Elevated cystatin-C concentration is associated with progression to prediabetes: the Western New York Study

OBJECTIVE – We conducted a nested case-control investigation to examine if elevated baseline concentrations of cystatin-C predicted progression from normoglycaemia to prediabetes over 6 years of follow-up from the Western New York Health Study. RESEARCH DESIGN AND METHODS – 1,455 participants from the Western New York Health Study, free of type 2 diabetes and known cardiovascular disease at baseline (1996-2001), were reexamined in 2002-2004. An incident case of prediabetes was defined as one with fasting glucose below 100 mg/dl at the baseline examination and ≥ 100 mg/dl and ≤ 125 mg/dl at the follow-up examination. All cases (n=91) were matched 1:3 to control participants based upon sex, race/ethnicity and year of study enrollment. All controls had fasting glucose levels < 100 mg/dl at both baseline and follow-up examinations. Cystatin-C concentrations and the urinary albumin to creatinine ratio were measured from frozen (-196 Cº) baseline blood and urine samples. Serum creatinine concentrations were available from the baseline examination. RESULTS –Multivariate conditional logistic regression analyses adjusted for age, baseline glucose level, HOMA-IR, body mass index, hypertension, eGFR, cigarette smoking, and alcohol use revealed a significantly increased risk of progression to prediabetes among those with elevated baseline concentrations of cystatin-C (Odds Ratio, 95% CI: 3.04, 1.34, 6.89) (upper quintile vs. the remainder). Results of secondary analyses that considered hs-CRP, IL-6, E-selectin, or sICAM did not alter these results. CONCLUSIONS - These results suggest that early renal impairment indexed with cystatin-C imparted a three-fold excess risk of progression to prediabetes in this study population. Recent evidence from randomized clinical trials (1,2) among people with prediabetes have provided convincing evidence that early intervention can significantly delay or prevent the progression to type 2 diabetes. The identification of those with prediabetes is assuming greater importance (3) especially in light of the fact that approximately 35 million adults aged 40-74 years old in the United States have prediabetes defined as impaired fasting glucose (4). Microalbuminuria occurs frequently in nondiabetic subjects and places them at increased risk for cardiovascular disease (5-7). The mechanisms behind this observation are poorly understood, however. Albuminuria may reflect underlying vascular damage (8), hypertension (9, 10) endothelial dysfunction (11, 12) and/or low-grade inflammation (13). A large percentage of type 2 individuals pass through a period of prediabetes (14) and may experience early renal dysfunction e.g., a glomerular filtration rate (GFR) above 60 ml/minute per 1.73m2. Currently used estimating equations are poor at identifying early renal impairment and better indices are of great interest (15, 16). Recently, several studies have suggested that cystatin-C levels may be a more sensitive marker of early renal impairment than either albuminuria or serum creatinine concentration (17-20). Therefore, a better understanding of a putative role for cystatin-C in the etiology of prediabetes could shed light on the renal/heart disease connection (21). Given the reported superiority of cystatin C over conventional measures of renal function, we hypothesized that cystatin-C would predict progression to prediabetes independent of serum creatinine or estimated GFR. We also investigated the role of intervening mechanisms including hypertension, insulin resistance, endothelial dysfunction and inflammation

Transport model analysis of particle correlations in relativistic heavy ion collisions at femtometer scales

The pion source as seen through HBT correlations at RHIC energies is investigated within the UrQMD approach. We find that the calculated transverse momentum, centrality, and system size dependence of the Pratt-HBT radii $R_L$ and $R_S$ are reasonably well in line with experimental data. The predicted $R_O$ values in central heavy ion collisions are larger as compared to experimental data. The corresponding quantity $\sqrt{R_O^{2}-R_S^{2}}$ of the pion emission source is somewhat larger than experimental estimates.Comment: 12 pages, 5 figures, to be published in PR

Modifying the Einstein Equations off the Constraint Hypersuface

A new technique is presented for modifying the Einstein evolution equations off the constraint hypersurface. With this approach the evolution equations for the constraints can be specified freely. The equations of motion for the gravitational field variables are modified by the addition of terms that are linear and nonlocal in the constraints. These terms are obtained from solutions of the linearized Einstein constraints.Comment: 4 pages, 1 figure, uses REVTe

Observations of Binary Stars with the Differential Speckle Survey Instrument. II. Hipparcos Stars Observed in 2010 January and June

The results of 497 speckle observations of Hipparcos stars and selected other targets are presented. Of these, 367 were resolved into components and 130 were unresolved. The data were obtained using the Differential Speckle Survey Instrument at the WIYN 3.5 m Telescope. (The WIYN Observatory is a joint facility of the University of Wisconsin-Madison, Indiana University, Yale University, and the National Optical Astronomy Observatories.) Since the first paper in this series, the instrument has been upgraded so that it now uses two electron-multiplying CCD cameras. The measurement precision obtained when comparing to ephemeris positions of binaries with very well known orbits is approximately 1-2 mas in separation and better than 0°.6 in position angle. Differential photometry is found to be in very good agreement with Hipparcos measures in cases where the comparison is most relevant. We derive preliminary orbits for two systems

Hydrodynamic emission of strange and non-strange particles at RHIC and LHC

The hydrodynamic model is used to describe the single-particle spectra and elliptic flow of hadrons at RHIC and to predict the emission angle dependence of HBT correlations at RHIC and LHC energies.Comment: 6 pages LaTeX, 3 postscript figures. Proceedings for the conference "Strange Quark Matter 2003", Atlantic Beach, NC, March 12-17, 2003, to appear in J. Phys.

Skeletal Muscle PGC-1β Signaling is Sufficient to Drive an Endurance Exercise Phenotype and to Counteract Components of Detraining in Mice

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response. Lastly, PGC-1β overexpression during the detraining period resulted in partial prevention of the detraining response. Specifically, an increase in the plateau at which O2 uptake (V̇o2) did not change from baseline with increasing treadmill speed [peak V̇o2 (ΔV̇o2max)] was maintained in trained mice with PGC-1β overexpression in muscle 6 wk after cessation of training. However, other detraining responses, including changes in running performance and in situ half relaxation time (a measure of contractility), were not affected by PGC-1β overexpression. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training, suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in preclinical models of muscle disuse atrophy

Metallicities of 0.3<z<1.0 Galaxies in the GOODS-North Field

We measure nebular oxygen abundances for 204 emission-line galaxies with redshifts 0.3<z<1.0 in the Great Observatories Origins Deep Survey North (GOODS-N) field using spectra from the Team Keck Redshift Survey (TKRS). We also provide an updated analytic prescription for estimating oxygen abundances using the traditional strong emission line ratio, R_{23}, based on the photoionization models of Kewley & Dopita (2003). We include an analytic formula for very crude metallicity estimates using the [NII]6584/Halpha ratio. Oxygen abundances for GOODS-N galaxies range from 8.2< 12+log(O/H)< 9.1 corresponding to metallicities between 0.3 and 2.5 times the solar value. This sample of galaxies exhibits a correlation between rest-frame blue luminosity and gas-phase metallicity (i.e., an L-Z relation), consistent with L-Z correlations of previously-studied intermediate-redshift samples. The zero point of the L-Z relation evolves with redshift in the sense that galaxies of a given luminosity become more metal poor at higher redshift. Galaxies in luminosity bins -18.5<M_B<-21.5 exhibit a decrease in average oxygen abundance by 0.14\pm0.05 dex from z=0 to z=1. This rate of metal enrichment means that 28\pm0.07% of metals in local galaxies have been synthesized since z=1, in reasonable agreement with the predictions based on published star formation rate densities which show that ~38% of stars in the universe have formed during the same interval. (Abridged)Comment: AASTeX, 49 pages, 16 figures, accepted for publication in The Astrophysical Journa

Branching principles of animal and plant networks identified by combining extensive data, machine learning, and modeling

Branching in vascular networks and in overall organismic form is one of the most common and ancient features of multicellular plants, fungi, and animals. By combining machine-learning techniques with new theory that relates vascular form to metabolic function, we enable novel classification of diverse branching networks--mouse lung, human head and torso, angiosperm and gymnosperm plants. We find that ratios of limb radii--which dictate essential biologic functions related to resource transport and supply--are best at distinguishing branching networks. We also show how variation in vascular and branching geometry persists despite observing a convergent relationship across organisms for how metabolic rate depends on body mass.Comment: 55 pages, 8 figures, 8 table

Incorporating Radial Flow in the Lattice Gas Model for Nuclear Disassembly

We consider extensions of the lattice gas model to incorporate radial flow. Experimental data are used to set the magnitude of radial flow. This flow is then included in the Lattice Gas Model in a microcanonical formalism. For magnitudes of flow seen in experiments, the main effect of the flow on observables is a shift along the $E^*/A$ axis.Comment: Version accepted for publication in Phys. Rev. C, Rapid Communicatio

An improved and highly sensitive microfluorimetric method for assessing susceptibility of Plasmodium falciparum to antimalarial drugs in vitro

BACKGROUND: The standard in vitro protocol currently in use for drug testing against Plasmodium falciparum, based on the incorporation of the purine [(3)H]-hypoxanthine, has two serious drawbacks. Firstly it is unsuitable for the testing of drugs that directly or indirectly impact on purine salvage or metabolism. Secondly, it relies on the use of expensive radiolabelled material, with added issues concerning detection, storage and waste disposal that make it unsuitable for use in many disease-endemic areas. Recently, the use of fluorochromes has been suggested as an alternative, but quenching of the fluorescence signal by the haemoglobin present in cultures of Plasmodium falciparum-infected erythrocytes severely limits the usefulness of this approach. METHODS: In order to resolve this problem, a new PicoGreen(®)-based procedure has been developed which incorporates additional steps to remove the interfering haemoglobin. The 50% inhibitory concentration (IC(50)) values of chloroquine and pyrimethamine against P. falciparum laboratory lines 3D7 and K1 were determined using the new protocol. RESULTS: The IC(50 )values of chloroquine and pyrimethamine against P. falciparum laboratory lines 3D7 and K1 determined with the new fluorescence-based protocol were statistically identical to those obtained using the traditional (3)H-hypoxanthine incorporation method, and consistent with literature values. CONCLUSION: The new method proved to be accurate, reproducible and sensitive, and has the advantage of being non-radioactive. The improved PicoGreen(® )method has the potential to replace traditional in vitro drug resistance assay techniques