Summary Objective Epidemiological data suggest low serum 25-hydroxyvitamin D3 (25-OH-D3 ) levels are associated with radiological progression of knee osteoarthritis (OA). This study aimed to assess ...whether vitamin D supplementation can slow the rate of progression. Method A 3 year, double-blind, randomised, placebo-controlled trial of 474 patients aged over 50 with radiographically evident knee OA comparing 800 IU cholecalciferol daily with placebo. Primary outcome was difference in rate of medial joint space narrowing (JSN). Secondary outcomes included lateral JSN, Kellgren and Lawrence grade, WOMAC pain, function, stiffness and the Get up and Go test. Results Vitamin D supplementation increased 25-OH-D3 from an average of 20·7 (SD 8·9) μg/L to 30·4 (SD 7·7) μg/L, compared to 20·7 (SD 8·1) μg/L and 20·3 (SD 8·1) μg/L in the placebo group. There was no significant difference in the rate of JSN over three years in the medial compartment of the index knee between the treatment group (average -0.01 mm/year) and placebo group (-0.08 mm/year), average difference 0.08 mm/year, (95% CI -0·14 to 0·29, p=0.49). No significant interaction was found between baseline vitamin D levels and treatment effect. There were no significant differences for any of the secondary outcome measures. Conclusion Vitamin D supplementation did not slow the rate of JSN or lead to reduced pain, stiffness or functional loss over a three year period. On the basis of these findings we consider that vitamin D supplementation has no role in the management of knee OA.
A precise measurement of the differential cross sections dσ/dΩ and the linearly polarized photon beam asymmetry Σ_{3} for Compton scattering on the proton below pion threshold has been performed with ...a tagged photon beam and almost 4π detector at the Mainz Microtron. The incident photons were produced by the recently upgraded Glasgow-Mainz photon tagging facility and impinged on a cryogenic liquid hydrogen target, with the scattered photons detected in the Crystal Ball/TAPS setup. Using the highest statistics Compton scattering data ever measured on the proton along with two effective field theories (both covariant baryon and heavy-baryon) and one fixed-t dispersion relation model, constraining the fits with the Baldin sum rule, we have obtained the proton electric and magnetic polarizabilities with unprecedented precision: α_{E1}=10.99±0.16±0.47±0.17±0.34, β_{M1}=3.14±0.21±0.24±0.20±0.35; in units of 10^{-4} fm^{3} where the errors are statistical, systematic, spin polarizability dependent, and model dependent.
We present Atacama Large Millimeter/submillimeter Array (ALMA) 1.3 mm (230 GHz) observations of the HD 32297 and HD 61005 debris disks, two of the most iconic debris disks because of their dramatic ...swept-back wings seen in scattered light images. These observations achieve sensitivities of 14 and 13 Jy beam−1 for HD 32297 and HD 61005, respectively, and provide the highest resolution images of these two systems at millimeter wavelengths to date. By adopting a Markov Chain Monte Carlo modeling approach, we determine that both disks are best described by a two-component model consisting of a broad (ΔR/R > 0.4) planetesimal belt with a rising surface density gradient and a steeply falling outer halo aligned with the scattered light disk. The inner and outer edges of the planetesimal belt are located at 78.5 8.1 au and 122 3 au for HD 32297, and 41.9 0.9 au and 67.0 0.5 au for HD 61005. The halos extend to 440 32 au and 188 8 au, respectively. We also detect 12CO J = 2-1 gas emission from HD 32297 co-located with the dust continuum. These new ALMA images provide observational evidence that larger, millimeter-sized grains may also populate the extended halos of these two disks previously thought to only be composed of small, micron-sized grains. We discuss the implications of these results for potential shaping and sculpting mechanisms of asymmetric debris disks.
Recent Atacama Large Millimeter/submillimeter Array observations present mounting evidence for the presence of exocometary gas released within Kuiper Belt analogs around nearby main-sequence stars. ...This represents a unique opportunity to study their ice reservoir at the younger ages when volatile delivery to planets is most likely to occur. We here present the detection of CO J = 2-1 emission colocated with dust emission from the cometary belt in the 440 Myr old Fomalhaut system. Through spectrospatial filtering, we achieve a 5.4 detection and determine that the ring's sky-projected rotation axis matches that of the star. The CO mass derived ( ) is the lowest of any circumstellar disk detected to date and must be of exocometary origin. Using a steady-state model, we estimate the CO+CO2 mass fraction of exocomets around Fomalhaut to be between 4.6% and 76%, consistent with solar system comets and the two other belts known to host exocometary gas. This is the first indication of a similarity in cometary compositions across planetary systems that may be linked to their formation scenario and is consistent with direct interstellar medium inheritance. In addition, we find tentative evidence that % of the detected flux originates from a region near the eccentric belt's pericenter. If confirmed, the latter may be explained through a recent impact event or CO pericenter glow due to exocometary release within a steady-state collisional cascade. In the latter scenario, we show how the azimuthal dependence of the CO release rate leads to asymmetries in gas observations of eccentric exocometary belts.
We present observations of the HD 15115 debris disk from the Atacama Large Millimeter/submillimeter Array (ALMA) at 1.3 mm that capture this intriguing system with the highest resolution (0 6 or 29 ...au) at millimeter wavelengths to date. This new ALMA image shows evidence for two rings in the disk separated by a cleared gap. By fitting models directly to the observed visibilities within a Markov Chain Monte Carlo framework, we are able to characterize the millimeter continuum emission and place robust constraints on the disk structure and geometry. In the best-fit model of a power-law disk with a Gaussian gap, the disk inner and outer edges are at 43.9 5.8 au (0 89 0 12) and 92.2 2.4 au (1 88 0 49), respectively, with a gap located at 58.9 4.5 au (1 2 0 10) with a fractional depth of 0.88 0.10 and a width of 13.8 5.6 au (0 28 0 11). Because we do not see any evidence at millimeter wavelengths for the dramatic east-west asymmetry seen in scattered light, we conclude that this feature most likely results from a mechanism that only affects small grains. Using dynamical modeling and our constraints on the gap properties, we are able to estimate a mass for the possible planet sculpting the gap to be 0.16 0.06 MJup.
Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls ...and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.
We report a measurement of the spin polarization of the recoiling neutron in deuterium photodisintegration, utilizing a new large acceptance polarimeter within the Crystal Ball at MAMI. The measured ...photon energy range of 300-700 MeV provides the first measurement of recoil neutron polarization at photon energies where the quark substructure of the deuteron plays a role, thereby providing important new constraints on photodisintegration mechanisms. A very high neutron polarization in a narrow structure centered around E_{γ}∼570 MeV is observed, which is inconsistent with current theoretical predictions employing nucleon resonance degrees of freedom. A Legendre polynomial decomposition suggests this behavior could be related to the excitation of the d^{*}(2380) hexaquark.
A DNA-based vaccine containing human immunodeficiency virus type 1 (HIV-1) env and rev genes was tested for safety and host immune response in 15 asymptomatic HIV-infected patients who were not using ...antiviral drugs and who had CD4+ lymphocyte counts of ⩾500 per microliter of blood. Successive groups received three doses of vaccine (30, 100, or 300 µg) at 10-week intervals in a dose-escalation trial. Vaccine administration induced no local or systemic reactions, and no laboratory abnormalities were detected. Specifically, no patient developed anti-DNA antibody or muscle enzyme elevations. No consistent change occurred in CD4 or CD8 lymphocyte counts or in plasma HIV concentration. Antibody against gp120 increased in individual patients in the 100- and 300-µg groups. Some increases were noted in cytotoxic T lymphocyte activity against gp160-bearing targets and in lymphocyte proliferative activity. The safety and potential immunogenicity of an HIV-directed DNA-based vaccine was demonstrated, a finding that should encourage further studies.
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