Surveillance of emerging drugs of abuse in Hong Kong: Validation of an analytical tool

© 2015, Hong Kong Academy of Medicine Press. All rights reserved. Objective: To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Design: Cross-sectional study. Setting: Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. Participants: A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Main outcome measures: Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. Results: The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. Conclusions: This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.Link_to_subscribed_fulltex

KL Estimation of the Power Spectrum Parameters from the Angular Distribution of Galaxies in Early SDSS Data

We present measurements of parameters of the 3-dimensional power spectrum of galaxy clustering from 222 square degrees of early imaging data in the Sloan Digital Sky Survey. The projected galaxy distribution on the sky is expanded over a set of Karhunen-Loeve eigenfunctions, which optimize the signal-to-noise ratio in our analysis. A maximum likelihood analysis is used to estimate parameters that set the shape and amplitude of the 3-dimensional power spectrum. Our best estimates are Gamma=0.188 +/- 0.04 and sigma_8L = 0.915 +/- 0.06 (statistical errors only), for a flat Universe with a cosmological constant. We demonstrate that our measurements contain signal from scales at or beyond the peak of the 3D power spectrum. We discuss how the results scale with systematic uncertainties, like the radial selection function. We find that the central values satisfy the analytically estimated scaling relation. We have also explored the effects of evolutionary corrections, various truncations of the KL basis, seeing, sample size and limiting magnitude. We find that the impact of most of these uncertainties stay within the 2-sigma uncertainties of our fiducial result.Comment: Fig 1 postscript problem correcte

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Single-cell sequencing reveals Hippo signaling as a driver of fibrosis in hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by abscesses, nodules, dissecting/draining tunnels, and extensive fibrosis. Here, we integrate single-cell RNA sequencing, spatial transcriptomics, and immunostaining to provide an unprecedented view of the pathogenesis of chronic HS, characterizing the main cellular players and defining their interactions. We found a striking layering of the chronic HS infiltrate and identified the contribution of 2 fibroblast subtypes (SFRP4+ and CXCL13+) in orchestrating this compartmentalized immune response. We further demonstrated the central role of the Hippo pathway in promoting extensive fibrosis in HS and provided preclinical evidence that the profibrotic fibroblast response in HS can be modulated through inhibition of this pathway. These data provide insights into key aspects of HS pathogenesis with broad therapeutic implications.</p

The 3D Power Spectrum from Angular Clustering of Galaxies in Early SDSS Data

Early photometric data from the Sloan Digital Sky Survey (SDSS) contain angular positions for 1.5 million galaxies. In companion papers, the angular correlation function $w(\theta)$ and 2D power spectrum $C_l$ of these galaxies are presented. Here we invert Limber's equation to extract the 3D power spectrum from the angular results. We accomplish this using an estimate of $dn/dz$, the redshift distribution of galaxies in four different magnitude slices in the SDSS photometric catalog. The resulting 3D power spectrum estimates from $w(\theta)$ and $C_l$ agree with each other and with previous estimates over a range in wavenumbers $0.03 < k/{\rm h Mpc}^{-1} < 1$. The galaxies in the faintest magnitude bin (21 < \rstar < 22, which have median redshift $z_m=0.43$) are less clustered than the galaxies in the brightest magnitude bin (18 < \rstar < 19 with $z_m=0.17$), especially on scales where nonlinearities are important. The derived power spectrum agrees with that of Szalay et al. (2001) who go directly from the raw data to a parametric estimate of the power spectrum. The strongest constraints on the shape parameter $\Gamma$ come from the faintest galaxies (in the magnitude bin 21 < \rstar < 22), from which we infer $\Gamma = 0.14^{+0.11}_{-0.06}$ (95% C.L.).Comment: 25 pages, 19 figure

Digital Signal Processing Research Program

Contains table of contents for Section 2, an introduction, reports on twenty-one research projects and a list of publications.U.S. Navy - Office of Naval Research Grant N00014-93-1-0686Lockheed Sanders, Inc. Contract P.O. BY5561U.S. Air Force - Office of Scientific Research Grant AFOSR 91-0034National Science Foundation Grant MIP 95-02885U.S. Navy - Office of Naval Research Grant N00014-95-1-0834MIT-WHOI Joint Graduate Program in Oceanographic EngineeringAT&T Laboratories Doctoral Support ProgramDefense Advanced Research Projects Agency/U.S. Navy - Office of Naval Research Grant N00014-89-J-1489Lockheed Sanders/U.S. Navy - Office of Naval Research Grant N00014-91-C-0125U.S. Navy - Office of Naval Research Grant N00014-89-J-1489National Science Foundation Grant MIP 95-02885Defense Advanced Research Projects Agency/U.S. Navy Contract DAAH04-95-1-0473U.S. Navy - Office of Naval Research Grant N00014-91-J-1628University of California/Scripps Institute of Oceanography Contract 1003-73-5

Cosmological parameters from SDSS and WMAP

We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a ``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1 sigma constraints on the Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running tilt, neutrino mass and equation of state in the list of free parameters, many constraints are still quite weak, but future cosmological measurements from SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt figures available at http://www.hep.upenn.edu/~max/sdsspars.htm

Bayesian Solar Wind Modeling with Pulsar Timing Arrays

Using Bayesian analyses we study the solar electron density with the NANOGrav 11-year pulsar timing array (PTA) dataset. Our model of the solar wind is incorporated into a global fit starting from pulse times-of-arrival. We introduce new tools developed for this global fit, including analytic expressions for solar electron column densities and open source models for the solar wind that port into existing PTA software. We perform an ab initio recovery of various solar wind model parameters. We then demonstrate the richness of information about the solar electron density, $n_E$, that can be gleaned from PTA data, including higher order corrections to the simple $1/r^2$ model associated with a free-streaming wind (which are informative probes of coronal acceleration physics), quarterly binned measurements of $n_E$ and a continuous time-varying model for $n_E$ spanning approximately one solar cycle period. Finally, we discuss the importance of our model for chromatic noise mitigation in gravitational-wave analyses of pulsar timing data and the potential of developing synergies between sophisticated PTA solar electron density models and those developed by the solar physics community.Comment: 22 pages, 7 figures, Submitted to Ap

Hyperleptinemia Is Required for the Development of Leptin Resistance

Leptin regulates body weight by signaling to the brain the availability of energy stored as fat. This negative feedback loop becomes disrupted in most obese individuals, resulting in a state known as leptin resistance. The physiological causes of leptin resistance remain poorly understood. Here we test the hypothesis that hyperleptinemia is required for the development of leptin resistance in diet-induced obese mice. We show that mice whose plasma leptin has been clamped to lean levels develop obesity in response to a high-fat diet, and the magnitude of this obesity is indistinguishable from wild-type controls. Yet these obese animals with constant low levels of plasma leptin remain highly sensitive to exogenous leptin even after long-term exposure to a high fat diet. This shows that dietary fats alone are insufficient to block the response to leptin. The data also suggest that hyperleptinemia itself can contribute to leptin resistance by downregulating cellular response to leptin as has been shown for other hormones

Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish

10.1371/journal.pone.0068759PLoS ONE87-POLN