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Methadone, a Mu-opioid receptor agonist, is currently used as a maintenance treatment in opioid dependant patients. However, its therapeutic index is narrow, and side effects are life threatening. Non-optimal dosing results in withdrawal symptoms and further heroin craving and use. The optimal dose is defined as the dose necessary to obtain a stable substitution. This optimal maximal dose can then be decreased, the final goal being to stop substitution.
To identify factors to optimize the methadone optimal daily dose.
We aimed to identify genetic variants (SNP) associated with the methadone optimal dose. In a candidate gene approach, we focused on OPRM1, which encodes the opioid receptor Mu, and on DRD2/ANKK1 SNP's, implied in the reward dopaminergic signalling.
Caucasians patients (n = 98) followed for methadone maintenance treatment were included in this prospective study. Candidate SNPs were genotyped (ANKK1: TaqI A; DRD2: c.957C>T; OPRM1: c.A118G). The plasmatic methadone level was determined using mass spectrometry in 59 patients.
Two polymorphisms were significantly associated to the optimal methadone doses: OPRM1 c.A118G (p = 0.03) and DRD2 TaqI A (p = 0.035).
The TaqIA polymorphism is located within ANKK1, which encodes a serine threonine kinase which role remains elusive. Its molecular link to methadone pharmacodynamy remains to be established. None of these polymorphisms was associated neither to the current methadone doses, nor to the methadone plasmatic concentration.
This description is the first step to optimize the prescription of methadone in caucasian populations.
The effect of laser intensity on characteristics of the plasma ablated from a low-Z (CH) planar target irradiated by a 250 ps, 0.438 µm laser pulse with the intensity of up to 1016 W/cm2 as well as on parameters of the laser-driven shock generated in the target for various scale-lengths of preformed plasma was investigated at the kilojoule Prague Asterix Laser System (PALS) laser facility. Characteristics of the plasma were measured with the use of 3-frame interferometry, ion diagnostics, an X-ray spectrometer, and Kα imaging. Parameters of the shock generated in a Cl doped CH target by the intense 3ω laser pulse were inferred by numerical hydrodynamic simulations from the measurements of craters produced by the shock in the massive Cu target behind the CH layer. It was found that the pressure of the shock generated in the plastic layer is relatively weakly influenced by the preplasma (the pressure drop due to the preplasma presence is ~10–20%) and at the pulse intensity of ~1016 W/cm2 the maximum pressure reaches ~80–90 Mbar. However, an increase in pressure of the shock with the laser intensity is slower than predicted by theory for a planar shock and the maximum pressure achieved in the experiment is by a factor of ~2 lower than predicted by the theory. Both at the preplasma absence and presence, the laser-to-hot electrons energy conversion efficiency is small, ~1% or below, and the influence of hot electrons on the generated shock is expected to be weak.
We report on an experimental study on the interaction of a high-contrast 40 fs duration 2 TW laser pulse with an argon-cluster target. A high-charge, homogeneous, large divergence electron beam with moderate kinetic energy (~2 MeV) is observed in the forward direction. The results show that an electron beam with a charge as high as 12 nC can be obtained using a table-top laser system. It was demonstrated that the accelerated electron beam is suitable for a variety of applications such as micro-radiography of thin samples in a wide field of view. It can also be applied for in vitro dosimetry studies.
Background: Social Cognition and Interaction Training (SCIT) is a manual-based group intervention designed to improve social cognition in schizophrenia. Initial studies conducted by the developers of SCIT suggest that the intervention has promise in ameliorating social cognitive dysfunction in both inpatients and outpatients. Aims: The current study is a preliminary evaluation of SCIT in community samples. Method: An uncontrolled, pre-post design was used in this initial feasibility study. A collaborative research-clinical approach was employed to enable research evaluation while also meeting the administrative goals of participating clinics, and working within the constraints of real-world clinical practice. Transportability, acceptability, and feasibility of SCIT were evaluated in terms of pre- and post-treatment evaluations, client attendance data (N = 50), and clinic administrators’ decisions about whether to integrate SCIT into regular programming. Social-cognitive outcome measures assessed emotion perception, Theory of Mind, and attributional bias. Results: These support the transportability, acceptability, and feasibility of SCIT in community settings. SCIT has been integrated into routine practice at several test sites. Tentative support was found for improvement in emotion perception and Theory of Mind, but not attributional bias. Conclusions: SCIT may be a promising intervention for community agencies serving individuals with psychotic disorders who seek to improve their social functioning.
