Red Blood Cell Transfusion Thresholds for Anemia of Prematurity

Anemia of prematurity affects the majority of preterm infants, particularly extremely low birthweight infants. Anemia of prematurity arises from both innate and iatrogenic causes and results in more than 80% of extremely preterm infants receiving red blood cell transfusions during the first month after birth. Multiple randomized controlled trials were conducted to evaluate the effect of using lower versus higher transfusion thresholds based on hemoglobin levels. These trials showed no difference in the primary outcome of neurodevelopmental impairment at 2 years of age between lower and higher thresholds. However, some uncertainties about transfusion thresholds remain. This review elaborates the following: 1) the etiology, prevention, and treatment of anemia of prematurity with a focus on red blood cell transfusions, 2) the history of randomized controlled trials on the treatment of anemia of prematurity, and 3) limitations of the evidence and remaining questions about thresholds for red blood cell transfusions in preterm infants

Trick or Heat? Manipulating Critical Temperature-Based Control Systems Using Rectification Attacks

Temperature sensing and control systems are widely used in the closed-loop control of critical processes such as maintaining the thermal stability of patients, or in alarm systems for detecting temperature-related hazards. However, the security of these systems has yet to be completely explored, leaving potential attack surfaces that can be exploited to take control over critical systems. In this paper we investigate the reliability of temperature-based control systems from a security and safety perspective. We show how unexpected consequences and safety risks can be induced by physical-level attacks on analog temperature sensing components. For instance, we demonstrate that an adversary could remotely manipulate the temperature sensor measurements of an infant incubator to cause potential safety issues, without tampering with the victim system or triggering automatic temperature alarms. This attack exploits the unintended rectification effect that can be induced in operational and instrumentation amplifiers to control the sensor output, tricking the internal control loop of the victim system to heat up or cool down. Furthermore, we show how the exploit of this hardware-level vulnerability could affect different classes of analog sensors that share similar signal conditioning processes. Our experimental results indicate that conventional defenses commonly deployed in these systems are not sufficient to mitigate the threat, so we propose a prototype design of a low-cost anomaly detector for critical applications to ensure the integrity of temperature sensor signals.Comment: Accepted at the ACM Conference on Computer and Communications Security (CCS), 201

Diaspores and related hydroxides' Spectral-compositional properties and implications for Mars

Differences in spectral reflectance properties (0.3-26 μm) of a suite of metal hydroxides (gibbsite, böhmite, diaspore, goethite, and manganite) have been found to be a function of both structural and compositional differences between these minerals. The properties of the O-H stretching fundamental bands in particular can be used to identify the presence of these minerals and to discriminate isostructural and heteromorphous species. This is due to the fact that the O-H stretching fundamental bands are very intense in these minerals and occur at longer wavelengths than those of other minerals, and also due to the fact that these metal hydroxides lack strong absorption bands at shorter wavelengths. In the case of dimorphous minerals such as böhmite (ϒ-A1O(OH)) and diaspore (α-A1O(OH)), differences in the wavelength positions of O-H stretching fundamental bands can be of the order of 0.1-0.3 μm. Reflectance spectra of metal hydroxide-bearing "ores" (bauxites) and impure samples indicate that accessory phases, in particular iron-bearing minerals, have a more pronounced eftect on spectral reflectance toward shorter wavelengths. Intimate mixtures of diaspore + orthopyroxene indicate that diaspore abundances as low as 5 wt% (or less) can be detected by the appearance of characteristic absorption bands at 3.33 and 3.41μm . This finding has particular relevance to the study of near-infrared spectra of Mars, in that the conditions which favor diaspore formation on the Earth may have also been prevalent early in Mars' history. If diaspore did form on Mars in the past, it is likely to have persisted to the present.This study was supported by the University of Winnipeg through a start-up grant and research grant through the Discretionary Grants Program (to E.A.C.) and a NASA Planetary Geology and Geophysics Program grant (to J.F.B.; NAG5-4333This study was supported by the University of Winnipeg through a start-up grant and research grant through the Discretionary 'Grants Program (to E.A.C.) and a NASA Planetary Geology and Geophysics Program grant (to J.F.B.; NAG5-433

Advantages of Bayesian monitoring methods in deciding whether and when to stop a clinical trial: an example of a neonatal cooling trial.

BackgroundDecisions to stop randomized trials are often based on traditional P value thresholds and are often unconvincing to clinicians. To familiarize clinical investigators with the application and advantages of Bayesian monitoring methods, we illustrate the steps of Bayesian interim analysis using a recent major trial that was stopped based on frequentist analysis of safety and futility.MethodsWe conducted Bayesian reanalysis of a factorial trial in newborn infants with hypoxic-ischemic encephalopathy that was designed to investigate whether outcomes would be improved by deeper (32 °C) or longer cooling (120 h), as compared with those achieved by standard whole body cooling (33.5 °C for 72 h). Using prior trial data, we developed neutral and enthusiastic prior probabilities for the effect on predischarge mortality, defined stopping guidelines for a clinically meaningful effect, and derived posterior probabilities for predischarge mortality.ResultsBayesian relative risk estimates for predischarge mortality were closer to 1.0 than were frequentist estimates. Posterior probabilities suggested increased predischarge mortality (relative risk > 1.0) for the three intervention groups; two crossed the Bayesian futility threshold.ConclusionsBayesian analysis incorporating previous trial results and different pre-existing opinions can help interpret accruing data and facilitate informed stopping decisions that are likely to be meaningful and convincing to clinicians, meta-analysts, and guideline developers.Trial registrationClinicalTrials.gov NCT01192776 . Registered on 31 August 2010

