Physical activity, weight, and outcomes in patients receiving chemotherapy for metastatic breast cancer (C40502/Alliance)

Background: Obesity and inactivity are associated with increased risk of cancer-related and overall mortality in breast cancer, but there are few data in metastatic disease. Methods: Cancer and Leukemia Group B 40502 was a randomized trial of first-line taxane-based chemotherapy for patients with metastatic breast cancer. Height and weight were collected at enrollment. After 299 patients enrolled, the study was amended to assess recreational physical activity (PA) at enrollment using the Nurses\u27 Health Study Exercise Questionnaire. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using stratified Cox modeling (strata included hormone receptor status, prior taxane, bevacizumab use, and treatment arm). All statistical tests were 2-sided. Results: A total of 799 patients were enrolled, and at the time of data lock, median follow-up was 60 months. At enrollment, median age was 56.7 years, 73.1% of participants had hormone receptor-positive cancers, 42.6% had obesity, and 47.6% engaged in less than 3 metabolic equivalents of task (MET) hours of PA per week (\u3c1 hour of moderate PA). Neither baseline body mass index nor PA was statistically significantly associated with PFS or OS, although there was a marginally statistically significant increase in PFS (hazard ratio = 0.83, 95% confidence interval = 0.79 to 1.02; Conclusions: In a trial of first-line chemotherapy for metastatic breast cancer, rates of obesity and inactivity were high. There was no statistically significant relationship between body mass index and outcomes. More information is needed regarding the relationship between PA and outcomes

Data from: Interactive effects of a non-native invasive grass Microstegium vimineum and herbivore exclusion on experimental tree regeneration under differing forest management

1. Invasive plants, herbivores and site management history can play crucial roles in determining plant community composition. The net effects of invasive species on plant communities are well known, but we have a poor understanding of the relative contributions of direct competitive effects of invasive species and their interactions with herbivores and management practices. Understanding interactions among plant invasions, herbivores and management history is critical for predicting and managing long-term ecological effects of invasions on native communities. 2. We investigated the effects of the invasive annual grass Microstegium vimineum, vertebrate herbivory, site management history and their interactions on seedling performance of five native tree species in six forest sites. Half of the sites had been subjected to recent timber harvesting and half had not been managed for timber for at least 20 years. We evaluated tree seedling survival and biomass after two growing seasons in blocked split-plots where the invasive grass was present or experimentally removed and where vertebrate herbivores were excluded by fencing or allowed onto the plots. 3. Removal of the invasive grass and herbivore exclosures both had positive effects on seedling survival. Survival of all species was significantly increased by removal or by the interaction of removal with exclosure or timber harvest history. There was a significant interaction between exclosure and removal on seedling biomass where seedlings were larger in exclosure treatments with the invasive removed but smaller in exclosure treatments when the invader was present. Mean seedling biomass was 79.6% greater in harvested sites than in non-harvested sites. The significant positive effects of removal and recent timber harvest on the biomass of two Quercus species suggests strong impacts of invasion and management history on this important genus. 4. Synthesis and applications. An invasive grass directly inhibited tree seedling performance but effects depended on herbivore exclusion treatment, timber harvest history and tree species. Our results suggest that forest management strategies should incorporate invasive plant control given that regeneration of desirable tree species can be influenced by plant invasions and their interactions with herbivores and previous management practices

Disco funerals: A risk situation for HIV infection among youth in Kisumu, Kenya

Objective: We investigated the so-called 'disco funeral' phenomenon in Kisumu, Kenya, whereby community members including adolescents congregate at the home of the deceased for several days, accompanied by music and dancing. We explored whether disco funerals are a risk situation for HIV/sexually transmitted infection infection among youth. Design: Cross-sectional qualitative study. Methods: We conducted 44 in-depth interviews with male and female adolescents aged 15-20 years in Kisumu municipality in Nyanza Province, Kenya. We also made observations during six disco funerals. Results: Disco funerals were an important place for young people to hang out; they increased the opportunities to meet and engage in (risky) sexual activities. Many adolescents reported having casual sex on these occasions, sometimes with multiple partners, and mostly without condoms. Some girls were forced into sex, and there were several accounts of gang rape. Sex in exchange for money was reported frequently. Drugs and alcohol seemed to facilitate unprotected, multiple-partner, coerced, and transactional sex. Conclusion: In Kisumu, a town with a generalized HIV/AIDS epidemic, the high AIDS mortality leads to frequent disco funerals. Because many adolescents are having unprotected, transactional, or coerced sex at these occasions, disco funerals might contribute to the high HIV prevalence among youth, especially among adolescent girls. HIV interventions urgently need to include outreach actions to youth who hang out at disco funerals and link up with parents and funeral organizers to reduce risk situations

Johnson etal. 2014 data

Seedling data used in this study

Prognostic variables in low and high risk stage III colon cancers treated in two adjuvant chemotherapy trials

Background: Stratification of patients with stage III colon cancer into low (T1-3N1) and high (T4 and/or N2) risk groups is used to guide the duration of adjuvant chemotherapy. We determined the relative contribution of clinical and molecular features to survival by risk group. Materials & methods: Stage III colon cancer (N = 5337) patients from two adjuvant trials of FOLFOX ± cetuximab [N0147 (Alliance), PETACC-8] were risk grouped, then subgrouped by clinical features and molecular variables [KRAS and BRAF/mismatch repair (MMR) combined variable]. Distributions of disease-free survival (DFS), overall survival (OS), and survival after recurrence (SAR) were estimated. In multivariable Cox models, backward elimination was performed for analysis of candidate predictors of outcomes. Relative contributions of model-selected variables to outcomes by risk group were calculated using χ2. Results: Among low risk tumours, mutant KRAS and male gender were significantly associated with poorer OS multivariately. In high risk tumours, significantly poorer OS was observed for right sidedness and for mutant KRAS and BRAFV600E/pMMR, subgroups. Specifically, BRAFV600E/pMMR (OS: HR = 1.75; 95% CI: 1.36–2.24; Padj<.0001) and right- versus left-sidedness were associated with significantly poorer DFS, OS (HR = 1.56; 95% CI: 1.31–1.83; Padj<.0001), and SAR (HR = 1.64; 95% CI: 1.37–1.95; Padj<.0001). Poor prognosis of mutant KRAS for DFS and OS was similar among risk groups. BRAF/MMR and sidedness were associated with poorer SAR in both low and high risk tumours. Age, gender, and KRAS were the top three relative contributors to DFS and OS among low risk tumours; sidedness ranked first for DFS and OS, and second to BRAF/MMR for SAR among high risk tumours. Conclusion: Sidedness and BRAF/MMR contributed the most to survival outcomes among high risk tumours and should be interpreted in the context of risk group.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Multi-Omic Factor Analysis uncovers immunological signatures with pathophysiologic and clinical implications in coronary syndromes

Acute and chronic coronary syndromes (ACS and CCS) are leading causes of mortality. Inflammation is considered to be a key pathogenic driver, but immune states in humans and their clinical implications remain poorly understood. We hypothesized that Multi-Omic blood analysis combined with Multi-Omic Factor Analysis (MOFA) might uncover hidden sources of variance providing pathophysiological insights linked to clinical needs. Here, we compile a single cell longitudinal dataset of the circulating immune states in ACS &amp; CCS (13x103 clinical &amp; Multi-Omic variables, n=117 subjects, n=838 analyzed samples) from two independent cohorts. Using MOFA, we identify multilayered factors, characterized by distinct classical monocyte and CD4+ &amp; CD8+ T cell states that explain a large proportion of inter-patient variance. Three factors either reflect disease course or predict outcome in coronary syndromes. The diagnostic performance of these factors reaches beyond established biomarkers highlighting the potential use of MOFA as a novel tool for multilayered patient risk stratification

Models for mature T-cell lymphomas-A critical appraisal of experimental systems and their contribution to current T-cell tumorigenic concepts

Mature T-cell lymphomas/leukemias (MTCL) have been understudied lymphoid neoplasms that currently receive growing attention. Our historically rudimentary molecular understanding and dissatisfactory interventional success in this complex and for the most part poor-prognostic group of tumors is only slightly improving. A major limiting aspect in further progress in these rare neoplasms is the lack of suitable model systems that would substantially facilitate pathogenic studies and pre-clinical drug evaluations. Such representations of MTCL have thus far not been systematically appraised. We therefore provide an overview on existing models and point out their particular advantages and limitations in the context of the specific scientific questions. After addressing issues of species-specific differences and classifications, we summarize data on MTCL cell lines of human as well as murine origin, on murine strain predispositions to MTCL, on available models of genetically engineered mice, and on transplant systems. From an in-silico meta-analysis of available primary data of gene expression profiles on human MTCL we cross-reference genes reported to transform T-cells in mice and reflect on their general vs entity-restricted relevance and on target-promoter influences. Overall, we identify the urgent need for new models of higher fidelity to human MTCL with respect to their increasingly recognized diversity and to predictions of drug response. (C) 2013 Elsevier Ireland Ltd. All rights reserved