The development activity of a new experimental technique for the study of the fast electron transport in high density matter is reported. This new diagnostic tool enables the X-ray 2D imaging of ultrahigh intensity laser plasmas with simultaneous spectral resolution in a very large energy range to be obtained. Results from recent experiments are discussed, in which the electron propagation in multilayer targets was studied by using the Kα. In particular, results highlighting the role of anisotropic Bremsstrahlung are reported, for the sake of the explanation of the capabilities of the new diagnostics. A discussion of a test experiment conceived to extend the technique to a single-shot operation is finally given.
We used X-ray spectroscopy as a diagnostic tool for investigating the properties of laser-cluster interactions at the stage in which non-adiabatic cluster expansion takes place and a quasi-homogeneous plasma is produced. The experiment was carried out with a 10 TW, 65 fs Ti:Sa laser focused on CO2 cluster jets. The effect of different laser-pulse contrast ratios and cluster concentrations was investigated. The X-ray emission associated to the Rydberg transitions allowed us to retrieve, through the density and temperature of the emitting plasma, the time after the beginning of the interaction at which the emission occurred. The comparison of this value with the estimated time for the “homogeneous” plasma formation shows that the degree of adiabaticity depends on both the cluster concentration and the pulse contrast. Interferometric measurements support the X-ray data concerning the plasma electron density.
We report and discuss experimental results on the propagation of CPA pulses of moderately relativistic intensity in gas: they evidence the effects of the precursor pedestals of the main pulse. Details of great interest were observed for the first time with high quality femtosecond 90-degree interferometry. The interferometric data are also correlated with imaging and spectroscopy data of laser pulse transmitted through the gas. The most relevant physical features are confirmed by a numerical code which simulates the laser pulse propagation self-consistently with the ionization of the gas. We found that in this regime, the propagation of the intense femtosecond pulse is basically stable apart from very weak refractive effects. In order to allow propagation at fixed intensity along an optical path larger than the Rayleigh range, we performed a first successful attempt at producing hollow plasma channels able to guide the pulse.
Laser matter interaction in the regime of super-intense and
ultra-short laser pulses is discovering common interests and goals for
plasma and elementary particles physics. Among them, the electron laser
wakefield acceleration and the X/γ tunable sources, based on the
Thomson scattering (TS) of optical photons on accelerated electrons,
represent the most challenging applications. The activity of the Intense
Laser Irradiation Laboratory in this field will be presented.
Laser Wake Field Acceleration of relativistic electron bunches is a
promising method to produce a large amount of energetic particles with
table top equipment. One of the possible methods to inject particles in
the appropriate acceleration phase of the wake behind the pulse takes
advantage of the partial longitudinal breaking of the wake crests
across a density downramp. In this paper results of 2.5D PIC
simulations, showing the production of an electron bunch with reduced
energy spread, are reported. Also, a possible method to produce the
required plasma density transition by laser explosion of a suitable
couple of thin foils is discussed.
Ray-tracing simulations of an optical X-ray system based on a
spherically bent crystal operating in Bragg configuration for
monochromatic projection imaging of thin samples are presented,
obtained using a code developed for that purpose. The code is
particularly suited for characterizing experimental arrangements
routinely used with laser-produced plasma X-ray sources. In particular,
the spatial resolution of the imaging system was investigated and a
careful study of the complex pattern of the X-ray backlighting beam was
The differential imaging technique is particularly suitable for the
detection of small concentrations of contrasts agents for biological
and medical applications in samples using X-ray radiography. In this
paper, we present an application of this technique using a laser-plasma
soft X-ray source combined with a bent crystal. Using a Fresnel plate
as a test object, we were able to obtain spatial resolutions of the
order of a few tens of microns. The use of our configuration to perform
differential imaging of a test-sample at the L2 edge of Br
at 1,596 eV is finally demonstrated.
