Durability and cross-reactivity of SARS-CoV-2 mRNA vaccine in adolescent children

Importance: Emergent SARS-CoV-2 variants and waning humoral immunity in vaccinated individuals are causing increased infections and hospitalizations. Children are not spared from infection nor complications of COVID-19, and the recent recommendation for boosters in individuals ages 12 years or older calls for broader understanding of the adolescent immune profile after mRNA vaccination. Objective: We sought to test the durability and cross-reactivity of anti-SARS-CoV-2 serologic responses over a six-month time course in vaccinated adolescents against the wildtype and Omicron antigens. Design, Setting and Participants: Adolescents who received a full (two-dose) series of the Pfizer-BioNTech mRNA vaccination participated in this longitudinal cohort study from May 2021 to January 2022. Blood samples were collected in clinical settings from thirty-one adolescents, nineteen of whom provided samples at four timepoints (prior to vaccination, two to three weeks after first dose, two to four weeks after second dose and six months after complete series). Sera were analyzed for antibody responses against wildtype and Omicron variant SARS-CoV-2-specific proteins. Main Outcomes and Measures: The main outcome was to analyze vaccine-induced immune responses over time by ELISA, as well as their cross-reactivity between antibody responses against wildtype SARS-CoV-2 and the Omicron variant of concern. Results: Thirty-one adolescents provided a blood sample for at least one timepoint. The median age of the cohort was 13.9 years. Half of the cohort was male, and one quarter of the population was Hispanic. Anti-Spike and anti-RBD antibodies waned after six months, nearing pre-vaccination levels. After the second dose of the vaccine, adolescent children displayed equal sensitivity for the Omicron-RBD and wildtype SARS-CoV-2-RBD, as well as an upward trend of Omicron-reactive antibodies six months after vaccination. Waning mRNA vaccine-induced immunity in adolescents highlights a vulnerability in pediatric protection against SARS-CoV-2 infection. Conclusions and Relevance: Vaccine-induced immunity wanes in adolescents over time to near pre-vaccinated levels. Cross-reactivity of antibodies generated by adolescents display efficacy against Omicron. These findings highlight the need for SARS-CoV-2 boosters to protect adolescents from highly infectious variants, illness and post-COVID-19 complications.

Bulking up CpBIG: A Penta-Terphenyl Cyclopentadienyl Ligand

The modification of cyclopentadienyl ligands with carefully selected substituents is a widely used strategy to tune their steric and electronic properties. We describe the synthesis of an extremely bulky penta-terphenyl cyclopentadienyl ligand (CpT5) by arylation of cyclopentadiene. Deprotonation reactions with various group 1 metals and bases afforded a complete series of alkali metal salts MCpT5 with M = Li to Cs. The compounds were isolated as solvate-free salts, which were characterized by multinuclear NMR spectroscopy, UV-vis spectroscopy and elemental analysis. Single-crystal X-ray diffraction studies on LiCpT5, NaCpT5 (crystallized as a solvate with one THF molecule per formula unit) and KCpT5 revealed the formation of metallocene-like sandwich structures in the solid state.

A complete biomimetic iron-sulfur cubane redox series

Synthetic iron-sulfur cubanes are essential models for biological cofactors in the more complex enzymatic environments. However, a complete series of [Fe4S4]n complexes spanning all biorelevant oxidation states (n = 0-3+) has never been prepared. Here, we demonstrate that the use of a bulky arylthiolate ligand promoting the encapsulation of alkali-metal cations in the vicinity of the cubane enables the synthesis of such a series. Characterization by EPR, 57Fe Mössbauer spectroscopy, UV-Vis electronic absorption and variable-temperature X-ray diffraction analysis reveals key trends for the Fe4S4 core’s geometry as well as for the Mössbauer isomer shift, which both correlate systematically with oxidation state. Furthermore, we confirm the S=4 electronic ground state of the most reduced member, [Fe4S4]0, in agreement with that proposed for the all-ferrous cubanes in Nature.

A complete biomimetic iron-sulfur cubane redox series

Synthetic iron-sulfur cubanes are essential models for biological cofactors in the more complex enzymatic environments. However, a complete series of [Fe4S4]n complexes spanning all biorelevant oxidation states (n = 0-3+) has never been prepared. Here, we demonstrate that the use of a bulky arylthiolate ligand promoting the encapsulation of alkali-metal cations in the vicinity of the cubane enables the synthesis of such a series. Characterization by EPR, 57Fe Mössbauer spectroscopy, UV-Vis electronic absorption and variable-temperature X-ray diffraction analysis reveals key trends for the Fe4S4 core’s geometry as well as for the Mössbauer isomer shift, which both correlate systematically with oxidation state. Furthermore, we confirm the S=4 electronic ground state of the most reduced member, [Fe4S4]0, in agreement with that proposed for the all-ferrous cubanes in Nature.

Kant and the Production of the Antinomy of Pure Reason

In this article, I claim that the Antinomy of pure reason emerges as the result of synthetic activities that require succession. In this regard, I show that cosmological conflicts involve different kinds of representations: (1) cosmological ideas, purely conceptual representations of the unconditioned and the product of non-temporal synthetic activities; and (2) putative complete series of spatiotemporal conditions, which require temporal synthetic activities. As I show, purely conceptual representations cannot produce cosmological conflicts: The Antinomy requires the interaction of reason, understanding, and sensibility. I also discuss the maxim and principle of pure reason, how they lead to the unconditioned (and its different notions), and how the cosmological syllogism produces the Antinomy.

Two poisson limit theorems for the coupon collector’s problem with group drawings

In the collector’s problem with group drawings, s out of n different types of coupon are sampled with replacement. In the uniform case, each s-subset of the types has the same probability of being sampled. For this case, we derive a Poisson limit theorem for the number of types that are sampled at most $c-1$ times, where $c \ge 1$ is fixed. In a specified approximate nonuniform setting, we prove a Poisson limit theorem for the special case $c=1$ . As corollaries, we obtain limit distributions for the waiting time for c complete series of types in the uniform case and a single complete series in the approximate nonuniform case.

Maximizing Completion of the Two-Dose COVID-19 Vaccine Series with Aid from Infographics

Two of the three COVID-19 vaccines approved in the United States require two doses to reach full efficacy, as do others available elsewhere in the world. The complete series of multidose COVID-19 vaccines offers stronger protection against infection by SARS-CoV-2 compared to single-dose injections with the same vaccines. Achieving perfect community-level adherence is a challenge in any public health campaign, even in non-pandemic times. Vaccines requiring multiple doses combined with a surge of vaccine hesitancy and misinformation that has been witnessed by the public during the COVID-19 pandemic are exacerbating the challenge of ensuring the world’s population achieves a sufficient level of immunity against COVID-19. Here, we describe the results of our study in which we sought to determine whether completion of a two-dose COVID-19 vaccine regimen could be improved by disseminating infographics that explain what the vaccine is and why returning for the second dose is beneficial. Our results show that the proportion of COVID-19 vaccine recipients returning for a second inoculation grew after COVID-19 vaccine infographics were distributed to first-time vaccine recipients. We suggest that extending communication and outreach initiatives into the clinic positively influences the rate of follow-up visits, and that infographics are useful tools to aid and bolster the deployment of COVID-19 vaccines.

Complete Public Law

Titles in the Complete series combine extracts from a wide range of primary materials with clear explanatory text to provide readers with a complete introductory resource. Complete Public Law combines clear explanatory text and practical learning features with extracts from a wide range of primary and secondary materials. The book has been structured with the needs of undergraduate courses in mind. Opening with consideration of basic constitutional principles (in which no previous knowledge is assumed), the chapters move on to cover all other essential areas, before closing with consideration of the principles and procedures of judicial review. This edition includes substantial updates to address the UK’s withdrawal from the European Union and the constitutional implications these new arrangements have, including in the context of devolution.

20. Judicial Review: Putting It All Together in Problem Answers

Titles in the Complete series combine extracts from a wide range of primary materials with clear explanatory text to provide readers with a complete introductory resource. This chapter ties together the loose strands of judicial review to provide a checklist of issues that must be considered in order to diagnose a judicial review problem and to provide a legal opinion for clients. The following questions are addressed: What are judicial review problem questions designed to test? How does one approach a judicial review problem question? How does one approach whether the body may be judicially reviewed? How does one approach whether the client has standing or may intervene in an action? How does one approach whether the other preconditions are met? How does one approach the grounds for review? How does one deal with issues of remedy? How does one provide a final assessment to the client?

19. Remedies

Titles in the Complete series combine extracts from a wide range of primary materials with clear explanatory text to provide readers with a complete introductory resource. This chapter discusses the remedies granted by the court. If a claimant successfully establishes that the public authority has acted in contravention of one of the grounds of review, then the court may grant a remedy. The purpose of a remedy is to tell the public authority what it has to do to comply with the judgment and to ensure, as far as possible, that it obeys the courts’ decision. There are two main types of remedies available in judicial review cases: ordinary remedies (injunction, declaration, and damages) and prerogative remedies (quashing order, prohibiting order, and mandatory order). The chapter also discusses situations that may cause the court to refuse a remedy and the courts’ powers to grant a remedy under the Human Rights Act 1998 (HRA 1998), including a declaration of incompatibility in accordance with section 4 HRA 1998.