimab in 10/11 cases. Notably, 100% of the <early> patients reached virological clearance at day 30 from the end of the therapy and were alive and well at follow-up, whereas corresponding figures in the <late> patients were 50% and 75%. Patients in late group more frequently needed oxygen supplementation (p=0.015) and steroid therapy (p=0.045) during admission and reached higher a COVID-19 severity (p=0.017). Discussion: The combination of antiviral and sotrovimab in early phase of COVID-19 in immunocompromised patients is well tolerated and associated with 100% of virological clearance. Patients treated later have lower response rate and higher disease severity, but a causative role of the therapy in such finding is yet to be demonstrated. +
++Excessive inflammation defines COVID-19 pathophysiology. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation. We conducted transcriptomic profiling of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, which revealed a pronounced type I interferon (IFN-I) gene signature in severe COVID-19, compared to mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 did not exhibit this signature and displayed a distinct immature neutrophil phenotype. PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation but reduced responsiveness to exogenous inflammasome priming. Interestingly, while mature neutrophils efficiently released IL-1? upon inflammasome activation, they were poor producers of IL-18. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes, which was confirmed in a COVID-19 mouse model. Overall, these findings underscore the crucial role of neutrophil inflammasomes in driving inflammation during severe COVID-19 and opens promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease. +
++The spatial and temporal changes of the COVID–19 pandemic have been monitored with wastewater–based surveillance, which many countries have applied to their national public health monitoring measures. The most commonly used methods for the detection of SARS–CoV–2 in wastewater are RT–qPCR and RT–ddPCR. Previous comparisons of the two methods have produced conflicting results; some found RT–ddPCR to be more sensitive, one found RT–qPCR to be more sensitive, and others found them to be equal in sensitivity. This research was conducted to further study these two methods as well as two different RNA extraction methodologies and gene assays for the detection of SARS–CoV–2 in wastewater. We compared two RT–qPCR kits and RT–ddPCR based on sensitivity, variability, and the correlation of SARS–CoV–2 gene copy numbers in wastewater with the incidence of COVID–19. Our results indicate that the most sensitive and low–variance method to detect SARS–CoV–2 in wastewater was RT–ddPCR. However, we obtained the best correlation between COVID-19 incidence and SARS–CoV–2 gene copy number in wastewater using RT–qPCR (CC = 0.697, p < 0.001). We found a significant difference in sensitivity between the two RT–qPCR kits, one having a significantly lower limit of detection and a higher percentage of positive samples than the other. Furthermore, the CDC N1 primers and probe were the most sensitive for both RT–qPCR kits, while there was no significant difference between the tested gene targets using RT–ddPCR. For the most sensitive RT–qPCR, the use of different RNA extraction kits affected the result. All methods showed a trend between COVID–19 incidence and SARS–CoV–2 gene copy numbers in wastewater. In addition, we tested an isothermal amplification method for the detection of SARS–CoV–2 RNA in wastewater. It proved to be a viable option if results are expected quickly, resources are limited, and presence–absence information is sufficient. +
++Importance: COVID–19 vaccines are authorized for use in children in the United States; real–world assessment of vaccine effectiveness in children is needed. Objective: To estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer–BioNTech) COVID-19 vaccine in US children. Design: A cohort study of children aged 5—17 years vaccinated with BNT162b2 matched with unvaccinated children. Setting: Participants identified in Optum and CVS Health insurance administrative claims databases were linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Participants: Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Exposure: BNT162b2 vaccinations were identified using IIS vaccination records and insurance claims. Main Outcomes and Measures: Two COVID–19 outcome definitions were evaluated: COVID–19 diagnosis in any medical setting and COVID–19 diagnosis in hospitals/emergency departments (EDs). Propensity score–weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant–specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. Results: There were 453,655 eligible vaccinated children one–to–one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person– years; CVS Health, 44.1 per 10,000 person– years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID–19 (meta–analyzed VE = 38% [95% CI, 36%–40%]) and hospital/ED–diagnosed COVID-19 (meta–analyzed VE = 61% [95% CI, 56%–65%]). VE estimates were lowest among children 5—11 years and during the omicron variant era. Conclusions and Relevance: Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID–19 and hospital/ED–diagnosed COVID–19 in children; observed VE estimates differed by age group and variant era. +
++Background: SARS-CoV-2 vaccines are highly effective in preventing severe COVID-19 but require boosting to maintain protection. Changes to circulating variants and prevalent natural immunity may impact on real-world effectiveness of boosters in different time periods and in different populations. Methods: With NHS England approval, we used linked routine clinical data from >24 million patients to evaluate the effectiveness of the 2022 combined COVID-19 autumn booster and influenza vaccine campaign in non-clinically vulnerable 50-year-olds in England using a regression discontinuity design. Our primary outcome was a composite of 6-week COVID-19 emergency attendance, COVID-19 unplanned hospitalisation, or death. The secondary outcomes were: respiratory hospitalisations or death; any unplanned hospitalisation; and any death. Results: Our study included 1,917,375 people aged 45-54 years with no evidence of being in a high-risk group prioritised for vaccination. By 26 November 2022, booster vaccine coverage was 11.1% at age 49.75 years increasing to 39.7% at age 50.25 years. The estimated effect of the campaign on the risk of the primary outcome in 50-year-olds during weeks 7-12 after the campaign start was -0.4 per 100,000 (95% CI -7.8, 7.1). For the secondary outcomes the estimated effects were: -0.6 per 100,000 (95%CI -13.5, 12.3) for respiratory outcomes; 5.0 per 100,000 (95%CI -40.7, 50.8) for unplanned hospitalisations; and 3.0 per 100,000 (95%CI -2.7, 8.6) for any death. The results were similar when using different follow-up start dates, different bandwidths, or when estimating the effect of vaccination (rather than the campaign). Conclusion: This study found little evidence that the autumn 2022 vaccination campaign in England was associated with a reduction in severe COVID-19-related outcomes among non-clinically vulnerable 50-year-olds. Possible explanations include the low risk of severe outcomes due to substantial pre-existing vaccine- and infection-induced immunity. Modest booster coverage reduced the precision with which we could estimate effectiveness. The booster campaign may have had effects beyond those estimated, including reducing virus transmission and incidence of mild or moderate COVID-19. +
++Background Lassa fever (LF) is a viral disease transmitted between animals and humans, commonly found in West Africa, including Nigeria. The region experiences an estimated annual total of about 2 million LF cases in humans, leading to 5,000 to 10,000 deaths. Strikingly, up to 80% of LF-infected individuals show no symptoms, making its true incidence hard to determine in endemic populations. We investigated LF distribution, mortality, survival patterns, and contributing factors during a local outbreak in Nigeria, from 2017 to 2021. Method Data from the Integrated Disease Surveillance and Response weekly line list for 2017 to 2021 were extracted. The survival pattern of LF patients was visualized with the Kaplan-Meier curve, binary logistic regression model was employed to explore LF-associated factors and level of statistical significance (α) was set at 5%. Result Overall, 4,554 participants were recruited between 2017 and 2021. Their average age varied from 31.82 ± 20.0 to 37.85 ± 17.89. LF-positive patients decreased from 26.9% in 2017 to 17.7% in 2021, paralleling the mortality trend. In 2021, patient survival ranged from 5 to 30 days. Male patients had lower survival odds in the initial 10 days of hospitalization, improved chances from days 10 to 20, and reduced probabilities beyond day 20. Residence location and age were significant factors (p<0.05) associated with LF in Ondo State. Conclusion The decline in LF cases in 2021 could be attributed to the ongoing intervention by Nigerian Centre for Disease Control or the disruption caused by the COVID-19 pandemic in 2020. To address LF challenges in hotspot areas, we propose Community Action Networks that would operate using the One Health approach involving local stakeholders sustainably to promote Early Warning/Early Response system in high-risk settings and mitigate LF-related issues. +
