Effect of Combination Folic Acid, Vitamin B6 , and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial.

Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B12 , B6 , and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard = 1.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B12 or B6 , or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease. © 2017 American Society for Bone and Mineral Research

Age-related hyperkyphosis, independent of spinal osteoporosis, is associated with impaired mobility in older community-dwelling women

While many assume hyperkyphosis reflects underlying spinal osteoporosis and vertebral fractures, our results suggest hyperkyphosis is independently associated with decreased mobility. Hyperyphosis is associated with slower Timed Up and Go performance times and may be a useful clinical marker signaling the need for evaluation of vertebral fracture and falling risk. While multiple studies have demonstrated negative effects of hyperkyphosis on physical function, none have disentangled the relationship between hyperkyphosis, impaired function, and underlying spinal osteoporosis. The purpose of this study is to determine whether kyphosis, independent of spinal osteoporosis, is associated with mobility on the Timed Up and Go, and to quantify effects of other factors contributing to impaired mobility. We used data for 3,108 community-dwelling women aged 55-80 years in the Fracture Intervention Trial. All participants had measurements of kyphosis, mobility time on the Timed Up and Go test, height, weight, total hip bone mineral density (BMD), grip strength, and vertebral fractures at baseline visits in 1993. Demographic characteristics included age and smoking status. We calculated mean Timed Up and Go time by quartile of kyphosis. Using multivariate linear regression, we estimated the independent association of kyphosis with mobility time, and quantified effects of other covariates on mobility. Mean mobility time increased from 9.3 s in the lowest to 10.1 s in the highest quartile of kyphosis. In a multivariate-adjusted model, mobility time increased 0.11 s (p = 0.02) for each standard deviation (11.9°) increase in kyphosis. Longer performance times were significantly associated with increasing age, decreasing grip strength, vertebral fractures, body mass index ≥25, and total hip BMD in the osteoporotic range. Kyphosis angle is independently associated with decreased mobility on the Timed Up and Go, which is in turn correlated with increased fall risk. Hyperkyphosis may be a useful clinical marker signaling the need for evaluation of vertebral fracture and falling risk

Pilot study of a brief provider and EMR-based intervention for overweight teens with asthma

INTRODUCTION: Asthma-related morbidity is increased in overweight patients, yet providers are given little guidance on how to discuss weight and asthma management with overweight teens. OBJECTIVE: We piloted an electronic medical record (EMR)-based tailored discussion guide (TDG) and a brief provider training, to address weight management in overweight teens with asthma. The primary outcome was intervention impact on patient-reported asthma outcomes (e.g., asthma control and morbidity). Secondary outcomes included change in BMI, patient-centeredness, and change in healthy behaviors. METHODS: Teens aged 13-18 years with persistent asthma and a body mass index ≥ 85th percentile for their age and sex were eligible. Parents of eligible teens were contacted before an upcoming appointment to allow teen enrollment during the clinic visit. Providers reviewed Motivational Interviewing (MI) concepts and were trained in the TDG for support of conversations around weight and asthma management. Measures included asthma outcomes retrieved from the EMR at 6- and 12-month post-baseline, teen impressions of patient-provider communication at 6-week post-enrollment, and teen report of healthy behaviors at 6- and 12-month post-baseline. RESULTS: Of 44 teens enrolled (77% African-American, 63% female), mean BMI for intervention (n=25) and control groups (n=19) at baseline were similar. Thirty participants (68%) completed a 6-week questionnaire. Compared to controls, at 6 months, intervention teens reported fewer days of limited activity and uncontrolled asthma, but at 12 months, only restricted activity remained lower, and BMI was not reduced. Intervention teens reported clinic visits that were more patient-centered than controls, including discussion of asthma treatment options with provider, feeling ready to follow an asthma treatment routine, and receiving helpful tips about reaching a healthy weight. The healthy behavior dinner with family showed improvement for intervention teens at 6 and 12 months. The feasibility study also revealed a need to improve recruitment strategies and to streamline intervention delivery. CONCLUSION: Modest improvements in patient-reported asthma outcomes and health behaviors were observed. There was strong evidence that the TDG supports provider discussion of weight and asthma to create a more patient-centered conversation from the perspective of participating teens. Challenges to recruitment and clinic adaptation must be addressed before advancing to a full-scale trial. TRIAL REGISTRATION: NCT02575326 Teen Asthma Control Encouraging a Healthier Lifestyle, www.cllinicaltrials.gov

