specific HLA-E restricted T cells are induced during infection but not after BCG administration in non-human primates and humans.

Novel vaccines targeting the world's deadliest pathogen () are urgently needed as the efficacy of the Bacillus Calmette-Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule and HLA-E restricted specific CD8 T cells can control intracellular growth, making HLA-E a promising vaccine target for . In this study, we evaluated the frequency and phenotype of HLA-E restricted specific CD4/CD8 T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally.

Cross-cultural conceptions of third-party intervention across childhood.

Third-party intervention is a cornerstone of cooperative societies, yet we know little about how children develop an understanding of this social behavior. The present work generates a cross-cultural and developmental picture of how 6-, 9-, and 12-year-olds ( = 447) across four societies (India, Germany, Uganda, and the United States) reason about third-party intervention. To do so, we measured children's obligation judgments and unstructured descriptions of third-party intervention.

Developing conceptions of forgiveness across the lifespan.

Understanding how to respond to transgressions is central to cooperation, yet little is known about how individuals understand the consequences of these responses. Accordingly, the current study explored children's (ages 5-9), adolescents' (ages 11-14), and adults' (N = 544, predominantly White, ~50% female, tested in 2021) understandings of three such responses-forgiveness, punishment, and doing nothing. At all ages, participants differentiated between the consequences of these three responses.

Does Distance Matter? How Physical and Social Distance Shape Our Perceived Obligations to Others.

Debates within moral philosophy have long centered on the question of whether we are more obligated to help those close to us compared to those who are farther away. Despite these debates, we have little understanding of our psychological intuitions about these issues. In the current study, we presented adults and children (5- to 9-year-olds) in the United States ( = 406) with hypothetical scenarios involving pairs of socially and physically close and far strangers and asked about their obligations to help one another.

Safety, tolerability, viral kinetics, and immune correlates of protection in healthy, seropositive UK adults inoculated with SARS-CoV-2: a single-centre, open-label, phase 1 controlled human infection study.

Background: A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×10 50% tissue culture infectious dose (TCID) pre-alpha SARS-CoV-2 virus. Given the increasing prevalence of seropositivity to SARS-CoV-2, a CHIM that could be used for vaccine development will need to induce infection in those with pre-existing immunity. Our aim was to find a dose of pre-alpha SARS-CoV-2 virus that induced infection in previously infected individuals.

Mycobacterium ulcerans challenge strain selection for a Buruli ulcer controlled human infection model.

Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics. Here we present microbiological evidence supporting M.

Safety of a controlled human infection model of tuberculosis with aerosolised, live-attenuated Mycobacterium bovis BCG versus intradermal BCG in BCG-naive adults in the UK: a dose-escalation, randomised, controlled, phase 1 trial.

Background: Mycobacterium tuberculosis is the main causative agent of tuberculosis. BCG, the only licensed vaccine, provides inadequate protection against pulmonary tuberculosis. Controlled human infection models are useful tools for vaccine development.

How retributive motives shape the emergence of third-party punishment across intergroup contexts.

This study examines how retributive motives-the desire to punish for the purpose of inflicting harm in the absence of future benefits-shape third-party punishment behavior across intergroup contexts. Six- to nine-year-olds (N = 151, M = 8.00, SD = 1.

Nontuberculous mycobacteria testing and culture positivity in the United States.

Background: Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been increasing in the United States and globally. The predominant clinically relevant species of NTM in the United States are Mycobacterium avium complex (MAC) species and Mycobacterium abscessus.

Safety and immunogenicity of ChAdOx1 85A prime followed by MVA85A boost compared with BCG revaccination among Ugandan adolescents who received BCG at birth: a randomised, open-label trial.

Background: BCG confers reduced, variable protection against pulmonary tuberculosis. A more effective vaccine is needed. We evaluated the safety and immunogenicity of candidate regimen ChAdOx1 85A-MVA85A compared with BCG revaccination among Ugandan adolescents.

Adopting human factors in early phase and experimental medicine research: A nested pilot study observing controlled human infection with SARS-CoV-2.

Aims: The influence of human factors on safety in healthcare settings is well established, with targeted interventions reducing risk and enhancing team performance. In experimental and early phase clinical research participant safety is paramount and safeguarded by guidelines, protocolized care and staff training; however, the real-world interaction and implementation of these risk-mitigating measures has never been subjected to formal system-based assessment.

Methods: Independent structured observations, systematic review of study documents, and interviews and focus groups were used to collate data on three key tasks undertaken in a clinical research facility (CRF) during a SARS CoV-2 controlled human infection model (CHIM) study.

Global Epidemiology of Nontuberculous Mycobacterial Pulmonary Disease: A Review.

Nontuberculous mycobacterial (NTM) isolation and pulmonary disease (NTM-PD) have continued to increase in most regions of the world, driven mainly by Mycobacterium avium. Single-center studies also support increasing trends as well as a persistent burden of undiagnosed NTM among persons suspected of having tuberculosis (TB), in countries with moderate-to-high TB prevalence. Cumulative exposure to water and soil presents an increased risk to susceptible hosts, and trace metals in water supply are recently recognized risk factors.

The risk of pulmonary NTM infections and water-quality constituents among persons with cystic fibrosis in the United States, 2010-2019.

Rationale: The prevalence of nontuberculous mycobacterial (NTM) pulmonary disease varies geographically in the United States. Previous studies indicate that the presence of certain water-quality constituents in source water increases NTM infection risk.

Objective: To identify water-quality constituents that influence the risk of NTM pulmonary infection in persons with cystic fibrosis in the United States.

Incidence of nontuberculous mycobacteria infections among persons with cystic fibrosis in the United States (2010-2019).

Background: Nontuberculous mycobacteria (NTM) are ubiquitous, environmental bacteria that can cause chronic lung disease. Persons with cystic fibrosis (pwCF) are at high risk for NTM. Approximately 1 in 5 pwCF in the United States (U.

A human model of Buruli ulcer: The case for controlled human infection and considerations for selecting a Mycobacterium ulcerans challenge strain.

Critical knowledge gaps regarding infection with Mycobacterium ulcerans, the cause of Buruli ulcer (BU), have impeded development of new therapeutic approaches and vaccines for prevention of this neglected tropical disease. Here, we review the current understanding of host-pathogen interactions and correlates of immune protection to explore the case for establishing a controlled human infection model of M. ulcerans infection.

Environmental risk of nontuberculous mycobacterial infection: Strategies for advancing methodology.

The National Institute of Allergy and Infectious Diseases organized a symposium in June 2022, to facilitate discussion of the environmental risks for nontuberculous mycobacteria exposure and disease. The expert researchers presented recent studies and identified numerous research gaps. This report summarizes the discussion and identifies six major areas of future research related to culture-based and culture independent laboratory methods, alternate culture media and culturing conditions, frameworks for standardized laboratory methods, improved environmental sampling strategies, validation of exposure measures, and availability of high-quality spatiotemporal data.

When not helping is nice: Children's changing evaluations of helping during COVID-19.

A key aspect of children's moral and social understanding involves recognizing the value of helpful behaviors. COVID-19 has complicated this process; behaviors generally considered praiseworthy were considered problematic during the COVID-19 pandemic. The present study examined whether 6- to 12-year-olds ( = 228; residing in the United States) adapt their evaluations of helpful behavior in response to shifting norms.

Detecting clusters of high nontuberculous mycobacteria infection risk for persons with cystic fibrosis - An analysis of U.S. counties.

Nontuberculous mycobacteria are ubiquitous environmental bacteria that frequently cause disease in persons with cystic fibrosis (pwCF). The risks for NTM infection vary geographically. Detection of high-risk areas is important for focusing prevention efforts.

Methods of isolation and identification of nontuberculous mycobacteria from environmental samples: A scoping review.

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment. Some species of NTM are pathogenic and cause lung disease in susceptible persons. Epidemiologic studies of environmental NTM infection risk rely on both culture-dependent and culture-independent techniques for NTM isolation and identification.

Black and White Patients With Staphylococcus aureus Bacteremia Have Similar Outcomes but Different Risk Factors.

Background: Staphylococcus aureus bacteremia (SAB) disproportionately affects Black patients. The reasons for this disparity are unclear.

Methods: We evaluated a prospectively ascertained cohort of patients with SAB from 1995 to 2020.