Developing Core Capabilities for Local Health Departments to Engage in Land Use and Transportation Decision Making for Active Transportation

OBJECTIVE: To develop a core set of capabilities and tasks for local health departments (LHDs) to engage in land use and transportation policy processes that promote active transportation. DESIGN: We conducted a 3-phase modified Delphi study from 2015 to 2017. SETTING: We recruited a multidisciplinary national expert panel for key informant interviews by telephone and completion of a 2-step online validation process. PARTICIPANTS: The panel consisted of 58 individuals with expertise in local transportation and policy processes, as well as experience in cross-sector collaboration with public health. Participants represented the disciplines of land use planning, transportation/public works, public health, municipal administration, and active transportation advocacy at the state and local levels. MAIN OUTCOME MEASURES: Key informant interviews elicited initial capabilities and tasks. An online survey solicited rankings of impact and feasibility for capabilities and ratings of importance for associated tasks. Feasibility rankings were used to categorize capabilities according to required resources. Results were presented via second online survey for final input. RESULTS: Ten capabilities were categorized according to required resources. Fewest resources were as follows: (1) collaborate with public officials; (2) serve on land use or transportation board; and (3) review plans, policies, and projects. Moderate resources were as follows: (4) outreach to the community; (5) educate policy makers; (6) participate in plan and policy development; and (7) participate in project development and design review. Most resources were as follows: (8) participate in data and assessment activities; (9) fund dedicated staffing; and (10) provide funding support. CONCLUSIONS: These actionable capabilities can guide planning efforts for LHDs of all resource levels

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance.Funder: The Canadian Cancer SocietyFunder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

ABIeS: A database for softwood identification

International audienceSoftwoods constitute an important part of the plant macro-remains that are found within the Carboniferous to the most recent fossil deposits. Their taxonomical study is mostly made possible thanks to classical references (Philips 1948, Greguss 1955, Esteban 2004, Philippe & Bamford 2008). As for hardwoods, in addition to similar standard publications, a dedicated database has started being developed seven years ago (Insidewood - Wheeler 2011). Today Insidewood constitutes a very useful and indispensable tool, in constant development, which allows online identification for extant and fossil hardwoods. Despite their abundance in fossil deposits, no tool dedicated to softwoods has been developed yet. To fill this gap, we initiated the implementation of a softwood database, ABIeS, on the biodiversity collaborative management platform Xper3 (Ung et al. 2010). The descriptive model is mainly based on IAWA list of softwood features (IAWA committee 2004) but we also propose original features linked for instance to cell size and cross-field characteristics. As a first step, we tried as much as possible to illustrate the softwoods diversity using local resources. Therefore, extant species were chosen among the one hosted at the MNHN-xylarium, Paris, whereas fossil species where chosen from the collection Boureau (UPMC, Paris). We finally carried a global analysis of the database in order to better understand the softwood variability regarding systematics and ecology. This project, although initiated in our laboratory in Paris has a collaborative aim. We invite all the researchers who are interested by the wood anatomy of extant and fossil conifers to join us. Esteban, L. G., de Palacios, P. D. P., Casasús, A. G., & Fernández, F. G. (2004). Characterisation of the xylem of 352 conifers. Forest Systems, 13(3): 452-478.Greguss, P. (1955). Identification of living gymnosperms on the basis of xylotomy. Akademiai Kiado, Budapest. 263 pp.IAWA committee (2004). IAWA list of microscopic features for softwood identification. IAWA J, 25(1): 1-70.Philippe, M., & Bamford, M. K. (2008). A key to morphogenera used for Mesozoic conifer-like woods. Review of Palaeobotany and Palynology, 148(2-4): 184-207.Phillips, E.W.J. 1948. Identification of Softwoods. Forest Products Research Bulletin 22, 56 p.Ung, V., Dubus, G., Zaragüeta-Bagils, R., Vignes-Lebbe, R. 2010. Xper2: introducing e-taxonomy. Bioinformatics, 26 (5): 703-704.Wheeler, E.A. (2011). InsideWood - a web resource for hardwood anatomy. IAWA J. 32 (2): 199-211