Locus of Control Among Arab and Jewish Israeli Parolees.

This research examines how participation in the Israeli Prisoner Rehabilitation Authority supervised therapy program for paroled prisoners can reinforce Jewish and Arab prisoners' locus of control given their cultural diversity. Research participants included 108 paroled prisoners who had taken part in the program during 2019 to 2020. The program appears to have made a positive contribution to participants' locus of control, particularly among Jewish parolees. For Arab parolees, the program's strongest contribution was alleviating their apprehensions about returning to prison. Possible Theoretical explanations are offered for this finding, by referring to the concept of "culture-sensitive care" and the potential contribution of a change in perspective regarding the process of ending delinquency.

Dropout from Treatment and Desistance from Crime among Released Prisoners in Jerusalem Halfway House for Prisoners with Substance Misuse Disorder.

The study aims to investigate the rates of recidivism among prisoners on parole with a substance misuse disorder who participated in the Jerusalem halfway-house, which combines supervision, employment, and a comprehensive therapeutic program. The study population included all participants who have been treated in the halfway-house (N = 125), whereas the comparison group included all prisoners with a substance misuse disorder who were released after serving their full sentences (N = 321). To reduce possible selection biases, the Propensity Score Matching method was used. Findings show that prisoners, who were treated at the Jerusalem halfway-house, are characterized by higher and frequent rates of recidivism. However, when only completers of the halfway-house were evaluated, it was found that they had lower and slower rates of recidivism. Findings suggest that completing treatment contributes to desistance from crime in the critical post-release years among participants and indicates the importance of optimal diagnostic processes before admitting prisoners to a halfway-house.

Does the Enlightened Youth Project See the Light? A New Enterprise for Youths at Risk.

The aim of the present research is to examine the relationship between participation in the Enlightened Youth project for youths at risk and integration in employment at the end of the process, type of employment, dropout from school, and enlistment in the army. A database was prepared containing information on all the youths (499 in number) who were admitted to a multidisciplinary day Centre for Youths at Risk in Israel, of whom 86 participated in the project. To match a comparison group to the youths participating in the project, the propensity score matching method was operated. The research findings show a significant correlation between participation in the project and all the parameters examined, with implications regarding employment as a contributing factor among youths at risk, in terms of their personal lives, as well as financial and social well-being.

Level of neo-epitope predecessor and mutation type determine T cell activation of MHC binding peptides.

BACKGROUND: Targeting epitopes derived from neo-antigens (or "neo-epitopes") represents a promising immunotherapy approach with limited off-target effects. However, most peptides predicted using MHC binding prediction algorithms do not induce a CD8 + T cell response, and there is a crucial need to refine the predictions to readily identify the best antigens that could mediate T-cell responses. Such a response requires a high enough number of epitopes bound to the target MHC. This number is correlated with both the peptide-MHC binding affinity and the number of peptides reaching the ER. Beyond this, the response may be affected by the properties of the neo-epitope mutated residues. METHODS: Herein, we analyzed several experimental datasets from cancer patients to elaborate better predictive algorithms for T-cell reactivity to neo-epitopes. RESULTS: Indeed, potent classifiers for epitopes derived from neo-antigens in melanoma and other tumors can be developed based on biochemical properties of the mutated residue, the antigen expression level and the peptide processing stage. Among MHC binding peptides, the present classifiers can remove half of the peptides falsely predicted to activate T cells while maintaining the absolute majority of reactive peptides. CONCLUSIONS: The classifier properties further highlight the contribution of the quantity of peptides reaching the ER and the mutation type to CD8 + T cell responses. These classifiers were then validated on neo-antigens obtained from other datasets, confirming the validity of our prediction. Algorithm Availability: http://peptibase.cs.biu.ac.il/Tcell_predictor/ or by request from the authors as a standalone code.

Work-Related Intervention Programs: Desistance From Criminality and Occupational Integration Among Released Prisoners on Parole.

The present research examines the integration into employment of prisoners on parole who had been under the supervision of the Prisoner Rehabilitation Authority during the period 2007-2010. The supervision program included rehabilitation in the community, with the emphasis on employment. The research compares integration in employment and rates of reincarceration for the supervised group with prisoners who had been released from prison after serving their full sentences. The findings indicate that among prisoners who had participated in the supervision program, there is better integration into employment, a higher wage level, and lower rate of reincarceration. Based on these results, it may be tentatively inferred that the supervision program possesses a high potential for reintegrating released prisoners into the community.

