Lifestyle and metabolic factors for nonalcoholic fatty liver disease:Mendelian randomization study

The risk factors for nonalcoholic fatty liver disease (NAFLD) have not been clearly identified. We conducted a Mendelian randomization (MR) study to explore this. Independent genetic variants strongly associated with 5 lifestyle and 9 metabolic factors were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for NAFLD were obtained from a GWAS meta-analysis of 8434 cases and 770,180 non-cases (discovery dataset) and another GWAS meta-analysis of 1483 cases and 17,781 non-cases (replication dataset). Univariable and multivariable MR analyses were performed. There were associations with NAFLD for lifetime smoking index (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.31-1.93 per SD-increase), body mass index (BMI, OR 1.33, 95% CI 1.23-1.43 per SD-increase), waist circumference (OR 1.82; 95% CI 1.48-2.24 per SD-increase), type 2 diabetes (OR 1.21, 95% CI 1.15-1.27 per unit increase in log-transformed odds), systolic blood pressure (OR 1.17; 95% CI 1.07-1.26 per 10 mmHg increase), high-density lipoprotein cholesterol (OR 0.84, 95% CI 0.77-0.90 per SD-increase), and triglycerides (OR 1.23, 95% CI 1.15-1.33 per SD-increase). The associations for type 2 diabetes, systolic blood pressure, triglycerides, but not for high-density lipoprotein cholesterol remained strong after adjusting for genetically-predicted BMI. Genetic liability to type 2 diabetes mediated 51.4% (95% CI 13.4-89.3%) of the BMI-effects on NAFLD risk. There were suggestive inverse associations of genetically-predicted alcohol, coffee, and caffeine consumption, and vigorous physical activity with NAFLD risk. This study identified several lifestyle and metabolic factors that may be causally implicated in NAFLD

Health effects of high serum calcium levels:Updated phenome-wide Mendelian randomisation investigation and review of Mendelian randomisation studies

BACKGROUND: Calcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for MR studies to comprehensively investigate the health effects of serum calcium. METHODS: One-hundred and thirty genetic variants strongly associated with serum calcium levels were used as instrumental variables. A phenome-wide association analysis (PheWAS) was conducted to examine the associations of genetically predicted serum calcium with 1473 distinct phenotypes in the UK Biobank including 339,197 individuals. Observed associations in PheWAS were further tested for replication in two-sample MR replication analysis. A systematic review for MR studies on serum calcium was performed to synthesize the published evidence and compare with the current MR-PheWAS findings. FINDINGS: Higher genetically predicted calcium levels were associated with decreased risk of 5 diseases in dermatologic and musculoskeletal systems and increased risk of 17 diseases in circulatory, digestive, endocrine, genitourinary and immune systems. Eight associations were replicated in two-sample MR analysis. These included decreased risk of osteoarthritis and increased risk of coronary artery disease, myocardial infarction, coronary atherosclerosis, hyperparathyroidism, disorder of parathyroid gland, gout, and calculus of kidney and ureter with increased serum calcium. Systematic review of 25 MR studies provided supporting evidence on five out of the eight disease outcomes, while the increased risk of gout, hyperparathyroidism and disorder of parathyroid gland were novel findings. INTERPRETATION: This study found wide-ranged health effects of high serum calcium, which suggests that the benefits and adversities of strategies promoting calcium intake should be assessed. FUNDING: ET is supported by a CRUK Career Development Fellowship (C31250/A22804). XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province. SCL acknowledges research funding from the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council (Vetenskapsrådet, 2019-00977), and the Swedish Cancer Society (Cancerfonden)

Optical Conductivity of Manganites: Crossover from Jahn-Teller Small Polaron to Coherent Transport in the Ferromagnetic State

We report on the optical properties of the hole-doped manganites Nd_{0.7}Sr _{0.3}MnO_{3}, La_{0.7}Ca_{0.3}MnO_{3}, and La_{0.7}Sr_{0.3}MnO_{3}. The low-energy optical conductivity in the paramagnetic-insulating state of these materials is characterized by a broad maximum near 1 eV. This feature shifts to lower energy and grows in optical oscillator strength as the temperature is lowered into the ferromagnetic state. It remains identifiable well below Tc and transforms eventually into a Drude-like response. This optical behavior and the activated transport in the paramagnetic state of these materials are consistent with a Jahn-Teller small polaron. The optical spectra and oscillator strength changes compare well with models that include both double exchange and the dynamic Jahn-Teller effect in the description of the electronic structure.Comment: 27 pages (Latex), 6 figures (PostScript

Estimation of the charge carrier localization length from Gaussian fluctuations in the magneto-thermopower of La_{0.6}Y_{0.1}Ca_{0.3}MnO_3

The magneto-thermoelectric power (TEP) $\Delta S(T,H)$ of perovskite type manganise oxide $La_{0.6}Y_{0.1}Ca_{0.3}MnO_3$ is found to exhibit a sharp peak at some temperature $T^{*}=170K$. By approximating the true shape of the measured magneto-TEP in the vicinity of $T^{*}$ by a linear triangle of the form $\Delta S(T,H)\simeq S_p(H)\pm B^{\pm}(H)(T^{*}-T)$, we observe that $B ^{-}(H)\simeq 2B ^{+}(H)$. We adopt the electron localization scenario and introduce a Ginzburg-Landau (GL) type theory which incorporates the two concurrent phase transitions, viz., the paramagnetic-ferromagnetic transition at the Curie point $T_C$ and the "metal-insulator" (M-I) transition at $T_{MI}$. The latter is characterized by the divergence of the field-dependent charge carrier localization length $\xi (T,H)$ at some characteristic field $H_0$. Calculating the average and fluctuation contributions to the total magnetization and the transport entropy related magneto-TEP $\Delta S(T,H)$ within the GL theory, we obtain a simple relationship between $T^{*}$ and the above two critical temperatures ($T_{C}$ and $T_{MI}$). The observed slope ratio $B ^{-}(H)/B ^{+}(H)$ is found to be governed by the competition between the electron-spin exchange $JS$ and the induced magnetic energy $M_sH_0$. The comparison of our data with the model predictions produce $T_{C}=195K$, $JS=40meV$, $M_0=0.4M_s$, $\xi_0=10\AA$, and $n_e/n_i=2/3$ for the estimates of the Curie temperature, the exchange coupling constant, the critical magnetization, the localization length, and the free-to-localized carrier number density ratio, respectively.Comment: 6 pages (REVTEX), 2 PS figures (epsf.sty); submitted to Phys.Rev.

Double-exchange is not the cause of ferromagnetism in doped manganites

The coexistence of ferromagnetism and metallic conduction in doped manganites has long been explained by a double-exchange model in which the ferromagnetic exchange arises from the carrier hopping. We evaluate the zero-temperature spin stiffness D(0) and the Curie temperature T_{C} on the basis of the double-exchange model using the measured values of the bare bandwidth W and the Hund's rule coupling J_{H}. The calculated D(0) and T_{C} values are too small compared with the observed ones even in the absence of interactions. A realistic onsite interorbital Coulomb repulsion can reduce D(0) substantially in the case of a 2-orbital model. Furthermore, experiment shows that D(0) is simply proportional to x in La_{1-x}Sr_{x}MnO_{3} system, independent of whether the ground state is a ferromagnetic insulator or metal. These results strongly suggest that the ferromagnetism in manganites does not originate from the double-exchange interaction. On the other hand, an alternative model based on the d-p exchange can semi-quantitatively explain the ferromagnetism of doped manganites at low temperatures.Comment: 6 pages, 3 figures, some modifications in scientific content

Study of Vibrations in a Short-Span Bridge Under Resonance Conditions Considering Train-Track Interaction

