Inequality Matters

This is one of a series of five papers outlining the particular domains and dimensions of inequality where new research may yield a better understanding of responses to this growing issue.The aim of this paper is to describe, in very broad brushstrokes, the state of academic scholarship regarding social inequality, with an eye toward identifying important gaps. The focus is on four key interacting social domains: 1) socioeconomic (financial and human capital)2) health (including physical and psychological) 3) political (access to power and political representation)4) sociocultural (identity, cultural freedoms, and human rights

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

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

Excerpt from Stubborn Roots: Race, Culture, and Inequality in U.S. and South African Schools

Prudence L. Carter takes on the formidable task of assessing the impact of race on the culture of public schools, among both students and faculty, in two nations marked by histories of extreme racial inequality: the United States and South Africa. Through school visits, interviews, and patient compilation of statistics, she examines the salience, and in some cases the slippery role, of race in interpersonal and professional relations. In the process, she bravely attempts to bring out the voices and subjectivities of the people on all sides of the color line(s) with whom she interacts

Excerpt from <i>Stubborn Roots: Race, Culture, and Inequality in U.S. and South African Schools</i>

Prudence L. Carter takes on the formidable task of assessing the impact of race on the culture of public schools, among both students and faculty, in two nations marked by histories of extreme racial inequality: the United States and South Africa. Through school visits, interviews, and patient compilation of statistics, she examines the salience, and in some cases the slippery role, of race in interpersonal and professional relations. In the process, she bravely attempts to bring out the voices and subjectivities of the people on all sides of the color line(s) with whom she interacts.</p

Educational Equality Is a Multifaceted Issue: Why We Must Understand the School’s Sociocultural Context for Student Achievement

The Coleman Report concluded that if students of color attended schools with more white students, they were likely to garner significantly better achievement results. Several contextual factors should be considered, however, before we make strong conclusions about the strength of the effect of racial and ethnic minority students attending school with white students. This paper makes a case for considering the necessity of both the “material” and “sociocultural” domains of schooling if we are to move toward a more holistic understanding of “school effects” on students’ academic well-being. Based on a case-study analysis of four high-performing, diverse schools in different regions, using ethnographic observations and random student surveys, this paper offers evidence that students who hail from similar socioeconomic and family backgrounds but who attend schools with different sociocultural contexts have disparate academic experiences. The findings draw our attention to new directions to consider as we seek to understand how educational outcomes vary depending on the school's organizational culture

Achievement Gaps Arise from Opportunity Gaps

The ideas of “achievement gap” and “test score gap” have dominated policy discussions over the past two decades about American youths’ overall educational well-being. Meanwhile, scant attention has been paid to a gap that is even more at odds with American ideals: the opportunity gap—a divide that exposes the wide chasm of resources and social inequality in our society. The latter constitute the inputs that shape the outputs of achievement and mobility. In this talk, I will examine what I call the “ecology of opportunity” (or lack thereof) and offer some insights, based on evidence-based research, about not only the challenges embedded in U.S. educational institutions but also the supports and resources that would create deep and substantial improvements in student learning and achievement