Transthoracic echocardiography reference values in juvenile and adult 129/Sv mice

Background In the recent years, the use of Doppler-echocardiography has become a standard non-invasive technique in the analysis of cardiac malformations in genetically modified mice. Therefore, normal values have to be established for the most commonly used inbred strains in whose genetic background those mutations are generated. Here we provide reference values for transthoracic echocardiography measurements in juvenile (3 weeks) and adult (8 weeks) 129/Sv mice. Methods Echocardiographic measurements were performed using B-mode, M-mode and Doppler-mode in 15 juvenile (3 weeks) and 15 adult (8 weeks) mice, during isoflurane anesthesia. M-mode measurements variability of left ventricle (LV) was determined. Results Several echocardiographic measurements significantly differ between juvenile and adult mice. Most of these measurements are related with cardiac dimensions. All B-mode measurements were different between juveniles and adults (higher in the adults), except for fractional area change (FAC). Ejection fraction (EF) and fractional shortening (FS), calculated from M-mode parameters, do not differ between juvenile and adult mice. Stroke volume (SV) and cardiac output (CO) were significantly different between juvenile and adult mice. SV was 31.93 ± 8.67 μl in juveniles vs 70.61 ± 24.66 μl in adults, ρ < 0.001. CO was 12.06 ± 4.05 ml/min in juveniles vs 29.71 ± 10.13 ml/min in adults, ρ < 0.001. No difference was found in mitral valve (MV) and tricuspid valve (TV) related parameters between juvenile and adult mice. It was demonstrated that variability of M-mode measurements of LV is minimal. Conclusions This study suggests that differences in cardiac dimensions, as wells as in pulmonary and aorta outflow parameters, were found between juvenile and adult mice. However, mitral and tricuspid inflow parameters seem to be similar between 3 weeks and 8 weeks mice. The reference values established in this study would contribute as a basis to future studies in post-natal cardiovascular development and diagnosing cardiovascular disorders in genetically modified mouse mutant lines.Peer Reviewe

MICE: The muon ionization cooling experiment. Step I: First measurement of emittance with particle physics detectors

Copyright @ 2011 APSThe Muon Ionization Cooling Experiment (MICE) is a strategic R&D project intended to demonstrate the only practical solution to providing high brilliance beams necessary for a neutrino factory or muon collider. MICE is under development at the Rutherford Appleton Laboratory (RAL) in the United Kingdom. It comprises a dedicated beamline to generate a range of input muon emittances and momenta, with time-of-flight and Cherenkov detectors to ensure a pure muon beam. The emittance of the incoming beam will be measured in the upstream magnetic spectrometer with a scintillating fiber tracker. A cooling cell will then follow, alternating energy loss in Liquid Hydrogen (LH2) absorbers to RF cavity acceleration. A second spectrometer, identical to the first, and a second muon identification system will measure the outgoing emittance. In the 2010 run at RAL the muon beamline and most detectors were fully commissioned and a first measurement of the emittance of the muon beam with particle physics (time-of-flight) detectors was performed. The analysis of these data was recently completed and is discussed in this paper. Future steps for MICE, where beam emittance and emittance reduction (cooling) are to be measured with greater accuracy, are also presented.This work was supported by NSF grant PHY-0842798

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

Contains fulltext : 109739.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. METHODS/DESIGN: Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. DISCUSSION: The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. TRIAL REGISTRATION: NTR2657

PEG Minocycline-Liposomes Ameliorate CNS Autoimmune Disease

Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS). Minocycline, a potent inhibitor of matrix metalloproteinase (MMP)-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG) minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs), we determined that PEG minocycline-liposome preparations stabilized with CaCl(2) are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN