Can cartilage loss be detected in knee osteoarthritis (OA) patients with 3–6 months' observation using advanced image analysis of 3T MRI?

SummaryPurposePrior investigations of magnetic resonance imaging (MRI) biomarkers of cartilage loss in knee osteoarthritis (OA) suggest that trials of interventions which affect this biomarker with adequate statistical power would require large clinical studies of 1–2 years duration. We hypothesized that smaller, shorter duration, “Proof of Concept” (PoC) studies might be achievable by: (1) selecting a population at high risk of rapid medial tibio-femoral (TF) progression, in conjunction with; (2) high-field MRI (3T), and; (3) using advanced image analysis. The primary outcome was the cartilage thickness in the central medial femur.MethodsMulti-centre, non-randomized, observational cohort study at four sites in the US. Eligible participants were females with knee pain, a body mass index (BMI)≥25kg/m2, symptomatic radiographic evidence of medial TF OA, and varus mal-alignment. The 29 participants had a mean age of 62 years, mean BMI of 36kg/m2, with eight index knees graded as Kellgren–Lawrence (K&L)=2 and 21 as K&L=3. Eligible participants had four MRI scans of one knee: two MRIs (1 week apart) were acquired as a baseline with follow-up MRI at 3 and 6 months. A trained operator, blind to time-point but not subject, manually segmented the cartilage from the Dual Echo Steady State water excitation MR images. Anatomically corresponding regions of interest were identified on each image by using a three-dimensional statistical shape model of the endosteal bone surface, and the cartilage thickness (with areas denuded of cartilage included as having zero thickness – ThCtAB) within each region was calculated. The percentage change from baseline at 3 and 6 months was assessed using a log-scale analysis of variance (ANOVA) model including baseline as a covariate. The primary outcome was the change in cartilage thickness within the aspect of central medial femoral condyle exposed within the meniscal window (w) during articulation, neglecting cartilage edges [nuclear (n)] (nwcMF·ThCtAB), with changes in other regions considered as secondary endpoints.ResultsAnatomical mal-alignment ranged from −1.9° to 6.3°, with mean 0.9°. With one exception, no changes in ThCtAB were detected at the 5% level for any of the regions of interest on the TF joint at 3 or 6 months of follow-up. The change in the primary variable (nwcMF·ThCtAB) from (mean) baseline at 3 months from the log-scale ANOVA model was −2.1% [95% confidence interval (CI) (−4.4%, +0.2%)]. The change over 6 months was 0.0% [95% CI (−2.7%, +2.8%)]. The 95% CI for the change from baseline did not include zero for the cartilage thickness within the meniscal window of the lateral tibia (wLT·ThCtAB) at 6 month follow-up (−1.5%, 95% CI [−2.9, −0.2]), but was not significant at the 5% level after correction for multiple comparisons.ConclusionsThe small inconsistent compartment changes, and the relatively high variabilities in cartilage thickness changes seen over time in this study, provide no additional confidence for a 3- or 6-month PoC study using a patient population selected on the basis of risk for rapid progression with the MRI acquisition and analyses employed

Multi-scale approaches for the simulation of cardiac electrophysiology: I – sub-cellular and stochastic calcium dynamics from cell to organ

Computational models of the heart at multiple spatial scales, from sub-cellular nanodomains to the whole-organ, are a powerful tool for the simulation of cardiac electrophysiology. Application of these models has provided remarkable insight into the normal and pathological functioning of the heart. In these two articles, we present methods for modelling cardiac electrophysiology at all of these spatial scales. In part one, presented here, we discuss methods and approaches for modelling sub-cellular calcium dynamics at the whole-cell and organ scales, valuable for modelling excitation–contraction coupling and mechanisms of arrhythmia triggers

The rationale for heart team decision-making for patients with stable, complex coronary artery disease

Stable complex coronary artery disease can be treated with coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Multidisciplinary decision-making has gained more emphasis over the recent years to select the most optimal treatment strategy for individual patients with stable complex coronary artery disease. However, the so-called 'Heart Team' concept has not been widely implemented. Yet, decision-making has shown to remain suboptimal; there is large variability in PCI-to-CABG ratios, which may predominantly be the consequence of physician-related factors that have raised concerns regarding overuse, underuse, and inappropriate selection of revascularization. In this review, we summarize these and additional data to support the statement that a multidisciplinary Heart Team consisting of at least a clinical/non-invasive cardiologist, interventional cardiologist, and cardiac surgeon, can together better analyse and interpret the available diagnostic evidence, put into context the clinical condition of the patient as well as consider individual preference and local expertise, and through shared decision-making with the patient can arrive at a most optimal joint treatment strategy recommendation for patients with stable co

Density Fluctuation Mediated Superconductivity

We conpare predictions of the mean-field theory of supercnductivity for metallic systems on the border of a density instability for cubic and tetragonal lattices. The calculations are based on a parametrisation of an effective interaction arising from the exchange of density fluctuations and assume that a single band is relevant for superconductivity. The results show that for comparable model parameters, desnity fluctuation mediated pairing is more robust in quasi-two dimensions than in three dimensions, and that the robustness of pairing increases gradually as one goes from a cubic to a more and more anisotropic tetragonal structure. We also find that the robustness of density fluctuation mediated pairing can depend sensitively on the incipient ordering wavevector. We discuss the similarities and differences between the mean-field theories of superconductivity for density and magnetically mediated pairing

