Union effectiveness: In Search of the Holy Grail

YesThis article revisits the concept of union effectiveness and proposes a conceptual model to inform its study and application. Previous conceptual and empirical work is examined to identify key strengths and weaknesses, and to relate the union effectiveness concept to union renewal and other key concepts. This leads to the proposal of a Goal-System framework that builds and improves on prior research

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial

Background: The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis. // Methods: In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I–III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0–2. Participants were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or chemoradiotherapy (two cycles of cisplatin 50 mg/m2 given intravenously during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2 given intravenously), by use of a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival and failure-free survival. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for failure-free survival and recurrence. We did a post-hoc analysis to analyse patterns of recurrence with 1 additional year of follow-up. The study was closed on Dec 20, 2013; follow-up is ongoing. This study is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. // Findings: Between Nov 23, 2006, and Dec 20, 2013, 686 women were enrolled, of whom 660 were eligible and evaluable (330 in the chemoradiotherapy group, and 330 in the radiotherapy-alone group). At a median follow-up of 72·6 months (IQR 59·9–85·6), 5-year overall survival was 81·4% (95% CI 77·2–85·8) with chemoradiotherapy versus 76·1% (71·6–80·9) with radiotherapy alone (adjusted hazard ratio [HR] 0·70 [95% CI 0·51–0·97], p=0·034), and 5-year failure-free survival was 76·5% (95% CI 71·5–80·7) versus 69·1% (63·8–73·8; HR 0·70 [0·52–0·94], p=0·016). Distant metastases were the first site of recurrence in most patients with a relapse, occurring in 78 of 330 women (5-year probability 21·4%; 95% CI 17·3–26·3) in the chemoradiotherapy group versus 98 of 330 (5-year probability 29·1%; 24·4–34·3) in the radiotherapy-alone group (HR 0·74 [95% CI 0·55–0·99]; p=0·047). Isolated vaginal recurrence was the first site of recurrence in one patient (0·3%; 95% CI 0·0–2·1) in both groups (HR 0·99 [95% CI 0·06–15·90]; p=0·99), and isolated pelvic recurrence was the first site of recurrence in three women (0·9% [95% CI 0·3–2·8]) in the chemoradiotherapy group versus four (0·9% [95% CI 0·3–2·8]) in the radiotherapy-alone group (HR 0·75 [95% CI 0·17–3·33]; p=0·71). At 5 years, only one grade 4 adverse event (ileus or obstruction) was reported (in the chemoradiotherapy group). At 5 years, reported grade 3 adverse events did not differ significantly between the two groups, occurring in 16 (8%) of 201 women in the chemoradiotherapy group versus ten (5%) of 187 in the radiotherapy-alone group (p=0·24). The most common grade 3 adverse event was hypertension (in four [2%] women in both groups). At 5 years, grade 2 or worse adverse events were reported in 76 (38%) of 201 women in the chemoradiotherapy group versus 43 (23%) of 187 in the radiotherapy-alone group (p=0·002). Sensory neuropathy persisted more often after chemoradiotherapy than after radiotherapy alone, with 5-year rates of grade 2 or worse neuropathy of 6% (13 of 201 women) versus 0% (0 of 187). No treatment-related deaths were reported. // Interpretation: This updated analysis shows significantly improved overall survival and failure-free survival with chemoradiotherapy versus radiotherapy alone. This treatment schedule should be discussed and recommended, especially for women with stage III or serous cancers, or both, as part of shared decision making between doctors and patients. Follow-up is ongoing to evaluate long-term survival

The Molecular Origin and Taxonomy of Mucinous Ovarian Carcinoma

Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across all histological grades, including benign and borderline mucinous ovarian tumors, and compare these to tumors from other potential extra-ovarian sites of origin. Here we show that MOC is distinct from tumors from other sites and supports a progressive model of evolution from borderline precursors to high-grade invasive MOC. Key drivers of progression identified are TP53 mutation and copy number aberrations, including a notable amplicon on 9p13. High copy number aberration burden is associated with worse prognosis in MOC. Our data conclusively demonstrate that MOC arise from benign and borderline precursors at the ovary and are not extra-ovarian metastases

The Role and Influence of Stakeholders in Organisational Decision Making: A Case Study of the 'Off-shoring' of Australian Jobs

The role of stakeholders in influencing corporate decision making on moral and social grounds appears a paradox in a global economy underpinned by a neo-liberal philosophy. Because of the diverse and complex nature of the issues, stakeholders and organisations, it is often difficult to interpret the dynamics which underlie and influence the decision making process. This paper aims to explore the literature on stakeholder theory to develop a framework for understanding the role and influence of stakeholders. Using this framework the issue of 'off-shoring' is examined through a case study of a major Australian organisation - Coles Myer Limited

Turning the Tables on Off-Shoring

The role of stakeholders in influencing corporate decision making on moral and social grounds appears a paradox in a global economy underpinned by a neo-liberal philosophy. Because of the diverse and complex nature of the issues, stakeholders and organisations, it is often difficult to interpret the dynamics which underlie and influence the decision making process. This paper aims to explore the literature on stakeholder theory to develop an interpretive framework for understanding the role and influence of stakeholders. Using this framework the issue of ‘off-shoring’ is examined through a case study of a major Australian organisation - Coles Myer Limited. It should be noted that this is an exploratory stud

Anatomic and surgical considerations in the design of a new receiver-stimulator suitable for implantation in young children

This is a publisher’s version of an article published in Annals of Otology, Rhinology & Laryngology published by Annals Publishing Company. This version is reproduced with permission from Annals Publishing Company. http://www.annals.com/The anatomy of the temporal bone was studied to determine the optimal shape and dimensions of a new receiver-stimulator for use in young children even less than 12 months of age. There was a need to make the receiver-stimulator electronic package smaller so that it could be placed within the mastoid cavity, and the antenna wider, for more efficient power and data transmission. The antenna needed to conform to the smaller radius of a young child's skull. Anatomic dissections were carried out on skulls of children from 3 to 11 months of age to establish the variations in dimensions relevant for implantation. Prototype implant designs were evaluated in these skulls and it was found that the maximum thickness the anterior section of the receiver-stimulator should be was 5.5 mm, and its maximum width, 18 mm. It was found that a prototype electronics package with these dimensions could be fitted comfortably into the average skull of an 8-month-old child. A particular constraint was the depth of the bone over the sigmoid sinus and middle fossa. The radius of curvature of the skull of young children also required the package to be bent in its center at an angle of 160°