"The Whole Is Greater Than the Sum of the Parts": Prison Staff Perceptions of Domestic Violence Rehabilitation Programs.

This qualitative study is part of a mixed methods research project that examined the effectiveness of the primary rehabilitation program for domestic violence offenders in the Israeli Prison Services-the "House of Hope." The quantitative part of the study showed that the "House of Hope" program was effective in reducing recidivism among participating inmates. The purpose of this qualitative study was to describe the rehabilitation program according to the perspectives of the program staff. For this purpose, semistructured interviews were conducted with the department staff during the study as well as with past directors. The qualitative findings suggested that the success of the program probably stemmed from a synergistic combination of several components, for example, identifying the characteristics of domestic violence offenders and adjusting treatment programs to their needs, along with exposure to psychological treatment in varied therapies (cognitive behavioral therapy, psychoeducational, and psychodynamic) and formats (group therapy and individual therapy) during a 1-year stay in a hierarchical therapeutic community. Other components mentioned are staff professionalism, stability, and the program's location in a therapeutic-oriented prison that is architecturally designed and built to create a less stressful environment for the inmates and the staff.

Selection of Shared and Neoantigen-Reactive T Cells for Adoptive Cell Therapy Based on CD137 Separation.

Adoptive cell therapy (ACT) of autologous tumor infiltrating lymphocytes (TIL) is an effective immunotherapy for patients with solid tumors, yielding objective response rates of around 40% in refractory patients with metastatic melanoma. Most clinical centers utilize bulk, randomly isolated TIL from the tumor tissue for ex vivo expansion and infusion. Only a minor fraction of the administered T cells recognizes tumor antigens, such as shared and mutation-derived neoantigens, and consequently eliminates the tumor. Thus, there are many ongoing effects to identify and select tumor-specific TIL for therapy; however, those approaches are very costly and require months, which is unreasonable for most metastatic patients. CD137 (4-1BB) has been identified as a co-stimulatory marker, which is induced upon the specific interaction of T cells with their target cell. Therefore, CD137 can be a useful biomarker and an important tool for the selection of tumor-reactive T cells. Here, we developed and validated a simple and time efficient method for the selection of CD137-expressing T cells for therapy based on magnetic bead separation. CD137 selection was performed with clinical grade compliant reagents, and TIL were expanded in a large-scale manner to meet cell numbers required for the patient setting in a GMP facility. For the first time, the methodology was designed to comply with both clinical needs and limitations, and its feasibility was assessed. CD137-selected TIL demonstrated significantly increased antitumor reactivity and were enriched for T cells recognizing neoantigens as well as shared tumor antigens. CD137-based selection enabled the enrichment of tumor-reactive T cells without the necessity of knowing the epitope specificity or the antigen type. The direct implementation of the CD137 separation method to the cell production of TIL may provide a simple way to improve the clinical efficiency of TIL ACT.

Adoptive Cell Therapy for Metastatic Melanoma.

Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) is a powerful form of immunotherapy by inducing durable complete responses that significantly extend the survival of melanoma patients. Mutation-derived neoantigens were recently identified as key factors for tumor recognition and rejection by TILs. The isolation of T-cell receptor (TCR) genes directed against neoantigens and their retransduction into peripheral T cells may provide a new form of ACT.Genetic modifications of T cells with chimeric antigen receptors (CARs) have demonstrated remarkable clinical results in hematologic malignancies, but are so far less effective in solid tumors. Only very limited reports exist in melanoma. Progress in CAR T-cell engineering, including neutralization of inhibitory signals or additional safety switches, may open opportunities also in melanoma.We review clinical results and latest developments of adoptive therapies with TILs, T-cell receptor, and CAR-modified T cells and discuss future directions for the treatment of melanoma.

Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens.

The antigenicity of cells is demarcated by the peptides bound by their Human Leucocyte Antigen (HLA) molecules. Through this antigen presentation, T cell specificity response is controlled. As a fraction of the expressed mutated peptides is presented on the HLA, these neo-epitopes could be immunogenic. Such neo-antigens have recently been identified through screening for predicted mutated peptides, using synthetic peptides or ones expressed from minigenes, combined with screening of patient tumor-infiltrating lymphocytes (TILs). Here we present a time and cost-effective method that combines whole-exome sequencing analysis with HLA peptidome mass spectrometry, to identify neo-antigens in a melanoma patient. Of the 1,019 amino acid changes identified through exome sequencing, two were confirmed by mass spectrometry to be presented by the cells. We then synthesized peptides and evaluated the two mutated neo-antigens for reactivity with autologous bulk TILs, and found that one yielded mutant-specific T-cell response. Our results demonstrate that this method can be used for immune response prediction and promise to provide an alternative approach for identifying immunogenic neo-epitopes in cancer.

Recidivism Among Licensed-Released Prisoners Who Participated in the EM Program in Israel.

Toward the end of 2006, a pilot program was launched in Israel wherein licensed-released prisoners were put under electronic monitoring (EM). In addition to EM, the pilot program, operated by the Prisoners' Rehabilitation Authority, provides programs of occupational supervision and personal therapy and is designed to allow for early release of those prisoners who, without increased supervision, would have been found unsuitable for early release. The aim of this study was to ascertain whether participation in the EM program among licensed-released prisoners in Israel might bring about lessened recidivism. For that matter, rates of arrests and incarceration were examined during a follow-up period of up to 4 years, among the entirety of licensed-released prisoners participating in the EM program between the years 2007 and 2009 (n = 155). To compare recidivism rates, a control group was assembled from among the entirety of released prisoners who were found unsuitable for early release in judicial conditions, and had therefore served the full term of their incarceration, to be released between the years 2005 and 2006 (a period of time during which an EM program was not yet operated among licensed-released prisoners in Israel). Study findings clearly show that while among the control group, 42% of released prisoners were re-incarcerated, at the end of a 4-year follow-up period, only 15% among the study group had returned to prison. These findings can be explained by combining the Social Control theory and the Self-Control theory which consider the period of time under EM program and the occupational and familial integration tools for reducing criminal connections and enhancing pro-social behavior.

Sociolegal characteristics and parole infractions among Israeli released prisoners during electronic monitoring.

The objective of this study is to examine the part played by sociolegal characteristics such as ethnic background, family status, or criminal past in the rate of infractions among ex-prisoners in Electronic Monitoring (EM) Programs. In addition, it focuses on the nature of the formal decisions made by community supervision agents regarding such infractions and their correlation with the sociolegal characteristics of the participants. The research population included all prisoners on license (i.e., prisoners who have been granted conditional early release) who took part in the EM project from mid-2007 until mid-2009 (24 months), altogether 155 participants. The data show no significant correlation between the number of infractions and the participant's sociolegal background. In spite of the fact that the EM coordinators have extensive discretionary power, which is likely to lead to discrimination attributable to variables such as ethnicity, this research shows that the most efficacious variable for explaining formal responses is an objective one-the number of infractions.

The role of RASSF1A in uveal melanoma.

PURPOSE: RASSF1A inactivation in uveal melanoma (UM) is common and methylation-induced. We investigated the effect of RASSF1A re-expression on the UM phenotype in vivo and in vitro. METHODS: The phenotypic effect of methylation-induced inactivation of RASSF1A in UM was explored using a stable RASSF1A-expressing UM-15 clone. RASSF1A expression was assessed using QRT-PCR. Proliferation was evaluated in vitro using MTT assays. Additionally, athymic NOD/SCID mice were injected subcutaneously or intraocularly with RASSF1A-expressing and -non-expressing UM-15 clones, and euthanized when tumors reached a volume of 1500 mm(3), or at 56 or 46 days, respectively. Tumor tissues, eyes, and livers were analyzed histologically. RESULTS: In vitro analysis confirmed the lack of RASSF1A expression and full methylation of the RASSF1A promoter region in the UM-15 cell line, which was reversible following treatment with 5-Aza-2-deoxycytidine. Cells expressing exogenous RASSF1A showed slower proliferation than controls and regained sensitivity to cisplatin. Compared to mice injected with control cells, mice treated with UM-15 cells expressing exogenous RASSF1A did not acquire intraocular tumors, and their subcutaneous tumors were relatively delayed and small. Neither group had liver metastases. CONCLUSIONS: UM cells reduced tumorigenicity in the presence of activated RASSF1A. RASSF1A apparently has an important role in the development of UM, and its reactivation might be applied in the development of new treatments.

Genetically modulating T-cell function to target cancer.

The adoptive transfer of tumor-specific T-lymphocytes holds promise for the treatment of metastatic cancer. Genetic modulation of T-lymphocytes using TCR transfer with tumor-specific TCR genes is an attractive strategy to generate anti-tumor response, especially against large solid tumors. Recently, several clinical trials have demonstrated the therapeutic potential of this approach which lead to impressive tumor regression in cancer patients. Still, several factors may hinder the clinical benefit of this approach, such as the type of cells to modulate, the vector configuration or the safety of the procedure. In the present review we will aim at giving an overview of the recent developments related to the immune modulation of the anti-tumor adaptive response using genetically engineered lymphocytes and will also elaborate the development of other genetic modifications to enhance their anti-tumor immune response.

