The 2019 Global Health Security (GHS) Index measured the capacities of countries to prepare for and respond to epidemics and pandemics. However, the COVID-19 pandemic revealed that GHS Index scores ...were poorly correlated with ability to respond to infectious disease threats. It is critical to understand how public health policies may reduce the negative impacts of pandemics.
To identify non-pharmaceutical interventions (NPIs) that can minimize morbidity and mortality during the COVID-19 and future pandemics, this study examined associations between country characteristics, NPI public health policies, and COVID-19 outcomes during the first year of the pandemic, prior to the introduction of the COVID-19 vaccine. This global analysis describes worldwide trends in policy implementation and generates a stronger understanding of how NPIs contributed to improved health outcomes.
This cross-sectional, retrospective study relied on information drawn from publicly available datasets through December 31, 2020.
We conducted multivariate regressions to examine associations between country characteristics and policies, and policies and health outcomes.
Countries with higher health service coverage prior to the pandemic implemented more policies and types of policies. Countries with more bordering countries implemented more border control policies (0.78
), and countries with denser populations implemented more masking policies (0.24
). Across all countries, fewer COVID-19 cases and deaths per million were associated with masking (-496.10
, -7.57), testing and tracing (-108.50
, -2.47
), and restriction of movement (-102.30
, -2.10
) policies, with stronger associations when these policies were mandatory rather than voluntary.
Country characteristics, including health service coverage, number of bordering countries, and population density, may predict the frequency and nature of public health interventions. Countries with higher health service coverage may have the infrastructure to react more efficiently to a pandemic, leading them to implement a greater number of policies. Mandatory masking, testing and tracing, and restriction of movement policies were associated with more favorable COVID-19 population health outcomes. While these results are consistent with existing COVID-19 mathematical models, policy effectiveness depends on how well they are implemented. Our results suggest that social distancing policies were less effective in reducing infectious disease risk, which may reflect difficulties with enforcement and monitoring.
Toxicity of nanoparticles developed for biomedical applications is extensively debated as no uniform guidelines are available for studying nanomaterial safety, resulting in conflicting data obtained ...from different cell types. This study demonstrates the varied toxicity of a selected type of nanoparticle, cadmium telluride quantum dots (QDs), in three increasingly complex cell models of the peripheral nervous system.
QD-induced cytotoxicity was assessed via cell viability assays and biomarkers of subcellular damage in PC12 cells and mixed primary dispersed dorsal root ganglia (DRG) cultures. Morphological analysis of neurite outgrowth was used to determine the viability of axotomized DRG explant cultures.
Cadmium telluride QDs and their core metals exert different degrees of toxicity in the three cell models, the primary dispersed DRGs being the most susceptible. alpha-lipoic acid is an effective, multimodal, cytoprotective agent that can act as an antioxidant, metal chelator and QD-surface modifier in these cell systems.
Complex multicellular model systems, along with homogenous cell models, should be utilized in standard screening and monitoring procedures for evaluating nanomaterial safety.
To assess the current and future development of influenza vaccines.
PubMed searches were performed cross-referencing the keywords influenza, influenza vaccine, host immune response, correlates of ...protection, vaccine development, vaccine efficacy. Articles were reviewed for additional citations.
Articles were reviewed and selected on the basis of relevance to subject matter.
In this review, we first introduce the influenza virus, its nomenclature, and the concepts of antigenic drift and shift. Second, we discuss the status of currently licensed influenza virus vaccines. We briefly focus on influenza vaccine responses beyond hemagglutination inhibition that may correlate with protection against influenza viruses of different subtypes. Third, we explain how studying host responses to influenza infection and vaccination with advanced serologic methods, B-cell receptor sequencing, and transcriptomic profiling can guide the development of improved influenza virus vaccines. Fourth, we provide 2 suggestions on how current influenza vaccines can be optimized by redirecting immune responses toward conserved viral antigens and the use of adjuvants.
Influenza vaccine design can benefit from novel insights obtained from the study of host responses to influenza virus infection and vaccination. Integration of the large amount of available clinical and preclinical data requires systems approaches that can elucidate novel correlates of protection and will guide further development of influenza vaccine.
Leveraging a combination of analytical frameworks and empirical assessments, this study investigates the effects of wait-for-free (WFF) pricing schemes on the monetization of serialized, digital ...entertainment content, which has become increasingly pervasive on online platforms. WFF pricing is a strategy in which consumers are given the option to either wait a certain amount of time to acquire digital content at no cost or pay to consume it immediately. We evaluate the extent to which habit formation and present-biased preferences driven by the consumption of addictive stock affect individual consumers’ willingness to wait (or pay) for content, which, in turn, determines the efficacy of WFF pricing. We also examine the conditions under which consumers switch from waiting for free content to instantaneously purchasing content. Our findings indicate that WFF pricing increases the sales of serialized digital content, generating new demand from customers who would otherwise forgo participation in the market. In addition, the pricing design effectively generates sustained profits in the long run. We found that most consumers who initiate a purchase either upon initial market entry or upon switching continue to purchase as new episodes become available. Moreover, the results indicate that as a user accumulates free episodes of a specific series, given extended waiting periods, the likelihood of their conversion from a wait-for-free customer to an instant-purchase customer increases. In particular, WFF pricing effectively augments the willingness to pay of low-valuation consumers as habit formation builds up through time with the free consumption of serialized content. One free episode can elevate the likelihood of consumer purchase by up to 13%. However, as the number of free episodes consumed goes beyond a threshold, the likelihood of conversion decreases. We conclude with a discussion of managerial implications that can help content providers monetize their serialized digital content products.
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has led to growing concerns over increased transmissibility and the ability of some variants to partially escape ...immunity. Sera from participants immunized on a prime-boost schedule with the mRNA-1273 COVID-19 vaccine were tested for neutralizing activity against several SARS-CoV-2 variants, including variants of concern (VOCs) and variants of interest (VOIs), compared to neutralization of the wild-type SARS-CoV-2 virus (designated D614G). Results showed minimal, statistically nonsignificant effects on neutralization titers against the B.1.1.7 (Alpha) variant (1.2-fold reduction compared with D614G); other VOCs, such as B.1.351 (Beta, including B.1.351-v1, B.1.351-v2, and B.1.351-v3), P.1 (Gamma), and B.1.617.2 (Delta), showed significantly decreased neutralization titers ranging from 2.1-fold to 8.4-fold reductions compared with D614G, although all remained susceptible to mRNA-1273-elicited serum neutralization. IMPORTANCE In light of multiple variants of SARS-CoV-2 that have been documented globally during the COVID-19 pandemic, it remains important to continually assess the ability of currently available vaccines to confer protection against newly emerging variants. Data presented herein indicate that immunization with the mRNA-1273 COVID-19 vaccine produces neutralizing antibodies against key emerging variants tested, including variants of concern and variants of interest. While the serum neutralization elicited by mRNA-1273 against most variants tested was reduced compared with that against the wild-type virus, the level of neutralization is still expected to be protective. Such data are crucial to inform ongoing and future vaccination strategies to combat COVID-19.
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19)
.... The development of a vaccine is likely to take at least 12-18 months, and the typical timeline for approval of a new antiviral therapeutic agent can exceed 10 years. Thus, repurposing of known drugs could substantially accelerate the deployment of new therapies for COVID-19. Here we profiled a library of drugs encompassing approximately 12,000 clinical-stage or Food and Drug Administration (FDA)-approved small molecules to identify candidate therapeutic drugs for COVID-19. We report the identification of 100 molecules that inhibit viral replication of SARS-CoV-2, including 21 drugs that exhibit dose-response relationships. Of these, thirteen were found to harbour effective concentrations commensurate with probable achievable therapeutic doses in patients, including the PIKfyve kinase inhibitor apilimod
and the cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825 and ONO 5334. Notably, MDL-28170, ONO 5334 and apilimod were found to antagonize viral replication in human pneumocyte-like cells derived from induced pluripotent stem cells, and apilimod also demonstrated antiviral efficacy in a primary human lung explant model. Since most of the molecules identified in this study have already advanced into the clinic, their known pharmacological and human safety profiles will enable accelerated preclinical and clinical evaluation of these drugs for the treatment of COVID-19.
