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Background: Pleural mesothelioma is a rare and incurable cancer, with complex physical and psychological symptoms. Despite recent advances in treatment, prognosis remains poor (average 8-15 months) with a lack of research on palliative and end-of-life care., Aim: To examine markers suggestive of quality palliative and end-of-life care, including receipt of specialist palliative care, advance care planning, fewer unplanned hospital admissions at end-of-life. To compare variables with socio-economic position to identify if inequalities exist., Design: A cohort study, retrospectively reviewing the medical notes from diagnosis to death for all patients diagnosed with pleural mesothelioma between 01/01/2016 and 31/12/2021., Setting/participants: Over 5 years, n  = 181 patients were diagnosed with pleural mesothelioma across Teesside (north-east England), n  = 30 were alive at study commencement and excluded. For the 151-patient cohort, demographics were as follows: 92% male, 79% aged 70-89 years and 26% in the lowest socio-economic quintile (based on area-level deprivation)., Results: Median survival was 246 days. Within the final 90 days of life, 69% of patients had at least 1 unplanned hospital admission, with 20% having 3+ (range 0-7). Those with the highest socio-economic position had less admissions on average. Specialist palliative care was received by patients, at home 34%, in hospital 26%, in hospice 11%. Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) decisions, were in the final 24 h of life for 18% of patients (median 7 days). Disease specific findings included police attendance for expected deaths and lack of signposting., Conclusion: Patients with pleural mesothelioma have unplanned admissions to hospital towards the end of life, with possible inequalities; they receive late advance care planning and face challenges unique to their disease. It is important that patients receive high quality palliative end-of-life care through accessing specialist palliative care or have guidance/signposting to other potential sources of support., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Reliable cell recovery and expansion are fundamental to the successful scale-up of chimeric antigen receptor (CAR) T cells or any therapeutic cell-manufacturing process. Here, we extend our previous work in whole blood by manufacturing a highly parallel deterministic lateral displacement (DLD) device incorporating diamond microposts and moving into processing, for the first time, apheresis blood products. This study demonstrates key metrics of cell recovery (80%) and platelet depletion (87%), and it shows that DLD T-cell preparations have high conversion to the T-central memory phenotype and expand well in culture, resulting in twofold greater central memory cells compared to Ficoll-Hypaque (Ficoll) and direct magnetic approaches. In addition, all samples processed by DLD converted to a majority T-central memory phenotype and did so with less variation, in stark contrast to Ficoll and direct magnetic prepared samples, which had partial conversion among all donors (<50%). This initial comparison of T-cell function infers that cells prepared via DLD may have a desirable bias, generating significant potential benefits for downstream cell processing. DLD processing provides a path to develop a simple closed system that can be automated while simultaneously addressing multiple steps when there is potential for human error, microbial contamination, and other current technical challenges associated with the manufacture of therapeutic cells.

Objectives: Type 2 diabetes mellitus (T2DM) clinical guidelines focus on optimizing glucose control, with therapy escalation classically initiated within a "failure-based" regimen. Within many diabetes models, HbA1c therapy escalation thresholds play a pivotal role, controlling duration of therapy and, consequently, incremental costs and benefits. The objective of this study was to assess the relationship between therapy escalation threshold and time to therapy escalation on predicted cost-effectiveness of T2DM treatments., Methods: This study used the Cardiff Diabetes Model to illustrate the relationship between costs and health outcomes associated with first-, second-, and third-line therapy as a function of time on each. Data from routine clinical practice were used to contrast predicted costs and health outcomes associated with guideline therapy escalation thresholds compared with clinical practice. The impact of baseline HbA1c and therapy escalation thresholds on cost-effectiveness was investigated, comparing a sodium/glucose cotransporter 2 inhibitor v. sulfonylurea added to metformin monotherapy., Results: Lower thresholds are associated with a shorter time spent on monotherapy, ranging from 1.1 years (escalation at 6.5%) to 13 years (escalation at 9.0%) and an increase in total lifetime cost of therapy. Treatment-related disutility is minimized with higher thresholds because progression to insulin is delayed. Using metformin combined with either dapagliflozin or a sulfonylurea to illustrate lower baseline HbA1c and/or higher therapy escalation thresholds was associated with increased cost-effectiveness ratios, driven by a longer duration of therapy., Discussion: A marked difference in treatment cost-effectiveness was demonstrated when comparing routine clinical practice with guideline-advocated therapy escalation. This is important to both health care professionals and the wider health economic community with respect to understanding the true cost-effectiveness profile of any particular T2DM therapy option., (© The Author(s) 2015.)

