Assessing vulnerability to risk of suicide and self-harm in prisoners : a Rasch analysis of the suicide concerns for offenders in the prison environment (SCOPE-2)

BACKGROUND: With increasing levels of suicide and self-harm behaviour in the criminal justice system professionals would benefit from a tool that can identify individuals who may be at risk of self-harm and/or suicidal behaviour. METHOD: The Suicide Concerns for Offenders in the Prison Environment (SCOPE) tool was originally devised and validated in six UK prisons between 2003 and 2004. The goal of this study is to re-evaluate the SCOPE using Rasch methodology to produce a psychometrically robust instrument. Data were presented from 1051 SCOPE assessments of male and female offenders. RESULTS: The analysis produced a revised SCOPE-2 tool reducing the tool from a 27 to a 19 items and simplifying the categorical six point scale to a four item scale. CONCLUSIONS: Further validation of the new SCOPE-2 tool is required in samples of male and female prisoners to assess different cut-off points for clinical and policy use

Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes.

Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony-stimulating factor (G-CSF) preserves β-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4-24 months) were randomized to ATG and pegylated G-CSF (ATG+G-CSF) (N = 17) or placebo (N = 8). Primary outcomes included C-peptide area under the curve (AUC) following a mixed-meal tolerance test (MMTT) and flow cytometry. "Responders" (12-month C-peptide ≥ baseline), "super responders" (24-month C-peptide ≥ baseline), and "nonresponders" (12-month C-peptide < baseline) were evaluated for biomarkers of outcome. At 24 months, MMTT-stimulated AUC C-peptide was not significantly different in ATG+G-CSF (0.49 nmol/L/min) versus placebo (0.29 nmol/L/min). Subjects treated with ATG+G-CSF demonstrated reduced CD4+ T cells and CD4+/CD8+ T-cell ratio and increased CD16+CD56hi natural killer cells (NK), CD4+ effector memory T cells (Tem), CD4+PD-1+ central memory T cells (Tcm), Tcm PD-1 expression, and neutrophils. FOXP3+Helios+ regulatory T cells (Treg) were elevated in ATG+G-CSF subjects at 6, 12, and 18 but not 24 months. Immunophenotyping identified differential HLA-DR expression on monocytes and NK and altered CXCR3 and PD-1 expression on T-cell subsets. As such, a group of metabolic and immunological responders was identified. A phase II study of ATG+G-CSF in patients with new-onset type 1 diabetes is ongoing and may support ATG+G-CSF as a prevention strategy in high-risk subjects

C-Reactive Protein Gene Variants Are Associated with Postoperative C-reactive Protein Levels After Coronary Artery Bypass Surgery

Background: Elevated baseline C-reactive protein (CRP) levels are associated with increased risk for developing cardiovascular disease. Several CRP gene variants have been associated with altered baseline CRP levels in ambulatory populations. However, the influence of CRP gene variants on CRP levels during inflammatory states, such as surgery, is largely unexplored. We describe the association between candidate CRP gene variants and postoperative plasma CRP levels in patients undergoing primary, elective coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB). Methods: Using a multicenter candidate gene association study design, we examined the association between seventeen candidate CRP single nucleotide polymorphisms (SNPs) and inferred haplotypes, and altered postoperative CRP levels in 604 patients undergoing CABG surgery with CPB. Perioperative CRP levels were measured immediately prior to surgery, post-CPB and on postoperative days (POD) 1–4. Results: CRP levels were significantly elevated at all postoperative time points when compared with preoperative levels (P < 0.0001). After adjusting for clinical covariates, the minor allele of the synonymous coding SNP, rs1800947 was associated with lower peak postoperative CRP levels ($P = 2.4 × 10^{-4}$) and lower CRP levels across all postoperative time points ($P = 4.8 × 10^{-5}$). rs1800947 remained highly significant after Bonferroni adjustment for multiple comparisons. Conclusion: We identified a CRP gene SNP associated with lower postoperative CRP levels in patients undergoing CABG surgery with CPB. Further investigation is needed to clarify the significance of this association between CRP gene variants and the acute-phase rise in postoperative CRP levels with regard to the risk of adverse postoperative outcomes

Novel Telomere-Anchored PCR Approach for Studying Sexual Stage Telomeres in Aspergillus nidulans

