Mild and moderate pre-dialysis chronic kidney disease is associated with increased coronary artery calcium.

BackgroundIt is increasingly evident that patients with chronic kidney disease (CKD) are more likely to die from heart disease than kidney failure. This study evaluated whether pre- dialysis CKD is an independent risk factor for coronary artery calcium (CAC).MethodsA total of 544 consecutive patients who underwent CAC scoring were analyzed. Eleven patients requiring hemodialysis were excluded. Patients were divided into three groups: normal glomerular filtration rate (GFR) (GFR > 90 mL/min/1.73 m²), mild CKD (90 ≥ GFR > 60 mL/min/1.73 m²), and moderate CKD (60 ≥ GFR > 30 mL/min/1.73 m²). Continuous and categorical variables were compared using analysis of variance and the χ² statistic. A multiple logistic regression model was used for detecting the association between total CAC score and GFR. An unadjusted model was used, followed by a second model adjusted for covariates known to be related to CAC. Another multivariable binary logistic model predicting the presence of CAC (>10) was performed and odds of incidence of CAC (>10) were calculated among the three GFR subgroups.ResultsAfter adjustment for covariates, patients with mild CKD had mean CAC scores 175 points higher than those with the referent normal GFR (P = 0.048), while those with moderate CKD had mean CAC scores 693 points higher than the referent (P < 0.001). After adjustment for covariates, patients with mild CKD were found to be 2.2 times more likely (95% confidence interval 1.3-3.7, P = 0.004) and patients with moderate CKD were 6.4 times more likely (95% confidence interval 2.9-14.3, P < 0.001) to have incident CAC compared with the group with normal GFR.ConclusionMild and moderate pre-dialysis CKD are independent risk factors for increased mean and incident CAC

Twist1 Inactivation in Dmp1-Expressing Cells Increases Bone Mass but Does Not Affect the Anabolic Response to Sclerostin Neutralization

Wnt signaling plays a major role in bone metabolism. Advances in our understanding of secreted regulators of Wnt have yielded several therapeutic targets to stimulate osteoanabolism—the most promising of which is the Wnt inhibitor sclerostin. Sclerostin antibody recently gained approval for clinical use to treat osteoporosis, but the biology surrounding sclerostin antagonism is still incompletely understood. Numerous factors regulate the efficacy of sclerostin inhibition on bone formation, a process known as self-regulation. In previous communications we reported that the basic helix-loop-helix transcription factor Twist1—a gene know to regulate skeletal development—is highly upregulated among the osteocyte cell population in mice treated with sclerostin antibody. In this communication, we tested the hypothesis that preventing Twist1 upregulation by deletion of Twist1 from late-stage osteoblasts and osteocytes would increase the efficacy of sclerostin antibody treatment, since Twist1 is known to restrain osteoblast activity in many models. Twist1-floxed loss-of-function mice were crossed to the Dmp1-Cre driver to delete Twist1 in Dmp1-expressing cells. Conditional Twist1 deletion was associated with a mild but significant increase in bone mass, as assessed by dual energy x-ray absorptiometry (DXA) and microCT (µCT) for many endpoints in both male and female mice. Biomechanical properties of the femur were not affected by conditional mutation of Twist1. Sclerostin antibody improved all bone properties significantly, regardless of Twist1 status, sex, or endpoint examined. No interactions were detected when Twist1 status and antibody treatment were examined together, suggesting that Twist1 upregulation in the osteocyte population is not an endogenous mechanism that restrains the osteoanabolic effect of sclerostin antibody treatment. In summary, Twist1 inhibition in the late-stage osteoblast/osteocyte increases bone mass but does not affect the anabolic response to sclerostin neutralization

New scalar resonances from sneutrino-Higgs mixing in supersymmetry with small lepton number (R-parity) violation

We consider new s-channel scalar exchanges in top quark and massive gauge-bosons pair production in e+e- collisions, in supersymmetry with a small lepton number violation. We show that a soft bilinear lepton number violating term in the scalar potential which mixes the Higgs and the slepton fields can give rise to a significant scalar resonance enhancement in e+e- -> ZZ, W+W- and in e+e- -> t t(bar). The sneutrino-Higgs mixed state couples to the incoming light leptons through its sneutrino component and to either the top quark or the massive gauge bosons through its Higgs component. Such a scalar resonance in these specific production channels cannot result from trilinear Yukawa-like R-parity violation alone, and may, therefore, stand as strong evidence for the existence of R-parity violating bilinears in the supersymmetric scalar potential. We use the LEP2 measurements of the WW and ZZ cross-sections to place useful constrains on this scenario, and investigate the expectations for the sensitivity of a future linear collider to these signals. We find that signals of these scalar resonances, in particular in top-pair production, are well within the reach of linear colliders in the small lepton number violation scenario.Comment: 22 pages in revtex, 10 figures embadded in the text using epsfi

Neutrino Oscillations and R-parity Violating Collider Signals

R-parity and L violation in the MSSM would be the origin of the neutrino oscillation observed in Super-Kamiokande. A distinctive feature of this framework is that it can be tested in colliders by observing decay products of the destabilized LSP. We examine all the possible decay processes of the neutralino LSP assuming the bilinear contribution to neutrino masses dominates over the trilinear one which gives rise to the solar neutrino mass. We find that it is possible to probe neutrino oscillations through colliders in most of the R-parity conserving MSSM parameter space.Comment: 23 pages, 8 figures, to appear in Phys. Rev.

A Supersymmetric Solution to the Solar and Atmospheric Neutrino Problems

The simplest unified extension of the Minimal Supersymmetric Standard Model with bi-linear R--Parity violation provides a predictive scheme for neutrino masses which can account for the observed atmospheric and solar neutrino anomalies in terms of bi-maximal neutrino mixing. The maximality of the atmospheric mixing angle arises dynamically, by minimizing the scalar potential, while the solar neutrino problem can be accounted for either by large or by small mixing oscillations. One neutrino picks up mass by mixing with neutralinos, while the degeneracy and masslessness of the other two is lifted only by loop corrections. Despite the smallness of neutrino masses R-parity violation is observable at present and future high-energy colliders, providing an unambiguous cross-check of the model.Comment: 5 pages, final version published in Phys. Rev. D61, 2000, 071703(R

A Collider Signature of the Supersymmetric Golden Region

Null results of experimental searches for the Higgs boson and the superpartners imply a certain amount of fine-tuning in the electroweak sector of the Minimal Supersymmetric Standard Model (MSSM). The "golden region" in the MSSM parameter space is the region where the experimental constraints are satisfied and the amount of fine-tuning is minimized. In this region, the stop trilinear soft term is large, leading to a significant mass splitting between the two stop mass eigenstates. As a result, the decay of the heavier stop into the lighter stop and a Z boson is kinematically allowed throughout the golden region. We propose that the experiments at the Large Hadron Collider (LHC) can search for this decay through an inclusive signature, Z+2jb+missing Et+X. We evaluate the Standard Model backgrounds for this channel, and identify a set of cuts that would allow detection of the supersymmetric contribution at the LHC for the MSSM parameters typical of the golden region. We also discuss other possible interpretations of a signal for new physics in the Z+2jb+missing Et+X channel, and suggest further measurements that could be used to distinguish among these interpretations.Comment: 23 pages, 5 figures. New in v4: an error fixed in Eq. (13); results unaffecte

Interaction-based quantum metrology showing scaling beyond the Heisenberg limit

Quantum metrology studies the use of entanglement and other quantum resources to improve precision measurement. An interferometer using N independent particles to measure a parameter X can achieve at best the "standard quantum limit" (SQL) of sensitivity {\delta}X \propto N^{-1/2}. The same interferometer using N entangled particles can achieve in principle the "Heisenberg limit" {\delta}X \propto N^{-1}, using exotic states. Recent theoretical work argues that interactions among particles may be a valuable resource for quantum metrology, allowing scaling beyond the Heisenberg limit. Specifically, a k-particle interaction will produce sensitivity {\delta}X \propto N^{-k} with appropriate entangled states and {\delta}X \propto N^{-(k-1/2)} even without entanglement. Here we demonstrate this "super-Heisenberg" scaling in a nonlinear, non-destructive measurement of the magnetisation of an atomic ensemble. We use fast optical nonlinearities to generate a pairwise photon-photon interaction (k = 2) while preserving quantum-noise-limited performance, to produce {\delta}X \propto N^{-3/2}. We observe super-Heisenberg scaling over two orders of magnitude in N, limited at large N by higher-order nonlinear effects, in good agreement with theory. For a measurement of limited duration, super-Heisenberg scaling allows the nonlinear measurement to overtake in sensitivity a comparable linear measurement with the same number of photons. In other scenarios, however, higher-order nonlinearities prevent this crossover from occurring, reflecting the subtle relationship of scaling to sensitivity in nonlinear systems. This work shows that inter-particle interactions can improve sensitivity in a quantum-limited measurement, and introduces a fundamentally new resource for quantum metrology

Constraining an R-parity violating supersymmetric theory from the SuperKamiokande data on atmospheric neutrinos

The constraints on an R-parity violating supersymmetric theory arising from the recent SuperKamiokande results on atmospheric neutrinos are studied, with special reference to a scenario with bilinear R-parity violating terms. Considering both the fermionic and scalar sectors, we find that a large area of the parameter space is allowed, in terms of both the lepton-number violating entries in the superpotential and the soft R-violating terms in the scalar potential, and that no fine-tuning is required. However, the need to avoid flavour changing neutral currents puts additional restrictions on the theory, requiring either the R-violating terms in the superpotential to be smaller than the R-conserving ones, or a hierarchy in the R-violating parameters for different lepton flavours in the superpotential.Comment: 18 pages, LaTex including postscript figure

Collider Signatures of Neutrino Masses and Mixing from R-parity Violation

R-parity violation in the supersymmetric standard model can be the source of neutrino masses and mixing. We analyze the neutrino mass matrix coming from either bilinear or trilinear R-parity violation and its collider signatures, assuming that the atmospheric and solar neutrino data are explained by three active neutrino oscillations. Taking the gauge mediated supersymmetry breaking mechanism, we show that the lightest neutralino decays well inside the detector and the model could be tested by observing its branching ratios in the future colliders. In the bilinear model where only the small solar neutrino mixing angle can be accommodated, the relation, $10^3$ BR($\nu e^\pm \tau^\mp$) $\sim$ BR($\nu \mu^\pm \tau^\mp$) $\approx$ BR($\nu \tau^\pm \tau^\mp$), serves as a robust test of the model. The large mixing angle solution can be realized in the trilinear model which predicts BR($\nu e^\pm \tau^\mp$) $\sim$ BR($\nu \mu^\pm \tau^\mp$) $\sim$ BR($\nu \tau^\pm \tau^\mp$). In either case, the relation, BR($e jj$) $\ll$ BR($\mu jj$) $\sim$ BR($\tau jj$), should hold to be consistent with the atmospheric neutrino and CHOOZ experiments.Comment: 24pages, Late