Cytomegalovirus-specific T cells restricted for shared and donor human leukocyte antigens differentially impact on cytomegalovirus reactivation risk after allogeneic hematopoietic stem cell transplantation

After allogeneic hematopoietic stem cell transplantation (HSCT), the emergence of circulating cytomegalovirus (CMV)- specific T cells correlates with protection from CMV reactivation, an important risk factor for non-relapse mortality. However, functional assays measuring CMV-specific cells are time-consuming and often inaccurate at early time-points. We report the results of a prospective single-center, non-interventional study that identified the enumeration of Dextramerpositive CMV-specific lymphocytes as a reliable and early predictor of viral reactivation. We longitudinally monitored 75 consecutive patients for 1 year after allogeneic HSCT (n=630 samples). The presence of ≥0.5 CMV-specific CD8+ cells/mL at day +45 was an independent protective factor from subsequent clinically relevant reactivation in univariate (P<0.01) and multivariate (P<0.05) analyses. Dextramer quantification correlated with functional assays measuring interferon-γ production, and allowed earlier identification of high-risk patients. In mismatched transplants, the comparative analysis of lymphocytes restricted by shared, donor- and host-specific HLA revealed the dominant role of thymic-independent CMV-specific reconstitution. Shared and donor-restricted CMV-specific T cells reconstituted with similar kinetics in recipients of CMV-seropositive donors, while donor-restricted T-cell reconstitution from CMV-seronegative grafts was impaired, indicating that in primary immunological responses the emergence of viral-specific T cells is largely sustained by antigen encounter on host infected cells rather than by cross-priming/presentation by non-infected donor-derived antigen-presenting cells. Multiparametric flow cytometry and high-dimensional analysis showed that shared-restricted CMV-specific lymphocytes display a more differentiated phenotype and increased persistence than donor-restricted counterparts. In this study, monitoring CMV-specific cells by Dextramer assay after allogeneic HSCT shed light on mechanisms of immune reconstitution and enabled risk stratification of patients, which could improve the clinical management of post-transplant CMV reactivations

Rates of adverse events in patients with ulcerative colitis undergoing colectomy during treatment with tofacitinib vs biologics : a multicenter observational study

Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-a agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-a agents (P 5 0.047) and of late VTE with vedolizumab (P 5 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06–3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12–20.58), and early redo surgery (OR 7.49, 95% CI 1.17–47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08–3.57), early surgical site complications (OR 2.03, 95% CI 1.01–4.09), and early redo surgery (OR 7.52, 95% CI 1.42–39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29–1.00), early infections (OR 0.39, 95% CI 0.18–0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12–1.00).peer-reviewe

PRISM (Polarized Radiation Imaging and Spectroscopy Mission): A White Paper on the Ultimate Polarimetric Spectro-Imaging of the Microwave and Far-Infrared Sky

PRISM (Polarized Radiation Imaging and Spectroscopy Mission) was proposed to ESA in response to the Call for White Papers for the definition of the L2 and L3 Missions in the ESA Science Programme. PRISM would have two instruments: (1) an imager with a 3.5m mirror (cooled to 4K for high performance in the far-infrared---that is, in the Wien part of the CMB blackbody spectrum), and (2) an Fourier Transform Spectrometer (FTS) somewhat like the COBE FIRAS instrument but over three orders of magnitude more sensitive. Highlights of the new science (beyond the obvious target of B-modes from gravity waves generated during inflation) made possible by these two instruments working in tandem include: (1) the ultimate galaxy cluster survey gathering 10e6 clusters extending to large redshift and measuring their peculiar velocities and temperatures (through the kSZ effect and relativistic corrections to the classic y-distortion spectrum, respectively) (2) a detailed investigation into the nature of the cosmic infrared background (CIB) consisting of at present unresolved dusty high-z galaxies, where most of the star formation in the universe took place, (3) searching for distortions from the perfect CMB blackbody spectrum, which will probe a large number of otherwise inaccessible effects (e.g., energy release through decaying dark matter, the primordial power spectrum on very small scales where measurements today are impossible due to erasure from Silk damping and contamination from non-linear cascading of power from larger length scales). These are but a few of the highlights of the new science that will be made possible with PRISM.Comment: 20 pages Late

