The Impact of Venous Thromboembolism on Risk of Death or Hemorrhage in Older Cancer Patients

BACKGROUND: Among older cancer patients, there is uncertainty about the degree to which venous thromboembolism (VTE) and its treatment increase the risk of death or major hemorrhage. OBJECTIVE: To determine the prevalence of VTE in a cohort of older cancer patients, as well as the degree to which VTE increased the risk of death or major hemorrhage. METHODS: We conducted a retrospective cohort study of linked Surveillance, Epidemiology, and End Results cancer registry and Medicare administrative claims data. Patients with any of ten invasive cancers diagnosed during 1995 through 1999 were included; the independent variable was VTE diagnosed concomitantly with cancer diagnosis. Outcomes included major hemorrhage during the first year after cancer diagnosis and all-cause mortality; RESULTS: Overall, about 1% of patients who were diagnosed with cancer also had a VTE diagnosed concomitantly. After adjusting for sociodemographic factors and cancer stage and grade, concomitant VTE was associated with a relative increase in the risk of death for 8 of the 10 cancer types; the increase in risk tended to range 20–40% across most cancer types. Approximately 16.8% (95% confidence interval [CI] 14.9–18.8%) of patients with a concomitant VTE and 7.9% (95% CI 7.7–8.0%) of patients without a VTE experienced a major hemorrhage during the year after cancer diagnosis (P value <.001). The excess risk of hemorrhage associated with VTE varied substantially across cancer types, ranging from no significant excess (kidney and uterine cancer) to 11.5% (lymphoma). CONCLUSION: Concomitant VTE is not only a marker and potential mediator of increased risk of death among older cancer patients, but patients with a VTE have a marked increased risk of major hemorrhage

The Context of Current Content Analysis of Gender Roles: An Introduction to a Special Issue

The aim of this paper is to provide context for the quantitative content analyses of gender roles that are to be included in both parts of this special issue. First, a timeline of historical uses of the content analysis methodology is presented. Second, research objectives that frequently drive content analysis of gender roles are described; these include: to support feminist claims, to compare media with real life, to predict effects on audiences, and to detect effects of media producers on content. Third, previous content analyses published in Sex Roles and other gender-focused journals are reviewed and categorized in terms of medium, genre, time span, gender, and nationality. Finally, contributions of each of the articles in this special issue are outlined

HIV-1 Nef Targets MHC-I and CD4 for Degradation Via a Final Common β-COP–Dependent Pathway in T Cells

To facilitate viral infection and spread, HIV-1 Nef disrupts the surface expression of the viral receptor (CD4) and molecules capable of presenting HIV antigens to the immune system (MHC-I). To accomplish this, Nef binds to the cytoplasmic tails of both molecules and then, by mechanisms that are not well understood, disrupts the trafficking of each molecule in different ways. Specifically, Nef promotes CD4 internalization after it has been transported to the cell surface, whereas Nef uses the clathrin adaptor, AP-1, to disrupt normal transport of MHC-I from the TGN to the cell surface. Despite these differences in initial intracellular trafficking, we demonstrate that MHC-I and CD4 are ultimately found in the same Rab7+ vesicles and are both targeted for degradation via the activity of the Nef-interacting protein, β-COP. Moreover, we demonstrate that Nef contains two separable β-COP binding sites. One site, an arginine (RXR) motif in the N-terminal α helical domain of Nef, is necessary for maximal MHC-I degradation. The second site, composed of a di-acidic motif located in the C-terminal loop domain of Nef, is needed for efficient CD4 degradation. The requirement for redundant motifs with distinct roles supports a model in which Nef exists in multiple conformational states that allow access to different motifs, depending upon which cellular target is bound by Nef

Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions

BackgroundTargeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing.ResultsAll panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5-20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden.ConclusionThis comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.Peer reviewe