Vitamin D Switches BAF Complexes to Protect ß Cells.

A primary cause of disease progression in type 2 diabetes (T2D) is ß cell dysfunction due to inflammatory stress and insulin resistance. However, preventing ß cell exhaustion under diabetic conditions is a major therapeutic challenge. Here, we identify the vitamin D receptor (VDR) as a key modulator of inflammation and ß cell survival. Alternative recognition of an acetylated lysine in VDR by bromodomain proteins BRD7 and BRD9 directs association to PBAF and BAF chromatin remodeling complexes, respectively. Mechanistically, ligand promotes VDR association with PBAF to effect genome-wide changes in chromatin accessibility and enhancer landscape, resulting in an anti-inflammatory response. Importantly, pharmacological inhibition of BRD9 promotes PBAF-VDR association to restore ß cell function and ameliorate hyperglycemia in murine T2D models. These studies reveal an unrecognized VDR-dependent transcriptional program underpinning ß cell survival and identifies the VDR:PBAF/BAF association as a potential therapeutic target for T2D.

Virtual Reality Job Interview Training for Adults Receiving Prison-Based Employment Services: A Randomized Controlled Feasibility and Initial Effectiveness Trial.

Returning citizens struggle to obtain employment after release from prison, and navigating job interviews is a critical barrier they encounter. Implementing evidence-based interview training is a major gap in prison-based vocational services. We conducted a randomized controlled trial (RCT) to evaluate the feasibility and initial effectiveness of Virtual Reality Job Interview Training within two prisons. Forty-four male returning citizens were randomized to receive service-as-usual (SAU) with VR-JIT (SAU+VR-JIT, n = 28) or SAU (n = 16). Participants reported VR-JIT was highly acceptable and usable. SAU+VR-JIT, as compared to SAU, had significant improvements (with large effect sizes) in interview skills, interview training motivation, and interview anxiety (all p < .05; ηp2 > .15), and greater employment by 6-month follow-up (OR = 7.4, p = .045). VR-JIT can potentially help fill a major gap in prison-based services. Future research is needed to validate VR-JIT effectiveness and evaluate VR-JIT implementation strategies within prisons.

Mixed methods implementation evaluation of virtual interview training for transition-age autistic youth in pre-employment transition services.

BACKGROUND: Autistic transition-age youth are employed at rates far lower than their non-disabled peers as well as youth with other disabilities. Meanwhile, very few studies have evaluated the implementation of job interviewing practices within pre-employment transition services. OBJECTIVE: We conducted an initial implementation evaluation as part of a Type I hybrid randomized controlled effectiveness-implementation trial where we trained teachers to deliver Virtual Interview Training for Transition-Age Youth (VIT-TAY) within five pre-employment transition services programs. METHODS: We used mixed methods to evaluate leader (n=5), teacher (n=15) and autistic transition age youth (n=48) perceptions of VIT-TAY. We used descriptive statistics and thematic network analysis to evaluate survey data. Mixed methods integration was then performed to make comparisons between quantitative and qualitative results. RESULTS: Quantitative survey data revealed that leaders and teachers found VIT-TAY to be highly acceptable and appropriate for pre-employment transition services; findings which were confirmed via thematic network analysis of qualitative interview data. Autistic students reported via quantitative surveys that VIT-TAY was acceptable and usable, which was confirmed via thematic network analysis of open-ended survey data. CONCLUSIONS: This initial implementation evaluation can be used to inform a larger scale implementation evaluation of VIT-TAY in schools.

Implementation Preparation Costs of Virtual Reality Job Interview Training in Prisons: A Budget Impact Analysis.

Virtual Reality Job Interview Training (VR-JIT) has increased employment rates for returning citizens when added to a successful prison-based employment readiness program. However, implementation preparation cost-expenses prior to offering VR-JIT to intended recipients-is unknown. We estimated the cost of implementation preparation activities (e.g., organizing workflow) for two prisons to deliver VR-JIT. We conducted a budget impact analysis and enumerated the labor costs incurred during this important stage of implementation. Labor costs were approximately $8,847 per prison. Our sensitivity analysis estimated the labor costs to replicate this effort in a new prison to range from $2,877 to $4,306 per prison. Thus, VR-JIT may be an affordable tool for prison-based employment readiness programs to improve gainful employment.

