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.

Although radiocarbon (14C) dating is commonly used for archeological music instruments, little research has been conducted on modern instruments (16th–19th centuries). New technology, based on the Mini Carbon Dating System (MICADAS), enables some of the recurring challenges (e.g. sampling size) to be circumvented and paves the way for a new field of investigation. We here address the Indian instrumentarium, about which very little is known. We investigate the making and the restoration phases of two vina, a kinnari vina (E.1444), and a rudra vina or bin (E.997.24.1). By comparing 14C measurements made on several samplings of elements of the instruments with museological information, we were able to specify a unique calibrated interval of ages [1666 AD–1690 AD] for the kinnari vina, with a restoration phase [1678 AD–1766 AD] for the upper nut. The bin is likely attributed to the [1650 AD–1683 AD] interval.

In 1895, Cantor showed that between every two countable dense real sets, there is an order isomorphism. In fact, there is always such an order isomorphism that is the restriction of a universal entire function.

We approximate the Riemann Zeta-Function by polynomials and Dirichlet polynomials with restricted zeros.

In this paper we study the zero sets of harmonic functions on open sets in ${{\mathbb{R}}^{N}}$ and holomorphic functions on open sets in ${{\mathbb{C}}^{N}}$ . We show that the non-extendability of such zero sets is a generic phenomenon.

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.

A logistic regression procedure was used to assess the impact of socioeconomic attributes on the best management practices (BMPs) adoption decision by Louisiana dairy farmers relative to cost-share and fixed incentive payments. Analysis of the steps in the BMP adoption decision process indicated visits between producers and the U.S. Department of Agriculture–Natural Resource Conservation Service significantly increase likelihood of BMP adoption. Producer willingness-to-pay results indicate that marginal increases in dairy BMP adoption and associated improvement in environmental quality require increased technical and financial assistance.

The Riemann zeta-function is employed to generate universally overconvergent power series.

The role of heterotrophic biofilm of water–sediment interface in detoxification processes was tested in abiotic and biotic conditions under laboratory conditions. Three toxicants, a herbicide (Diuron), a fungicide (Dimethomorph) and an insecticide (Chlorpyrifos-ethyl) have been tested in water percolating into columns reproducing hyporheic sediment. The detoxification processes were tested by comparing the water quality after 18 days of percolation with and without heterotrophic biofilm. Tested concentrations were 30 μg.L−1 of Diuron diluted in 0.1% dimethyl sulfoxide (DMSO), 2 μg.L−1 of Dimethomorph and 0.1 μg.L−1 of Chlorpyrifos-ethyl. To characterise the detoxification efficiency of the system, we performed  genotoxicity bioassays in amphibian larvae and rotifers and measured the respiration and denitrification of sediments. Although the presence of biofilm increased the production of N-(3,4 dichlorophenyl)-N-(methyl)-urea, a metabolite of diuron, the toxicity did not decrease irrespective of the bioassay. In the presence of biofilm, Dimethomorph concentrations decreased compared with abiotic conditions, from 2 μg.L−1 to 0.4 μg.L−1 after 18 days of percolation. For both Dimethomorph and Chlorpyrifos-ethyl additions, assessment of detoxification level by the biofilm depended on the test used: detoxification effect was found with amphibian larvae bioassay and no detoxification was observed with the rotifer test. Heterotrophic biofilm exerts a major influence in the biochemical transformation of contaminants such as pesticides, suggesting that the interface between running water and sediment plays a role in self-purification of stream reaches.

A domain $\Omega $ is called a domain of injective holomorphy if there exists an injective holomorphic function $f\,:\,\Omega \,\to \,\mathbb{C}$ that is non-extendable. We give examples of domains that are domains of injective holomorphy and others that are not. In particular, every regular domain $(\overset{\multimap }{\mathop{\Omega }}\,\,=\,\Omega )$ is a domain of injective holomorphy, and every simply connected domain is a domain of injective holomorphy as well.

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 31 P NMR and high frequency impedance for monitoring the CPC setting. The presence of Alendronate in the cement was also demonstrated by 31 P 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.