Planck intermediate results XXIV : Constraints on variations in fundamental constants

Any variation in the fundamental physical constants, more particularly in the fine structure constant, a, or in the mass of the electron, me, affects the recombination history of the Universe and cause an imprint on the cosmic microwave background angular power spectra. We show that the Planck data allow one to improve the constraint on the time variation of the fine structure constant at redshift z - 10(3) by about a factor of 5 compared to WMAP data, as well as to break the degeneracy with the Hubble constant, H-0. In addition to a, we can set a constraint on the variation in the mass of the electron, me, and in the simultaneous variation of the two constants. We examine in detail the degeneracies between fundamental constants and the cosmological parameters, in order to compare the limits obtained from Planck and WMAP and to determine the constraining power gained by including other cosmological probes. We conclude that independent time variations of the fine structure constant and of the mass of the electron are constrained by Planck to Delta alpha/alpha = (3.6 +/- 3.7) x 10(-3) and Delta m(e)/m(e) = (4 +/- 11) x 10(-3) at the 68% confidence level. We also investigate the possibility of a spatial variation of the fine structure constant. The relative amplitude of a dipolar spatial variation in a (corresponding to a gradient across our Hubble volume) is constrained to be delta alpha/alpha = (-2.4 +/- 3.7) x 10(-2).Peer reviewe

VizieR Online Data Catalog: 1Jy northern AGN sample (Planck+, 2016)

The complete sample presented in this paper consists of 104 northern and equatorial radio-loud AGN. It includes all AGN with declination >=-10° that have a measured average radio flux density at 37GHz exceeding 1Jy. Most of the sample sources have been monitored at Metsahovi Radio Observatory for many years, and the brightest sources have been observed for up to 30yr. (1 data file)

VizieR Online Data Catalog: Planck high-z source candidates catalog (PHZ) (Planck+, 2016)

We present in this work the Planck List of Highredshift Source Candidates (the "PHZ"), which includes 2151 sources distributed over 26% of the sky, with redshifts likely to be greater than 2. (2 data files)

VizieR Online Data Catalog: Planck Catalogue of Galactic cold clumps (PGCC) (Planck+, 2016)

The Planck Catalogue of Galactic Cold Clumps (PGCC) is a list of 13188 Galactic sources and 54 sources located in the Small and Large Magellanic Clouds. The sources have been identified in Planck data as sources colder than their environment. It has been built using the 48 months Planck data at 857, 545, and 353GHz combined with the 3THz IRAS data. (1 data file)

VizieR Online Data Catalog: Second Planck Catalogue of Compact Sources (PCCS2) (Planck+, 2016)

The Low Frequency Instrument (LFI) DPC produced the 30, 44, and 70GHz maps after the completion of eight full surveys (spanning the period 12 August 2009 to 3 August 2013). In addition, special LFI maps covering the period 1 April 2013 to 30 June 2013 were produced in order to compare the Planck flux-density scales with those of the Very Large Array and the Australia Telescope Compact Array, by performing simultaneous observations of a sample of sources over that period. The High Frequency Instrument (HFI) DPC produced the 100, 143, 217, 353, 545, and 857GHz maps after five full surveys (2009 August 12 to 2012 January 11). (16 data files)

VizieR Online Data Catalog: Planck Sunyaev-Zeldovich sources (PSZ2) (Planck+, 2016)

Three pipelines are used to detect SZ clusters: two independent implementations of the Matched Multi-Filter (MMF1 and MMF3), and PowellSnakes (PwS). The main catalogue is constructed as the union of the catalogues from the three detection methods. The completeness and reliability of the catalogues have been assessed through internal and external validation as described in section 4 of the paper. (5 data files)