Accelerated Calvarial Healing in Mice Lacking Toll-Like Receptor 4

The bone and immune systems are closely interconnected. The immediate inflammatory response after fracture is known to trigger a healing cascade which plays an important role in bone repair. Toll-like receptor 4 (TLR4) is a member of a highly conserved receptor family and is a critical activator of the innate immune response after tissue injury. TLR4 signaling has been shown to regulate the systemic inflammatory response induced by exposed bone components during long-bone fracture. Here we tested the hypothesis that TLR4 activation affects the healing of calvarial defects. A 1.8 mm diameter calvarial defect was created in wild-type (WT) and TLR4 knockout (TLR4-/-) mice. Bone healing was tested using radiographic, histologic and gene expression analyses. Radiographic and histomorphometric analyses revealed that calvarial healing was accelerated in TLR4-/- mice. More bone was observed in TLR4-/- mice compared to WT mice at postoperative days 7 and 14, although comparable healing was achieved in both groups by day 21. Bone remodeling was detected in both groups on postoperative day 28. In TLR4-/- mice compared to WT mice, gene expression analysis revealed that higher expression levels of IL-1β, IL-6, TNF-α,TGF-β1, TGF-β3, PDGF and RANKL and lower expression level of RANK were detected at earlier time points (≤ postoperative 4 days); while higher expression levels of IL-1β and lower expression levels of VEGF, RANK, RANKL and OPG were detected at late time points (> postoperative 4 days). This study provides evidence of accelerated bone healing in TLR4-/- mice with earlier and higher expression of inflammatory cytokines and with increased osteoclastic activity. Further work is required to determine if this is due to inflammation driven by TLR4 activation. © 2012 Wang et al

Not Just Full of Hot Air: Hyperbaric Oxygen Therapy Increases Survival in Cases of Necrotizing Soft Tissue Infections

INTRODUCTION: The utility of hyperbaric oxygen therapy (HBOT) in the treatment for necrotizing soft tissue infections (NSTI) has not been proven. Previous studies have been subject to significant selection bias since HBOT is not universally available at all medical centers and there is often considerable delay associated with its initiation. We examined the utility of HBOT for the treatment of NSTI in the modern era by isolating centers that have their own HBOT facilities. METHODS: We queried all centers in the University Health Consortium (UHC) database from 2008 to 2010 that have their own HBOT facilities (N=14). Cases of NSTI were identified by ICD-9 diagnosis codes, which included Fournier’s gangrene (608.83), necrotizing fascitis (728.86), and gas gangrene (040.0). HBOT treatment status was identified by the presence (HBOT) or absence (CONTROL) of ICD-9 procedure code (93.95). We then risk stratified and matched our cohort by UHC’s validated severity of illness (SOI) score. Comparisons were then made using univariate tests of association and multivariable logistic regression. RESULTS: There were 1,583 NSTI cases at the 14 HBOT-capable centers. 117 (7%) cases were treated with HBOT. Risk stratified univariate outcomes are summarized in the table. There was no difference between HBOT and CONTROL groups in hospital length of stay (LOS), direct cost, complications, and mortality across the three less severe SOI classes (minor, moderate, and major). However, for extreme SOI the HBOT group had fewer complications (45% vs. 66%; p CONCLUSION: At HBOT capable centers, receiving HBOT was associated with a significant survival benefit. HBOT in conjunction with current practices for the treatment of NSTI can be both a cost effective and life saving therapy

Science data quality assessment for the Large Synoptic Survey Telescope

LSST will have a Science Data Quality Assessment (SDQA) subsystem for the assessment of the data products that will be produced during the course of a 10 yr survey. The LSST will produce unprecedented volumes of astronomical data as it surveys the accessible sky every few nights. The SDQA subsystem will enable comparisons of the science data with expectations from prior experience and models, and with established requirements for the survey. While analogous systems have been built for previous large astronomical surveys, SDQA for LSST must meet a unique combination of challenges. Chief among them will be the extraordinary data rate and volume, which restricts the bulk of the quality computations to the automated processing stages, as revisiting the pixels for a post-facto evaluation is prohibitively expensive. The identification of appropriate scientific metrics is driven by the breadth of the expected science, the scope of the time-domain survey, the need to tap the widest possible pool of scientific expertise, and the historical tendency of new quality metrics to be crafted and refined as experience grows. Prior experience suggests that contemplative, off-line quality analyses are essential to distilling new automated quality metrics, so the SDQA architecture must support integrability with a variety of custom and community-based tools, and be flexible to embrace evolving QA demands. Finally, the time-domain nature of LSST means every exposure may be useful for some scientific purpose, so the model of quality thresholds must be sufficiently rich to reflect the quality demands of diverse science aims

Incorporation and retention of 99-Tc(IV) in magnetite under high pH conditions

Technetium incorporation into magnetite and its behavior during subsequent oxidation has been investigated at high pH to determine the technetium retention mechanism(s) on formation and oxidative perturbation of magnetite in systems relevant to radioactive waste disposal. Ferrihydrite was exposed to Tc(VII)(aq) containing cement leachates (pH 10.5-13.1), and crystallization of magnetite was induced via addition of Fe(II)aq. A combination of X-ray diffraction (XRD), chemical extraction, and X-ray absorption spectroscopy (XAS) techniques provided direct evidence that Tc(VII) was reduced and incorporated into the magnetite structure. Subsequent air oxidation of the magnetite particles for up to 152 days resulted in only limited remobilization of the incorporated Tc(IV). Analysis of both X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) data indicated that the Tc(IV) was predominantly incorporated into the magnetite octahedral site in all systems studied. On reoxidation in air, the incorporated Tc(IV) was recalcitrant to oxidative dissolution with less than 40% remobilization to solution despite significant oxidation of the magnetite to maghemite/goethite: All solid associated Tc remained as Tc(IV). The results of this study provide the first direct evidence for significant Tc(IV) incorporation into the magnetite structure and confirm that magnetite incorporated Tc(IV) is recalcitrant to oxidative dissolution. Immobilization of Tc(VII) by reduction and incorporation into magnetite at high pH and with significant stability upon reoxidation has clear and important implications for limiting technetium migration under conditions where magnetite is formed including in geological disposal of radioactive wastes

Controls on the fate and speciation of Np(V) during iron (oxyhydr)oxide crystallization

The speciation and fate of neptunium as Np(V)O2+ during the crystallization of ferrihydrite to hematite and goethite was explored in a range of systems. Adsorption of NpO2+ to iron(III) (oxyhydr)oxide phases was reversible and, for ferrihydrite, occurred through the formation of mononuclear bidentate surface complexes. By contrast, chemical extractions and X-ray absorption spectroscopy (XAS) analyses showed the incorporation of Np(V) into the structure of hematite during its crystallization from ferrihydrite (pH 10.5). This occurred through direct replacement of octahedrally coordinated Fe(III) by Np(V) in neptunate-like coordination. Subsequent analyses on mixed goethite and hematite crystallization products (pH 9.5 and 11) showed that Np(V) was incorporated during crystallization. Conversely, there was limited evidence for Np(V) incorporation during goethite crystallization at the extreme pH of 13.3. This is likely due to the formation of a Np(V) hydroxide precipitate preventing incorporation into the goethite particles. Overall these data highlight the complex behavior of Np(V) during the crystallization of iron(III) (oxyhydr)oxides, and demonstrate clear evidence for neptunium incorporation into environmentally important mineral phases. This extends our knowledge of the range of geochemical conditions under which there is potential for long-term immobilization of radiotoxic Np in natural and engineered environments

Single chip camera active pixel sensor

A totally digital single chip camera includes communications to operate most of its structure in serial communication mode. The digital single chip camera include a D/A converter for converting an input digital word into an analog reference signal. The chip includes all of the necessary circuitry for operating the chip using a single pin