A Comprehensive Framework for Evaluating the Value Created by Real-World Evidence for Diverse Stakeholders: The Case for Coordinated Registry Networks.

Objectives: This manuscript presents a comprehensive framework for the assessment of the value of real-world evidence (RWE) in healthcare decision-making. While RWE has been proposed to overcome some limitations of traditional, one-off studies, no systematic framework exists to measure if RWE actually lowers the burden. This framework aims to fill that gap by providing conceptual approaches for evaluating the time and cost efficiencies of RWE, thus guiding strategic investments in RWE infrastructure.

Psychedelic Science, Contemplative Practices, and Indigenous and Other Traditional Knowledge Systems: Towards Integrative Community-Based Approaches in Global Health.

As individuals and communities around the world confront mounting physical, psychological, and social threats, three complimentary mind-body-spirit pathways toward health, wellbeing, and human flourishing remain underappreciated within conventional practice among the biomedical, public health, and policy communities. This paper reviews literature on psychedelic science, contemplative practices, and Indigenous and other traditional knowledge systems to make the case that combining them in integrative models of care delivered through community-based approaches backed by strong and accountable health systems could prove transformative for global health. Both contemplative practices and certain psychedelic substances reliably induce self-transcendent experiences that can generate positive effects on health, well-being, and prosocial behavior, and combining them appears to have synergistic effects.

Recommendations for achieving interoperable and shareable medical data in the USA.

Easy access to large quantities of accurate health data is required to understand medical and scientific information in real-time; evaluate public health measures before, during, and after times of crisis; and prevent medical errors. Introducing a system in the USA that allows for efficient access to such health data and ensures auditability of data facts, while avoiding data silos, will require fundamental changes in current practices. Here, we recommend the implementation of standardized data collection and transmission systems, universal identifiers for individual patients and end users, a reference standard infrastructure to support calibration and integration of laboratory results from equivalent tests, and modernized working practices.

Global Summit on Regulatory Science 2013.

Regulatory science has been defined as the science that is used to develop regulatory decisions by government bodies. Regulatory science encompasses many scientific disciplines that oversee many studies producing a wide array of data. These may include fundamental research into the cellular interaction or response to a particular chemical or substance, hazard-assessment and dose-response studies in animal species, neurophysiological or neurobehavioral studies, best practices for the generation and analysis of genomics data, bioinformatics approaches, and mathematical modeling of risk.

Correlation of screening and confirmatory results in tiered immunogenicity testing by solution-phase bridging assays.

Biotherapeutic proteins induce undesired immune responses that can affect drug efficacy and safety. For this reason, immunogenicity assessment is an integral part of drug development and is mandated by the regulatory authorities. Immunogenicity is typically evaluated by a tiered approach consisting of a screening assay followed by a competitive inhibition with unlabeled drug serving as confirmatory assay and additional characterization of the immune response.

Prime-boost vaccination with rBCG/rAd35 enhances CD8⁺ cytolytic T-cell responses in lesions from Mycobacterium tuberculosis-infected primates.

To prevent the global spread of tuberculosis (TB) infection, a novel vaccine that triggers potent and long-lived immunity is urgently required. A plasmid-based vaccine has been developed to enhance activation of major histocompatibility complex (MHC) class I-restricted CD8⁺ cytolytic T cells using a recombinant Bacille Calmette-Guérin (rBCG) expressing a pore-forming toxin and the Mycobacterium tuberculosis (Mtb) antigens Ag85A, 85B and TB10.4 followed by a booster with a nonreplicating adenovirus 35 (rAd35) vaccine vector encoding the same Mtb antigens.

Human leukocyte antigens A*3001 and A*3002 show distinct peptide-binding patterns of the Mycobacterium tuberculosis protein TB10.4: consequences for immune recognition.

High-tuberculosis (TB)-burden countries are located in sub-Saharan Africa. We examined the frequency of human leukocyte antigen (HLA) alleles, followed by recombinant expression of the most frequent HLA-A alleles, i.e.

Extensive major histocompatibility complex class I binding promiscuity for Mycobacterium tuberculosis TB10.4 peptides and immune dominance of human leucocyte antigen (HLA)-B*0702 and HLA-B*0801 alleles in TB10.4 CD8 T-cell responses.

The molecular definition of major histocompatibility complex (MHC) class I-presented CD8(+) T-cell epitopes from clinically relevant Mycobacterium tuberculosis (Mtb) target proteins will aid in the rational design of T-cell-based diagnostics of tuberculosis (TB) and the measurement of TB vaccine-take. We used an epitope discovery system, based on recombinant MHC class I molecules that cover the most frequent Caucasian alleles [human leucocyte antigen (HLA)-A*0101, A*0201, A*0301, A*1101, A*2402, B*0702, B*0801 and B*1501], to identify MHC class I-binding peptides from overlapping 9-mer peptides representing the Mtb protein TB10.4.

rBCG induces strong antigen-specific T cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector.

Background: BCG vaccination, combined with adenoviral-delivered boosts, represents a reasonable strategy to augment, broaden and prolong immune protection against tuberculosis (TB). We tested BCG (SSI1331) (in 6 animals, delivered intradermally) and a recombinant (rBCG) AFRO-1 expressing perfringolysin (in 6 animals) followed by two boosts (delivered intramuscullary) with non-replicating adenovirus 35 (rAd35) expressing a fusion protein composed of Ag85A, Ag85B and TB10.4, for the capacity to induce antigen-specific cellular immune responses in rhesus macaques (Macaca mulatta).

A new recombinant bacille Calmette-Guérin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers.

Background: One strategy for improving anti-tuberculosis (TB) vaccination involves the use of recombinant bacille Calmette-Guérin (rBCG) overexpressing protective TB antigens. rBCG30, which overexpresses the Mycobacterium tuberculosis secreted antigen Ag85b, was the first rBCG shown to induce significantly greater protection against TB in animals than parental BCG.

Methods: We report here the first double-blind phase 1 trial of rBCG30 in 35 adults randomized to receive either rBCG30 or parental Tice BCG intradermally.

Immunological outcomes of new tuberculosis vaccine trials: WHO panel recommendations.

Willem Hanekom and colleagues make recommendations on assay harmonization for novel tuberculosis vaccine trials.

Antitumorigenic effects of HIV protease inhibitor ritonavir: inhibition of Kaposi sarcoma.

Treatment of patients with human immunodeficiency virus (HIV) protease inhibitors such as ritonavir can result in increases in CD4(+) T-cell counts that are independent of a reduction in HIV-1 viral load. This lack of correlation between the 2 has led to the identification of additional effects of ritonavir that potentially alter HIV disease pathogenesis. Our previous studies indicated that ritonavir directly affects immune cell activation, proliferation, and susceptibility to apoptosis.