++Background: Vaccination helps prevent SARS-CoV-2 infection and severe COVID-19. However, vaccine-induced humoral immune responses vary among individuals and wane over time. We aimed to describe the SARS-CoV-2 anti-spike IgG antibody response to vaccination and identify health and demographic factors associated with this response among children and adults. Methods: We studied a subset of double-vaccinated children (n= 151; mean age: 12 ±1.5 years, 46% female) and adults (n= 995; 44 ±6.0 years, 60% female) from the Canadian CHILD Cohort. Dried blood spots were collected over two time periods (March 2021 to September 2021; October 2021 to January 2022). Antibody levels were quantified using automated chemiluminescent ELISAs. Demographic, vaccination, and health data were collected via online questionnaires. Associations were determined using multivariable regression. Results: Our cohort had SARS-CoV-2 anti-spike seropositivity rate of 97% following two COVID-19 vaccine doses. In both children and adults, the highest antibody levels were observed around three months post-vaccination and did not differ by biological sex. Higher antibody levels were associated with: prior SARS-CoV-2 infection (β=0.15 scaled luminescence units, 95%CI, 0.06-0.24), age <18 years (β=0.15, 95%CI 0.05-0.26) and receiving the Moderna mRNA (β=0.23, 95%CI 0.11-0.34) or Pfizer-BioNTech mRNA vaccines (β= 0.10, 95%CI, 0.02-0.18) vs. a combination of mRNA and Oxford-AstraZeneca viral vector vaccines. There were no differences in antibody levels when comparing a 3-8 vs. 9-16-week interval between vaccine doses. Interpretation: We identified key factors associated with post-vaccination antibody responses in children and adults, which could help improve future vaccine development and deployment among different population subgroups. +
++Objective: Research impact is difficult to measure, evaluate and report. This study aims to demonstrate how computational scientometric methods, including bibliometric, network analytic, and thematic summary measures can efficiently characterize complex scientific disciplines, such as primary care research. Methods: We used a retrospective cohort design. The study included N=17 international academic primary care research departments. A scientometric database was curated using a bottom-up methodology, which included peer-reviewed research articles/reviews, and associated meta-data, published between 01/01/2017 and 31/12/2022. Publication-level bibliometric information was queried from the Scopus application programming interface (API). The Altmetrics API was used to extract publication-level indicators of social engagement. Network analytic visualizations and statistics characterized research collaboration. Topic models and keyword mining characterized the main thematic areas of primary care research. At an author-level, we investigated correlations between bibliometric, altmetric, network analytic and topical summary measures. Results: Our analysis included N=591 primary care researchers (from 17 institutions) who produced 13,047 unique peer-reviewed articles over the study timeframe. These 13,047 research articles were published in 2,237 unique journal titles; cited 231,121 times; and received broad social uptake (605,349 Twitter tweets, 36,982 mainstream media mentions, 884 Wikipedia references, and 1,127 policy document citations). The 591 researchers collaborated with 35,585 unique co-authors resulting in 20,808,886 pair-wise collaborations. The median number of authors per publication was 7 (IQR: 4-10; min=1; max=3,391). Frequently occurring keywords/n-grams and latent topical vectors, highlighted the diversity of primary care research. Clinical research themes included: physical/mental health conditions, disease prevention and screening, issues in primary/obstetric/emergency/palliative-care, and public health. Methodological research themes included: research synthesis/appraisal, statistical/epidemiological inference, study design, qualitative research, mixed methods, health economics, medical education, and quality improvement. Many themes were stable over the study timeframe. COVID-19 emerged as an important research theme from 2020 through 2022. Topic vectors encoding clinical medicine were positively correlated with bibliometric, altmetric and network centrality measures, whereas, vectors encoding qualitative methods, medical education, and public health were negatively correlated with these same metrics. Conclusions: Multi-metric, computational scientometric methods offer an efficient, transparent, and reproducible means for characterizing the research output of complex scientific disciplines, such as primary care research. +
+A 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL - Condition: COVID-19
Interventions: Biological: hAd5-S-Fusion+N-ETSD; Biological: Placebo (0.9% (w/v) saline)
Sponsor: ImmunityBio, Inc.
Completed
Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome - Conditions: Post-COVID-19 Syndrome; Long-COVID-19 Syndrome
Intervention: Behavioral: Aerobic Exercise Training
Sponsors: University of Witten/Herdecke; Institut für Rehabilitationsforschung Norderney
Completed
Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations - Conditions: Immunosuppression; COVID-19
Intervention: Biological: NVX-CoV2372
Sponsors: University of Wisconsin, Madison; Novavax
Not yet recruiting
Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations - Conditions: Influenza; COVID-19; Influenza Immunogencity; COVID-19 Immunogenicity
Interventions: Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster); Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster); Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)
Sponsors: Duke University; Centers for Disease Control and Prevention; Arizona State University; University Hospitals Cleveland Medical Center; University of Pittsburgh; Washington University School of Medicine; Valleywise Health; VA Northeast Ohio Health Care; Senders Pediatrics
Not yet recruiting
Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia - Condition: Bronchoalveolar Lavage
Intervention: Procedure: Bronchoalveolar Lavage
Sponsors: Mohamed Abd Elmoniem Mohamed; Marwa Salah Abdelrazek Ghanem; Mohammad Khairy El-Badrawy; Tamer Ali Elhadidy; Dalia Abdellateif Abdelghany
Completed
Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults - Condition: SARS-CoV-2 Infection
Intervention: Biological: B/HPIV3/S-6P
Sponsors: National Institute of Allergy and Infectious Diseases (NIAID); Johns Hopkins Bloomberg School of Public Health; National Institutes of Health (NIH)
Recruiting
Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition - Condition: Cognitive Behavioral Therapy
Intervention: Behavioral: cognitive behavioral therapy
Sponsor: Tri-Service General Hospital
Not yet recruiting
The Effectiveness of Natural Resources for Reducing Stress - Conditions: Distress, Emotional; COVID-19
Interventions: Combination Product: Balneotherapy plus complex; Combination Product: Combined nature resources treatment; Other: Nature therapy procedure
Sponsors: Klaipėda University; Research Council of Lithuania
Active, not recruiting
Pre-probiotic Supplementation for Post-covid Fatigue Syndrome - Condition: Long COVID
Interventions: Dietary Supplement: Dietary Supplement: Experimental; Dietary Supplement: Dietary Supplement: Placebo
Sponsor: University of Novi Sad, Faculty of Sport and Physical Education
Active, not recruiting
Long COVID Immune Profiling - Conditions: Long COVID; POTS - Postural Orthostatic Tachycardia Syndrome; Autonomic Dysfunction
Interventions: Diagnostic Test: IL-6; Diagnostic Test: cytokines (IL-17, and IFN-ɣ); Behavioral: Compass 31
Sponsors: Vanderbilt University Medical Center; American Heart Association
Not yet recruiting
A Study of Healthy Microbiome, Healthy Mind - Conditions: Critical Illness; COVID-19; PICS; Cognitive Impairment; Mental Health Impairment; Weakness, Muscle; Dysbiosis
Intervention: Behavioral: Fermented Food Diet
Sponsor: Mayo Clinic
Not yet recruiting
Nirmatrelvir/ritonavir-induced elevation of blood tacrolimus levels in a patient in the maintenance phase post liver transplantation - Nirmatrelvir is an orally administered anti-SARS-CoV-2 drug used in combination with ritonavir, the drug-metabolizing cytochrome P450 (CYP) 3A inhibitor, to evade metabolism and extend bioavailability. Meanwhile, the immunosuppressant tacrolimus is a CYP3A4/5 substrate, and CYP3A inhibition results in drug-drug interactions. Herein, we report the case of a coronavirus disease 19 (COVID-19) patient in the maintenance phase post liver transplantation, receiving tacrolimus treatment, with a marked…
Comparison of Zinc Oxide Nanoparticle Integration into Non-Woven Fabrics Using Different Functionalisation Methods for Prospective Application as Active Facemasks - The development of advanced facemasks stands out as a paramount priority in enhancing healthcare preparedness. In this work, different polypropylene non-woven fabrics (NWF) were characterised regarding their structural, physicochemical and comfort-related properties. The selected NWF for the intermediate layer was functionalised with zinc oxide nanoparticles (ZnO NPs) 0.3 and 1.2wt% using three different methods: electrospinning, dip-pad-dry and exhaustion. After the confirmation of ZnO NP…
Membrane-Targeting Perylenylethynylphenols Inactivate Medically Important Coronaviruses via the Singlet Oxygen Photogeneration Mechanism - Perylenylethynyl derivatives have been recognized as broad-spectrum antivirals that target the lipid envelope of enveloped viruses. In this study, we present novel perylenylethynylphenols that exhibit nanomolar or submicromolar antiviral activity against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and feline infectious peritonitis virus (FIPV) in vitro. Perylenylethynylphenols incorporate into viral and cellular membranes and block the entry of the virus into the host cell….
Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients? - Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE-AAT) in which the two proteins are covalently bound. The lack of this complex, together with the…
Small Molecules Targeting Viral RNA - The majority of antivirals available target viral proteins; however, RNA is emerging as a new and promising antiviral target due to the presence of highly structured RNA in viral genomes fundamental for their replication cycle. Here, we discuss methods for the identification of RNA-targeting compounds, starting from the determination of RNA structures either from purified RNA or in living cells, followed by in silico screening on RNA and phenotypic assays to evaluate viral inhibition. Moreover,…
Screening, Synthesis and Biochemical Characterization of SARS-CoV-2 Protease Inhibitors - The severe acute respiratory syndrome-causing coronavirus 2 (SARS-CoV-2) papain-like protease (PL^(pro)) and main protease (M^(pro)) play an important role in viral replication events and are important targets for anti-coronavirus drug discovery. In search of these protease inhibitors, we screened a library of 1300 compounds using a fluorescence thermal shift assay (FTSA) and identified 53 hits that thermally stabilized or destabilized PL^(pro). The hit compounds structurally belonged to two…
The Influence of KE and EW Dipeptides in the Composition of the Thymalin Drug on Gene Expression and Protein Synthesis Involved in the Pathogenesis of COVID-19 - Thymalin is an immunomodulatory drug containing a polypeptide extract of thymus that has demonstrated efficacy in the therapy of acute respiratory distress syndrome and chronic obstructive pulmonary disease, as well as in complex therapy related to severe COVID-19 in middle-aged and elderly patients.. KE and EW dipeptides are active substances of Thymalin. There is evidence that KE stimulates cellular immunity and nonspecific resistance in organisms, exerting an activating effect on macrophages,…
Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants - The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown…
Nano-Enabled Antivirals for Overcoming Antibody Escaped Mutations Based SARS-CoV-2 Waves - This review discusses receptor-binding domain (RBD) mutations related to the emergence of various SARS-CoV-2 variants, which have been highlighted as a major cause of repetitive clinical waves of COVID-19. Our perusal of the literature reveals that most variants were able to escape neutralizing antibodies developed after immunization or natural exposure, pointing to the need for a sustainable technological solution to overcome this crisis. This review, therefore, focuses on nanotechnology and…
Macrophage-Derived Chemokine MDC/CCL22: An Ambiguous Finding in COVID-19 - Macrophage-derived chemokine (MDC/CCL22) is a chemokine of the C-C subfamily. It is involved in T-cellular maturation and migration. Our previous research shows that plasma CCL22/MDC tends to show a statistically significant depletion of concentrations in acute patients and convalescents when compared to healthy donors. In the current work, we investigate existing views on MDC/CCL22 dynamics in association with various pathologies, including respiratory diseases and, specifically, COVID-19….
USE OF RECOMBINANT S1 PROTEIN WITH hFc FOR ANALYSIS OF SARS-COV-2 ADSORPTION AND EVALUATION OF DRUGS THAT INHIBIT ENTRY INTO VERO E6 CELLS - The significant number of deaths and cases of infection by the new coronavirus SARS-CoV-2 requires an urgent demand for effective and available drugs for the treatment of COVID-19.However, the need for biosafety level 3 (NB-3) laboratories for experiments with the virus has made it very difficult for such research to meet this demand. It is known that angiotensin-converting enzyme 2 (ACE2), located on the surface of host cells, is the viral receptor for the spike (S) protein of SARS-CoV-2. This…
Discovery of new non-covalent and covalent inhibitors targeting SARS-CoV-2 papain-like protease and main protease - Global coronavirus disease 2019 (COVID-19) pandemic still threatens human health and public safety, and the development of effective antiviral agent is urgently needed. The SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) are vital proteins in viral replication and promising therapeutic targets. Additionally, PLpro also modulates host immune response by cleaving ubiquitin and interferon-stimulated gene product 15 (ISG15) from ISGylated host proteins. In this report, we identified…
Broad-Spectrum Antiviral Effect of Cannabidiol Against Enveloped and Nonenveloped Viruses - Introduction: Cannabidiol (CBD), the main non-psychoactive cannabinoid of the Cannabis sativa plant, is a powerful antioxidant compound that in recent years has increased interest due to causes effects in a wide range of biological functions. Zika virus (ZIKV) is a virus transmitted mainly by the Aedes aegypti mosquitoes, which causes neurological diseases, such as microcephaly and Guillain-Barre syndrome. Although the frequency of viral outbreaks has increased recently, no vaccinations or…
SARS-CoV-2 Nsp15 suppresses type I interferon production by inhibiting IRF3 phosphorylation and nuclear translocation - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), poses a significant threat to global public health security. Like other coronaviruses, SARS-CoV-2 has developed various strategies to inhibit the production of interferon (IFN). Here, we have discovered that SARS-CoV-2 Nsp15 obviously reduces the expression of IFN-β and IFN-stimulated genes (ISG56, CXCL10), and also inhibits IRF3 phosphorylation and nuclear translocation by…
Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19 - CONCLUSION: High Lp(a) concentration provides a possible explanation for low endogenous tPA enzymatic activity, and poor clinical outcomes in patients with COVID-19.
