Overtreatment of low-grade ductal carcinoma in situ

Importance: While the prevalence of ductal carcinoma in situ (DCIS) of the breast has increased substantially following the introduction of breast-screening methods, the clinical significance of early detection and treatment for DCIS remains unclear. Objective: To investigate the survival benefit of breast surgery for low-grade DCIS. Design, Setting, and Participants: A retrospective longitudinal cohort study using the Surveillance, Epidemiology, and End Results (SEER) database from October 9, 2014, to January 15, 2015, at the Dana-Farber/Brigham and Women’s Cancer Center. Between 1988 and 2011, 57 222 eligible cases of DCIS with known nuclear grade and surgery status were identified. Exposures: Patients were divided into surgery and nonsurgery groups. Main: Outcomes and Measures Propensity score weighting was used to balance patient backgrounds between groups. A log-rank test and multivariable Cox proportional hazards model was used to assess factors related to overall and breast cancer–specific survival. Results: Of 57 222 cases of DCIS identified in this study, 1169 cases (2.0%) were managed without surgery and 56 053 cases (98.0%) were managed with surgery. With a median follow-up of 72 months from diagnosis, there were 576 breast cancer–specific deaths (1.0%). The weighted 10-year breast cancer–specific survival was 93.4% for the nonsurgery group and 98.5% for the surgery group (log-rank test, P < .001). The degree of survival benefit among those managed surgically differed according to nuclear grade (P = .003). For low-grade DCIS, the weighted 10-year breast cancer–specific survival of the nonsurgery group was 98.8% and that of the surgery group was 98.6% (P = .95). Multivariable analysis showed there was no significant difference in the weighted hazard ratios of breast cancer–specific survival between the surgery and nonsurgery groups for low-grade DCIS. The weighted hazard ratios of intermediate- and high-grade DCIS were significantly different (low grade: hazard ratio, 0.85; 95% CI, 0.21-3.52; intermediate grade: hazard ratio, 0.23; 95% CI, 0.14-0.42; and high grade: hazard ratio, 0.15; 95% CI, 0.11-0.23) and similar results were seen for overall survival. Conclusions and Relevance: The survival benefit of performing breast surgery for low-grade DCIS was lower than that for intermediate- or high-grade DCIS. A prospective clinical trial is warranted to investigate the feasibility of active surveillance for the management of low-grade DCIS

Does Vocational Guidance Become Gendered When Discussing Construction?

The Australian construction industry is highly reliant on the local labour force and those employed within it undertake a wide variety of roles ranging from labouring to management. In the past 20 years construction has seen record levels of employment; however lack of skilled labour is becoming problematic. Australia, like most industrialised countries, has an ageing population due to falling birth rates, increased life expectancy and the ageing of the large post-World War II ‘baby boom’ generation. Deciding on a career is one of the most fundamental activities in a young person’s life and the role of the school career counsellor is crucial in this process. This research examined secondary school career counsellor’s knowledge of construction, their perceptions of it as a good career choice and how often they directed male and female students to investigate construction as a career. Comparisons using paired t-tests found career counsellors perceived construction to be a better career option for young men, and directed them more frequently than women, to explore construction careers. The findings also indicate that an educative model, where students and counsellors gain firsthand knowledge from people working in the industry, may counter negative gender stereotypes associated with this area of work and encourage more young people, both male and female, to consider a career in the construction industry

A Pain in the Wrist: Stingray Envenomation

[West J Emerg Med. 2012;13(1):80–81.

