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"Appelbaum, Stanley"
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Qualitative Evaluation of Acceptability and Feasibility of a Behavioral Intervention to Reduce Violence Among Young Adults with Early Psychosis
Young adults with early psychosis are at higher risk of violent behavior, but no studies have explored using CBT-based interventions to reduce violence in specialized early intervention services (EIS) settings. This study describes formative research about the acceptability and feasibility of the Psychological Intervention for Complex PTSD and Schizophrenia-Spectrum disorder (PICASSO) to reduce violence, using interviews with EIS participants and staff. Generated themes regarding acceptability included negative experiences of violence and the desire to control and minimize violence. Themes regarding feasibility raised concerns about time constraints, consistency of participation in the intervention, and implementation issues in the context of stigma related to both psychosis and perpetration of violence. Findings from this study suggest there is a need for an intervention addressing violence risk. If adequate resources are devoted to addressing implementation issues, a CBT intervention for violence like PICASSO appears both acceptable and feasible for EIS participants and staff.
Journal Article
Verification of prognostic expression biomarkers is improved by examining enriched leukemic blasts rather than mononuclear cells from acute myeloid leukemia patients
Background
Studies have not systematically compared the ability to verify performance of prognostic transcripts in paired bulk mononuclear cells versus viable CD34-expressing leukemic blasts from patients with acute myeloid leukemia. We hypothesized that examining the homogenous leukemic blasts will yield different biological information and may improve prognostic performance of expression biomarkers.
Methods
To assess the impact of cellular heterogeneity on expression biomarkers in acute myeloid leukemia, we systematically examined paired mononuclear cells and viable CD34-expressing leukemic blasts from SWOG diagnostic specimens. After enrichment, patients were assigned into discovery and validation cohorts based on availability of extracted RNA. Analyses of RNA sequencing data examined how enrichment impacted differentially expressed genes associated with pre-analytic variables, patient characteristics, and clinical outcomes.
Results
Blast enrichment yielded significantly different expression profiles and biological pathways associated with clinical characteristics (e.g., cytogenetics). Although numerous differentially expressed genes were associated with clinical outcomes, most lost their prognostic significance in the mononuclear cells and blasts after adjusting for age and ELN risk, with only 11 genes remaining significant for overall survival in both cell populations (
CEP70
,
COMMD7
,
DNMT3B
,
ECE1
,
LNX2
,
NEGR1
,
PIK3C2B
,
SEMA4D
,
SMAD2
,
TAF8
,
ZNF444
). To examine the impact of enrichment on biomarker verification, these 11 candidate biomarkers were examined by quantitative RT/PCR in the validation cohort. After adjusting for ELN risk and age, expression of 4 genes (
CEP70
,
DNMT3B
,
ECE1
, and
PIK3CB
) remained significantly associated with overall survival in the blasts, while none met statistical significance in mononuclear cells.
Conclusions
This study provides insights into biological information gained/lost by examining viable CD34-expressing leukemic blasts versus mononuclear cells from the same patient and shows an improved verification rate for expression biomarkers in blasts.
Journal Article