Guidelines for analysis and reporting of clinical trials in oncology.

When analyzing and reporting the results of clinical trials, investigators should follow a simple approach. The purpose of a trial is to estimate an effect or treatment difference, which if present would have clinical utility when treating new patients. Procedures or methods that do not facilitate precisely and impartially estimating and reporting the treatment effect are likely to mislead investigators. Most often in clinical trials, investigators are interested in estimates of risk ratios (specifically odds or hazard ratios) between the treatment groups or levels of a prognostic factor. These simple ideas suggest that the most useful results from clinical trials will be estimated risk ratios and their confidence limits. Especially in cancer, where disease progression, recurrence, and death are common events following treatment, estimates of risk difference are very relevant. Hypothesis tests and associated P-values, although often (or exclusively) reported, are of lesser utility because they do not fully summarize the data. These recommendations may be seen by some investigators to be contrary to accepted practice. It is true that they are somewhat contrary to common practice but their general acceptance is evident in many journals and presentations by clinical trial methodologists. Despite some disagreement among statisticians regarding the need for adjustment of analyses for imbalanced prognostic factors, it is helpful to see if treatment effects change after accounting for imbalances. When this occurs, it may be of clinical interest. Although we discourage analyses that exclude any patients who meet the eligibility criteria, some circumstances will require that this be done (e.g., when a patient refuses to participate after randomization). Investigators should report, and emphasize as primary, those analyses that include all eligible patients. It is our hope and belief that analysis and reporting of trial results along the guidelines suggested here will result in impartial and useful information for journal readers

Secure Implementation Experiments: Do Strategy-proof Mechanisms Really Work?

Strategy-proofness, requiring that truth-telling is a dominant strategy, is a standard concept used in social choice theory. Saijo et al. (2003) argue that this concept has serious drawbacks. In particular, many strategy-proof mechanisms have a continuum of Nash equilibria, including equilibria other than dominant strategy equilibria. For only a subset of strategy-proof mechanisms do the set of Nash equilibria and the set of dominant strategy equilibria coincide. For example, this double coincidence occurs in the Groves mechanism when preferences are single-peaked. We report experiments using two strategy-proof mechanisms. One of them has a large number of Nash equilibria, but the other has a unique Nash equilibrium. We found clear differences in the rate of dominant strategy play between the two.Experiment, Laboratory, Secure Implementation, Groves-Clarke, Pivotal, Learning

Secure Implementation Experiments: Do Strategy-proof Mechanisms Really Work?

Strategy-proofness, requiring that truth-telling is a dominant strategy, is a standard concept used in social choice theory. Saijo et al. (2003) argue that this concept has serious drawbacks. In particular, announcing one's true preference may not be a unique dominant strategy, and almost all strategy-proof mechanisms have a continuum of Nash equilibria. For only a subset of strategy-proof mechanisms do the set of Nash equilibria and the set of dominant strategy equilibria coincide. For example, this double coincidence occurs in the Groves mechanism when preferences are single-peaked. We report experiments using two strategy-proof mechanisms where one of them has a large number of Nash equilibria, but the other has a unique Nash equilibrium. We found clear differences in the rate of dominant strategy play between the two.

Secure Implementation Experiments:Do Strategy-proof Mechanisms Really Work?

Strategy-proofness, requiring that truth-telling is a dominant strategy, is a standard concept used in social choice theory. Saijo et al. (2003) argue that this concept has serious drawbacks. In particular, announcing one's true preference may not be a unique dominant strategy, and almost all strategy-proof mechanisms have a continuum of Nash equilibria. For only a subset of strategy-proof mechanisms do the set of Nash equilibria and the set of dominant strategy equilibria coincide. For example, this double coincidence occurs in the Groves mechanism when preferences are single-peaked. We report experiments using two strategy-proof mechanisms where one of them has a large number of Nash equilibria, but the other has a unique Nash equilibrium. We found clear differences in the rate of dominant strategy play between the two. Journal of Economic Literature Classification Number: C92, D71, D78, and H41.

Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia.

Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material.The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimer's and Parkinson's diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in terms of activity and subcellular localization. We demonstrate that counteracting the repressive effect of cIAP2 on caspase-3 activation, using small interfering RNA targeting cIAP2 or a SMAC mimetic such as the BV6 compound, reduced the pro-inflammatory activation of microglia cells and promoted their death. We propose that the different caspase-3 functions in microglia, and potentially other cell types, reside in the active caspase-3 complexes formed. These results also could indicate cIAP2 as a possible therapeutic target to modulate microglia pro-inflammatory activation and associated neurotoxicity observed in neurodegenerative disorders