A molecular signature of myalgia in myotonic dystrophy 2

Background: Chronic muscle pain affects close to 20% of the population and is a major health burden. The underlying mechanisms of muscle pain are difficult to investigate as pain presents in patients with very diverse histories. Treatment options are therefore limited and not tailored to underlying mechanisms. To gain insight into the pathophysiology of myalgia we investigated a homogeneous group of patients suffering from myotonic dystrophy type 2 (DM2), a monogenic disorder presenting with myalgia in at least 50% of affected patients. Methods: After IRB approval we performed an observational cross-sectional cohort study and recruited 42 patients with genetically confirmed DM2 plus 20 healthy age and gender matched control subjects. All participants were subjected to an extensive sensory-testing protocol. In addition, RNA sequencing was performed from 12 muscle biopsy specimens obtained from DM2 patients. Findings: Clinical sensory testing as well as RNA sequencing clearly separated DM2 myalgic from non-myalgia patients and also from healthy controls. In particular pressure pain thresholds were significantly lowered for all muscles tested in myalgic DM2 patients but were not significantly different between non-myalgic patients and healthy controls. The expression of fourteen muscle expressed genes in myalgic patients was significantly up or down-regulated in myalgic compared to non-myalgic DM2 patients. Interpretation: Our data support the idea that molecular changes in the muscles of DM2 patients are associated with muscle pain. Further studies should address whether muscle-specific molecular pathways play a significant role in myalgia in order to facilitate the development of mechanism-based therapeutic strategies to treat musculoskeletal pain

Nonequilibrium GW+EDMFTGW+\mathrm{EDMFT}: Antiscreening and Inverted Populations from Nonlocal Correlations

We study the dynamics of screening in photodoped Mott insulators with long-ranged interactions using a nonequilibrium implementation of the GW plus extended dynamical mean-field theory formalism. Our study demonstrates that the complex interplay of the injected carriers with bosonic degrees of freedom (charge fluctuations) can result in long-lived transient states with properties that are distinctly different from those of thermal equilibrium states. Systems with strong nonlocal interactions are found to exhibit a self-sustained population inversion of the doublons and holes. This population inversion leads to low-energy antiscreening which can be detected in time- resolved electron-energy-loss spectra

The X-ray Spectrum and Light Curve of Supernova 1995N

We report on multi-epoch X-ray observations of the Type IIn (narrow emission line) supernova SN 1995N with the ROSAT and ASCA satellites. The January 1998 ASCA X-ray spectrum is well fitted by a thermal bremsstrahlung (kT~10 keV, N_H~6e20 cm^-2) or power-law (alpha~1.7, N_H~1e21 cm^-2) model. The X-ray light curve shows evidence for significant flux evolution between August 1996 and January 1998: the count rate from the source decreased by 30% between our August 1996 and August 1997 ROSAT observations, and the X-ray luminosity most likely increased by a factor of ~2 between our August 1997 ROSAT and January 1998 ASCA observations, although evolution of the spectral shape over this interval is not ruled out. The high X-ray luminosity, L_X~1e41 erg/sec, places SN 1995N in a small group of Type IIn supernovae with strong circumstellar interaction, and the evolving X-ray luminosity suggests that the circumstellar medium is distributed inhomogeneously.Comment: MNRAS accepted. 6 pages, 2 figures; uses mn.sty and psfi

Theoretical characterization of a model of aragonite crystal orientation in red abalone nacre

Nacre, commonly known as mother-of-pearl, is a remarkable biomineral that in red abalone consists of layers of 400-nm thick aragonite crystalline tablets confined by organic matrix sheets, with the $(001)$ crystal axes of the aragonite tablets oriented to within $\pm$ 12 degrees from the normal to the layer planes. Recent experiments demonstrate that this orientational order develops over a distance of tens of layers from the prismatic boundary at which nacre formation begins. Our previous simulations of a model in which the order develops because of differential tablet growth rates (oriented tablets growing faster than misoriented ones) yield patterns of tablets that agree qualitatively and quantitatively with the experimental measurements. This paper presents an analytical treatment of this model, focusing on how the dynamical development and eventual degree of order depend on model parameters. Dynamical equations for the probability distributions governing tablet orientations are introduced whose form can be determined from symmetry considerations and for which substantial analytic progress can be made. Numerical simulations are performed to relate the parameters used in the analytic theory to those in the microscopic growth model. The analytic theory demonstrates that the dynamical mechanism is able to achieve a much higher degree of order than naive estimates would indicate.Comment: 20 pages, 3 figure