New easy spectrally tunable backlighting schemes based on a
spherically bent crystal are considered. Contrary to traditional
backlighting scheme, in which the investigated objects should be placed
between the backlighter and the crystal, for the considered schemes an
object is placed downstream of the crystal, before the tangential or
after the sagittal focus and an image of the object is recorded at the
distance from the object corresponding to the needed magnification. The
magnification is defined by the ratio of the distances from the
sagittal focus to the detector and from the object to the sagittal
focus. A ray-tracing modeling and experimental images of test meshes,
obtained at incidence angles of the backlighter radiation of 10°
and 22°, are presented. It is demonstrated that a simple linear
transformation of the obtained astigmatic images allows reconstructing
them as a stigmatic with an accuracy of 5–15%. For the spectral
range around 9 Å a spatial resolution about 10 μm in a field
of view of some square millimeters is achieved experimentally and
confirmed by ray-tracing simulations.
The early stages of stress development during epitaxial growth of metal layers with a large misfit in lattice parameters still need in-depth understanding. In this particular study we have focused on Ag-Cu system, which is immiscible and exhibit a large 14% misfit in lattice parameters. Ag/Cu multilayers have been grown by ultrahigh-vacuum evaporation on Si (111) maintained at -20°C, 35°C or 110°C. The thickness of the individual layers is about 100 Å. All the films present the same (111) orientation with a well defined in-plane orientation: <110> Cu or Ag // <110> Si. The stress was monitored during growth with a home-made laser curvature measurement device. The stress vs thickness behaviour is highly asymmetric when comparing Ag/Cu and Cu/Ag. Indeed Ag grown on Cu does not develop any measurable stress at any thickness or temperature, whereas Cu grows on Ag under tensile temperature and thickness-dependent stress. The temperature dependence of this stress relaxation cannot be interpreted with a standard relaxation model including dislocation motion. A possible way to understand the stress temperature dependence is to consider the evolution of microstructure during growth.
High dynamic range, space-resolved X-ray spectra, obtained
using a TlAP crystal and a cooled CCD camera as a detector,
were used to investigate the electron density and temperature
profiles of an aluminum laser plasma with micrometer resolution.
The electron density profile retrieved from the measurements
is compared with numerical predictions from the two hydrodynamics
codes MEDUSA (1D) and POLLUX (2D). It is shown that 2D density
profiles can be successfully reproduced by 1D simulations using
a spherical geometry with an ad hoc initial radius, leading
to similar electron temperature profiles.
The formation of defects during the LCM processing of composite parts
depends on various injection parameters. Industrial users need to realize pieces
with good physical and mechanical properties and appearance. This requires to
predict what is named a “processability window”. This term defines a range of
parameters which will ensure a nearly absence of defects. Knowing that most
of the defects created during an injection are voids, a bibliographical background
about the formation and removal of these voids is presented. An original model
of void fraction prediction is developed. This model is based on an empirical
analysis of void formation and of the flow behaviour. An experimental qualitative
validation of the model is presented.The proposed model can be
used as an effective prediction tool at the design stage of a composite part.
High dynamic range, space-resolved X-ray spectra of an
aluminum laser–plasma in the 5.5–8 Å
range were obtained using a TlAP crystal and a cooled CCD
camera as a detector. This technique was used to investigate
the emission region in the longitudinal direction over
a distance of approximately 350 μm from the solid target
surface. These data show that the electron density profile
varies by two orders of magnitude with the temperature
ranging from about 180 eV in the overdense region to about
650 eV in the underdense region. Accordingly, different
equilibria take place across the explored region which
can be identified with this experimental technique. Detailed
studies on highly ionized atomic species in different plasma
conditions can therefore be performed simultaneously under
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