Stroke impact on mortality and psychologic morbidity within the Childhood Cancer Survivor Study.

BackgroundPoor socioeconomic and health-related quality of life (HRQOL) outcomes in survivors of childhood cancer can lead to distress and overall negatively impact the lives of these individuals. The current report has highlighted the impact of stroke and stroke recurrence on mortality, psychological HRQOL, and socioeconomic outcomes within the Childhood Cancer Survivor Study (CCSS).MethodsThe CCSS is a retrospective cohort study with longitudinal follow-up concerning survivors of pediatric cancer who were diagnosed between 1970 and 1986. Mortality rates per 100 person-years were calculated across 3 periods: 1) prior to stroke; 2) after first stroke and before recurrent stroke; and 3) after recurrent stroke. Socioeconomic outcomes, the standardized Brief Symptoms Inventory-18, the Medical Outcomes Study 36-Item Short Form Health Survey, and the CCSS-Neurocognitive Questionnaire also were assessed.ResultsAmong 14,358 participants (median age, 39.7 years), 224 had a stroke after their cancer diagnosis (single stroke in 161 patients and recurrent stroke in 63 patients). Based on 2636 deaths, all-cause late mortality rates were 0.70 (95% CI, 0.68-0.73) prior to stroke, 1.03 (95% CI, 0.73-1.46) after the first stroke, and 2.42 (95% CI, 1.48-3.94) after the recurrent stroke. Among 7304 survivors, those with stroke were more likely to live with a caregiver (single stroke odds ratio [OR], 2.3 [95% CI, 1.4-3.8]; and recurrent stroke OR, 5.3 [95% CI, 1.7-16.8]) compared with stroke-free survivors. Stroke negatively impacted task efficiency (single stroke OR, 2.4 [95% CI, 1.4-4.1] and recurrent stroke OR, 3.3 [95% CI, 1.1-10.3]) and memory (single stroke OR, 2.1 [95% CI, 1.2-3.7]; and recurrent stroke OR, 3.5 [95% CI, 1.1-10.5]).ConclusionsStroke and stroke recurrence are associated with increased mortality and negatively impact HRQOL measures in survivors of pediatric cancer

Bioprocess characterization at the micro-scale: Optical sensor integration in a novel capillary-wave micro-bioreactor

Due to the high demand of new biopharmaceuticals and bioproducts, the development of new cultivation platforms for high-throughput screenings, cell-based assays and bioprocess development is of high interest. Therefore, micro-bioreactors (MBRs) are a promising alternative to conventional cultivation platforms like shake flasks due to their minimal volume, sensor integration and high ability for automatization and parallelization. Especially, MBRs with a volume below 10 µL can reduce the amount of needed testing substances for cell-based assays, which is advantageous mostly for testing new biopharmaceuticals with limited availability. However, characterization of a cell culture in the lower micro-liter scale is challenging due to the limited space and the insufficient volume for sampling and offline analysis. Optical sensors are one suitable possibility to close this gap. Therefore, a novel capillary-wave micro-bioreactor (cwMBR) with a working volume of 7 µL and optical sensors for biomass, glucose, oxygen, pH and fluorescence intensity measurement was developed. Please click Additional Files below to see the full abstract

A Differentially Private Weighted Empirical Risk Minimization Procedure and its Application to Outcome Weighted Learning

