Objective We sought to test the hypothesis that sildenafil citrate (SC) at low concentrations potentiates the tocolytic effects of nifedipine in vitro. Study Design Myometrial biopsies were obtained ...from 22 term nonlaboring women undergoing scheduled cesarean delivery. Tissue strips were suspended in organ chambers for isometric tension recording, and incubated for 30 minutes with either SC at 231 ng/mL or solvent. The effects of cumulative doses (10–10 to 10–5 mol/L) of nifedipine on spontaneous and oxytocin-induced uterine contractility were then determined. Areas under the contraction curve were compared using 1-way analysis of variance with Tukey post hoc test (significance: P < .05). Results Nifedipine significantly inhibited spontaneous and oxytocin-induced myometrial contractility. Preincubation with SC increased response to nifedipine and significantly potentiated its inhibitory effect at 10–8 mol/L, without affecting oxytocin-induced contractile response. Conclusion At concentrations within a therapeutic window, SC increases myometrial sensitivity to nifedipine.
The extraction of neutrino mixing parameters from accelerator-based neutrino oscillation experiments relies on proper modeling of neutrino-nucleus scattering processes using neutrino-interaction ...event generators. Experimental tests of these generators are difficult due to the broad range of neutrino energies produced in accelerator-based beams and the low statistics of current experiments. Here we overcome these difficulties by exploiting the similarity of neutrino and electron interactions with nuclei to test neutrino event generators using high-precision inclusive electron scattering data. To this end, we revised the electron-scattering mode of the GENIE event generator (\(e\)-GENIE) to include electron-nucleus bremsstrahlung radiation effects and to use, when relevant, the exact same physics models and model parameters, as the standard neutrino-scattering version. We also implemented new models for quasielastic (QE) scattering and meson exchange currents (MEC) based on the theory-inspired SuSAv2 approach. Comparing the new \(e\)-GENIE predictions with inclusive electron scattering data, we find an overall adequate description of the data in the QE- and MEC-dominated lower energy transfer regime, especially when using the SuSAv2 models. Higher energy transfer-interactions, which are dominated by resonance production, are still not well modeled by \(e\)-GENIE.
Objective The purpose of this study was to test the hypothesis that prepregnancy obesity and soluble fms-like tyrosine kinase-1 (sFlt-1)–induced preeclampsia lead to altered vascular function in the ...offspring later in life. Study Design CD-1 female mice were placed on a low-fat (LF) or high-fat (HF) diet before mating. On day 8 of pregnancy, the HF mice were injected with adenovirus that carried either sFlt-1 (HF sFlt-1) or murine immunoglobulin G2α Fc fragment (HF mFc). LF dams received saline solution. After being weaned, all offspring were placed on a standard diet. At 3 months of age, the carotid artery was isolated for in vitro vascular reactivity studies. Results Among male offspring, the response to phenylephrine was significantly lower in the HF sFlt-1 group. The response to serotonin in males and to thromboxane in females was lower in the HF sFlt-1 and HF mFc groups. In females, the HF sFlt-1 and LF groups displayed less relaxation to acetylcholine. The response to phenylephrine was significantly lower in females than males in the HF mFc and LF groups. The response to thromboxane was significantly lower in the HF sFlt-1 females, compared with males. Conclusion Prepregnancy obesity and preeclampsia alter fetal programming of adult vascular function. The mechanism is complex and gender specific.
NOvA is a long-baseline neutrino experiment using an off-axis neutrino beam produced by the NuMI neutrino beam at Fermilab. The NOvA experiment will study neutrino \(\nu_{\mu}\rightarrow\nu_{e}\) ...oscillations. A short term goal for the NOvA experiment is to develop a good understanding of the response of the detector. These studies are being carried out with the full Near Detector installed on the surface (NDOS) at Fermilab. This detector is currently running and will acquire neutrino data for a year. Using beam muon neutrino data, quasi-elastic charged-current interactions will be studied. Status of the NDOS running and early data will be shown.
While drotrecogin alfa (activated) was shown to decrease absolute 28-day mortality by 6.1% in patients with severe sepsis in the Recombinant Human Protein C Worldwide Evaluation in Severe Sepsis ...(PROWESS) study, no mortality benefit was observed in the subset of patients with only one organ system failure. Consequently, some institutions restrict drotrecogin alfa (activated) use to patients with severe sepsis with >/=2 organ system failures.
To measure the cost effectiveness of drotrecogin alfa (activated) for treatment of severe sepsis in relation to the number of organ system failures and determine the economic impact of restricting drotrecogin alfa (activated) use based on the number of organ system failures.
