Analyzing Competing Risk Data Using the R timereg Package

In this paper we describe flexible competing risks regression models using the comp.risk() function available in the timereg package for R based on Scheike et al. (2008). Regression models are specified for the transition probabilities, that is the cumulative incidence in the competing risks setting. The model contains the Fine and Gray (1999) model as a special case. This can be used to do goodness-of-fit test for the subdistribution hazardsâ proportionality assumption (Scheike and Zhang 2008). The program can also construct confidence bands for predicted cumulative incidence curves. We apply the methods to data on follicular cell lymphoma from Pintilie (2007), where the competing risks are disease relapse and death without relapse. There is important non-proportionality present in the data, and it is demonstrated how one can analyze these data using the flexible regression models.

Elevated expression of human bHLH factor ATOH7 accelerates cell cycle progression of progenitors and enhances production of avian retinal ganglion cells.

The production of vertebrate retinal projection neurons, retinal ganglion cells (RGCs), is regulated by cell-intrinsic determinants and cell-to-cell signaling events. The basic-helix-loop-helix (bHLH) protein Atoh7 is a key neurogenic transcription factor required for RGC development. Here, we investigate whether manipulating human ATOH7 expression among uncommitted progenitors can promote RGC fate specification and thus be used as a strategy to enhance RGC genesis. Using the chicken retina as a model, we show that cell autonomous expression of ATOH7 is sufficient to induce precocious RGC formation and expansion of the neurogenic territory. ATOH7 overexpression among neurogenic progenitors significantly enhances RGC production at the expense of reducing the progenitor pool. Furthermore, forced expression of ATOH7 leads to a minor increase of cone photoreceptors. We provide evidence that elevating ATOH7 levels accelerates cell cycle progression from S to M phase and promotes cell cycle exit. We also show that ATOH7-induced ectopic RGCs often exhibit aberrant axonal projection patterns and are correlated with increased cell death during the period of retinotectal connections. These results demonstrate the high potency of human ATOH7 in promoting early retinogenesis and specifying the RGC differentiation program, thus providing insight for manipulating RGC production from stem cell-derived retinal organoids

Analyzing Competing Risk Data Using the R timereg Package

In this paper we describe flexible competing risks regression models using the comp.risk() function available in the timereg package for R based on Scheike et al. (2008). Regression models are specified for the transition probabilities, that is the cumulative incidence in the competing risks setting. The model contains the Fine and Gray (1999) model as a special case. This can be used to do goodness-of-fit test for the subdistribution hazards’ proportionality assumption (Scheike and Zhang 2008). The program can also construct confidence bands for predicted cumulative incidence curves.We apply the methods to data on follicular cell lymphoma from Pintilie (2007), where the competing risks are disease relapse and death without relapse. There is important non-proportionality present in the data, and it is demonstrated how one can analyze these data using the flexible regression models

Kainic Acid-Induced Neurotoxicity: Targeting Glial Responses and Glia-Derived Cytokines

Glutamate excitotoxicity contributes to a variety of disorders in the central nervous system, which is triggered primarily by excessive Ca2+ influx arising from overstimulation of glutamate receptors, followed by disintegration of the endoplasmic reticulum (ER) membrane and ER stress, the generation and detoxification of reactive oxygen species as well as mitochondrial dysfunction, leading to neuronal apoptosis and necrosis. Kainic acid (KA), a potent agonist to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate class of glutamate receptors, is 30-fold more potent in neuro-toxicity than glutamate. In rodents, KA injection resulted in recurrent seizures, behavioral changes and subsequent degeneration of selective populations of neurons in the brain, which has been widely used as a model to study the mechanisms of neurodegenerative pathways induced by excitatory neurotransmitter. Microglial activation and astrocytes proliferation are the other characteristics of KA-induced neurodegeneration. The cytokines and other inflammatory molecules secreted by activated glia cells can modify the outcome of disease progression. Thus, anti-oxidant and anti-inflammatory treatment could attenuate or prevent KA-induced neurodegeneration. In this review, we summarized updated experimental data with regard to the KA-induced neurotoxicity in the brain and emphasized glial responses and glia-oriented cytokines, tumor necrosis factor-α, interleukin (IL)-1, IL-12 and IL-18

The largest virialized dark halo in the universe

Using semi-analytic approach, we present an estimate of the properties of the largest virialized dark halos in the present universe for three different scenarios of structure formation: SCDM, LCDM and OCDM models. The resulting virial mass and temperature increase from the lowest values of $1.6 \times 10^{15}h^{-1}M_{\odot}$ and 9.8 keV in OCDM, the mid-range values of $9.0 \times 10^{15}h^{-1}M_{\odot}$ and 31 keV in LCDM, to the highest values of $20.9 \times 10^{15}h^{-1}M_{\odot}$, 65 keV in SCDM. As compared with the largest virialized object seen in the universe, the richest clusters of galaxies, we can safely rule out the OCDM model. In addition, the SCDM model is very unlikely because of the unreasonably high virial mass and temperature. Our computation favors the prevailing LCDM model in which superclusters may be marginally regarded as dynamically-virialized systems.Comment: 5 pages, Accepted by Int. J. Mod. Phys.