The multi-dimensional challenges of controlling respiratory virus transmission in indoor spaces: Insights from the linkage of a microscopic pedestrian simulation and SARS-CoV-2 transmission model -
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+SARS-CoV-2 transmission in indoor spaces, where most infection events occur, depends on the types and duration of human interactions, among others. Understanding how these human behaviours interface with virus characteristics to drive pathogen transmission and dictate the outcomes of non-pharmaceutical interventions is important for the informed and safe use of indoor spaces. To better understand these complex interactions, we developed the Pedestrian Dynamics - Virus Spread model (PeDViS): an individual-based model that combines pedestrian behaviour models with virus spread models that incorporate direct and indirect transmission routes. We explored the relationships between virus exposure and the duration, distance, respiratory behaviour, and environment in which interactions between infected and uninfected individuals took place, and compared this to benchmark at risk interactions (1.5 metres for 15 minutes). When considering aerosol transmission, individuals adhering to distancing measures may be at risk due to build-up of airborne virus in the environment when infected individuals spend prolonged time indoors. In our restaurant case, guests seated at tables near infected individuals were at limited risk of infection but could, particularly in poorly ventilated places, experience risks that surpass that of benchmark interactions. Combining interventions that target different transmission routes can aid in accumulating impact, for instance by combining ventilation with face masks. The impact of such combined interventions depends on the relative importance of transmission routes, which is hard to disentangle and highly context dependent. This uncertainty should be considered when assessing transmission risks upon different types of human interactions in indoor spaces. We illustrated the multi-dimensionality of indoor SARS-CoV-2 transmission that emerges from the interplay of human behaviour and the spread of respiratory viruses. A modelling strategy that incorporates this in risk assessments can help inform policy makers and citizens on the safe use of indoor spaces with varying inter-human interactions.
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How can selective processing of vaccination information be diminished? Effects of mindsets and kinds of information -
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+Background: Selective processing of attitude-consistent information is a substantial obstacle in convincing vaccine-skeptical people of the benefits of vaccinations. This study tests (i) which types of information are particularly prone to such selective information processing, and (ii) whether a deliberative (vs. implemental) mindset focusing on potential benefits and harms may diminish its effects. Design: 612 Mturk participants were randomized into an implemental or deliberative mindset and received a flu vaccine-skeptical narrative, a flu vaccination facts box transparently summarizing risks and benefits, and a message by the Center for Disease Prevention and Control (CDC) in favor of the flu vaccine either referring to COVID-19 or not. We tested how these variations affected the acceptance of and the willingness to share each message. Furthermore, we evaluated their impact on flu vaccination attitudes and intentions. Results: The mindset manipulation failed to diminish generally prevalent selective information processing. While vaccine-skeptics did not accept and like the CDC message referring to COVID-19 (particularly in a deliberative mindset), they generally accepted the vaccination facts box more readily compared to both CDC messages. Conclusion: While mindsets were ineffective, more general and transparent information may be more likely to reach an anti-vaccine audience.
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Predicting Depression and Anxiety Among Adults with Disabilities During the COVID-19 Pandemic -
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+Purpose/Objective: Emerging research has highlighted sources of magnified stress and trauma for people with disabilities during the COVID-19 pandemic, as compared to others in the general population. However, little research has examined the mental health impact of the pandemic on people with disabilities in relation to disability-related stigma, social isolation, and demographic characteristics. The present study therefore sought to identify predictors of depression and anxiety symptoms among U.S. adults with disabilities during the COVID-19 pandemic. Research Methods/Designs: Data were collected online between October and December 2020. U.S. adults with disabilities (n = 441) completed self-report measures of depression, anxiety, psychosocial processes, and a range of demographic and disability characteristics. Results: In our sample, 61.0% and 50.0% of participants met criteria for a probable diagnosis of major depressive disorder and generalized anxiety disorder, respectively. Participants also experienced significantly higher levels of disability-related stigma and social isolation compared to pre-pandemic norms. Hierarchical regression analyses identified higher social isolation, presence of chronic pain, younger age, higher disability-related stigma, and higher worries about contracting COVID-19 as significant predictors of both depression and anxiety symptoms. Conclusion/implications: This study highlights important demographic and psychosocial predictors of mental health risks for people with disabilities in the context of COVID-19. Findings further underscore the need to attend to those at elevated risk within the disability community as rehabilitation professionals, disability organizations, and policymakers work to support people with disabilities in post-pandemic recovery and create a more equitable response to ongoing and future public health crises.
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Narrative identity among people with disabilities during the COVID-19 pandemic: The interdependent self -
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+This study examines narrative identity among a large, diverse (American) sample of people with disabilities (PWDs) during the “second wave” of the COVID-19 pandemic (October-December, 2020). The study relied on abductive analyses, combining a purely inductive phase of inquiry followed by two rounds of investigation that filtered inductive insights through three theoretical lenses: social-ecological theory, the theory of narrative identity, and perspectives from the interdisciplinary field of disability studies. The central result was the identification of a particular configuration of self, one that was demonstrably interdependent with both immediate interpersonal contexts and with broader cultural contexts. This interdependent self was interpreted in both positive and negative ways by PWDs. These findings invite future inquiry into commonplace conceptualizations of an independent self at the center of personality research.
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Design of SARS-CoV-2 protease inhibitors with improved affinity and reduced sensitivity to mutations -
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+Inhibitors of the SARS-CoV-2 main protease (Mpro) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function on these mutants are thus urgently needed. We hypothesized that the covalent HCV protease inhibitor boceprevir (BPV) could serve as the basis for orally bioavailable drugs that inhibit SARS-CoV-2 Mpro more tightly than existing drugs. Performing structure-guided modifications of BPV, we developed a picomolar-affinity inhibitor, ML2006a4, with antiviral activity, oral pharmacokinetics, and therapeutic efficacy similar or superior to NTV. A crucial feature of ML2006a4 is a novel derivatization of the ketoamide reactive group that improves cell permeability and oral bioavailability. Finally, ML2006a4 is less sensitive to several mutations that cause resistance to NTV or ETV and occur in the natural SARS-CoV-2 population. Thus, anticipatory drug design can preemptively address potential resistance mechanisms.
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+The continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.5 and XBB.1.16, highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters. Vaccination strategies that can counter immune imprinting are critically needed. In this study, we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. Our results show that in mice, the efficacy of single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB, while the concerning situation could be largely mitigated by a second Omicron booster. Similarly, in humans, we found that repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers against XBB.1.5 and XBB.1.16 in both plasma and nasal mucosa. By isolating 781 RBD-targeting mAbs from repeated Omicron infection cohorts, we revealed that double Omicron exposure alleviates immune imprinting by generating a large proportion of highly matured and potent Omicron-specific antibodies. Importantly, epitope characterization using deep mutational scanning (DMS) showed that these Omicron-specific antibodies target distinct RBD epitopes compared to WT-induced antibodies, and the bias towards non-neutralizing epitopes observed in single Omicron exposures due to imprinting was largely restored after repeated Omicron stimulation, together leading to a substantial neutralizing epitope shift. Based on the DMS profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated the combinations of these mutations could further boost XBB.1.5’s immune-evasion capability while maintaining high ACE2 binding affinity. Our findings suggest the WT component should be abandoned when updating COVID-19 vaccine antigen compositions to XBB lineages, and those who haven’t been exposed to Omicron yet should receive two updated vaccine boosters.
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Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease -
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+Nonstructural protein 5 (Nsp5) is the main protease of SARS-CoV-2 that cleaves viral polyproteins into individual polypeptides necessary for viral replication. Here, we show that Nsp5 binds and cleaves human tRNA methyltransferase 1 (TRMT1), a host enzyme required for a prevalent post-transcriptional modification in tRNAs. Human cells infected with SARS-CoV-2 exhibit a decrease in TRMT1 protein levels and TRMT1-catalyzed tRNA modifications, consistent with TRMT1 cleavage and inactivation by Nsp5. Nsp5 cleaves TRMT1 at a specific position that matches the consensus sequence of SARS-CoV-2 polyprotein cleavage sites, and a single mutation within the sequence inhibits Nsp5-dependent proteolysis of TRMT1. The TRMT1 cleavage fragments exhibit altered RNA binding activity and are unable to rescue tRNA modification in TRMT1-deficient human cells. Compared to wildtype human cells, TRMT1- deficient human cells infected with SARS-CoV-2 exhibit reduced levels of intracellular viral RNA. These findings provide evidence that Nsp5-dependent cleavage of TRMT1 and perturbation of tRNA modification patterns contribute to the cellular pathogenesis of SARS-CoV-2 infection.
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Faith and Outgroup Dehumanization During COVID -
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+We explore how Christians and Buddhists, of different religiosity, react to death within the context of the Covid-19 pandemic. Previous research has found that the interaction between cultural level, individual level and situational level factors are necessary to consider for a more comprehensive grasp of a phenomenon. We look at how Religion x Religiosity x Threat of Covid interact and show different relationships between these variables and dehumanization. We find that at higher levels of disruption by Covid-19 on religious practice (but not lower levels), Christians high on extrinsic religiosity (but low on intrinsic religiosity) dehumanized religious outgroups the most, whereas Christians high on extrinsic and high on intrinsic religiosity dehumanized religious outgroups significantly less. At low levels of impact of Covid-19 on religious practice, only higher levels of extrinsic religiosity were related to higher levels of dehumanization. Buddhists, regardless of level of religiosity and impact of Covid-19 to religious practice, consistently showed a relatively low level of dehumanization against religious outgroups. Findings are triangulated through multiple sources of data and further elaborated through qualitative coding of open-ended responses. These enactment patterns contribute to the religion and terror management literature and offer insights for potentially developing inclusive understanding with outgroup members.
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Predicting the impact of COVID-19 non-pharmaceutical intervention on short- and medium-term dynamics of enterovirus D68 in the US -
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+Recent outbreaks of enterovirus D68 (EV-D68) infections, and their causal linkage with acute flaccid myelitis (AFM), continue to pose a serious public health concern. During 2020 and 2021, the dynamics of EV-D68 and other pathogens have been significantly perturbed by non-pharmaceutical interventions against COVID-19; this perturbation presents a powerful natural experiment for exploring the dynamics of these endemic infections. In this study, we analyzed publicly available data on EV-D68 infections, originally collected through the New Vaccine Surveillance Network, to predict their short- and long-term dynamics following the COVID-19 interventions. Although there are large uncertainties in our predictions, the likelihood of a large outbreak in 2023 appears to be low. Comprehensive surveillance data are needed to narrow uncertainties in future dynamics of EV-D68. The limited incidence of AFM cases in 2022, despite large EV-D68 outbreaks, poses further questions for the timing of the next AFM outbreaks.
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Application of Machine Learning in Prediction of COVID-19 Diagnosis for Indonesian Healthcare Workers -
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+The COVID-19 pandemic poses a heightened risk to health workers, especially in low-and middle-income countries such as Indonesia. Due to the limitations of implementing mass RT-PCR testing for health workers, high-performing and cost-effective methodologies must be developed to help identify COVID-19 positive health workers and protect the spearhead of the battle against the pandemic. This study aimed to investigate the application of machine learning classifiers to predict the risk of COVID-19 positivity (by RT-PCR) using data obtained from a survey specific to health workers. Machine learning tools can enhance COVID-19 screening capacity in high-risk populations such as health workers in environments where cost is a barrier to the accessibility of adequate testing and screening supplies. We built two sets of COVID-19 Likelihood Meter (CLM) models: one trained on data from a broad population of health workers in Jakarta and Semarang (full model) and tested on the same, and one trained on health workers from Jakarta only (Jakarta model) and tested on both the same and an independent population of Semarang health workers. The area under the receiver-operating-characteristic curve (AUC), average precision (AP), and the Brier score (BS) were used to assess model performance. Shapely additive explanations (SHAP) were used to analyse future importance. The final dataset for the study included 5,393 healthcare workers. For the full model, the random forest was selected as the algorithm choice. It achieved cross-validation of mean AUC of 0.832 ± 0.015, AP of 0.513 ± 0.039, and BS of 0.124 ± 0.005, and was high performing during testing with AUC and AP of 0.849 and 0.51, respectively. The random forest classifier also displayed the best and most robust performance for the Jakarta model, with AUC of 0.856 ± 0.015, AP of 0.434 ± 0.039, and BS of 0.08 ± 0.0003. The performance when testing on the Semarang healthcare workers was AUC of 0.745 and AP of 0.694. Meanwhile, the performance for Jakarta 2022 test set was an AUC of 0.761 and AP of 0.535. Our models yielded high predictive performance and can be used as an alternative COVID-19 methodology for healthcare workers in Indonesia, therefore helping in predicting an increased trend of transmission during the transition into endemic.
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Complete Protection from SARS-CoV-2 Lung Infection in Mice Through Combined Intranasal Delivery of PIKfyve Kinase and TMPRSS2 Protease Inhibitors -
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+Emerging variants of concern of SARS-CoV-2 can significantly reduce the prophylactic and therapeutic efficacy of vaccines and neutralizing antibodies due to mutations in the viral genome. Targeting cell host factors required for infection provides a complementary strategy to overcome this problem since the host genome is less susceptible to variation during the life span of infection. The enzymatic activities of the endosomal PIKfyve phosphoinositide kinase and the serine protease TMPRSS2 are essential to meditate infection in two complementary viral entry pathways. Simultaneous inhibition in cultured cells of their enzymatic activities with the small molecule inhibitors apilimod dimesylate and nafamostat mesylate synergistically prevent viral entry and infection of native SARS-CoV-2 and vesicular stomatitis virus (VSV)-SARS-CoV-2 chimeras expressing the SARS-CoV-2 surface spike (S) protein and of variants of concern. We now report prophylactic prevention of lung infection in mice intranasally infected with SARS-CoV-2 beta by combined intranasal delivery of very low doses of apilimod dimesylate and nafamostat mesylate, in a formulation that is stable for over 3 months at room temperature. Administration of these drugs up to 6 hours post infection did not inhibit infection of the lungs but substantially reduced death of infected airway epithelial cells. The efficiency and simplicity of formulation of the drug combination suggests its suitability as prophylactic or therapeutic treatment against SARS-CoV-2 infection in households, point of care facilities, and under conditions where refrigeration would not be readily available.
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No evidence for the association between COVID-19 and neuroinflammation: A diffusion basis spectrum imaging study. -
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+COVID continues to be a major international public health concern, the underlying mechanisms of which are not fully understood. Recent studies suggest that COVID may cause prolonged inflammation within the central nervous system. However, the evidence so far has been limited to few small-scale case studies. To address this, this study leveraged a longitudinal dataset from the UK Biobank that included neuroimaging data prior to and following COVID testing (analytic N=416 including n=224 COVID-positive cases) and applied a novel and non-invasive Diffusion Basis Spectrum Imaging (DBSI) technique to derive putative indices of neuroinflammation (i.e., restricted fraction; DBSI-RF) for gray matter structures and white matter tracts in the brain. We hypothesized that SARS-CoV-2 infection would be associated with elevated DBSI markers of putative neuroinflammation and conducted linear regression analyses with adjustment for age, sex, race, body mass index, smoking frequency, and data acquisition interval. After multiple testing correction using false discovery rate, we found no evidence that COVID is associated with variability in neuroinflammation. Several brain regions showed nominally significant differences in DBSI-RF between COVID cases and controls including psychopathology-related regions linked that are either part of (i.e., orbitofrontal cortex) or functionally connected to the olfactory network (e.g., amygdala, caudate). It remains possible that there are acute and transitory neuroinflammatory effects associated with COVID that were not observed in our study due to potential resolution of COVID prior to the scan. Future research is warranted to examine whether neuroinflammation is associated with SARS-CoV-2 infection in a time- and/or symptom-dependent manner.