Evaluating the role of Burkholderia pseudomallei K96243 toxins BPSS0390, BPSS0395, and BPSS1584 in persistent infection.

Burkholderia pseudomallei is the causative agent of melioidosis, a disease with a mortality rate of up to 40% even with treatment. Despite the ability of certain antibiotics to control initial infection, relapse occurs in treated patients. The inability of antibiotics to clear this bacterial infection is in part due to persistence, an evasion mechanism against antibiotics and the effect of host defenses. Evaluation of antibiotic efficacy against B. pseudomallei revealed that up to 48% of in vitro grown populations can survive in a persister state. Toxin-antitoxin (TA) systems have been previously implicated in modulating bacterial persistence. We generated three isogenic TA mutants and found that loss of each toxin gene did not alter antibiotic persistence or macrophage survival. In response to macrophage-induced persistence, all three toxin mutants demonstrated increased intracellular susceptibility to levofloxacin which in part was due to the inability of the mutants to induce persistence after nitric oxide or nutrient starvation. In an inhalational model of murine melioidosis, both ΔBPSS0395 and ΔBPSS1584 strains were attenuated, and treatment with levofloxacin led to significant reduction in lung colonisation and reduced splenic colonisation by ΔBPSS0395. Based on our findings, these toxins deserve additional evaluation as putative therapeutic targets.

Increased Mortality in Mice following Immunoprophylaxis Therapy with High Dosage of Nicotinamide in Burkholderia Persistent Infections.

Bacterial persistence, known as noninherited antibacterial resistance, is a factor contributing to the establishment of long-lasting chronic bacterial infections. In this study, we examined the ability of nicotinamide (NA) to potentiate the activity of different classes of antibiotics against Burkholderia thailandensis persister cells. Here we demonstrate that addition of NA in in vitro models of B. thailandensis infection resulted in a significant depletion of the persister population in response to various classes of antibiotics. We applied microfluidic bioreactors with a continuous medium flow to study the effect of supplementation with an NA gradient on the recovery of B. thailandensis persister populations. A coculture of human neutrophils preactivated with 50 µM NA and B. thailandensis resulted in the most efficient reduction in the persister population. Applying single-cell RNA fluorescence in situ hybridization analysis and quantitative PCR, we found that NA inhibited gene expression of the stringent response regulator relA, implicated in the regulation of the persister metabolic state. We also demonstrate that a therapeutic dose of NA (250 mg/kg of body weight), previously applied as immunoprophylaxis against antibiotic-resistant bacterial species, produced adverse effects in an in vivo murine model of infection with the highly pathogenic bacterium Burkholderia pseudomallei, indicating that therapeutic dose and metabolite effects have to be carefully evaluated and tailored for every case of potential clinical application.

Development of Subunit Vaccines That Provide High-Level Protection and Sterilizing Immunity against Acute Inhalational Melioidosis.

Burkholderia pseudomallei, the etiologic agent of melioidosis, causes severe disease in humans and animals. Diagnosis and treatment of melioidosis can be challenging, and no licensed vaccines currently exist. Several studies have shown that this pathogen expresses a variety of structurally conserved protective antigens that include cell surface polysaccharides and cell-associated and cell-secreted proteins. Based on those findings, such antigens have become important components of the subunit vaccine candidates that we are currently developing. In the present study, the 6-deoxyheptan capsular polysaccharide (CPS) from B. pseudomallei was purified, chemically activated, and covalently linked to recombinant CRM197 diphtheria toxin mutant (CRM197) to produce CPS-CRM197. Additionally, tandem nickel-cobalt affinity chromatography was used to prepare highly purified recombinant B. pseudomallei Hcp1 and TssM proteins. Immunization of C57BL/6 mice with CPS-CRM197 produced high-titer IgG and opsonizing antibody responses against the CPS component of the glycoconjugate, while immunization with Hcp1 and TssM produced high-titer IgG and robust gamma interferon-secreting T cell responses against the proteins. Extending upon these studies, we found that when mice were vaccinated with a combination of CPS-CRM197 and Hcp1, 100% of the mice survived a lethal inhalational challenge with B. pseudomallei Remarkably, 70% of the survivors had no culturable bacteria in their lungs, livers, or spleens, indicating that the vaccine formulation had generated sterilizing immune responses. Collectively, these studies help to better establish surrogates of antigen-induced immunity against B. pseudomallei as well as provide valuable insights toward the development of a safe, affordable, and effective melioidosis vaccine.

