Screening Prisoners for Intellectual Disabilities in Three English Prisons.

BACKGROUND: Prisoners with intellectual disabilities are known to be disadvantaged in prisons and to be more susceptible to bullying, segregation, depression and anxiety than other prisoners. METHOD: In this study, nearly 3000 new prisoners entering three English prisons were offered screening for intellectual disabilities, using the LDSQ. RESULTS: On average, 75% of all new prisoners entering prison were offered screening, and only 14% refused screening. Overall, just less than 7% were screened positive on the LDSQ and prisons made some reasonable adjustments as a result. CONCLUSIONS: It is argued that it is feasible to screen for intellectual disabilities in prisons and, given the inequalities to which prisoners with intellectual disabilities are subject in prison, it is time for such screening to be rolled out to all prisons.

Effects of remote ischemic preconditioning in high-risk patients undergoing cardiac surgery (Remote IMPACT): a randomized controlled trial.

BACKGROUND: Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. METHODS: Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase-myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization. RESULTS: We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] -0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI -0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). INTERPRETATION: Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01071265.

Multidimensional single-cell analysis of BCR signaling reveals proximal activation defect as a hallmark of chronic lymphocytic leukemia B cells.

PURPOSE: Chronic Lymphocytic Leukemia (CLL) is defined by a perturbed B-cell receptor-mediated signaling machinery. We aimed to model differential signaling behavior between B cells from CLL and healthy individuals to pinpoint modes of dysregulation. EXPERIMENTAL DESIGN: We developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled BCR signaling in 67 CLL patients using Partial Least Squares Regression (PLSR). Results from multidimensional modeling were validated using an independent test cohort of 38 patients. RESULTS: We identified a dynamic and variable imbalance between proximal (pSYK, pBTK) and distal (pPLCγ2, pBLNK, ppERK) phosphoresponses. PLSR identified the relationship between upstream tyrosine kinase SYK and its target, PLCγ2, as maximally predictive and sufficient to distinguish CLL from healthy samples, pointing to this juncture in the signaling pathway as a hallmark of CLL B cells. Specific BCR pathway signaling signatures that correlate with the disease and its degree of aggressiveness were identified. Heterogeneity in the PLSR response variable within the B cell population is both a characteristic mark of healthy samples and predictive of disease aggressiveness. CONCLUSION: Single-cell multidimensional analysis of BCR signaling permitted focused analysis of the variability and heterogeneity of signaling behavior from patient-to-patient, and from cell-to-cell. Disruption of the pSYK/pPLCγ2 relationship is uncovered as a robust hallmark of CLL B cell signaling behavior. Together, these observations implicate novel elements of the BCR signal transduction as potential therapeutic targets.

Relaxin receptor LGR7 (RXFP1) is regulated by estrogen.

Estrogen regulates LGR7 (RXFP1) mRNA expression in an in vitro model of human term pregnancy cervix that utilizes lower uterine segment fibroblasts. LGR7 mRNA levels were increased by estradiol to mean levels of 152%+/- 5.9% above those in untreated control cells. Therefore, estradiol may amplify relaxin's actions in the cervix.

Factor V Leiden with deep venous thrombosis.

Factor V Leiden (FVL) is an autosomal co-dominantly inherited Arg506-->Gly substitution of the activated protein C cleavage site affecting 5% of the Caucasian population. FVL results in impaired anticoagulant function without procoagulant modification. Heterozygotes experience a seven-fold increase in thrombotic events, whereas homozygotes may incur a 50 to 100 fold increase. Even though patients are at increased risk for deep venous thrombi, they experience a smaller risk of pulmonary embolism compared to individuals affected by other coagulopathies.

Stabilizing unstable steady states using extended time-delay autosynchronization.

We describe a method for stabilizing unstable steady states in nonlinear dynamical systems using a form of extended time-delay autosynchronization. Specifically, stabilization is achieved by applying a feedback signal generated by high-pass-filtering in real time the dynamical state of the system to an accessible system parameter or variables. Our technique is easy to implement, does not require knowledge of the unstable steady state coordinates in phase space, automatically tracks changes in the system parameters, and is more robust to broadband noise than previous schemes. We demonstrate the controller's efficacy by stabilizing unstable steady states in an electronic circuit exhibiting low-dimensional temporal chaos. The simplicity and robustness of the scheme suggests that it is ideally suited for stabilizing unstable steady states in ultra-high-speed systems. (c) 1998 American Institute of Physics.