5-fluorouracil induced cardiotoxicity: Review of the literature

5-fluorouracil (5-FU) is a key chemotherapeutic agent in the treatment of many gastrointestinal tract adenocarcinomas. Despite its proven therapeutic efficacy, 5-FU also possesses several undesired cardiac toxicities, including coronary vasospasm, coronary thrombosis, cardiomyopathy, and sudden cardiac death. This review addresses the incidence, mechanisms of action, clinical presentation, risk stratification, and management of 5-FU associated cardiotoxicity; it also highlights the importance of careful pre-administration cardiac risk stratification and close monitoring during and after drug administration. (Cardiol J 2012; 19, 5: 453-458

A 1-D PLANAR SOLID OXIDE FUEL CELL MODEL FOR SIMULATION OF SOFC-BASED ENERGY SYSTEMS

ABSTRACT A one-dimensional steady-state model for planar solid oxide fuel cells (SOFCs) is presented. Appropriately simplified, the model includes sufficient detail for supporting ongoing investigations involving the simulation of SOFC-based advanced energy systems. The presentation focuses on a set of nonlinear equations accounting for conservation of mass and energy along a single SOFC in a co-flow configuration. Electrochemical models also are employed, including one previously used for a zero dimensional approach. The equations are described through a phenomenological approach based on the best recent work in the field and model validation is carried out in two distinct phases using previously published information. Potential areas of application for the model presented are noted. INTRODUCTION The objective of this paper is to report on work in progress aimed at simulating advanced energy systems having a solid oxide fuel cell as a principal component. For such work it is sufficient to employ a simplified SOFC model that captures the salient physical/chemical effects. Accordingly, efforts thus far have centered on the development of a one-dimensional SOFC model resting solidly on the best recent work in the field, while being convenient and effective for achieving the larger goal of simulating SOFC-based advanced energy systems. The intent of this modeling effort is to be able to handle both the hydrogen and internal reforming cases, while representing the electrochemistry using either a grey box approach or black box approach. Specifically in this paper, a 1-D model has been developed that captures the dominant physical and electrochemical phenomena taking place in a co-flow planar SOFC, accounting for internal reforming while retaining computational simplicity and good accuracy. The objective of the model is to simulat

Design of a dual species atom interferometer for space

Atom interferometers have a multitude of proposed applications in space including precise measurements of the Earth's gravitational field, in navigation & ranging, and in fundamental physics such as tests of the weak equivalence principle (WEP) and gravitational wave detection. While atom interferometers are realized routinely in ground-based laboratories, current efforts aim at the development of a space compatible design optimized with respect to dimensions, weight, power consumption, mechanical robustness and radiation hardness. In this paper, we present a design of a high-sensitivity differential dual species $^{85}$Rb/$^{87}$Rb atom interferometer for space, including physics package, laser system, electronics and software. The physics package comprises the atom source consisting of dispensers and a 2D magneto-optical trap (MOT), the science chamber with a 3D-MOT, a magnetic trap based on an atom chip and an optical dipole trap (ODT) used for Bose-Einstein condensate (BEC) creation and interferometry, the detection unit, the vacuum system for $10^{-11}$ mbar ultra-high vacuum generation, and the high-suppression factor magnetic shielding as well as the thermal control system. The laser system is based on a hybrid approach using fiber-based telecom components and high-power laser diode technology and includes all laser sources for 2D-MOT, 3D-MOT, ODT, interferometry and detection. Manipulation and switching of the laser beams is carried out on an optical bench using Zerodur bonding technology. The instrument consists of 9 units with an overall mass of 221 kg, an average power consumption of 608 W (819 W peak), and a volume of 470 liters which would well fit on a satellite to be launched with a Soyuz rocket, as system studies have shown.Comment: 30 pages, 23 figures, accepted for publication in Experimental Astronom