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Structure, Dynamics and Free Energy Studies on the Effect of Spot Mutations on SARS-CoV-2 Spike Protein Binding with ACE2 Receptor -
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+The ongoing COVID-19 pandemic continues to infect people worldwide, and the virus continues to evolve in significant ways which can pose challenges to the efficiency of available vaccines and therapeutic drugs and cause future pandemic. Therefore, it is important to investigate the binding and interaction of ACE2 with different RBD variants. A comparative study using all-atom MD simulations was conducted on ACE2 binding with 8 different RBD variants, including N501Y, E484K, P479S, T478I, S477N, N439K, K417N and N501Y-E484K-K417N on RBD. Based on the RMSD, RMSF, and DSSP results, the overall the binding of RBD variants with ACE2 is stable, and the secondary structure of RBD and ACE2 are consistent after the spot mutation. Besides that, a similar buried surface area, a consistent binding interface and a similar amount of hydrogen bonds formed between RBD with ACE2 although the exact residue pairs on the binding interface were modified. The change of binding free energy from spot mutation was predicted using the free energy perturbation (FEP) method. It is found that N501Y, N439K, and K417N can strengthen the binding of RBD with ACE2, while E484K and P479S weaken the binding, and S477N and T478I have negligible effect on the binding. Spot mutations modified the dynamic correlation of residues in RBD based on the dihedral angle covariance matrix calculation. Doing dynamic network analysis, a common intrinsic network community extending from the tail of RBD to central, then to the binding interface region was found, which could communicate the dynamics in the binding interface region to the tail thus to the other sections of S protein. The result can supply unique methodology and molecular insight on studying the molecular structure and dynamics of possible future pandemics and design novel drugs.
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Activated interstitial macrophages are a predominant target of viral takeover and focus of inflammation in COVID-19 initiation in human lung -
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+Early stages of deadly respiratory diseases such as COVID-19 have been challenging to elucidate due to lack of an experimental system that recapitulates the cellular and structural complexity of the human lung while allowing precise control over disease initiation and systematic interrogation of molecular events at cellular resolution. Here we show healthy human lung slices cultured ex vivo can be productively infected with SARS-CoV-2, and the cellular tropism of the virus and its distinct and dynamic effects on host cell gene expression can be determined by single cell RNA sequencing and reconstruction of “infection pseudotime” for individual lung cell types. This revealed that the prominent SARS-CoV-2 target is a population of activated interstitial macrophages (IMs), which as infection proceeds accumulate thousands of viral RNA molecules per cell, comprising up to 60% of the cellular transcriptome and including canonical and novel subgenomic RNAs. During viral takeover of IMs, there is cell-autonomous induction of a pro-fibrotic program (TGFB1, SPP1), and an inflammatory program characterized by the early interferon response, chemokines (CCL2, 7, 8, 13, CXCL10) and cytokines (IL6, IL10), along with destruction of cellular architecture and formation of dense viral genomic RNA bodies revealed by super-resolution microscopy. In contrast, alveolar macrophages (AMs) showed neither viral takeover nor induction of a substantial inflammatory response, although both purified AMs and IMs supported production of infectious virions. Spike-dependent viral entry into AMs was neutralized by blockade of ACE2 or Sialoadhesin/CD169, whereas IM entry was neutralized only by DC-SIGN/CD209 blockade. These results provide a molecular characterization of the initiation of COVID-19 in human lung tissue, identify activated IMs as a prominent site of viral takeover and focus of inflammation and fibrosis, and suggest therapeutic targeting of the DC-SIGN/CD209 entry mechanism to prevent IM infection, destruction and early pathology in COVID-19 pneumonia. Our approach can be generalized to define the initiation program and evaluate therapeutics for any human lung infection at cellular resolution.
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+Background: Societal separation of unvaccinated people from public spaces has been a novel and controversial COVID-era public health practice in many countries. Models exploring potential consequences of vaccination-status-based separation have not considered how separation influences the contact frequencies in the separated groups; we systematically investigate implementing effects of separation on population-specific contact frequencies and show this critically determines the predicted epidemiological outcomes, focusing on the attack rates in the vaccinated and unvaccinated populations and the share of infections among vaccinated people that were due to contacts with infectious unvaccinated people. Methods: We describe a susceptible-infectious-recovered (SIR) two-population model for vaccinated and unvaccinated groups of individuals that transmit an infectious disease by person-to-person contact. The degree of separation between the two groups, ranging from zero to complete separation, is implemented using the like-to-like mixing approach developed for sexually-transmitted diseases [1-3], adapted for presumed SARS-CoV-2 transmission. We allow the contact frequencies for individuals in the two groups to be different and depend, with variable strength, on the degree of separation. Results: Separation can either increase or decrease the attack rate among the vaccinated, depending on the type of separation (isolating or compounding), and the contagiousness of the disease. For diseases with low contagiousness, separation can cause an attack rate in the vaccinated, which does not occur without separation. Interpretation: There is no blanket epidemiological advantage to separation, either for the vaccinated or the unvaccinated. Negative epidemiological consequences can occur for both groups.
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Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3) - Condition: COVID-19 Interventions: Drug: theophylline; Drug: Placebo Sponsor: Washington University School of Medicine Recruiting
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Lymph Node Aspiration to Decipher the Immune Response of Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine. - Condition: COVID-19 Intervention: Procedure: Lymph node aspiration / Blood sampling Sponsor: Assistance Publique - Hôpitaux de Paris Recruiting
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COVID-19 Trial of the Candidate Vaccine MVA-SARS-2-S in Adults - Condition: Covid19 Interventions: Biological: MVA-SARS-2-S; Other: Placebo Sponsors: Universitätsklinikum Hamburg-Eppendorf; German Center for Infection Research; Philipps University Marburg Medical Center; Ludwig-Maximilians - University of Munich; University Hospital Tuebingen; CTC-NORTH Withdrawn
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Treatment of Long COVID (TLC) Feasibility Trial - Condition: COVID-19 Interventions: Drug: Low-dose Naltrexone (LDN); Drug: Cetirizine; Drug: Famotidine; Drug: LDN Placebo; Drug: Cetirizine Placebo; Drug: Famotidine Placebo Sponsors: Emory University; CURE Drug Repurposing Collaboratory (CDRC) Not yet recruiting
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Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease - Conditions: COVID-19; Renal Insufficiency, Chronic Intervention: Drug: Nirmatrelvir/ritonavir Sponsor: Chinese PLA General Hospital Recruiting
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Safety, Efficacy, and Dosing of VIX001 in Patients With Neurological Symptoms of Post Acute COVID-19 Syndrome (PACS). - Conditions: Post-Acute COVID-19 Syndrome; Cognitive Impairment; Neurological Complication Intervention: Drug: VIX001 Sponsor: Neobiosis, LLC Not yet recruiting
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PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Condition: SARS-CoV-2 Interventions: Drug: Upamostat; Drug: Placebo (PO) Sponsors: Henry M. Jackson Foundation for the Advancement of Military Medicine; Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies; FHI Clinical, Inc.; RedHill Biopharma Limited Not yet recruiting
