The MobyDick Project: A Mobile Heterogeneous All-IP Architecture

Proceedings of Advanced Technologies, Applications and Market Strategies for 3G (ATAMS 2001). Cracow, Poland: 17-20 June, 2001.This paper presents the current stage of an IP-based architecture for heterogeneous environments, covering UMTS-like W-CDMA wireless access technology, wireless and wired LANs, that is being developed under the aegis of the IST Moby Dick project. This architecture treats all transmission capabilities as basic physical and data-link layers, and attempts to replace all higher-level tasks by IP-based strategies. The proposed architecture incorporates aspects of mobile-IPv6, fast handover, AAA-control, and Quality of Service. The architecture allows for an optimised control on the radio link layer resources. The Moby dick architecture is currently under refinement for implementation on field trials. The services planned for trials are data transfer and voice-over-IP.Publicad

Early markers of prolonged hospital stay in demented inpatients: A multicentre and prospective study

Background: Dementia is a serious, chronic, and costly public health problem. Prior studies have described dementia as increasing length of hospital stay, but so far no explanations have been proposed. Methods: To identify early markers for prolonged hospital stay in demented elderly inpatients, 178 community-dwelling or institutionalized subjects aged 75+, hospitalized through an emergency department in 9 teaching hospitals in France, were analyzed. Prolonged hospital stays were defined according a limit adjusted for Diagnosis Related Group. All patients underwent a comprehensive geriatric assessment at admission. Logistic regression multifactorial mixed model was performed. Center effect was considered as a random effect. Results: Of the 178 stays, 52 were prolonged. Most concerned community-dwelling patients (86%). Multifactor analysis demonstrated that demographic variables had no influence on the length of stay, while diagnosis of delirium (OR 2.31; 95% CI 1.77-2.91), walking difficulties (OR 1.94; 95% CI 1.62-2.43) and report by the informal caregiver of moderate or severe burden (OR 1.52; 95% CI 1.19-1.86) or low social quality-of-life score (OR 1.25; 95% CI 1.03-1.40), according to the Zarit's Burden Inventory short scale (12 items) and the Duke's Health Profile respectively, were identified as early markers for prolonged hospital stays. Conclusion: At the time of the rising incidence of cognitive disorders, these results suggest that preventive approaches might be possible. In a hospital setting as well as in a community-dwelling population, more specific, specialized and coordinated care, using the expertise of multiple disciplines appears as a probable effective measure to limit prolonged hospital stay. Such approaches require (i) clear patient-oriented goal definition, (ii) understanding and appreciation of roles among various health care and social disciplines and, (iii) cooperation between partners in patient's management. However, the cost- and health-effectiveness of such approaches should be evaluate

The Waveform Digitiser of the Double Chooz Experiment: Performance and Quantisation Effects on PhotoMultiplier Tube Signals

We present the waveform digitiser used in the Double Chooz experiment. We describe the hardware and the custom-built firmware specifically developed for the experiment. The performance of the device is tested with regards to digitising low light level signals from photomultiplier tubes and measuring pulse charge. This highlights the role of quantisation effects and leads to some general recommendations on the design and use of waveform digitisers.Comment: 14 pages, 8 figures, accepted for publication in JINS

Tradeoff between short-term and long-term adaptation in a changing environment

We investigate the competition dynamics of two microbial or viral strains that live in an environment that switches periodically between two states. One of the strains is adapted to the long-term environment, but pays a short-term cost, while the other is adapted to the short-term environment and pays a cost in the long term. We explore the tradeoff between these alternative strategies in extensive numerical simulations, and present a simple analytic model that can predict the outcome of these competitions as a function of the mutation rate and the time scale of the environmental changes. Our model is relevant for arboviruses, which alternate between different host species on a regular basis.Comment: 9 pages, 3 figures, PRE in pres

Evolution on a smooth landscape

We study in detail a recently proposed simple discrete model for evolution on smooth landscapes. An asymptotic solution of this model for long times is constructed. We find that the dynamics of the population are governed by correlation functions that although being formally down by powers of $N$ (the population size) nonetheless control the evolution process after a very short transient. The long-time behavior can be found analytically since only one of these higher-order correlators (the two-point function) is relevant. We compare and contrast the exact findings derived herein with a previously proposed phenomenological treatment employing mean field theory supplemented with a cutoff at small population density. Finally, we relate our results to the recently studied case of mutation on a totally flat landscape.Comment: Revtex, 15 pages, + 4 embedded PS figure

Mutator Dynamics on a Smooth Evolutionary Landscape

We investigate a model of evolutionary dynamics on a smooth landscape which features a ``mutator'' allele whose effect is to increase the mutation rate. We show that the expected proportion of mutators far from equilibrium, when the fitness is steadily increasing in time, is governed solely by the transition rates into and out of the mutator state. This results is a much faster rate of fitness increase than would be the case without the mutator allele. Near the fitness equilibrium, however, the mutators are severely suppressed, due to the detrimental effects of a large mutation rate near the fitness maximum. We discuss the results of a recent experiment on natural selection of E. coli in the light of our model.Comment: 4 pages, 3 figure

PAM-2 decreases neuropathic pain in mice and modulates chemokine/cytokine production in human microglial cells

Background: People worldwide suffer from neuropathic pain, and indicated medications are often either not effective or induce tolerance and abuse. Therefore, there is an urgent need to identify additional therapeutic options to treat this form of pain. Nicotinic acetylcholine receptors (nAChRs), particularly a7-nAChRs, have been implicated in pain signaling. Therefore, this study was designed to investigate the extent to which the selective positive allosteric modulator (PAM) of a7 AChRs, PAM-2, modulates neuropathic pain. The working hypothesis, that PAM-2 inhibits inflammatory signaling and neuropathic pain, was tested using animal and cellular models.Methods: The anti-neuropathic pain activity of PAM-2 was assessed in two independent murine models of neuropathic pain. Briefly, neuropathic pain was induced in adult, male CD-1 mice (n=10/condition) via i.p. administration of either streptozotocin (STZ) or oxaliplatin (OXA). After 14 days, when neuropathic pain was present, mice were administrated with PAM-2 (1.0 or 3.0 mg/kg, p.o.) or vehicle. The pain threshold was subsequently determined by the cold plate test before and 15, 30, 45, and 60 min after treatment. In addition, C20 human microglial cells were exposed to interleukin (IL)-1B (20 ng/ml) or vehicle alone, and in combination with nicotine (3 uM), PAM-2 (1-100 uM), or nicotine + PAM-2 for 24 h. After 24 h, cytokine/chemokine levels in the culture media were measured by ELISA.Results: A single dose of PAM-2 (3.0 mg/kg) decreased both STZ- and OXA-induced neuropathic pain in mice. Repeated treatment with an inactive dose (1.0 mg/kg) of PAM-2 showed anti-pain activity in OXA-treated mice after 14, but not 7, days of treatment. Additionally, methyllycaconitine blocked the anti-pain effects elicited by PAM-2, supporting the view that a7 AChRs are instrumental in the anti-pain actions of PAM-2. Cellular experiments revealed that nicotine minimally inhibited IL-1B-induced IL-6 and interferon-gamma-induced chemotactic protein 10 expression in C20 human microglial cells, and that this inhibition was potentiated by PAM-2 (100 uM). However, we cannot rule out the possibility that PAM- 2 was cytotoxic in this cell culture model.Conclusions: These findings indicate that a7 AChRs are involved in neuropathic pain signaling and that a7-PAMs may potentially be used therapeutically. The extent to which these protective effects involve reduced neuroinflammation remains to be determined