Advanced magnetic resonance imaging of cartilage components in haemophilic joints reveals that cartilage hemosiderin correlates with joint deterioration.

IntroductionEvidence suggests that toxic iron is involved in haemophilic joint destruction.AimTo determine whether joint iron deposition is linked to clinical and imaging outcomes in order to optimize management of haemophilic joint disease.MethodsAdults with haemophilia A or haemophilia B (n = 23, ≥ age 21) of all severities were recruited prospectively to undergo assessment with Hemophilia Joint Health Scores (HJHS), pain scores (visual analogue scale [VAS]) and magnetic resonance imaging (MRI) at 3T using conventional MRI protocols and 4-echo 3D-UTE-Cones sequences for one affected arthropathic joint. MRI was scored blinded by two musculoskeletal radiologists using the International Prophylaxis Study Group (IPSG) MRI scale. Additionally, UTE-T2* values of cartilage were quantified. Correlations between parameters were performed using Spearman rank correlation. Two patients subsequently underwent knee arthroplasty, which permitted linking of histological findings (including Perl's reaction) with MRI results.ResultsMRI scores did not correlate with pain scores or HJHS. Sixteen joints had sufficient cartilage for UTE-T2* analysis. T2* values for cartilage correlated inversely with HJHS (rs  = -0.81, P < 0.001) and MRI scores (rs  = -0.52, P = 0.037). This was unexpected since UTE-T2* values decrease with better joint status in patients with osteoarthritis, suggesting that iron was present and responsible for the effects. Histological analysis of cartilage confirmed iron deposition within chondrocytes, associated with low UTE-T2* values.ConclusionsIron accumulation can occur in cartilage (not only in synovium) and shows a clear association with joint health. Cartilage iron is a novel biomarker which, if quantifiable with innovative joint-specific MRI T2* sequences, may guide treatment optimization

Estimation of conditional laws given an extreme component

Let $(X,Y)$ be a bivariate random vector. The estimation of a probability of the form $P(Y\leq y \mid X >t)$ is challenging when $t$ is large, and a fruitful approach consists in studying, if it exists, the limiting conditional distribution of the random vector $(X,Y)$, suitably normalized, given that $X$ is large. There already exists a wide literature on bivariate models for which this limiting distribution exists. In this paper, a statistical analysis of this problem is done. Estimators of the limiting distribution (which is assumed to exist) and the normalizing functions are provided, as well as an estimator of the conditional quantile function when the conditioning event is extreme. Consistency of the estimators is proved and a functional central limit theorem for the estimator of the limiting distribution is obtained. The small sample behavior of the estimator of the conditional quantile function is illustrated through simulations.Comment: 32 pages, 5 figur

Inhalation Toxicity of Brevetoxin 3 in Rats Exposed for Twenty-Two Days

Brevetoxins are potent neurotoxins produced by the marine dinoflagellate Karenia brevis. Exposure to brevetoxins may occur during a K. brevis red tide when the compounds become aerosolized by wind and surf. This study assessed possible adverse health effects associated with inhalation exposure to brevetoxin 3, one of the major brevetoxins produced by K. brevis and present in aerosols collected along beaches affected by red tide. Male F344 rats were exposed to brevetoxin 3 at 0, 37, and 237 μg/m(3) by nose-only inhalation 2 hr/day, 5 days/week for up to 22 exposure days. Estimated deposited brevetoxin 3 doses were 0.9 and 5.8 μg/kg/day for the low-and high-dose groups, respectively. Body weights of the high-dose group were significantly below control values. There were no clinical signs of toxicity. Terminal body weights of both low- and high-dose-group rats were significantly below control values. Minimal alveolar macrophage hyperplasia was observed in three of six and six of six of the low- and high-dose groups, respectively. No histopathologic lesions were observed in the nose, brain, liver, or bone marrow of any group. Reticulocyte numbers in whole blood were significantly increased in the high-dose group, and mean corpuscular volume showed a significant decreasing trend with increasing exposure concentration. Humoral-mediated immunity was suppressed in brevetoxin-exposed rats as indicated by significant reduction in splenic plaque-forming cells in both low- and high-dose-group rats compared with controls. Results indicate that the immune system is the primary target for toxicity in rats after repeated inhalation exposure to relatively high concentrations of brevetoxins

The New Legal Pluralism

Scholars studying interactions among multiple communities have often used the term legal pluralism to describe the inevitable intermingling of normative systems that results from these interactions. In recent years, a new application of pluralist insights has emerged in the international and transnational realm. This review aims to survey and help define this emerging field of global legal pluralism. I begin by briefly describing sites for pluralism research, both old and new. Then I discuss how pluralism has come to be seen as an attractive analytical framework for those interested in studying law on the world stage. Finally, I identify advantages of a pluralist approach and respond to criticisms, and I suggest ways in which pluralism can help both in reframing old conceptual debates and in generating useful normative insights for designing procedural mechanisms, institutions, and discursive practices for managing hybrid legal/cultural spaces

Observation of an Exotic S=+1S=+1 Baryon in Exclusive Photoproduction from the Deuteron

In an exclusive measurement of the reaction $\gamma d \to K^+ K^- p n$, a narrow peak that can be attributed to an exotic baryon with strangeness $S=+1$ is seen in the $K^+n$ invariant mass spectrum. The peak is at $1.542\pm 0.005$ GeV/c$^2$ with a measured width of 0.021 GeV/c$^2$ FWHM, which is largely determined by experimental mass resolution. The statistical significance of the peak is $5.2 \pm 0.6 \sigma$. The mass and width of the observed peak are consistent with recent reports of a narrow $S=+1$ baryon by other experimental groups.Comment: 5 pages, 5 figure

Two-Nucleon Momentum Distributions Measured in 3He(e,e'pp)n

We have measured the 3He(e,e'pp)n reaction at 2.2 GeV over a wide kinematic range. The kinetic energy distribution for `fast' nucleons (p > 250 MeV/c) peaks where two nucleons each have 20% or less, and the third nucleon has most of the transferred energy. These fast pp and pn pairs are back-to-back with little momentum along the three-momentum transfer, indicating that they are spectators. Experimental and theoretical evidence indicates that we have measured distorted two-nucleon momentum distributions by striking the third nucleon and detecting the spectator correlated pair.Comment: 6 pages, 5 figures, submitted to PR

Search for the Θ+\Theta^+ pentaquark in the reaction γd→pK−K+n\gamma d \to p K^- K^+ n

A search for the \thp in the reaction $\gamma d \to pK^-K^+n$ was completed using the CLAS detector at Jefferson Lab. A study of the same reaction, published earlier, reported the observation of a narrow \thp resonance. The present experiment, with more than 30 times the integrated luminosity of our earlier measurement, does not show any evidence for a narrow pentaquark resonance. The angle-integrated upper limit on \thp production in the mass range of 1.52 to 1.56 GeV/c$^2$ for the $\gamma d \to pK^-\Theta^+$ reaction is 0.3 nb (95% CL). This upper limit depends on assumptions made for the mass and angular distribution of \thp production. Using \lamstar production as an empirical measure of rescattering in the deuteron, the cross section upper limit for the elementary $\gamma n \to K^-\Theta^+$ reaction is estimated to be a factor of 10 higher, {\it i.e.}, $\sim 3$ nb (95% CL).Comment: 5 figures, submitted to PRL, revised for referee comment

Survey of A_LT' asymmetries in semi-exclusive electron scattering on He4 and C12

Single spin azimuthal asymmetries A_LT' were measured at Jefferson Lab using 2.2 and 4.4 GeV longitudinally polarized electrons incident on He4 and C12 targets in the CLAS detector. A_LT' is related to the imaginary part of the longitudinal-transverse interference and in quasifree nucleon knockout it provides an unambiguous signature for final state interactions (FSI). Experimental values of A_LT' were found to be below 5%, typically |A_LT'| < 3% for data with good statistical precision. Optical Model in Eikonal Approximation (OMEA) and Relativistic Multiple-Scattering Glauber Approximation (RMSGA) calculations are shown to be consistent with the measured asymmetries.Comment: 9 pages, 5 figure

Onset of asymptotic scaling in deuteron photodisintegration

We investigate the transition from the nucleon-meson to quark-gluon description of the strong interaction using the photon energy dependence of the $d(\gamma,p)n$ differential cross section for photon energies above 0.5 GeV and center-of-mass proton angles between $30^{\circ}$ and $150^{\circ}$. A possible signature for this transition is the onset of cross section $s^{-11}$ scaling with the total energy squared, $s$, at some proton transverse momentum, $P_T$. The results show that the scaling has been reached for proton transverse momentum above about 1.1 GeV/c. This may indicate that the quark-gluon regime is reached above this momentum.Comment: Accepted by PRL; 5 pages, 2 figure

Observation of an Exotic Baryon with S=+1 in Photoproduction from the Proton

The reaction $\gamma p \to \pi^+K^-K^+n$ was studied at Jefferson Lab using a tagged photon beam with an energy range of 3-5.47 GeV. A narrow baryon state with strangeness S=+1 and mass $M=1555\pm 10$ MeV/c$^2$ was observed in the $nK^+$ invariant mass spectrum. The peak's width is consistent with the CLAS resolution (FWHM=26 MeV/c$^2$), and its statistical significance is 7.8 $\pm$ 1.0 ~$\sigma$. A baryon with positive strangeness has exotic structure and cannot be described in the framework of the naive constituent quark model. The mass of the observed state is consistent with the mass predicted by a chiral soliton model for the $\Theta^+$ baryon. In addition, the $pK^+$ invariant mass distribution was analyzed in the reaction $\gamma p\to K^-K^+p$ with high statistics in search of doubly-charged exotic baryon states. No resonance structures were found in this spectrum.Comment: 5 pages, 5 figures, add reference