Not immune to inequity: minority under-representation in immunotherapy trials for breast and gynecologic cancers.

OBJECTIVE: To describe the participation of minority women in clinical trials using immunologic agents for breast and gynecologic cancers. METHODS: A retrospective review of completed clinical trials involving immunotherapy for breast and gynecologic cancers was performed. Completed trials were examined for data on race, tumor type, and start year. Minority enrollment was stratified by tumor site. Based on Center for Disease Control and Prevention age-adjusted incidence for race, expected and observed ratios of racial participation were calculated and compared using Χ2 testing, p≤0.05. RESULTS: A total of 53 completed immunotherapy clinical trials involving 8820 patients were reviewed. Breast cancer trials were most common (n=24) and involved the most patients (n=6248, 71%). Racial breakdown was provided in 41 studies (77%) for a total of 7201 patients. Race reporting was lowest in uterine (n=4, 67%) and cervical cancer trials (n=6, 67%), and highest in ovarian cancer trials (n=12, 86%). White patients comprised 70% (n=5022) of all the patients included. Only 5% of patients involved were black (n=339), and 83% of these patients (n=282) were enrolled in breast cancer trials. Observed enrollment of black women was 32-fold lower for ovarian, 19-fold lower for cervical, 15-fold lower for uterine, and 11-fold lower for breast cancer than expected. While all trials reported race between 2013 and 2015, no consistent trend was seen towards increasing race reporting or in enrollment of black patients over time. CONCLUSION: Racial disparities exist in clinical trials evaluating immunologic agents for breast and gynecologic cancers. Recruitment of black women is particularly low. In order to address inequity in outcomes for these cancers, it is crucial that significant attention be directed towards minority representation in immuno-oncologic clinical trials.

Contaminated fish consumption in California's Central Valley Delta.

Extensive mercury contamination and angler selection of the most contaminated fish species coincide in California's Central Valley. This has led to a policy conundrum: how to balance the economic and cultural impact of advising subsistence anglers to eat less fish with the economic cost of reducing the mercury concentrations in fish? State agencies with regulatory and other jurisdictional authority lack sufficient data and have no consistent approach to this problem. The present study focused on a critical and contentious region in California's Central Valley (the Sacramento-San Joaquin Rivers Delta) where mercury concentrations in fish and subsistence fishing rates are both high. Anglers and community members were surveyed for their fish preferences, rates of consumption, the ways that they receive health information, and basic demographic information. The rates of fish consumption for certain ethnicities were higher than the rates used by state agencies for planning pollution remediation. A broad range of ethnic groups were involved in catching and eating fish. The majority of anglers reported catching fish in order to feed to their families, including children and women of child-bearing age. There were varied preferences for receiving health information and no correlation between knowledge of fish contamination and rates of consumption. Calculated rates of mercury intake by subsistence anglers were well above the EPA reference dose. The findings here support a comprehensive policy strategy of involvement of the diverse communities in decision-making about education and clean-up and an official recognition of subsistence fishers in the region.

Multiple protonation states of vesicular acetylcholine transporter detected by binding of [3H]vesamicol.