The aim of this qualitative study was to explore perspectives on rehabilitation of those detained in a New Zealand forensic hospital setting. Twenty forensic service users participated in individual interviews, which were audio-taped, transcribed verbatim, and subjected to thematic analysis. The analysis identified seven themes that were broadly categorized into those that concerned the rehabilitation context (external) and those that more directly reflected the forensic service user's personal experience (internal). External themes highlighted a person-centered approach, the nature of relationships with staff, consistency of care, and awareness of the rehabilitation pathway. Internal themes related to forensic service users' self-evaluations, agency, and coping strategies. These findings are discussed within the broader context in which rehabilitation took place., (© The Author(s) 2014.)

The good lives model (GLM) has become an increasingly popular theoretical framework underpinning sex offender treatment programs, and preliminary research suggests that the GLM may enhance the efficacy of programs that adhere to the Risk, Need, and Responsivity (RNR) principles. However, this potential rests on the appropriate operationalization of the GLM in practice. Operationalized appropriately, the GLM aims to facilitate risk reduction alongside equipping clients with the tools to live personally meaningful and fulfilling lives. However, misguided operationalization of the GLM could result in ineffective treatment and ultimately higher rates of reoffending. This article presents findings from a multisite study exploring how the GLM has been operationalized and the degree to which the GLM has been integrated in a sample of 13 North American treatment programs. A comprehensive coding protocol was developed that included items related to program aims and client induction/orientation, assessment, intervention planning, intervention content, and intervention delivery. Each site was visited and items were rated through a review of program documentation, interviews with program directors/managers, and observations of treatment groups. Findings from inductive (how the GLM was operationalized) and deductive (the extent to which the GLM was integrated) analyses are presented and GLM consistent and inconsistent practices are highlighted. The article concludes with suggestions for ways in which program responsiveness to the GLM could be enhanced.

Purpose: To assess the feasibility of mindfulness-based stress reduction (MBSR) for veterans with mental health conditions and to evaluate its efficacy on psychological well-being and stress reduction., Design: Single-group, pretest-posttest design., Method: 30 veterans within a mental health clinic of a VA (Veterans Administration) medical center were enrolled in an 8-week standard MBSR program. Perceived stress, sleep, mindfulness, and depression were measured via self-reports at baseline and study end. Feasibility was measured by compliance and satisfaction with the course., Findings: Scores on the Perceived Stress Scale (p =.002) and Beck Depression Inventory-II (p = .005) were significantly reduced (p = .002). The global measure for sleep from the Pittsburgh Sleep Quality Index improved significantly (p = .035). Satisfaction and compliance were high., Conclusion: MBSR is a feasible intervention that has potential efficacy for veterans with mental health conditions. Future controlled trials are needed in this area.

The good lives model (GLM) represents a new theoretical framework informing sex offender treatment programs; however, substantial variation has been observed in terms of how GLM-related ideas and practices have been applied. Integrated appropriately, the GLM offers potential for improving outcomes of programs following a cognitive-behavioral therapy (CBT) approach and operating according to a narrow operationalization of risk, need, responsivity (RNR) principles. Conversely, misguided or otherwise poor integration could increase the very risk practitioners work to prevent and manage. The purpose of this article is to provide an introduction and overview on how to integrate the GLM into treatment using CBT and RNR. The authors describe clinical implications of the GLM as they relate to program aims and orientation, assessment and intervention planning, content, and delivery.

Cognitive distortions in sex offenders are specific or general beliefs/attitudes that violate commonly accepted norms of rationality that have been shown to be associated with the onset and maintenance of sexual offending. In this article, we describe the major theories that have been formulated to explain the role of distorted cognition in initiating and maintaining sexual offending. We evaluate each theory in light of a set of theory appraisal criteria and the available empirical research. Finally, we conclude by drawing together the results of this theory evaluation process and highlight the major implications for treatment and future research.

Rehabilitation and treatment perspectives and interventions have concentrated efforts on areas where perpetrators of sexual abuse are deficient, neglecting those where offenders actively seek and strategically plan sexual offence situations and scenarios. Whereas sexual offenders may display deficiencies in some aspects of their lives, there are domain-relevant competencies such as the selection and manipulation of victims, decision making and problem solving, and eluding detection, in which some individuals appear to excel. Semistructured interviews are conducted with 47 male child sexual offenders in New Zealand, and data are analyzed using grounded theory to generate a model of offence-specific decision making. The outcome of the research is a descriptive model of expertise-related competency (ERC) of child sexual offending. The model identifies and emphasizes the variability of knowledge and skill acquisition among offenders.

The aim of the study was to investigate the process of desistance from sexual crime by comparing two groups of child molesters: One group was deemed to be desisting, while men in the other group were deemed as being still potentially active offenders. Men in the desisting group reported being optimistic for the future, reported an enhanced sense of personal agency and a more internalized locus of control, and identified treatment as being a turning point in their lives. In comparison, men in the active group were found to be more pessimistic and were more likely to blame external events, or situations, for their problems. One of the most striking findings of the research was that the desisting group had found a place within a social group or network, unlike the still potentially active offenders who all described a life of social isolation and alienation.

The ethics of care acknowledges the importance of establishing and maintaining practices that help people to meet their needs, develop and protect basic capabilities for problem solving, emotional functioning, and social interaction, and avoid pain and suffering. In this article, we explore the contribution an ethics of care perspective can make to work with sex offenders. First, we briefly describe five classes of ethical problems evident in work with sex offenders. Second, the concept of care is defined and a justification for a version of care theory provided. Third, we apply the care ethical theory to ethical issues with sex offenders and demonstrate its value in responding to the five classes of problems outlined earlier.

Research on offending behavior rehabilitation suggests that offenders would gain the maximum benefit from programs that reflect the individual needs of different types of offender. Multivariate theories of offending behavior are thus required to inform individualized rehabilitation. The aim of the current study was to construct a multivariate model for the prolific offense of assault. Qualitative methodology was used to construct a descriptive model of assault for 25 adult assault offenders. The model incorporated the development of violent behavior, types of anger, violence motivation, and the assault offense. The model consisted of 14 categories, 10 of which allowed for individual differences in behavior. A total of 35 participant transcripts were then coded through the model where the individual differences occurred. Five main offense types were found. The characteristics of the types of assault offense gave indications for how rehabilitation may be targeted for each group.

Although violent offenders are widely considered to be difficult to engage in therapeutic change, few methods of assessing treatment readiness currently exist. In this article the validation of a brief self-report measure designed to assess treatment readiness in offenders who have been referred to violent offender treatment programs is described. The measure, which is an adaptation of a general measure of treatment readiness developed in a previous work, displayed acceptable levels of convergent and discriminant validity and was able to successfully predict treatment engagement in violent offender treatment. These results suggest that the measure has utility in the assessment of treatment readiness in violent offenders.

Although considerable efforts have been made to develop and validate etiological models of male sexual offending, no theory is available to guide research or practice with female sexual offenders (FSOs). In this study, the authors developed a descriptive, offense process model of female sexual offending. Systematic qualitative analyses (i.e., grounded theory) of 22 FSOs' offense interviews were used to develop a temporal model documenting the contributory roles of cognitive, behavioral, affective, and contextual factors in female sexual abuse. The model highlights notable similarities and divergences between male and female sexual offenders' vulnerability factors and offense styles. In particular, the model incorporates male co-offender and group co-offender influences and describes how these interact with vulnerability factors to generate female sexual offending. The gender-specific research and clinical implications of the model are discussed.

In this article, the authors examine the relevance of the concept of moral repair for sex offenders who have been victims of sexual or physical abuse. First, they briefly review the literature on victimization rates and effects in sexual offenders. Second, the notion of moral repair and its constituent tasks is examined with particular emphasis given to Margaret Walker's recent analysis of the concept. Third, the concept of moral repair is applied to offenders and its implications and possible constraints discussed. Fourth, the authors outline a normative framework for addressing victimization issues with sexual offenders, drawing on the resources of human rights theory and strength-based treatment approaches. Finally, they conclude with a brief consideration of the ethical and clinical implications of their normative model.

We identified gene expression signatures predicting responsiveness to a Kinesin-5 (KIF11) inhibitor (Kinesin-5i) in cultured colon tumor cell lines. Genes predicting resistance to Kinesin-5i were enriched for those from chromosome 20q, a region of frequent amplification in a number of tumor types. siRNAs targeting genes in this chromosomal region identified AURKA, TPX2 and MYBL2 as genes whose disruption enhances response to Kinesin-5i. Taken together, our results show functional interaction between these genes, and suggest that their overexpression is involved in resistance to Kinesin-5i. Furthermore, our results suggest that patients whose tumors overexpress AURKA due to amplification of 20q will more likely resist treatment with Kinesin-5 inhibitor, and that inactivation of AURKA may sensitize these patients to treatment.

Human rights create a protective zone around persons and allow them the opportunity to further their own valued personal projects without interference from others. All human beings hold human rights and that includes sex offenders, although some of their freedom rights may be legitimately curtailed by the State. In this paper we apply the concept of human rights to sex offenders. First we briefly analyze the concept of human rights, their structure, and justification. Second, we apply our own model of human rights to the assessment and treatment of sex offenders. We conclude that a significant advantage of a human rights approach is that it is able to integrate the value and capability aspects of offender treatment.

A qualitative analysis of interview data with 41 rapists determined that five implicit theories (ITs) underlie rapists' offense supportive beliefs/feelings/motives: (a) dangerous world (DW)-where men have feelings of generalized anger and/or resentment toward others; (b) women are dangerous-where men hold a set of attitudes that are hostile toward women; (c) women as sexual objects (WSO)-where women are seen as primarily sexual objects; (d) male sex drive is uncontrollable-where sexual urges are seen all consuming; (e) entitlement-where men feel that they can do exactly what they want. Consideration of whether DW or WSO ITs were present or absent indicated that three main groups could be identified: Group 1: violently motivated-presence of DW and/or absence of WSO; Group 2: sexually motivated-presence of WSO and/or absence of DW; Group 3: sadistically motivated-presence of DW and WSO. These results are discussed in terms of treatment needs of rapists.

Mutations in both p53 and BRCA2 are commonly seen together in human tumors suggesting that the loss of both genes enhances tumor development. To elucidate this interaction in an animal model, mice lacking the carboxy terminal domain of Brca2 were crossed with p53 heterozygous mice. Females from this intercross were then irradiated with an acute dose of 5 Gy ionizing radiation at 5 weeks of age and compared to nonirradiated controls. We found decreased survival and timing of tumor onsets, and significantly higher overall tumor incidences and prevalence of particular tumors, including stomach tumors and squamous cell carcinomas, associated with the homozygous loss of Brca2, independent of p53 status. The addition of a p53 mutation had a further impact on overall survival, incidence of osteosarcomas and stomach tumors, and tumor latency. The spectrum of tumors observed for this Brca2 germline mouse model suggest that it faithfully recapitulates some human disease phenotypes associated with BRCA2 loss. In addition, these findings include extensive in vivo data demonstrating that germline Brca2 and p53 mutations cooperatively affect animal survivals, tumor susceptibilities, and tumor onsets.