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

Variability in aerobic methane oxidation over the past 1.2 Myrs recorded in microbial biomarker signatures from Congo fan sediments

Methane (CH4) is a strong greenhouse gas known to have perturbed global climate in the past, especially when released in large quantities over short time periods from continental or marine sources. It is therefore crucial to understand and, if possible, quantify the individual and combined response of these variable methane sources to natural climate variability. However, past changes in the stability of greenhouse gas reservoirs remain uncertain and poorly constrained by geological evidence. Here, we present a record from the Congo fan of a highly specific bacteriohopanepolyol (BHP) biomarker for aerobic methane oxidation (AMO), 35-aminobacteriohopane-30,31,32,33,34-pentol (aminopentol), that identifies discrete periods of increased AMO as far back as 1.2 Ma. Fluctuations in the concentration of aminopentol, and other 35-aminoBHPs, follow a pattern that correlates with late Quaternary glacial-interglacial climate cycles, with highest concentrations during warm periods. We discuss possible sources of aminopentol, and the methane consumed by the precursor methanotrophs, within the context of the Congo River setting, including supply of methane oxidation markers from terrestrial watersheds and/or marine sources (gas hydrate and/or deep subsurface gas reservoir). Compound-specific carbon isotope values of −30‰ to −40‰ for BHPs in ODP 1075 and strong similarities between the BHP signature of the core and surface sediments from the Congo estuary and floodplain wetlands from the interior of the Congo River Basin, support a methanotrophic and likely terrigenous origin of the 35-aminoBHPs found in the fan sediments. This new evidence supports a causal connection between marine sediment BHP records of tropical deep sea fans and wetland settings in the feeding river catchments, and thus tropical continental hydrology. Further research is needed to better constrain the different sources and pathways of methane emission. However, this study identifies the large potential of aminoBHPs, in particular aminopentol, to trace and, once better calibrated and understood, quantify past methane sources and fluxes from terrestrial and potentially also marine sources

Spectral properties of the one-dimensional two-channel Kondo lattice model

We have studied the energy spectrum of a one-dimensional Kondo lattice, where the localized magnetic moments have SU(N) symmetry and two channels of conduction electrons are present. At half filling, the system is shown to exist in two phases: one dominated by RKKY-exchange interaction effects, and the other by Kondo screening. A quantum phase transition point separates these two regimes at temperature $T = 0$. The Kondo-dominated phase is shown to possess soft modes, with spectral gaps much smaller than the Kondo temperature.Comment: 4 pages + 2 figures. Submitted for publicatio

Holography: 2-D or not 2-D?

As was recently pointed out by Cadoni, a certain class of two-dimensional gravitational theories will exhibit (black hole) thermodynamic behavior that is reminiscent of a free field theory. In the current letter, a direct correspondence is established between these two-dimensional models and the strongly curved regime of (arbitrary-dimensional) anti-de Sitter gravity. On this basis, we go on to speculatively argue that two-dimensional gravity may ultimatley be utilized for identifying and perhaps even understanding holographic dualities.Comment: 8 pages, Revtex; (v2) references and footnote added; (v3) discussion on page 5 revise

The extremal limits of the C-metric: Nariai, Bertotti-Robinson and anti-Nariai C-metrics

In two previous papers we have analyzed the C-metric in a background with a cosmological constant, namely the de Sitter (dS) C-metric, and the anti-de Sitter (AdS) C-metric, following the work of Kinnersley and Walker for the flat C-metric. These exact solutions describe a pair of accelerated black holes in the flat or cosmological constant background, with the acceleration A being provided by a strut in-between that pushes away the two black holes. In this paper we analyze the extremal limits of the C-metric in a background with generic cosmological constant. We follow a procedure first introduced by Ginsparg and Perry in which the Nariai solution, a spacetime which is the direct topological product of the 2-dimensional dS and a 2-sphere, is generated from the four-dimensional dS-Schwarzschild solution by taking an appropriate limit, where the black hole event horizon approaches the cosmological horizon. Similarly, one can generate the Bertotti-Robinson metric from the Reissner-Nordstrom metric by taking the limit of the Cauchy horizon going into the event horizon of the black hole, as well as the anti-Nariai by taking an appropriate solution and limit. Using these methods we generate the C-metric counterparts of the Nariai, Bertotti-Robinson and anti-Nariai solutions, among others. One expects that the solutions found in this paper are unstable and decay into a slightly non-extreme black hole pair accelerated by a strut or by strings. Moreover, the Euclidean version of these solutions mediate the quantum process of black hole pair creation, that accompanies the decay of the dS and AdS spaces

New Approach to GUTs

We introduce a new string-inspired approach to the subject of grand unification which allows the GUT scale to be small, \lesssim 200 TeV, so that it is within the reach of {\em conceivable} laboratory accelerated colliding beam devices. The key ingredient is a novel use of the heterotic string symmetry group physics ideas to render baryon number violating effects small enough to have escaped detection to date. This part of the approach involves new unknown parameters to be tested experimentally. A possible hint at the existence of these new parameters may already exist in the EW precision data comparisons with the SM expectations.Comment: 8 pages; improved text and references, note added; extended text, 1 figure added; extended text for publication in Eur. Phys. Journal

Convenient Versus Unique Effective Action Formalism in 2D Dilaton-Maxwell Quantum Gravity

The structure of one-loop divergences of two-dimensional dilaton-Maxwell quantum gravity is investigated in two formalisms: one using a convenient effective action and the other a unique effective action. The one-loop divergences (including surface divergences) of the convenient effective action are calculated in three different covariant gauges: (i) De Witt, (ii) $\Omega$-degenerate De Witt, and (iii) simplest covariant. The on-shell effective action is given by surface divergences only (finiteness of the $S$-matrix), which yet depend upon the gauge condition choice. Off-shell renormalizability is discussed and classes of renormalizable dilaton and Maxwell potentials are found which coincide in the cases of convenient and unique effective actions. A detailed comparison of both situations, i.e. convenient vs. unique effective action, is given. As an extension of the procedure, the one-loop effective action in two-dimensional dilaton-Yang-Mills gravity is calculated.Comment: 25 pages, LaTeX file, HUPD-93-0

Examining Periodic Solar Wind Density Structures Observed in the SECCHI Heliospheric Imagers

We present an analysis of small-scale, periodic, solar-wind density enhancements (length-scales as small as \approx 1000 Mm) observed in images from the Heliospheric Imager (HI) aboard STEREO A. We discuss their possible relationship to periodic fluctuations of the proton density that have been identified at 1 AU using in-situ plasma measurements. Specifically, Viall, Kepko, and Spence (2008) examined 11 years of in-situ solar-wind density measurements at 1 AU and demonstrated that not only turbulent structures, but also non-turbulent periodic density structures exist in the solar wind with scale sizes of hundreds to one thousand Mm. In a subsequent paper, Viall, Spence, and Kasper (2009) analyzed the {\alpha} to proton solar-wind abundance ratio measured during one such event of periodic density structures, demonstrating that the plasma behavior was highly suggestive that either temporally or spatially varying coronal source plasma created those density structures. Large periodic density structures observed at 1 AU, which were generated in the corona, can be observable in coronal and heliospheric white-light images if they possess sufficiently high density contrast. Indeed, we identify such periodic density structures as they enter the HI field of view and follow them as they advect with the solar wind through the images. The smaller periodic density structures that we identify in the images are comparable in size to the larger structures analyzed in-situ at 1 AU, yielding further evidence that periodic density enhancements are a consequence of coronal activity as the solar wind is formed.Comment: 15 pages, 12 figures. The final publication is available at http://www.springerlink.co

Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality

OBJECTIVES: Height is inversely associated with cardiovascular disease mortality risk and has shown variable associations with cancer incidence and mortality. The interpretation of findings from previous studies has been constrained by data limitations. Associations between height and specific causes of death were investigated in a large general population cohort of men and women from the West of Scotland. DESIGN: Prospective observational study. SETTING: Renfrew and Paisley, in the West of Scotland. SUBJECTS: 7052 men and 8354 women aged 45-64 were recruited into a study in Renfrew and Paisley, in the West of Scotland, between 1972 and 1976. Detailed assessments of cardiovascular disease risk factors, morbidity and socioeconomic circumstances were made at baseline. MAIN OUTCOME MEASURES: Deaths during 20 years of follow up classified into specific causes. RESULTS: Over the follow up period 3347 men and 2638 women died. Height is inversely associated with all cause, coronary heart disease, stroke, and respiratory disease mortality among men and women. Adjustment for socioeconomic position and cardiovascular risk factors had little influence on these associations. Height is strongly associated with forced expiratory volume in one second (FEV1) and adjustment for FEV1 considerably attenuated the association between height and cardiorespiratory mortality. Smoking related cancer mortality is not associated with height. The risk of deaths from cancer unrelated to smoking tended to increase with height, particularly for haematopoietic, colorectal and prostate cancers. Stomach cancer mortality was inversely associated with height. Adjustment for socioeconomic position had little influence on these associations. CONCLUSION: Height serves partly as an indicator of socioeconomic circumstances and nutritional status in childhood and this may underlie the inverse associations between height and adulthood cardiorespiratory mortality. Much of the association between height and cardiorespiratory mortality was accounted for by lung function, which is also partly determined by exposures acting in childhood. The inverse association between height and stomach cancer mortality probably reflects Helicobacter pylori infection in childhood resulting inor being associated withshorter height. The positive associations between height and several cancers unrelated to smoking could reflect the influence of calorie intake during childhood on the risk of these cancers

Chiral and Gluon Condensates at Finite Temperature

We investigate the thermal behaviour of gluon and chiral condensates within an effective Lagrangian of pseudoscalar mesons coupled to a scalar glueball. This Lagrangian mimics the scale and chiral symmetries of QCD. (Submitted to Z. Phys. C)Comment: 20 pages + 7 figures (uuencoded compressed postscript files), University of Regensburg preprint TPR-94-1