Vesicular acetylcholine transporter (VAChT) is inhibited by (-)-vesamicol [(-)-trans-2-(4-phenylpiperidino)cyclohexanol], which binds tightly to an allosteric site. The tertiary alkylamine center in (-)-vesamicol is protonated and positively charged at acidic and neutral pH and unprotonated and uncharged at alkaline pH. Deprotonation of the amine has been taken to explain loss of (-)-vesamicol binding at alkaline pH. However, binding data deviate from a stereotypical bell shape, and more binding occurs than expected at alkaline pH. The current study characterizes the binding of (-)-vesamicol from pH 5 to pH 10 using filter assays, (-)-[3H]vesamicol (hereafter called [3H]vesamicol), and human VAChT expressed in PC12(A123.7) cells. At acidic pH, protons and [3H]vesamicol compete for binding to VAChT. Preexposure or long-term exposure of VAChT to high pH does not affect binding, thus eliminating potential denaturation of VAChT and failure of the filter assay. The dissociation constant for the complex between protonated [3H]vesamicol and VAChT decreases from 12 nM at neutral pH to 2.1 nM at pH 10. The simplest model of VAChT that explains the behavior requires a proton at site 1 to dissociate with pK1 = 6.5 +/- 0.1, a proton at site A to dissociate with pKA = 7.6 +/- 0.2, and a proton at site B to dissociate with pKB = 10.0 +/- 0.1. Deprotonation of the site 1 proton is obligatory for [3H]vesamicol binding. Deprotonation of site A decreases affinity (2.2 +/- 0.5)-fold, and deprotonation of site B increases affinity (18 +/- 4)-fold. Time-dependent dissociation of bound [3H]vesamicol is biphasic, but equilibrium saturation curves are not. The contrasting phasicity suggests that the pathway to and from the [3H]vesamicol binding site exists in open and at least partially closed states. The potential significance of the findings to development of PET and SPECT ligands based on (-)-vesamicol for human diagnostics also is discussed.

Patient reported dry mouth: Instrument comparison and model performance for correlation with quality of life in head and neck cancer survivors.

PURPOSE: To identify a clinically meaningful cut-point for the single item dry mouth question of the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). METHODS: Head and neck cancer survivors who had received radiation therapy (RT) completed the MDASI-HN, the University of Michigan Hospital Xerostomia Questionnaire (XQ), and the health visual analog scale (VAS) of the EuroQol Five Dimension Questionnaire (EQ-5D). The Bayesian information criteria (BIC) were used to test the prediction power of each tool for EQ-5D VAS. The modified Breiman recursive partitioning analysis (RPA) was used to identify a cut point of the MDASI-HN dry mouth score (MDASI-HN-DM) with EQ-5D VAS, using a ROC-based approach; regression analysis was used to confirm the threshold effect size. RESULTS: Two-hundred seven respondents formed the cohort. Median follow-up from the end of RT to questionnaire completion was 88 months. The single item MDASI-HN-DM score showed a linear relationship with the XQ composite score (ρ = 0.80, p < 0.001). The MDASI-HN-DM displayed improved model performance for association with EQ-5D VAS as compared to XQ (BIC of 1803.7 vs. 2016.9, respectively). RPA showed that an MDASI-HN-DM score of ≥6 correlated with EQ-5D VAS decline (LogWorth 5.5). CONCLUSION: The single item MDASI-HN-DM correlated with the multi-item XQ and performed favorably in the prediction of QOL. A MDASI-HN-DM cut point of ≥6 correlated with decline in QOL.

Machine Learning Applications in Head and Neck Radiation Oncology: Lessons From Open-Source Radiomics Challenges.

Radiomics leverages existing image datasets to provide non-visible data extraction via image post-processing, with the aim of identifying prognostic, and predictive imaging features at a sub-region of interest level. However, the application of radiomics is hampered by several challenges such as lack of image acquisition/analysis method standardization, impeding generalizability. As of yet, radiomics remains intriguing, but not clinically validated. We aimed to test the feasibility of a non-custom-constructed platform for disseminating existing large, standardized databases across institutions for promoting radiomics studies. Hence, University of Texas MD Anderson Cancer Center organized two public radiomics challenges in head and neck radiation oncology domain. This was done in conjunction with MICCAI 2016 satellite symposium using Kaggle-in-Class, a machine-learning and predictive analytics platform. We drew on clinical data matched to radiomics data derived from diagnostic contrast-enhanced computed tomography (CECT) images in a dataset of 315 patients with oropharyngeal cancer. Contestants were tasked to develop models for (i) classifying patients according to their human papillomavirus status, or (ii) predicting local tumor recurrence, following radiotherapy. Data were split into training, and test sets. Seventeen teams from various professional domains participated in one or both of the challenges. This review paper was based on the contestants' feedback; provided by 8 contestants only (47%). Six contestants (75%) incorporated extracted radiomics features into their predictive model building, either alone (n = 5; 62.5%), as was the case with the winner of the "HPV" challenge, or in conjunction with matched clinical attributes (n = 2; 25%). Only 23% of contestants, notably, including the winner of the "local recurrence" challenge, built their model relying solely on clinical data. In addition to the value of the integration of machine learning into clinical decision-making, our experience sheds light on challenges in sharing and directing existing datasets toward clinical applications of radiomics, including hyper-dimensionality of the clinical/imaging data attributes. Our experience may help guide researchers to create a framework for sharing and reuse of already published data that we believe will ultimately accelerate the pace of clinical applications of radiomics; both in challenge or clinical settings.