ELGAR—a European Laboratory for Gravitation and Atom-interferometric Research

Gravitational waves (GWs) were observed for the first time in 2015, one century after Einstein predicted their existence. There is now growing interest to extend the detection bandwidth to low frequency. The scientific potential of multi-frequency GW astronomy is enormous as it would enable to obtain a more complete picture of cosmic events and mechanisms. This is a unique and entirely new opportunity for the future of astronomy, the success of which depends upon the decisions being made on existing and new infrastructures. The prospect of combining observations from the future space-based instrument LISA together with third generation ground based detectors will open the way toward multi-band GW astronomy, but will leave the infrasound (0.1–10 Hz) band uncovered. GW detectors based on matter wave interferometry promise to fill such a sensitivity gap. We propose the European Laboratory for Gravitation and Atom-interferometric Research (ELGAR), an underground infrastructure based on the latest progress in atomic physics, to study space–time and gravitation with the primary goal of detecting GWs in the infrasound band. ELGAR will directly inherit from large research facilities now being built in Europe for the study of large scale atom interferometry and will drive new pan-European synergies from top research centers developing quantum sensors. ELGAR will measure GW radiation in the infrasound band with a peak strain sensitivity of $3.3{\times}1{0}^{-22}/\sqrt{\text{Hz}}$ at 1.7 Hz. The antenna will have an impact on diverse fundamental and applied research fields beyond GW astronomy, including gravitation, general relativity, and geology.AB acknowledges support from the ANR (project EOSBECMR), IdEx Bordeaux—LAPHIA (project OE-TWR), theQuantERA ERA-NET (project TAIOL) and the Aquitaine Region (projets IASIG3D and USOFF).XZ thanks the China Scholarships Council (No. 201806010364) program for financial support. JJ thanks ‘AssociationNationale de la Recherche et de la Technologie’ for financial support (No. 2018/1565).SvAb, NG, SL, EMR, DS, and CS gratefully acknowledge support by the German Space Agency (DLR) with funds provided by the Federal Ministry for Economic Affairs and Energy (BMWi) due to an enactment of the German Bundestag under Grants No. DLR∼50WM1641 (PRIMUS-III), 50WM1952 (QUANTUS-V-Fallturm), and 50WP1700 (BECCAL), 50WM1861 (CAL), 50WM2060 (CARIOQA) as well as 50RK1957 (QGYRO)SvAb, NG, SL, EMR, DS, and CS gratefully acknowledge support by ‘Niedersächsisches Vorab’ through the ‘Quantum- and Nano-Metrology (QUANOMET)’ initiative within the project QT3, and through ‘Förderung von Wissenschaft und Technik in Forschung und Lehre’ for the initial funding of research in the new DLR-SI Institute, the CRC 1227 DQ-mat within the projects A05 and B07DS gratefully acknowledges funding by the Federal Ministry of Education and Research (BMBF) through the funding program Photonics Research Germany under contract number 13N14875.RG acknowledges Ville de Paris (Emergence programme HSENS-MWGRAV), ANR (project PIMAI) and the Fundamental Physics and Gravitational Waves (PhyFOG) programme of Observatoire de Paris for support. We also acknowledge networking support by the COST actions GWverse CA16104 and AtomQT CA16221 (Horizon 2020 Framework Programme of the European Union).The work was also supported by the German Space Agency (DLR) with funds provided by the Federal Ministry for Economic Affairs and Energy (BMWi) due to an enactment of the German Bundestag under Grant Nos.∼50WM1556, 50WM1956 and 50WP1706 as well as through the DLR Institutes DLR-SI and DLR-QT.PA-S, MN, and CFS acknowledge support from contracts ESP2015-67234-P and ESP2017-90084-P from the Ministry of Economy and Business of Spain (MINECO), and from contract 2017-SGR-1469 from AGAUR (Catalan government).SvAb, NG, SL, EMR, DS, and CS gratefully acknowledge support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC-2123 QuantumFrontiers—390837967 (B2) andCRC1227 ‘DQ-mat’ within projects A05, B07 and B09.LAS thanks Sorbonne Universités (Emergence project LORINVACC) and Conseil Scientifique de l'Observatoire de Paris for funding.This work was realized with the financial support of the French State through the ‘Agence Nationale de la Recherche’ (ANR) in the frame of the ‘MRSEI’ program (Pre-ELGAR ANR-17-MRS5-0004-01) and the ‘Investissement d'Avenir’ program (Equipex MIGA: ANR-11-EQPX-0028, IdEx Bordeaux—LAPHIA: ANR-10-IDEX-03-02).Peer Reviewe

STE-QUEST - Test of the Universality of Free Fall Using Cold Atom Interferometry

In this paper, we report about the results of the phase A mission study of the atom interferometer instrument covering the description of the main payload elements, the atomic source concept, and the systematic error sources

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies.publishedVersio

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies

Frontotemporal dementia and its subtypes: a genome-wide association study

SummaryBackground Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with {FTD} and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with {FTD} and 4308 controls), we did separate association analyses for each {FTD} subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and {FTD} overlapping with motor neuron disease FTD-MND), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, \{HLA\} locus (immune system), for rs9268877 (p=1·05 × 10−8; odds ratio=1·204 95% \{CI\} 1·11–1·30), rs9268856 (p=5·51 × 10−9; 0·809 0·76–0·86) and rs1980493 (p value=1·57 × 10−8, 0·775 0·69–0·86) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural \{FTD\} subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10−7; 0·814 0·71–0·92). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies