An international working group consensus report for the prioritization of molecular biomarkers for Ewing sarcoma

The advent of dose intensified interval compressed therapy has improved event-free survival for patients with localized Ewing sarcoma (EwS) to 78% at 5 years. However, nearly a quarter of patients with localized tumors and 60-80% of patients with metastatic tumors suffer relapse and die of disease. In addition, those who survive are often left with debilitating late effects. Clinical features aside from stage have proven inadequate to meaningfully classify patients for risk-stratified therapy. Therefore, there is a critical need to develop approaches to risk stratify patients with EwS based on molecular features. Over the past decade, new technology has enabled the study of multiple molecular biomarkers in EwS. Preliminary evidence requiring validation supports copy number changes, and loss of function mutations in tumor suppressor genes as biomarkers of outcome in EwS. Initial studies of circulating tumor DNA demonstrated that diagnostic ctDNA burden and ctDNA clearance during induction are also associated with outcome. In addition, fusion partner should be a pre-requisite for enrollment on EwS clinical trials, and the fusion type and structure require further study to determine prognostic impact. These emerging biomarkers represent a new horizon in our understanding of disease risk and will enable future efforts to develop risk-adapted treatment

N-(4-Chlorophenyl)-9H-fluoren-9-imine

The title compound, C19H12ClN, was synthesized via reaction of 9-fluorenone and 4-chloroaniline using p-toluenesulfonic acid in toluene. The dihedral angle between the fluorene moiety (r.m.s. deviation = 0.027 Å) and the chlorophenyl ring is 64.59 (6)° and a possible weak intramolecular C—H...π interaction occurs

An international working group consensus report for the prioritization of molecular biomarkers for Ewing sarcoma.

The advent of dose intensified interval compressed therapy has improved event-free survival for patients with localized Ewing sarcoma (EwS) to 78% at 5 years. However, nearly a quarter of patients with localized tumors and 60-80% of patients with metastatic tumors suffer relapse and die of disease. In addition, those who survive are often left with debilitating late effects. Clinical features aside from stage have proven inadequate to meaningfully classify patients for risk-stratified therapy. Therefore, there is a critical need to develop approaches to risk stratify patients with EwS based on molecular features. Over the past decade, new technology has enabled the study of multiple molecular biomarkers in EwS. Preliminary evidence requiring validation supports copy number changes, and loss of function mutations in tumor suppressor genes as biomarkers of outcome in EwS. Initial studies of circulating tumor DNA demonstrated that diagnostic ctDNA burden and ctDNA clearance during induction are also associated with outcome. In addition, fusion partner should be a pre-requisite for enrollment on EwS clinical trials, and the fusion type and structure require further study to determine prognostic impact. These emerging biomarkers represent a new horizon in our understanding of disease risk and will enable future efforts to develop risk-adapted treatment

Abusive Experiences and Young Women's Sexual Health Outcomes: Is Condom Negotiation Self-Efficacy a Mediator?

CONTEXT: Intimate partner violence and reproductive coercion are associated with unintended pregnancies and STDs. Greater condom negotiation self-efficacy among young women may mediate these associations. METHODS: A sample of 841 female adolescents (aged 16–19) and 1,387 young adult women (aged 20–24) recruited from 24 family planning clinics in western Pennsylvania in 2011–2012 reported on intimate partner violence, reproductive coercion, condom negotiation self-efficacy and sexual health outcomes at baseline and four- and 12-month follow-ups. Mixed models were used to test associations of intimate partner violence and reproductive coercion with unintended pregnancy and STD diagnosis. The Sobel test of mediation was used to measure indirect effects of condom negotiation self-efficacy. RESULTS: At baseline, 15% of adolescents and 11% of young adults reported recent intimate partner violence victimization; 7% and 6%, respectively, reported recent reproductive coercion. For both age-groups, intimate partner violence and reproductive coercion were associated with a reduced level of condom negotiation self-efficacy (coefficients, −0.27 to −0.13) and increased odds of STD diagnosis (odds ratios, 1.03–1.1). However, only reproductive coercion was associated with unintended pregnancy (odds ratios, 1.1 for each group). The only association that condom negotiation self-efficacy mediated was between reproductive coercion and unintended pregnancy among young adults (17% of total effect). CONCLUSIONS: Targeting condom negotiation self-efficacy alone in abusive relationships would likely not translate into improved sexual health outcomes in this population. Other strategies are needed to prevent unintended pregnancy and STDs