EFFECT OF PELVIC MOTION ON SOCCER KICKING PERFORMANCE

When two-dimensionally simulating proximal to distal movement patterns (i.e. gait, sprint, kicking and throwing movements) pelvic (or shoulder) motion is usually not modelled individually for each leg (or arm). However, it can be observed that during these motions, pelvic rotation and translation causes hip acceleration (Dbrge et ai, 1999). Hence, the purpose of the present study was to investigate the effect of pelvic motion on the succes of a soccer kicking motion

Persistent clinical efficacy and safety of anti-tumour necrosis factor \textgreeka therapy with infliximab in patients with ankylosing spondylitis over 5 years: evidence for different types of response

Background: There is insufficient evidence for the long-term efficacy and safety of anti-tumour necrosis factor therapy in patients with ankylosing spondylitis (AS). This is the first report on the treatment with infliximab over 5 years.Methods: As part of a multicentre randomised trial, 69 patients with active AS at baseline (BL) have been continuously treated with infliximab (5 mg/kg i.v. every 6 weeks)---except for a short discontinuation after 3 years (FU1). The primary outcome of this extension was remission according to the ASsessment in Ankylosing Spondylitis (ASAS) criteria at the end of year 5 of the study (FU2).Results: Of the 43 patients who completed year 3, 42 agreed to continue, 38 of which (90.5%) finished year 5 (55% of 69 initially). Partial clinical remission was achieved in 13 of 38 patients (34.2%) at FU1 and FU2. At FU2, the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 2.5±1.9 (BL:6.4, FU1:2.5). BASDAI values <4 were seen in 79% of patients at both, FU1 and FU2. ASAS 20% and 40% responses were seen in 32 (84%) and 24 (63%) patients at FU2, respectively. Most patients classified as non-responders at FU2 were part-time responders, as all but one patient achieved an ASAS 20% response at least once within the last 2 years. Three types of responders were identified. No major side effects occurred during years 4 and 5 of infliximab therapy.Conclusions: Infliximab is safe and efficacious in AS patients over 5 years. The majority of the patients remained on treatment and had rather persistent levels of low disease activity. Different response types could be identified

Munc18-1: sequential interactions with the fusion machinery stimulate vesicle docking and priming

Exocytosis of secretory or synaptic vesicles is executed by a mechanism including the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins. Munc18-1 is a part of this fusion machinery, but its role is controversial because it is indispensable for fusion but also inhibits the assembly of purified SNAREs in vitro. This inhibition reflects the binding of Munc18-1 to a closed conformation of the target-SNARE syntaxin1. The controversy would be solved if binding to closed syntaxin1 were shown to be stimulatory for vesicle fusion and/or additional essential interactions were identified between Munc18-1 and the fusion machinery. Here, we provide evidence for both notions by dissecting sequential steps of the exocytotic cascade while expressing Munc18 variants in the Munc18-1 null background. In Munc18-1 null chromaffin cells, vesicle docking is abolished and syntaxin levels are reduced. A mutation that diminished Munc18 binding to syntaxin1 in vitro attenuated the vesicle-docking step but rescued vesicle priming in excess of docking. Conversely, expressing the Munc18-2 isoform, which also displays binding to closed syntaxin1, rescued vesicle docking identical with Munc18-1 but impaired more downstream vesicle priming steps. All Munc18 variants restored syntaxin1 levels at least to wild-type levels, showing that the docking phenotype is not caused by syntaxin1 reduction. None of the Munc18 variants affected vesicle fusion kinetics or fusion pore duration. In conclusion, binding of Munc18-1 to closed syntaxin1 stimulates vesicle docking and a distinct interaction mode regulates the consecutive priming step. Copyright © 2007 Society for Neuroscience

An analysis of the Taguchi method for tuning a memetic algorithm with reduced computational time budget

Determining the best initial parameter values for an algorithm, called parameter tuning, is crucial to obtaining better algorithm performance; however, it is often a time-consuming task and needs to be performed under a restricted computational budget. In this study, the results from our previous work on using the Taguchi method to tune the parameters of a memetic algorithm for cross-domain search are further analysed and extended. Although the Taguchi method reduces the time spent finding a good parameter value combination by running a smaller size of experiments on the training instances from different domains as opposed to evaluating all combinations, the time budget is still larger than desired. This work investigates the degree to which it is possible to predict the same good parameter setting faster by using a reduced time budget. The results in this paper show that it was possible to predict good combinations of parameter settings with a much reduced time budget. The good final parameter values are predicted for three of the parameters, while for the fourth parameter there is no clear best value, so one of three similarly performing values is identified at each time instant

Dams and Dynasty, and the Colonial Transformation of Balinese Irrigation Management

This article takes issue with Stephen Lansing’s bottom-up model of Balinese irrigation management. Based on archival research and extensive fieldwork in the former south Balinese kingdom of Mengwi, it is argued that in pre-colonial days large scale irrigation depended largely on dynastic involvement. During the colonial period (1906–1942) the Dutch took over the role of regional irrigation management while they strengthened the autonomy of local irrigation associations

Composing first species counterpoint with a variable neighbourhood search algorithm

In this article, a variable neighbourhood search (VNS) algorithm is developed that can generate musical fragments consisting of a melody for the cantus firmus and the first species counterpoint. The objective function of the algorithm is based on a quantification of existing rules for counterpoint. The VNS algorithm developed in this article is a local search algorithm that starts from a randomly generated melody and improves it by changing one or two notes at a time. A thorough parametric analysis of the VNS reveals the significance of the algorithm's parameters on the quality of the composed fragment, as well as their optimal settings. A comparison of the VNS algorithm with a developed genetic algorithm shows that the VNS is more efficient. The VNS algorithm has been implemented in a user-friendly software environment for composition, called Optimuse. Optimuse allows a user to specify a number of characteristics such as length, key and mode. Based on this information, Optimuse 'composes' both cantus firmus and first species counterpoint. Alternatively, the user may specify a cantus firmus, and let Optimuse compose the accompanying first species counterpoint. © 2012 Taylor & Francis

Trapped electron coupled to superconducting devices

We propose to couple a trapped single electron to superconducting structures located at a variable distance from the electron. The electron is captured in a cryogenic Penning trap using electric fields and a static magnetic field in the Tesla range. Measurements on the electron will allow investigating the properties of the superconductor such as vortex structure, damping and decoherence. We propose to couple a superconducting microwave resonator to the electron in order to realize a circuit QED-like experiment, as well as to couple superconducting Josephson junctions or superconducting quantum interferometers (SQUIDs) to the electron. The electron may also be coupled to a vortex which is situated in a double well potential, realized by nearby pinning centers in the superconductor, acting as a quantum mechanical two level system that can be controlled by a transport current tilting the double well potential. When the vortex is trapped in the interferometer arms of a SQUID, this would allow its detection both by the SQUID and by the electron.Comment: 13 pages, 5 figure

Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study

BACKGROUND: In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis. METHODS: Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients received ≤ 6 monthly doses of dezamizumab in the Phase 2 trial (n = 7), ≤ 2 doses of non-radiolabelled dezamizumab plus [89Zr]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (n = 2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [89Zr]Zr-dezamizumab cardiac uptake assessed via PET. RESULTS: Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [89Zr]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks. CONCLUSIONS: Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018)