Social class, COVID-19 and care: Schools on the front line in Ireland during the COVID-19 pandemic

Schools have a duty of care to children that extends beyond educational performance to include wellbeing and welfare. Yet, research has highlighted the tensions that arise when ‘care' and ‘learning' are treated as binaries, especially when schools operate within unequal socio-­economic conditions. Extended COVID-19 school closures brought these issues into sharp relief, highlighting the central role of schools as a front line service in the lives of poorer children. This paper provides qualitative insights into the classed experiences of extended school closure and the role and response of schools through the eyes of parents, teachers and principals in Ireland. We frame these responses in the context of the provision of a careful education, exploring the role of normative and affective relations in teaching and learning. Questions are posed in relation to schools as care regimes and the ‘mission creep' between educational and welfare provision in schools serving poorer children. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

Political trust in the first year of the COVID-19 pandemic: a meta-analysis of 67 studies

Trust in political actors and institutions has long been seen as essential for effective democratic governance. During the COVID-19 pandemic, trust was widely identified as key for mitigation of the crisis through its influence on compliance with public policy, vaccination and many other social attitudes and behaviours. We study whether trust did indeed predict these outcomes through a meta-analysis of 67 studies and 426 individual effect sizes derived from nearly 1.5 million observations worldwide. Political trust as an explanatory variable has small to moderate correlations with outcomes such as vaccine uptake, belief in conspiracy theories, and compliance. These correlations are heterogenous, and we show that trust in health authorities is more strongly related to vaccination than trust in the government;but compliance is more strongly related to the government than other institutions. Moreover, the unique case of the United States indicates that trust in President Trump had negative effects across all observed outcomes, except in increasing conspiracy beliefs. Our analysis also shows that research design features (such as response scales) and publication bias do not importantly change the results. These results indicate that trust was important for the management of the pandemic and supports existing work highlighting the importance of political trust.

Increased Handpiece Speeds without Air Coolant: Aerosols and Thermal Impact.

This study assessed the impact of increased speed of high-speed contra-angle handpieces (HSCAHs) on the aerosolization of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surrogate virus and any concomitant thermal impact on dental pulp. A bacteriophage phantom-head model was used for bioaerosol detection. Crown preparations were performed with an NSK Z95L Contra-Angle 1:5 (HSCAH-A) and a Bien Air Contra-Angle 1:5 Nova Micro Series (HSCAH-B) at speeds of 60,000, 100,000, and 200,000 revolutions per minute (rpm), with no air coolant. Bioaerosol dispersal was measured with Φ6-bacteriophage settle plates, air sampling, and particle counters. Heating of the internal walls of the pulp chambers during crown preparation was assessed with an infrared camera with HSCAH-A and HSCAH-B at 200,000 rpm (water flows ≈15 mL min-1 and ≈30 mL min-1) and an air-turbine control (≈23.5 mL min-1) and correlated with remaining tissue thickness measurements. Minimal bacteriophage was detected on settle or air samples with no notable differences observed between handpieces or speeds (P > 0.05). At all speeds, maximum settled aerosol and average air detection was 1.00 plaque-forming units (pfu) and 0.08 pfu/m3, respectively. Irrespective of water flow rate or handpiece, both maximum temperature (41.5°C) and temperature difference (5.5°C) thresholds for pulpal health were exceeded more frequently with reduced tissue thickness. Moderate and strong negative correlations were observed based on Pearson's correlation coefficient, between remaining dentine thickness and either differential (r = -0.588) or maximum temperature (r = -0.629) measurements, respectively. Overall, HSCAH-B generated more thermal energy and exceeded more temperature thresholds compared to HSCAH-A. HSCAHs without air coolant operating at speeds of 200,000 rpm did not increase bioaerosolization in the dental surgery. Thermal risk is variable, dependent on handpiece design and remaining dentine thickness.

Expression of exogenous proteins in donor platelets treated with lipid nanoparticles encapsulating mRNA

Background: Platelets are transfused therapeutically for hemostasis, and are an integral part of hemorrhage management. However, transfusions can be ineffective in the most severe cases of hemorrhage. Platelets are also a potential cell therapy in other applications, but development has been hindered by inadequate methods to control which proteins are expressed by platelets. Currently, there are no methods to express exogenous proteins in transfusable platelets, which would expand their use to help treat the diseases they modulate. A method is therefore needed to modify transfusable platelets, and thus enhance their protein composition for specific applications. Aim(s): To produce engineered, transfusable platelets to enhance their natural coagulability and functional repertoire by directly transfecting donor-derived platelets with mRNA via lipid nanoparticle (LNP)-mediated delivery. The recent advances through the COVID-19 mRNA vaccines demonstrates the clinical safety and efficacy of LNP-mediated gene therapy, and thus offers a promising strategy to effectively engineer modified platelets. Method(s): Donor-derived platelets were washed and subsequently incubated with a systematic array of LNPs encapsulating Cy5-labeled mRNA encoding for nanoluciferase in comparison to commercial transfection reagents. LNP uptake and platelet activation via CD62p levels was assessed following 4 hours by flow cytometry, while luciferase expression was assessed by normalizing the luminescence intensity to the total protein content. Result(s): Platelets took up the mRNA through all conditions tested;nanoluciferase was only expressed, however, in platelets treated with LNPs and not commercial reagents. Systematically optimizing LNPs increased nanoluciferase expression nine-fold relative to pre-optimized LNPs. Exogenous protein expression did not appear to correlate with mRNA uptake nor platelet activation. Conclusion(s): Platelets transfected with LNPs can express exogenous protein. Further optimization can eventually lead to the creation of a platform technology that in the long-term will allow platelets to deliver therapeutic proteins and yield more effective platelet products.

Platelets Genetically Modified with mRNA-Lipid Nanoparticles Are Functionally Similar to Clinically Transfused Platelets in Vitro

Background/Case Studies: Platelet transfusions are an essential treatment for attenuating bleeding but are often ineffective in cases of intractable hemorrhage. Although anucleate, mature platelets synthesize protein de novo, making them amenable to mRNA gene therapy;however, there remains to be an effective transfection technique. Advancements in lipid nanoparticle (LNP) technology has enabled leading COVID vaccines and is an efficient method to deliver nucleic acids into target cells. Recently, a LNP approach to successfully express exogenous protein in donor platelets [unpublished data] has been developed, a first step towards demonstrating that donor platelet coagulability can be engineered. However, the effects of LNP treatment on platelet function has yet to be investigated. Study Design/Methods: Donated, pooled platelets were obtained from a regional blood for research centre. The hemostatic profiles of LNP-treated and clinical donor platelets were assessed using an adapted rotational thromboelastometry model of dilutional coagulopathy. Coagulability of whole blood (WB) and hemodiluted WB were assessed. Untreated and LNP-treated platelets were then supplemented into hemodiluted WB and activated using INTEM (ellagic acid) to generate a hemostatic profile. LNP-treated platelets were also stimulated with platelet agonists thrombin (0.1U/mL) and ADP (10 mM) and CD62p levels were evaluated to test if the activation response was similar to clinical platelets using flow cytometry. Statistical analysis was conducted by one-way ANOVA and significance defined by P < 0.05. Results/Findings: LNP-treated platelets have a comparable hemostatic profile to clinically transfused platelets and significantly contributed to clot strength when spiked into hemodiluted WB. After INTEM activation, the maximum clot firmness (MCF) of LNP-treated (45.67 +/-1.15) and untreated platelets (49.77 +/- 0.58) was significantly increased (P < 0.05) compared to diluted WB alone (35.00 +/- 1.00). No significant difference between untreated and LNP-treated donor platelets was observed although MCF trended down. No statistical difference in thrombin or ADP responsiveness, indicated by median fluorescent intensity of CD62p surface presentation, was observed between LNP treated and untreated platelets (P > 0.05). Conclusion(s): LNPs are an effective way to deliver exogenous nucleic acids into platelets;they do not significantly impair the platelet contribution to clot strength or responsiveness to agonists stimulation. The minimal effect of LNP exposure on in vitro platelet characteristics demonstrate that LNP engineering is a promising new approach to load platelets with nucleic acids encoding therapeutic protein to enhance their function.

Expression of Exogenous Proteins in Donor Platelets Treated with Lipid Nanoparticles Encapsulating mRNA

Background/Case Studies: Platelets are transfused therapeutically for hemostasis and are an integral part of hemorrhage management. Transfusions, however, can be ineffective in the most severe cases of hemorrhage. Platelets are also a potential cell therapy in other applications, but development has been hindered by inadequate methods to control which proteins are expressed by platelets. Currently, there are no methods to express exogenous proteins in transfusable platelets, which would expand their use to help treat the diseases they modulate. A method is therefore needed to modify transfusable platelets, and thus enhance their protein composition for specific applications. Lipid nanoparticles (LNPs) represent the most clinically advanced system for non-viral gene delivery, and can potentially be used to transfect donor-derived platelets with mRNA to produce transfusable platelets with an enhanced functional repertoire. The recent advances through the COVID-19 mRNA vaccines demonstrates the clinical safety and efficacy of LNP-mediated gene therapy, and thus offers a promising strategy to effectively engineer modified platelets. Study Design/Methods: Donor-derived platelets were washed and subsequently incubated with a systematic array of LNPs encapsulating Cy5-labeled mRNA encoding for nanoluciferase in comparison to the commercial transfection reagents, lipofectamine and Ribojuice. LNP uptake and platelet activation via CD62p levels was assessed following 4 h by flow cytometry, while nanoluciferase expression was assessed by normalizing the luminescence intensity (RLU) to the total protein content. Data was analyzed via a one-way unpaired Student or Welch's t-test or one-way analysis of variance (ANOVA) as appropriate. A p-value < 0.05 was considered significant. Results/Findings: Platelets internalized the mRNA through all conditions tested, with Ribojuice yielding the highest significant increase in Cy5 median fluorescence intensity relative to the LNP (59815 +/- 6466 A.U. vs. 1253 +/- 44 A.U., respectively, p = 0.002). Nanoluciferase was only expressed, however, in platelets treated with LNPs, yielding a normalized luminescence signal of 62 +/- 17 RLU/mug protein, and not with either of the commercial reagents. Systematically optimizing LNPs increased nanoluciferase expression nine-fold to 589 +/- 241 RLU/mug protein relative to pre-optimized LNPs (p = 0.031). A Pearson correlation analysis revealed that the expression of exogenous protein expression did not appear to correlate with the mRNA uptake (Pearson correlation coefficient, r = -0.35) nor platelet activation (r = -0.07). Conclusion(s): Transfecting platelets with LNPs containing mRNA enable the expression of exogenous protein. Further optimization can eventually lead to the creation of a platform technology that in the long-term will allow platelets to deliver therapeutic proteins and yield more effective platelet products.

Platelets genetically modified with mRNA-lipid nanoparticles are functionally similar to clinically transfused platelets in vitro

Background: Platelet transfusions are an essential treatment for attenuating bleeding but are often ineffective in cases of intractable haemorrhage. Although anucleate, mature platelets synthesize protein de novo, making them amenable to mRNA gene therapy;however, there remains to be an effective transfection technique. Advancements in lipid nanoparticle technology has enabled leading COVID vaccines and is an efficient method to deliver nucleic acids into target cells. Recently, we developed a LNP approach to successfully express exogenous protein in platelets [unpublished data], a first step towards demonstrating that donor platelet coagulability can be engineered. However, the effects of LNP treatment on platelet function has yet to be investigated. Aims: To determine whether LNP-treated donor platelets are functionally similar, or better, in vitro, than platelets currently transfused clinically as a next step to establish LNP engineered platelets as a new cell therapy. Methods: The hemostatic profiles of LNP-treated and clinical donor platelets were assessed using an adapted rotational thromboelastometry model of dilutional coagulopathy. LNP-treated platelets were also stimulated with conventional platelet agonists to test if responsiveness is similar, or better than clinical platelets using flow cytometry. Results: LNP-treated platelets have a comparable hemostatic profile to clinically transfused platelets and significantly improved clotting dynamics when spiked into hemodiluted whole blood in an in vitro transfusion simulation. LNP-treated platelets also respond comparably, and in some cases more potently to agonist simulation compared to untreated platelets as indicated by similar p-selectin surface presentation. Summary/Conclusions: LNPs are an effective way to deliver exogenous nucleic acids into platelets;they do not significantly change platelet coagulability or responsiveness to agonists. LNP platelet engineering is a promising new approach to load platelets with procoagulant protein to enhance their function.

Dental Mitigation Strategies to Reduce Aerosolization of SARS-CoV-2.

Limiting infection transmission is central to the safety of all in dentistry, particularly during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Aerosol-generating procedures (AGPs) are crucial to the practice of dentistry; it is imperative to understand the inherent risks of viral dispersion associated with AGPs and the efficacy of available mitigation strategies. In a dental surgery setting, crown preparation and root canal access procedures were performed with an air turbine or high-speed contra-angle handpiece (HSCAH), with mitigation via rubber dam or high-volume aspiration and a no-mitigation control. A phantom head was used with a 1.5-mL min-1 flow of artificial saliva infected with Φ6-bacteriophage (a surrogate virus for SARS-CoV-2) at ~108 plaque-forming units mL-1, reflecting the upper limits of reported salivary SARS-CoV-2 levels. Bioaerosol dispersal was measured using agar settle plates lawned with the Φ6-bacteriophage host, Pseudomonas syringae. Viral air concentrations were assessed using MicroBio MB2 air sampling and particle quantities using Kanomax 3889 GEOα counters. Compared to an air turbine, the HSCAH reduced settled bioaerosols by 99.72%, 100.00%, and 100.00% for no mitigation, aspiration, and rubber dam, respectively. Bacteriophage concentrations in the air were reduced by 99.98%, 100.00%, and 100.00% with the same mitigations. Use of the HSCAH with high-volume aspiration resulted in no detectable bacteriophage, both on nonsplatter settle plates and in air samples taken 6 to 10 min postprocedure. To our knowledge, this study is the first to report the aerosolization in a dental clinic of active virus as a marker for risk determination. While this model represents a worst-case scenario for possible SARS-CoV-2 dispersal, these data showed that the use of HSCAHs can vastly reduce the risk of viral aerosolization and therefore remove the need for clinic fallow time. Furthermore, our findings indicate that the use of particle analysis alone cannot provide sufficient insight to understand bioaerosol infection risk.