Thiazolidinediones induce osteocyte apoptosis and increase sclerostin expression

Aims  Thiazolidinediones (TZDs) are associated with a higher risk of bone fracture in women compared with men. The aim of the present study was to investigate whether TZDs could influence osteocyte behaviour and contribute to the skeletal phenotype observed in TZD-treated patients.Methods  The murine MLO-Y4 cell line was used as a source of osteocytes. These cells were cultured for 24 h with 0, 10−8 m, 10−7 m, 10−6 m, 10−5 m or 10−4 m of pioglitazone, rosiglitazone or troglitazone in the presence or absence of 17β-oestradiol. The extent of osteocyte apoptosis was assessed, as was the expression of the bone formation inhibitor sclerostin and receptor activator for nuclear factor κB ligand (RANKL) also.Results  In the absence of 17β-oestradiol, pioglitazone, rosiglitazone and troglitazone induced osteocyte apoptosis dose-dependently even at the lowest concentration of 10−8 m. Furthermore, the expression of sclerostin but not RANKL was significantly increased in TZD-treated cultures compared with untreated cultures. The presence of 17β-oestradiol significantly reduced TZD-induced osteocyte apoptosis and also sclerostin up-regulation.Conclusions  These findings therefore raise the potential concern of using TZDs in post-menopausal women where the lack of oestrogen would not prevent osteocyte apoptosis and sclerostin up-regulation and may aggravate the reduction in bone mass in these patients

Recurrence and differential relations for spherical spinors

We present a comprehensive table of recurrence and differential relations obeyed by spin one-half spherical spinors (spinor spherical harmonics) $\Omega_{\kappa\mu}(\mathbf{n})$ used in relativistic atomic, molecular, and solid state physics, as well as in relativistic quantum chemistry. First, we list finite expansions in the spherical spinor basis of the expressions $\mathbf{A}\cdot\mathbf{B}\,\Omega_{\kappa\mu}(\mathbf{n})$ and {$\mathbf{A}\cdot(\mathbf{B}\times\mathbf{C})\, \Omega_{\kappa\mu}(\mathbf{n})$}, where $\mathbf{A}$, $\mathbf{B}$, and $\mathbf{C}$ are either of the following vectors or vector operators: $\mathbf{n}=\mathbf{r}/r$ (the radial unit vector), $\mathbf{e}_{0}$, $\mathbf{e}_{\pm1}$ (the spherical, or cyclic, versors), $\boldsymbol{\sigma}$ (the $2\times2$ Pauli matrix vector), $\hat{\mathbf{L}}=-i\mathbf{r}\times\boldsymbol{\nabla}I$ (the dimensionless orbital angular momentum operator; $I$ is the $2\times2$ unit matrix), $\hat{\mathbf{J}}=\hat{\mathbf{L}}+1/2\boldsymbol{\sigma}$ (the dimensionless total angular momentum operator). Then, we list finite expansions in the spherical spinor basis of the expressions $\mathbf{A}\cdot\mathbf{B}\,F(r)\Omega_{\kappa\mu}(\mathbf{n})$ and $\mathbf{A}\cdot(\mathbf{B}\times\mathbf{C})\, F(r)\Omega_{\kappa\mu}(\mathbf{n})$, where at least one of the objects $\mathbf{A}$, $\mathbf{B}$, $\mathbf{C}$ is the nabla operator $\boldsymbol{\nabla}$, while the remaining ones are chosen from the set $\mathbf{n}$, $\mathbf{e}_{0}$, $\mathbf{e}_{\pm1}$, $\boldsymbol{\sigma}$, $\hat{\mathbf{L}}$, $\hat{\mathbf{J}}$.Comment: LaTeX, 12 page

Finite covers of random 3-manifolds

A 3-manifold is Haken if it contains a topologically essential surface. The Virtual Haken Conjecture posits that every irreducible 3-manifold with infinite fundamental group has a finite cover which is Haken. In this paper, we study random 3-manifolds and their finite covers in an attempt to shed light on this difficult question. In particular, we consider random Heegaard splittings by gluing two handlebodies by the result of a random walk in the mapping class group of a surface. For this model of random 3-manifold, we are able to compute the probabilities that the resulting manifolds have finite covers of particular kinds. Our results contrast with the analogous probabilities for groups coming from random balanced presentations, giving quantitative theorems to the effect that 3-manifold groups have many more finite quotients than random groups. The next natural question is whether these covers have positive betti number. For abelian covers of a fixed type over 3-manifolds of Heegaard genus 2, we show that the probability of positive betti number is 0. In fact, many of these questions boil down to questions about the mapping class group. We are lead to consider the action of mapping class group of a surface S on the set of quotients pi_1(S) -> Q. If Q is a simple group, we show that if the genus of S is large, then this action is very mixing. In particular, the action factors through the alternating group of each orbit. This is analogous to Goldman's theorem that the action of the mapping class group on the SU(2) character variety is ergodic.Comment: 60 pages; v2: minor changes. v3: minor changes; final versio

