The economics of treating stroke as an acute brain attack

Abstract Currently, treatments for ischemic stroke focus on restoring or improving perfusion to the ischemic area using thrombolytics. The increased hospitalization costs related to thrombolysis are offset by a decrease in rehabilitation costs, for a net cost savings to the healthcare system. However, early treatment is essential. The benefit of thrombolysis is time-dependent but only a very small proportion of patients, 2%, are presently being treated with tPA. In the United States, if the proportion of all ischemic stroke patients that receive tPA were increased to 4, 6, 8, 10, 15, or 20%, the realized cost saving would be approximately $ 15, 22, 30, 37, 55, and 74 million, respectively. Being so, efforts should be made to educate the public and paramedics regarding early stroke signs. Furthermore, additional acute stroke therapy training programs need to be established for emergency departments. Finally, hospital systems need to be re-engineered to treat patients as quickly as possible in order to optimize thrombolytic benefit as well as maximize cost-effectiveness.</p

Historical collaborative geocoding

The latest developments in digital have provided large data sets that can increasingly easily be accessed and used. These data sets often contain indirect localisation information, such as historical addresses. Historical geocoding is the process of transforming the indirect localisation information to direct localisation that can be placed on a map, which enables spatial analysis and cross-referencing. Many efficient geocoders exist for current addresses, but they do not deal with the temporal aspect and are based on a strict hierarchy (..., city, street, house number) that is hard or impossible to use with historical data. Indeed historical data are full of uncertainties (temporal aspect, semantic aspect, spatial precision, confidence in historical source, ...) that can not be resolved, as there is no way to go back in time to check. We propose an open source, open data, extensible solution for geocoding that is based on the building of gazetteers composed of geohistorical objects extracted from historical topographical maps. Once the gazetteers are available, geocoding an historical address is a matter of finding the geohistorical object in the gazetteers that is the best match to the historical address. The matching criteriae are customisable and include several dimensions (fuzzy semantic, fuzzy temporal, scale, spatial precision ...). As the goal is to facilitate historical work, we also propose web-based user interfaces that help geocode (one address or batch mode) and display over current or historical topographical maps, so that they can be checked and collaboratively edited. The system is tested on Paris city for the 19-20th centuries, shows high returns rate and is fast enough to be used interactively.Comment: WORKING PAPE

Precise vehicle location as a fundamental parameter for intelligent selfaware rail-track maintenance systems

The rail industry in the UK is undergoing substantial changes in response to a modernisation vision for 2040. Development and implementation of these will lead to a highly automated and safe railway. Real-time regulation of traffic will optimise the performance of the network, with trains running in succession within an adjacent movable safety zone. Critically, maintenance will use intelligent trainborne and track-based systems. These will provide accurate and timely information for condition based intervention at precise track locations, reducing possession downtime and minimising the presence of workers in operating railways. Clearly, precise knowledge of trains’ real-time location is of paramount importance. The positional accuracy demand of the future railway is less than 2m. A critical consideration of this requirement is the capability to resolve train occupancy in adjacent tracks, with the highest degree of confidence. A finer resolution is required for locating faults such as damage or missing parts, precisely. Location of trains currently relies on track signalling technology. However, these systems mostly provide an indication of the presence of trains within discrete track sections. The standard Global Navigation Satellite Systems (GNSS), cannot precisely and reliably resolve location as required either. Within the context of the needs of the future railway, state of the art location technologies and systems were reviewed and critiqued. It was found that no current technology is able to resolve location as required. Uncertainty is a significant factor. A new integrated approach employing complimentary technologies and more efficient data fusion process, can potentially offer a more accurate and robust solution. Data fusion architectures enabling intelligent self-aware rail-track maintenance systems are proposed

Expert survey and classification of tools for modeling and simulating hybrid energy networks

Sector coupling is expected to play a key role in the decarbonization of the energy system by enabling the integration of decentralized renewable energy sources and unlocking hitherto unused synergies between generation, storage and consumption. Within this context, a transition towards hybrid energy networks (HENs), which couple power, heating/cooling and gas grids, is a necessary requirement to implement sector coupling on a large scale. However, this transition poses practical challenges, because the traditional domain-specific approaches struggle to cover all aspects of HENs. Methods and tools for conceptualization, system planning and design as well as system operation support exist for all involved domains, but their adaption or extension beyond the domain they were originally intended for is still a matter of research and development. Therefore, this work presents innovative tools for modeling and simulating HENs. A categorization of these tools is performed based on a clustering of their most relevant features. It is shown that this categorization has a strong correlation with the results of an independently carried out expert review of potential application areas. This good agreement is a strong indicator that the proposed classification categories can successfully capture and characterize the most important features of tools for HENs. Furthermore, it allows to provide a guideline for early adopters to understand which tools and methods best fit the requirements of their specific applications

Homeostatic NF-κB Signaling in Steady-State Migratory Dendritic Cells Regulates Immune Homeostasis and Tolerance