"Signs of honor" among Russian inmates in Israel's prisons.

The unique nature of Israeli society as an immigrant society has also affected the prison population in Israel. This article focuses on a social and cultural phenomenon that particularly characterizes the prisoners of Russian origin, the phenomenon of tattoos. Using postmodernist theories, the article examines the function of the tattoo among Russian prisoners and the role it plays in constructing the criminal self-identity of these inmates in Israeli prisons. The tattoos observed during 2005-2006 among the Russian prisoners in four major Israeli prisons reflect the values of the Russian criminal subculture from which they evolved and were imported. This subculture is characterized by a hierarchical class structure and manifestations of machismo, domination, defiance, rebellion, and open antagonism against the Establishment and its representatives.

PI3K/Akt pathway mutations in retinoblastoma.

PURPOSE: Many malignancies are known to be associated with abnormal activation of the PI3K-AKT pathway. Recently, a somatic mutation in the AKT1 gene (E17K) was identified in a small proportion of human tumors. This mutation activated AKT1 by means of abnormal membrane recruitment and stimulated downstream signaling. This study was designed to analyze AKT1 mutations in retinoblastoma and gain insights into the role PI3K-AKT pathway plays in the development of this tumor. METHODS: Twenty-four samples of retinoblastoma from children were analyzed for mutations in the AKT1, PTEN and K-RAS genes, using a chip-based matrix-assisted laser desorption-time-of-flight (MALDI-TOF) mass spectrometer. Mutations in the PIK3CA gene were analyzed in 16 retinoblastoma samples using direct sequencing. RESULTS: These results show that the mutation E17K/AKT1 was not detected in the 24 samples of retinoblastoma analyzed. K-RAS mutations were identified in two samples. There were no mutations in any of the other genes analyzed by a mass array system. On direct sequencing of 16 samples for the PIK3CA gene, one sample showed gain of function mutation in exon 9. In another sample, a genetic polymorphism of unknown significance (rs17849079) was detected in exon 20. CONCLUSIONS: Although the PI3K-AKT pathway is known to be dysregulated in retinoblastoma, the low frequency of oncogenic mutations in the AKT1, PIK3CA, and PTEN genes, suggests a different activating mechanism.

Hypermethylation of CpG island loci of multiple tumor suppressor genes in retinoblastoma.

Epigenetic silencing of tumor suppressor genes by methylation of discrete regions of the CpG islands is a major mechanism underlying tumorigenesis. Methylation of at least three of five specific genes may represent a distinct trait, termed the CpG island methylator phenotype (CIMP). Positive CIMP is associated with BRAF mutations. The present study sought to investigate the presence of BRAF mutations in human retinoblastoma and the role of epigenetic silencing of multiple tumor suppression genes in a search for methylation phenotype. Twenty-five archival retinoblastoma samples were analyzed for BRAF mutations with polymerase chain reaction, Mutector assay, and direct sequencing. Nineteen samples were also analyzed for the promoter methylation status of eight candidate cancer-related genes using real-time quantitative methylation-specific polymerase chain reaction after sodium bisulfite modification. The CIMP status was determined. No BRAF mutations were found. The frequencies of cancer-related gene methylation were as follows: 89% for RASSF1A, 52% for NEUROG1, 5% for DAP-kinase, RUNX3 and CACNA1G, and 0 for RAR-beta2, SOCS-1 and IGF-2. The lack of BRAF mutations in retinoblastoma is in accord with the negative CIMP status and the high hypermethylation rate for RASSF1A. The high methylation status for NEUROG1 may point to an alternative pathway in the development and progression of retinoblastoma, but further studies are needed.

Gender, traditionalism, and attitudes toward domestic violence within a closed community.

This research was aimed at examining the attitudes toward domestic violence of people living in communal secular and religious kibbutzim. The findings, disregarding gender or traditionalism, indicate that most of the kibbutz members examined view the kibbutz as almost totally lacking any problem of violence toward women by their partners. The belief that the kibbutz home is a secure place for women within the family framework appears, surprisingly, at a higher frequency among women than among men. There are two possible theoretical explanations for this finding. First, the kibbutz lifestyle has indeed brought about equal power relationships, which explains why domestic violence is not viewed as a social problem, mostly by secular women. Second, women, who play a relatively minor role in constructing the public agenda in the kibbutz, have not become aware of the existence of this issue in the closed community.