Nursing home nurses' and community-dwelling older adults' reported knowledge, attitudes, and behavior toward antibiotic use.

BACKGROUND: Antibiotic overuse causes antibiotic resistance, one of the most important threats to human health. Older adults, particularly those in nursing homes, often receive antibiotics when they are not indicated. METHODS: To understand knowledge, attitudes, and behaviors of nursing home (NH) nurses and community-dwelling older adults towards antibiotic use, especially in clinical situations consistent with antibiotic overuse, we conducted a mixed-method survey in two NHs and one Family Medicine clinic in North Carolina, among English-speaking nurses and community-dwelling, cognitively intact adults aged 65 years or older. Based on the Knowledge-Attitude-Practice model, the survey assessed knowledge, attitudes, and behavior towards antibiotic use, including three vignettes designed to elicit possible antibiotic overuse: asymptomatic bacteriuria (ASB), a viral upper respiratory illness (URI), and a wound from a fall. RESULTS: Of 31 NH nurses and 66 community-dwelling older adults, 70% reported knowledge of the dangers of taking antibiotics. Nurses more often reported evidence-based attitudes towards antibiotics than older adults, except 39% agreed with the statement "by the time I am sick enough to go to the doctor with a cold, I expect an antibiotic", while only 28% of older adults agreed with it. A majority of nurses did not see the need for antibiotics in any of the three vignettes: 77% for the ASB vignette, 87% for the URI vignette, and 97% for the wound vignette. Among older adults, 50% did not perceive a need for antibiotics in the ASB vignette, 58% in the URI vignette, and 74% in the wound vignette. CONCLUSIONS: While a substantial minority had no knowledge of the dangers of antibiotic use, non-evidence-based attitudes towards antibiotics, and behaviors indicating inappropriate management of suspected infections, most NH nurses and community-dwelling older adults know the harms of antibiotic use and demonstrate evidence-based attitudes and behaviors. However, more work is needed to improve the knowledge, attitudes and behaviors that may contribute to antibiotic overuse.

Finding Regulators Associated with the Expression of the Long Polar Fimbriae in Enteropathogenic Escherichia coli.

UNLABELLED: Enteropathogenic Escherichia coli (EPEC) is a human pathogen that requires initial adhesion to the intestine in order to cause disease. Multiple adhesion factors have been identified in E. coli strains, among them the long polar fimbriae (Lpf), a colonization factor associated with intestinal adhesion. The conditions of Lpf expression are well understood in enterohemorrhagic E. coli (EHEC); however, the expression of EPEC lpf has been found to be repressed under any in vitro condition tested. Therefore, we decided to identify those factors silencing expression of EPEC lpf. Because histone-like nucleoid structuring protein (H-NS) is a known repressor of EHEC lpf, we tested it and found that H-NS is a repressor of EPEC lpf. We also found that the adhesion of the EPEC Δhns strain was significantly enhanced compared to the wild-type strain. Because lpf expression was modestly increased in the hns mutant, transposon mutagenesis was performed to find a strain displaying higher lpf expression than EPEC Δhns. One Tn5 insertion was identified within the yhjX gene, and further in vitro characterization revealed increased lpf expression and adhesion to Caco-2 cells compared with EPEC Δhns. However, in a murine model of intestinal infection, the EPEC Δhns and EPEC Δhns Tn5 mutants had only a slight change in colonization pattern compared to the wild-type strain. Our data showed that EPEC Lpf is transcribed, but its role in EPEC intestinal colonization requires further analysis. IMPORTANCE: Data are presented demonstrating that the long polar fimbriae (lpf) operon in enteropathogenic E. coli (EPEC) is highly regulated; however, derepression occurs by mutagenizing two proteins associated with its control. The study demonstrates that the EPEC lpf operon can be expressed and, therefore, participates in the EPEC adherence phenotype.