Strategies for Maintaining Credit Union Profitability in Grenada

Nonbank financial institutions (NBFIs), of which credit unions comprise, constitute an important part of the financial sector because of their contribution to economic development, particularly in developing economies. This multiple case study explored strategies for maintaining credit union profitability against the backdrop of numerous closures in the past decade. The conceptual framework for this study was agency theory. Data were collected from 6 purposefully selected managers or directors representing individual credit unions in Grenada. Data were also collected from publicly available sources and used to conduct methodological triangulation. The interview data were coded using a computer-aided software package, and the interpretations of the data subjected to member checking. The emergent themes from both sources were then aggregated into 6 major strategies for maintaining credit union profitability, namely credit risk management, portfolio growth and development, operational efficiency, advertising and promotion, performance metrics, and strategy review. Agency problems exist in the credit union environment and influence the strategies leaders of credit unions in Grenada employ to maintain profitability. Findings from this study represent a corollary against the participants\u27 position that agency theory is not applicable in the credit union environment because of the existence of the common bond. Implications for social change include safeguarding the financial wellbeing of credit union members by contributing to the soundness of Grenada\u27s NBFIs. This is social implication is an important consideration given the mission of the credit union sector to serving the disenfranchised and to the growth and stability of developing economies

Low grade Ductal Carcinoma in situ (DCIS): how best to describe it?

BACKGROUND: In the absence of definitive data about the natural history of DCIS the appropriateness of describing DCIS as cancer is controversial. METHODS: We conducted a survey amongst British Breast Group (BBG) members, to determine which descriptions of DCIS were deemed most accurate and appropriate. RESULTS: 54/73 (74%) attendees completed the survey: A majority (34/54; 63%) said they would be comfortable using the description that explained DCIS as abnormal cells in the milk ducts that had not spread into other breast tissue and which did not need urgent treatment as if it was breast cancer and this description was overall the most preferred (24/54; 44%). CONCLUSIONS: Little consensus exists regarding how best to explain low grade DCIS to patients

Evaluation of the emotional phenotype and serotonergic neurotransmission of fatty acid amide hydrolase-deficient mice

By enhancing brain anandamide tone, inhibitors of fatty acid amide hydrolase (FAAH) induce anxiolytic-like effects in rodents and enhance brain serotonergic transmission. Mice lacking the faah gene (FAAH(-/-)) show higher anandamide levels. However, their emotional phenotype is still debated and their brain serotonergic tone remained unexplored. In this study, we tested FAAH(-/-) mice in the social interaction and the open field tests performed under different lighting conditions (dim and bright) since variations of the experimental context were proposed to explain opposite findings. Moreover, by microdialysis performed under dim light, we analyzed their serotonergic transmission in frontal cortex (FC) and ventral hippocampus (vHIPP). In both light conditions, FAAH(-/-) mice showed reduced emotionality, compared to wt controls, as suggested by the increased rearing and reduced thigmotaxis displayed in the open field and by the longer time spent in social interaction. Basal serotonergic tone was higher in the FC of mutant mice as compared to control mice, while no difference was observed in the vHIPP. K(+)-induced depolarization produced similar increases of serotonin in both areas of both genotypes. An acute treatment with the CB1 antagonist rimonabant completely abolished the emotional phenotype of FAAH(-/-) mice and prevented the K(+)-stimulated release of serotonin in their FC and vHIPP, without producing any effect in wt mice. Our results support the role of FAAH in the regulation of emotional reactivity and suggest that anandamide-mediated hyperactivation of CB1 is responsible for the emotional phenotype of FAAH(-/-) mice and for their enhanced serotonergic tone

PRMT5 is a critical regulator of breast cancer stem cell function via Histone Methylation and FOXP1 expression

Breast cancer progression, treatment resistance, and relapse are thought to originate from a small population of tumor cells, breast cancer stem cells (BCSCs). Identification of factors critical for BCSC function is therefore vital for the development of therapies. Here, we identify the argininemethyltransferase PRMT5 as a key in vitro and in vivo regulator of BCSC proliferation and self-renewal and establish FOXP1, a winged helix/forkhead transcription factor, as a critical effector of PRMT5-induced BCSC function. Mechanistically, PRMT5 recruitment to the FOXP1 promoter facilitates H3R2me2s, SET1 recruitment, H3K4me3, and gene expression. Our findings are clinically significant, as PRMT5 depletion within established tumor xenografts or treatment of patient- derived BCSCs with a pre-clinical PRMT5 inhibitor substantially reduces BCSC numbers. Together, our findings highlight the importance of PRMT5 in BCSC maintenance and suggest that small-molecule inhibitors of PRMT5 or downstream targets could be an effective strategy eliminating this cancer-causing population

Addressing overtreatment of screen detected DCIS; the LORIS trial

Abstract Overdiagnosis, and thus overtreatment, are inevitable consequences of most screening programmes; identification of ways of minimising the impact of overdiagnosis demands new prospective research, in particular the need to separate clinically relevant lesions that require active treatment from those that can be safely left alone or monitored and only need treated if they change characteristics. Breast cancer screening has led to a large increase in ductal carcinoma in situ (DCIS) diagnoses. This is a widely heterogeneous disease and most DCIS detected through screening is of high cytonuclear grade and therefore likely to be important clinically. However, the historic practice of surgical treatment for all DCIS is unlikely to be optimal for lower risk patients. A clearer understanding of how to manage DCIS is required. This article describes the background and development of ‘The low risk’ DCIS trial (LORIS), a phase III trial of surgery versus active monitoring. LORIS will determine if it is appropriate to manage women with screen detected or asymptomatic, low grade and intermediate grade DCIS with low grade features, by active monitoring rather than by surgical treatment

DETECT schools study protocol: A prospective observational cohort surveillance study investigating the impact of COVID-19 in Western Australian schools

Introduction: Amidst the evolving COVID-19 pandemic, understanding the transmission dynamics of the SARS-CoV-2 virus is key to providing peace of mind for the community and informing policy-making decisions. While available data suggest that school-aged children are not significant spreaders of SARS-CoV-2, the possibility of transmission in schools remains an ongoing concern, especially among an aging teaching workforce. Even in low-prevalence settings, communities must balance the potential risk of transmission with the need for students\u27 ongoing education. Through the roll out of high-throughput school-based SARS-CoV-2 testing, enhanced follow-up for individuals exposed to COVID-19 and wellbeing surveys, this study investigates the dynamics of SARS-CoV-2 transmission and the current psychosocial wellbeing impacts of the pandemic in school communities. Methods: The DETECT Schools Study is a prospective observational cohort surveillance study in 79 schools across Western Australia (WA), Australia. To investigate the incidence, transmission and impact of SARS-CoV-2 in schools, the study comprises three “modules”: Module 1) Spot-testing in schools to screen for asymptomatic SARS-CoV-2; Module 2) Enhanced surveillance of close contacts following the identification of any COVID-19 case to determine the secondary attack rate of SARS-CoV-2 in a school setting; and Module 3) Survey monitoring of school staff, students and their parents to assess psycho-social wellbeing following the first wave of the COVID-19 pandemic in WA. Clinical Trial Registration: Trial registration number: ACTRN1262000092297

Translation of clinical problems in osteoarthritis into pathophysiological research goals

Osteoarthritis (OA) accounts for more disability among the elderly than any other disease and is associated with an increased mortality rate. The prevalence in Europe will rise in the future since this continent has a strongly ageing population and an obesity epidemic; obesity and age both being major risk factors for OA. No adequate therapeutic options, besides joint replacement, are available, although they are greatly needed and should be acquired by adequate research investments. However, the perspective on OA from a researcher's point of view is not always aligned with the perspective of a patient with OA. Researchers base their views on OA mainly on abnormalities in structure and function while patients consider OA as a collection of symptoms. In this viewpoint paper, we discuss the possibility of translating the most important clinical problems into pathophysiological research goals to facilitate the translation from bench to bedside and vice versa. This viewpoint is the outcome of a dialogue within the 'European League Against Rheumatism study group on OA' and People with Arthritis/Rheumatism across Europe (PARE) representatives