Abstract
Eosinophils play a critical role in mucosal tissue homeostasis, anti-helminth responses, and allergy. Lung eosinophilia is associated with aberrant T cell responses to respiratory viral ...infection and is also a consequence of vaccine-associated enhanced respiratory disease (VAERD). A growing body of literature has demonstrated there are different phenotypic subsets of eosinophils and, depending on subset, can play a protective role and aid in lung recovery following infection. Previous work by Choi et al. showed recruitment of eosinophils to the lung in BALB/c mice vaccinated with alum-adjuvanted trivalent inactivated influenza vaccine (TIV) following a sub-lethal H1N1 (A/New Caledonia/20/1999; NC99) influenza challenge. In this study, flow cytometric analysis of the lung showed an increase in total lung eosinophil numbers in all NC99-challenged mice compared to controls. Furthermore, in TIV-vaccinated then challenged mice, flux of inflammatory eosinophil (iEos) and resident eosinophil (rEos) numbers at 7 days post-infection (DPI) resulted in iEos/rEos ratios similar to that of OVA-sensitized allergic control mice; this effect was independent of alum adjuvant. Treatment groups with increased lung eosinophil numbers did not show signs of enhanced morbidity or inflammatory cytokine signatures compared to unvaccinated mice. Unsupervised clustering using CATALYST confirmed findings from manual gating analysis and revealed differences in eosinophil activation status based on surface expression levels of MHC Class II. Our findings provide a starting point for more sophisticated phenotypic characterization of eosinophil subsets and their distinct functional contributions to vaccine- and infection-induced immunity.
This research was partly funded by NIAID T32 Virus-Host Interactions Training Grant (5T32AI007647-22) and CRIP (Center for Research for Influenza Pathogenesis), a NIAID supported Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C).
Factors leading to successful professional learning communities (PLCs) have been widely discussed in the West, but little is known about how/whether teachers' beliefs contribute to PLCs in the ...Chinese context. This qualitative case study aimed to investigate teachers' beliefs about teacher learning in PLCs and their influence on collegial learning activities in two departments of a Hong Kong secondary school. Semi-structured interviews and observations were employed to collect data. The findings indicate that teachers in the Chinese Department believed that learning could be achieved in PLCs and their practices of collegial activities were conducive to teacher learning. Conversely, teachers in the English Department did not believe that interacting with colleagues would foster learning and their collegial activities yielded limited accomplishment in teacher growth. It is suggested that teachers' beliefs play an important role in facilitating or impeding reform initiatives on teacher development. Implications for teacher education and further studies are discussed.
Abstract
Eosinophils are critical cells in Type 2 immune responses and mucosal tissue homeostasis. Historically, lung eosinophilia has been linked to aberrant Th2 responses in response to inhaled ...allergens or as a consequence of vaccine-associated enhanced respiratory disease in viral infection. In some animal models of respiratory viral infection, lung eosinophilia has been observed in the absence of overt pathology. Here, we interrogated the phenotype and function of eosinophil subsets recruited to the lung after a sublethal, vaccine-matched intranasal challenge, modeling breakthrough infection. We observed an enrichment for eosinophils in the lungs of TIV-vaccinated mice post-challenge that were phenotypically similar to that of OVA-sensitized allergic mice, but with a marked absence of strong inflammatory cytokine signatures, detectable viral titers, and enhanced morbidity. Moreover, we did not observe an influx of eosinophils in the lungs of challenged unvaccinated mice, which were unable to control viral replication and had strong pro-inflammatory cytokine profiles. This suggests that vaccine-matched viral infection of the respiratory mucosa after priming with antigen in the periphery can result in lung eosinophilia that is neither pathological nor disease-enhancing, but correlates more so with clearance during a breakthrough infection. We longitudinally discerned the differential cellular kinetics of lung eosinophils and the lung microenvironment after breakthrough influenza infection or OVA sensitization across multiple parameters, including pathology. We are further analyzing the eosinophil compartment via RNA-seq, imaging, and spectral flow cytometry for in-depth characterization of this phenomenon.
Supported by NIH Public Health Service Institutional Research T32 Training Award (AI07647) and Centers of Excellence for Influenza Research and Response (CEIRR) contract (75N93021C00014-0-9999-1).
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