Development of the International Severe Asthma Registry (ISAR) : A Modified Delphi Study

This study is cofunded by Optimum Patient Care Global and AstraZeneca.Peer reviewedPostprin

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

Timing and selectivity of mortality in reared Atlantic cod revealed by otolith analysis

In juvenile fish production, large samples of known-aged material can be sampled at pre-determined time intervals from the same population. This enables an accurate determination of size-selective mortality by means of repeated samplings of fish and comparison of otolith size-at-age based on samples from different dates. An example is provided from an experiment with larval and juvenile Atlantic cod, Gadus morhua, where groups fed smaller sized enriched rotifers did not reveal any size-selective mortality during weaning to formulated feed, while those groups that were fed larger live natural zooplankton lost a significant fraction of the smaller-sized individuals during the same time period. This was contrary to the overall mortality which was higher among the rotifer fed groups during weaning. Part of this difference may be attributed to size differences between the groups, where larger zooplankton fed larvae were more prone to engage in cannibalistic behaviour

Att stängas ute, eller att inte vilja komma in : Om de hemlösas situation i Helsingborg

The intention of this study was to inquiry how the social workers at the social service offices in Helsingborg perceive the homeless and their situation, and what kind of aid and support the homeless are getting so they can change their situation. We have also examined how the homeless describe their own situation and how they experience the treatment and the help they get from the social workers. Our main questions were: 1. How does the social workers describe the situation of the homeless in Helsingborg? 2. What are the social workers doing to help the homeless acquire and maintain an own flat? 3. How do the homeless look at their situation? 4. How do the homeless experience the treatment they get from the social workers? The study was based on a qualitative method using interviews with persons who were, or had been, homeless and with social workers. As a theoretical perspective we used "social exclusion" and the theory of the British sociologist, Norbert Elias, we also compared our study with earlier research. We found that the homeless are living in a difficult situation and that they not feel as participating in the society. They experience that they are outsiders and not been accepted buy the "ordinary" citizens in the community. They also thought that it was difficult to influence the help they get from the social services. They had experienced that the treatment they got from the social workers sometimes felt insulting. The causes to homelessness are both structural and individual. Drug abuse was seen as a main cause to homelessness both by the homeless and by the social workers. One structural cause is the housing shortage, especially when it comes to small and affordable apartments. The social workers describe the situation of the homeless as a difficult problem to solve. It was difficult for the homeless to be accepted as tenants both by the landlords and by other tenants. The social services in Helsingborg have many different housing alternatives where the homeless can live for a shorter or longer period. To get a place in the housing that the social services can offer the homeless often must live up to different demands. A demand can for an example be that they must stop using drugs before the can achieve a place in a more stable and lasting housing solution. We have understood that the problem of homelessness is not an easy issue to solve and that there is no universal solution that could give every homeless person a housing that he or she can maintain

The Role of Broadcasting in the First Direct Elections to the European Parliament

The 1979 Media Study investigates the role of television in the first direct European Elections in 1979. It is a cross-national empirical research across nine nations. The research team included scholars from each of the European Community countries and involved the collection and analysis of data from each country about the campaigning activities of participating parties, journalists’ attitudes toward Europe and the elections, campaign coverage on television, and voters’ exposure and responses to the campaign.Die Media Study 1979 untersucht die Rolle des Fernsehens in der ersten Direktwahl des Europäischen Parlaments im Jahr 1979. Es ist eine länderübergreifende empirische Studie in neun Ländern. Dem Forscherteam gehören Wissenschaftler aus jedem Land der Europäischen Gemeinschaft an und beinhaltet die Sammlung und Analyse von Daten über die Kampagnen-Aktivitäten der beteiligten Parteien, die Haltung von Journalisten gegenüber Europa und den Wahlen, Berichterstattung über die Wahlkampagne im Fernsehen, Wahrnehmung und Reaktionen der Wähler auf die Kampagne aus jedem Land