Reversibility and Improved Hydrogen Release of Magnesium Borohydride

Desorption and subsequent rehydrogenation of Mg(BH_4)_2 with and without 5 mol % TiF_3 and ScCl_3 have been investigated. Temperature programmed desorption (TPD) experiments revealed a significant increase in the rate of desorption as well as the weight percentage of hydrogen released with additives upon heating to 300 °C. Stable Mg(B_xH_y)_n intermediates were formed at 300 °C, whereas MgB_2 was the major product when heated to 600 °C. These samples were then rehydrogenated and subsequently characterized with powder X-ray diffraction (pXRD), Raman, and NMR spectroscopy. We confirmed significant conversion of MgB_2 to fully hydrogenated Mg(BH_4)_2 for the sample with and without additives. TPD and NMR studies revealed that the additives have a significant effect on the reaction pathway during both dehydrogenation and rehydrogenation reactions. This work suggests that the use of additives may provide a valid pathway for improving intrinsic hydrogen storage properties of magnesium borohydride

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Activity-Based Funding of Hospitals and Its Impact on Mortality, Readmission, Discharge Destination, Severity of Illness, and Volume of Care: A Systematic Review and Meta-Analysis

Background: Activity-based funding (ABF) of hospitals is a policy intervention intended to re-shape incentives across health systems through the use of diagnosis-related groups. Many countries are adopting or actively promoting ABF. We assessed the effect of ABF on key measures potentially affecting patients and health care systems: mortality (acute and post-acute care); readmission rates; discharge rate to post-acute care following hospitalization; severity of illness; volume of care.     Methods: We undertook a systematic review and meta-analysis of the worldwide evidence produced since 1980. We included all studies reporting original quantitative data comparing the impact of ABF versus alternative funding systems in acute care settings, regardless of language. We searched 9 electronic databases (OVID MEDLINE, EMBASE, OVID Healthstar, CINAHL, Cochrane CENTRAL, Health Technology Assessment, NHS Economic Evaluation Database, Cochrane Database of Systematic Reviews, and Business Source), hand-searched reference lists, and consulted with experts. Paired reviewers independently screened for eligibility, abstracted data, and assessed study credibility according to a pre-defined scoring system, resolving conflicts by discussion or adjudication.     Results: Of 16,565 unique citations, 50 US studies and 15 studies from 9 other countries proved eligible (i.e. Australia, Austria, England, Germany, Israel, Italy, Scotland, Sweden, Switzerland). We found consistent and robust differences between ABF and no-ABF in discharge to post-acute care, showing a 24% increase with ABF (pooled relative risk = 1.24, 95% CI 1.18–1.31). Results also suggested a possible increase in readmission with ABF, and an apparent increase in severity of illness, perhaps reflecting differences in diagnostic coding. Although we found no consistent, systematic differences in mortality rates and volume of care, results varied widely across studies, some suggesting appreciable benefits from ABF, and others suggesting deleterious consequences.     Conclusions: Transitioning to ABF is associated with important policy- and clinically-relevant changes. Evidence suggests substantial increases in admissions to post-acute care following hospitalization, with implications for system capacity and equitable access to care. High variability in results of other outcomes leaves the impact in particular settings uncertain, and may not allow a jurisdiction to predict if ABF would be harmless. Decision-makers considering ABF should plan for likely increases in post-acute care admissions, and be aware of the large uncertainty around impacts on other critical outcomes

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Coherent Vibrational Oscillations Of Hollow Gold Nanospheres

Ultrafast pump-probe spectroscopy was used to characterize coherent vibrational oscillations of hollow gold nanospheres (HGNs) composed of a polycrystalline Au shell and a hollow, solvent-filled interior. Different HGN samples show heavily damped radial breathing mode oscillations with a period ranging from 28 ± 2 to 33 ± 3 ps. We theoretically modeled the oscillation period of HGNs while varying both the shell thicknesses and particle radii. Creation of a hollow cavity was predicted to increase the oscillation period relative to solid gold nanoparticles, and this result was verified experimentally. Our theoretical predictions of oscillation period are significantly lower than the experimental measurements. We propose that this difference is due to the polycrystalline nature of HGNs that softens the vibration of the lattice compared with a single-crystalline shell. We compare our system to solid Au nanoparticles and Au nanoparticle aggregates and find a general trend of longer oscillation period with increasing particle polycrystallinity. © 2011 American Chemical Society

Optical Properties And Persistent Spectral Hole Burning Of Near Infrared-Absorbing Hollow Gold Nanospheres

We report on the characteristics and mechanism of persistent spectral hole burning of hollow gold nanospheres (HGNs) with near IR (NIR) surface plasmon resonance (SPR) absorption induced by femtosecond (fs) laser pulses. The HGNs were exposed to pulsed laser light at 810 nm, on resonance with their absorption band, at various laser powers while the total photon flux incident on the samples was kept constant. Depletion of HGNs responsible for 830 nm absorption was observed while simultaneous growth of bluer-absorbing HGNs, solid gold nanoparticles (AuNPs), or a mixture thereof was observed. This occurred only with fs pulsed laser irradiation and did not occur with continuous wave (CW) laser irradiation. Based on combined UV-vis spectroscopy and transmission electron microscopy data, the mechanism behind the persistent hole burning with fs laser irradiation is proposed to involve two possible processes: (i) conversion of NIR-absorbing HGNs to bluer-absorbing HGNs, and (ii) breakdown of NIR-absorbing HGNs into solid AuNPs directly. The branching ratio between these two processes depends on the peak power of the fs laser pulses with higher peak power favoring the second process. This hole-burning study is useful for understanding and exploring the potential use of HGNs in drug delivery with a laser as a trigger for release. In conjunction, theoretical calculations have been carried out to gain further insight into the optical absorption of HGNs, especially in terms of how the extinction coefficient depends on the structure of the HGNs in comparison to solid AuNPs. One interesting finding is that HGNs with thicker shells not only absorb at bluer wavelengths, but also have lower absorption as well as extinction coefficient. An HGN with the same outer diameter as a solid AuNP has a substantially larger extinction coefficient. These theoretical findings are supported by experimental results. The enhanced extinction coefficient is advantageous for applications such as photothermal ablation therapy (PTA) for cancer treatment. The dependence of the absorption coefficients on the HGN structure is also important for interpreting the hole-burning results that rely on changes in spectral position as well as intensity. © 2010 American Chemical Society

Understanding and Mitigating the Effects of Stable Dodecahydro-<i>closo</i>-dodecaborate Intermediates on Hydrogen-Storage Reactions

Alkali metal borohydrides can reversibly store hydrogen; however, the materials display poor cyclability, oftentimes linked to the occurrence of stable <i>closo</i>-polyborate intermediate species. In an effort to understand the role of such intermediates on the hydrogen storage properties of metal borohydrides, several alkali metal dodecahydro-<i>closo</i>-dodecaborate salts were isolated in anhydrous form and characterized by diffraction and spectroscopic techniques. Mixtures of Li₂B₁₂H₁₂, Na₂B₁₂H₁₂, and K₂B₁₂H₁₂ with the corresponding alkali metal hydrides were subjected to hydrogenation conditions known to favor partial or full reversibility in metal borohydrides. The stoichiometric mixtures of MH and M₂B₁₂H₁₂ salts form the corresponding metal borohydrides MBH₄ (M = Li, Na, K) in almost quantitative yield at 100 MPa H₂ and 500 °C. In addition, stoichiometric mixtures of Li₂B₁₂H₁₂ and MgH₂ were found to form MgB₂ at 500 °C and above upon desorption in vacuum. The two destabilization strategies outlined above suggest that metal polyhydro-<i>closo</i>-polyborate species can be converted into the corresponding metal borohydrides or borides, albeit under rather harsh conditions of hydrogen pressure and temperature