Learning from failure

We study decentralized learning in organizations. Decentralization is captured through a symmetry constraint on agents’ strategies. Among such attainable strategies, we solve for optimal and equilibrium strategies. We model the organization as a repeated game with imperfectly observable actions. A fixed but unknown subset of action profiles are successes and all other action profiles are failures. The game is played until either there is a success or the time horizon is reached. For any time horizon, including infinity, we demonstrate existence of optimal attainable strategies and show that they are Nash equilibria. For some time horizons, we can solve explicitly for the optimal attainable strategies and show uniqueness. The solution connects the learning behavior of agents to the fundamentals that characterize the organization: Agents in the organization respond more slowly to failure as the future becomes more important, the size of the organization increases and the probability of success decreases.Game theory

Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands

Measles causes a transient immune suppression, leading to increased susceptibility to opportunistic infections. In experimentally infected non-human primates (NHPs) measles virus (MV) infects and depletes pre-existing memory lymphocytes, causing immune amnesia. A measles outbreak in the Dutch Orthodox Prote

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Peritoneal, systemic, and distant organ inflammatory responses are reduced by a laparoscopic approach and carbon dioxide vs air

Advantages of laparoscopic surgery have, among other factors, been attributed to a shorter length of abdominal incision and the use of CO2 versus air. An analysis of these factors taking pressure-induced alterations into account is lacking. The objective of the study was to determine the impact of laparoscopy and laparotomy with exposure to CO2 and room air under a similar pressure on local, systemic, and distant organ immune responses. Methods: Twenty piglets were randomized into four groups: CO2 laparoscopy, air laparoscopy, CO2 laparotomy, and air laparotomy. Laparotomy was performed in a sterile balloon pressurized similar to laparoscopy. Peritoneal interleukin-1, interleukin-6, tumor necrosis factor-a, and counts of polymorphnuclear cells (PMNs), and macrophages (MFs) were determined in abdominal lavage fluids at 0, 2, and 48 h. Macrophages were assessed for reactive oxygen species (ROS) production. Systemic responses were gauged by white blood cell count (WBC) and cytokines. Alveolar lavage was performed at 48 h to determine cytokine levels, cell counts, and MF ROS production. Blood, lavage fluids, and mesenteric lymph nodes were tested for bacterial translocation. Results: Regarding the peritoneal response, laparotomy versus laparoscopy when performed with CO2 significantly increased PMN and decreased the percentage of macrophages (%MF) up to 48 h. There was a significant increase in interleukin-6, and there was a fourfold increase in MF ROS production. Similar differences between the procedures were found with exposure to air. The use of air versus CO2 in laparoscopy, but not in laparotomy, resulted in an increase of peritoneal PMN and a decrease of the %MF up to 48 h. Air increased the local interleukin-6 release in both procedures and increased MF ROS production fourfold. Regarding the systemic response, laparotomy produced a significant increase in WBC, which was significantly more pronounced with exposure to air. No alteration of other systemic cytokines was seen. Regarding the pulmonary response, the number of MFs and MF ROS production were significantly increased after air versus CO2 laparoscopy. There were no such differences between the laparotomy groups. Regarding bacterial translocation, no bacteria were cultured from peritoneal fluids, lymphnodes, or blood. Conclusions: Inflammatory responses were reduced by a laparoscopic approach and by exposure to CO2 versus air. Peritoneal responses were affected to a larger degree than systemic parameters. La

Peritoneal, systemic, and distant organ inflammatory responses are reduced by a laparoscopic approach and carbon dioxide vs air

Advantages of laparoscopic surgery have, among other factors, been attributed to a shorter length of abdominal incision and the use of CO2 versus air. An analysis of these factors taking pressure-induced alterations into account is lacking. The objective of the study was to determine the impact of laparoscopy and laparotomy with exposure to CO2 and room air under a similar pressure on local, systemic, and distant organ immune responses. Methods: Twenty piglets were randomized into four groups: CO2 laparoscopy, air laparoscopy, CO2 laparotomy, and air laparotomy. Laparotomy was performed in a sterile balloon pressurized similar to laparoscopy. Peritoneal interleukin-1, interleukin-6, tumor necrosis factor-a, and counts of polymorphnuclear cells (PMNs), and macrophages (MFs) were determined in abdominal lavage fluids at 0, 2, and 48 h. Macrophages were assessed for reactive oxygen species (ROS) production. Systemic responses were gauged by white blood cell count (WBC) and cytokines. Alveolar lavage was performed at 48 h to determine cytokine levels, cell counts, and MF ROS production. Blood, lavage fluids, and mesenteric lymph nodes were tested for bacterial translocation. Results: Regarding the peritoneal response, laparotomy versus laparoscopy when performed with CO2 significantly increased PMN and decreased the percentage of macrophages (%MF) up to 48 h. There was a significant increase in interleukin-6, and there was a fourfold increase in MF ROS production. Similar differences between the procedures were found with exposure to air. The use of air versus CO2 in laparoscopy, but not in laparotomy, resulted in an increase of peritoneal PMN and a decrease of the %MF up to 48 h. Air increased the local interleukin-6 release in both procedures and increased MF ROS production fourfold. Regarding the systemic response, laparotomy produced a significant increase in WBC, which was significantly more pronounced with exposure to air. No alteration of other systemic cytokines was seen. Regarding the pulmonary response, the number of MFs and MF ROS production were significantly increased after air versus CO2 laparoscopy. There were no such differences between the laparotomy groups. Regarding bacterial translocation, no bacteria were cultured from peritoneal fluids, lymphnodes, or blood. Conclusions: Inflammatory responses were reduced by a laparoscopic approach and by exposure to CO2 versus air. Peritoneal responses were affected to a larger degree than systemic parameters. La