SummaryMigratory non-lymphoid tissue dendritic cells (NLT-DCs) transport antigens to lymph nodes (LNs) and are required for protective immune responses in the context of inflammation and to promote tolerance to self-antigens in steady-state. However, the molecular mechanisms that elicit steady-state NLT-DC maturation and migration are unknown. By comparing the transcriptome of NLT-DCs in the skin with their migratory counterparts in draining LNs, we have identified a novel NF-κB-regulated gene network specific to migratory DCs. We show that targeted deletion of IKKβ in DCs, a major activator of NF-κB, prevents NLT-DC accumulation in LNs and compromises regulatory T cell conversion in vivo. This was associated with impaired tolerance and autoimmunity. NF-κB is generally considered the prototypical pro-inflammatory transcription factor, but this study describes a role for NF-κB signaling in DCs for immune homeostasis and tolerance that could have implications in autoimmune diseases and immunity

Optical properties of high-quality oxide coating materials used in gravitational-wave advanced detectors

High-reflection interference mirrors for current gravitational wave detectors (aLIGO, Advanced Virgo, KAGRA) are made of high-quality oxide multi-layers deposited by ion beam sputtering (IBS) at the Laboratoire des Mat\ue9riaux Avanc\ue9s (LMA). For this task, LMA uses a large IBS custom-made machine (the grand coater GC) able to deposit very uniform coatings over very large surfaces, with diameter of some tens of cm. We report for the first time about the optical characterization by spectroscopic ellipsometry of oxide coatings deposited by the GC under strictly the same conditions used for the production of interference mirrors. We have investigated oxide materials like silica (SiO2), tantala (Ta2O5) and titania-doped tantala (Ti:Ta2O5), providing for each material a broad-band (190\u20131700 nm) accurate determination of the complex index of refraction, with particular attention to wavelengths used in interferometers. Particular focus has been dedicated to the influence of Ti-doping on tantala coating. The doping induces a red-shift of the optical gap and an increase of the NIR refractive index. Furthermore, doping induces a decrease of the so-called Urbach energy, consistent with the well-known reduction of the internal friction in these kind of systems

High-reflection coatings for gravitational-wave detectors: State of the art and future developments

We report on the optical, mechanical and structural characterization of the sputtered coating materials of Advanced LIGO, Advanced Virgo and KAGRA gravitational-waves detectors. We present the latest results of our research program aiming at decreasing coating thermal noise through doping, optimization of deposition parameters and post-deposition annealing. Finally, we propose sputtered Si3N4as a candidate material for the mirrors of future detectors

Collaborative peer validation of a harmonized SPME-GC-MS method for analysis of selected volatile compounds in virgin olive oils [intervalidazione di un metodo armonizzato SPME-GC-MS per l¿analisi di composti volatili selezionati in oli di oliva vergini]

Final version is available in open access in publisher’s site.-- This abstract is based on the published article: Ramón Aparicio-Ruiz, Clemente Ortiz Romero, Enrico Casadei, Diego L. García-González, Maurizio Servili, Roberto Selvaggini, Florence Lacoste, Julien Escobessa, Stefania Vichi, Beatriz Quintanilla-Casas, Pierre-Alain Golay, Paolo Lucci, Erica Moret, Enrico Valli, Alessandra Bendini, Tullia Gallina Toschi. Collaborative peer validation of a harmonized SPME-GC-MS method for analysis of selected volatile compounds in virgin olive oils, Food Control, Volume 135, 2022, 108756, https://doi.org/10.1016/j.foodcont.2021.108756.-- http://hdl.handle.net/10261/258960The evaluation of the sensory attributes in virgin olive oil (VOO) is carried out according to the standard method of panel test [1, 2]. Recently, it has been proposed as SPME-GC-FID method as the most ade- quate instrumental method to determine volatiles compounds in VOO to support the sensory panels test [3]. This method developed in the European funded project OLEUM, in which all the variables have been defined and harmonized, has been tested in three laboratories to perform an inter-laboratory validation of the quantification of the most relevant VOCs that are responsible for VOO sensory attributes. The valida- tion study was carried out for each one of the selected molecules in order to have an individual infor- mation for each analyte. With the same objective, in the present work, five laboratories, all being active partners in the OLEUM project, carried out an inter-lab evaluation of the SPME-GC-MS joint protocol. The validation was carried out by each laboratory following the same analytical conditions and on the same samples, in order to make the results obtained by each laboratory comparable in a harmonized procedure and methodology, as previously done with FID [3]

A specific nanobody prevents amyloidogenesis of D76N \u3b22-microglobulin in vitro and modifies its tissue distribution in vivo

Systemic amyloidosis is caused by misfolding and aggregation of globular proteins in vivo for which effective treatments are urgently needed. Inhibition of protein self-aggregation represents an attractive therapeutic strategy. Studies on the amyloidogenic variant of \u3b22-microglobulin, D76N, causing hereditary systemic amyloidosis, have become particularly relevant since fibrils are formed in vitro in physiologically relevant conditions. Here we compare the potency of two previously described inhibitors of wild type \u3b22-microglobulin fibrillogenesis, doxycycline and single domain antibodies (nanobodies). The \u3b22-microglobulin -binding nanobody, Nb24, more potently inhibits D76N \u3b22-microglobulin fibrillogenesis than doxycycline with complete abrogation of fibril formation. In \u3b22-microglobulin knock out mice, the D76N \u3b22-microglobulin/ Nb24 pre-formed complex, is cleared from the circulation at the same rate as the uncomplexed protein; however, the analysis of tissue distribution reveals that the interaction with the antibody reduces the concentration of the variant protein in the heart but does not modify the tissue distribution of wild type \u3b22-microglobulin. These findings strongly support the potential therapeutic use of this antibody in the treatment of systemic amyloidosis