The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimization of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimization. Here, an automated, HRR-compatible system produced high-fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimization of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimization of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources.

We present the development and characterization of a high-stability, multi-material, multi-thickness tape-drive target for laser-driven acceleration at repetition rates of up to 100 Hz. The tape surface position was measured to be stable on the sub-micrometre scale, compatible with the high-numerical aperture focusing geometries required to achieve relativistic intensity interactions with the pulse energy available in current multi-Hz and near-future higher repetition-rate lasers ($>$kHz). Long-term drift was characterized at 100 Hz demonstrating suitability for operation over extended periods. The target was continuously operated at up to 5 Hz in a recent experiment for 70,000 shots without intervention by the experimental team, with the exception of tape replacement, producing the largest data-set of relativistically intense laser–solid foil measurements to date. This tape drive provides robust targetry for the generation and study of high-repetition-rate ion beams using next-generation high-power laser systems, also enabling wider applications of laser-driven proton sources.

There is wide acknowledgement that apathy is an important behavioural syndrome in Alzheimer’s disease and in various neuropsychiatric disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy, and in its treatments, it is important to develop criteria for apathy that will be widely accepted, have clear operational steps, and that will be easily applied in practice and research settings. Meeting these needs is the focus of the task force work reported here.

The task force includes members of the Association Française de Psychiatrie Biologique, the European Psychiatric Association, the European Alzheimer’s Disease Consortium and experts from Europe, Australia and North America. An advanced draft was discussed at the consensus meeting (during the EPA conference in April 7th 2008) and a final agreement reached concerning operational definitions and hierarchy of the criteria.

Apathy is defined as a disorder of motivation that persists over time and should meet the following requirements. Firstly, the core feature of apathy, diminished motivation, must be present for at least four weeks; secondly two of the three dimensions of apathy (reduced goal-directed behaviour, goal-directed cognitive activity, and emotions) must also be present; thirdly there should be identifiable functional impairments attributable to the apathy. Finally, exclusion criteria are specified to exclude symptoms and states that mimic apathy.

Genetic linkage analysis requires the identification and documentation of large families with many affected members present, preferably in more than one generation. The IMAGE Project has been establishing a population- based Alzheimer disease (AD) registry in the Saguenay - Lac-Saint-Jean region of the Province of Quebec. The population of this region has a well-documented ancestry, with reliable genealogical records (since 1842) computerized by SORER We have recently begun to investigate the pedigrees of selected probands (definite, probable and possible) from the IMAGE registry in order to identify informative pedigrees for genetic linkage analysis. Interviews were carried out with close relatives of the probands (at least one informant per sibship) to identify secondary AD cases. The questionnaires used pertain to the accuracy of genealogical records, to family medical history and to a retrospective diagnosis of AD for people with cognitive deficits. By these means, we have documented a large extended pedigree in which a total of 15 individuals with cognitive deficits were ascertained over three generations. Of these cases, 7 are still living and there is autopsy confirmation in another one. Computer simulations using the program SIMLINK revealed that this is a potentially informative family for linkage analysis. Horizontal extension of the pedigree to second cousins of the proband is now being carried out. This will render the family IMAGE/1 even more informative in genetic linkage analysis studies.

Since the discovery of a significant depletion of acetylcholine in discrete areas of the brain of patients affected by Alzheimer's disease, attempts at symptomatic therapy have concentrated on acetylcholine supplementation, an approach that is based upon the efficacy of dopaminergic supplementation therapy for Parkinson's disease. Choline, then lecithin, used orally, failed to improve symptoms but the hypothesis that long-term choline supplementation might stabilize the course of Alzheimer's disease remains to be tested. Nerve growth factor may also offer that possibility. Bethanechol administered intracerebroventricularly did not help when a fixed dose was used but individual titration of more selective muscarinic agonists may prove more effective. In this article we report that tetrahydroaminoacridine (THA), given together with highly concentrated lecithin, appears to bring improvement in cognition and in functional autonomy using the Mini Mental State and the Rapid Disability Rating Scale-2 respectively, without change in behavior as reflected by the Behave-AD. Double-blind cross-over studies are in progress to establish its efficacy. Improvement in study design and means of assessment of cognition, functional autonomy and behavior have been made possible by these drug trials.

High-order discretization techniques offer the potential to significantly reduce the computational costs necessary to obtain accurate predictions when compared to lower-order methods. However, efficient and universally-applicable high-order discretizations remain somewhat illusive, especially for more arbitrary unstructured meshes and for incompressible/low-speed flows. A novel, high-order, central essentially non-oscillatory (CENO), cell-centered, finite-volume scheme is proposed for the solution of the conservation equations of viscous, incompressible flows on three-dimensional unstructured meshes. Similar to finite element methods, coordinate transformations are used to maintain the scheme’s order of accuracy even when dealing with arbitrarily-shaped cells having non-planar faces. The proposed scheme is applied to the pseudo-compressibility formulation of the steady and unsteady Navier-Stokes equations and the resulting discretized equations are solved with a parallel implicit Newton-Krylov algorithm. For unsteady flows, a dual-time stepping approach is adopted and the resulting temporal derivatives are discretized using the family of high-order backward difference formulas (BDF). The proposed finite-volume scheme for fully unstructured mesh is demonstrated to provide both fast and accurate solutions for steady and unsteady viscous flows.

Combining Bisphophonates (BPs) and Calcium Phosphate Cement (CPC) to form a new medical device for the local treatment of Osteoporosis is a promising challenge. Our formulation was optimized from an apatitic-type CPC and we have shown that the best solution consists in introducing the bisphosphonate (Alendronate) in the calcium deficient apatite (CDA), a solid component of the cement, through a chemical exchange reaction. The cement obtained was characterized by 31P NMR and high frequency impedance for monitoring the CPC setting. The presence of Alendronate in the cement was also demonstrated by 31P NMR which has been also used to characterize the chemical transformation of α-TCP (main component of the apatitic cement) during the setting process. BP absorption/desorption experiments have been realized on cement blocks, under continuous flow condition, to model the release profile of the Alendronate. In vivo experiments showed promising results in terms of resorbability of the Alendronate–loaded cement while promoting new bone formation. The same methodology is considered to introduce gallium, a potential inhibitor of osteoclastic resorption, in a CPC formulation. First experiments have shown that gallium can be incorporated in calcium phosphate ceramics (i.e. β-TCP) where gallium is part of the network.

Background: Neuropsychiatric symptoms (NPS) affect almost all patients with dementia and are a major focus of study and treatment. Accurate assessment of NPS through valid, sensitive and reliable measures is crucial. Although current NPS measures have many strengths, they also have some limitations (e.g. acquisition of data is limited to informants or caregivers as respondents, limited depth of items specific to moderate dementia). Therefore, we developed a revised version of the NPI, known as the NPI-C. The NPI-C includes expanded domains and items, and a clinician-rating methodology. This study evaluated the reliability and convergent validity of the NPI-C at ten international sites (seven languages).

Methods: Face validity for 78 new items was obtained through a Delphi panel. A total of 128 dyads (caregivers/patients) from three severity categories of dementia (mild = 58, moderate = 49, severe = 21) were interviewed separately by two trained raters using two rating methods: the original NPI interview and a clinician-rated method. Rater 1 also administered four additional, established measures: the Apathy Evaluation Scale, the Brief Psychiatric Rating Scale, the Cohen-Mansfield Agitation Index, and the Cornell Scale for Depression in Dementia. Intraclass correlations were used to determine inter-rater reliability. Pearson correlations between the four relevant NPI-C domains and their corresponding outside measures were used for convergent validity.

Results: Inter-rater reliability was strong for most items. Convergent validity was moderate (apathy and agitation) to strong (hallucinations and delusions; agitation and aberrant vocalization; and depression) for clinician ratings in NPI-C domains.

Conclusion: Overall, the NPI-C shows promise as a versatile tool which can accurately measure NPS and which uses a uniform scale system to facilitate data comparisons across studies.

The emissivity of the rear of a shocked foil is spectrally and temporally resolved by coupling a transmission grating (1000 I/mm) and an X-UV streak camera (with a low density Csl photocathode), providing a high temporal resolution over a large spectral range. The shock is generated with two techniques: direct illumination of a single Al foil with a 0.26 μm wavelength laser (ablation pressure ≈ 50 Mbars) or by colliding an Al foil with a laser accelerated CH foil (generated pressures greater than 100–200 Mbars). Different thicknesses of Al are used in single foil experiments, and different initial spacing and impacted foil thicknesses are used in double foil experiments. Double foil experiments indicate that targets can be optimized for high pressure generation, and single foil experiments show that there is a radiative heat wave, around 200 eV, due to the heating of the foil by X rays emitted in the ablated region during the laser pulse. Double foil experiments have been compared with 2-D hydrodynamic Lagrangian simulations and single foil experiments have been compared with 1-D hydrodynamic Lagrangian simulations taking into account radiative heat transfer.

We have studied experimentally the relation between the preionization of a plasma micro-channel in Argon at atmospheric pressure and the dynamics of the discharge initiated by preionization. Preionization is obtained in two different ways: (a) injecting the soft X rays produced by a 3 J, 3 ns YAG laser focused on a copper target through a pinhole (b) direct focusing of a 4ω laser (0·26 μm) along the Argon column. Both experiments and simple numerical models are presented in this paper.