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A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression - Conditions: COVID 19 Disease; Mild to Moderate COVID 19 Disease; SARS-CoV-2; Infectious Disease; Severe Acute Respiratory Syndrome Coronavirus 2 Interventions: Drug: Tafenoquine Oral Tablet; Drug: Placebo Sponsor: 60P Australia Pty Ltd Not yet recruiting
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A Study to Evaluate the Efficacy, Safety, Tolerability and PK of SNS812 in Mild to Moderate COVID-19 Patients - Condition: Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder) Interventions: Drug: MBS-COV; Drug: Placebo Sponsor: Oneness Biotech Co., Ltd. Not yet recruiting
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Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19 - Conditions: Asthenia; COVID-19; Functional MRI; Cognitive Impairment Interventions: Other: Structural and functional MRI; Drug: Ethyl methyl hydroxypyridine succinate + Meldonium; Drug: Placebo Sponsor: Promomed, LLC Completed
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NDV-HXP-S Vaccine Clinical Trial (COVIVAC) - Condition: COVID-19 Intervention: Biological: COVIVAC vaccine Sponsors: Institute of Vaccines and Medical Biologicals, Vietnam; National Institute of Hygiene and Epidemiology (NIHE), Vietnam; Center for Disease Control of Thai Binh Province, Vietnam Completed
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Immunoadsorption vs. Sham Treatment in Post COVID Patients With Chronic Fatigue Syndrome - Conditions: Fatigue; Post-Acute COVID-19 Syndrome Intervention: Procedure: Immunoadsorption vs. sham immunoadsorption Sponsor: Hannover Medical School Not yet recruiting
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MR-spectroscopy in Post-covid Condition Prior to and Following a Yoga Breathing Intervention - Conditions: Post COVID-19 Condition; Somatic Symptom Disorder Interventions: Behavioral: yoga; Behavioral: social contact Sponsor: Medical University Innsbruck Recruiting
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Clinical Evaluation of SARS-COV-2 (COVID-19), Influenza and RSV 8-Well MT-PCR Panel for In Vitro Diagnostics - Condition: Respiratory Viral Infection Interventions: Diagnostic Test: SARS-COV-2, Influenza and RSV 8-Well MT-PCR Panel; Diagnostic Test: BioFire Respiratory Panel 2.1 Sponsor: AusDiagnostics Pty Ltd. Not yet recruiting
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Expressive Interviewing Agents to Support Health-Related Behavior Change - Condition: Mental Stress Intervention: Other: Expressive Interviewing Sponsors: University of Michigan; University of Texas at Austin Completed
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From PubMed
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Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants - Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge to worldwide public health. The SARS-CoV-2 receptor-binding domain (RBD) is a hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated the impact of RBD mutations, including 5 variants of concern (VOC) or interest-including Omicron (BA.2)-and 33 common point mutations, both on IgG recognition and ACE2-binding inhibition, as well as…
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A quantum chemical study on the anti-SARS-CoV-2 activity of TMPRSS2 inhibitors - Nafamostat and camostat are known to inhibit the spike protein-mediated fusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by forming a covalent bond with the human transmembrane serine protease 2 (TMPRSS2) enzyme. Previous experiments revealed that the TMPRSS2 inhibitory activity of nafamostat surpasses that of camostat, despite their structural similarities; however, the molecular mechanism of TMPRSS2 inhibition remains elusive. Herein, we report the energy profiles of the…
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Effects of Sulforaphane on SARS‑CoV‑2 infection and NF‑κB dependent expression of genes involved in the COVID‑19 ‘cytokine storm’ - Since its spread at the beginning of 2020, the coronavirus disease 2019 (COVID‑19) pandemic represents one of the major health problems. Despite the approval, testing, and worldwide distribution of anti‑severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) vaccines, the development of specific antiviral agents targeting the SARS‑CoV‑2 life cycle with high efficiency, and/or interfering with the associated ‘cytokine storm’, is highly required. A recent study, conducted by the authors’…
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New Viral Diseases and New Possible Remedies by Means of the Pharmacology of the Renin-Angiotensin System - All strains of SARS-CoV-2, as well as previously described SARS-CoV and MERS-CoV, bind to ACE2, the cell membrane receptor of β-coronaviruses. Monocarboxypeptidase ACE2 activity stops upon viral entry into cells, leading to inadequate tissue production of angiotensin 1-7 (Ang1-7). Acute lung injury due to the human respiratory syncytial virus (hRSV) or avian influenza A H7N9 and H5N1 viruses is also characterized by significant downregulation of lung ACE2 and increased systemic levels of…
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Development of nanozymes for promising alleviation of COVID-19-associated arthritis - The COVID-19 pandemic caused by SARS-CoV-2 has been identified as a culprit in the development of a variety of disorders, including arthritis. Although the emergence of arthritis following SARS-CoV-2 infection may not be immediately discernible, its underlying pathogenesis is likely to involve a complex interplay of infections, oxidative stress, immune responses, abnormal production of inflammatory factors, cellular destruction, etc. Fortunately, recent advancements in nanozymes with enzyme-like…
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Toxic effects of aging mask microplastics on E. coli and dynamic changes in extracellular polymeric matter - Contamination of disposable medical masks has become a growing problem globally in the wake of Covid-19 due to their widespread use and improper disposal. Three different mask layers, namely the outer layer, the meltblown (MB) filler layer and the inner layers release three different types of microplastics, whose physical and chemical properties change after prolonged environmental weathering. In this study, physical and chemical changes of mask microplastics before and after aging were…
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New cyclic arylguanidine scaffolds as a platform for development of antimicrobial and antiviral agents - According to WHO, infectious diseases are still a significant threat to public health. The combine effects of antibiotic resistance, immunopressure, and mutations within the bacterial and viral genomes necessitates the search for new molecules exhibiting antimicrobial and antiviral activities. Such molecules often contain cyclic guanidine moiety. As part of this work, we investigated the selected antimicrobial and antiviral activity of compounds from the cyclic arylguanidine group. Molecules…
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C-2 Thiophenyl Tryptophan Trimers Inhibit Cellular Entry of SARS-CoV-2 through Interaction with the Viral Spike (S) Protein - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, by infecting cells via the interaction of its spike protein (S) with the primary cell receptor angiotensin-converting enzyme (ACE2). To search for inhibitors of this key step in viral infection, we screened an in-house library of multivalent tryptophan derivatives. Using VSV-S pseudoparticles, we identified compound 2 as a potent entry inhibitor lacking cellular toxicity. Chemical optimization of 2 rendered compounds…
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Modulation of NRF2: biological dualism in cancer, targets and possible therapeutic applications - SIGNIFICANCE: The NRF2-KEAP1 system is a master regulator of redox homeostasis and cell adaptation to a variety of exogenous and endogenous stressors. Accumulating evidence from the last decade indicates that the impairment of the redox balance leads to oxidative stress (OS), a common alteration occurring in many human acute and chronic inflammatory diseases,, such as cancer, diabetes, neurodegeneration, and metabolic disorders, and aging.
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Efficacy of low-intensity pulsed ultrasound in the treatment of COVID-19 pneumonia - Purpose As a public health emergency of international concern, the coronavirus disease 2019 (COVID-19) still lacks specific antiviral drugs, and symptomatic treatment is currently the mainstay. The overactivated inflammatory response in COVID-19 patients is associated with a high risk of critical illness or even death. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of LIPUS therapy for COVID-19 pneumonia….
