Oxytocin and oxytocinase in the obese and nonobese parturients during induction and augmentation of labor

Abstract Objective To investigate differences in oxytocin (OXT) biodistribution between nonobese and obese parturients during labor. Study Design Patients with body mass index (BMI) of either ≥ 18 ≤ 24.9 kg/m2 (“nonobese”) or ≥ 30 kg/m2 (“obese”) undergoing elective induction of labor were included (N = 25 each). Blood samples were collected at baseline (T0), and 20 minutes after maximal OXT augmentation or adequate uterine contractions (T1) for OXT and oxytocinase assays. A mixed-model repeated-measures analysis of variance was used to test for group versus time interaction and analysis of covariance to detect a difference in OXT level at T1. Data presented as mean ± standard deviation or median (interquartile range), with p < 0.05 considered significant. Results The mean BMIs (kg/m2) were 22.1 ± 1.6 and 35.9 ± 5.1 in the nonobese and obese groups, respectively. No differences were observed in either the duration of OXT infusion, total dose of OXT, or plasma OXT (pg/mL) either at T0 or T1. However, plasma oxytocinase (ng/mL) was significantly lower at T0 (1.41 [0.67, 3.51] vs. 0.40 [0.29, 1.12]; p = 0.03) in the obese group. Conclusion We provide preliminary evidence that the disposition of OXT may not be different between obese and nonobese women during labor

Three-Dimensional Relativistic Magnetohydrodynamic Simulations of Current-Driven Instability with A Sub-Alfvenic Jet: Temporal Properties

We have investigated the influence of a velocity shear surface on the linear and non-linear development of the CD kink instability of force-free helical magnetic equilibria in 3D. In this study we follow the temporal development within a periodic computational box and concentrate on flows that are sub-Alfvenic on the cylindrical jet's axis. Displacement of the initial force-free helical magnetic field leads to the growth of CD kink instability. We find that helically distorted density structure propagates along the jet with speed and flow structure dependent on the radius of the velocity shear surface relative to the characteristic radius of the helically twisted force-free magnetic field. At small velocity shear surface radius the plasma flows through the kink with minimal kink propagation speed. The kink propagation speed increases as the velocity shear radius increases and the kink becomes more embedded in the plasma flow. A decreasing magnetic pitch profile and faster flow enhance the influence of velocity shear. Simulations show continuous transverse growth in the nonlinear phase of the instability. The growth rate of the CD kink instability and the nonlinear behavior also depend on the velocity shear surface radius and flow speed, and the magnetic pitch radial profile. Larger velocity shear radius leads to slower linear growth, makes a later transition to the nonlinear stage, and with larger maximum amplitude than occur for a static plasma column. However, when the velocity shear radius is much greater than the characteristic radius of the helical magnetic field, linear and non-linear development can be similar to the development of a static plasma column.Comment: 38 pages, 18 figures, accepted for publication in Ap

A FcγRIII-engaging bispecific antibody expands the range of HER2-expressing breast tumors eligible to antibody therapy

International audienceTrastuzumab is established as treatment of HER2high metastatic breast cancers but many limitations impair its efficacy. Here, we report the design of a Fab-like bispecific antibody (HER2bsFab) that displays a moderate affinity for HER2 and a unique, specific and high affinity for FcγRIII. In vitro characterization showed that ADCC was the major mechanism of action of HER2bsFab as no significant HER2-driven effect was observed. HER2bsFab mediated ADCC at picomolar concentration against HER2high, HER2low as well as trastuzumab-refractive cell lines. In vivo HER2bsFab potently inhibited HER2high tumor growth by recruitment of mouse FcγRIII and IV-positive resident effector cells and more importantly, exhibited a net superiority over trastuzumab at inhibiting HER2low tumor growth. Moreover, FcγRIIIA-engagement by HER2bsFab was independent of V/F158 polymorphism and induced a stronger NK cells activation in response to target cell recognition. Thus, taking advantage of its epitope specificity and affinity for HER2 and FcγRIIIA, HER2bsFab exhibits potent anti-tumor activity against HER2low tumors while evading most of trastuzumab Fc-linked limitations thereby potentially enlarging the number of patients eligible for breast cancer immunotherapy

Deterministically Driven Avalanche Models of Solar Flares

We develop and discuss the properties of a new class of lattice-based avalanche models of solar flares. These models are readily amenable to a relatively unambiguous physical interpretation in terms of slow twisting of a coronal loop. They share similarities with other avalanche models, such as the classical stick--slip self-organized critical model of earthquakes, in that they are driven globally by a fully deterministic energy loading process. The model design leads to a systematic deficit of small scale avalanches. In some portions of model space, mid-size and large avalanching behavior is scale-free, being characterized by event size distributions that have the form of power-laws with index values, which, in some parameter regimes, compare favorably to those inferred from solar EUV and X-ray flare data. For models using conservative or near-conservative redistribution rules, a population of large, quasiperiodic avalanches can also appear. Although without direct counterparts in the observational global statistics of flare energy release, this latter behavior may be relevant to recurrent flaring in individual coronal loops. This class of models could provide a basis for the prediction of large solar flares.Comment: 24 pages, 11 figures, 2 tables, accepted for publication in Solar Physic