The IbeA invasin of adherent-invasive Escherichia coli mediates interaction with intestinal epithelia and macrophages.

Adherent-invasive Escherichia coli (AIEC) pathogroup isolates are a group of isolates from the intestinal mucosa of Crohn's disease patients that can invade intestinal epithelial cells (IECs) or macrophages and survive and/or replicate within. We have identified the ibeA gene in the genome of AIEC strain NRG857c and report the contribution of IbeA to the interaction of AIEC with IECs and macrophages and colonization of the mouse intestine. An ibeA deletion mutant strain (NRG857cΔibeA) was constructed, and the in vitro effect on AIEC adhesion and invasion of nonpolarized and polarized Caco-2 cells, the adhesion and transcytosis of M-like cells, the intracellular survival in THP-1 macrophages, and the contribution to intestinal colonization of the CD-1 murine model of infection were evaluated. A significant reduction in invasion was observed with the ibeA mutant in Caco-2 and M-like cells, whereas adhesion was not affected. Complementation of the mutant reestablished Caco-2 invasive phenotype to wild-type levels. Reduction in invasion did not significantly affect transcytosis through M-like cells at early time points. The absence of ibeA significantly affected AIEC intramacrophage survival up to 24 h postinfection. No significant changes associated with IbeA were found in AIEC colonization across the murine gastrointestinal tract, but a slight reduction of gamma interferon was observed in the ceca of mice infected with the ibeA mutant. In addition, a decrease in the pathology scores was observed in the ilea and ceca of mice infected with the ibeA mutant. Our data support the function of IbeA in the AIEC invasion process, macrophage survival, and inflammatory response in the murine intestine.

Phosphatase inhibition prevents the activity-dependent trafficking of GABAA receptors during status epilepticus in the young animal.

OBJECTIVES: To determine if the activity-dependent trafficking of γ2 subunit-containing γ-aminobutyric acid type A receptors (GABAA Rs) that has been observed in older animals and posited to contribute to benzodiazepine pharmacoresistance during status epilepticus (SE) is age-dependent, and to evaluate whether blockade of protein phosphatases can inhibit or reverse the activity-dependent plasticity of these receptors. METHODS: The efficacy and potency of diazepam 0.2-10 mg/kg administered 3 or 60 min after the onset of a lithium/pilocarpine-induced seizure in postnatal day 15-16 rats was evaluated using video-electroencephalography (EEG) recordings. The surface expression of γ2 subunit-containing GABAA Rs was assessed using a biotinylation assay, and GABAA R-mediated miniature inhibitory postsynaptic currents (mIPSCs) were recorded using whole-cell patch-clamp recording techniques from dentate granule cells in hippocampal slices acutely obtained 60 min after seizure onset (SE-treated). The effect of the protein phosphatase inhibitors FK506 and okadaic acid (OA) on the surface expression of these receptors was determined in organotypic slice cultures exposed to high potassium and N-methyl-d-aspartate (NMDA) or in SE-treated slices. RESULTS: Diazepam terminated seizures of 3 min but not 60 min duration, even at the highest dose. In the SE-treated slices, the surface expression of γ2 subunit-containing GABAA Rs was reduced and the amplitude of the mIPSCs was diminished. Inhibition of protein phosphatases prevented the activity-induced reduction of the γ2 subunit-containing GABAA Rs in organotypic slice cultures. Furthermore, treatment of SE-treated slices with FK506 or OA restored the surface expression of the γ2 subunit-containing GABAA Rs and the mIPSC amplitude. SIGNIFICANCE: This study demonstrates that the plasticity of γ2 subunit-containing GABAA Rs associated with the development of benzodiazepine resistance in young and adult animals is similar. The findings of this study suggest that the mechanisms regulating the activity-dependent trafficking of GABAA Rs during SE can be targeted to develop novel adjunctive therapy for the treatment of benzodiazepine-refractory SE.

