A Randomised, Blinded, Placebo-Controlled, Dose Escalation Study of the Tolerability and Efficacy of Filgrastim for Haemopoietic Stem Cell Mobilisation in Patients With Severe Active Rheumatoid Arthritis

Autologous haemopoietic stem cell transplantation (HSCT) represents a potential therapy for severe rheumatoid arthritis (RA). As a prelude to clinical trails, the safety and efficacy of haemopoietic stem cell (HSC) mobilisation required investigation as colony-stimulating factors (CSFs) have been reported to flare RA. A double-blind, randomised placebo-controlled dose escalation study was performed. Two cohorts of eight patients fulfilling strict eligibility criteria for severe active RA (age median 40 years, range 24-60 years; median disease duration 10.5 years, range 2-18 years) received filgrastim (r-Hu-methionyl granulocyte(G)-(SF) at 5 and 10 microg/kg/day, randomised in a 5:3 ratio with placebo. Patients were unblinded on the fifth day of treatment and those randomised to filgrastim underwent cell harvesting (leukapheresis) daily until 2 X 10^6/kg CD34+ cells (haemopoietic stem and progenitor cells) were obtained. Patients were assessed by clinical and laboratory parameters before, during and after filgrastim administration. RA flare was defined as an increase of 30% or more in two of the following parameters: tender joint count, swollen joint count or pain score. Efficacy was assessed by quantitation of CD34+ cells and CFU-GM. One patient in the 5 microg/kg/day group and two patients in the 10 microg/kg/day group fulfilled criteria for RA flare, although this did not preclude successful stem cell collection. Median changes in swollen and tender joint counts were not supportive of filgrastim consistently causing exacerbation of disease, but administration of filgrastim at 10 microg/kg/day was associated with rises in median C-reactive protein and median rheumatoid factor compared with placebo. Other adverse events were well recognised for filgrastim and included bone pain (80%) and increases in alkaline phosphatase (four-fold) and lactate dehydrogenase (two-fold). With respect to efficacy, filgrastim at 10 microg/kg/day was more efficient with all patients (n = 5) achieving target CD34+ cell counts with a single leukapheresis (median = 2.8, range = 2.3-4.8 X 10^6/kg, median CFU-GM = 22.1, range = 4.2-102.9 X 10^4/kg), whereas 1-3 leukaphereses were necessary to achieve the target yield using 5 microg/kg/day. We conclude that filgrastim may be administered to patients with severe active RA for effective stem cell mobilisation. Flare of RA occurs in a minority of patients and is more likely with 10 than 5 microg/kg/day. However, on balance, 10 microg/kg/day remains the dose of choice in view of more efficient CD34+ cell mobilisation

Displacement power spectrum measurement of a macroscopic optomechanical system at thermal equilibrium

The mirror relative motion of a suspended Fabry-Perot cavity is studied in the frequency range 3-10 Hz. The experimental measurements presented in this paper, have been performed at the Low Frequency Facility, a high finesse optical cavity 1 cm long suspended to a mechanical seismic isolation system identical to that one used in the VIRGO experiment. The measured relative displacement power spectrum is compatible with a system at thermal equilibrium within its environmental. In the frequency region above 3 Hz, where seismic noise contamination is negligible, the measurement distribution is stationary and Gaussian, as expected for a system at thermal equilibrium. Through a simple mechanical model it is shown that: applying the fluctuation dissipation theorem the measured power spectrum is reproduced below 90 Hz and noise induced by external sources are below the measurement.Comment: 11 pages, 9 figures, 2 tables, to be submitte

Robot-assisted arm training in patients with Parkinson's disease: a pilot study.

BACKGROUND: Despite the growing diffusion of robotic devices in neurorehabilitation, no previous study investigated the effects of robotic training on arm impairment due to Parkinson's disease. The aim of this pilot study was to evaluate whether robot-assisted arm training might improve upper limb function in patients with Parkinson's disease.FINDINGS: Ten patients with Parkinson's disease (Hoehn and Yahr stage 2.5-3) received ten, 45-minute, treatment sessions, five days a week, for two consecutive weeks. Robot-assisted arm training was performed with the Bi-Manu-Track (Reha-Stim, Berlin, Germany) that provides a computer-controlled, repetitive, bilateral, mirror-like practice of forearm pronation/supination and wrist extension/flexion. Patients were trained according to the following modalities: passive-passive (both arms moved by the machine) and active-active (both arms actively moving against resistance). The dominant upper limb was evaluated before and immediately after treatment as well as at two weeks of follow-up. Outcomes were the nine-hole peg test, the Fugl-Meyer assessment (upper limb section) and the Unified Parkinson's Disease Rating Scale. After treatment, a significant improvement was found in the nine-hole peg test (P\u2009=\u20090.007) as well as in the upper limb section of the Fugl-Meyer assessment (P\u2009=\u20090.012). Findings were confirmed at the 2-week follow-up evaluation only for the nine-hole peg test (P\u2009=\u20090.007). No significant improvement was found in the Unified Parkinson's Disease Rating Scale at both post-treatment and follow-up evaluations.CONCLUSIONS: Our findings support the hypothesis that robot-assisted arm training might be a promising tool in order to improve upper limb function in patients with Parkinson's disease