Telomere length varies between germline and somatic cells of the same organism, leading to the hypothesis that telomeres are lengthened during meiosis. However, little is known about the meiotic telomere length in many organisms. In the filamentous fungus Aspergillus nidulans, the telomere lengths in hyphae and asexual spores are invariant. No study using existing techniques has determined the telomere length of the sexual ascospores due to the relatively low abundance of pure meiotic cells in A. nidulans and the small quantity of DNA present. To address this, we developed a simple and sensitive PCR strategy to measure the telomere length of A. nidulans meiotic cells. This novel technique, termed telomere-anchored PCR, measures the length of the telomere on chromosome II-L using a small fraction of the DNA required for the traditional terminal restriction fragment (TRF) Southern analysis. Using this approach, we determined that the A. nidulans ascospore telomere length is virtually identical to telomeres of other cell types from this organism, approximately 110 bp, indicating that a surprisingly strict telomere length regulation exists in the major cell types of A. nidulans. When the hyphal telomeres were measured in a telomerase reverse transcriptase (TERT) knockout strain, small decreases in length were readily detected. Thus, this technique can detect telomeres in relatively rare cell types and is particularly sensitive in measuring exceptionally short telomeres. This rapid and inexpensive telomere-anchored PCR method potentially can be utilized in other filamentous fungi and types of organisms

Cultural adaptation of a UK evidence-based problem-solving intervention to support Polish prisoners at risk of suicidal behaviour : a cross-sectional survey using an Ecological Validity Model

OBJECTIVE: To complete a cultural adaptation of a UK evidence-based problem-solving intervention to support Polish prisoners at risk of suicidal behaviour. DESIGN: A cross-sectional survey participatory design using an Ecological Validity Model. SETTING: The study was a collaboration between: the Academy of Justice, in Warsaw, the University of Lodz, two Polish prisons (ZK Raciborz and ZK Klodzko) and the University of York (UK). METHODS: The adaptation process included an examination of the use of language, metaphors and content (ie, culturally appropriate and syntonic language), the changing of case study scenarios (relevance and acceptability) and maintenance of the theoretical underpinning of the problem-solving model (intervention comprehensibility and completeness). Four stages used: (1) a targeted demonstration for Polish prison staff, (2) a wider audit of the skills with Polish prison staff and students, (3) forward and back-translation of the adapted package, and (4) two iterative consultations with participants from stages (1) and (2) and prison officers from two Polish prisons. PARTICIPANTS: Self-selecting volunteer participants included: targeted prison staff (n=10), prison staff from the wider Polish penitentiary system (n=39), students from the University of Lodz (n=28) and prison officers from two Polish prisons (n=12). MAIN OUTCOMES AND MEASURES: Acceptability and feasibility of the training package, reported in a series of knowledge user surveys. RESULTS: The recognised benefits of using the skills within the training package included: enhancing communication, reflective development, collaborative working, changing behaviour, empowering decision-making, relevance to crisis management situations and use of open-ended questions. The skills were endorsed to be used as part of future penitentiary training for prison officers in Poland. CONCLUSIONS: The skills had widespread appeal for use across the Polish penitentiary system. The materials were deemed relevant while adhering to the comprehensibility of the intervention. Further evaluation of the intervention should be explored using a randomised controlled trial design

Decontamination Strategies Used for AFB Culture Significantly Reduce the Viability of Mycobacterium abscessus Complex in Sputum Samples from Patients with Cystic Fibrosis

Nontuberculous mycobacteria are important respiratory pathogens in patients with cystic fibrosis (CF). For diagnosis, international guidelines recommend culture of sputum that has been decontaminated via chemical treatment. Fifty-six sputum samples from 32 patients known to be previously colonized or infected with NTM were subdivided, and the aliquots were subjected to six different decontamination strategies, followed by quantitative culture for NTM. Thirty sputum samples contained Mycobacterium abscessus complex (MABSC) and 11 contained Mycobacterium avium complex (MAC). Decontamination strategies included treatment with N-acetyl L-cysteine with 2 sodium hydroxide (NALC-NaOH), 4 NaOH, 1 chlorhexidine, 0.5 N sulfuric acid, 5 oxalic acid, double decontamination with NALC-NaOH, followed by 5 oxalic acid, and saline (0.85) as a control. The samples were also cultured directly with no treatment. Treatment with NALC-NaOH resulted in an average reduction in colony count of 87 for MABSC when compared with direct culture. NaOH at 4 caused a 98.3 average reduction in colony count. All treatments that included NaOH resulted in colony counts that were statistically lower than those obtained from direct culture or the saline-treated control (p &lt; 0.05). Standard treatments using sulfuric or oxalic acids were less deleterious, but still resulted in an average reduction in colony count of at least 30. The viability of MAC was much less affected by most decontamination treatments. In conclusion, the viability of MABSC was severely compromised by standard decontamination regimens. This supports recent evidence showing that optimal recovery of MABSC is achieved by culture on an appropriate selective agar without decontamination of sputum samples