Position resolution and particle identification with the ATLAS EM calorimeter

In the years between 2000 and 2002 several pre-series and series modules of the ATLAS EM barrel and end-cap calorimeter were exposed to electron, photon and pion beams. The performance of the calorimeter with respect to its finely segmented first sampling has been studied. The polar angle resolution has been found to be in the range 50-60 mrad/sqrt(E (GeV)). The neutral pion rejection has been measured to be about 3.5 for 90% photon selection efficiency at pT=50 GeV/c. Electron-pion separation studies have indicated that a pion fake rate of (0.07-0.5)% can be achieved while maintaining 90% electron identification efficiency for energies up to 40 GeV.Comment: 32 pages, 22 figures, to be published in NIM

Les Houches 2013: Physics at TeV Colliders: Standard Model Working Group Report

This Report summarizes the proceedings of the 2013 Les Houches workshop on Physics at TeV Colliders. Session 1 dealt primarily with (1) the techniques for calculating standard model multi-leg NLO and NNLO QCD and NLO EW cross sections and (2) the comparison of those cross sections with LHC data from Run 1, and projections for future measurements in Run 2.Comment: Proceedings of the Standard Model Working Group of the 2013 Les Houches Workshop, Physics at TeV Colliders, Les houches 3-21 June 2013. 200 page

Effects of combined treatment with rapamycin and cotylenin A, a novel differentiation-inducing agent, on human breast carcinoma MCF-7 cells and xenografts

INTRODUCTION: Rapamycin, an inhibitor of the serine/threonine kinase target of rapamycin, induces G(1 )arrest and/or apoptosis. Although rapamycin and its analogues are attractive candidates for cancer therapy, their sensitivities with respect to growth inhibition differ markedly among various cancer cells. Using human breast carcinoma cell line MCF-7 as an experimental model system, we examined the growth-inhibitory effects of combinations of various agents and rapamycin to find the agent that most potently enhances the growth-inhibitory effect of rapamycin. METHOD: We evaluated the growth-inhibitory effect of rapamycin plus various agents, including cotylenin A (a novel inducer of differentiation of myeloid leukaemia cells) to MCF-7 cells, using either MTT assay or trypan blue dye exclusion test. The cell cycle was analyzed using propidium iodide-stained nuclei. Expressions of several genes in MCF-7 cells with rapamycin plus cotylenin A were studied using cDNA microarray analysis and RT-PCR. The in vitro results of MCF-7 cells treated with rapamycin plus cotylenin A were further confirmed in vivo in a mouse xenograft model. RESULTS: We found that the sensitivity of rapamycin to MCF-7 cells was markedly affected by cotylenin A. This treatment induced growth arrest of the cells at the G(1 )phase, rather than apoptosis, and induced senescence-associated β-galactosidase activity. We examined the gene expression profiles associated with exposure to rapamycin and cotylenin A using cDNA microarrays. We found that expressions of cyclin G(2), transforming growth factor-β-induced 68 kDa protein, BCL2-interacting killer, and growth factor receptor-bound 7 were markedly induced in MCF-7 cells treated with rapamycin plus cotylenin A. Furthermore, combined treatment with rapamycin and cotylenin A significantly inhibited the growth of MCF-7 cells as xenografts, without apparent adverse effects. CONCLUSION: Rapamycin and cotylenin A cooperatively induced growth arrest in breast carcinoma MCF-7 cells in vitro, and treatment with rapamycin and cotylenin A combined more strongly inhibited the growth of MCF-7 cells as xenografts in vivo than treatment with rapamycin or cotylenin A alone, suggesting that this combination may have therapeutic value in treating breast cancer. We also identified several genes that were markedly modulated in MCF-7 cells treated with rapamycin plus cotylenin A

Energy Linearity and Resolution of the ATLAS Electromagnetic Barrel Calorimeter in an Electron Test-Beam

A module of the ATLAS electromagnetic barrel liquid argon calorimeter was exposed to the CERN electron test-beam at the H8 beam line upgraded for precision momentum measurement. The available energies of the electron beam ranged from 10 to 245 GeV. The electron beam impinged at one point corresponding to a pseudo-rapidity of eta=0.687 and an azimuthal angle of phi=0.28 in the ATLAS coordinate system. A detailed study of several effects biasing the electron energy measurement allowed an energy reconstruction procedure to be developed that ensures a good linearity and a good resolution. Use is made of detailed Monte Carlo simulations based on Geant which describe the longitudinal and transverse shower profiles as well as the energy distributions. For electron energies between 15 GeV and 180 GeV the deviation of the measured incident electron energy over the beam energy is within 0.1%. The systematic uncertainty of the measurement is about 0.1% at low energies and negligible at high energies. The energy resolution is found to be about 10% sqrt(E) for the sampling term and about 0.2% for the local constant term