The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.:the results of the LRF AML14 trial

The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.

Opportunity cost based analysis of corporate eco-efficiency: A methodology and its application to the CO2-efficiency of German companies

In this paper, we propose the return-to-cost-ratio (RCR) as an alternative approach to the analysis of operational eco-efficiency of companies based on the notion of opportunity costs. RCR helps to overcome two fundamental deficits of existing approaches to eco-efficiency. (1) It translates eco-efficiency into managerial terms by applying the well-established notion of opportunity costs to eco-efficiency analysis. (2) RCR allows to identify and quantify the drivers behind changes in corporate eco-efficiency. RCR is applied to the analysis of the CO2-efficiency of German companies in order to illustrate its usefulness for a detailed analysis of changes in corporate eco-efficiency as well as for the development of effective environmental strategies. (C) 2010 Elsevier Ltd. All rights reserved.

Prognostic and Predictive Biomarkers in Resected Colon Cancer: Current Status and Future Perspectives for Integrating Genomics into Biomarker Discovery

The number of agents that are potentially effective in the adjuvant treatment of locally advanced resectable colon cancer is increasing. Consequently, it is important to ascertain which subgroups of patients will benefit from a specific treatment. Despite more than two decades of research into the molecular genetics of colon cancer, there is a lack of prognostic and predictive molecular biomarkers with proven utility in this setting. A secondary objective of the Pan European Trials in Adjuvant Colon Cancer-3 trial, which compared irinotecan in combination with 5-fluorouracil and leucovorin in the postoperative treatment of stage III and stage II colon cancer patients, was to undertake a translational research study to assess a panel of putative prognostic and predictive markers in a large colon cancer patient cohort. The Cancer and Leukemia Group B 89803 trial, in a similar design, also investigated the use of prognostic and predictive biomarkers in this setting. In this article, the authors, who are coinvestigators from these trials and performed similar investigations of biomarker discovery in the adjuvant treatment of colon cancer, review the current status of biomarker research in this field, drawing on their experiences and considering future strategies for biomarker discovery in the postgenomic era. The Oncologist 2010; 15: 390-404

Unconscious Vigilance: Worldview Defense without Adaptations for Terror, Coalition or Uncertainty Management

Individuals subtly reminded of death, coalitional challenges, or feelings of uncertainty display exaggerated preferences for affirmations and against criticisms of their cultural in-groups. Terror management, coalitional psychology, and uncertainty management theories postulate this “worldview defense” effectas the output of mechanisms evolved either to allay the fear of death, foster social support, or reduce anxiety by increasing adherence to cultural values. In 4 studies, we report evidence for an alternative perspective. We argue that worldview defense owes to unconscious vigilance, a state of accentuatedreactivity to affective targets (which need not relate to cultural worldviews) that follows detection of subtle alarm cues (which need not pertain to death, coalitional challenges, or uncertainty). In Studies 1 and 2, death-primed participants produced exaggerated ratings of worldview-neutral affective targets. In Studies 3 and 4, subliminal threat manipulations unrelated to death, coalitional challenges, or uncertaintyevoked worldview defense. These results are discussed as they inform evolutionary interpretations of worldview defense and future investigations of the influence of unconscious alarm on judgment.