Tremor in motor neuron disease may be central rather than peripheral in origin

BACKGROUND AND PURPOSE: Motor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post-mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated. METHODS: A total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients. RESULTS: Action tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning. CONCLUSIONS: Our data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition

Lattice QCD with mixed actions

We discuss some of the implications of simulating QCD when the action used for the sea quarks is different from that used for the valence quarks. We present exploratory results for the hadron mass spectrum and pseudoscalar meson decay constants using improved staggered sea quarks and HYP-smeared overlap valence quarks. We propose a method for matching the valence quark mass to the sea quark mass and demonstrate it on UKQCD clover data in the simpler case where the sea and valence actions are the same.Comment: 15 pages, 10 figures some minor modification to text and figures. Accepted for publicatio

B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis

Objective: To comparatively assess the B-cell composition in blood and CSF of patients with pediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS). / Methods: In this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8–18 years) and 40 patients with adMS (23–65 years) and blood specimens from 66 controls (1–55 years). By using multicolor flow cytometry, we identified naive, transitional, isotype class-switched memory, nonswitched memory, and double-negative memory B-cell subsets as well as plasmablasts (PB) and terminally differentiated plasma cells (PC). Flow cytometric data were compared to concentrations of B-cell-specific cytokines in serum and CSF as determined by ELISA. / Results: Frequencies of circulating naive B-cells decreased with higher age in controls but not in patients with multiple sclerosis (MS). B-cell patterns in CSF differed between pedMS and adMS with an acute relapse: in pedMS-derived CSF samples, high frequencies of nonswitched memory B cells and PB were present, whereas class-switched memory B cells and PC dominated in the CSF of patients with adMS. In pedMS, PB were also elevated in the periphery. Accumulation of PB in the CSF correlated with high intrathecal CXCL-13 levels and augmented intrathecal synthesis of immunoglobulin G and immunoglobulin M. / Conclusions: We demonstrate distinct changes in intrathecal B-cell homeostasis in patients with pedMS during active disease, which differ from those in adults by an expansion of plasmablasts in blood and CSF and similarly occur in prototypic autoantibody-driven autoimmune disorders. This emphasizes the particular importance of activated B-lymphocyte subsets for disease progression in the earliest clinical stages of MS

Educational recommendations for the conduct, content and format of EULAR musculoskeletal ultrasound Teaching the Teachers Courses

To produce educational guidelines for the conduct, content and format of theoretical and practical teaching at EULAR musculoskeletal ultrasound (MSUS) Teaching the Teachers (TTT) Courses

Calculations of time-dependent observables in non-Hermitian quantum mechanics: The problem and a possible solution

The solutions of the time independent Schrodinger equation for non-Hermitian (NH) Hamiltonians have been extensively studied and calculated in many different fields of physics by using L^2 methods that originally have been developed for the calculations of bound states. The existing non-Hermitian formalism breaks down when dealing with wavepackets(WP). An open question is how time dependent expectation values can be calculated when the Hamiltonian is NH ? Using the F-product formalism, which was recently proposed, [J. Phys. Chem., 107, 7181 (2003)] we calculate the time dependent expectation values of different observable quantities for a simple well known study test case model Hamiltonian. We carry out a comparison between these results with those obtained from conventional(i.e., Hermitian) quantum mechanics (QM) calculations. The remarkable agreement between these results emphasizes the fact that in the NH-QM, unlike standard QM, there is no need to split the entire space into two regions; i.e., the interaction region and its surrounding. Our results open a door for a type of WP propagation calculations within the NH-QM formalism that until now were impossible.Comment: 20 pages, 5 Postscript figures. To be Published in Physical Review

Localization and chiral symmetry in 2+1 flavor domain wall QCD

We present results for the dependence of the residual mass of domain wall fermions (DWF) on the size of the fifth dimension and its relation to the density and localization properties of low-lying eigenvectors of the corresponding hermitian Wilson Dirac operator relevant to simulations of 2+1 flavor domain wall QCD. Using the DBW2 and Iwasaki gauge actions, we generate ensembles of configurations with a $16^3\times 32$ space-time volume and an extent of 8 in the fifth dimension for the sea quarks. We demonstrate the existence of a regime where the degree of locality, the size of chiral symmetry breaking and the rate of topology change can be acceptable for inverse lattice spacings $a^{-1} \ge 1.6$ GeV.Comment: 59 Pages, 23 figures, 1 MPG linke

A powerful intervention: general practitioners' use of sickness certification in depression

<b>Background</b> Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.<p></p> <b>Methods</b> A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.<p></p> <b>Results</b> A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.<p></p> <b>Conclusions</b> GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network

Several homeodomain (HD) proteins are critical for skeletal patterning and respond directly to BMP2 as an early step in bone formation. RUNX2, the earliest transcription factor proven essential for commitment to osteoblastogenesis, is also expressed in response to BMP2. However, there is a gap in our knowledge of the regulatory cascade from BMP2 signaling to the onset of osteogenesis. Here we show that BMP2 induces DLX3, a homeodomain protein that activates Runx2 gene transcription. Small interfering RNA knockdown studies in osteoblasts validate that DLX3 is a potent regulator of Runx2. Furthermore in Runx2 null cells, DLX3 forced expression suffices to induce transcription of Runx2, osteocalcin, and alkaline phosphatase genes, thus defining DLX3 as an osteogenic regulator independent of RUNX2. Our studies further show regulation of the Runx2 gene by several homeodomain proteins: MSX2 and CDP/cut repress whereas DLX3 and DLX5 activate endogenous Runx2 expression and promoter activity in non-osseous cells and osteoblasts. These HD proteins exhibit distinct temporal expression profiles during osteoblast differentiation as well as selective association with Runx2 chromatin that is related to Runx2 transcriptional activity and recruitment of RNA polymerase II. Runx2 promoter mutagenesis shows that multiple HD elements control expression of Runx2 in relation to the stages of osteoblast maturation. Our studies establish mechanisms for commitment to the osteogenic lineage directly through BMP2 induction of HD proteins DLX3 and DLX5 that activate Runx2, thus delineating a transcriptional regulatory pathway mediating osteoblast differentiation. We propose that the three homeodomain proteins MSX2, DLX3, and DLX5 provide a key series of molecular switches that regulate expression of Runx2 throughout bone formation. <br/

Multi-layered Ruthenium-modified Bond Coats for Thermal Barrier Coatings

Diffusional approaches for fabrication of multi-layered Ru-modified bond coats for thermal barrier coatings have been developed via low activity chemical vapor deposition and high activity pack aluminization. Both processes yield bond coats comprising two distinct B2 layers, based on NiAl and RuAl, however, the position of these layers relative to the bond coat surface is reversed when switching processes. The structural evolution of each coating at various stages of the fabrication process has been and subsequent cyclic oxidation is presented, and the relevant interdiffusion and phase equilibria issues in are discussed. Evaluation of the oxidation behavior of these Ru-modified bond coat structures reveals that each B2 interlayer arrangement leads to the formation of α-Al 2 O 3 TGO at 1100°C, but the durability of the TGO is somewhat different and in need of further improvement in both cases