Inertial control of the mirror suspensions of the VIRGO interferometer for gravitational wave detection

In order to achieve full detection sensitivity at low frequencies, the mirrors of interferometric gravitational wave detectors must be isolated from seismic noise. The VIRGO vibration isolator, called 'superattenuator', is fully effective at frequencies above 4 Hz. Nevertheless, the residual motion of the mirror at the mechanical resonant frequencies of the system are too large for the interferometer locking system and must be damped. A multidimensional feedback system, using inertial sensors and digital processing, has been designed for this purpose. An experimental procedure for determining the feedback control of the system has been defined. In this paper a full description of the system is given and experimental results are presented.Comment: 17 pages, 11 figures, accepted for publication on Review of Scientific Instrument

Manifestações patológicas oriundas da falta de estanqueidade em pavilhão de laboratórios de uma instituição de ensino pública

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Evaluation of the potential improvement in the environmental footprint of geopolymers using waste-derived activators

Geopolymers produced from an aluminosilicate precursor and an alkaline activating solution have emerged as low carbon alternative binders which can substitute for Portland cement (PC) in many applications. The presence of soluble silicate in the activating solution of a geopolymer is known to yield a denser and more compact material with higher mechanical strength compared to hydroxide-activated geopolymers. However, these silicate solutions are the most expensive component of geopolymer cements, as well as the highest contributors to their environmental impacts in most life cycle categories. Geopolymers are widely accepted as a more environmental friendly material due to their claimed lower CO2 emissions due to their synthesis from industrial by-products or wastes, as well the low energy demand during their production. However, the use of alkali-silicate activators can significantly increase other environmental impacts, leading to controversies regarding whether geopolymers can really be considered as a more sustainable material. Thus, this study evaluates the life cycle impacts of a geopolymer produced from a kaolin sludge residue from the Brazilian mining industry. Alkaline solutions derived from sodium hydroxide solutions and two different soluble silica sources were used as activators: a commercial sodium silicate (waterglass), and chemically modified rice husk ash (RHA). The processes which contribute the most to the life cycle impacts of geopolymers are thermal curing, waterglass production, and sodium hydroxide production. The use of RHA-derived sodium silicate may reduce environmental impacts by more than 60% in 6 of the 9 categories assessed, indicating that this is a favourable alternative where RHA is locally available. Although the binders evaluated here have differences in mechanical properties, those using RHA-derived activators exhibit impacts lower than PC for 4 of the 8 categories evaluated, and a reduction of more than 70% in global warming potential. RHA-based activators are identified as a promising alternative for impact reduction in geopolymer production, and more detailed assessments of the performance and reactivity of these activators should be conducted

Piezoelectric actuators control unit

Proceedings of the 1st International Particle Accelerator Conference, IPAC2010, Kyoto, Japa

Sensitivity Studies for Third-Generation Gravitational Wave Observatories

Advanced gravitational wave detectors, currently under construction, are expected to directly observe gravitational wave signals of astrophysical origin. The Einstein Telescope, a third-generation gravitational wave detector, has been proposed in order to fully open up the emerging field of gravitational wave astronomy. In this article we describe sensitivity models for the Einstein Telescope and investigate potential limits imposed by fundamental noise sources. A special focus is set on evaluating the frequency band below 10Hz where a complex mixture of seismic, gravity gradient, suspension thermal and radiation pressure noise dominates. We develop the most accurate sensitivity model, referred to as ET-D, for a third-generation detector so far, including the most relevant fundamental noise contributions.Comment: 13 pages, 7 picture

The variable finesse locking technique

Virgo is a power recycled Michelson interferometer, with 3 km long Fabry-Perot cavities in the arms. The locking of the interferometer has been obtained with an original lock acquisition technique. The main idea is to lock the instrument away from its working point. Lock is obtained by misaligning the power recycling mirror and detuning the Michelson from the dark fringe. In this way, a good fraction of light escapes through the antisymmetric port and the power build-up inside the recycling cavity is extremely low. The benefit is that all the degrees of freedom are controlled when they are almost decoupled, and the linewidth of the recycling cavity is large. The interferometer is then adiabatically brought on to the dark fringe. This technique is referred to as variable finesse, since the recycling cavity is considered as a variable finesse Fabry-Perot. This technique has been widely tested and allows us to reach the dark fringe in few minutes, in an essentially deterministic way

Scientific Potential of Einstein Telescope

Einstein gravitational-wave Telescope (ET) is a design study funded by the European Commission to explore the technological challenges of and scientific benefits from building a third generation gravitational wave detector. The three-year study, which concluded earlier this year, has formulated the conceptual design of an observatory that can support the implementation of new technology for the next two to three decades. The goal of this talk is to introduce the audience to the overall aims and objectives of the project and to enumerate ET's potential to influence our understanding of fundamental physics, astrophysics and cosmology.Comment: Conforms to conference proceedings, several author names correcte