Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]

To determine the efficacy and safety of risedronate in patients with knee osteoarthritis (OA), the British study of risedronate in structure and symptoms of knee OA (BRISK), a 1-year prospective, double-blind, placebo-controlled study, enrolled patients (40–80 years of age) with mild to moderate OA of the medial compartment of the knee. The primary aims were to detect differences in symptoms and function. Patients were randomized to once-daily risedronate (5 mg or 15 mg) or placebo. Radiographs were taken at baseline and 1 year for assessment of joint-space width using a standardized radiographic method with fluoroscopic positioning of the joint. Pain, function, and stiffness were assessed using the Western Ontario and McMaster Universities (WOMAC) OA index. The patient global assessment and use of walking aids were measured and bone and cartilage markers were assessed. The intention-to-treat population consisted of 284 patients. Those receiving risedronate at 15 mg showed improvement of the WOMAC index, particularly of physical function, significant improvement of the patient global assessment (P < 0.001), and decreased use of walking aids relative to patients receiving the placebo (P = 0.009). A trend towards attenuation of joint-space narrowing was observed in the group receiving 15 mg risedronate. Eight percent (n = 7) of patients receiving placebo and 4% (n = 4) of patients receiving 5 mg risedronate exhibited detectable progression of disease (joint-space width ≥ 25% or ≥ 0.75 mm) versus 1% (n = 1) of patients receiving 15 mg risedronate (P = 0.067). Risedronate (15 mg) significantly reduced markers of cartilage degradation and bone resorption. Both doses of risedronate were well tolerated. In this study, clear trends towards improvement were observed in both joint structure and symptoms in patients with primary knee OA treated with risedronate

Maternal obesity is associated with the formation of small dense LDL and hypoadiponectinemia in the third trimester

Context: Maternal obesity is associated with high plasma triglyceride, poor vascular function, and an increased risk for pregnancy complications. In normal-weight pregnant women, higher triglyceride is associated with increased small, dense low-density lipoprotein (LDL). Hypothesis: In obese pregnancy, increased plasma triglyceride concentrations result in triglyceride enrichment of very low-density lipoprotein-1 particles and formation of small dense LDL via lipoprotein lipase. Design: Women (n = 55) of body mass index of 18–46 kg/m2 were sampled longitudinally at 12, 26, and 35 weeks' gestation and 4 months postnatally. Setting: Women were recruited at hospital antenatal appointments, and study visits were in a clinical research suite. Outcome Measures: Plasma concentrations of lipids, triglyceride-rich lipoproteins, lipoprotein lipase mass, estradiol, steroid hormone binding globulin, insulin, glucose, leptin, and adiponectin were determined. Results: Obese women commenced pregnancy with higher plasma triglyceride, reached the same maximum, and then returned to higher postnatal levels than normal-weight women. Estradiol response to pregnancy (trimester 1–3 incremental area under the curve) was positively associated with plasma triglyceride response (r2 adjusted 25%, P &#60; .001). In the third trimester, the proportion of small, dense LDL was 2-fold higher in obese women than normal-weight women [mean (SD) 40.7 (18.8) vs 21.9 (10.9)%, P = .014], and 35% of obese, 14% of overweight, and none of the normal-weight women displayed an atherogenic LDL subfraction phenotype. The small, dense LDL mass response to pregnancy was inversely associated with adiponectin response (17%, P = .013). Conclusions: Maternal obesity is associated with an atherogenic LDL subfraction phenotype and may provide a mechanistic link to poor vascular function and adverse pregnancy outcome

Preeclampsia is associated with compromized maternal synthesis of long chain polyunsaturated fatty acids leading to offspring deficiency

Obesity and excessive lipolysis are implicated in preeclampsia (PE). Intrauterine growth restriction is associated with low maternal body mass index and decreased lipolysis. Our aim was to assess how maternal and offspring fatty acid metabolism is altered in mothers in the third trimester of pregnancy with PE (n=62) or intrauterine growth restriction (n=23) compared with healthy pregnancies (n=164). Markers of lipid metabolism and erythrocyte fatty acid concentrations were measured. Maternal adipose tissue fatty acid composition and mRNA expression of adipose tissue fatty acid–metabolizing enzymes and placental fatty acid transporters were compared. Mothers with PE had higher plasma triglyceride (21%, P&#60;0.001) and nonesterified fatty acid (50%, P&#60;0.001) concentrations than controls. Concentrations of major n−6 and n−3 long-chain polyunsaturated fatty acids in erythrocytes were 23% to 60% lower (all P&#60;0.005) in PE and intrauterine growth restriction mothers and offspring compared with controls. Subcutaneous adipose tissue Δ−5 and Δ−6 desaturase and very long-chain fatty acid elongase mRNA expression was lower in PE than controls (respectively, mean [SD] control 3.38 [2.96] versus PE 1.83 [1.91], P=0.030; 3.33 [2.25] versus 1.03 [0.96], P&#60;0.001; 0.40 [0.81] versus 0.00 [0.00], P=0.038 expression relative to control gene [square root]). Low maternal and fetal long-chain polyunsaturated fatty acid concentrations in PE may be the result of decreased maternal synthesis

Sympathetic cooling of 9Be+^9Be^+ and 24Mg+^{24}Mg^+ for quantum logic

We demonstrate the cooling of a two species ion crystal consisting of one $^9Be^+$ and one $^{24}Mg^+$ ion. Since the respective cooling transitions of these two species are separated by more than 30 nm, laser manipulation of one ion has negligible effect on the other even when the ions are not individually addressed. As such this is a useful system for re-initializing the motional state in an ion trap quantum computer without affecting the qubit information. Additionally, we have found that the mass difference between ions enables a novel method for detecting and subsequently eliminating the effects of radio frequency (RF) micro-motion.Comment: Submitted to PR

Computer simulation of bistable switching in a nematic device containing pear-shaped particles

We study the microscopic basis of bistable switching of a confined liquid crystal via Monte Carlo simulations of hard pear-shaped particles. Using both dielectric and dipolar field couplings to this intrinsically flexoelectric fluid, it is shown that pulsed fields of opposing polarity can be used to switch between the vertical and hybrid aligned states. Further, it is shown that the field-susceptibility of the surface polarisation, rather than the bulk flexoelectricity, is the main driver of this switching behaviour.</p

Tilt order parameters, polarity and inversion phenomena in smectic liquid crystals

The order parameters for the phenomenological description of the smectic-{\it A} to smectic-{\it C} phase transition are formulated on the basis of molecular symmetry and structure. It is shown that, unless the long molecular axis is an axis of two-fold or higher rotational symmetry, the ordering of the molecules in the smectic-{\it C} phase gives rise to more than one tilt order parameter and to one or more polar order parameters. The latter describe the indigenous polarity of the smectic-{\it C} phase, which is not related to molecular chirality but underlies the appearance of spontaneous polarisation in chiral smectics. A phenomenological theory of the phase transition is formulated by means of a Landau expansion in two tilt order parameters (primary and secondary) and an indigenous polarity order parameter. The coupling among these order parameters determines the possibility of sign inversions in the temperature dependence of the spontaneous polarisation and of the helical pitch observed experimentally for some chiral smectic-{\it $C^{\ast}$} materials. The molecular interpretation of the inversion phenomena is examined in the light of the new formulation.Comment: 12 pages, 5 figures, RevTe

Statistical analysis and the equivalent of a Thouless energy in lattice QCD Dirac spectra

Random Matrix Theory (RMT) is a powerful statistical tool to model spectral fluctuations. This approach has also found fruitful application in Quantum Chromodynamics (QCD). Importantly, RMT provides very efficient means to separate different scales in the spectral fluctuations. We try to identify the equivalent of a Thouless energy in complete spectra of the QCD Dirac operator for staggered fermions from SU(2) lattice gauge theory for different lattice size and gauge couplings. In disordered systems, the Thouless energy sets the universal scale for which RMT applies. This relates to recent theoretical studies which suggest a strong analogy between QCD and disordered systems. The wealth of data allows us to analyze several statistical measures in the bulk of the spectrum with high quality. We find deviations which allows us to give an estimate for this universal scale. Other deviations than these are seen whose possible origin is discussed. Moreover, we work out higher order correlators as well, in particular three--point correlation functions.Comment: 24 pages, 24 figures, all included except one figure, missing eps file available at http://pluto.mpi-hd.mpg.de/~wilke/diff3.eps.gz, revised version, to appear in PRD, minor modifications and corrected typos, Fig.4 revise