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OBJECTIVE: Opening Doors to Recovery (ODR) is a community navigation and recovery support model created in southeast Georgia by diverse, collaborative stakeholders. Following promising results from a quasi-experimental study, this randomized controlled trial hypothesized that, among patients with serious mental illnesses being discharged from inpatient psychiatric settings, compared to those randomized to traditional case management (CM) services, those randomized to ODR would have (1) lower likelihood of hospitalization, fewer hospitalizations, and fewer inpatient days; (2) lower likelihood of arrest, fewer arrests, and longer time to arrest; and, secondarily, (3) greater housing satisfaction and housing stability; and (4) higher scores on several scales measuring recovery-related constructs. METHODS: 240 individuals with Structured Clinical Interview for DSM-5 Disorders–based psychotic or mood disorders, functional impairment, and repeated hospitalizations were randomized (December 2014 to June 2018) to ODR or CM. Hospitalization and arrest data were collected from State agencies after 12 months, and housing- and recovery-related measures were collected in person, longitudinally at 4, 8, and 12 months. Intention-to-treat analyses were conducted. Effects of dropout were accounted for, and sensitivity analyses were run. RESULTS: ODR was associated with fewer days hospitalized (RR = 0.86, P = .001), a lower incidence of arrests (OR = 0.35, P < .0005), and longer time to arrest (HR = 0.42, P = .001). In addition, measures of housing satisfaction (Cohen d = 0.45) and recovery (Cohen d = 0.33) were significantly more improved in ODR patients compared to CM patients. CONCLUSIONS: The ODR model appears to have advantages over more traditional CM services and could fill a gap in the service array. Studying the mediators of success, cost benefit, dissemination, fidelity, and financing of the model is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04612777

We will be replicating experiment 3 of Sparkman and Walton's study.

Additional file 1: Supplementary Figure 1. Expression of different markers inantigen-specific CD8+ cells. Supplementary Figure 2. Percentageof CD28+ antigen-specific TN, TCM and totalCD8+ Tcells. Supplementary Figure 3. ERK1/2 phosphorylation in sorted IAV+and CMV+ TCM cells. Supplementary Figure 4. CD70 expression in Jurkat cells and CD27-CD70 signaling.

Infectious bronchitis virus causes an acute, highly contagious respiratory disease, responsible for significant economic losses to the poultry industry. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, have been associated with poor cross-protection. Available vaccines give poor cross-protection and rationally designed live attenuated vaccines, based on apathogenic BeauR, could address these. Here, to determine the role of S1 in protection, a series of homologous vaccination trials with rIBVs were conducted. Single vaccinations with chimeric rIBVs induced virus-specific partial protective immunity, characterized by reduction in viral load and serum antibody titers. However, BeauR-M41(S) was the only vaccination to improve the level of protection against clinical signs and the loss of tracheal ciliary activity. Growth characteristics show that all of the rIBVs replicated in vitro to similar levels. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection., Vaccination regimes against Infectious bronchitis virus (IBV), which are based on a single virus serotype, often induce insufficient levels of cross-protection against serotypes and two or more antigenically diverse vaccines are used in attempt to provide broader protection. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, are associated with poor cross-protection. Here, homologous vaccination trials with recombinant IBVs (rIBVs), based on the apathogenic strain, BeauR, were conducted to elucidate the role of S1 in protection. A single vaccination of specific-pathogen-free chickens with rIBV expressing S1 of virulent strains M41 or QX, BeauR-M41(S1) and BeauR-QX(S1), gave incomplete protection against homologous challenge, based on ciliary activity and clinical signs. There could be conformational issues with the spike if heterologous S1 and S2 are linked, suggesting a homologous S2 might be essential. To address this, a homologous vaccination-challenge trial incorporating rIBVs expressing full spike from M41, BeauR-M41(S), and S2 subunit from M41, BeauR-M41(S2) was conducted. All chimeric viruses grew to similar titers in vitro, induced virus-specific partial protective immunity, evident by cellular infiltrations, reductions in viral RNA load in the trachea and conjunctiva and higher serum anti-IBV titers. Collectively, these findings show that vaccination with rIBVs primed the birds for challenge but the viruses were cleared rapidly from the mucosal tissues in the head. Chimeric S1 and S2 viruses did not protect as effectively as BeauR-M41(S) based on ciliary activity and clinical signs. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection. IMPORTANCE Infectious bronchitis virus causes an acute, highly contagious respiratory disease, responsible for significant economic losses to the poultry industry. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, have been associated with poor cross-protection. Available vaccines give poor cross-protection and rationally designed live attenuated vaccines, based on apathogenic BeauR, could address these. Here, to determine the role of S1 in protection, a series of homologous vaccination trials with rIBVs were conducted. Single vaccinations with chimeric rIBVs induced virus-specific partial protective immunity, characterized by reduction in viral load and serum antibody titers. However, BeauR-M41(S) was the only vaccination to improve the level of protection against clinical signs and the loss of tracheal ciliary activity. Growth characteristics show that all of the rIBVs replicated in vitro to similar levels. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection.

Baseline characteristics of patients excluded from analysis. (DOC 35Â kb)

Baseline characteristics of patients excluded from analysis. (DOC 35Â kb)

GAP stage calculation. (DOC 30Â kb)

Drug resistance is a major concern in the treatment of numerous diseases caused by infectious agents, creating an urgent need for new treatments. In this study, I assessed the effectiveness of compounds against two medically important lung pathogens, Mycobacterium tuberculosis and Pseudomonas aeruginosa, using complementary methods of drug discovery and assessment. The first approach identified high-affinity iron chelators of the pyridoxal isonicotinoyl hydrazone (PIH) class that could restrict the growth of clinically significant mycobacteria, using both in vitro and in vivo infection models. In a second study, novel chemical scaffolds, termed metal-cyclam complexes (MCyC), were found to be specifically active against pathogenic mycobacteria, displayed relatively low toxicity and in some cases displayed a synergistic effect with currently used treatments. The final study used high-throughput screening assays to identify a small subset of compounds that could inhibit the growth of Pseudomonas and mycobacterial species, from a library of 1920 compounds made up of a diverse series of natural and synthetic products. In conclusion, this thesis has identified lead products that with additional study/modification could lead to viable compounds for future treatment of pathogenic bacterial infection in humans.

Tuberculosis (TB) accounted for 1.5 million deaths in 2014 and new classes of anti-TB drugs are required. We re-port a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic myco-bacteria. These compounds inhibit intracellular growth of Mycobacterium tuberculosis, are non-toxic to human cell lines and are active against multidrug-resistant M. tuberculosis strains, indicating a distinct mode of action. These compounds warrant further appraisal as novel agents to control TB in humans. This work was supported by the National Health and Medical Research Council (NHMRC) Project APP1084266, the NHMRC Center of Research Excellence in Tuberculosis Control (APP1043225) and the University of Sydney Sydnovate Fund. We acknowledge the Centre for Drug Candidate Optimization, Monash University for the ADME studies