7,336 research outputs found

    Low LDL-C and High HDL-C Levels Are Associated with Elevated Serum Transaminases amongst Adults in the United States: A Cross-sectional Study

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    Background: Dyslipidemia, typically recognized as high serum triglyceride, high low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein cholesterol (HDL-C) levels, are associated with nonalcoholic fatty liver disease (NAFLD). However, low LDL-C levels could result from defects in lipoprotein metabolism or impaired liver synthetic function, and may serve as ab initio markers for unrecognized liver diseases. Whether such relationships exist in the general population has not been investigated. We hypothesized that despite common conception that low LDL-C is desirable, it might be associated with elevated liver enzymes due to metabolic liver diseases. Methods and Findings: We examined the associations between alanine aminotransferase (ALT), aspartate aminotransferase (AST) and major components of serum lipid profiles in a nationally representative sample of 23,073 individuals, who had no chronic viral hepatitis and were not taking lipid-lowering medications, from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. ALT and AST exhibited non-linear U-shaped associations with LDL-C and HDL-C, but not with triglyceride. After adjusting for potential confounders, individuals with LDL-C less than 40 and 41–70 mg/dL were associated with 4.2 (95% CI 1.5–11.7, p = 0.007) and 1.6 (95% CI 1.1–2.5, p = 0.03) times higher odds of abnormal liver enzymes respectively, when compared with those with LDL-C values 71–100 mg/dL (reference group). Surprisingly, those with HDL-C levels above 100 mg/dL was associated with 3.2 (95% CI 2.1–5.0, p<0.001) times higher odds of abnormal liver enzymes, compared with HDL-C values of 61–80 mg/dL. Conclusions: Both low LDL-C and high HDL-C, often viewed as desirable, were associated with significantly higher odds of elevated transaminases in the general U.S. adult population. Our findings underscore an underestimated biological link between lipoprotein metabolism and liver diseases, and raise a potential need for liver evaluation among over 10 million people with particularly low LDL-C or high HDL-C in the United States

    First results on the performance of the CMS global calorimeter trigger

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    The CMS Global Calorimeter Trigger (GCT) uses data from the CMS calorimeters to compute a number kinematical quantities which characterize the LHC event. The GTC output is used by the Global Trigger (GT) along with data from the Global Muon Trigger (GMT) to produce the Level-1 Accept (L1A) decision. The design for the current GCT system commenced early in 2006. After a rapid development phase all the different GCT components have been produced and a large fraction of them have been installed at the CMS electronics cavern (USC-55). There the GCT system has been under test since March 2007. This paper reports results from tests which took place at the USC-55. Initial tests aimed to test the integrity of the GCT data and establish that the proper synchronization had been achieved both internally within GCT as well as with the Regional Calorimeter Trigger (RCT) which provides the GCT input data and with GT which receives the GCT results. After synchronization and data integrity had been established, Monte Carlo Events with electrons in the final state were injected at the GCT inputs and were propagated to the GCT outputs. The GCT output was compared with the predictions of the GCT emulator model in the CMS Monte Carlo and were found to be identical

    Revised CMS Global Calorimeter Trigger Functionality & Algorithms

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    The Global Calorimeter Trigger (GCT) is a device which uses data from the CMS calorimeters to search for jets, produce isolated and non-isolated electron lists and compute all the transverse and missing transverse energy sums used for the Level-1 trigger decision (L1A). GCT performs these functions by receiving and processing the data from the Regional Calorimeter Trigger (RCT) and transmitting a summary to the Global Trigger (GT) which computes the L1A decision. The GCT must also transmit a copy of the RCT and GCT data to the CMS DAQ. The vast amount of data received by the GCT (230 Gb/s) as well as the necessity for data sharing required by the jet finder impose severe constrains on the GCT design. This paper presents an overview of the revised design, in particular, the algorithms, data flow and associated latency within the revised GCT

    Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization

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    The identity of nicotinic receptor subtypes sufficient to elicit both the acute and chronic effects of nicotine dependence is unknown. We engineered mutant mice with α4 nicotinic subunits containing a single point mutation, Leu^(9′) → Ala^(9′) in the pore-forming M2 domain, rendering α4* receptors hypersensitive to nicotine. Selective activation of α4* nicotinic acetylcholine receptors with low doses of agonist recapitulates nicotine effects thought to be important in dependence, including reinforcement in response to acute nicotine administration, as well as tolerance and sensitization elicited by chronic nicotine administration. These data indicate that activation of α4* receptors is sufficient for nicotine-induced reward, tolerance, and sensitization

    Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

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    Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype

    Performance of the CMS Global Calorimeter Trigger

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    The CMS Global Calorimeter Trigger system performs a wide-variety of calorimeter data processing functions required by the CMS Level-1 trigger. It is responsible for finding and classifying jets and tau-jets, calculating total and missing transverse energy, total transverse energy identified within jets, sorting e/γ\gamma candidates, and calculating several quantities based on forward calorimetry for minimum-bias triggers. The system is based on high-speed serial optical links and large FPGAs. The system has provided CMS with calorimeter triggers during commissioning and cosmic runs throughout 2008. The performance of the system in validation tests and cosmic runs is presented here

    Exome sequencing in classic hairy cell leukaemia reveals widespread variation in acquired somatic mutations between individual tumours apart from the signature BRAF V(600)E lesion

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    In classic Hairy cell leukaemia (HCLc), a single case has thus far been interrogated by whole exome sequencing (WES) in a treatment naive patient, in which BRAF V(600)E was identified as an acquired somatic mutation and confirmed as occurring near-universally in this form of disease by conventional PCR-based cohort screens. It left open however the question whether other genome-wide mutations may also commonly occur at high frequency in presentation HCLc disease. To address this, we have carried out WES of 5 such typical HCLc cases, using highly purified splenic tumour cells paired with autologous T cells for germline. Apart from BRAF V(600)E, no other recurrent somatic mutation was identified in these HCLc exomes, thereby excluding additional acquired mutations as also prevalent at a near-universal frequency in this form of the disease. These data then place mutant BRAF at the centre of the neoplastic drive in HCLc. A comparison of our exome data with emerging genetic findings in HCL indicates that additional somatic mutations may however occur recurrently in smaller subsets of disease. As mutant BRAF alone is insufficient to drive malignant transformation in other histological cancers, it suggests that individual tumours utilise largely differing patterns of genetic somatic mutations to coalesce with BRAF V(600)E to drive pathogenesis of malignant HCLc disease

    Maternal age and risk of cesarean section in women with induced labor at term - a Nordic register-based study

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    Abstract Introduction Over the last decades, induction of labor has increased in many countries along with increasing maternal age. We assessed the effects of maternal age and labor induction on cesarean section at term among nulliparous and multiparous women without previous cesarean section. Material and methods We performed a retrospective national registry-based study from Denmark, Finland, Iceland, Norway and Sweden including 3 398 586 deliveries between 2000 and 2011. We investigated the impact of age on cesarean section among 196 220 nulliparous and 188 158 multiparous women whose labor was induced, had single cephalic presentation at term and no previous cesarean section. Confounders comprised country, time-period and gestational age. Results In nulliparous women with induced labor the rate of cesarean section increased from 14.0% in women less than 20 years of age to 39.9% in women 40 years and older. Compared to women aged 25-29 years, the corresponding relative risk were 0.60 (95% confidence interval (CI); 0.57 to 0.64) and 1.72 (95% CI; 1.66 to 1.79). In multiparous induced women the risk of cesarean section was 3.9% in women less than 20 years rising to 9.1% in women 40 years and older. Compared to women aged 25-29 years, the relative risk were 0.86 (95% CI; 0.54 to 1.37) and 1.98 (95% CI; 1.84 to 2.12), respectively. There were minimal confounding effects of country, time-period and gestational age on risk for cesarean section. Conclusions Advanced maternal age is associated with increased risk of cesarean section in women undergoing labor induction with a single cephalic presentation at term without a previous cesarean section. The absolute risk of cesarean section is 3-5 times higher across 5-year age groups in nulliparous relative to multiparous women having induced labor.Peer reviewe

    The design, construction and performance of the MICE scintillating fibre trackers

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    This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2011 ElsevierCharged-particle tracking in the international Muon Ionisation Cooling Experiment (MICE) will be performed using two solenoidal spectrometers, each instrumented with a tracking detector based on diameter scintillating fibres. The design and construction of the trackers is described along with the quality-assurance procedures, photon-detection system, readout electronics, reconstruction and simulation software and the data-acquisition system. Finally, the performance of the MICE tracker, determined using cosmic rays, is presented.This work was supported by the Science and Technology Facilities Council under grant numbers PP/E003214/1, PP/E000479/1, PP/E000509/1, PP/E000444/1, and through SLAs with STFC-supported laboratories. This work was also supportedby the Fermi National Accelerator Laboratory, which is operated by the Fermi Research Alliance, under contract No. DE-AC02-76CH03000 with the U.S. Department of Energy, and by the U.S. National Science Foundation under grants PHY-0301737,PHY-0521313, PHY-0758173 and PHY-0630052. The authors also acknowledge the support of the World Premier International Research Center Initiative (WPI Initiative), MEXT, Japan
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