Applied Research

This Phase 3b, double-blind, randomized, placebo-controlled, multicenter study is being undertaken at up to 170 sites internationally to evaluate the effect of OCA on clinical outcomes in 350 subjects with PBC. The study will include a screening period of up to 8 weeks, requiring two clinic visits. Eligible participants will be randomly allocated (1:1) to treatment with either OCA 5 mg or matching placebo tablets, taken orally once daily. Randomization will be stratified by standard treatment with UDCA (yes/no) and baseline liver function.

Non-Alcoholic Steatohepatitis (NASH) is a growing epidemic in the western world due to the contemporary eating habits and life styles.NASH can lead to cirrhosis, hepatic carcinoma and other liver complications. There are currently some treatments available. The only definitive way of detecting NASH in patients with advanced liver disease is by liver biopsy. However, liver biopsy has disadvantages, such as sampling errors, chance of complications and does not lend itself to following up after treatment.

Factors in the tumor microenvironment promote immunosuppression that permits tumor escape from immune destruction. Our data show that tumor PD-L1 (CD274, B7-H1) is a major regulator of tumor inflammatory lymphocyte (TIL) infiltrate. PD-L1 is widely expressed in many tumors and is the target of two successful new cancer immunotherapy approaches, but is a poor predictor of treatment efficacy.

Basic Research

T lymphocytes are critical mediators of immunity; however they are continuously lost for a variety of reasons throughout life, and therefore must be replaced. Generation of new T cells is the function of the thymus, and the unique stromal microenvironment in the thymus directs T cell development and the selection of self- tolerant, self-restricted T cell population. Unfortunately, the thymus undergoes a precipitous age-induced atrophy resulting in reduced naÔve T cell production.

This randomized clinical trial proposes to consent 240 Veterans and active-duty military personnel with antidepressant-resistant posttraumatic stress disorder (PTSD) at two sites (VA Connecticut Healthcare System, West Haven Campus and the San Antonio Military Medical Center; SAMMC) to test the safety and efficacy of repeated doses of intravenously administered ketamine as compared to placebo, in reducing symptoms of PTSD. At SAMMC, up to 120 active duty military personnel will be consented to randomize 99 and obtain complete data on 80 for analysis.

The goals of this program are: Project 1) Biology of the human lung mucosa in aging and tuberculosis; Project 2) Biology of alveolar macrophages in aging and tuberculosis; Project 3) Defining age-associated immune correlates of susceptibility to M. tuberculosis; and Project 4) Defining immune correlates of susceptibility to M. tuberculosis infection in the elderly" Txbiomed Project: 4696

The purpose of this randomized controlled trial is to compare the efficacy and potential biological mechanisms of action of 10 sessions of a web version of Prolonged Exposure (PE), Web PE, delivered over 8 weeks to 10 sessions of Present Centered Treatment (PCT) delivered over 8 weeks by a therapist in 120 active duty military personnel and veterans with PTSD. Up to 170 individuals will be consented to obtain data from 120 for analysis. Participants will be assessed at pre treatment, mid treatment, and 1, 3 and 6 months after treatment completion.