The effect of three years of TNF alpha blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study

INTRODUCTION: The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-alpha) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS). METHODS: This is a prospective cohort study of 111 consecutive AS outpatients who started TNF-alpha blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly. RESULTS: After three years, 72 patients (65%) were still using their first TNF-alpha blocking agent. In these patients, TNF-alpha blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physician's global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life. CONCLUSIONS: Three years of TNF-alpha blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-alpha blocking therapy in AS, in addition to the currently used more subjective measures

Two-dimensional superconductivity at the (111)LaAlO3_3/SrTiO3_3 interface

We report on the discovery and transport study of the superconducting ground state present at the (111)LaAlO$_3$/SrTiO$_3$ interface. The superconducting transition is consistent with a Berezinskii-Kosterlitz-Thouless transition and its 2D nature is further corroborated by the anisotropy of the critical magnetic field, as calculated by Tinkham. The estimated superconducting layer thickness and coherence length are 10 nm and 60 nm, respectively. The results of this work provide a new platform to clarify the microscopic details of superconductivity at LaAlO$_3$/SrTiO$_3$ interfaces, in particular in what concerns the link with orbital symmetry.Comment: 4 pages, 4 figure

Pure cervical radiculopathy due to spontaneous spinal epidural haematoma (SSEH): report of a case solved conservatively

Introduction: Spontaneous spinal epidural haematoma (SSEH) is widely recognised throughout the literature as a cause of myelopathy, radicular compression being very rarely reported. Surgical management is almost always recommended, especially in the cases of spinal cord compression. Conservative treatment is reported as a curiosity and only in the case of spontaneous improvement. This report presents the particular case of a 64-year-old patient undergoing anticoagulant therapy that had a cervical radiculopathy due to a SSEH confirmed by MRI. The patient improved spontaneously and symptoms were solved with unconventional conservative treatment and without stopping the anticoagulant therapy. Conclusions: Spontaneous epidural haematoma must be kept in mind when patients undergoing anticoagulant therapy have a sudden onset of cervicobrachialgia. Even though most spinal surgeons advocate surgical treatment, a conservative approach may lead to a complete recovery and may be considered as a good option in the case of radicular involvement. Discontinuation of the anticoagulant therapy may not always be needed, especially when the clinical syndrome improves spontaneously

PyCOOL - a Cosmological Object-Oriented Lattice code written in Python

There are a number of different phenomena in the early universe that have to be studied numerically with lattice simulations. This paper presents a graphics processing unit (GPU) accelerated Python program called PyCOOL that solves the evolution of scalar fields in a lattice with very precise symplectic integrators. The program has been written with the intention to hit a sweet spot of speed, accuracy and user friendliness. This has been achieved by using the Python language with the PyCUDA interface to make a program that is easy to adapt to different scalar field models. In this paper we derive the symplectic dynamics that govern the evolution of the system and then present the implementation of the program in Python and PyCUDA. The functionality of the program is tested in a chaotic inflation preheating model, a single field oscillon case and in a supersymmetric curvaton model which leads to Q-ball production. We have also compared the performance of a consumer graphics card to a professional Tesla compute card in these simulations. We find that the program is not only accurate but also very fast. To further increase the usefulness of the program we have equipped it with numerous post-processing functions that provide useful information about the cosmological model. These include various spectra and statistics of the fields. The program can be additionally used to calculate the generated curvature perturbation. The program is publicly available under GNU General Public License at https://github.com/jtksai/PyCOOL . Some additional information can be found from http://www.physics.utu.fi/tiedostot/theory/particlecosmology/pycool/ .Comment: 23 pages, 12 figures; some typos correcte

Plasma oxyphytosterols most likely originate from hepatic oxidation and subsequent spill-over in the circulation

We evaluated oxyphytosterol (OPS) concentrations in plasma and various tissues of two genetically modified mouse models with either increased cholesterol (apoE KO mice) or increased cholesterol and plant sterol (PS) concentrations (apoExABCG8 dKO mice). Sixteen female apoE KO and 16 dKO mice followed the same standard, low OPS-chow diet. Animals were euthanized at 36 weeks to measure PS and OPS concentrations in plasma, brain, liver and aortic tissue. Cholesterol and oxysteml (OS) concentrations were analyzed as reference for sterol oxidation in general. Plasma campesterol (24.1 +/- 4.3 vs. 11.8 +/- 3.0 mg/dL) and sitosterol (67.4 +/- 12.7 vs. 4.9 +/- 1.1 mg/dL) concentrations were severely elevated in the dKO compared to the apoE KO mice (p < 0.001). Also, in aortic and brain tissue, PS levels were significantly elevated in dKO. However, plasma, aortic and brain OPS concentrations were comparable or even lower in the dKO mice. In contrast, in liver tissue, both PS and OPS concentrations were severely elevated in the dKO compared to apoE KO mice (sum OPS: 7.4 +/- 1.6 vs. 4.1 +/- 0.8 ng/mg, p < 0.001). OS concentrations followed cholesterol concentrations in plasma and all tissues suggesting ubiquitous oxidation. Despite severely elevated PS concentrations, OPS concentrations were only elevated in liver tissue, suggesting that OPS are primarily formed in the liver and plasma concentrations originate from hepatic spill-over into the circulation