Sustainable Sourcing of Global Agricultural Raw Materials: Assessing Gaps in Key Impact and Vulnerability Issues and Indicators.

Understanding how to source agricultural raw materials sustainably is challenging in today's globalized food system given the variety of issues to be considered and the multitude of suggested indicators for representing these issues. Furthermore, stakeholders in the global food system both impact these issues and are themselves vulnerable to these issues, an important duality that is often implied but not explicitly described. The attention given to these issues and conceptual frameworks varies greatly--depending largely on the stakeholder perspective--as does the set of indicators developed to measure them. To better structure these complex relationships and assess any gaps, we collate a comprehensive list of sustainability issues and a database of sustainability indicators to represent them. To assure a breadth of inclusion, the issues are pulled from the following three perspectives: major global sustainability assessments, sustainability communications from global food companies, and conceptual frameworks of sustainable livelihoods from academic publications. These terms are integrated across perspectives using a common vocabulary, classified by their relevance to impacts and vulnerabilities, and categorized into groups by economic, environmental, physical, human, social, and political characteristics. These issues are then associated with over 2,000 sustainability indicators gathered from existing sources. A gap analysis is then performed to determine if particular issues and issue groups are over or underrepresented. This process results in 44 "integrated" issues--24 impact issues and 36 vulnerability issues--that are composed of 318 "component" issues. The gap analysis shows that although every integrated issue is mentioned at least 40% of the time across perspectives, no issue is mentioned more than 70% of the time. A few issues infrequently mentioned across perspectives also have relatively few indicators available to fully represent them. Issues in the impact framework generally have fewer gaps than those in the vulnerability framework.

Group-item and directed scanning: examining preschoolers' accuracy and efficiency in two augmentative communication symbol selection methods.

PURPOSE: The current investigation compared directed scanning and group-item scanning among typically developing 4-year-old children. Of specific interest were their accuracy, selection speed, and efficiency of cursor movement in selecting colored line drawn symbols representing object vocabulary. METHOD: Twelve 4-year-olds made selections in both directed and group-item scanning conditions using a 36-symbol array that required matching line drawn symbols to pictures. RESULTS: The majority of participants took more time in the directed scanning condition. Though not statistically significant, participants tended to be more accurate in their use of directed scanning. The cursor movements required (as a proportion of optimal cursor movements) were similar for both scanning selection techniques. CONCLUSIONS: Among typically developing 4-year-olds, there appears to be a trade-off between speed and accuracy in symbol selection when using directed or group-item scanning. Better accuracy with directed scanning appears to come at the cost of a slower response time. Whereas group-item scanning may be faster, it results in a decreased number of accurate responses. Applications for clinical practice and implications for future research are discussed.

Equilibrium binding and transport by vesicular acetylcholine transporter.

The method describes production and the selection of neurosecretory PC12A123.7 cells stably transfected with human vesicular acetylcholine transporter (hVAChT). Transfected cells provide postnuclear supernatant used to characterize equilibrium binding of the neurotransmitter acetylcholine (ACh), the pH dependence for transport of ACh, and the rate behavior for dissociation of the allosteric, high-affinity inhibitor vesamicol. Retention of radiolabeled ACh or vesamicol, mediated by hVAChT in synaptic-like microvesicles of postnuclear supernatant, is measured using filter assays. The procedure for regression analysis of data also is described.