Impact of molecular profiling on overall survival of patients with advanced ovarian cancer

OBJECTIVE: Patients with recurrent epithelial ovarian cancer (EOC) have limited treatment options. Studies have reported that biomarker profiling may help predict patient response to available treatments. This study sought to determine the value of biomarker profiling in recurrent EOC. RESULTS: Patients in the Matched cohort had a median OS of 36 months compared to 27 months for patients in the Unmatched cohort (HR 0.62, 95% CI 0.41-0.96; p < 0.03). Individual biomarkers were analyzed, with TUBB3, and PGP prognostic for survival. Biomarker analysis also identified a molecular subtype (positive for at least two of the following markers: ERCC1, RRM1, TUBB3, PGP) with particularly poor overall survival. METHODS: 224 patients from a commercial registry (NCT02678754) with stage IIIC/IV EOC at diagnosis, or restaged to IIIC/IV EOC at the time of molecular profiling, were retrospectively divided into two cohorts based on whether or not the drugs they received matched their profile recommendations. The Matched cohort received no drugs predicted to be lack-of-benefit while the Unmatched cohort received at least one drug predicted to be lack-of-benefit. Profile biomarker/drug associations were based on multiple test platforms including immunohistochemistry, fluorescent in situ hybridization and DNA sequencing. CONCLUSIONS: This report demonstrates the ability of multi-platform molecular profiling to identify EOC patients at risk of inferior survival. It also suggests a potential beneficial role of avoidance of lack-of-benefit therapies which, when administered, resulted in decreased survival relative to patients who received only therapies predicted to be of benefit

Site staff perspectives on communicating trial results to participants : Cost and feasibility results from the Show RESPECT cluster randomised, factorial, mixed-methods trial

We are grateful to the patients and site staff who participated in this study. We dedicate this article to the memory of Amanda Hunn, who was part of the steering group for this study until she passed away in 2022. We thank other members of the steering group for their input into the study, especially Conor Tweed and Liz James. We acknowledge the hard work and diligence of Cara Purvis, the trial manager, and the data managers for Show RESPECT. We also thank the ICON8 trial team for their support, particularly Babasola Popoola, Francesca Schiavone, Jonathan Badrock, Andrew Clamp and Rick Kaplan.Peer reviewe

Site staff perspectives on communicating trial results to participants: Cost and feasibility results from the Show RESPECT cluster randomised, factorial, mixed-methods trial

BACKGROUND/AIMS: Sharing trial results with participants is an ethical imperative but often does not happen. Show RESPECT (ISRCTN96189403) tested ways of sharing results with participants in an ovarian cancer trial (ISRCTN10356387). Sharing results via a printed summary improved patient satisfaction. Little is known about staff experience and the costs of communicating results with participants. We report the costs of communication approaches used in Show RESPECT and the views of site staff on these approaches. METHODS: We allocated 43 hospitals (sites) to share results with trial participants through one of eight intervention combinations (2 × 2 × 2 factorial; enhanced versus basic webpage, printed summary versus no printed summary, email list invitation versus no invitation). Questionnaires elicited data from staff involved in sharing results. Open- and closed-ended questions covered resources used to share results and site staff perspectives on the approaches used. Semi-structured interviews were conducted. Interview and free-text data were analysed thematically. The mean additional site costs per participant from each intervention were estimated jointly as main effects by linear regression. RESULTS: We received questionnaires from 68 staff from 41 sites and interviewed 11 site staff. Sites allocated to the printed summary had mean total site costs of sharing results £13.71/patient higher (95% confidence interval (CI): -3.19, 30.60; p = 0.108) than sites allocated no printed summary. Sites allocated to the enhanced webpage had mean total site costs £1.91/patient higher (95% CI: -14, 18.74; p = 0.819) than sites allocated to the basic webpage. Sites allocated to the email list had costs £2.87/patient lower (95% CI: -19.70, 13.95; p = 0.731) than sites allocated to no email list. Most of these costs were staff time for mailing information and handling patients' queries. Most site staff reported no concerns about how they had shared results (88%) and no challenges (76%). Most (83%) found it easy to answer queries from patients about the results and thought the way they were allocated to share results with participants would be an acceptable standard approach (76%), with 79% saying they would follow the same approach for future trials. There were no significant effects of the randomised interventions on these outcomes. Site staff emphasised the importance of preparing patients to receive the results, including giving opt-in/opt-out options, and the need to offer further support, particularly if the results could confuse or distress some patients. CONCLUSIONS: Adding a printed summary to a webpage (which significantly improved participant satisfaction) may increase costs to sites by ~£14/patient, which is modest in relation to the cost of trials. The Show RESPECT communication interventions were feasible to implement. This information could help future trials ensure they have sufficient resources to share results with participants

Eye care delivery models to improve access to eye care for Indigenous peoples in high-income countries: a scoping review.