Policy perspective specific to our 340-bed, level I trauma centre.
A Monte Carlo simulation analysis was conducted to evaluate a hypothetical cohort of 10 000 patients with severe sepsis in four scenarios restricting treatment with drotrecogin alfa (activated) to patients with >/=1, >/=2, >/=3 or >/=4 organ system failures. The primary outcomes of 28-day all-cause mortality and serious bleeding were obtained from the PROWESS study. Costs (year 2002 values) were obtained from institutional financial records and literature estimates. The incremental cost per life saved at 28 days with drotrecogin alfa (activated) plus best standard care versus best standard care alone (placebo) was calculated. The incidence of severe sepsis and number of drotrecogin alfa (activated) candidates were estimated through chart review, and projected annual institutional expenditures were derived according to these data.
With increasing number of organ system failures, the proportion of lives saved with drotrecogin alfa (activated) increased, and consequently the ICER decreased. Restriction of drotrecogin alfa (activated) to patients with >/=4 organ system failures was the most cost-effective scenario (0.11 lives saved; 56727 US dollars per life saved). For the nine patients that would be treated annually by our institution under this policy, one life would be saved at a total additional cost of 56160 US dollars per year. Use of the drug in patients with >/=1 or >/=2 organ system failures would save the greatest number of lives per year (4-5); however, restricting drotrecogin alfa (activated) to patients with >/=2 organ system failures would be the cheaper alternative (total additional cost 356022 US dollars vs 462204 US dollars .
While restriction of drotrecogin alfa (activated) use to patients with sepsis with >/=4 organ system failures is the most cost-effective alternative, restriction to those with >/=2 organ system failures is the preferred alternative for our institution according to the number of lives saved and available financial resources.
A tropical marine bioassay was developed with juveniles of Pacific white shrimp, Litopenaeus vannamei, in order to test the acute and sublethal toxicity of Tilt, which is the commercial formulation ...of the fungicide propiconazole. A 10-d acute toxicity and a 32-d sublethal test were performed. A median lethal concentration (LC50) was determined for different exposure times, resulting in a 24-h LC50 of 1167 (1101-1386) microg/L (concentration based on active ingredient propiconazole), and reaching a threshold LC50 (72-h) at 1043 (1018-1068) microg/L. The sublethal exposure test was performed with propiconazole concentrations ranging from 367 to 825 microg/L. Animals in most treatments showed a significant increase in intermoult duration compared to those in the control treatment, although this did not seem to be concentration-dependent. However, the shrimps exposed to the sublethal concentrations of this fungicide showed morphological deformities, with a significant positive relationship between concentration and deformities of the rostrum, paraeopods, and uropods. Altogether, the results presented indicate the potential effects of Tilt on shrimp, particularly under long-term exposures, although these were found to occur at concentrations exceeding those reported in natural environments.
Processes with precisely known cross sections, like neutrino electron elastic
scattering ($\nu e^{-} \!\rightarrow \nu e^{-}$) and inverse muon decay
($\nu_\mu e^{-} \!\rightarrow \mu^{-} \nu_e$) ...have been used by MINERvA to
constrain the uncertainty on the NuMI neutrino beam flux. This work presents a
new measurement of neutrino elastic scattering with electrons using the medium
energy \numubar enhanced NuMI beam. A sample of 578 events after background
subtraction is used in combination with the previous measurement on the \numu
beam and the inverse muon decay measurement to reduce the uncertainty on the
\numu flux in the \numu-enhanced beam from 7.6\% to 3.3\% and the \numubar flux
in the \numubar-enhanced beam from 7.8\% to 4.7\%.
MINERvA has measured the $\nu_{\mu}$-induced coherent $\pi^{+}$ cross section
simultaneously in hydrocarbon (CH), graphite (C), iron (Fe) and lead (Pb)
targets using neutrinos from 2 to 20 GeV. The ...measurements exceed the
predictions of the Rein-Sehgal and Berger-Sehgal PCAC based models at multi-GeV
$\nu_{\mu}$ energies and at produced $\pi^{+}$ energies and angles, $E_{\pi}>1$
GeV and $\theta_{\pi}<10^{\circ}$. Measurements of the cross-section ratios of
Fe and Pb relative to CH reveal the effective $A$-scaling to increase from an
approximate $A^{1/3}$ scaling at few GeV to an $A^{2/3}$ scaling for
$E_{\nu}>10$ GeV.
PDF