Predictors of Lumbar Spine Degeneration and Low Back Pain in the Community: The Johnston County Osteoarthritis Project

Objective: To determine the incidence and worsening of lumbar spine structure and low back pain (LBP) and whether they are predicted by demographic characteristics or clinical characteristics or appendicular joint osteoarthritis (OA). Methods: Paired baseline (2003–2004) and follow-up (2006–2010) lumbar spine radiographs from the Johnston County Osteoarthritis Project were graded for osteophytes (OST), disc space narrowing (DSN), spondylolisthesis, and presence of facet joint OA (FOA). Spine OA was defined as at least mild OST and mild DSN at the same level for any level of the lumbar spine. LBP, comorbidities, and back injury were self-reported. Weibull models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of spine phenotypes accounting for potential predictors including demographic characteristics, clinical characteristics, comorbidities, obesity, and appendicular OA. Results: Obesity was a consistent and strong predictor of incidence of DSN (HR 1.80 [95% CI 1.09–2.98]), spine OA (HR 1.56 [95% CI 1.01–2.41]), FOA (HR 4.99 [95% CI 1.46–17.10]), spondylolisthesis (HR 1.87 [95% CI 1.02–3.43]), and LBP (HR 1.75 [95% CI 1.19–2.56]), and worsening of DSN (HR 1.51 [95% CI 1.09–2.09]) and LBP (HR 1.51 [95% CI 1.12–2.06]). Knee OA was a predictor of incident FOA (HR 4.18 [95% CI 1.44–12.2]). Spine OA (HR 1.80 [95% CI 1.24–2.63]) and OST (HR 1.85 [95% CI 1.02–3.36]) were predictors of incidence of LBP. Hip OA (HR 1.39 [95% CI 1.04–1.85]) and OST (HR 1.58 [95% CI 1.00–2.49]) were predictors of LBP worsening. Conclusion: Among the multiple predictors of spine phenotypes, obesity was a common predictor for both incidence and worsening of lumbar spine degeneration and LBP

Inflammatory, Structural, and Pain Biochemical Biomarkers May Reflect Radiographic Disc Space Narrowing: The Johnston County Osteoarthritis Project

The purpose of this work is to determine the relationship between biomarkers of inflammation, structure, and pain with radiographic disc space narrowing (DSN) in community-based participants. A total of 74 participants (37 cases and 37 controls) enrolled in the Johnston County Osteoarthritis Project during 2006–2010 were selected. The cases had at least mild radiographic DSN and low back pain (LBP). The controls had neither radiographic evidence of DSN nor LBP. The measured analytes from human serum included N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, IL-17, IL-6, BDNF, OPG, and NPY. A standard dolorimeter measured pressure-pain threshold. The coefficients of variation were used to evaluate inter- and intra-assay reliability. Participants with similar biomarker profiles were grouped together using cluster analysis. The binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) in propensity score-matched models. Significant associations were found between radiographic DSN and OPG (RR = 3.90; 95% CI: 1.83, 8.31), IL-6 (RR = 2.54; 95% CI: 1.92, 3.36), and NPY (RR = 2.06 95% CI: 1.62, 2.63). Relative to a cluster with low levels of biomarkers, a cluster representing elevated levels of OPG, RANTES, Lumican, Keratin-19, and NPY (RR = 3.04; 95% CI: 1.22, 7.54) and a cluster representing elevated levels of NPY (RR = 2.91; 95% CI: 1.15, 7.39) were significantly associated with radiographic DSN. Clinical Significance: These findings suggest that individual and combinations of biochemical biomarkers may reflect radiographic DSN. This is just one step toward understanding the relationships between biochemical biomarkers and DSN that may lead to improved intervention delivery

Can three-flavor oscillations solve the solar neutrino problem?

