Measurement of pharmacokinetic parameters in histologically graded invasive breast tumours using dynamic contrast-enhanced MRI

Dynamic contrast-enhanced MRI (DCE-MRI) has demonstrated high sensitivity for detection of breast cancer. Analysis of correlation between quantitative DCE-MRI findings and prognostic factors (such as histological tumour grade) is important for defining the role of this technique in the diagnosis of breast cancer as well as the monitoring of neoadjuvant therapies. This paper presents a practical clinical application of a quantitative pharmacokinetic model to study histologically confirmed and graded invasive human breast tumours. The hypothesis is that, given a documented difference in capillary permeability between benign and malignant breast tumours, a relationship between permeability-related DCE-MRI parameters and tumour aggressiveness persists within invasive breast carcinomas. In addition, it was hypothesized that pharmacokinetic parameters may demonstrate stronger correlation with prognostic factors than the more conventional black-box techniques, so a comparison was undertaken. Significant correlations were found between pharmacokinetic and black-box parameters in 59 invasive breast carcinomas. However, statistically significant variation with tumour grade was demonstrated in only two permeability-related pharmacokinetic parameters: kep (p,0.05) and Ktrans (p,0.05), using one-way analysis of variance. Parameters kep and Ktrans were significantly higher in Grade 3 tumours than in low-grade tumours. None of the measured DCE-MRI parameters varied significantly between Grade 1 and Grade 2 tumours. Measurement of kep and Ktrans might therefore be used to monitor the effectiveness of neoadjuvant treatment of high-grade invasive breast carcinomas, but is unlikely to demonstrate remission in low-grade tumours

Surface reconstructions of In-enriched InGaAs alloys

The atomic structure of In0.81Ga0.19As/InPIn0.81Ga0.19As/InP alloy layers was examined using in situ scanning tunneling microscopy. The (2×3) reconstruction observed during growth by reflection high-energy electron diffraction represents a combination of surface structures, including a β2(2×4) commonly observed on GaAs(001) and InAs(001) surfaces, and a disordered (4×3) that is unique to alloy systems. The proposed (4×3) structure is comprised of both anion and cation dimers. Empty and filled states images show that the features reverse contrast with sample bias, in agreement with the model. © 2003 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70065/2/APPLAB-83-7-1361-1.pd

A comparison of extremal optimization with flat-histogram dynamics for finding spin-glass ground states

We compare the performance of extremal optimization (EO), flat-histogram and equal-hit algorithms for finding spin-glass ground states. The first-passage-times to a ground state are computed. At optimal parameter of tau=1.15, EO outperforms other methods for small system sizes, but equal-hit algorithm is competitive to EO, particularly for large systems. Flat-histogram and equal-hit algorithms offer additional advantage that they can be used for equilibrium thermodynamic calculations. We also propose a method to turn EO into a useful algorithm for equilibrium calculations. Keywords: extremal optimization. flat-histogram algorithm, equal-hit algorithm, spin-glass model, ground state.Comment: 10 LaTeX pages, 2 figure

A dominant magnetic dipole for the evolved Ap star candidate EK Eridani

EK Eri is one of the most slowly rotating active giants known, and has been proposed to be the descendant of a strongly magnetic Ap star. We have performed a spectropolarimetric study of EK Eri over 4 photometric periods with the aim of inferring the topology of its magnetic field. We used the NARVAL spectropolarimeter at the Bernard Lyot telescope at the Pic du Midi Observatory, along with the least-squares deconvolution method, to extract high signal-to-noise ratio Stokes V profiles from a timeseries of 28 polarisation spectra. We have derived the surface-averaged longitudinal magnetic field Bl. We fit the Stokes V profiles with a model of the large-scale magnetic field and obtained Zeeman Doppler images of the surface magnetic strength and geometry. Bl variations of up to about 80 G are observed without any reversal of its sign, and which are in phase with photometric ephemeris. The activity indicators are shown to vary smoothly on a timescale compatible with the rotational period inferred from photometry (308.8 d.), however large deviations can occur from one rotation to another. The surface magnetic field variations of EK Eri appear to be dominated by a strong magnetic spot (of negative polarity) which is phased with the dark (cool) photometric spot. Our modeling shows that the large-scale magnetic field of EK Eri is strongly poloidal. For a rotational axis inclination of i = 60{\deg}, we obtain a model that is almost purely dipolar. In the dipolar model, the strong magnetic/photometric spot corresponds to the negative pole of the dipole, which could be the remnant of that of an Ap star progenitor of EK Eri. Our observations and modeling conceptually support this hypothesis, suggesting an explanation of the outstanding magnetic properties of EK Eri as the result of interaction between deep convection and the remnant of an Ap star magnetic dipole.Comment: 8 pages, 6 figures, accepted for publication in Astronomy & Astrophysic

Molecular and morphometric variation in European populations of the articulate brachiopod <i>Terebeatulina retusa</i>

Molecular and morphometric variation within and between population samples of the articulate brachiopod &lt;i&gt;Terebratulina&lt;/i&gt; spp., collected in 1985-1987 from a Norwegian fjord, sea lochs and costal sites in western Scotland, the southern English Channel (Brittany) and the western Mediterranean, were measured by the analysis of variation in the lengths of mitochondrial DNA (mtDNA) fragments produced by digestion with nine restriction endonucleases and by multivariate statistical analysis of six selected morphometric parameters. Nucleotide difference within each population sample was high. Nucleotide difference between population samples from the Scottish sites, both those that are tidally contiguous and those that appear to be geographically isolated, were not significantly different from zero. Nucleotide differences between the populations samples from Norway, Brittany, Scotland and the western Mediterranean were also very low. Morphometric analysis confirmed the absence of substantial differentiation

Rich Pickings Near Large Communal Roosts Favor ‘Gang’ Foraging by Juvenile Common Ravens, Corvus corax

Ravens (Corvus corax) feed primarily on rich but ephemeral carcasses of large animals, which are usually defended by territorial pairs of adults. Non-breeding juveniles forage socially and aggregate in communal winter roosts, and these appear to function as ‘information centers’ regarding the location of the rare food bonanzas: individuals search independently of one another and pool their effort by recruiting each other at roosts. However, at a large raven roost in Newborough on Anglesey, North Wales, some juveniles have been observed recently to forage in ‘gangs’ and to roost separately from other birds. Here we adapt a general model of juvenile common raven foraging behavior where, in addition to the typical co-operative foraging strategy, such gang foraging behavior could be evolutionarily stable near winter raven roosts. We refocus the model on the conditions under which this newly documented, yet theoretically anticipated, gang-based foraging has been observed. In the process, we show formally how the trade off between search efficiency and social opportunity can account for the existence of the alternative social foraging tactics that have been observed in this species. This work serves to highlight a number of fruitful avenues for future research, both from a theoretical and empirical perspective

Uncertainties in Theoretical HeI Emissivities: HII Regions, Primordial Abundance, and Cosmological Recombination

A number of recent works in astronomy and cosmology have relied upon theoretical He I emissivities, but we know of no effort to quantify the uncertainties in the atomic data. We analyze and assign uncertainties to all relevant atomic data, perform Monte Carlo analyses, and report standard deviations in the line emissivities. We consider two sets of errors, which we call "optimistic" and "pessimistic." We also consider three different conditions, corresponding to prototypical Galactic and extragalactic H II regions and the epoch of cosmological recombination. In the extragalactic H II case, the errors we obtain are comparable to or larger than the errors in some recent $Y_p$ calculations, including those derived from CMB observations. We demonstrate a systematic effect on primordial abundance calculations; this effect cannot be reduced by observing a large number of objects. In the cosmological recombination case, the errors are comparable to many of the effects considered in recent calculations.Comment: 5 pages, 3 figures, accepted to MNRAS Letter

A double-blind, placebo-controlled, phase II, randomized study of lovastatin therapy in the treatment of mildly active rheumatoid arthritis

© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (statins) are standard treatment for hyperlipidaemia. In addition to lipid-lowering abilities, statins exhibit multiple anti-inflammatory effects. The objectives of this study were to determine whether treatment of patients with RA with lovastatin decreased CRP or reduced disease activity. Methods: We conducted a randomized double-blind placebo-controlled 12 week trial of lovastatin vs placebo in 64 RA patients with mild clinical disease activity but an elevated CRP. The primary efficacy end point was the reduction in mean log CRP. Secondary end points included disease activity, RF and anti-CCP antibody titres. Mechanistic end points included levels of serum cytokines. Safety was assessed; hepatic and muscle toxicities were of particular interest. Results: Baseline features were similar between groups. No significant difference in mean log CRP reduction between the two groups was observed, and disease activity did not change from baseline in either treatment group. Mechanistic analyses did not reveal significant changes in any biomarkers. A post hoc analysis of subjects not using biologic therapy demonstrated a significantly greater proportion achieving ≥20% reduction in CRP from baseline in the lovastatin group compared with placebo (P-value = 0.007). No difference was observed in subjects receiving biologics. Lovastatin was well tolerated with no serious safety concerns. Conclusion: This study showed no anti-inflammatory or clinical effects on RA disease activity after 12 weeks of treatment with lovastatin. Lovastatin had a modest effect on CRP in subjects not using biologics, suggesting statins may be anti-inflammatory in selected patients. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00302952