The Rise of Massive Red Galaxies: the color-magnitude and color-stellar mass diagrams for z < ~2 from the MUltiwavelength Survey by Yale-Chile (MUSYC)

We present the color-magnitude and color-stellar mass diagrams for galaxies with z_phot < ~2, based on a K < 22 (AB) catalog of the Extended Chandra Deep Field South (ECDFS) from the MUltiwavelength Survey by Yale-Chile (MUSYC). Our main sample of 7840 galaxies contains 1297 M_* > 10^11 M_Sol galaxies in the range 0.2 < z_phot < 1.8. We show empirically that this catalog is approximately complete for M_* > 10^11 M_Sol galaxies for z_phot < 1.8. For this mass-limited sample, we show that the locus of the red sequence color-stellar mass relation evolves as Del(u-r) ~ (-0.44+/-0.02) z_phot for z_phot ~1.3, however, we are no longer able to reliably distinguish red and blue subpopulations from the observed color distribution; we show that this would require much deeper near infrared data. At 1.5 < z_phot 10^11 M_Sol galaxies is ~50% of the local value, with a red fraction of ~33%. Making a parametric fit to the observed evolution, we find n_tot(z) ~ (1+z_phot)^(-0.52+/-0.12(+/-0.20)). We find stronger evolution in the red fraction: f_red(z) ~ (1+z_phot)^(-1.17+/-0.18(+/-0.21)). Through a series of sensitivity analyses, we show that the most important sources of systematic error are: 1. systematic differences in the analysis of the z~0 and z>>0 samples; 2. systematic effects associated with details of the photometric redshift calculation; and 3. uncertainties in the photometric calibration. With this in mind, we show that our results based on photometric redshifts are consistent with a completely independent analysis which does not require redshift information for individual galaxies. Our results suggest that, at most, 1/5 of local red sequence galaxies with M_* >10^11 M_Sol were already in place at z ~ 2.Comment: Accepted for publication in ApJ. 31 pages in emulateapj format; 18 figues (14 in main text). Additional online data available through http://www.strw.leidenuniv.nl/~ent

Great Circle tidal streams: evidence for a nearly spherical massive dark halo around the Milky Way

An all high-latitude sky survey for cool carbon giant stars in the Galactic halo has revealed 75 such stars, of which the majority are new detections. Of these, more than half are clustered on a Great Circle on the sky which intersects the center of Sagittarius dwarf galaxy (Sgr) and is parallel to its proper motion vector, while many of the remainder are outlying Magellanic Cloud C-stars. A pole-count analysis of the carbon star distribution clearly indicates that the Great Circle stream we have isolated is statistically significant, being a 5-6 sigma over-density. These two arguments strongly support our conclusion that a large fraction of the Halo carbon stars originated in Sgr. The stream orbits the Galaxy between the present location of Sgr, 16 kpc from the Galactic center, and the most distant stream carbon star, at ~60 kpc. It follows neither a polar nor a Galactic plane orbit, so that a large range in both Galactic R and z distances are probed. That the stream is observed as a Great Circle indicates that the Galaxy does not exert a significant torque upon the stream, so the Galactic potential must be nearly spherical in the regions probed by the stream. We present N-body experiments simulating this disruption process as a function of the distribution of mass in the Galactic halo. A likelihood analysis shows that, in the Galactocentric distance range 16 kpc < R < 60 kpc, the dark halo is most likely almost spherical. We rule out, at high confidence levels, the possibility that the Halo is significantly oblate, with isodensity contours of aspect q_m < 0.7. This result is quite unexpected and contests currently popular galaxy formation models. (Abridged)Comment: 26 pages, 13 figures (6 in color, 8 chunky due to PS compression), minor revisions, accepted by Ap

Outcome Prediction in Newborn Infants: Past, Present, and Future

The perinatal and neonatal periods are the periods of considerable organ development and maturation. Perinatal and neonatal illnesses can result in mortality and morbidities that burden families and the healthcare system. Outcome prediction is essential for informing perinatal and intensive care management, prognosis, and post-discharge interventions. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) research databases include hospital and neurodevelopment follow-up outcomes of infants with various underlying diseases and conditions receiving intensive care, providing a unique opportunity to assess outcome risk prediction. The NRN has developed outcome risk prediction tools for use in infants with various diseases and conditions that allow data-driven, transparent discussions to inform family-focused communications and clinical management. This review presents the published neonatal outcome risk prediction research from the NRN, their present clinical utility, and possible future directions for advanced individualized risk prediction