siRNA-Based Targeting of Cyclin E Overexpression Inhibits Breast Cancer Cell Growth and Suppresses Tumor Development in Breast Cancer Mouse Model

Cyclin E is aberrantly expressed in many types of cancer including breast cancer. High levels of the full length as well as the low molecular weight isoforms of cyclin E are associated with poor prognosis of breast cancer patients. Notably, cyclin E overexpression is also correlated with triple-negative basal-like breast cancers, which lack specific therapeutic targets. In this study, we used siRNA to target cyclin E overexpression and assessed its ability to suppress breast cancer growth in nude mice. Our results revealed that cyclin E siRNA could effectively inhibit overexpression of both full length and low molecular weight isoforms of cyclin E. We found that depletion of cyclin E promoted apoptosis of cyclin E-overexpressing cells and blocked their proliferation and transformation phenotypes. Significantly, we further demonstrated that administration of cyclin E siRNA could inhibit breast tumor growth in nude mice. In addition, we found that cyclin E siRNA synergistically enhanced the cell killing effects of doxorubicin in cell culture and this combination greatly suppressed the tumor growth in mice. In conclusion, our results indicate that cyclin E, which is overexpressed in 30% of breast cancer, may serve as a novel and effective therapeutic target. More importantly, our study clearly demonstrates a very promising therapeutic potential of cyclin E siRNA for treating the cyclin E-overexpressing breast cancers, including the very malignant triple-negative breast cancers

Do all health and social care professionals interact equally: A study of interactions in multidisciplinary teams in the United Kingdom.

Problems around deficits in interprofessional collaboration have been identified since the National Health Service (NHS) was introduced. It is within the context of the current policy focus on improving collaborative working that this study was undertaken. A direct observational study using the Bales’ Interaction Process Analysis tool was carried out in two older persons teams to explore patterns of interaction in the multidisciplinary team meetings. Analysis revealed some key differences in the way in which different professions interacted. Occupational therapists, physiotherapists, social workers (SW) and nurses rarely asked for opinions and for orientation. The consultant (the individual in charge of the medical team) tended to have high rates for asking for orientation, giving opinions and giving orientation. Although some nurses did have high individual rates for the giving of orientation. The data from the research has highlighted that therapists, SWs and nurses are reluctance to voice their opinions in multidisciplinary teams and thus conformity may dominate its culture. It is suggested that therapists, SWs and nurses need to cite their opinions in teams more effectively if they are to be competent and committed patient-centred practitioners

Assessing the impact of imprisonment on recidivism

Objectives There is debate about the extent to which imprisonment deters reoffending. Further, while there is a large literature on the effects of imprisonment, methodologically sound and rigorous studies are the exception due to problematic sample characteristics and study designs. This paper assesses the effect of imprisonment on reoffending relative to a prison diversion program, Community Control, for over 79,000 felons sentenced to state prison and 65,000 offenders sentenced to Community Control between 1994 and 2002 in Florida. Methods The effect of imprisonment on recidivism is examined within one-, two-, and three-year follow-up periods using Logistic Regression, Precision Matching, and Propensity Score Matching. Results Findings indicate that imprisonment exerts a criminogenic effect and that this substantive conclusion holds across all three methods. Conclusions The main contribution of this study is that various methods yield results that are at least in a similar direction and support overall conclusions of prior literature that imprisonment has a criminogenic effect on reoffending compared to non-incarcerative sanctions. Limitations and directions for future research are noted.No Full Tex

Evolutionary regression? Assessing the problem of hidden biases in criminal justice applications using propensity scores

Objectives Propensity score methods rely on an untestable assumption of unconfoundedness for making causal inference. Yet, empirical applications using propensity scores in criminology routinely invoke this assumption without careful scrutiny. We use a dataset with a wide range of observable, potential confounders, which allows us to evaluate recidivism outcomes for adolescent offenders who are sentenced to either placement or probation. We then systematically withhold important known confounders from the matching process to demonstrate the effectiveness of sensitivity checks in sizing up the robustness of these treatment effect estimates in the case where hidden biases clearly exist. We find important variability in the estimated treatment effect, and a large degree of imbalance in 'unobserved' covariates, which we did not explicitly control for. The hidden biases observed in our controlled analysis would have at least been suggested in an actual application by the low gamma statistics that attended our analysis, a statistic that is not reported in most criminological applications of propensity score analysis. Researchers who use propensity score methods should openly discuss potential limitations of their analysis due to hidden bias and report bias sensitivity checks based on the gamma statistic when statistically significant treatment effects are reported