3D Relativistic Magnetohydrodynamic Simulations of Current-Driven Instability. I. Instability of a static column

We have investigated the development of current-driven (CD) kink instability through three-dimensional relativistic MHD simulations. A static force-free equilibrium helical magnetic configuration is considered in order to study the influence of the initial configuration on the linear and nonlinear evolution of the instability. We found that the initial configuration is strongly distorted but not disrupted by the kink instability. The instability develops as predicted by linear theory. In the non-linear regime the kink amplitude continues to increase up to the terminal simulation time, albeit at different rates, for all but one simulation. The growth rate and nonlinear evolution of the CD kink instability depends moderately on the density profile and strongly on the magnetic pitch profile. The growth rate of the kink mode is reduced in the linear regime by an increase in the magnetic pitch with radius and the non-linear regime is reached at a later time than for constant helical pitch. On the other hand, the growth rate of the kink mode is increased in the linear regime by a decrease in the magnetic pitch with radius and reaches the non-linear regime sooner than the case with constant magnetic pitch. Kink amplitude growth in the non-linear regime for decreasing magnetic pitch leads to a slender helically twisted column wrapped by magnetic field. On the other hand, kink amplitude growth in the non-linear regime nearly ceases for increasing magnetic pitch.Comment: 24 pages, 10 figures, and 1 table, submitted to Ap

Effect of a 14-day course of systemic corticosteroids on the hypothalamic-pituitary-adrenal-axis in patients with acute exacerbation of chronic obstructive pulmonary disease

<p/> <p>Background</p> <p>As supra-physiological intake of corticosteroids is a well known risk factor for the development of adrenal insufficiency, we investigated the function of the hypothalamic-pituitary-adrenal (HPA) axis during a 14-day course of systemic corticosteroids in patients with acute exacerbation of chronic obstructive pulmonary disease using clinical and laboratory measures.</p> <p>Methods</p> <p>A systematic clinical and laboratory assessment including measurement of basal cortisol levels and the response to low dose (1 μg) ACTH stimulation was performed in nine patients before, on the first and the last day of treatment, as well as 2, 7 and 21 days after corticosteroid withdrawal.</p> <p>Results</p> <p>At baseline, all nine patients had normal responses to 1 μg ACTH. On the first day of steroid treatment, 78% had a blunted peak cortisol response. This percentage increased to 89% after 14 days of steroid treatment. 78%, 33% and 33% of the patients had a blunted cortisol response to ACTH 2, 7, and 21 days after corticosteroid withdrawal, respectively. ROC curve analysis revealed that only basal cortisol concentrations (AUC 0.89), but not ACTH concentrations (AUC 0.49) or clinical signs (AUC 0.47) were predictive of an impaired function of the HPA axis. Basal cortisol levels of > 400 and < 150 nmol/l were 96% and 100% sensitive for a normal or pathological response to the ACTH stimulation test, respectively.</p> <p>Conclusion</p> <p>Immediate and prolonged suppression of the HPA axis is a common finding in otherwise asymptomatic patients undergoing systemic steroid treatment for acute exacerbation of chronic obstructive pulmonary disease and can reliably be assessed with the low-dose ACTH test.</p

Intercalibration of the barrel electromagnetic calorimeter of the CMS experiment at start-up

Calibration of the relative response of the individual channels of the barrel electromagnetic calorimeter of the CMS detector was accomplished, before installation, with cosmic ray muons and test beams. One fourth of the calorimeter was exposed to a beam of high energy electrons and the relative calibration of the channels, the intercalibration, was found to be reproducible to a precision of about 0.3%. Additionally, data were collected with cosmic rays for the entire ECAL barrel during the commissioning phase. By comparing the intercalibration constants obtained with the electron beam data with those from the cosmic ray data, it is demonstrated that the latter provide an intercalibration precision of 1.5% over most of the barrel ECAL. The best intercalibration precision is expected to come from the analysis of events collected in situ during the LHC operation. Using data collected with both electrons and pion beams, several aspects of the intercalibration procedures based on electrons or neutral pions were investigated

Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective Multicenter Study

Background: Management of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. Objective: To assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. Design, setting, and participants: We conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. Outcome measurements and statistical analysis: Progression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. Results and limitations: The median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6-33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08-1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38-8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10-26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61-8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12-3.16; p = 0.02, respectively). Conclusions: Salvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. Patient summary: We found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer

Radiation hardness qualification of PbWO4 scintillation crystals for the CMS Electromagnetic Calorimeter

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 IOPEnsuring the radiation hardness of PbWO4 crystals was one of the main priorities during the construction of the electromagnetic calorimeter of the CMS experiment at CERN. The production on an industrial scale of radiation hard crystals and their certification over a period of several years represented a difficult challenge both for CMS and for the crystal suppliers. The present article reviews the related scientific and technological problems encountered

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO