Modeling Breast Cancer Dormancy and Recurrence Following Oncogenic Pathway Inhibition

Breast cancer recurrence is the primary cause of mortality in breast cancer, and although advances have been made in the treatment of primary breast cancer, recurrent breast cancer remains uncurable. Targeted therapy has had a major impact on survival across multiple cancer types, including breast cancer, however patients who respond to targeted therapy ultimately relapse. Residual disease, the tumor cells that survive initial therapy, represent an attractive therapeutic target, however little is known about the biology of these cells. We use mouse models of breast cancer to investigate the phenotype of residual disease that survives targeted therapy, and to explore approaches to inhibit tumor recurrence. Residual disease exhibits cellular dormancy in models driven by distinct oncogenic pathways. Gene expression profiling reveals that residual tumor cells are enriched for a phenotype associated with normal and neoplastic stem-like cells, but are not enriched for tumor initiative cells. Interventions that inhibit inflammatory signaling inhibit tumor recurrence, however increasing inflammation promotes tumor recurrence. Inflammatory macrophages may be leukocytes that promote inflammation and drive recurrence in these models. Together, our findings present a more comprehensive picture of residual tumor cells surviving targeted therapy, and suggest possible therapeutic strategies for targeting residual disease that gives rise to cancer recurrence

Operating theatre time, where does it all go? A prospective observational study

Objective To assess the accuracy of surgeons and anaesthetists in predicting the time it will take them to complete an operation or procedure and therefore explain some of the difficulties encountered in operating theatre scheduling. Design Single centre, prospective observational study. Setting Plastic, orthopaedic, and general surgical operating theatres at a level 1 trauma centre serving a population of about 370 000. Participants 92 operating theatre staff including surgical consultants, surgical registrars, anaesthetic consultants, and anaesthetic registrars. Intervention Participants were asked how long they thought their procedure would take. These data were compared with actual time data recorded at the end of the case. Primary outcome measure Absolute difference between predicted and actual time. Results General surgeons underestimated the time required for the procedure by 31 minutes (95% confidence interval 7.6 to 54.4), meaning that procedures took, on average, 28.7% longer than predicted. Plastic surgeons underestimated by 5 minutes (−12.4 to 22.4), with procedures taking an average of 4.5% longer than predicted. Orthopaedic surgeons overestimated by 1 minute (−16.4 to 14.0), with procedures taking an average of 1.1% less time than predicted. Anaesthetists underestimated by 35 minutes (21.7 to 48.7), meaning that, on average, procedures took 167.5% longer than they predicted. The four specialty mean time overestimations or underestimations are significantly different from each other (P=0.01). The observed time differences between anaesthetists and both orthopaedic and plastic surgeons are significantly different (P<0.05), but the time difference between anaesthetists and general surgeons is not significantly different. Conclusion The inability of clinicians to predict the necessary time for a procedure is a significant cause of delay in the operating theatre. This study suggests that anaesthetists are the most inaccurate and highlights the potential differences between specialties in what is considered part of the “anaesthesia time.

The Organizational Handbook to Promote Critical Thinking and Decision Making

This handbook has been created as a conceptual framework to assist leaders within the critical thinking process of making decisions. Today, society, environments and experiences dictate outcomes and on-the-go decisions, that negatively impact organizational outcomes, are made rather than examining the perspective to consider when making decisions. By detailing the importance of thinking for the greater good, this handbook serves as a platform that provides insight, perspectives, examples, and details how leaders make decisions that are crucial for their organization. Importantly, the handbook conceptualizes leadership characteristics that determine decisions, reviews the implications of organizational cultures and climates that influence decisions, and provides an analysis of how decisions are made. The goal of the handbook is to better understand the process of making decisions while providing tools and reference points to assist leader

Perspective effects during reading: evidence from text change-detection

We report two text change-detection studies in which we investigate the influence of reading perspective on text memory. In Experiment 1, participants read from the perspective of one of two characters in a series of short stories, and word changes were either semantically close or distant. Participants correctly reported more changes to perspective-relevant than -irrelevant words, and for distant than close changes. However, distance and perspective did not interact, suggesting that adopting a particular perspective did not lead to a more fine-grained analysis of perspective-relevant information. In Experiment 2, participants read one long narrative from the perspective of either a burglar or house-buyer. Results showed that only participants with a low working memory span showed perspective effects, suggesting that individual differences in working memory capacity appear to influence processing of perspective-relevant information

Relative Contributions of Geographic, Socioeconomic, and Lifestyle Factors to Quality of Life, Frailty, and Mortality in Elderly

Background: To date, few studies address disparities in older populations specifically using frailty as one of the health outcomes and examining the relative contributions of individual and environmental factors to health outcomes. Methodology/Principal Findings: Using a data set from a health survey of 4,000 people aged 65 years and over living in all regions of Hong Kong, we examined regional variations in self-rated health, frailty, and four-year mortality, and analyzed the relative contributions of lifestyle, socioeconomic status, and geographical location of residence to these outcomes using path analysis. We hypothesize that lifestyle, socioeconomic status, and regional characteristics directly and indirectly through interactions contribute to self-rated physical and psychological health, frailty, and four-year mortality. District variations directly affect self-rated physical health, and also exert an effect through socioeconomic position as well as lifestyle factors. Socioeconomic position in turn directly affects self-rated physical health, as well as indirectly through lifestyle factors. A similar pattern of interaction is observed for self-rated mental health, frailty, and mortality, although there are differences in different lifestyle factors and district associations. Lifestyle factors also directly affect physical and mental components of health, frailty, and mortality. The magnitude of direct district effect is comparable to those of lifestyle and socioeconomic position. Conclusions/Significance: We conclude that district variations in health outcomes exist in the Hong Kong elderl

Bridging the gap -- the disappearance of the intermediate period gap for fully convective stars, uncovered by new ZTF rotation periods

The intermediate period gap, discovered by Kepler, is an observed dearth of stellar rotation periods in the temperature-period diagram at $\sim$ 20 days for G dwarfs and up to $\sim$ 30 days for early-M dwarfs. However, because Kepler mainly targeted solar-like stars, there is a lack of measured periods for M dwarfs, especially those at the fully convective limit. Therefore it is unclear if the intermediate period gap exists for mid- to late-M dwarfs. Here, we present a period catalog containing 40,553 rotation periods (9,535 periods $>$ 10 days), measured using the Zwicky Transient Facility (ZTF). To measure these periods, we developed a simple pipeline that improves directly on the ZTF archival light curves and reduces the photometric scatter by 26%, on average. This new catalog spans a range of stellar temperatures that connect samples from Kepler with MEarth, a ground-based time domain survey of bright M-dwarfs, and reveals that the intermediate period gap closes at the theoretically predicted location of the fully convective boundary ($G_{\rm BP} - G_{\rm RP} \sim 2.45$ mag). This result supports the hypothesis that the gap is caused by core-envelope interactions. Using gyro-kinematic ages, we also find a potential rapid spin-down of stars across this period gap

Media Portrayal of GM Science and Citrus Greening in State and National Newspapers

Huanglongbing (HLB), commonly known as citrus greening, is a bacterial disease severely affecting the profitability and continuation of the citrus industry in Florida and is threatening the citrus industry in other states as well. Currently, the disease only can be managed, not cured. Gene-based therapies, such as GM science, have been identified as a viable long-term solution. However, consumer acceptance of genetically modified food is low and their understanding and acceptance of new technologies is largely dependent on what they receive through mass media. Therefore, the purpose of this research is to understand news coverage of both citrus greening and gene modification science. This content analysis studied news articles of either citrus greening or gene modification science in national and state-specific newspapers and identified that while citrus greening is not highly covered by newspapers, it is accurately described via appropriate terminology. Genetic modification science is more commonly a topic of news coverage and is somewhat neutral and balanced in coverage. This research shows that source use in media coverage of gene modification science is balanced, but sources are most commonly chosen from organizations with a directed opinion or position on the topic