Slitrk gene duplication and expression in the developing zebrafish nervous system.

BACKGROUND: The Slitrk family of leucine-rich repeat (LRR) transmembrane proteins bears structural similarity to the Slits and the Trk receptor families, which exert well-established roles in directing nervous system development. Slitrks are less well understood, although they are highly expressed in the developing vertebrate nervous system. Moreover, slitrk variants are associated with several sensory and neuropsychiatric disorders, including myopia, deafness, obsessive-compulsive disorder (OCD), schizophrenia, and Tourette syndrome. Loss-of-function studies in mice show that Slitrks modulate neurite outgrowth and inhibitory synapse formation, although the molecular mechanisms of Slitrk function remain poorly characterized. RESULTS: As a prelude to examining the functional roles of Slitrks, we identified eight slitrk orthologs in zebrafish and observed that seven of the eight orthologs were actively transcribed in the nervous system at embryonic, larval, and adult stages. Similar to previous findings in mice and humans, zebrafish slitrks exhibited unique but overlapping spatial and temporal expression patterns in the developing brain, retina, and spinal cord. CONCLUSIONS: Zebrafish express Slitrks in the developing central nervous system at times and locations important to neuronal morphogenesis and synaptogenesis. Future studies will use zebrafish as a convenient, cost-effective model organism to characterize the functional roles of Slitrks in nervous system development.

Implementing Virtual Interview Training for Transition-Age Youth: Practical Strategies for Educators.

This column shares strategies for implementing a technology-based intervention within secondary special education transition services. Virtual Interview Training for Transition-Age Youth is a web-based job interview training that uses educational content and virtual hiring managers (Rita and Travis) to help teach job interview skills. Eight strategies were assembled by research staff, teachers, and administrators during two research studies conducted across n=47 schools that delivered the program (commonly called "Rita and Travis") to n=561 students in secondary special education transition programs. Eight support strategies for implementing Rita and Travis are described. Strategies include: prepare for implementation, ensure administrative support, prioritize training and support, address logistical challenges, integrate the program into the curriculum, take advantage of the administrative center, individualize student support, and offer virtual delivery. The purpose of this column is to prepare others for successful implementation of Virtual Interview Training for Transition-Age Youth within special education transition programs.

Implementation Preparation Costs of Virtual Interview Training in Pre-Employment Transition Services: A Budget Impact Analysis.

Virtual Reality Job Interview Training (VR-JIT) and Virtual Interview Training for Transition Age Youth (VIT-TAY) demonstrated initial effectiveness at increasing employment among transition-age youth with disabilities engaged in pre-employment transition services. We characterized activities and estimated the labor and non-labor costs required to prepare schools to implement VR-JIT or VIT-TAY. Implementation preparation and support teams reported labor hours throughout the implementation preparation process. Implementation preparation labor hours at 43 schools cost approximately $1,427 per school, while non-labor costs were $100 per trainee (student). We estimated the replication of implementation preparation labor activities would cost $1,024 per school (range: $841-$1,208). Most costs were spent in delivery planning and teacher training. Given that implementation preparation costs can be barriers to intervention adoption, our results provide critical information for contemplating future implementation of VR-JIT or VIT-TAY.

A Mixed-Methods Implementation Evaluation of Virtual Reality Job Interview Training in IPS Supported Employment.

OBJECTIVE: Employment rates among individuals with serious mental illness may be improved by engagement in the individual placement and support (IPS) model of supported employment. Results from a recent randomized controlled trial (RCT) indicate that virtual reality job interview training (VR-JIT) improves employment rates among individuals with serious mental illness who have been actively engaged in IPS for at least 90 days. This study reports on an initial implementation evaluation of VR-JIT during the RCT in a community mental health agency. METHODS: A sequential, complementary mixed-methods design included use of qualitative data to improve understanding of quantitative findings. Thirteen IPS staff trained to lead VR-JIT implementation completed VR-JIT acceptability, appropriateness, and feasibility surveys. Participants randomly assigned to IPS with VR-JIT completed acceptability (N=42) and usability (N=28) surveys after implementation. The authors also conducted five focus groups with IPS staff (N=11) and VR-JIT recipients (N=13) and semistructured interviews with IPS staff (N=9) and VR-JIT recipients (N=4), followed by an integrated analysis process. RESULTS: Quantitative results suggest that IPS staff found VR-JIT to be highly acceptable, appropriate for integration with IPS, and feasible for delivery. VR-JIT was highly acceptable to recipients. Qualitative results add important context to the quantitative findings, including benefits of VR-JIT for IPS staff as well as adaptations for delivering technology-based interventions to individuals with serious mental illness. CONCLUSIONS: These qualitative and quantitative findings are consistent with each other and were influenced by VR-JIT's adaptability and perceived benefits. Tailoring VR-JIT instruction and delivery to individuals with serious mental illness may help optimize VR-JIT implementation within IPS.