Research-based versus clinical serum creatinine measurements and the association of acute kidney injury with subsequent kidney function: findings from the Chronic Renal Insufficiency Cohort study.

Background:Observational studies relying on clinically obtained data have shown that acute kidney injury (AKI) is linked to accelerated chronic kidney disease (CKD) progression. However, prior reports lacked uniform collection of important confounders such as proteinuria and pre-AKI kidney function trajectory, and may be susceptible to ascertainment bias, as patients may be more likely to undergo kidney function testing after AKI. Methods:We studied 444 adults with CKD who participated in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study and were concurrent members of a large integrated healthcare delivery system. We estimated glomerular filtration rate (eGFR) trajectories using serum creatinine measurements from (i) the CRIC research protocol (yearly) and (ii) routine clinical care. We used linear mixed effects models to evaluate the associations of AKI with acute absolute change in eGFR and post-AKI eGFR slope, and explored whether these varied by source of creatinine results. Models were adjusted for demographic characteristics, diabetes status and albuminuria. Results:During median follow-up of 8.5 years, mean rate of eGFR loss was -0.31 mL/min/1.73&nbsp;m2/year overall, and 73 individuals experienced AKI (55% Stage 1). A significant interaction existed between AKI and source of serum creatinine for acute absolute change in eGFR level after discharge; in contrast, AKI was independently associated with a faster rate of eGFR decline (mean additional loss of -0.67 mL/min/1.73&nbsp;m2/year), which was not impacted by source of serum creatinine. Conclusions:AKI is independently associated with subsequent steeper eGFR decline regardless of the serum creatinine source used, but the strength of association is smaller than observed in prior studies after taking into account key confounders such as pre-AKI eGFR slope and albuminuria

Utilising survey data and qualitative information to inform a logic model to support older people in custody with common mental and physical health problems:Addressing the physical and mental health needs of older prisoners (the PAMHOP study)

A growing number of older people remain in custody each year resulting in an increasing number of common mental and physical health concerns. No prior evidenced-based targeted psychological interventions support this group of people, and little is known about their needs, current activities, and health-related problems. We addressed these gaps through a project involving older prisoners, prison staff and a project advisory group in one male and one female prison site in the North of England. Systematic review evidence supports the development of an implementation tool kit addressing strategies to develop and deliver interventions that are sustainable, acceptable, and feasible in the prison environment. Prison strategies need to specifically address the needs of older people in custody. Relatively inexpensive activities, with some thought to delivery and flexibility have the potential to benefit common mental and physical health, increasing quality of life, reducing high economic and social cost, mortality, and reoffending in this age group

Docetaxel-Loaded PLGA Nanoparticles Improve Efficacy in Taxane-Resistant Triple-Negative Breast Cancer

Novel treatment strategies, including nanomedicine, are needed for improving management of triple-negative breast cancer. Patients with triple-negative breast cancer, when considered as a group, have a worse outcome after chemotherapy than patients with breast cancers of other subtypes, a finding that reflects the intrinsically adverse prognosis associated with the disease. The aim of this study was to improve the efficacy of docetaxel by incorporation into a novel nanoparticle platform for the treatment of taxane-resistant triple-negative breast cancer. Rod-shaped nanoparticles encapsulating docetaxel were fabricated using an imprint lithography based technique referred to as Particle Replication in Nonwetting Templates (PRINT). These rod-shaped PLGA-docetaxel nanoparticles were tested in the C3(1)-T-antigen (C3Tag) genetically engineered mouse model (GEMM) of breast cancer that represents the basal-like subtype of triple-negative breast cancer and is resistant to therapeutics from the taxane family. Thi..