Manipulating a qubit through the backaction of sequential partial measurements and real-time feedback

Quantum measurements not only extract information from a system but also alter its state. Although the outcome of the measurement is probabilistic, the backaction imparted on the measured system is accurately described by quantum theory. Therefore, quantum measurements can be exploited for manipulating quantum systems without the need for control fields. We demonstrate measurement-only state manipulation on a nuclear spin qubit in diamond by adaptive partial measurements. We implement the partial measurement via tunable correlation with an electron ancilla qubit and subsequent ancilla readout. We vary the measurement strength to observe controlled wavefunction collapse and find post-selected quantum weak values. By combining a novel quantum non-demolition readout on the ancilla with real-time adaption of the measurement strength we realize steering of the nuclear spin to a target state by measurements alone. Besides being of fundamental interest, adaptive measurements can improve metrology applications and are key to measurement-based quantum computing.Comment: 6 pages, 4 figure

Intraoperative neurophysiological monitoring during scoliosis surgery in patients with Duchenne muscular dystrophy

PURPOSE: Little is known about the reliability and value of intraoperative neurophysiological monitoring (IONM) in patients with Duchenne muscular dystrophy (DMD) undergoing scoliosis correction surgery. The aim of this study was to investigate the feasibility of IONM and the cortical excitability in these patients. METHODS: Fifteen patients with DMD and scoliosis and 15 patients with adolescent idiopathic scoliosis (AIS) underwent scoliosis correction surgery with the use of IONM. IONM consisted of transcranial electrical stimulation motor evoked potential (Tc-MEP) and somatosensory evoked potential (SSEP) monitoring. The highest Tc-MEP amplitudes were collected to test the feasibility. Preoperative compound muscle action potentials (CMAPs) and transcranial magnetic stimulation (TMS)-MEPs were recorded to test the cortical excitability. SSEPs were scored as elicitable or not elicitable. RESULTS: Tc-MEP amplitudes were significantly lower in the DMD group for both the gastrocnemius and tibialis anterior muscles. However, the abductor hallucis muscle had similar amplitudes in both the DMD as the AIS group. TMS/CMAP and Tc-MEP/CMAP ratios were similar in the DMD and AIS group (P = 0.126 and P = 0.792 respectively). CONCLUSIONS: Tc-MEP and SSEP monitoring is feasible, particularly when Tc-MEPs are recorded from the abductor hallucis muscle in patients with DMD. Similar TMS/CMAP and Tc-MEP/CMAP ratios show that there were no differences observed in cortical excitability between the groups. IONM seems a feasible and valuable neurophysiological tool to signal possible surgically induced damage to the spinal cord during scoliosis correction surgery in patients with DMD

Anomalous superconducting state gap size versus Tc behavior in underdoped Bi_2Sr_2Ca_1-xDy_xCu_2O_8+d

We report angle-resolved photoemission spectroscopy measurements of the excitation gap in underdoped superconducting thin films of Bi_2Sr_2Ca_{1-x}Dy_xCu_2O_{8+d}. As Tc is reduced by a factor of 2 by underdoping, the superconducting state gap \Delta does not fall proportionally, but instead stays constant or increases slightly, in violation of the BCS mean-field theory result. The different doping dependences of \Delta and kT_c indicate that they represent different energy scales. The measurements also show that \Delta is highly anisotropic and consistent with a d_{x^2-y^2} order parameter, as in previous studies of samples with higher dopings. However, in these underdoped samples, the anisotropic gap persists well above T_c. The existence of a normal state gap is related to the failure of \Delta to scale with T_c in theoretical models that predict pairing without phase coherence above T_c.Comment: 10 pages, 4 postscript figures, revtex forma

Isotope effects in underdoped cuprate superconductors: a quantum phenomenon

We show that the unusual doping dependence of the isotope effects on transition temperature and zero temperature in - plane penetration depth naturally follows from the doping driven 3D-2D crossover, the 2D quantum superconductor to insulator transition (QSI) in the underdoped limit and the change of the relative doping concentration upon isotope substitution. Close to the QSI transition both, the isotope coefficient of transition temperature and penetration depth approach the coefficient of the relative dopant concentration, and its divergence sets the scale. These predictions are fully consistent with the experimental data and imply that close to the underdoped limit the unusual isotope effect on transition temperature and penetration depth uncovers critical phenomena associated with the quantum superconductor to insulator transition in two dimensions.Comment: 6 pages, 3 figure