Community health workers at the dawn of a new era: 3. Programme governance

Background: Community health workers (CHWs) can play a critical role in primary healthcare and are seen widely as important to achieving the health-related Sustainable Development Goals (SDGs). The COVID-19 pandemic has emphasized the key role of CHWs. Improving how CHW programmes are governed is increasingly recognized as important for achieving universal access to healthcare and other health-related goals. This paper, the third in a series on “Community Health Workers at the Dawn of a New Era”, aims to raise critical questions that decision-makers need to consider for governing CHW programmes, illustrate the options for governance using examples of national CHW programmes, and set out a research agenda for understanding how CHW programmes are governed and how this can be improved. Methods: We draw from a review of the literature as well as from the knowledge and experience of those involved in the planning and management of CHW programmes. Results: Governing comprises the processes and structures through which individuals, groups, programmes, and organizations exercise rights, resolve diferences, and express interests. Because CHW programmes are located between the formal health system and communities, and because they involve a wide range of stakeholders, their governance is complex. In addition, these programmes frequently fall outside of the governance structures of the formal health system or are poorly integrated with it, making governing these programmes more challenging. We discuss the following important questions that decision-makers need to consider in relation to governing CHW programmes: (1) How and where within political structures are policies made for CHW programmes? (2) Who implements decisions regarding CHW programmes and at what levels of government? (3) What laws and regulations are needed to support the programme? (4) How should the programme be adapted across diferent settings or groups within the country or region? Conclusion: The most appropriate and acceptable models for governing CHW programmes depend on communities, on local health systems, and on the political system in which the programme is located. Stakeholders in each setting need to consider what systems are currently in place and how they might be adapted to local needs and systems

Symmetry Breaking of Relativistic Multiconfiguration Methods in the Nonrelativistic Limit

The multiconfiguration Dirac-Fock method allows to calculate the state of relativistic electrons in atoms or molecules. This method has been known for a long time to provide certain wrong predictions in the nonrelativistic limit. We study in full mathematical details the nonlinear model obtained in the nonrelativistic limit for Be-like atoms. We show that the method with sp+pd configurations in the J=1 sector leads to a symmetry breaking phenomenon in the sense that the ground state is never an eigenvector of L^2 or S^2. We thereby complement and clarify some previous studies.Comment: Final version, to appear in Nonlinearity. Nonlinearity (2010) in pres

Mesoscopic Electron and Phonon Transport through a Curved Wire

There is great interest in the development of novel nanomachines that use charge, spin, or energy transport, to enable new sensors with unprecedented measurement capabilities. Electrical and thermal transport in these mesoscopic systems typically involves wave propagation through a nanoscale geometry such as a quantum wire. In this paper we present a general theoretical technique to describe wave propagation through a curved wire of uniform cross-section and lying in a plane, but of otherwise arbitrary shape. The method consists of (i) introducing a local orthogonal coordinate system, the arclength and two locally perpendicular coordinate axes, dictated by the shape of the wire; (ii) rewriting the wave equation of interest in this system; (iii) identifying an effective scattering potential caused by the local curvature; and (iv), solving the associated Lippmann-Schwinger equation for the scattering matrix. We carry out this procedure in detail for the scalar Helmholtz equation with both hard-wall and stress-free boundary conditions, appropriate for the mesoscopic transport of electrons and (scalar) phonons. A novel aspect of the phonon case is that the reflection probability always vanishes in the long-wavelength limit, allowing a simple perturbative (Born approximation) treatment at low energies. Our results show that, in contrast to charge transport, curvature only barely suppresses thermal transport, even for sharply bent wires, at least within the two-dimensional scalar phonon model considered. Applications to experiments are also discussed.Comment: 9 pages, 11 figures, RevTe

New XMM-Newton analysis of three bright X-ray sources in M31 globular clusters, including a new black hole candidate