Quantitative comparison of single- and two-particle properties in the cuprates

We explore the strong variations of the electronic properties of copper-oxygen compounds across the doping phase diagram in a quantitative way. To this end we calculate the electronic Raman response on the basis of results from angle-resolved photoemission spectroscopy (ARPES). In the limits of our approximations we find agreement on the overdoped side and pronounced discrepancies at lower doping. In contrast to the successful approach for the transport properties at low energies, the Raman and the ARPES data cannot be reconciled by adding angle-dependent momentum scattering. We discuss possible routes towards an explanation of the suppression of spectral weight close to the $(\pi,0)$ points which sets in abruptly close to 21% doping.Comment: 7 pages, 4 figure

The electronic structure of poly(pyridine-2,5-diyl) investigated by soft x-ray absorption and emission spectroscopies

The electronic structure of the poly-pyridine conjugated polymer has been investigated by resonant and nonresonant inelastic X-ray scattering and X-ray absorption spectroscopies using synchrotron radiation. The measurements were made for both the carbon and nitrogen contents of the polymer. The analysis of the spectra has been carried out in comparison with molecular orbital calculations taking the repeat-unit cell as a model molecule of the polymer chain. The simulations indicate no significant differences in the absorption and in the non-resonant X-ray scattering spectra for the different isomeric geometries, while some isomeric dependence of the resonant spectra is predicted. The resonant emission spectra show depletion of the {\pi} electron bands in line with symmetry selection and momentum conservation rules. The effect is most vizual for the carbon spectra; the nitrogen spectra are dominated by lone pair n orbital emission of {\sigma} symmetry and are less frequency dependent.Comment: 11 pages, 7 figures, 1 table, http://www.sciencedirect.com/science/article/pii/S030101049800262

Advances in ab-initio theory of Multiferroics. Materials and mechanisms: modelling and understanding

Within the broad class of multiferroics (compounds showing a coexistence of magnetism and ferroelectricity), we focus on the subclass of "improper electronic ferroelectrics", i.e. correlated materials where electronic degrees of freedom (such as spin, charge or orbital) drive ferroelectricity. In particular, in spin-induced ferroelectrics, there is not only a {\em coexistence} of the two intriguing magnetic and dipolar orders; rather, there is such an intimate link that one drives the other, suggesting a giant magnetoelectric coupling. Via first-principles approaches based on density functional theory, we review the microscopic mechanisms at the basis of multiferroicity in several compounds, ranging from transition metal oxides to organic multiferroics (MFs) to organic-inorganic hybrids (i.e. metal-organic frameworks, MOFs)Comment: 22 pages, 9 figure

Nest-site competition between bumblebees (Bombidae), social wasps (Vespidae) and cavity-nesting birds in Britain and the Western Palearctic

Capsule: There is no evidence of widespread significant nest-site competition in Britain or the Western Palearctic between cavity-nesting birds and bumblebees or social wasps. Aims: To investigate competition between cavity-nesting birds and bumblebees and wasps, particularly the range-expanding Tree Bumblebee, Saxon Wasp and European Hornet in Britain, and review evidence throughout the Western Palearctic. Methods: We compared field data from English and Polish studies of tits and woodpeckers breeding in nest-boxes and/or tree holes to assess nest-site competition with bumblebees and wasps. We reviewed the literature quantifying nest-site competition between birds and these insects in the Western Palearctic. Results: Bumblebees and wasps are capable of usurping small passerines from nests. In England, these insects commandeered a mean annual 4.1% of tit nests initiated in nest-boxes; occurrence of hornets showed a long-term increase, but not other wasps or bumblebees. Across the Western Palearctic, insect occupation of nest-boxes was generally low, and was lower in England than in Poland. No insects were discovered in tree cavities, including those created by woodpeckers (Picidae). Conclusion: Nest-site competition between cavity-nesting birds and bumblebees and wasps appears to be a ‘nest-box phenomenon’, which may occasionally interfere with nest-box studies, but appears negligible in natural nest-sites

The exposure of the hybrid detector of the Pierre Auger Observatory

The Pierre Auger Observatory is a detector for ultra-high energy cosmic rays. It consists of a surface array to measure secondary particles at ground level and a fluorescence detector to measure the development of air showers in the atmosphere above the array. The "hybrid" detection mode combines the information from the two subsystems. We describe the determination of the hybrid exposure for events observed by the fluorescence telescopes in coincidence with at least one water-Cherenkov detector of the surface array. A detailed knowledge of the time dependence of the detection operations is crucial for an accurate evaluation of the exposure. We discuss the relevance of monitoring data collected during operations, such as the status of the fluorescence detector, background light and atmospheric conditions, that are used in both simulation and reconstruction.Comment: Paper accepted by Astroparticle Physic