[EN] Resonance is a phenomenon of utmost importance in railways engineering, leading to vast damages both in track and vehicles. A short-span bridge has been modeled by means of a finite elements method model, calibrated and validated with real data, to study resonance vibrations induced by the passage of trains. Furthermore, the influence of vehicle speed and track damping on the vibrations registered on the rail, the sleeper and the bridge has been assessed. Different track and vehicle pathologies have been proposed and their effect on the resonance of the bridge has been evaluated.Ribes-Llario, F.; Velarte-González, JL.; Pérez-Garnes, JL.; Real Herráiz, JI. (2016). Study of Vibrations in a Short-Span Bridge Under Resonance Conditions Considering Train-Track Interaction. Latin American Journal of Solids and Structures. 13(7):1236-1249. doi:10.1590/1679-78252773S12361249137Ahlström, J., & Karlsson, B. (1999). Microstructural evaluation and interpretation of the mechanically and thermally affected zone under railway wheel flats. Wear, 232(1), 1-14. doi:10.1016/s0043-1648(99)00166-0Bian, X., Chao, C., Jin, W., & Chen, Y. (2011). A 2.5D finite element approach for predicting ground vibrations generated by vertical track irregularities. Journal of Zhejiang University-SCIENCE A, 12(12), 885-894. doi:10.1631/jzus.a11gt012Grassie, S. L., & Kalousek, J. (1993). Rail Corrugation: Characteristics, Causes and Treatments. Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit, 207(1), 57-68. doi:10.1243/pime_proc_1993_207_227_02Gupta, A., & Singh Ahuja, A. (2014). Dynamic Analysis of Railway Bridges under High Speed Trains. Universal Journal of Mechanical Engineering, 2(6), 199-204. doi:10.13189/ujme.2014.020604Ju, S. H., & Lin, H. T. (2003). Resonance characteristics of high-speed trains passing simply supported bridges. Journal of Sound and Vibration, 267(5), 1127-1141. doi:10.1016/s0022-460x(02)01463-3Kwark, J. W., Choi, E. S., Kim, Y. J., Kim, B. S., & Kim, S. I. (2004). Dynamic behavior of two-span continuous concrete bridges under moving high-speed train. Computers & Structures, 82(4-5), 463-474. doi:10.1016/s0045-7949(03)00054-3Lu, Y., Mao, L., & Woodward, P. (2012). Frequency characteristics of railway bridge response to moving trains with consideration of train mass. Engineering Structures, 42, 9-22. doi:10.1016/j.engstruct.2012.04.007Makino, T., Yamamoto, M., & Fujimura, T. (2002). Effect of material on spalling properties of railroad wheels. Wear, 253(1-2), 284-290. doi:10.1016/s0043-1648(02)00117-5Mao, L., & Lu, Y. (2013). Critical Speed and Resonance Criteria of Railway Bridge Response to Moving Trains. Journal of Bridge Engineering, 18(2), 131-141. doi:10.1061/(asce)be.1943-5592.0000336Museros, P., Romero, M. ., Poy, A., & Alarcón, E. (2002). Advances in the analysis of short span railway bridges for high-speed lines. Computers & Structures, 80(27-30), 2121-2132. doi:10.1016/s0045-7949(02)00261-4Pal, S., Valente, C., Daniel, W., & Farjoo, M. (2012). Metallurgical and physical understanding of rail squat initiation and propagation. Wear, 284-285, 30-42. doi:10.1016/j.wear.2012.02.013Sheng, X., Jones, C. J. C., & Thompson, D. J. (2004). A theoretical model for ground vibration from trains generated by vertical track irregularities. Journal of Sound and Vibration, 272(3-5), 937-965. doi:10.1016/s0022-460x(03)00782-xSimon, S., Saulot, A., Dayot, C., Quost, X., & Berthier, Y. (2013). Tribological characterization of rail squat defects. Wear, 297(1-2), 926-942. doi:10.1016/j.wear.2012.11.011Wang, Y., Wei, Q., Shi, J., & Long, X. (2010). Resonance characteristics of two-span continuous beam under moving high speed trains. Latin American Journal of Solids and Structures, 7(2), 185-199. doi:10.1590/s1679-78252010000200005Xia, H., Zhang, N., & Guo, W. W. (2006). Analysis of resonance mechanism and conditions of train–bridge system. Journal of Sound and Vibration, 297(3-5), 810-822. doi:10.1016/j.jsv.2006.04.022Yang, Y. B., & Lin, C. W. (2005). Vehicle–bridge interaction dynamics and potential applications. Journal of Sound and Vibration, 284(1-2), 205-226. doi:10.1016/j.jsv.2004.06.03

Exploring the complex relationship between gut microbiota and risk of colorectal neoplasia using bidirectional Mendelian Randomization analysis