A study of the effects of photoionization of a laser-produced plasma has been carried out by modeling the fluorescence of resonance lines due to cascades. The photoionization source is the X-ray M-band emission of a laser-produced high-Z plasma and it perturbs a ground state He-like aluminum plasma. Simulations have been performed to study the conditions necessary to maximize the fluorescence and guide future experiments. A collisional-radiative model is used to determine the optimal temperature and density of the pumped plasma, while hydrodynamic models are used to produce realistic plasma gradients and explore the optimum time delay of the photopumping.

The spectra of laser-produced plasmas of various materials of Z>70 have been interpreted as spin-orbit-split arrays of the 3d – 4f and 3d – 5f transitions for Ni-like to Ge-like ions. The excellent agreement between the model and the experiments indicated the possibility of their use for plasma diagnostics. First results from targets of Gold alloyed with Aluminium give an alternative diagnostic.

A prerequisite to studying the specific interactions involved in the persistent transmission of luteoviruses such as the potato leafroll virus (PLRV) is the characterization of both the virus and its vectors. A range of techniques was used to assess genetic differentiation among 27 clones belonging to the Myzus persicae complex (M. persicae (Sulzer), M. antirrhinii (Macchiati) and M. nicotianaeBlackman) and showing different efficiencies in transmitting PLRV isolates. All M. persicae/M. nicotianae clones belonged to one of two karyotypes, both 2n = 12, either normal or carrying an autosomal translocation (A1,3), and all M. antirrhinii clones had 13 or 14 chromosomes. Amplified esterase 4 genes were detected by PCR–REN assay in M. persicae/M. nicotianae taxa, with gene expression being modified by methylation. Similarly, amplified E4 genes were revealed in M. antirrhinii but they all showed unmethylated. Two allozyme and 11 microsatellite loci discriminated 10 different genotypic classes among the 27 clones. Analysis of genetic relatedness between these genotypic classes revealed that M. nicotianae clones were very closely related to M. persicaeclones, whereas the genetic differentiation between M. antirrhinii and M. persicae was greater. The implications of these results for the taxonomic status of these genotypes within the complex, and the transmission of PLRV, are discussed.

It is shown that there exists an inner function $I$ defined on the unit ball ${{\text{B}}^{n}}$ of ${{\mathbb{C}}^{n}}$ such that each function holomorphic on ${{\text{B}}^{n}}$ and bounded by 1 can be approximated by “non-Euclidean translates” of $I$.

Due to their particular properties (low emittance, short duration, and large number density), the beams of multi-MeV protons generated during the interaction of ultraintense (I > 1019 W/cm2) short pulses with thin solid targets are suited for use as a particle probe in laser-plasma experiments. When traversing a sample, the proton density distribution is, in general, affected by collisional stopping, scattering and deflections via electromagnetic fields, and each of these effects can be used for diagnostic purposes. In particular, in the limit of very thin targets, the proton beams represent a valuable diagnostic tool for the detection of quasi-static electromagnetic fields. The proton imaging and deflectometry techniques employ these beams, in a point-projection imaging scheme, as an easily synchronizable diagnostic tool in laser- plasma interactions, with high temporal and spatial resolution. By providing diagnostic access to electro-magnetic field distributions in dense plasmas, this novel diagnostics opens up to investigation a whole new range of unexplored phenomena. Several transient processes were investigated employing this technique, via the detection of the associated electric fields. Examples provided in this paper include the detection of pressure-gradient electric field in extended plasmas, and the study of the electrostatic fields associated to the emission of MeV proton beams in high-intensity laser-foil interactions.

The construction of short pulse (<200 fs) tunable X-ray laser sources based on the X-ray free electron laser (XFEL) concept will be a watershed for plasma-based and warm dense matter research. These new fourth generation light sources will have extremely high fields and short wavelengths (∼0.1 nm) with peak spectral brightnesses 1010 greater than third generation sources. Further, the high intensity upgrade of the GSI accelerator facilities will lead to specific energy depositions up to 200 kJ/g and temperatures between 1 and 10 eV at almost solid-state densities, enabling interesting experiments in the regime of nonideal plasmas, such as the evolution of intense ion beams in the interior of a Jovian planet. Below we discuss several applications: the creation of warm dense matter (WDM) research, probing of near solid density plasmas, and laser–plasma spectroscopy of ions in plasmas. The study of dense plasmas has been severely hampered by the fact that laser-based methods have been unavailable and these new fourth generation sources will remove these restrictions.