Spatial Variability in the Ratio of Interstellar Atomic Deuterium to Hydrogen. I. Observations toward delta Orionis by the Interstellar Medium Absorption Profile Spectrograph

Studies of the abundances of deuterium in different astrophysical sites are of fundamental importance to answering the question about how much deuterium was produced during big bang nucleosynthesis and what fraction of it was destroyed later. With this in mind, we used the Interstellar Medium Absorption Profile Spectrograph (IMAPS) on the ORFEUS-SPAS II mission to observe at a wavelength resolution of 4 km/s (FWHM) the L-delta and L-epsilon absorption features produced by interstellar atomic deuterium in the spectrum of delta Ori A. A chi-square analysis indicated that 0.96 < N(D I)< 1.45e15 cm^{-2} at a 90% level of confidence, and the gas is at a temperature of about 6000K. To obtain an accurate value of N(H I) needed for a determination of the atomic ratio of D to H, we measured the L-alpha absorption features in 57 spectra of delta Ori in the IUE archive. From our measurement of N(H I)= 1.56e20 cm^{-2}, we found that N(D I)/N(H I)= 7.4(+1.9,-1.3)e-6 (90% confidence). Our result for D/H contrasts with the more general finding along other lines of sight that D/H is approximately 1.5e-5. The underabundance of D toward delta Ori A is not accompanied by an overabundance of N or O relative to H, as one might expect if the gas were subjected to more stellar processing than usual.Comment: 37 pages, 6 figures. Submitted to the Astrophysical Journa

HELIUM PHOTODISINTEGRATION AND NUCLEOSYNTHESIS: IMPLICATIONS FOR TOPOLOGICAL DEFECTS, HIGH ENERGY COSMIC RAYS, AND MASSIVE BLACK HOLES

We consider the production of $^3$He and $^2$H by $^4$He photodisintegration initiated by non-thermal energy releases during early cosmic epochs. We find that this process cannot be the predominant source of primordial $^2$H since it would result in anomalously high $^3$He/D ratios in conflict with standard chemical evolution assumptions. We apply this fact to constrain topological defect models of highest energy cosmic ray (HECR) production. Such models have been proposed as possible sources of ultrahigh energy particles and gamma-rays with energies above $10^{20}$eV. The constraints on these models derived from $^4$He-photodisintegration are compared to corresponding limits from spectral distortions of the cosmic microwave background radiation (CMBR) and from the observed diffuse gamma-ray background. It is shown that for reasonable primary particle injection spectra superconducting cosmic strings, unlike ordinary strings or annihilating monopoles, cannot produce the HECR flux at the present epoch without violating at least the $^4$He-photodisintegration bound. The constraint from the diffuse gamma-ray background rules out the dominant production of HECR by the decay of Grand Unification particles in models with cosmological evolution assuming standard fragmentation functions. Constraints on massive black hole induced photodisintegration are also discussed.Comment: 20 latex pages, 1 figure added via figures comman

Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry

OBJECTIVES: This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. METHODS: RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. RESULTS: Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. CONCLUSION: Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies

Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions

Myoglobin, encoded by MB, is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O-2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C>T ( p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O-2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.Peer reviewe

Search for B⁺c decays to the pp‾π⁺ final state

A search for the decays of the B + c meson to pp-π + is performed for the first time using a data sample corresponding to an integrated luminosity of 3.0 fb -1 collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV. No signal is found and an upper limit, at 95% confidence level, is set, fcfu×B(B + c →ppπ + ) < 3.6×10-8 in the kinematic region m(pp) < 2.85 GeV/c2, p T (B) < 20 GeV/c and 2.0 < y(B) < 4.5, where B is the branching fraction and f c (f u ) is the fragmentation fraction of the b quark into a B c + (B + ) meson

Big Bang nucleosynthesis and physics beyond the Standard Model

The Hubble expansion of galaxies, the 2.73\dK blackbody radiation background and the cosmic abundances of the light elements argue for a hot, dense origin of the universe --- the standard Big Bang cosmology --- and enable its evolution to be traced back fairly reliably to the nucleosynthesis era when the temperature was of \Or(1) MeV corresponding to an expansion age of \Or(1) sec. All particles, known and hypothetical, would have been created at higher temperatures in the early universe and analyses of their possible effects on the abundances of the synthesized elements enable many interesting constraints to be obtained on particle properties. These arguments have usefully complemented laboratory experiments in guiding attempts to extend physics beyond the Standard SU(3)_{\c}{\otimes}SU(2)_{\L}{\otimes}U(1)_{Y} Model, incorporating ideas such as supersymmetry, compositeness and unification. We first present a pedagogical account of relativistic cosmology and primordial nucleosynthesis, discussing both theoretical and observational aspects, and then proceed to examine such constraints in detail, in particular those pertaining to new massless particles and massive unstable particles. Finally, in a section aimed at particle physicists, we illustrate applications of such constraints to models of new physics.Comment: 156 pages LaTeX, including 18 PostScript figures; uses ioplppt.sty, epsf, and personal style file (incl.); Revised and updated to include, e.g. implications of new deuterium observations in primordial clouds; 2-up PostScript version (78 pages) available at ftp://ftp.physics.ox.ac.uk/pub/local/users/sarkar/BBNreview.ps.gz ; to appear in Reports on Progress in Physic

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

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Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

Search for single production of a heavy vector-like T quark decaying to a Higgs boson and a top quark with a lepton and jets in the final state

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