Narendra Modi’s New New Delhi - A multibillion-dollar revamp of India’s capital complex reflects the Prime Minister’s vision for the country’s future—and what he wants to erase from its past. - link
Did Authoritarianism Cause China’s Economic Crisis? - An erosion of trust between the government and its people now threatens the country’s decades-long boom. - link
Can Teachers and Parents Get Better at Talking to One Another? - Families are more anxious than ever to find out what happens in school. But there may be value in a measure of not-knowing and not-telling. - link
The Wisconsin G.O.P.’s Looming Judicial Attack - A state Supreme Court justice—recently elected in a landslide—may be impeached before she ever hears a case. - link
David Grann on Turning Best-Sellers Into Movies - The author of “Killers of the Flower Moon” and “The Wager” on his reporting process and adapting his work to the screen. Plus, Richard Brody makes the case for keeping your DVDs. - link
+If your friends have started throwing lavish, time-intensive birthday celebrations, here’s how to navigate. +
++The celebration was threefold: a dinner, a boozy art class, and a day party, held over the course of a weekend last October. Ashlee Kelly, 35, had committed to attending every festivity during the multi-day function, all in honor of a friend she’d known since high school. To get there, Kelly, a college and career coach, her husband, and their two young children caught a flight from Tampa Bay, where they live, to Maryland, to the hometown of the guest of honor. +
++The dinner, on a Saturday night, went off without incident. But by Sunday, after the four-hour paint-and-sip, Kelly was starting to have second thoughts about the party, scheduled to begin immediately after. She was exhausted from the long day of artistry and wine, and felt she’d spent enough time away from her husband and children. So Kelly decided not to complete the trifecta and bowed out of the final event. Kelly’s friend, the host, was not pleased. +
++“She just stopped talking to me,” Kelly says. The pair haven’t spoken since. +
++The weekend-long celebration in question was not commemorating a hugely significant milestone, such as upcoming nuptials or the birth of a child, but something far more mundane and universal: a birthday. That a nearly two-decade friendship crumbled over a missed birthday party — one she crossed state lines to attend — was painful, Kelly says. “I’m still mourning it,” she says, “because it’s honestly like you’re grieving.” +
++Kelly has grown accustomed to big asks from her friends on their birthdays. This spring, one pal suggested for her special day flying to Las Vegas to see Usher perform, a trip that Kelly says would’ve cost her thousands. Another friend recently hosted a dinner party at a restaurant, followed by a no-kids-allowed bash on the beach a few days later. “She has two sons, so it’s not like she doesn’t have kids,” Kelly says. She estimates she attends five to six blowout birthday parties a year. +
++While Kelly tries her best to accommodate her friends’ wishes on their birthdays, she is often put in a tough position, having to choose between her family and her companions. For the invitations she does decline, some friends see it as a personal rebuff. +
++Depending on who you talk to, birthdays rank as one of the most significant days of the year. Who better to spend it with than your closest confidantes? A YouGov poll of 1,000 Americans showed that 72 percent spend at least some of their birthdays with friends. +
++Among certain circles, however, birthday parties have ballooned beyond the standard dinner and cake. While lavish birthday celebrations give single and child-free adults an opportunity to bask in the spotlight for a day (or week) similar to the effect of weddings and baby showers, throwing yearly massive events can strain a relationship. Fêtes can now encompass weekend trips, expensive experiences — think multi-course meals, excursions, and concerts — or multiple events over many days. TikToker Sabrina Brier pithily parodied the “birthday weekend” archetype in a recent clip: “This weekend it’s Katie’s birthday weekend, so we have a lot of birthday plans she’s lined up,” she tells an off-camera friend. “So I’m going to be kind of out of commission.” In the Unpopular Opinion subreddit, a lively debate ensued on a 2020 thread titled “Your birthday is a DAY, not a weekend, not a week.” “Omg yes,” one Redditor wrote. “My bf’s stupid ass friend has a birthday week and demands gifts everyday. 1st day: a gift from her past that she used to like 2nd day: a gift for the future 3rd day: something random 4: food 5: idk 6: idk 7th: her actual birthday and more gifts from family.” +
++These lavish affairs are even causing some to go into debt. According to a recent Credit Karma report, 36 percent of Gen Z and millennials said they have a friend who drives them to overspend; of those, 15 percent of Gen Z, 21 percent of millennials, and 29 percent of Gen X respondents cite birthday celebrations as the reason for their spendthrift behavior, according to additional unpublished Credit Karma data shared with Vox. Birthdays that start to look more like bachelorette parties can be off-putting for those accustomed to more modest celebrations or for those whose budgets can’t accommodate high-priced affairs. Hosts may misread their friends’ lack of enthusiasm or funds as rejection, potentially causing a rift in the relationship. +
++A confluence of factors has contributed to the birthday scope creep, experts say. Pandemic lockdowns and foregone birthday celebrations created a demand for parties. The years surrounding a 21st birthday are crucial years for friendships, says Grace Vieth, a PhD student at the Social Interaction Lab at the University of Minnesota. Being isolated from friends during your early 20s — years meant for bonding and adventuring with peers — can exacerbate the feeling that you need to play catch-up. “People are seeking those experiences that they had, or that they wanted to have, in their early 20s, but now it’s really hard for people to do that because they’re investing in their jobs, in their career, in their romantic partnerships. Maybe they’re even having kids,” Vieth says. +
++Social media, notably TikTok and Instagram, can create the false narrative that everyone you know is having a blowout bash. Celebrators may also hold the belief that they aren’t sufficiently loved unless they are being celebrated in a visible way. As Americans rethink traditional milestones — like delaying or forgoing marriage and having children — perhaps birthdays can fulfill the need for a memorable celebration. +
++Birthday parties are a relatively recent phenomenon. While some ancient cultures such as the Greeks, Persians, and Egyptians marked the anniversary of birth, only high-ranking adult men were awarded such an honor. By the end of the 18th century, upper-class families in North America and Western Europe began more regularly celebrating children’s birthdays, but these events took place in the home and were centered around family. +
++The democratization of birthdays arrived in the early 20th century when everyone, regardless of age, gender, and social class, partook in the tradition of blowing out candles on the cake as a means of “understanding the individual existence as worth celebrating.” For children, birthday parties were seen as part of a normal and happy childhood. In the 1980s, birthday parties went through a commercial transformation: No longer hosted primarily at home, celebrations were held at venues like fast food restaurants, museums, bowling alleys, arcades, and other recreation centers. +
++As these children of the 1980s — and beyond — aged into adulthood, the love affair with birthday parties remained. Over half of Americans say they attended at least one birthday party in the last year, according to a YouGov poll, and 84 percent of people say they like or love the event — more than any other type of special occasion (such as a wedding or housewarming party). +
++The impending anniversary of your birth provides ample opportunity to reflect on your life and the people in it. Birthdays, according to one academic paper, strengthen one’s sense of belonging and importance: “[T]he birthday ceremony allows the celebrant to absorb positive impressions about himself.” When a friend fails to recognize your birthday, you may begin to question whether they’re a true friend after all. “I would argue that this is a day when, compared to all other days, you are looking for some demonstration that [friends] support you,” says friendship coach Danielle Bayard Jackson. +
++While Jackson’s coaching clients may not initially seek her out with specific birthday-related conundrums in mind, very often the roots of their conflicts trace back to a slight or disappointment that transpired during a birthday. The tension around birthday expectations arises frequently enough that Jackson dedicated an episode of her podcast to the phenomenon. “Some of this is tied to the idea that a true marker of friendship is you shouldn’t have to say what you need” on your birthday, Jackson says. “That’s very romantic, but you’re never going to get to a point of closeness where it transcends the need to communicate.” +
++Kenneth Miller has admittedly always set high expectations for his birthday, but “something always happens,” he says. On his 19th birthday, for instance, he planned a massive house party, but in an effort to not invite a certain acquaintance, Miller lied and said he wanted a low-key celebration. The acquaintance “turned around and told everybody else that I just wanted to keep it small, so nobody came,” Miller says. +
