Identifying Cancer Specific Metabolic Signatures Using Constraint-Based Models

Cancer metabolism differs remarkably from the metabolism of healthy surrounding tissues, and it is extremely heterogeneous across cancer types. While these metabolic differences provide promising avenues for cancer treatments, much work remains to be done in understanding how metabolism is rewired in malignant tissues. To that end, constraint-based models provide a powerful computational tool for the study of metabolism at the genome scale. To generate meaningful predictions, however, these generalized human models must first be tailored for specific cell or tissue sub-types. Here we first present two improved algorithms for (1) the generation of these context-specific metabolic models based on omics data, and (2) Monte-Carlo sampling of the metabolic model ux space. By applying these methods to generate and analyze context-specific metabolic models of diverse solid cancer cell line data, and primary leukemia pediatric patient biopsies, we demonstrate how the methodology presented in this study can generate insights into the rewiring differences across solid tumors and blood cancers

Counterpoint. Early intervention for psychosis risk syndromes: Minimizing risk and maximizing benefit

Background: Malhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis. Method: Response to points of critique. Results: We agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not “extremely difficult”; e) the pattern of progression, although heterogenous, is discernible; f) “psychosis-like symptoms” are common but are not used to identify CHR; and g) on the point described as ‘the real risk,’ CHR diagnosis does not frequently cause harmful stigma. Discussion: Malhi et al.'s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the “real risk” of stigma associated with a CHR “label,” however, our view is that avoiding words like “risk” and “psychosis” reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them

Information and digital literacies; a review of concepts

A detailed literature reviewing, analysing the multiple and confusing concepts around the ideas of information literacy and digital literacy at the start of the millennium. The article was well-received, and is my most highly-cited work, with over 1100 citations

Benefit cost analysis progress report : applications to IDRC impact indicators research

In IDL-1460

Stable carbon isotopes as potential sea-level indicators in salt marshes, North Carolina, USA

We compared the use of δ13C values and C:N ratios from salt-marsh sediments to reconstruct relative sea level (RSL) with an established approach using foraminifera. Analysis of bulk-organic sediment and plant samples collected along transects at two sites in North Carolina, USA demonstrates that sediment δ13C values can be used to distinguish between Spartina alterniflora-dominated low marsh (C photosynthetic pathway, δ13C values from —17.6‰ to 16.1‰) and Juncus roemerianus-dominated high marsh (C 3 photosynthetic pathway, δ13C values from —28.2‰ to —21.8‰) environments. Juncus roemerianus plants undergo little decompositional change in δ13C (average 0.8‰), although there is a clear difference between Spartina alterniflora tissue and bulk-organic sediments (approximately 4‰). C:N ratios on bulk-organic sediment from freshwater upland and salt-marsh environments converge during early diagenesis, rendering them of little use in reconstructing RSL. The utility of δ13C values as a sea-level indicator is limited by the elevational range of C4 plants, making it difficult to recognize salt-marsh subenvironments and improve the precision of RSL reconstructions. Furthermore, Juncus roemerianus-dominated high marsh and freshwater upland sediments cannot be adequately distinguished with δ13C values