151 research outputs found
Mirabegron-induced brown fat activation does not exacerbate atherosclerosis in mice with a functional hepatic ApoE-LDLR pathway
Activation of brown adipose tissue (BAT) with the ÎČ3-adrenergic receptor agonist CL316,243 protects mice from atherosclerosis development, and the presence of metabolically active BAT is associated with cardiometabolic health in humans. In contrast, exposure to cold or treatment with the clinically used ÎČ3-adrenergic receptor agonist mirabegron to activate BAT exacerbates atherosclerosis in apolipoprotein E (ApoE)- and low-density lipoprotein receptor (LDLR)-deficient mice, both lacking a functional ApoE-LDLR pathway crucial for lipoprotein remnant clearance. We, therefore, investigated the effects of mirabegron treatment on dyslipidemia and atherosclerosis development in APOE*3-Leiden.CETP mice, a humanized lipoprotein metabolism model with a functional ApoE-LDLR clearance pathway. Mirabegron activated BAT and induced white adipose tissue (WAT) browning, accompanied by selectively increased fat oxidation and attenuated fat mass gain. Mirabegron increased the uptake of fatty acids derived from triglyceride (TG)-rich lipoproteins by BAT and WAT, which was coupled to increased hepatic uptake of the generated cholesterol-enriched core remnants. Mirabegron also promoted hepatic very low-density lipoprotein (VLDL) production, likely due to an increased flux of fatty acids from WAT to the liver, and resulted in transient elevation in plasma TG levels followed by a substantial decrease in plasma TGs. These effects led to a trend toward lower plasma cholesterol levels and reduced atherosclerosis. We conclude that BAT activation by mirabegron leads to substantial metabolic benefits in APOE*3-Leiden.CETP mice, and mirabegron treatment is certainly not atherogenic. These data underscore the importance of the choice of experimental models when investigating the effect of BAT activation on lipoprotein metabolism and atherosclerosis.</p
Modelling and Interpreting The Effects of Spatial Resolution on Solar Magnetic Field Maps
Different methods for simulating the effects of spatial resolution on
magnetic field maps are compared, including those commonly used for
inter-instrument comparisons. The investigation first uses synthetic data, and
the results are confirmed with {\it Hinode}/SpectroPolarimeter data. Four
methods are examined, one which manipulates the Stokes spectra to simulate
spatial-resolution degradation, and three "post-facto" methods where the
magnetic field maps are manipulated directly. Throughout, statistical
comparisons of the degraded maps with the originals serve to quantify the
outcomes. Overall, we find that areas with inferred magnetic fill fractions
close to unity may be insensitive to optical spatial resolution; areas of
sub-unity fill fractions are very sensitive. Trends with worsening spatial
resolution can include increased average field strength, lower total flux, and
a field vector oriented closer to the line of sight. Further-derived quantities
such as vertical current density show variations even in areas of high average
magnetic fill-fraction. In short, unresolved maps fail to represent the
distribution of the underlying unresolved fields, and the "post-facto" methods
generally do not reproduce the effects of a smaller telescope aperture. It is
argued that selecting a method in order to reconcile disparate spatial
resolution effects should depend on the goal, as one method may better preserve
the field distribution, while another can reproduce spatial resolution
degradation. The results presented should help direct future inter-instrument
comparisons.Comment: Accepted for publication in Solar Physics. The final publication
(including full-resolution figures) will be available at
http://www.springerlink.co
ANĂLISE DE AGROTĂXICOS ORGANOCLORADOS EM CAMARĂO E PESCADO POR CROMATOGRAFIA A GĂS COM DETECTOR DE MICRO CAPTURA DE ELETRONS (GC-”ECD)
Otimizou-se um mĂ©todo analĂtico para a determinação de multirresĂduos de organoclorados em camarĂŁo marinho para a espĂ©cie Litopenaeus vannamei e em mĂșsculo de peixes da espĂ©cie Oreochromis sp., chamada popularmente de tilĂĄpia-vermelha. Utilizou-se a tĂ©cnica de extração denominada QuEChERS, empregando cromatografia a gĂĄs com detector de micro captura de elĂ©trons (CG-”ECD) para anĂĄlise dos seguintes organoclorados em amostras de camarĂŁo e em mĂșsculo de peixes: hexaclorobenzeno, lindano, DDE, DDT, clorpirifĂłs, endossulfan sulfato, endossulfan beta, endossulfan alfa, heptacloro, aldrin, endrin e dieldrin. O limite de detecção para todos os compostos foi de 0,0005 ”gâg-1 e o limite de quantificação do mĂ©todo foi estabelecido em 0,005 ”gâg-1. Os valores de recuperação variaram entre 80 % e 120 % com desvio padrĂŁo (RSD) abaixo de 20 % para todos os compostos
ADVANCE database characterisation and fit for purpose assessment for multi-country studies on the coverage, benefits and risks of pertussis vaccinations
Introduction: The public-private ADVANCE consortium (Accelerated development of vaccine benefit-risk collaboration in Europe) aimed to assess if electronic healthcare databases can provide fit-for purpose data for collaborative, distributed studies and monitoring of vaccine coverage, benefits and risks of vaccines. Objective: To evaluate if European healthcare databases can be used to estimate vaccine coverage, benefit and/or risk using pertussis-containing vaccines as an example. Methods: Characterisation was conducted using open-source Java-based (Jerboa) software and R scripts. We obtained: (i) The general characteristics of the database and data source (meta-data) and (ii) a detailed description of the database population (size, representatively of age/sex of national population, rounding of birth dates, delay between birth and database entry), vaccinations (number of vaccine doses, recording of doses, pattern of doses by age and coverage) and events of interest (diagnosis codes, incidence rates). A total of nine databases (primary care, regional/national record linkage) provided data on events (pertussis, pneumonia, death, fever, convulsions, injection site reactions, hypotonic hypo-responsive episode, persistent crying) and vaccines (acellular pertussis and whole cell pertussis) related to the pertussis proof of concept studies. Results: The databases contained data for a total population of 44 million individuals. Seven databases had recorded doses of vaccines. The pertussis coverage estimates were similar to those reported by the World Health Organisation (WHO). Incidence rates of ev