++This year, for his 21st birthday, Miller, a student, spent months planning a weekend road trip from his hometown of Phoenix to San Diego with three friends he’s known since middle school. Not only did Miller struggle to get his friends to commit to the trip, once the group arrived, Miller says, his friends slept in late, claimed food prices were too expensive, and seemed disinterested while at bars. While Miller acknowledges these friends are fairly introverted and don’t celebrate their own birthdays, he wanted to honor the milestone year with the people he knows best. “I think it really just came down to we had different priorities,” Miller says. +
++Potential conflict arises when reality doesn’t align with expectations. Written into the social contract of any friendship are a number of expectations, according to Jeffrey Hall, a professor of communication studies and the director of the Relationships and Technology Lab at the University of Kansas. Hall has narrowed the expectations of an ideal friendship down to six buckets, ranging from similarity with the other person to enjoying their company. Where does acknowledging a birthday fall within these defined assumptions of friendship? “It doesn’t,” Hall says. Conflict in friendship arises when two people have differing ideas on what it is to be a friend, Hall explains. In this gray area, tensions brew, say, if the birthday honoree expects their best friend to throw them a surprise party but the BFF considers a thoughtful text message sufficient acknowledgment. +
++If people aren’t clearly sharing their birthday expectations with their friends, they might be letting these expectations get shaped by social media. When social feeds are populated with images and videos of birthday vacations and ornate balloon backdrops, people begin to take these over-the-top gestures as commonplace. Just as social media comparison fueled the excesses of the wedding industry, a similar normalization of grandeur is transforming birthdays. “There’s an amount of consumerism that’s a part of this,” says therapist Shade Adekunle. “This desire of ‘I have to do it bigger and better than other people.’” +
++Tori D’Amico thought organizing a picnic for her 22nd birthday would be simple to execute, but the two days she spent baking a bright pink cake proved otherwise. The inspiration for the picnic came from TikTok, where the Philadelphia-based writer saw clips of other women with picturesque spreads. “It was all because I wanted to have something that felt special,” D’Amico, now 23, says, “because it looked like it felt special for other people.” +
++Rather than let online trends dictate the nature of a celebration, Jackson suggests removing outside influence altogether. “If you weren’t allowed to take pictures of your birthday gathering, what would you do?” she says. The pomp and circumstance of an event — and how that event is portrayed online — can overshadow the celebrant’s true intentions: to honor life and relationships. +
++As priorities shift and companions see each other less frequently, the more birthday parties are used as an excuse for friends to get together. However, when these celebrations begin to have the time and financial obligation typically associated with weddings or bachelorette parties, attendees need to prioritize certain events over others. Savannah, Georgia-based Aysia Woods has reached an age where many of her peers are simultaneously celebrating 30th birthdays, engagements, and marriages. “There’s so much to pay for,” says the 30-year-old entrepreneur and graduate student, “and it’s a bummer because I want to say yes to everybody’s wedding, everybody’s bachelorette, and everybody’s birthday, but it’s just like, I can’t afford it.” When weighing what events to attend, Woods considers how close she is with the host and whether she can show her support in other ways to the invites she declines. Due to academic and financial obligations, Woods turned down an invite to Miami for a friend’s 30th birthday but helped the host plan the event by curating a list of hotel and Airbnb options. +
++Considering the abundance of events afforded to coupled adults and parents — bridal and baby showers, bachelor and bachelorette parties, weddings, housewarming parties — some people may see celebrating their birthday as settling the score. “I have certainly had conversations with women who are single and child-free who speak to feeling a certain disappointment because they feel that there’s a lack of reciprocity in how they’re celebrated,” Jackson says. “Feeling like, I have to show up in all these ways because these milestones have more of a cultural reference than the milestones I’m experiencing in my life.” +
++Woods even attended a birthday that had the aesthetics of a wedding. A family friend’s 43rd birthday was held in a banquet hall, complete with a DJ and catering. “I just couldn’t figure out why are we doing this for a 43rd?” she says. “I’m so conflicted. Because I’m like, you made it to another year. That’s always a reason to celebrate.” +
++Surviving another revolution around the sun is significant enough for many to honor their birth. “I really disliked myself for a really long time,” says Kenneth Miller, the student in Phoenix who was disappointed by his friends’ lax attitudes during his birthday trip. Now that he’s more at home in his skin and empowered to ask for what he wants on his birthday, Miller wants the moments he celebrates himself to live up to his expectations. +
++“Now that I’m at a spot where I’m more comfortable with that,” he says, “it makes me want to do even more because I didn’t have the chance to do it at all growing up.” +
+A massive quake near Marrakesh on Friday night has killed more than 1,000. +
++More than 1,000 people are dead after a powerful earthquake with a magnitude of at least 6.8 hit Morocco Friday night near the city of Marrakesh, the largest such quake to hit the country decades. +
++The death toll is rapidly climbing as rescue workers search the towns and villages around the epicenter in the High Atlas Mountains and make their way through the rubble of Marrakesh’s old city, located about 70 kilometers north. Morocco’s leader, King Mohammed VI, has called upon the military to conduct search and rescue efforts, and other nations including France, the United Arab Emirates, and Turkey have pledged their support with the operation. +
++The area near the quake’s epicenter is known for its small, scenic villages tucked into the mountains while Marrakesh is an international tourist destination with a history dating back to the Middle Ages. The famous red walls representing the city’s boundary, as well as the Kutubiyya mosque in the old city, had both been damaged in the quake, but the full extent is still unknown. +
++Many Buildings in the old city are hundreds of years old; the Kutubiyya mosque dates back to the 12th century. Because earthquakes are rare in Morocco, structures are not built to withstand them as they might be in a city like San Francisco or Tokyo. Additionally, the quake was just 18 kilometers below ground, according to the United States Geological Survey, likely increasing the damage and portending a high death toll. “I would expect the final death toll to climb into the thousands once more is known,” Bill McGuire, professor emeritus of geophysical and climate hazards at University College London told the Associated Press. “As with any big quake, aftershocks are likely, which will lead to further casualties and hinder search and rescue.” +
++Both Marrakesh and the surrounding areas have a high population density, which will likely impact the casualty count. Though the impacted region itself has a population of around 1.8 million, parts of Marrakesh are more densely populated than Manhattan, according to a New York Times analysis of data from WorldPop, a project from the University of Southampton in Britain. +
++Earthquake science has improved in recent decades and insight into fault lines and possible quake locations is far clearer than it was in the past, which can help drive policy and preparation. But it’s still impossible to predict when earthquakes will happen — making it all the more important that vulnerable regions are prepared to withstand the disaster. +
++Morocco does have a prime minister, Aziz Akhannouch, but the king has final say in matters of state, according to Morocco’s constitution. Any international aid will have to be at Mohammed’s invitation. +
++The monarchy is an important institution to Morocco’s national identity, and dates back to the 8th century. Mohammed’s father, Hassan II, ruled for 38 years at a time of post-colonial transition for Morocco and the African continent more broadly; though he has a complicated legacy, he was a notable presence on the world stage and cultivated friendships with the US and Israel. +
++Mohammed, however, is often absent from his country, and not for diplomatic trips — he returned to Morocco this spring after extended trips abroad to France and Gabon, and is often seen in the company of German-born Moroccan Ultimate Fighting Championship fighter Abu Bakr Azaitar and his brothers. Though they haven’t been nearly as visible since Mohamed’s return, Moroccan press outlets often denigrate the brothers and express concern about their influence over the monarch, the Financial Times reported last month. +