Semen-derived enhancer of viral infection (SEVI) binds bacteria, enhances bacterial phagocytosis by macrophages, and can protect against vaginal infection by a sexually transmitted bacterial pathogen.

The semen-derived enhancer of viral infection (SEVI) is a positively charged amyloid fibril that is derived from a self-assembling proteolytic cleavage fragment of prostatic acid phosphatase (PAP(248-286)). SEVI efficiently facilitates HIV-1 infection in vitro, but its normal physiologic function remains unknown. In light of the fact that other amyloidogenic peptides have been shown to possess direct antibacterial activity, we investigated whether SEVI could inhibit bacterial growth. Neither SEVI fibrils nor the unassembled PAP(248-286) peptide had significant direct antibacterial activity in vitro. However, SEVI fibrils bound to both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli and Neisseria gonorrhoeae) bacteria, in a charge-dependent fashion. Furthermore, SEVI fibrils but not the monomeric PAP(248-286) peptide promoted bacterial aggregation and enhanced the phagocytosis of bacteria by primary human macrophages. SEVI also enhanced binding of bacteria to macrophages and the subsequent release of bacterially induced proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and IL-1ß). Finally, SEVI fibrils inhibited murine vaginal colonization with Neisseria gonorrhoeae. These findings demonstrate that SEVI has indirect antimicrobial activity and that this activity is dependent on both the cationic charge and the fibrillar nature of SEVI.

Psychometric properties of the mock interview rating scale for autistic transition-age youth.

Background: Employment is a major contributor to quality of life. However, autistic people are often unemployed and underemployed. One potential barrier to employment is the job interview. However, the availability of psychometrically-evaluated assessments of job interviewing skills is limited for autism services providers and researchers. Objective: We analyzed the psychometric properties of the Mock Interview Rating Scale that was adapted for research with autistic transition-age youth (A-MIRS; a comprehensive assessment of video-recorded job interview role-play scenarios using anchor-based ratings for 14 scripted job scenarios). Methods: Eighty-five transition-age youth with autism completed one of two randomized controlled trials to test the effectiveness of two interventions focused on job interview skills. All participants completed a single job interview role-play at pre-test that was scored by raters using the A-MIRS. We analyzed the structure of the A-MIRS using classical test theory, which involved conducting both exploratory and confirmatory factor analyzes, Rasch model analysis and calibration techniques. We then assessed internal consistency, inter-rater reliability, and test-retest reliability. Pearson correlations were used to assess the A-MIRS' construct, convergent, divergent, criterion, and predictive validities by comparing it to demographic, clinical, cognitive, work history measures, and employment outcomes. Results: Results revealed an 11-item unidimensional construct with strong internal consistency, inter-rater reliability, and test-retest reliability. Construct [pragmatic social skills (r = 0.61, p < 0.001), self-reported interview skills (r = 0.34, p = 0.001)], divergent [e.g., age (r = -0.13, p = 0.26), race (r = 0.02, p = 0.87)], and predictive validities [competitive employment (r = 0.31, p = 0.03)] received initial support via study correlations, while convergent [e.g., intrinsic motivation (r = 0.32, p = 0.007), job interview anxiety (r = -0.19, p = 0.08)] and criterion [e.g., prior employment (r = 0.22, p = 0.046), current employment (r = 0.21, p = 0.054)] validities were limited. Conclusion: The psychometric properties of the 11-item A-MIRS ranged from strong-to-acceptable, indicating it may have utility as a reliable and valid method for assessing the job interview skills of autistic transition-age youth.

Psychometric properties of the mock interview rating scale for schizophrenia and other serious mental illnesses.

Background: Over the past 10 years, job interview training has emerged as an area of study among adults with schizophrenia and other serious mental illnesses who face significant challenges when navigating job interviews. The field of mental health services research has limited access to assessments of job interview skills with rigorously evaluated psychometric properties. Objective: We sought to evaluate the initial psychometric properties of a measure assessing job interview skills via role-play performance. Methods: As part of a randomized controlled trial, 90 adults with schizophrenia or other serious mental illnesses completed a job interview role-play assessment with eight items (and scored using anchors) called the mock interview rating scale (MIRS). A classical test theory analysis was conducted including confirmatory factor analyses, Rasch model analysis and calibration, and differential item functioning; along with inter-rater, internal consistency, and test-retest reliabilities. Pearson correlations were used to evaluate construct, convergent, divergent, criterion, and predictive validity by correlating the MIRS with demographic, clinical, cognitive, work history measures, and employment outcomes. Results: Our analyses resulted in the removal of a single item (sounding honest) and yielded a unidimensional total score measurement with support for its inter-rater reliability, internal consistency, and test-retest reliability. There was initial support for the construct, convergent, criterion, and predictive validities of the MIRS, as it correlated with measures of social competence, neurocognition, valuing job interview training, and employment outcomes. Meanwhile, the lack of correlations with race, physical health, and substance abuse lent support for divergent validity. Conclusion: This study presents initial evidence that the seven-item version of the MIRS has acceptable psychometric properties supporting its use to assess job interview skills reliably and validly among adults with schizophrenia and other serious mental illnesses. Clinical Trial Registration: NCT03049813.

Enhancing pre-employment transition services: A type 1 hybrid randomized controlled trial protocol for evaluating WorkChat: A Virtual Workday among autistic transition-age youth.

Autistic transition-age youth experience high rates of unemployment and underemployment, in part due to the social challenges they may face when having conversations in the workplace. In an effort to help enhance conversational abilities in the workplace, our collaborative team partnered to develop WorkChat: A Virtual Workday. Specifically, our team of scientists, community partners, and diversity and inclusion experts participated in a community-engaged process to develop WorkChat using iterative feedback from autistic transition-age youth and their teachers. With initial development complete, this study reports on the protocol that our collaborative team developed, reviewed, and approved to conduct a randomized controlled trial (RCT) to evaluate the real-world effectiveness and initial implementation process outcomes of WorkChat when integrated into post-secondary pre-employment transition services (Pre-ETS). Our aims are to: 1) evaluate whether services-as-usual in combination with WorkChat, compared to services-as-usual with an attention control, enhances social cognition and work-based social ability (between pre- and post-test); reduces anxiety about work-based social encounters (between pre- and post-test), and increases sustained employment by 9-month follow-up; 2) evaluate whether social cognitive ability and work-based social ability mediate the effect of WorkChat on sustained employment; and 3) conduct a multilevel, mixed-method process evaluation of WorkChat implementation.

Scaling Out Virtual Interview Training for Transition-Age Youth: A Quasi-Experimental Hybrid Effectiveness-Implementation Study.

In a previous randomized controlled trial (RCT), Virtual Interview Training for Transition Age Youth (VIT-TAY) enhanced employment for autistic youth receiving transition services. For this study, a non-randomized hybrid effectiveness-implementation trial evaluated whether VIT-TAY maintained its core implementation and effectiveness functions when scaled out to students with disabilities in 32 schools. Also, we compared the implementation and effectiveness between VIT-TAY and Virtual Reality Job Interview Training (VR-JIT; developed for adults and previously evaluated in students with disabilities). Core implementation functions did not differ between VIT-TAY and VR-JIT. Greater engagement with either training was significantly associated with employment (both p < 0.05). Overall, VIT-TAY was feasibly implemented with high adherence and may be effective at enhancing employment for students with disabilities. Limitations and implications for research and practice are discussed.