Optimization of a dynamic perfusion process using a combination of high throughput experimentation and hybrid modeling approaches

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New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer

BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009)

In the space of reasonable doubt

This paper explores ‘reasonable doubt’ as an enlightening notion to think of reasoning and decision-making generally, beyond the judicial domain. The paper starts from a decision-theoretic understanding of the notion, whereby it can be defined in terms of degrees of belief and a probabilistic confirmation threshold for action. It then highlights some of the limits of this notion, and proposes a richer analysis of epistemic states and reasoning through the lens of ‘reasonable doubt’, which in turn is likely to supplement the DT framework. The strategy consists in fighting on two fronts: with DT, the paper claims that there is no absolute (i.e. decision-independent) notion of ‘reasonable doubt’ but, pace DT, it shows that reasonable doubt cannot be accounted for only in terms of degrees of belief and probabilistic threshold. We argue that the lens of reasonable doubt sheds light on aspects of belief dynamics, as well as of the nature of epistemic attitudes, which are often obscured by belief-centred approaches. In particular, when it comes to acknowledging the necessary ignorance and irreducible uncertainty that we face in our everyday-life decisions, studying the various facets of doubt rather than focusing on what can be believed, enables one to do justice to the richness and diversity of the mental states in play

City of Milwaukee: Construction Mitigation Program

Produced for PA 869, Workshop in Public Affairs.This report designs a package of construction mitigation services that the City of Milwaukee could implement to limit the negative impact construction projects have on surrounding businesses. After researching such services in cities across the country, the study evaluates alternatives against the goals of cost-effectiveness, ease of implementation, political feasibility, and equity. It recommends implementing a package of services that includes public meetings, communication with affected businesses, signage, a website, and business education. It also recommends that a program liaison coordinate these services and that the City of Milwaukee implement an evaluation system

Safe Space Programs In K-12 Schools: Creating A Visible Presence Of Lgbtq Allies

Safe Space Programs can provide school staff with critical knowledge and skills to create a supportive learning milieu for lesbian, gay, bisexual, transgender, and questioning (LGBTQ) youth in K-12 schools. The literature related to Safe Space Programs suggests that they may be instrumental in helping alter anti-LGBTQ climates in schools. This article illustrates how Seattle University\u27s Graduate Counseling program developed a student advocacy organization to provide Safe Space programming to school personnel in local area schools. © 2013 Copyright Taylor and Francis Group, LLC