++Morocco’s Royal Armed Forces have deployed helicopters, drones, and airplanes in the search and rescue mission, according to the Associated Press; travel by land to affected areas has been made extremely challenging due to traffic and debris from the quake. Mèdecins sans Frontières announced Saturday that it would send a team to Morocco and was already coordinating with local authorities. +
++Mohammed himself has not been seen or heard from since the quake; even his order to deploy forces for search and rescue was relayed through the Moroccan Army. Even though countries like Japan, Israel, and Turkey have offered support — and three French regions have even pledged $2 million for relief efforts— it’s not clear whether the king has accepted that aid. +
++Though Morocco is relatively stable in comparison with neighbors like Libya and Tunisia, it’s still contending with serious economic strife — including an agricultural sector suffering from prolonged droughts, and a tourism industry still recovering form the Covid-19 pandemic, not to mention crippling inflation due to the war in Ukraine. +
++Friday night’s earthquake is reminiscent of the one that rocked southern Turkey and parts of northern Syria in February, where inadequate infrastructure also contributed to the high casualty count and delayed search and rescue efforts. Though reforms to improve the buildings’ resistance to earthquakes were introduced in 2011, they have not been uniformly adopted in all of Morocco’s earthquake zones, the New York Times reported, and quality checks in poorer and rural areas are infrequent. +
+A massive quake in Morocco killed more than a thousand people. Here are eight things to know about these seismic events. +
++A powerful magnitude 6.8 earthquake rocked Morocco Friday night, the largest tremor to hit the country in at least 120 years. Officials report more than 1,000 people have died and expect the death toll to rise as rescuers reach remote afflicted areas. +
++Such strong earthquakes are rare in North Africa, which means few structures are designed to withstand them and residents have little experience responding when a quake occurs. +
++But earthquakes can still be deadly in earthquake-prone regions. In February, a huge magnitude 7.8 earthquake rattled across Turkey and Syria early Monday morning. Another quake with a magnitude of 7.7 rocked the region a few hours later. The quakes killed more than 50,000 people and toppled more than 6,600 buildings in the region. +
++Two major fault lines cross the Turkey and trigger shocks on a regular basis. Larger quakes are less frequent, but still a regular occurrence. Last November, Turkey suffered a magnitude 5.9 quake. A magnitude 7.0 quake rocked the Aegean Sea between Turkey and Greece in 2020. +
++While scientists have drastically improved their understanding of where earthquakes are likely to occur, forecasting when one will occur is still impractical. The rumbling earth can easily catch people off-guard, worsening the ensuing death and destruction. +
++In light of the recent disasters, here’s a refresher on earthquakes, along with some of the latest science on measuring and predicting them. +
++An earthquake occurs when massive blocks of the earth’s crust suddenly move past each other. These blocks, called tectonic plates, lie on top of the earth’s mantle, a layer that behaves like a very slow-moving liquid over millions of years. +
++That means tectonic plates jostle each other over time. They can also slide on top of each other, a phenomenon called subduction. The places on the planet where one plate meets another are the most prone to earthquakes. The specific surfaces where parcels of earth slip past each other are called faults. As plates move, pressure builds up across their boundaries, while friction holds them in place. When the former overwhelms the latter, the earth shakes as the pent-up energy dissipates. +
++Scientists understand these kinds of earthquakes well, which include those stemming from the San Andreas Fault in California and the East Anatolian Fault in Turkey. However, earthquakes can also occur within tectonic plates, as pressure along their edges cause deformations in the middle. These risks are harder to detect and measure. +
++“Our understanding of these within-plate earthquakes is not as good,” said Stanford University geophysics professor Greg Beroza. An earthquake within a tectonic plate has fewer telltale signs than those that occur at fault lines, he added. +
++The Richter scale, developed by Charles Richter in 1935 to measure quakes in Southern California, has fallen out of fashion. +
++It uses a logarithmic scale, rather than a linear scale, to account for the fact that there is such a huge difference between the tiniest tremors and tower-toppling temblors. On a logarithmic scale, a magnitude 7 earthquake is 10 times more intense than a magnitude 6 and 100 times more intense than a magnitude 5. +
++The Richter scale is actually measuring the peak amplitude of seismic waves, making it an indirect estimate of the earthquake itself. So if an earthquake is like a rock dropped in a pond, the Richter scale is measuring the height of the largest wave, not the size of the rock nor the extent of the ripples. +
++And in the case of an earthquake, the ripples aren’t traveling through a homogenous medium like water, but through solid rock that comes in different shapes, sizes, densities, and arrangements. Solid rock also supports multiple kinds of waves. (Some geologic structures can dampen big earthquakes while others can amplify lesser tremors.) +
++While Richter’s scale, calibrated to Southern California, was useful to compare earthquakes at the time, it provides an incomplete picture of risks and loses accuracy for stronger events. It also misses some of the nuances of other earthquake-prone regions in the world, and it isn’t all that useful for people trying to build structures to withstand them. +
++“We can’t use that in our design calculations,” said Steven McCabe, leader of the earthquake engineering group at the National Institute of Standards and Technology. “We deal in displacements.” +
++Displacement, or how much the ground actually moves, is one alternative way to describe earthquakes. Another is the moment magnitude scale. It accounts for multiple types of seismic waves, drawing on more precise instruments and better computing to provide a reliable measuring stick to compare seismic events. +
++When you hear about an earthquake’s magnitude in the news — like Turkey’s recent magnitude 7.8 quake — moment magnitude is usually the scale being used. +
++But this is still a proxy for the size of the earthquake. And with only indirect measurements, it can take up to a year to decipher the scale of an event, like the 2004 Indian Ocean earthquake, said Marine Denolle, an earthquake researcher at Harvard University. +
++“We prefer to use peak ground acceleration,” she said. This is a metric that measures how the speed and direction of the ground changes and has proven the most useful for engineers. +
++So, yes, earthquake scales have gotten a lot more complicated and specific over time. But that’s also helped scientists and engineers take much more precise measurements — which makes a big difference in planning for them. +
++Predicting earthquakes is a touchy issue for scientists, in part because it has long been a game of con artists and pseudoscientists who claim to be able to forecast earthquakes. (Their declarations have, of course, withered under scrutiny.) +
++Scientists do have a good sense of where earthquakes could happen. Using historical records and geologic measurements, they can highlight potential seismic hot spots and the kinds of tremors they face. (You can check out the US Geological Survey’s interactive map of fault lines and NOAA’s interactive map of seismic events.) +
++As for when quakes will hit, that’s still murky. +
++“Lots of seismologists have worked on that problem for many decades. We’re not predicting earthquakes in the short term,” said Beroza. “That requires us to know all kinds of information we don’t have.” +
++It’s difficult to figure out when an earthquake will occur, since the forces that cause them happen slowly over a vast area but are dispersed rapidly over a narrow region. What’s amazing is that forces built up across continents over millions of years can hammer cities in minutes. +
++Forecasting earthquakes would require high-resolution measurements deep underground over the course of decades, if not longer, coupled with sophisticated simulations. And even then, it’s unlikely to yield an hour’s worth of lead time. So there are ultimately too many variables at play and too few tools to analyze them in a meaningful way. +
++Some research shows that foreshocks can precede a larger earthquake, but it’s difficult to distinguish them from the hundreds of smaller earthquakes that occur on a regular basis. +
++On shorter time scales, texts and tweets can actually race ahead of seismic waves. In the 2011 Tohoku earthquake in Japan, for example, warnings from near the epicenter reached Tokyo 232 miles away, buying residents about a minute of warning time. +
++Many countries are now setting up warning systems to harness modern electronic communications to detect tremors and transmit alerts ahead of shaking ground, buying a few precious minutes to seek shelter. +
++Meanwhile, after a large earthquake, aftershocks often rock the afflicted region. “If we just had a big one, we know there will be smaller ones soon,” Denolle said. +
