FOCUS on women: Program evaluation of a pilot probation and primary care transitions clinic collaboration☆.

Gender-specific probation programs are needed for rising numbers of women on probation, as women's paths to probation differ from men's and are not as frequently addressed. Substance use, mental illness, health disparities, and barriers to treatment can contribute to women clients' unsuccessful completion of probation. The current study describes a process evaluation of the pilot Female Offenders Can Ultimately Succeed (FOCUS) program, which aimed to meet women probation clients' complex needs and improve their probation outcomes. Two women FOCUS Probation Officers had smaller-than-typical caseloads of 132 Medium- to Greatest-Risk women clients and received ongoing training in motivational and trauma-specific supervision strategies. To facilitate linkage to all needed treatment and social services, clients were referred to a primary care Transitions Clinic. Comparing non-FOCUS to FOCUS women clients with Violations of Probation, FOCUS clients had more successful completions of probation (higher non-punitive Restorations of Probation and lower punitive Revocations of Probation). At the Transitions Clinic, 52% of FOCUS clients received treatment. FOCUS clients and stakeholders provided narrative feedback reflecting a range of experiences in FOCUS, guiding future program implementation efforts. Promising outcomes from FOCUS demonstrate the potential of theory-based supervision and probation-medical collaboration to facilitate women clients' success in probation.

Cool-1-mediated inhibition of c-Cbl modulates multiple critical properties of glioblastomas, including the ability to generate tumors in vivo.

We discovered that glioblastoma (GBM) cells use Cool-1/ß-pix to inhibit normal activation of the c-Cbl ubiquitin ligase via the redox/Fyn/c-Cbl pathway and that c-Cbl inhibition is critical for GBM cell function. Restoring normal c-Cbl activity by Cool-1 knockdown in vitro reduced GBM cell division, almost eliminated generation of adhesion-independent spheroids, reduced the representation of cells expressing antigens thought to identify tumor initiating cells (TICs), reduced levels of several proteins of critical importance in TIC function (such as Notch-1 and Sox2), and increased sensitivity to BCNU (carmustine) and temozolomide (TMZ). In vivo, Cool-1 knockdown greatly suppressed the ability of GBM cells to generate tumors, an outcome that was c-Cbl dependent. In contrast, Cool-1 knockdown did not reduce division or increase BCNU or TMZ sensitivity in primary glial progenitor cells and Cool-1/c-Cbl complexes were not found in normal brain tissue. Our studies provide the first evidence that Cool-1 may be critical in the biology of human tumors, that suppression of c-Cbl by Cool-1 may be critical for generation of at least a subset of GBMs and offer a novel target that appears to be selectively necessary for TIC function and modulates chemoresistance in GBM cells. Targeting such proteins that inhibit c-Cbl offers potentially attractive opportunities for therapeutic development.