Quantifying outcome misclassification in multi-database studies: The case study of pertussis in the ADVANCE project
Background: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines using European healthcare databases. Event misclassification can result in biased estimates. Using different algorithms for identifying cases of Bordetella pertussis (BorPer) infection as a test case, we aimed to describe a strategy to quantify event misclassification, when manual chart review is not feasible. Methods: Four participating databases retrieved data from primary care (PC) setting: BIFAP: (Spain), THIN and RCGP RSC (UK) and PEDIANET (Italy); SIDIAP (Spain) retrieved data from both PC and hospital settings. BorPer algorithms were defined by healthcare setting, data domain (diagnoses, drugs, or laboratory tests) and concept sets (specific or unspecified pertussis). Algorithm- and database-specific BorPer incidence rates (IRs) were estimated in children aged 0â14 years enrolled in 2012 and 2014 and followed up until the end of each calendar year and compared with IRs of confirmed pertussis from the ECDC surveillance system (TESSy). Novel formulas were used to approximate validity indices, based on a small set of assumptions. They were applied to approximately estimate positive predictive value (PPV) and sensitivity in SIDIAP. Results: The number of cases and the estimated BorPer IRs per 100,000 person-years in PC, using data representing 3,173,268 person-years, were 0 (IR = 0.0), 21 (IR = 4.3), 21 (IR = 5.1), 79 (IR = 5.7), and 2 (IR = 2.3) in BIFAP, SIDIAP, THIN, RCGP RSC and PEDIANET respectively. The IRs for combined specific/unspecified pertussis were higher than TESSy, suggesting that some false positives had been included. In SIDIAP the estimated IR was 45.0 when discharge diagnoses were included. The sensitivity and PPV of combined PC specific and unspecific diagnoses for BorPer cases in SIDIAP were approximately 85% and 72%, respectively. Conclusion: Retrieving BorPer cases using only specific concepts has low sensitivity in PC databases, while including cases retrieved by unspecified concepts introduces false positives, which were approximately estimated to be 28% in one database. The share of cases that cannot be retrieved from a PC database because they are only seen in hospital was approximately estimated to be 15% in one database. This study demonstrated that quantifying the impact of different event-finding algorithms across databases and benchmarking with disease surveillance data can provide approximate estimates of algorithm validity
Efeitos genéticos e de ambiente sobre produção de leite e intervalo de partos em rebanhos leiteiros monitorados por sistema de informação
Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC
Measurements of inclusive jet suppression in heavy ion collisions at the LHC
provide direct sensitivity to the physics of jet quenching. In a sample of
lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated
luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with
a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the
transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the
anti-kt algorithm with values for the distance parameter that determines the
nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of
the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp.
Jet production is found to be suppressed by approximately a factor of two in
the 10% most central collisions relative to peripheral collisions. Rcp varies
smoothly with centrality as characterized by the number of participating
nucleons. The observed suppression is only weakly dependent on jet radius and
transverse momentum. These results provide the first direct measurement of
inclusive jet suppression in heavy ion collisions and complement previous
measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables,
submitted to Physics Letters B. All figures including auxiliary figures are
available at
http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02
Incidence Rates of Autoimmune Diseases in European Healthcare Databases: A Contribution of the ADVANCE Project
Introduction: The publicâprivate ADVANCE collaboration developed and tested a system to generate evidence on vaccine benefits and risks using European electronic healthcare databases. In the safety of vaccines, background incidence rates are key to allow proper monitoring and assessment. The goals of this study were to compute age-, sex-, and calendar-year stratified incidence rates of nine autoimmune diseases in seven European healthcare databases from four countries and to assess validity by comparing with published data. Methods: Event rates were calculated for the following outcomes: acute disseminated encephalomyelitis, Bellâs palsy, GuillainâBarrĂ© syndrome, immune thrombocytopenia purpura, Kawasaki disease, optic neuritis, narcolepsy, systemic lupus erythematosus, and transverse myelitis. Cases were identified by diagnosis codes. Participating organizations/databases originated from Denmark, Italy, Spain, and the UK. The source population comprised all persons registered, with at least 1 year of data prior to the study start, or follow-up from birth. Stratified incidence rates were computed per database over the period 2003 to 2014. Results: Between 2003 and 2014, 148,947 incident cases of nine autoimmune diseases were identified. Crude incidence rates were highest for Bellâs palsy [23.8/100,000 person-years (PYs), 95% confidence interval (CI) 23.6â24.1] and lowest for Kawasaki disease (0.7/100,000 PYs, 95% CI 0.6â0.7). Specific patterns were observed by sex, age, calendar time, and data sources. Rates were comparable with published estimates. Conclusion: A range of autoimmune events could be identified in the ADVANCE system. Estimation of rates indicated consistency across selected European healthcare databases, as well as consistency with US published data
Search for non-Gaussian events in the data of the VIRGO E4 engineering run
International audienc
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