++When it comes to prediction, researchers understandably want to make sure they don’t overpromise and underdeliver, especially when thousands of lives and billions of dollars in damages are at stake. But even this caution has had consequences. +
++In 2012, six Italian scientists were sentenced to six years in prison for accurately saying the risks of a large earthquake in the town of L’Aquila were low after a small cluster of earthquakes struck the region in 2009. Six days after the scientists convened to assess the risk, a large quake struck and killed 309 people. Those convictions were later overturned and the ordeal has become a case study for how scientists convey uncertainty and risk to the public. +
++Reports of animals acting strange ahead of earthquakes date back to ancient Greece. But a useful pattern remains elusive. Feathered and furry forecasters emerge every time there’s an earthquake and there’s a cute animal to photograph, but this phenomenon is largely confirmation bias. Animals do weird things (by our standards) all the time and we don’t attach any significance to them until an earthquake happens. +
++“On any given day, there will be hundreds of pets doing things they’ve never done before and have never done afterward,” Beroza said. Bottom line: Don’t wait for weird animal behavior to signal that an earthquake is coming. +
++The gargantuan expansion of hydraulic fracturing across the United States has left an earthquake epidemic in its wake. It’s not the actual fracturing of shale rock that leads to tremors, but the injection of millions of gallons of wastewater underground. +
++Scientists say the injected water makes it easier for rocks to slide past each other. “When you inject fluid, you lubricate faults,” Denolle said. +
+ ++The US Geological Survey calls these “induced earthquakes” and reported that in Oklahoma, the number of earthquakes surged to 2,500 in 2014, 4,000 in 2015, and 2,500 in 2016. +
++“The decline in 2016 may be due in part to injection restrictions implemented by the state officials,” the USGS wrote in a release. “Of the earthquakes last year, 21 were greater than magnitude 4.0 and three were greater than magnitude 5.0.” +
++This is up from an average of two earthquakes per year of magnitude 2.7 or greater between 1980 and 2000. (“Natural” earthquakes, on the other hand, are not becoming more frequent, according to Beroza.) +
++Humans are causing earthquakes another way, too: Rapidly drawing water from underground reservoirs has also been shown to cause quakes in cities like Jakarta, Denolle said. +
++In general, scientists haven’t measured any effect on earthquakes from climate change. But they’re not ruling out the possibility. +
++As average temperatures rise, massive ice sheets are melting, shifting billions of tons of water from exposed land into the ocean and allowing land masses to rebound. That global rebalancing could have seismic consequences, but signals haven’t emerged yet. +
++“What might occur is enough ice melts that could unload the crust,” Beroza said, but added there is no evidence for this, nor for which parts of the world will reveal a signal. Denolle agreed that this could be a mechanism, but if there is any impact from climate change on earthquakes, she says she suspects it will be very small. +
++About 90 percent of the world’s earthquakes occur in the Ring of Fire, the region around the Pacific Ocean running through places like the Philippines, Japan, Alaska, California, Mexico, and Chile. The ring is also home to three-quarters of all active volcanoes. +
+ ++Mexico is an especially interesting case study. The country sits on top of three tectonic plates, making it seismically active. In 1985, an earthquake struck the capital, killing more than 10,000. Denolle noted that the geology of the region makes it so that tremors from nearby areas are channeled toward Mexico City, making any seismic activity a threat. +
++The Mexican capital is built on the site of the ancient Aztec city of Tenochtitlan, an island in the middle of a lake. The dry lakebed that is now the foundation of the modern metropolis amplifies shaking from earthquakes. +
++The 1985 earthquake originated closer to the surface, and the seismic waves it produced had a relatively long time between peaks and valleys. This low-frequency vibration sends skyscrapers swaying, according to Denolle. “The recent earthquakes were deeper, so they had a higher frequency,” she said. +
++The biggest factor in preventing deaths from earthquakes is building codes. Designing buildings to move with the earth while remaining standing can save thousands of lives, but putting them into practice can be expensive and frequently becomes a political issue. +
++“Ultimately, that information has got to get implemented, and you can pretty much get that implemented in new construction,” McCabe said. “The trickier problem is existing buildings and older stock.” +
++Earthquake-prone countries know this well: Japan has been aggressive about updating its building codes regularly to withstand earthquakes. The revised standards have in part fueled Japan’s construction boom despite its declining population. +
++Mexico has also raised standards for new construction. Laws enacted after the 1985 earthquake required builders to account for the soft lakebed soil in the capital and tolerate some degree of movement. +
++Meanwhile, Iran has gone through several versions of its national building standards for earthquake resilience. And Alaska has been developing earthquake damage mitigation strategies and response plans for years. +
++But codes are not always enforced, and the new rules only apply to new buildings. A school that collapsed in a 2017 Mexico City earthquake apparently was an older building that was not earthquake-resistant. And because the more recent earthquakes in Mexico shook the ground in a different way, even some of the buildings that survived the 1985 earthquake collapsed after tremors in 2017. +
++In countries like Iran, there is a wide gulf between how buildings are constructed in cities versus the countryside. More than a quarter of the country’s population lives in rural areas, where homes are built using traditional materials like mud bricks and stone rather than reinforced concrete and steel. This is a big part of why casualties are so high when earthquakes strike remote parts of the country. +
++The biggest risks fall to countries that don’t have a major earthquake in living memory and therefore haven’t prepared for them, or don’t have the resources to do so. A lack of a unified building code led to many of the more than 150,000 deaths in Haiti stemming from the 2010 magnitude 7.0 earthquake. +
++The really big one you keep hearing about is real. +
++The New Yorker won a Pulitzer Prize in 2015 for its reporting on the potential for massive earthquake that would rock the Pacific Northwest — “the worst natural disaster in the history of North America,” which would impact 7 million people and span a region covering 140,000 square miles. +
++The potential quake could reach a magnitude between 8.7 and 9.2, bigger than the largest expected earthquake from the San Andreas Fault, which scientist expect to top out at magnitude 8.2. +
++Large earthquakes are also in store for Japan, New Zealand, and other parts of the Ring of Fire. We don’t know when these earthquakes will rock us; we just have a rough estimate of the average time between them, which changes from region to region. +
++“In the business, we’ve been talking about that [Pacific Northwest] scenario for decades,” Beroza said. “I wouldn’t say we’re overdue, but it could happen at any time.” +
++“It is a threat,” echoed Denolle. “We forget about this threat because we have not had an earthquake there for a while.” “A while” means more than 300 years. +
++So while California has long been steeling itself for big earthquakes with building codes and disaster planning, the Pacific Northwest may be caught off guard, though the author of the New Yorker piece, Kathryn Schulz, helpfully provided a guide to prepare. +
++Update, September 9, 2023, 1:00 pm: This story was originally published in 2018 and has been updated to include news of the earthquake in Morocco. +
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Delay in bridge work makes students from A.P. villages to cross railway track to reach school near Tirupattur - We told our students not to cross the track but the detour is longer for them, says the headmaster of the government school
Plan to make Guntur market yard Asia’s largest energy-efficient chili trading hub - The transformation is planned through implementation of latest technologies and comprehensive energy audits, says official
There are no takers for Kannada medium engineering courses in Karnataka - Similarly, the response to the four year B.Sc. Honours engineering course is very poor; with the State government’s decision to withdraw the NEP, the future of these courses is to be reviewed
Vilachery artisans in Madurai see a slight increase in price of Ganesha idols - In some nooks, big size Ganeshas are being prepared and this year, the tallest that is being made here is an eight-feet idol, which is getting its final coat of paint
West Bengal Education department notifies new State Education Policy - The Education department issued the notification on September 9 which mooted the continuation of the State’s 5+4+2+2 school structure
Ukraine offensive could have only 30 days left - US Army chief - Gen Mark Milley tells Laura Kuenssberg the autumn weather will make Ukraine’s manoeuvres much harder.
Ukraine war: Kyiv foils big Russian drone attack, officials say - Ukraine’s capital is showered in debris from intercepted Russian drones, city officials say.
Greek floods: PM Mitsotakis warns of very unequal battle with nature - Rescuers try to reach hundreds of people trapped by floods in Greece where 10 people have died.
Elon Musk says he withheld Starlink over Crimea to avoid escalation - A senior Ukrainian official says this enabled Russian attacks and accuses him of “committing evil”.
Ukraine condemns ‘sham’ elections in Russian-occupied regions - Many taking part in early polling have been asked to vote in the presence of armed Russian soldiers.
The truth is out there: Celebrate 30 years of The X-Files with our 30 favorite episodes - From alien abductions to monsters of the week, this sci-fi series had something for everyone. - link
Microsoft offers legal protection for AI copyright infringement challenges - “Some customers are concerned about the risk of IP infringement claims,” says Microsoft. - link
Teen’s death after eating a single chip highlights risks of ultra-spicy foods - The hot pepper linked to teen’s death can cause arteries in the brain to spasm. - link
The MonsterVerse comes to Apple TV+ with Monarch: Legacy of Monsters teaser - “If you come with me, you’ll know everything, I promise.” - link
X sues Calif. to avoid revealing how it makes “controversial” content decisions - X decried law’s “draconian financial penalties” up to $15K per violation per day. - link
Three friends celebrate with a night on the town… -
++Three friends celebrate with a night on the town. The day after, hung over, the three friends meet. +
++The first friend says, “I can’t believe how much we drank last night! I was so drunk, I blew chunks!” +
++The second friend shakes his head and says, “You think that’s bad? I got so drunk last night, I’m pretty sure I peed in my own backpack thinking it was a urinal.” +
++The third friend, not to be outdone, goes, “If that’s the worst thing that happened to the both of you, then you got off easy! I slept with my wife’s sister! My wife already found out and wants a divorce..” +
++The first friend looking deadly serious goes, “I don’t think you two understand.. Chunks is my dog..” +
+ submitted by /u/Ok_Star_4136
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The spoon -
++Customer at restaurant drops a spoon. Waiter nearby immediately replaces the dropped spoon with a clean one from his breast pocket. Next time the customer sees him, the waiter has a new spoon in his breast pocket so the customer asks about the spoon. +
++“The owners hired a consultant some time ago to improve out efficiency” the waiter says. “They found that the spoon is the most often dropped utensil in our restaurant and told us to carry a clean spoon in our breast pockets so that we can immediately replace the dropped spoon instead of walking back to get a clean one; this saves us an average of three minutes per shift.” +
++The customer thanks him for the explanation and continues the meal. When the waiter brings the check, the customer notices a piece of string dangling from the waiter’s pants zipper area and discreetly lets him know. The waiter explains “oh this was another efficiency improvement. The consultants figured out that we could save 45 seconds hand-washing time each trip to the bathroom if we avoided touching our junk. This string allows me to bring my penis out when I use the bathroom.” +
++“Weird, but OK” says the customer “but how do you put it back in?” +
++“They didn’t tell us that part. I personally use the spoon.” +
+ submitted by /u/zalanthir
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A guy goes into a restaurant for lunch. -
++After careful consideration, he decides he will have a bowl of the day’s soup. The waiter praises him for his decision. +
++"Ah, excellent choice. The chef makes the soup fresh each day from only the freshest, locally-sourced ingredients. It is completely organic, and there are no additives or preservatives. +
++“Well, it sounds delicious,” the man says. “I can’t wait to try it.” +
++“Very good sir!” the waiter says. “I guarantee you will not be disappointed.” +
++A few minutes later, the waiter brings out the soup and places it in front of the man. +
++“Bon appetit!” he says and strides off. However, after a few moments, he spots the man waving him over. +
++“Yes sir?” +
++“Taste this soup,” the man says. +
++“I beg your pardon?” +
++“Taste the soup,” the man says. +
++“Is there a problem? I cannot imagine there could be a problem. The chef is renowned for his recipes, and this soup is one of his specialties.” +
++“Taste the soup,” the man says again. +
++“Perhaps I should get the headwaiter,” the waiter says nervously. He dashes off. +
++After a minute or two, the waiter appears with the headwaiter. +
++“I understand there is a problem?” he says. +
++“Taste the soup,” the man says. +
++“Sir, I’ll have you know we have never had a complaint in the history of this establishment. Our chef has a reputation for excellence, and has in fact won a number of culinary awards. His work is beyond reproach.” +
++“Taste the soup,” the man says again. +
++“I think I need to fetch the house manager,” the headwaiter says, and rushes off. +
++He returns a few moments later with the tuxedoed house manager. +
++“What seems to be the problem?” the house manager asks. +
++“Taste the soup,” the man says. +
++“Monsieur. I will have you know that this establishment is among the most respected and revered in the country. The chef is brilliant, known for his innovative and imaginative recipes. He trained at the most prestigious European culinary schools, and has won the acclaim and admiration of his peers the world over. Even questioning his abilities is a grave insult.” +
++“Taste the soup,” the man says again. +
++“This is outrageous. I shall call the chef himself!” the house manager says, and rushes to the kitchen. +
++A few moments later, he returns with the chef, a burly, humourless man with large hands and a red face. He glares at the man. +
++“You have something you wish to say?” the chef says. +
++“Taste the soup,” the man says. The chef’s eyes narrow as he leans over the table. +
++“I have been the chef in this establishment for 25 years. I have prepared meals for presidents and kings. My reputation is unequalled, and every day I receive offers of employment. I can work anywhere in the world for anyone I choose. Yet you would sit here and impugn my reputation?” +
++“Taste the soup,” the man says. +
++“Taste the soup? Taste the soup? Good sir, I made this soup myself from a recipe that has been handed down through the generations in my family. This was my great-great-grandmother’s own recipe and it is beloved.” +
++“Taste the soup,” the man says. +
++“Taste the soup? TASTE THE SOUP?? I have never been so affronted! Taste the soup? Fine. I will taste the soup!!” +
++He leans across the table and stops in confusion. +
++“But where is the spoon? You have no spoon,” the chef says. +
++“Right,” the man says. +
+ submitted by /u/brother_p
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3500 years ago, the Greeks discovered that you couldn’t get pregnant through anal sex. -
++700 years later, the Romans discovered that it also worked with women. +
+ submitted by /u/scottcmu
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A man asked how much half a head of lettuce costs. -
++A guy is working at a grocery store when a man approaches him, asking how much half a head of lettuce costs. After some arguing, the worker goes to his manager and says, “Boss, some jackass wants to buy half a head of lettuce.” +
++They turn around and see that the customer has followed them to listen in. The worker says, “It’s okay, though. This fine gentlemen agreed to buy the other half!” +
+ submitted by /u/notaredditreader
[link] [comments]