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

Superlinear and sublinear urban scaling in geographical network model of the city

Using a geographical scale-free network to describe relations between people in a city, we explain both superlinear and sublinear allometric scaling of urban indicators that quantify activities or performances of the city. The urban indicator $Y(N)$ of a city with the population size $N$ is analytically calculated by summing up all individual activities produced by person-to-person relationships. Our results show that the urban indicator scales superlinearly with the population, namely, $Y(N)\propto N^{\beta}$ with $\beta>1$ if $Y(N)$ represents a creative productivity and the indicator scales sublinearly ($\beta<1$) if $Y(N)$ is related to the degree of infrastructure development. These coincide with allometric scaling observed in real-world urban indicators. We also show how the scaling exponent $\beta$ depends on the strength of the geographical constraint in the network formation.Comment: 9 pages, 5 figure

Possible direct method to determine the radius of a star from the spectrum of gravitational wave signals

We computed the spectrum of gravitational waves from a dust disk star of radius R inspiraling into a Kerr black hole of mass M and specific angular momentum a. We found that when R is much larger than the wave length of the quasinormal mode, the spectrum has several peaks and the separation of peaks $\Delta\omega$ is proportional to $R^{-1}$ irrespective of M and a. This suggests that the radius of the star in coalescing binary black hole - star systems may be determined directly from the observed spectrum of gravitational wave. This also suggests that the spectrum of the radiation may give us important information in gravitational wave astronomy as in optical astronomy.Comment: 4 pages with 3 eps figures, revtex.sty, accepted for publication in Phys. Rev. Let

Dynamic black holes through gravitational collapse: Analysis of multipole moment of the curvatures on the horizon

We have investigated several properties of rapidly rotating dynamic black holes generated by gravitational collapse of rotating relativistic stars. At present, numerical simulations of the binary black hole merger are able to produce a Kerr black hole of J_final / M_final^2 up to = 0.91, of gravitational collapse from uniformly rotating stars up to J_final / M_final^2 ~ 0.75, where J_final is the total angular momentum and M_final the total gravitational mass of the hole. We have succeeded in producing a dynamic black hole of spin J_final / M_final^2 ~ 0.95 through the collapse of differentially rotating relativistic stars. We have investigated those dynamic properties through diagnosing multipole moment of the horizon, and found the following two features. Firstly, two different definitions of the angular momentum of the hole, the approximated Killing vector approach and dipole moment of the current multipole approach, make no significant difference to our computational results. Secondly, dynamic hole approaches a Kerr by gravitational radiation within the order of a rotational period of an equilibrium star, although the dynamic hole at the very forming stage deviates quite far from a Kerr. We have also discussed a new phase of quasi-periodic waves in the gravitational waveform after the ringdown in terms of multipole moment of the dynamic hole.Comment: 13 pages with 19 figures, revtex4-1.cls. Accepted for publication in the Physical Review

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