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Research Progress of Immunomodulation on Anti-COVID-19 and the Effective Components from Traditional Chinese Medicine - SARS-CoV-2 has posed a threat to the health of people around the world because of its strong transmission and high virulence. Currently, there is no specific medicine for the treatment of COVID-19. However, for a wide variety of medicines used to treat COVID-19, traditional Chinese medicine (TCM) plays a major role. In this paper, the effective treatment of COVID-19 using TCM was consulted first, and several Chinese medicines that were frequently used apart from their huge role in treating it…
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A Phase 2 randomised study to establish efficacy, safety and dosing of a novel oral cathepsin C inhibitor, BI 1291583, in adults with bronchiectasis: Airleaf - New therapies are needed to prevent exacerbations, improve quality of life and slow disease progression in bronchiectasis. Inhibition of cathepsin C (CatC) activity has the potential to decrease activation of neutrophil-derived serine proteases in patients with bronchiectasis, thereby reducing airway inflammation, improving symptoms, reducing exacerbations and preventing further airway damage. Here we present the design of a phase 2 trial (Airleaf™; NCT05238675) assessing the efficacy and safety…
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Immunogenicity and safety of inactivated SARS-CoV-2 vaccine in haemodialysis patients: a prospective cohort study - End-stage renal disease patients on haemodialysis (HD) have been largely excluded from SARS-CoV-2 vaccine trials due to safety reasons and shown to mount lower responses to vaccination. This study aims to evaluate the immunogenicity and safety of inactivated COVID-19 vaccine among HD patients compared to healthy controls. All subjects who received the primary inactivated COVID-19 vaccination had their blood samples tested 21 days after the second dose. We report the immunogenicity based on…
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Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe acute respiratory symptoms in humans. Controlling the coronavirus disease pandemic is a worldwide priority. The number of SARS-CoV-2 studies has dramatically increased, and the requirement for analytical tools is higher than ever. Here, we propose monolayered-intestinal epithelial cells (IECs) derived from human induced pluripotent stem cells (iPSCs) instead of three-dimensional cultured intestinal organoids as a suitable…
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Picolinic acid is a broad-spectrum inhibitor of enveloped virus entry that restricts SARS-CoV-2 and influenza A virus in vivo - The COVID-19 pandemic highlights an urgent need for effective antivirals. Targeting host processes co-opted by viruses is an attractive antiviral strategy with a high resistance barrier. Picolinic acid (PA) is a tryptophan metabolite endogenously produced in mammals. Here, we report the broad-spectrum antiviral activity of PA against enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), flaviviruses, herpes simplex virus, and…
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From Patent Search
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+Daily-Dose
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A New Lawsuit Alleges That Leonard Leo Called for the Arrest of a Pro-Choice Protester - The court filing claims that the Federalist Society leader, a champion of free speech, urged police to violate the First Amendment rights of a demonstrator near his Maine home. - link
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The Puzzling, Increasingly Rightward Turn of Mario Vargas Llosa - The writer has shocked many by endorsing Latin America and Spain’s rising authoritarian movements. - link
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A Day in the Life of Congress’s “Traffic Cop” - The House Committee on Rules decides which bills go forward. Jim McGovern, the ranking Democrat, has watched a decades-long erosion of the process. - link
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Wrestling with the Ghost of Boris Johnson - An election for the seat in Parliament once held by the disgraced former Prime Minister goes down to the wire. - link
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The Life of J. Robert Oppenheimer - David Remnick talks with Kai Bird, whose biography was the foundation for the new film “Oppenheimer.” Plus, Colson Whitehead; and Greta Gerwig on finding herself as a director. - link
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From Vox
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“Cry baby scientist”: What Oppenheimer the film gets wrong about Oppenheimer the man -
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+American theoretical physicist and professor of physics J. Robert Oppenheimer at the University of California, Berkeley | Photo 12/Universal Images Group via Getty Images
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+The so-called “father of the bomb” helped bring us prematurely into the age of existential risk.
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+One would be tempted to describe J. Robert Oppenheimer as a tragic figure — that’s certainly how Christopher Nolan portrays him in the biopic Oppenheimer. The father of the atomic bomb who spent the rest of his life agonizing over what he had helped birth; the ultimate insider who was humbled and brought low; the hopeful scientist who started the nuclear arms race. But then, tragic figures don’t generally spend their retirement yachting around the Caribbean. Or maybe he was a tragic figure in the mold of Lord Byron — interestingly dark and mystical, remarkably pretty, and rich as Midas.
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+Oppenheimer grew up in privilege, and remained swaddled in it for his whole life. His father immigrated to New York with nothing, and rose up to become a wealthy textile company executive. His parents spoiled their little genius. When he started a childhood rock collection, it grew to cover every surface in their apartment, which itself covered an entire floor overlooking the Hudson River. The Oppenheimers had a chauffeur, a French governess, three live-in maids and three van Gogh paintings. He corresponded with the New York Mineralogical Club, but when they invited him to speak they were surprised and delighted when he turned out to be only 12. His 16th birthday present was a 28-foot yacht (to go with the family’s 40-foot Lorelei) which he calledTrimethy, after a chemical compound. As Oppenheimer remarked when he bought his first holiday home in New Mexico, the state where he would later spearhead the development of the atomic bomb: “hot dog!”
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+Oppenheimer was a slightly odd student. He was a nerd at Harvard, excluded for his introversion and, in the intensely antisemitic environment of the 1920s, for his Jewishness. He was a somewhat troubled youth. At Cambridge University, he once left a poisoned apple on his tutor’s desk; on vacation when a friend told him of his engagement, Oppenheimer tried to strangle him; and in Gottingen, where he was a PhD student, his classmates presented a petition to get him to stop interrupting seminars.
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+However, he began to come out of his shell as a postdoctoral researcher in Leiden and Zurich, and became positively cool when he moved to California in 1929. He cooked nasi goreng — his colleagues called it “nasty gory” — and “eggs a la Oppie,” made with lots of Mexican chiles. He had a house with a Picasso on the wall, New Mexican rugs on the floor and a view of the Golden Gate Bridge. He fundraised for Republican forces in the Spanish Civil War and flirted with communism. With his blackboard chalk and his cigarettes, he made significant breakthroughs, inspired his graduate students, and built one of the finest theoretical physics departments in the world. And he was lucky: His father’s fortune was unscathed by the Crash of 1929. Once after a crash of Oppenheimer’s own, speeding in his Chrysler while racing a train and knocking unconscious and almost killing his passenger Natalie Raymond, his dad gave her a Cezanne drawing by way of an apology. Hot dog!
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+After the war, he got the cushiest job imaginable, as director of the Institute for Advanced Study in Princeton, New Jersey. As director, he was given the 265-acre Olden Manor, parts of which dated to 1696. He had no teaching responsibilities, and a $120,000 fund to spend on inviting whoever he liked to spend anything from a few months (T.S. Eliot, whose poem “The Wasteland” Oppenheimer is depicted absorbing onscreen) to the rest of their career (the diplomat George Kennan, he of the Cold War containment policy). It sounds like a great gig. And if I had it, I also would have essentially stopped producing research, as Oppenheimer did.
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+Eventually McCarthyism, red-baiting FBI director J. Edgar Hoover, and Oppenheimer’s own political mistakes came for him, and he lost his security clearance and his political appointments in 1954, events that serve as the framing device for Nolan’s film. But Oppenheimer remained as director of the institute until his death. The sheer ludicrous unfairness of the Republican show-trial security hearing — puppet-mastered by the banker turned atomic energy adviser Lewis Strauss — made him a martyr, and when the Democrats got back into the White House they gave him a special award. Oppenheimer spent much of the 50s and 60s in his holiday home at Hawksnest Bay on the Caribbean island of Saint John (where he imported champagne by the case) or on his yacht.
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+By comparison, his brother Frank became a Communist Party member in 1937 while attempting to desegregate his local swimming pool in Pasadena; was an early campaigner at Los Alamos on international arms control; and then was blacklisted from academia, denied a passport, and left to spend a decade as a cattle rancher.
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+Los Alamos’s camp counselor-in-chief
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+But the central location in Oppenheimer’s life wasn’t the Upper West Side, the Bay Shore mansion on Long Island, his bachelor pad in California, the manor in Princeton, or his Caribbean island. The central location was Los Alamos. This scientific base was built from scratch, up in the hills of northern New Mexico. It was Oppenheimer’s favorite part of the country; indeed, Los Alamos was a day’s horse ride from his holiday home. It was like locating CERN, the massive intergovernmental particle physics lab, in the pleasant English countryside of the Cotswolds.
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+Los Alamos during wartime sounds like great fun. Married scientists were permitted to bring their families. There were barn dances or piano recitals on a Saturday night, hikes and horse-riding on a Sunday. It had a local cinema, 15 cents a ticket. It had a local theater group: Oppenheimer even played a corpse in the comedy Arsenic and Old Lace. And it had large quantities of booze — Oppenheimer was famous for mixing very strong, very cold martinis, while the tipple of choice for the less well-heeled bachelor scientists was half lab alcohol and half grapefruit juice, chilled with a chunk of smoking dry ice. The average age was 25. And everyone, in between the work of creating the atom bomb, was apparently having sex: 80 children were born the first year, and 10 a month after that. All in all, it makes for a better war than storming beaches in Normandy or Iwo Jima.
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+The comforts provided to the scientists and their families have been described as “army socialism.” But the soldiers who emptied the bins and the local Indigenous women who cleaned the houses must have had a pretty clear sense of the pecking order. In the many Manhattan Project memoirs, Los Alamos reminds one far more of the summer camp it was before the war than a top-secret government project to develop a weapon of mass destruction
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+Oppenheimer’s historic contribution was as scientific director of Los Alamos. But what was the nature of that contribution to the Manhattan Project? Not the science — the real breakthroughs were from Otto Hahn and Fritz Strassmann, who showed nuclear fission was possible, or specialists like Robert Christy, who designed the plutonium implosion “Christy gadget” successfully tested at Trinity Site near Los Alamos, and later dropped on Nagasaki. And not the direction — 90 percent of Manhattan Project director Gen. Leslie Groves’s budget went to the Fordist feats of administration, logistics, and industrial engineering that were the Oak Ridge and Hanford production plants, churning out the plutonium and enriched uranium that fueled the atom bombs. Oppenheimer’s chief contribution was as camp counselor of Los Alamos.
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+Oppenheimer encouraged them on, and his charisma cast a sort of spell over the campers. It is no coincidence that much of the serious thinking about the bomb — morally and politically — happened elsewhere, in Chicago under Leo Szilard or in the giant head of the Danish genius Niels Bohr. Oppenheimer whipped them up with a simple message: we need to get the bomb before Hitler.
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+As it turns out, this was all mistaken. We now know that the Nazis had decided against a nuclear fission program by 1942. Nazi planners needed raw materials and manpower for armaments production, and Nazi scientists thought a bomb couldn’t be delivered in time to affect the war in Europe, which very much proved to be the case. So the Manhattan Project did not in fact deter, and did not need to deter, Hitler from developing and using the bomb. The scientists were working based on a mistake.
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+The main effect of the Manhattan Project was to bring forward in time the era of the bomb and the era of the nuclear arms race. The existential risk researcher Toby Ord calls this era “the Precipice”: the first period in which humanity can destroy itself. The US would likely not have “sprinted” to the same extent, spending 0.4 percent of GDP, for a peacetime Manhattan Project. And Oppenheimer’s nemesis Lewis Strauss may have been right, if for the wrong reasons, when he accused Oppenheimer of helping the Soviet nuclear program. Quite simply, it would have taken the Soviets years longer if they couldn’t just copy the secrets of the Manhattan Project. Szilard and Albert Einstein, whose 1939 letter prompted President Franklin Roosevelt to begin the US nuclear program, later described their advocacy for the project as the greatest mistake of their life.
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+This was not simply an honest mistake. Joseph Rotblat — the only scientist to resign from the Manhattan Project — got a nasty shock in May 1944 when, at a dinner, Groves said, “You realize, of course, that the main purpose of this project is to subdue the Russians.” Later, Groves testified that “there was never, from about two weeks from the time I took charge of this Project, any illusion on my part but that Russia was our enemy.” It is hard to reconcile this bloodlessness with Matt Damon’s blithe face as Groves in Christopher Nolan’s film.
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+How complicit was Oppenheimer? David Hawkins, Oppenheimer’s aide and the Manhattan Project’s official historian, claims that Groves told Oppenheimer at the end of 1943 that the Nazis had abandoned their attempt — and Oppenheimer shrugged. Oppenheimer dominated the ethical discussions among scientists in late 1944, as both the war and the race to the atomic bomb were nearing their end stages, arguing that scientists had no right to a louder voice than other citizens, and that if the war ended without nuclear use, the next war would be fought with nuclear weapons. Was Oppenheimer swept up by the same patriotic fervor that prompted him to have a colonel’s uniform tailored for himself? Was the bomb just too “technically sweet” for him to resist? It is unclear. Perhaps the best we can say in his defense was that Oppenheimer was chumped into doing it (to some extent), and inadvertently or not, he chumped the other scientists as well.
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+“Would you like to wipe your hands?”
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+Oppenheimer’s complicity did give him prestige and access. However, he squandered that, and lost four key political battles over the use and future of nuclear weapons: on a demonstration attack, on beginning talks at the Potsdam conference, on arms control proposals after the war, and on not racing for the far more powerful hydrogen bomb.
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+The two key issues on the agenda at the May 31, 1945, meeting of the “Interim Committee,” a government advisory group on atomic research, were how to use the bomb, and how to communicate to the Soviets. Oppenheimer, the vast majority of Los Alamos scientists, and indeed Gen. Dwight Eisenhower, all supported a demonstration attack on an empty island. But Harvard President James Conant instead suggested “a vital war plant … surrounded by workers’ houses.”
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+At this crucial decision-making meeting, Oppenheimer did not disagree with the targeting of civilians, instead merely noting the visual effect of a bomb and the feasibility of simultaneous strikes. He also stayed quiet when Groves got approval to purge dissenting scientists like Szilard from the project. Oppenheimer thought that he had traded these betrayals for a commitment that the USSR was to be clearly informed of the bomb and its planned use. These discussions would mean that the Soviets would not be blindsided in a frightening manner that would spur an arms race. But instead, in his meeting with Soviet leader Joseph Stalin at the Potsdam conference, just after the successful Trinity test, Truman only casually and vaguely mentioned a new weapon, and had no serious discussion with his opposite number. Oppenheimer had lost on both counts.
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+The first time he met Truman, after the atomic bombings of Japan, out of frustration and passion Oppenheimer blurted out, “There is blood on my hands.” Truman would stew on this for years, retelling and embellishing the anecdote, once claiming he pulled out his handkerchief and said “Well, here, would you like to wipe your hands?” Immediately after he left, Truman called him a “cry baby scientist,” and would never trust him again.
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+Oppenheimer’s postwar record was just as bad. He was the main intellectual force behind the 1946 Acheson-Lilienthal Report, which proposed a single worldwide Atomic Development Agency with a monopoly over all uranium mines, labs, enrichment facilities, and power plants. Control over nuclear technology would be international, rather than national. However, as Oppenheimer later acknowledged, this was infeasible and naive. Stalin would never have agreed to renunciation of sovereignty, to the inspections, or to the depth of cooperation with the capitalist West the plan would have demanded. Bernard Baruch, proposer of the failed Baruch Plan, was a convenient scapegoat.
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+When the Soviets exploded their first bomb in 1949, Oppenheimer told David Lilienthal, the first chair of the Atomic Energy Commission, that “we mustn’t muff it this time,” meaning the arms race. But they did muff it, and the US stockpile grew from 50 warheads in 1948 to 300 in 1950. The next fight was on whether to build a “Super” or hydrogen bomb, much more destructive than the atomic bomb. Oppenheimer opposed it on scientific, technical, and moral grounds. But when the decision came to Truman, the president had one question: can the Russians do it? The answer was yes. “In that case,” Truman replied, “we have no choice.” The meeting took 7 minutes. The cry baby scientist’s concerns were completely dismissed.
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+How Oppenheimer was outplayed
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+The two most notable facts about Oppenheimer’s life are that he first sped up the creation of nuclear weapons, and then failed utterly to restrict the nuclear arms race he had helped begin. The arms racers used his scientific credibility to support their reckless buildup, and outplayed him in every important political battle. It would take a further 18 years after his 1954 defrocking before the first bilateral arms control agreement on nuclear weapons. This removal of his security clearance can be seen as the final mercy kill of an utterly defanged and defeated political opponent.
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+It’s hard to overemphasize how much the authors of American Prometheus, the book on which the film is based, are on Team Oppenheimer. One author, Kai Bird, spent 25 years interviewing Oppenheimer’s friends and family. They spend 88 pages on a minute-by-minute account of the mistrial of his hearing. They refer to him frequently as “Oppie.” And even their assessment is that he “won nothing and acquiesced to everything.”
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+How should we remember Oppenheimer: A tragic martyr? Death, the destroyer of worlds? The “American Prometheus” of the title? Another descriptive phrase comes to mind, one that would be more familiar to one of his father’s employees in a New York textile factory: “What a schmuck.”
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+Haydn Belfield has been academic project managerat the University of Cambridge’s Centre for the Study of Existential Risk for the past six years. He is also an associate fellow at the Leverhulme Centre for the Future of Intelligence.
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+People are redefining the 9-to-5 and that’s a good thing.
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+Hybrid work is the new millennials. It’s being blamed for destroying everything.
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+Most recently, hybrid work is apparently making it really hard to schedule meetings from 4 to 6 pm, since workers are ducking out slightly early to pick up their kids or get a workout in, according to the Wall Street Journal. Some workers make up for the time missed by logging on again in the evening. (Personally, I never got the memo that the 9-to-5 now ends at 6.) In other words, people are trying to find a compromise between their work lives and the rest of their lives.
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+Still, some managers are lamenting that these absences make it difficult for their teams to be productive because getting things done at work apparently requires everyone to be present at the same time, right before dinner. But perhaps 4 to 6 pm — the final hours of a long work day when many aren’t at their most clear-headed — was never a good time to schedule a meeting.
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+“People tend by that time of day to not be as productive as they were in the morning,” said Caitlin Duffy, a director in Gartner’s HR practice. Plus, there are better ways to encourage productivity, like scheduling meetings when people arealert and available.
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+“Even though there’s a sense that you might not be able to predict as well when people are going to be available or people might not be available at the same time, that doesn’t have to mean it’s harder to get things done,” Duffy said. “It just means that you’re not optimizing your approach to hybrid work for your team.”
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+Duffy recommends that teams be transparent about their availability so that managers can use that information to set norms around when people are expected to be available for meetings and other collaborative activities.
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+It’s also important for bosses to consider whether something actually needs to be a meeting in the first place, since meetings in general are often not the best way to accomplish tasks.
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+“I really hope that we aren’t defining productivity by the number of meetings that we’re in,” Christina Janzer, SVP of research and analytics at Slack, told Vox. “The first thing I’d challenge is that the number of meetings equals productivity.”
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+Her research has found that people are in too many meetings as it is, and that more than 40 percent of them could be deleted without any real consequences. Many meetings could be an email or a Slack conversation instead.
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+“Spending less time in meetings shouldn’t hurt productivity,” Janzer said.
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+One important thing to note in this discussion is that productivity in the amorphous world of white-collar work is incredibly difficult to measure. Many managers have struggled to find new ways to gauge productivity, since the shift to remote work during the pandemic meant they could no longer rely on the time-worn proxy of counting butts in seats. Often, they now look to inputs, like keystrokes or emails sent, rather than outputs, because those are easier to measure. Of course, those measurements can incentivize looking productive rather than being productive.
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+What we do know is that about half of employees — it’s higher for women and parents — say they’re more likely to put family, personal life, health, and well-being over work than they were before the pandemic, according to Microsoft’s Work Trend Index. And that’s maybe a good thing, both for individuals and for their work.
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+The 9-to-5 (or 9-to-6, apparently) never lined up for parents or other caregivers, who were forced to figure out what to do with their children after school, which typically ends earlier than the work day. This incongruity was a huge source of stress for working parents, one that remote and hybrid work has helped alleviate. By making the demands of their lives outside of work more manageable, remote and flexible work has actually been a boon for all employees. And the benefits can also be seen at work. In general, employees equate work flexibility with a whole number of positive outcomes, from higher productivity to less burnout and turnover.
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+By shoehorning employees into late-in-the-day meetings, managers are running the risk of lost productivity, not gained. And their companies can become unattractive places to work. Data from hybrid software firm Scoop Technologies recently showed that companies offering remote or hybrid work are growing headcount much more quickly than those with strict in-office requirements.
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+Making remote or hybrid work work for everyone is going to require some effort, but it’s better than reverting back to the way things used to be. That means managers need to get input from their employees to decide the best times for collaborative or focused work, and then set up norms for people to follow.
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+“It may be the mornings are really the magic time with their kids, getting everyone off to school, and it could be that the afternoon is good,” Boston Consulting Group managing director and senior partner Debbie Lovich said.
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+“The point is that managers should orchestrate conversations with their teams about when, where, and how work gets done,” she added. “That’s not a muscle managers had needed before.”
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What to do (and avoid) in extreme heat -
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+Getty Images/fStop
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+Tips for keeping kids, adults, and the elderly cool and safe — even without air conditioning.
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+Children produce more body heat and sweat less than adults, and tend to not stay as hydrated, making them more sensitive to the heat. “Their skin is also vulnerable,” says Joanna Cohen, a pediatric emergency medicine physician at Johns Hopkins Children’s Center. “They can get sunburned more easily and sunburns actually increase your body temperature and can contribute to overheating and dehydration as well.”
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+Like children, older adults don’t have as rapid or efficient a thermoregulatory response as other adults, explains Raleigh Todman, an emergency medicine physician at Columbia University Medical Center. The body doesn’t cool down as quickly as the rest of the population, she says.
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+However, everyone should take precautions to stay cool and hydrated during extreme heat. When humidity exceeds 75 percent, the body’s ability to cool off by sweating is not as effective, Todman says, making heat safety all the more important. Here’s what to keep in mind.
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+Keep your home and your body as cool as possible
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+One of the most effective ways to fend off heat-related illness is to stay in an air-conditioned building (even though air conditioning is a contributor to climate change). According to the 2020 Residential Energy Consumption Survey, 88 percent of US households use air conditioning. The survey also found that half of households in the Northeast use individual AC units, like window and wall units, mini-splits, and portable units.
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+You can lower the temperature in your home by closing your shades to prevent the sunlight from heating up the house and avoiding the use of your stove and oven. Electric fans may feel nice, but will not prevent heat-related illness. If you have individual air-conditioning units, try to contain the cold air to one area by keeping the doors closed to one room.
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+Other at-home ways of cooling down include avoiding exercise or strenuous activities, taking a cool bath or shower, placing wet cloths or ice on your wrists, neck, and temples, and wearing light-colored, loose-fitting fabrics like cotton and linen — and dressing your children in loose, light clothes as well.
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+If your home does not have air conditioning or if you still feel hot, find a cooling center — an air-conditioned indoor location where the public can stay safe from the heat — in your area by calling 211 and asking for information about local cooling centers. Some states have lists of cooling centers online. Museums, libraries, movie theaters, cafes, malls, and stores can offer respites from the heat as well. Parents should remember to never leave children and pets unattended in the car. Cohen suggests placing your purse or phone next to your child or pet in the backseat as a double reminder to take them all with you.
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+Children may want to take advantage of sunny days outdoors with trips to the park, beach, or pool. Outdoor activities can be safe for children so long as there’s shade and water available, Cohen says, like a pool, beach, or backyard or park with sprinklers. “If they’re going to be doing exercise, like playing soccer outside, they should take frequent breaks and go into the shade,” Cohen says. “If they do start to get overheated, get inside in air conditioning, if you can.”
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+Everyone, regardless of age, should take plenty of rest breaks in the shade and wear sunscreen and a hat if you’re spending time outdoors, though Todman suggests avoiding going outside between noon and 4 pm. “If you need to do something and you have your elderly parents and your baby and you need to go get groceries,” Todman says, “if you can possibly do it in the morning before noon, or in the afternoon after 4, that’s your best bet for avoiding the most direct sun and the hottest part of the day.”
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+Aside from avoiding the heat in a cool location, staying hydrated is another crucial aspect of hot weather safety because it helps regulate your body temperature. On hot days, you need to increase your water intake, even if you don’t feel thirsty or aren’t physically exerting yourself. Avoid alcoholic or caffeinated beverages, which can contribute to dehydration. Try to consistently sip water all day and encourage kids to always have a water bottle with them, Cohen says. If your kids are resistant to drinking water, Todman suggests giving them sports drinks or drinks with electrolytes, like Pedialyte, coconut water, and Gatorade, and even milk, which will help replenish the electrolytes lost in sweat. You’ll know if you’re properly hydrated if you use the bathroom every two to three hours and your urine is light yellow; if it’s dark yellow or gold, drink more water. One way to determine if children are dehydrated is by gently pinching their skin. If they’re hydrated, the skin should bounce back, Todman says, if they’re dehydrated, the skin will stay pinched.
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+Ideally, everyone should drink 32 ounces of water a day, Todman says, although “I know it’s not easy to convince elderly people or small children to drink that much water.” People who work outside should drink one cup of water every 15 to 20 minutes (and ensure you’re wearing sunscreen). Cold treats and foods with a high water content, like ice cream and watermelon, can keep you hydrated and cool, Todman says.
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+Treat your pets the same way you would a baby, Todman says: Don’t leave them outdoors, keep them in the air conditioning, and always keep their water bowl filled.
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+Recognize the signs of heat exhaustion and heat stroke
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+If you, a family member, or a neighbor start to exhibit signs of heat exhaustion or heat stroke, it’s important to recognize the symptoms and react swiftly.
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+According to the CDC, symptoms of heat exhaustion include:
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+Heavy sweating
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+Cold, pale, clammy skin
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+Fast, weak pulse
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+Nausea or vomiting
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+Muscle cramps
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+Tiredness or weakness
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+Dizziness
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+Headache
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+Fainting
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+Here’s what to do if you or someone else is experiencing heat exhaustion:
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+Move to a cool place
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+Loosen clothes
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+Put cool, wet cloths on your body or take a cool bath
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+Get medical help if you or someone else is vomiting, or the symptoms get worse or persist for more than an hour
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+According to the CDC, symptoms of heat stroke include:
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+Body temperature of 103 degrees Fahrenheit or higher
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+Hot, red, dry, or damp skin
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+Fast, strong pulse
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+Headache
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+Dizziness
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+Nausea
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+Confusion
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+Fainting
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+Here’s what to do if you or someone else is experiencing heat stroke:
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+Call 911
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+Move the person to a cooler place
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+Put cool, wet cloths on their body or place them in a cool bath
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+Do not give the person anything to drink
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+The signs of heat exhaustion and heat stroke are the same for both adults and children, Cohen says, but a baby or younger kid may not be able to vocalize how they’re feeling. Ensure children are consistently drinking, urinating frequently, and that they look alert.
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+Best practices for dealing with extreme heat are to stay hydrated, avoid strenuous or prolonged activities outdoors, keep your environment as cool as possible, and ensure members of the community are doing the same. Keep in touch with elderly neighbors or folks with young children or pets who may not have access to an air-conditioned location.
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+“This sort of neighborly mindfulness,” Todman says, “is something, if possible, to keep in mind.”
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From The Hindu: Sports
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Bangladesh women vs India women third ODI | Indian batswomen stutter as Bangladesh fights back to tie the match - The three-match ODI series, thus, ended at 1-1 with the hosts winning the first ODI and India bouncing back to win the second in a comprehensive manner.
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Korea Open Super 500 badminton tournament | Satwiksairaj Rankireddy-Chirag Shetty enter final - The world number three Indian pair notched up a 21-15 24-22 win over the second seeded Chinese in a 40-minute duel at the Jinnam stadium.
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After hitting 29th Test ton, Kohli says he’s ‘charged up’ when faced with challenges - Kohli equalled Sir Don Bradman’s record of 29 Test centuries in India’s commendable first innings score of 438, hitting a polished 121 in 206 balls
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Lionel Messi scores dramatic game-winning goal in his Inter Miami debut against Cruz Azul - Lebron James, Serena Williams, Kim Kardashian and many more celebrities came at Messi’s debut match to witness unquestionably the greatest moment so far in Inter Miami’s brief history
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PSG drops Kylian Mbappe from Asian pre-season tour squad, to be put on sale - According to media reports the Parisian club believe he has already agreed on terms to join Real Madrid for free next summer
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From The Hindu: National News
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Textiles worth lakhs of rupees gutted at Balaji Market in A.P.’s Vizianagaram -
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Women misusing anti-rape law as weapon against partners: Uttarakhand HC - Justice Sharad Kumar Sharma made the observation on July 5 while quashing criminal proceedings against a man who was accused of rape by a woman after he refused to marry her. They were having consensual relations since 2005
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In absence of inflows, KRMB asks TS, AP to utilise available water judiciously - It orders release of 12.7 tmc ft water from N’sagar to AP, TS for drinking, irrigation needs
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Maharashtra rains | 45 people stranded due to floods in Yavatmal; IAF roped in for rescue - Deputy Chief Minister Devendra Fadnavis in a tweet said 45 people were stranded due to floods in Anandnagar village of Mahagaon taluka.
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Nobel Peace Prize Laureate Kailash Satyarthi wants influencers to take the Green India concept to children - Kailash Satyarthi was speaking after planting a sapling at the IIIT campus in Gachibowli on Saturday as a part of inaugurating “Green India Challenge 6.0” along with the Green India Challenger Founder and Rajya Sabha MP, Joginipalli Santosh Kumar
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From BBC: Europe
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Europe heatwave: Temperatures to soar in Greece as fires still burn - Officials warn this could be Greece’s hottest July weekend in 50 years, with temperatures hitting 45C.
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Jamshid Sharmahd: Iran could execute my dad at any time, says German woman - An Iranian-German businessman on death row may have made his last phone call, his daughter fears.
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Russian hardline Putin critic and commander Strelkov detained in Moscow - A key player in Russia’s Ukraine landgrab in 2014, he has bitterly criticised the flagging campaign.
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Berlin ‘lioness’: Wild animal probably a boar, authorities say - Authorities call off a search for a suspected big cat spotted near the German capital.
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Iraq expels Swedish ambassador as Quran row escalates - The ambassador is told to leave amid protests that began over the burning of a Quran in Stockholm.
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From Ars Technica
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Amazon is getting ready to launch a lot of broadband satellites - Amazon unveils satellite facility in Florida, may switch prototype launch to Atlas V - link
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A promising Internet satellite is rendered useless by power supply issues - “The mission of providing Internet connectivity in Alaska will be delayed.” - link
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Zyxel users still getting hacked by DDoS botnet emerge as public nuisance No. 1 - 12 weeks after critical vulnerability was patched, devices are still being wrangled. - link
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This LiDAR-equipped, 30-pound robot dog can be yours for $1,600 - It’s not quite as good as a Boston Dynamics bot, but it is a lot cheaper. - link
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IMAX emulates PalmPilot software to power Oppenheimer’s 70 mm release - IMAX TikTok shows an emulated Palm PDA controlling Oppenheimer’s 600-lb reel. - link
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From Jokes Subreddit
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A young guy goes into a drug store owned by two spinster sisters. -
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+He awkwardly says to the one lady at the pharmacy counter, “Um, this is embarrassing but I have this condition where about once a day I become incredibly aroused and overcome by the desire to have sex with any woman at all. It’s overwhelming! What can you give me for it?”
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+“Hmm,” replied the lady, “This is a tough one. I’ll have to confer with my sister.” After talking to her sister she came back and said, “Well, the best we can do is a furnished apartment, $500 a week and half ownership of the pharmacy.”
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A man walks into a bar and sees another man at the bar with a dog next to him. -
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+He says to him, “Hey there, does your dog bite?” and the man says “No mate, my dog’s the friendliest creature in the world, you can do anything with him.”
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+So he goes to pat the dog and it absolutely goes for him and by the time three other men in the bar manage to get it off him he’s bleeding in half a dozen places and his clothes are torn to shreds. He says to the man at the bar “I thought you said your dog didn’t bite?!”
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