Background: Human gut microbiome has complex relation-ships with the host, contributing to metabolism, immunity, and carcinogenesis. Methods: Summary-level data for gut microbiota and metabo-lites were obtained from MiBioGen, FINRISK and human meta-bolome consortia. Summary-level data for colorectal cancer were derived from a genome-wide association study meta-analysis. In forward Mendelian randomization (MR), we employed genetic instrumental variables (IV) for 24 gut microbiota taxa and six bacterial metabolites to examine their causal relationship with colorectal cancer. We also used a lenient threshold for nine apriori gut microbiota taxa as secondary analyses. In reverse MR, we explored association between genetic liability to colorectal neoplasia and abundance of microbiota studied above using 95, 19, and 7 IVs for colorectal cancer, adenoma, and polyps, respectively. Results: Forward MR did not find evidence indicating causal relationship between any of the gut microbiota taxa or six bacterial metabolites tested and colorectal cancer risk. However, reverse MR supported genetic liability to colorectal adenomas was causally related with increased abundance of two taxa: Gammaproteobacteria (b = 0.027, which represents a 0.027 increase in log-transformed relative abundance values of Gam-maproteobacteria for per one-unit increase in log OR of adenoma risk; P = 7.06x10-8), Enterobacteriaceae (b = 0.023, P = 1.29x10-5). Conclusions: We find genetic liability to colorectal neoplasia may be associated with abundance of certain microbiota taxa. It is more likely that subset of colorectal cancer genetic liability variants changes gut biology by influencing both gut microbiota and colo-rectal cancer risk.Impact: This study highlights the need of future complemen-tary studies to explore causal mechanisms linking both host genetic variation with gut microbiome and colorectal cancer susceptibility

Planck Galactic Cold Clumps at High Galactic Latitude-a Study with CO Lines

Gas at high Galactic latitude is a relatively little noticed component of the interstellar medium. In an effort to address this, 41 Planck Galactic Cold Clumps at high Galactic latitude (HGal; divide b divide > 25 degrees) were observed in (CO)-C-12, (CO)-C-13, and (CO)-O-18 J = 1-0 lines, using the Purple Mountain Observatory 13.7 m telescope. (CO)-C-12 (1-0) and (CO)-C-13 (1-0) emission was detected in all clumps, while (CO)-O-18 (1-0) emission was only seen in 16 clumps. The highest and average latitudes are 71.degrees 4 and 37.degrees 8, respectively. Fifty-one velocity components were obtained, and then each was identified as a single clump. Thirty-three clumps were further mapped at 1 ' resolution, and 54 dense cores were extracted. Among dense cores, the average excitation temperature T (ex) of (CO)-C-12 is 10.3 K. The average line widths of thermal and nonthermal velocity dispersions are 0.19 and 0.46 km s(-1), respectively, suggesting that these cores are dominated by turbulence. Distances of the HGal clumps given by Gaia dust reddening are about 120-360 pc. The ratio of X (13)/X (18) is significantly higher than that in the solar neighborhood, implying that HGal gas has a different star formation history compared to the gas in the Galactic disk. HGal cores with sizes from 0.01 to 0.1 pc show no notable Larson's relation, and the turbulence remains supersonic down to a scale of slightly below 0.1 pc. None of the HGal cores that bear masses from 0.01 to 1 M (circle dot) are gravitationally bound, and all appear to be confined by outer pressure.Peer reviewe

Measurement of the Total Cross Section for Hadronic Production by e+e- Annihilation at Energies between 2.6-5 Gev

Using the upgraded Beijing Spectrometer (BESII), we have measured the total cross section for $e^+e^-$ annihilation into hadronic final states at center-of-mass energies of 2.6, 3.2, 3.4, 3.55, 4.6 and 5.0 GeV. Values of $R$, $\sigma(e^+e^-\to {hadrons})/\sigma(e^+e^-\to\mu^+\mu^-)$, are determined.Comment: Submitted to Phys. Rev. Let

Measurement of the Inclusive Charm Cross Section at 4.03 GeV and 4.14 GeV

The cross section for charmed meson production at $\sqrt{s} = 4.03$ and 4.14 GeV has been measured with the Beijing Spectrometer. The measurement was made using 22.3 $pb^{-1}$ of $e^+e^-$ data collected at 4.03 GeV and 1.5 $pb^{-1}$ of $e^+e^-$ data collected at 4.14 GeV. Inclusive observed cross sections for the production of charged and neutral D mesons and momentum spectra are presented. Observed cross sections were radiatively corrected to obtain tree level cross sections. Measurements of the total hadronic cross section are obtained from the charmed meson cross section and an extrapolation of results from below the charm threshold.Comment: 11 pages, 13 figures. The top level tex file is paper.tex. It builds the paper from other tex files in this .tar and the .eps file