Mass spectrometry based metabolomics comparison of liver grafts from donors after circulatory death (DCD) and donors after brain death (DBD) used in human orthotopic liver transplantation

Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2). Furthermore 6 biopsies from DBD donors prior to the organ donation (T0) were also profiled. Considering DBD and DCD together, significant metabolic differences were discovered between T1 and T2 (688 peaks) that were primarily related to amino acid metabolism, meanwhile T0 biopsies grouped together with T2, denoting the distinctively different metabolic activity of the perfused state. Major metabolic differences were discovered between DCD and DBD during cold-phase (T1) primarily related to glucose, tryptophan and kynurenine metabolism, and in the post-reperfusion phase (T2) related to amino acid and glutathione metabolism. We propose tryptophan/kynurenine and S-adenosylmethionine as possible biomarkers for the previously established higher graft failure of DCD livers, and conclude that the associated pathways should be targeted in more exhaustive and quantitative investigations

Comparison theory and smooth minimal C*-dynamics

We prove that the C*-algebra of a minimal diffeomorphism satisfies Blackadar's Fundamental Comparability Property for positive elements. This leads to the classification, in terms of K-theory and traces, of the isomorphism classes of countably generated Hilbert modules over such algebras, and to a similar classification for the closures of unitary orbits of self-adjoint elements. We also obtain a structure theorem for the Cuntz semigroup in this setting, and prove a conjecture of Blackadar and Handelman: the lower semicontinuous dimension functions are weakly dense in the space of all dimension functions. These results continue to hold in the broader setting of unital simple ASH algebras with slow dimension growth and stable rank one. Our main tool is a sharp bound on the radius of comparison of a recursive subhomogeneous C*-algebra. This is also used to construct uncountably many non-Morita-equivalent simple separable amenable C*-algebras with the same K-theory and tracial state space, providing a C*-algebraic analogue of McDuff's uncountable family of II_1 factors. We prove in passing that the range of the radius of comparison is exhausted by simple C*-algebras.Comment: 30 pages, no figure

Structural Probe of a Glass Forming Liquid: Generalized Compressibility

We introduce a new quantity to probe the glass transition. This quantity is a linear generalized compressibility which depends solely on the positions of the particles. We have performed a molecular dynamics simulation on a glass forming liquid consisting of a two component mixture of soft spheres in three dimensions. As the temperature is lowered (or as the density is increased), the generalized compressibility drops sharply at the glass transition, with the drop becoming more and more abrupt as the measurement time increases. At our longest measurement times, the drop occurs approximately at the mode coupling temperature $T_C$. The drop in the linear generalized compressibility occurs at the same temperature as the peak in the specific heat. By examining the inherent structure energy as a function of temperature, we find that our results are consistent with the kinetic view of the glass transition in which the system falls out of equilibrium. We find no size dependence and no evidence for a second order phase transition though this does not exclude the possibility of a phase transition below the observed glass transition temperature. We discuss the relation between the linear generalized compressibility and the ordinary isothermal compressibility as well as the static structure factor.Comment: 18 pages, Latex, 26 encapsulated postscript figures, revised paper is shorter, to appear in Phys. Rev.

Search for Global Dipole Enhancements in the HiRes-I Monocular Data above 10^{18.5} eV

Several proposed source models for Ultra-High Energy Cosmic Rays (UHECRs) consist of dipole distributions oriented towards major astrophysical landmarks such as the galactic center, M87, or Centaurus A. We use a comparison between real data and simulated data to show that the HiRes-I monocular data for energies above 10^{18.5} eV is, in fact, consistent with an isotropic source model. We then explore methods to quantify our sensitivity to dipole source models oriented towards the Galactic Center, M87, and Centaurus A.Comment: 17 pages, 31 figure

Common and low frequency variants in MERTK are independently associated with multiple sclerosis susceptibility with discordant association dependent upon HLA-DRB1*15:01 status

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients

Observation of the Ankle and Evidence for a High-Energy Break in the Cosmic Ray Spectrum

We have measured the cosmic ray spectrum at energies above $10^{17}$ eV using the two air fluorescence detectors of the High Resolution Fly's Eye experiment operating in monocular mode. We describe the detector, PMT and atmospheric calibrations, and the analysis techniques for the two detectors. We fit the spectrum to models describing galactic and extragalactic sources. Our measured spectrum gives an observation of a feature known as the ``ankle'' near $3\times 10^{18}$ eV, and strong evidence for a suppression near $6\times 10^{19}$ eV.Comment: 14 pages, 9 figures. To appear in Physics Letters B. Accepted versio

International Study of the Epidemiology of Paediatric Trauma : PAPSA Research Study

Objectives: Trauma is a significant cause of morbidity and mortality worldwide. The literature on paediatric trauma epidemiology in low- and middle-income countries (LMICs) is limited. This study aims to gather epidemiological data on paediatric trauma. Methods: This is a multicentre prospective cohort study of paediatric trauma admissions, over 1 month, from 15 paediatric surgery centres in 11 countries. Epidemiology, mechanism of injury, injuries sustained, management, morbidity and mortality data were recorded. Statistical analysis compared LMICs and high-income countries (HICs). Results: There were 1377 paediatric trauma admissions over 31 days; 1295 admissions across ten LMIC centres and 84 admissions across five HIC centres. Median number of admissions per centre was 15 in HICs and 43 in LMICs. Mean age was 7 years, and 62% were boys. Common mechanisms included road traffic accidents (41%), falls (41%) and interpersonal violence (11%). Frequent injuries were lacerations, fractures, head injuries and burns. Intra-abdominal and intra-thoracic injuries accounted for 3 and 2% of injuries. The mechanisms and injuries sustained differed significantly between HICs and LMICs. Median length of stay was 1 day and 19% required an operative intervention; this did not differ significantly between HICs and LMICs. No mortality and morbidity was reported from HICs. In LMICs, in-hospital morbidity was 4.0% and mortality was 0.8%. Conclusion: The spectrum of paediatric trauma varies significantly, with different injury mechanisms and patterns in LMICs. Healthcare structure, access to paediatric surgery and trauma prevention strategies may account for these differences. Trauma registries are needed in LMICs for future research and to inform local policy

Nonstable K-Theory for graph algebras

We compute the monoid V (LK(E)) of isomorphism classes of finitely generated projective modules over certain graph algebras LK(E), and we show that this monoid satisfies the refinement property and separative cancellation. We also show that there is a natural isomorphism between the lattice of graded ideals of LK(E) and the lattice of order-ideals of V (LK(E)). When K is the field C of complex numbers, the algebra LC(E) is a dense subalgebra of the graph C -algebra C (E), and we show that the inclusion map induces an isomorphism between the corresponding monoids. As a consequence, the graph C*-algebra of any row-finite graph turns out to satisfy the stable weak cancellation propert

Study of the B^0 Semileptonic Decay Spectrum at the Upsilon(4S) Resonance

We have made a first measurement of the lepton momentum spectrum in a sample of events enriched in neutral B's through a partial reconstruction of B0 --> D*- l+ nu. This spectrum, measured with 2.38 fb**-1 of data collected at the Upsilon(4S) resonance by the CLEO II detector, is compared directly to the inclusive lepton spectrum from all Upsilon(4S) events in the same data set. These two spectra are consistent with having the same shape above 1.5 GeV/c. From the two spectra and two other CLEO measurements, we obtain the B0 and B+ semileptonic branching fractions, b0 and b+, their ratio, and the production ratio f+-/f00 of B+ and B0 pairs at the Upsilon(4S). We report b+/b0=0.950 (+0.117-0.080) +- 0.091, b0 = (10.78 +- 0.60 +- 0.69)%, and b+ = (10.25 +- 0.57 +- 0.65)%. b+/b0 is equivalent to the ratio of charged to neutral B lifetimes, tau+/tau0.Comment: 14 page, postscript file also available at http://w4.lns.cornell.edu/public/CLN