The most promising solution to the solar neutrino problem are neutrino oscillations, which usually are analyzed within the reduced 2-flavor scheme, because the solutions found therein reasonably well reproduce the recent data of Super-Kamiokande about the recoil-electron energy spectrum, zenith-angle and seasonal variations, and the event rate data of all the neutrino detectors. In this work, however, a survey of the complete parameter space of 3-flavor oscillations is performed. Basically eight new additional solutions could be identified, where the best one with \Delta m(12)^2=2.7x10^(-10) eV^2, \Delta m(13)^2=1.0x10^(-5) eV^2, \Theta(12)=23, and \Theta(13)=1.3 (denoted SVO) is slightly more probable than any 2-flavor solution. However, including the results of the atmospheric neutrino problem excludes all 3-flavour solutions apart from the SLMA-solution (\Delta m(12)^2=7.9x10^(-6) eV^2, \Delta m(13)^2=2.5x10^(-4) eV^2, \Theta(12)=1.4, and \Theta(13)=20). Besides, the ability of SNO and Borexino to discriminate the various 2- and 3-flavor solutions is investigated. Only with very good statistics in these experiments the correct solution to the solar neutrino problem can be identified unambiguously.Comment: 22 pages, 19 figures, REVTeX, submitted to Phys.Rev.D, article with better resolved figures available under http://www.mpa-garching.mpg.de/~schlattl/public.htm

Global Analysis with SNO: Toward the Solution of the Solar Neutrino Problem

We perform a global analysis of the latest solar neutrino data including the SNO result on the CC-event rate. This result further favors the LMA solution of the solar neutrino problem. The best fit values of parameters we find are: \Delta m^2 = (4.8 - 5.0)10^{-5} eV^2, tan^2 \theta = 0.35 - 0.38, f_B = 1.08 - 1.12, and f_{hep} = 1 - 4. With respect to this best fit the LOW solution is accepted at 90% C.L.. The Vacuum oscillation solution with \Delta m^2 = 1.4 10^{-10} eV^2, gives good fit of the data provided that the boron neutrino flux is substantially smaller than the SSM flux (f_B \sim 0.5). The SMA solution is accepted only at 3\sigma level. We find that vacuum oscillations to sterile neutrino, VAC(sterile), with f_B \sim 0.5 also give rather good global fit of the data. All other sterile solutions are strongly disfavored. We check the quality of the fit by constructing the pull-off diagrams of observables. Predictions for the day-night asymmetry, spectrum distortion and NC/CC ratio at SNO are calculated. In the best fit points of the global solutions we find: A_{DN}^{CC} \approx (7 - 8)% for LMA, \sim 3% for LOW, and (2 - 3)% for SMA. It will be difficult to see the distortion of the spectrum expected for LMA as well as LOW solutions. However, future SNO spectral data can significantly affect the VAC and SMA solutions. We also calculate expectations for the BOREXINO rate.Comment: 35 pages, latex, 9 figures; results of analysis slightly changed due to different treatment of the hep neutrino flux; predictions for NC/CC ratio and Borexino rate adde

Polymorphisms in DNA repair genes, recreational physical activity and breast cancer risk

The mechanisms driving the inverse association between recreational physical activity (RPA) and breast cancer risk are complex. While exercise is associated with increased reactive oxygen species production it may also improve damage repair systems, particularly those that operate on single-strand breaks including base excision repair (BER), nucleotide excision repair (NER) and mismatch repair (MMR). Of these repair pathways, the role of MMR in breast carcinogenesis is least investigated. Polymorphisms in MMR or other DNA repair gene variants may modify the association between RPA and breast cancer incidence. We investigated the individual and joint effects of variants in three MMR pathway genes (MSH3, MLH1 and MSH2) on breast cancer occurrence using resources from the Long Island Breast Cancer Study Project. We additionally characterized interactions between RPA and genetic polymorphisms in MMR, BER and NER pathways. We found statistically significant multiplicative interactions (p < 0.05) between MSH2 and MLH1, as well as between postmenopausal RPA and four variants in DNA repair (XPC-Ala499Val, XPF-Arg415Gln, XPG-Asp1104His and MLH1-lle219Val). Significant risk reductions were observed among highly active women with the common genotype for XPC (OR = 0.54; 95% CI, 0.36-0.81) and XPF (OR = 0.62; 95% CI, 0.44-0.87), as well as among active women who carried at least one variant allele in XPG (OR = 0.46; 95% CI, 0.29-0.77) and MLH1 (OR = 0.46; 95% CI, 0.30-0.71). Our data show that women with minor alleles in both MSH2 and MLH1 could be at increased breast cancer risk. RPA may be modified by genes in the DNA repair pathway, and merit further investigation

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

A joint Fermi-GBM and Swift-BAT analysis of gravitational-wave candidates from the third gravitational-wave observing run

We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift-BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers