Pan-Cancer, Genome-Scale Metabolic Network Analysis of over 10,000 Patients Elucidates Relationship between Metabolism and Survival.

Despite the high variability in cancer biology, cancers nevertheless exhibit cohesive hallmarks across multiple cancer types, notably dysregulated metabolism. Metabolism plays a central role in cancer biology, and shifts in metabolic pathways have been linked to tumor aggressiveness and likelihood of response to therapy. We therefore sought to interrogate metabolism across cancer types and understand how intrinsic modes of metabolism vary within and across indications and how they relate to patient prognosis. We used context specific genome-scale metabolic modeling to simulate metabolism across 10,915 patients from 34 cancer types from The Cancer Genome Atlas and the MMRF-COMMPASS study. We found that cancer metabolism clustered into modes characterized by differential glycolysis, oxidative phosphorylation, and growth rate. We also found that the simulated activities of metabolic pathways are intrinsically prognostic across cancer types, especially tumor growth rate, fatty acid biosynthesis, folate metabolism, oxidative phosphorylation, steroid metabolism, and glutathione metabolism. This work shows the prognostic power of individual patient metabolic modeling across multiple cancer types. Additionally, it shows that analyzing large-scale models of cancer metabolism with survival information provides unique insights into underlying relationships across cancer types and suggests how therapies designed for one cancer type may be repurposed for use in others.

Same people, different group: Social structures are a central component of group concepts.

We examine whether people conceptualize organized groups as having at least two parts: In addition to members (e.g., Alice), they also have social structures (i.e., roles and relations). If groups have members and social structures, then numerically distinct groups can have the same members if they differ in their structures. In Studies 1-4, participants numerically distinguished groups that had the same members when they had different structures. Participants numerically distinguished even when groups had the same function-the same people playing chess together Monday and Tuesday can be numerically distinct groups. In Study 4, we compare clubs to tables, and find that participants numerically distinguish tables by their structures too (i.e., the configuration of their parts) even when they have the same parts (which can be disassembled and then reassembled with ease). In Study 5, we find that participants rate groups as existing in space and time like concrete objects, suggesting that participants represent groups as at least partially concrete, such that groups have at least two parts (their structures and their members). Finally, in Study 6, we show that people will judge the same person as exemplary with respect to one group but condemnable with respect to another-even when those groups have the same members.

Evidence for multiple sources of inductive potential: Occupations and their relations to social institutions.

Several current theories have essences as primary drivers of inductive potential: e.g., people infer dogs share properties because they share essences. We investigated the possibility that people take occupational roles as having robust inductive potential because of a different source: their position in stable social institutions. In Studies 1-4, participants learned a novel property about a target, and then decided whether two new individuals had the property (one with the same occupation, one without). Participants used occupational roles to robustly generalize rights and obligations, functional behaviors, personality traits, and skills. In Studies 5-6, we contrasted occupational roles (via label) with race/gender (via visual face cues). Participants reliably favored occupational roles over race/gender for generalizing rights and obligations, functional behaviors, personality traits, and skills (they favored race/gender for inferring leisure behaviors and physiological properties). Occupational roles supported inferences to the same extent as animal categories (Studies 4 and 6). In Study 7, we examined why members of occupational roles share properties. Participants did not attribute the inductive potential of occupational roles to essences, they attributed it to social institutions. In combination, these seven studies demonstrate that any theory of inductive potential must pluralistically allow for both essences and social institutions to form the basis of inductive potential.

Kindhood and essentialism: Evidence from language.

A large body of existing research suggests that people think very differently about categories that are seen as kinds (e.g., women) and categories that are not seen as kinds (e.g., people hanging out in the park right now). Drawing on work in linguistics, we suggest that people represent these two sorts of categories using fundamentally different representational formats. Categories that are not seen as kinds are simply represented as collections of individuals. By contrast, when it comes to kinds, people have two distinct representations: a representation of a collection of individual people and a representation of the kind itself. The distinction between these two representational formats helps to shed light on otherwise puzzling findings about stereotyping and essentialism. Stereotyping appears to involve a representation of a collection of people, while essentialism involves a representation of a kind itself.

Incidence of adverse outcomes associated with gestational diabetes mellitus in low- and middle-income countries.

BACKGROUND: The contribution of medical conditions such as diabetes mellitus to maternal and neonatal ill-health in low- and middle-income countries is not well documented. OBJECTIVES: To ascertain the incidence of adverse outcomes associated with gestational diabetes mellitus (GDM) in these countries. SEARCH STRATEGY: Electronic databases were searched between 1990 and 2011. SELECTION CRITERIA: Observational, experimental, and quasi-experimental studies reporting adverse outcomes associated with GDM in mothers and their infants in low- and middle-income countries were included. DATA COLLECTION AND ANALYSIS: Titles and abstracts were screened, and full-text articles were independently assessed by at least 2 reviewers. Characteristics of studies were tabulated and quality assessment performed. Median and interquartile range (IQR) were computed for each adverse outcome. MAIN RESULTS: 25 articles were included from an initial 1282 citations. High median incidences of cesarean (43.8%; IQR, 34.9%-65.9%), neonatal jaundice (17.1%; IQR, 8.5%-22.9%), and macrosomia (17.0%; IQR, 8.3%-32.5%) were reported in women with GDM. CONCLUSIONS: The high incidence of some complications of GDM is a concern and may indicate poorer care for women with GDM in low-resource settings. The wide IQRs found indicate uncertainty about the burden of GDM in these settings.