We present detailed analysis of three globular cluster X-ray sources in the XMM-Newton extended survey of M31. The X-ray counterpart to the M31 globular cluster Bo 45 (XBo 45) was observed with XMM-Newton on 2006 December 26. Its combined pn+MOS 0.3--10 keV lightcurve exhibited a r.m.s variability of ~10%, and its 0.3--7.0 keV emission spectrum was well described by an absorbed power law with photon index 1.44$\pm$0.12. Its variability and emission is characteristic of low mass X-ray binaries (LMXBs) in the low-hard state, whether the accretor is a neutron star or black hole. Such behaviour is typically observed at luminosities \la10% Eddington. However, XBo 45 exhibited this behaviour at an unabsorbed, 0.3--10 keV luminosity of 2.5$\pm0.2\times 10^{38}$ erg s$^{-1}$, or{~140%} Eddington for a 1.4 $M_{\odot}$ neutron star accreting hydrogen. Hence, we identify XBo 45 as a new candidate black hole LMXB. XBo 45 appears to have been consistently bright for ~30 years, consistent with theoretical prediction for a globular cluster black hole binary formed via tidal capture. Bo 375 was observed in the 2007, January 2 XMM-Newton observation, and has a two-component spectrum that is typical for a bright neutron star LMXB. Bo 135 was observed in the same field as Bo 45, and could contain either a black hole or neutron star.Comment: Accepted by ApJ, 16 pages, 5 figures. This version includes the final changes made at the request of the refere

Thymic plasmacytoid dendritic cells are susceptible to productive HIV-1 infection and efficiently transfer R5 HIV-1 to thymocytes in vitro

<p>Abstract</p> <p>Background</p> <p>HIV-1 infection of the thymus contributes to the defective regeneration and loss of CD4⁺T cells in HIV-1-infected individuals. As thymic dendritic cells (DC) are permissive to infection by HIV-1, we examined the ability of thymic DC to enhance infection of thymocytes which may contribute to the overall depletion of CD4⁺T cells. We compared productive infection in isolated human thymic and blood CD11c⁺myeloid DC (mDC) and CD123⁺plasmacytoid DC (pDC) using enhanced green fluorescent protein (EGFP) CCR5 (R5)-tropic NL(AD8) and CXCR4 (X4)-tropic NL4-3 HIV-1 reporter viruses. Transfer of productive HIV-1 infection from thymic mDC and pDC was determined by culturing these DC subsets either alone or with sorted thymocytes.</p> <p>Results</p> <p>Productive infection was observed in both thymic pDC and mDC following exposure to R5 HIV-1 and X4 HIV-1. Thymic pDC were more frequently productively infected by both R5 and X4 HIV-1 than thymic mDC (p = 0.03; n = 6). Thymic pDC efficiently transferred productive R5 HIV-1 infection to both CD3^hi(p = 0.01; mean fold increase of 6.5; n = 6) and CD3^lothymocytes (mean fold increase of 1.6; n = 2). In comparison, transfer of productive infection by thymic mDC was not observed for either X4 or R5 HIV-1.</p> <p>Conclusions</p> <p>The capacity of thymic pDC to efficiently transfer R5 HIV-1 to both mature and immature thymocytes that are otherwise refractory to R5 virus may represent a pathway to early infection and impaired production of thymocytes and CD4⁺T cells in HIV-1-infected individuals.</p

Master integrals with 2 and 3 massive propagators for the 2-loop electroweak form factor - planar case

We compute the master integrals containing 2 and 3 massive propagators entering the planar amplitudes of the 2-loop electroweak form factor. The masses of the $W$, $Z$ and Higgs bosons are assumed to be degenerate. This work is a continuation of our previous evaluation of master integrals containing at most 1 massive propagator. The 1/\epsilon poles and the finite parts are computed exactly in terms of a {\it new} class of 1-dimensional harmonic polylogarithms of the variable x, with \epsilon=2-D/2 and D the pace-time dimension. Since thresholds and pseudothresholds in s=\pm 4m^2 do appear in addition to the old ones in s=0,\pm m^2, an extension of the basis function set involving complex constants and radicals is introduced, together with a set of recursion equations to reduce integrals with semi-integer powers. It is shown that the basic properties of the harmonic polylogarithms are maintained by the generalization. We derive small-momentum expansions |s| << m^2 of all the 6-denominator amplitudes. We also present large momentum expansions |s| >> m^2 of all the 6-denominator amplitudes which can be represented in terms of ordinary harmonic polylogarithms. Comparison with previous results in the literature is performed finding complete agreement.Comment: 68 pages, 7 figure