It is commonplace to use data containing personal information to build predictive models in the framework of empirical risk minimization (ERM). While these models can be highly accurate in prediction, results obtained from these models with the use of sensitive data may be susceptible to privacy attacks. Differential privacy (DP) is an appealing framework for addressing such data privacy issues by providing mathematically provable bounds on the privacy loss incurred when releasing information from sensitive data. Previous work has primarily concentrated on applying DP to unweighted ERM. We consider an important generalization to weighted ERM (wERM). In wERM, each individual's contribution to the objective function can be assigned varying weights. In this context, we propose the first differentially private wERM algorithm, backed by a rigorous theoretical proof of its DP guarantees under mild regularity conditions. Extending the existing DP-ERM procedures to wERM paves a path to deriving privacy-preserving learning methods for individualized treatment rules, including the popular outcome weighted learning (OWL). We evaluate the performance of the DP-wERM application to OWL in a simulation study and in a real clinical trial of melatonin for sleep health. All empirical results demonstrate the viability of training OWL models via wERM with DP guarantees while maintaining sufficiently useful model performance. Therefore, we recommend practitioners consider implementing the proposed privacy-preserving OWL procedure in real-world scenarios involving sensitive data.Comment: 24 pages and 2 figures for the main manuscript, 5 pages and 2 figures for the supplementary material

PRAS40 suppresses atherogenesis through inhibition of mTORC1-dependent pro-inflammatory signaling in endothelial cells

Endothelial pro-inflammatory activation plays a pivotal role in atherosclerosis, and many pro-inflammatory and atherogenic signals converge upon mechanistic target of rapamycin (mTOR). Inhibitors of mTOR complex 1 (mTORC1) reduced atherosclerosis in preclinical studies, but side effects including insulin resistance and dyslipidemia limit their clinical use in this context. Therefore, we investigated PRAS40, a cell type-specific endogenous modulator of mTORC1, as alternative target. Indeed, we previously found PRAS40 gene therapy to improve metabolic profile; however, its function in endothelial cells and its role in atherosclerosis remain unknown. Here we show that PRAS40 negatively regulates endothelial mTORC1 and pro-inflammatory signaling. Knockdown of PRAS40 in endothelial cells promoted TNFα-induced mTORC1 signaling, proliferation, upregulation of inflammatory markers and monocyte recruitment. In contrast, PRAS40-overexpression blocked mTORC1 and all measures of pro-inflammatory signaling. These effects were mimicked by pharmacological mTORC1-inhibition with torin1. In an in vivo model of atherogenic remodeling, mice with induced endothelium-specific PRAS40 deficiency showed enhanced endothelial pro-inflammatory activation as well as increased neointimal hyperplasia and atherosclerotic lesion formation. These data indicate that PRAS40 suppresses atherosclerosis via inhibition of endothelial mTORC1-mediated pro-inflammatory signaling. In conjunction with its favourable effects on metabolic homeostasis, this renders PRAS40 a potential target for the treatment of atherosclerosis

The Far-Ultraviolet "Continuum" in Protoplanetary Disk Systems I: Electron-Impact H2 and Accretion Shocks

We present deep spectroscopic observations of the classical T Tauri stars DF Tau and V4046 Sgr in order to better characterize two important sources of far-ultraviolet continuum emission in protoplanetary disks. These new Hubble Space Telescope-Cosmic Origins Spectrograph observations reveal a combination of line and continuum emission from collisionally excited H2 and emission from accretion shocks. H2 is the dominant emission in the 1400-1650 A band spectrum of V4046 Sgr, while an accretion continuum contributes strongly across the far-ultraviolet spectrum of DF Tau. We compare the spectrum of V4046 Sgr to models of electron-impact induced H2 emission to constrain the physical properties of the emitting region, after making corrections for attenuation within the disk. We find reasonable agreement with the broad spectral characteristics of the H2 model, implying N(H2) ~ 10^{18} cm^{-2}, T(H2) = 3000^{+1000}_{-500} K, and a characteristic electron energy in the range of ~ 50 - 100 eV. We propose that self-absorption and hydrocarbons provide the dominant attenuation for H2 line photons originating within the disk. For both DF Tau and V4046 Sgr, we find that a linear fit to the far-UV data can reproduce near-UV/optical accretion spectra. We discuss outstanding issues concerning how these processes operate in protostellar/protoplanetary disks, including the effective temperature and absolute strength of the radiation field in low-mass protoplanetary environments. We find that the 912-2000A continuum in low-mass systems has an effective temperature of ~10^{4} K with fluxes 10^{5-7} times the interstellar level at 1 AU.Comment: 14 pages, 8 figures, 3 tables. ApJ, accepte

The Distance to NGC 2264

We determine the distance to the open cluster NGC 2264 using a statistical analysis of cluster member inclinations. We derive distance-dependent values of sin i (where i is the inclination angle) for 97 stars in NGC 2264 from the rotation periods, luminosities, effective temperatures, and projected equatorial rotation velocities, v sin i, measured for these stars. We have measured 96 of the v sin i values in our sample by analyzing high-resolution spectra with a cross-correlation technique. We model the observed distribution of sin i for the cluster by assuming that member stars have random axial orientations and by adopting prescriptions for the measurement errors in our sample. By adjusting the distance assumed in the observed sin i distribution until it matches the modeled distribution, we obtain a best-fit distance for the cluster. We find the data to be consistent with a distance to NGC 2264 of 913 pc. Quantitative tests of our analysis reveals uncertainties of 40 and 110 pc due to sampling and systematic effects, respectively. This distance estimate suggests a revised age for the cluster of 1.5 Myrs, although more detailed investigations of the full cluster membership are required to draw strong conclusions.Comment: 12 pages, 11 figure

The Angular Momentum Content and Evolution of Class I and Flat-Spectrum Protostars

We report on the angular momentum content of heavily embedded protostars based on our analysis of the projected rotation velocities (v sin i s) of 38 Class I/flat spectrum young stellar objects presented by Doppmann et al (2005). After correcting for projection effects, we find that infrared-selected Class I/flat spectrum objects rotate significantly more quickly (median equatorial rotation velocity ~ 38 km/sec) than Classical T Tauri stars (CTTSs; median equatorial rotation velocity ~ 18 km/sec) in the Rho Ophiuchi and Taurus-Aurigae regions. The detected difference in rotation speeds between Class I/flat spectrum sources and CTTSs proves difficult to explain without some mechanism which transfers angular momentum out of the protostar between the two phases. Assuming Class I/flat spectrum sources possess physical characteristics (M_*,R_*,B_*) typical of pre-main sequence stars, fully disk locked Class I objects should have co-rotation radii within their protostellar disks that match well (within 30%) with the predicted magnetic coupling radii of Shu et al (1994). The factor of two difference in rotation rates between Class I/flat spectrum and CTTS sources, when interpreted in the context of disk locking models, also imply a factor of 5 or greater difference in mass accretion rates between the two phases.Comment: 13 pages, 6 figures. Accepted for publication in the Astronomical Journal (tentatively for June 2005 edition

Characterizing CO Fourth Positive Emission in Young Circumstellar Disks

Carbon Monoxide is a commonly used IR/sub-mm tracer of gas in protoplanetary disks. We present an analysis of ultraviolet CO emission in {HST}-COS spectra for 12 Classical T Tauri stars. Several ro-vibrational bands of the CO A^1\Pi - X^1\Sigma^+ (Fourth Positive) electronic transition system are spectrally resolved from emission of other atoms and H_2. The CO A^1\Pi v'=14 state is populated by absorption of Ly\alpha photons, created at the accretion column on the stellar surface. For targets with strong CO emission, we model the Ly\alpha radiation field as an input for a simple fluorescence model to estimate CO rotational excitation temperatures and column densities. Typical column densities range from N_{CO} = 10^{18} - 10^{19} cm^{-2}. Our measured excitation temperatures are mostly below T_{CO} = 600 K, cooler than typical M-band CO emission. These temperatures and the emission line widths imply that the UV emission originates in a different population of CO than that which is IR-emitting. We also find a significant correlation between CO emission and the disk accretion rate M_{acc} and age. Our analysis shows that ultraviolet CO emission can be a useful diagnostic of CTTS disk gas