PURPOSE: Globally, there are ~370 million Indigenous peoples. Indigenous peoples typically experience worse health compared with non-Indigenous people, including higher rates of avoidable vision impairment. Much of this gap in eye health can be attributed to barriers that impede access to eye care services. We conducted a scoping review to identify and summarise service delivery models designed to improve access to eye care for Indigenous peoples in high-income countries. METHODS: Searches were conducted on MEDLINE, Embase and Global Health in January 2019 and updated in July 2020. All study designs were eligible if they described a model of eye care service delivery aimed at populations with over 50% Indigenous peoples. Two reviewers independently screened titles, abstracts and full-text articles and completed data charting. We extracted data on publication details, study context, service delivery interventions, outcomes and evaluations, engagement with Indigenous peoples and access dimensions targeted. We summarised findings descriptively following thematic analysis. RESULTS: We screened 2604 abstracts and 67 studies fulfilled our eligibility criteria. Studies were focused on Indigenous peoples in Australia (n=45), USA (n=11), Canada (n=7), New Zealand (n=2), Taiwan (n=1) and Greenland (n=1). The main disease focus was diabetic retinopathy (n=30, 45%), followed by 'all eye care' (n=16, 24%). Most studies focused on targeted interventions to increase availability of services. Fewer than one-third of studies reported involving Indigenous communities when designing the service. 41 studies reflected on whether the model improved access, but none undertook rigorous evaluation or quantitative assessment. CONCLUSIONS: The geographical and clinical scope of service delivery models to improve access to eye care for Indigenous peoples in high-income countries is narrow, with most studies focused on Australia and services for diabetic retinopathy. More and better engagement with Indigenous communities is required to design and implement accessible eye care services

Modelling interactions of acid–base balance and respiratory status in the toxicity of metal mixtures in the American oyster Crassostrea virginica

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Comparative Biochemistry and Physiology - Part A: Molecular & Integrative Physiology 155 (2010): 341-349, doi:10.1016/j.cbpa.2009.11.019.Heavy metals, such as copper, zinc and cadmium, represent some of the most common and serious pollutants in coastal estuaries. In the present study, we used a combination of linear and artificial neural network (ANN) modelling to detect and explore interactions among low-dose mixtures of these heavy metals and their impacts on fundamental physiological processes in tissues of the Eastern oyster, Crassostrea virginica. Animals were exposed to Cd (0.001 – 0.400 μM), Zn (0.001 – 3.059 μM) or Cu (0.002 – 0.787 μM), either alone or in combination for 1 to 27 days. We measured indicators of acid-base balance (hemolymph pH and total CO2), gas exchange (Po2), immunocompetence (total hemocyte counts, numbers of invasive bacteria), antioxidant status (glutathione, GSH), oxidative damage (lipid peroxidation; LPx), and metal accumulation in the gill and the hepatopancreas. Linear analysis showed that oxidative membrane damage from tissue accumulation of environmental metals was correlated with impaired acid-base balance in oysters. ANN analysis revealed interactions of metals with hemolymph acid-base chemistry in predicting oxidative damage that were not evident from linear analyses. These results highlight the usefulness of machine learning approaches, such as ANNs, for improving our ability to recognize and understand the effects of sub-acute exposure to contaminant mixtures.This study was supported by NOAA’s Center of Excellence in Oceans and Human Health at HML and the National Science Foundation

Outplayed: Regaining Strategic Initiative in the Gray Zone, A Report Sponsored by the Army Capabilities Integration Center in Coordination with Joint Staff J-39/Strategic Multi-Layer Assessment Branch

U.S. competitors pursuing meaningful revision or rejection of the current U.S.-led status quo are employing a host of hybrid methods to advance and secure interests contrary to those of the United States. These challengers employ unique combinations of influence, intimidation, coercion, and aggression to incrementally crowd out effective resistance, establish local or regional advantage, and manipulate risk perceptions in their favor. So far, the United States has not come up with a coherent countervailing approach. It is in this “gray zone”—the awkward and uncomfortable space between traditional conceptions of war and peace—where the United States and its defense enterprise face systemic challenges to U.S. position and authority. Gray zone competition and conflict present fundamental challenges to U.S. and partner security and, consequently, should be important pacers for U.S. defense strategy.https://press.armywarcollege.edu/monographs/1924/thumbnail.jp

An analysis of monthly home range size in the critically endangered California Condor Gymnogyps californianus

Condors and vultures comprise the only group of terrestrial vertebrates in the world that are obligate scavengers, and these species move widely to locate ephemeral, unpredictable, and patchily-distributed food resources. In this study, we used high-resolution GPS location data to quantify monthly home range size of the critically endangered California Condor Gymnogyps californianus throughout the annual cycle in California. We assessed whether individual-level characteristics (age, sex and breeding status) and factors related to endangered species recovery program efforts (rearing method, release site) were linked to variation in monthly home range size. We found that monthly home range size varied across the annual cycle, with the largest monthly home ranges observed during late summer and early fall (July-October), a pattern that may be linked to seasonal changes in thermals that facilitate movement. Monthly home ranges of adults were significantly larger than those of immatures, but males and females used monthly home ranges of similar size throughout the year and breeding adults did not differ from non-breeding adults in their average monthly home range size. Individuals from each of three release sites differed significantly in the size of their monthly home ranges, and no differences in monthly home range size were detected between condors reared under captive conditions relative to those reared in the wild. Our study provides an important foundation for understanding the movement ecology of the California Condor and it highlights the importance of seasonal variation in space use for effective conservation planning for this critically endangered species