Magnetic susceptibilities of diluted magnetic semiconductors and anomalous Hall-voltage noise

The carrier spin and impurity spin densities in diluted magnetic semiconductors are considered using a semiclassical approach. Equations of motions for the spin densities and the carrier spin current density in the paramagnetic phase are derived, exhibiting their coupled diffusive dynamics. The dynamical spin susceptibilities are obtained from these equations. The theory holds for p-type and n-type semiconductors doped with magnetic ions of arbitrary spin quantum number. Spin-orbit coupling in the valence band is shown to lead to anisotropic spin diffusion and to a suppression of the Curie temperature in p-type materials. As an application we derive the Hall-voltage noise in the paramagnetic phase. This quantity is critically enhanced close to the Curie temperature due to the contribution from the anomalous Hall effect.Comment: 18 pages, 1 figure include

Gone but Not Lost: Implications for Estimating HIV Care Outcomes When Loss to Clinic Is Not Loss to Care

Background: In some time-to-event analyses, it is unclear whether loss to follow up should be treated as a censoring event or competing event. Such ambiguity is particularly common in HIV research that uses routinely collected clinical data to report the timing of key milestones along the HIV care continuum. In this setting, loss to follow up may be viewed as a censoring event, under the assumption that patients who are "lost" from a study clinic immediately enroll in care elsewhere, or a competing event, under the assumption that people "lost" are out of care all together. Methods: We illustrate an approach to address this ambiguity when estimating the 2-year risk of antiretroviral treatment initiation among 19,506 people living with HIV who enrolled in the IeDEA Central Africa cohort between 2006 and 2017, along with published estimates from tracing studies in Africa. We also assessed the finite sample properties of the proposed approach using simulation experiments. Results: The estimated 2-year risk of treatment initiation was 69% if patients were censored at loss to follow up or 59% if losses to follow up were treated as competing events. Using the proposed approach, we estimated that the 2-year risk of antiretroviral therapy initiation was 62% (95% confidence interval: 61, 62). The proposed approach had little bias and appropriate confidence interval coverage under scenarios examined in the simulation experiments. Conclusions: The proposed approach relaxes the assumptions inherent in treating loss to follow up as a censoring or competing event in clinical HIV cohort studies

Standardized Definitions of In Utero Human Immunodeficiency Virus and Antiretroviral Drug Exposure Among Children

In countries with high human immunodeficiency virus (HIV) prevalence, up to 30% of pregnant women are living with HIV, with fetal exposure to both HIV and antiretroviral therapy during pregnancy. In addition, pregnant women without HIV but at high risk of HIV acquisition are increasingly receiving HIV preexposure antiretroviral prophylaxis (PrEP). Investments are being made to establish and follow cohorts of children to evaluate the long-term effects of in utero HIV and antiretroviral exposure. Agreement on a key set of definitions for relevant exposures and outcomes is important both for interpreting individual study results and for comparisons across cohorts. Harmonized definitions of in utero HIV and antiretroviral drug (maternal treatment or PrEP) exposure will also facilitate improved classification of these exposures in future observational studies and clinical trials. The proposed definitions offer a uniform approach to facilitate the consistent description and estimation of effects of HIV and antiretroviral exposures on key child health outcomes

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio

D* Production in Deep Inelastic Scattering at HERA

This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel $D^{*+}\to (D^0 \to K^- \pi^+) \pi^+$ (+ c.c.) has been used in the study. The $e^+p$ cross section for inclusive D^{*\pm} production with $5<Q^2<100 GeV^2$ and $y<0.7$ is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {$1.3<p_T(D^{*\pm})<9.0$ GeV and $| \eta(D^{*\pm}) |<1.5$}. Differential cross sections as functions of p_T(D^{*\pm}), $\eta(D^{*\pm}), W$ and $Q^2$ are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and $\eta$(D^{*\pm}), the charm contribution $F_2^{c\bar{c}}(x,Q^2)$ to the proton structure function is determined for Bjorken $x$ between 2 $\cdot$ 10$^{-4}$ and 5 $\cdot$ 10$^{-3}$.Comment: 17 pages including 4 figure

Observation of Scaling Violations in Scaled Momentum Distributions at HERA

Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of $x$ and $Q^2$ using the ZEUS detector. The evolution of the scaled momentum, $x_p$, with $Q^2,$ in the range 10 to 1280 $GeV^2$, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of $Q^2$.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio