The Spin-Dependent Structure Functions of Nuclei in the Meson-Nucleon Theory

A theoretical approach to the investigation of spin-dependent structure functions in deep inelastic scattering of polarized leptons off polarized nuclei, based on the effective meson-nucleon theory and operator product expansion method, is proposed and applied to deuteron and $^3He$. The explicit forms of the moments of the deuteron and $^3He$ spin-dependent structure functions are found and numerical estimates of the influence of nuclear structure effects are presented.Comment: 42 pages revtex, 7 postscript figures available from above e-mail upon request. Perugia preprint DFUPG 92/9

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

X-shooter and ALMA spectroscopy of GRB 161023A A study of metals and molecules in the line of sight towards a luminous GRB

Context. Long gamma-ray bursts (GRBs) are produced during the dramatic deaths of massive stars with very short lifetimes, meaning that they explode close to the birth place of their progenitors. Over a short period they become the most luminous objects observable in the Universe, being perfect beacons to study high-redshift star-forming regions. Aims. We aim to use the afterglow of GRB 161023A at a redshift z = 2.710 as a background source to study the environment of the explosion and the intervening systems along its line of sight. Methods. For the first time, we complement ultraviolet (UV), optical and near-infrared (NIR) spectroscopy with millimetre spectroscopy using the Atacama Large Millimeter Array (ALMA), which allows us to probe the molecular content of the host galaxy. The X-shooter spectrum shows a plethora of absorption features including fine-structure and metastable transitions of Fe, Ni, Si, C, and O. We present photometry ranging from 43 s to over 500 days after the burst. Results. We infer a host-galaxy metallicity of [Zn/H] = −1.11 ± 0.07, which, corrected for dust depletion, results in [X/H] = −0.94 ± 0.08. We do not detect molecular features in the ALMA data, but we derive limits on the molecular content of log(NCO/cm−2) < 15.7 and log(NHCO+/cm−-12, which are consistent with those that we obtain from the optical spectra, log(NH2/cm−2)< 15.2 and log(NCO/cm−2) < 14.5. Within the host galaxy, we detect three velocity systems through UV, optical and NIR absorption spectroscopy, all with levels that were excited by the GRB afterglow. We determine the distance from these systems to the GRB to be in the range between 0.7 and 1.0 kpc. The sight line to GRB 161023A shows nine independent intervening systems, most of them with multiple components. Conclusions. Although no molecular absorption was detected for GRB 161023A, we show that GRB millimetre spectroscopy is now feasible and is opening a new window on the study of molecular gas within star-forming galaxies at all redshifts. The most favoured lines of sight for this purpose will be those with high metallicity and dust

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Apremilast increases IL-10-producing regulatory B cells and decreases proinflammatory T cells and innate cells in psoriatic arthritis and psoriasis

Objectives: Psoriatic arthritis (PsA) and psoriasis are immune-mediated inflammatory diseases sharing common immunological mechanisms. Regulatory B cells (Breg cells) producing IL-10 (B10 cells), a critical anti-inflammatory B-cell subset, were found to be decreased in both PsA and psoriasis. Apremilast, a phosphodiesterase-4(PDE4) inhibitor, increases IL-10 and therefore, we examined the effect of apremilast on Breg cells. Methods: Fifty patients, including 20 with PsA and 30 with psoriasis, were included in the study. The effect of apremilast on Breg cells at 3, 6 and 12 months post-treatment, was examined by flow cytometry in ODN2006 (TLR9)-stimulated peripheral blood mononuclear cells and magnetically-isolated cells. Th1 cells, Th17 cells and NKT were also measured. Results: Ex vivo stimulated cell analysis identified that post-apremilast (IL-10+CD19+) B10 cells were increased in all PsA and psoriasis patients and correlated with psoriatic skin and joint clinical improvement. Apremilast decreased IFNγ(+) T and NKT cells and IL-17(+)NKT cells. B10 cells also inversely correlated with Th1 cells, and IFNγ(+)NKT cells. Conclusion: These results suggest that Breg cells are a major target of apremilast in PsA and psoriasis and that apremilast-induced increase of Breg cells is associated with a decrease of Th1 cells, IFNγ-producing NKT cells and IL-17-producing NKT cells. © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected]

Autoantibodies against specific nuclear antigens are present in psoriatic disease and are diminished by secukinumab

Anti-nuclear antibodies (ANA) are frequently detected in patients with psoriasis (Ps) and psoriatic arthritis (PsA), but their target autoantigens remain unknown. We assessed antibody (ab) reactivity against 23 known nuclear antigens in patients with Ps and PsA and assess the effects of secukinumab (anti-IL17A) treatment on ANA levels. A total of 201 patients, 101 with Ps and 100 with PsA, and 50 ANA-negative healthy controls (HCs) were tested for ANAs by a line immunoassay testing reactivity to 23 nuclear antigens. Ab reactivity to at least 1 antigen was found in 20.4% psoriatic disease patients (25.7% Ps and 15% PsA) compared to 8% HCs (p = ns), the most frequent being against dense fine speckled 70 (DFS70) (6.5%). In Ps and PsA patients with secukinumab-induced remission, anti-DFS70 and other antigen-specific autoantibodies were diminished over time. No decline was noted for IgG abs against antigens from pathogens such as cytomegalovirus, Epstein–Barr virus and Helicobacter pylori. Autoantibody decrease was associated with significant reduction of plasmablasts, follicular B and follicular T cells. In conclusion, one third of antigen-specific ANA patients with psoriatic disease recognize DFS70. Secukinumab decreases nuclear antigen autoreactivity, plasmablasts, follicular B and follicular T cells, highlighting a new mechanism of its action. © 2020 Elsevier B.V