Search

To identify parameters of comprehensive geriatric assessment (CGA) CGA including ABCDEF score, a multidomain frailty assessment, associated with poor outcome after TAVI and to assess the evolution of CGA parameters at 6-months follow-up. One-year monocentric prospective cohort study. Departments of geriatric medicine and cardiology in Rouen University Hospital, Normandy, France. All patients over 70, selected for TAVI by a multidisciplinary “heart team”. 8-areas CGA was performed before TAVI and at 6-months follow-up. Poor outcome was defined as decrease in 1 BADL or unplanned readmission at 6 months or death within the first year after TAVI. Geriatric characteristics associated with poor outcome were assessed by logistic regression with surgical scores as bivariable. Geriatric characteristics were compared between baseline and 6-months follow-up. 114 patients (mean age 85.8±5.3 years) were included. Mean EuroSCORE was 19.1±10.6%. Poor outcome occurred in 57(50.0%) patients. Loss of one BADL (OR: 1.66, 95CI[1.11–2.48]), decrease in IADL (OR: 1.41, 95CI[1.14–1.74]), in plasmatic albumin (OR: 1.10, 95CI[1.01–1.20]), in MMSe (OR: 1.13, 95CI[1.02–1.26]), low walking speed (OR: 1.53, 95CI[1.01–2.33]) and ABCDEF score ≥2 (OR: 1.63, 95CI[1.09–2.42]) were independently associated with poor outcome. In survivors with complete follow-up (n=80), most geriatric parameters were maintained 6 months after TAVI, but IADL decreased (5.6±1.9 to 4.9±2.2, p more...

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564 more...

Characterization data for the Icarus 2 hybrid-CMOS (hCMOS) imager using near-infrared (NIR) laser pulses is presented. The Icarus 2 hCMOS imagers are four-frame burst mode cameras, with a 1024 x 512 pixel array and 25μm spatial resolution. Designed and built by Sandia National Laboratory for the Ultra-Fast X-ray Imager (UXI) program where they have been used to capture X-ray images at LLNL’s National Ignition Facility and during HED physics experiments. Temporal and spatial characterization is performed using NIR, 1053nm and 1064nm, laser pulses ranging from 43-ps to 20ns. Specific results include gate response, internal reflections, off-gate sensitivity, side-to-side timing skew, and response to a characteristic NIF-like laser pulse. Comparisons between a commercial gated, intensified CCD camera and a commercial time-integrated CMOS camera are included when relevant. more...

Heavy metals (HMs) in crops and processed foods are a concern and pose a potential serious health hazard. This study investigated possible presence of HMs in grains and processed products in the Region of Arequipa in Peru. Concentrations of Cd, As, Sn, Pb, and Hg were determined for commonly consumed grains in 18 districts of the region and processed products from 3 popular markets of Arequipa city, using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Cold Vapor Atomic Absorption Spectroscopy (CVAAS). HM concentrations above the Codex General Standard limits were found for As (0.17 mg kg−1) and Cd (0.11 mg kg−1) in cereal grains. Elevated Pb concentrations of 0.55, 0.75, and 5.08 mg kg−1 were found for quinoa, maize, and rice products, respectively; and attributed to processing conditions. The Total Hazard Index (HI) for polished rice and rice products had values between 1 and 10, showing non-carcinogenic adverse effects. Total Target Cancer Risk (TRT) and uncertainty analysis of percentile P90% for polished rice and quinoa products gave values above permissible limit of 10−4, indicating an unacceptable cancer risk. The Nemerow Composite Pollution Index method (NCPI) showed that processed products had a significant pollution level due to the presence of Pb. While most crops grains had acceptable low HM levels, this is the first report of concerning HM concentrations in some consumed grains and processed products in southern Peru and indicates the necessity to find ways to decrease certain toxic metals in foods. more...

A major upgrade has been implemented for the ns-gated laser entrance hole imager on the National Ignition Facility (NIF) to obtain high-quality data for Hohlraum physics study. In this upgrade, the single “Furi” hCMOS sensor (1024 × 448 pixel arrays with two-frame capability) is replaced with dual “Icarus” sensors (1024 × 512 pixel arrays with four-frame capability). Both types of sensors were developed by Sandia National Laboratories for high energy density physics experiments. With the new Icarus sensors, the new diagnostic provides twice the detection area with improved uniformity, wider temporal coverage, flexible timing setup, and greater sensitivity to soft x rays ( more...

The ribbed mussel has been demonstrated to tolerate high levels of urban pollution and inhabits intertidal regions of the New York City estuary. The ability of this bivalve to filter bacteria raises the question of whether it can remove from the water column the fecal bacteria introduced to urban waterways by septic system leakage or sewer overflow. The study here addresses the hypothesis that ribbed mussel filters bacteria introduced by combined sewer overflow (CSO) discharge. Mussels and water were collected from a highly polluted region of the NYC estuary in order to conduct two sets of five trials for filtration of coliform and coccoid fecal indicator bacteria, respectively, Escherichia coli and Enterococcus species. Mussels and water samples were collected in proximity to a major CSO outfall within 1-2 days of a rainfall event to ensure high baseline values of bacterial contamination for filtration trials. For any given Enterococcus or E. coli trial, equal volume water samples were serially distributed across aerated tanks either containing a mussel or not. Comparison of with-mussel versus no-mussel tank water contamination across pooled trials showed significant (P 0.05) reduction in water exposed to mussel filtration for both, Enterococcus and E. coli trials. For Enterococcus trials, measures of turbidity (suspended particle density) were taken concurrently with measures of bacterial contamination. Regression of contamination against turbidity, with measures standardized across trials, yielded a significant positive association (n = 50, P 0.0001) across all tank water with a mussel. Thus, contamination reduction was associated with particle removal by mussel filtration. more...

This paper describes the test plan and the main results achieved by UMS during a space evaluation of its second generation 0.5 μm GaN RF power bar technology, called GH50-20. The space evaluation tests results are summarised: a life time higher than 5.106 h @ 200 °C is found, SEE, TID and DD radiation hardness safe area were defined, and failure rate below 10 FIT @ 200 °C was determined. The results also include demonstration of representative integrated circuits up to 130 W RF power level when operated in L-band in continuous wave (CW) mode. The GH50-20 technology has successfully passed the space evaluation program and is deemed suitable for use in space. more...

The temporal response of a microchannel plate photomultiplier tube used in the suite of neutron time of flight (nToF) diagnostics at the National Ignition Facility has been characterized to reduce uncertainty in, and understanding of, shot parameters obtained from nTOF data. A short pulse laser, neutral density glass filters, and electrical attenuators were used to gather statistically significant samples of photodetector impulse response functions (IRF) in rapid succession. Individual components have been absolutely calibrated to minimize systematic uncertainties. The zeroth (collected charge), first (transit time), and second central moments (transit time spread) of the IRF were calculated as either the bias voltage or the amount of light incident on the detector was varied. Timing reference was provided by a monitor photodiode viewing a pickoff of the incident laser pulse. The primary sources of uncertainty are jitter in the monitor photodiode and the statistical variation across our measurement period. The spreads in the first moment, with respect to the timing photodiode, and the square root of the second central moment were found to be less than 50 ps and 150 ps, respectively. more...

A new conduction cooled compact laser for laser induced spectroscopy is presented. An oscillator combined to an amplifier is designed to generate 30mJ at 1≠m with a good spatial quality.

A new conduction cooled compact laser for Laser Induced Breakdown Spectroscopy (LIBS) on Mars is presented. The laser provides pulses with energy higher than 30mJ at 1μm of wavelength with a good spatial quality. Three development prototypes of this laser have been built and functional and environmental tests have been done. Then, the Qualification and Flight models have been developed and delivered. A spare model is now developed. This laser will be mounted on the ChemCam Instrument of the NASA mission MSL 2009. ChemCam Instrument is developed in collaboration between France (CESR and CNES) and USA (LANL). The goal of this Instrument is to study the chemical composition of Martian rocks. A laser source (subject of this presentation) emits a pulse which is focused by a telescope. It creates a luminous plasma on the rock; the light of this plasma is then analysed by three spectrometers to obtain information on the composition of the rock. The laser source is developed by the French company Thales Laser, with a technical support from CNES and CESR. This development is funded by CNES. The laser is compact, designed to work in burst mode. It doesn't require any active cooling. more...

ChemCam is a LIBS Instrument mounted on the MSL 2011 NASA mission. The laser transmitter of this Instrument has been developed by the French society Thales Optronique (former Thales Laser) with a strong technical support from CNES. The paper will first rapidly present the performance of this laser and will then describe the postChemCam developments realized on and around this laser for new planetology programs. more...

The Daedalus camera is a second-generation imager for the Ultra-Fast X-ray Imager (UXI) program, achieving 1 ns, time-gated, multi-frame image sets for High Energy Density (HED) physics experiments. Daedalus includes a 1024 x 512 pixel array with 25 μm spatial resolution with three frames of storage per pixel with three times larger full well (1.5 million e-) than the last generation camera, Icarus. Daedalus incorporates an improved timing generation and distribution concept to facilitate broader user configurability and application space while improving timing resolution to 1 ns. Electrical timing measurements demonstrated 1 nanosecond shutters. Analog dynamic range is sufficient to provide the expected full well. Read noise of 210 e- has been measured, exceeding design goals. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia LLC, a wholly owned subsidiary of Honeywell International Inc. for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525. more...

Objective To document eating practices and socio-economic profiles of patients seen in the social and medical healthcare centres (CASOs in its French acronym) run by Doctors of the World (Medecins du Monde, MdM) in France and evaluate their nutritional and health status. Study design The survey was carried out between April and May 2014 in seven CASOs in France. Methods All the patients attending MdM clinics were given a nutrition and health questionnaire. Their anthropometric measurements were taken on site. Results 77.7% of the households surveyed were food insecure due to constrained resources. On average, the patients interviewed declared spending €2.5 per person per day on food. A total of 46.3% of adults declared not having eaten for a whole day at least once in the month preceding the survey. One third of the patients declared having lost weight over the last two weeks. A chronic pathology was diagnosed in more than one in two patients; 19% were obese and 34% were overweight. Conclusions Constrained resources lead people living in very precarious conditions to eat without adequate nutrition, which could have consequences for their health, such as diabetes, obesity and cardiovascular disease. more...

Resume La technique de spectroscopie de proche infrarouge near infrared spectroscopy (NIRS) parait etre un outil interessant pour etudier la dysfonction microcirculatoire. De telles alterations ont ete decrites apres chirurgie cardiaque et circulation extracorporelle (CEC). Nous rapportons deux cas cliniques de patients ayant presente des complications hemodynamiques apres chirurgie cardiaque et ayant beneficie d’un monitorage de la saturation tissulaire en oxygene et d’un calcul des pentes de resaturation apres un test d’occlusion. Ces deux parametres sont alteres de facon tres precoce notamment en cas de dysfonction cardiaque. Nous discutons l’interet d’un monitorage microcirculatoire dans ce contexte. more...

Objectives The National Hospital of Saint Maurice (HNSM) for Physical Medicine and Rehabilitation aims at strengthening its position as a pivot rehabilitation and physical therapy center. The opening in 2011 of a new unit for the evaluation and treatment of motor disabilities meets this objective. This project includes several parts: clinical, financial, architectural, organizational, applied clinical research as well as dealing with medical equipments and information system. This study focuses on the risk assessment of this future technical unit. Methods This study was conducted by a group of professionals working for the hospital. It started with the design of a functional model to better comprehend the system to be analyzed. Risk assessment consists in confronting this functional model to a list of dangers in order to determine the vulnerable areas of the system. Then the team designed some scenarios to identify the causes, securities barriers and consequences in order to rank the risks. Results The analysis targeted various dangers, e.g. political, strategic, financial, economical, marketing, clinical and operational. The team identified more than 70 risky scenarios. For 75% of them the criticality level was deemed initially tolerable and under control or unacceptable. The implementation of an action plan for reducing the level of risks before opening this technical unit brought the system down to an acceptable level at 66%. Conclusion A year prior to opening this technical unit for the evaluation and treatment of motor disabilities, conducting this preliminary risk assessment, with its exhaustive and rigorous methodology, enabled the concerned professionals to work together around an action plan for reducing the risks. more...

Renal function impairment can be monitored by many tests. Measurement of plasma-creatinine level is the most used method, 24 h plasma-creatininclearance with urine collection is used by others and also other alternative but indirect methods exist. However, the use of radionuclide-clearances is by far the easiest performed method with the highest accuracy and precision and gives very low irradiation dose. In the following we will discuss the different radiopharmaceuticals in use, their plus and minus, the different clearance methods in use, their limitations and give some clinically important indications to perform clearance investigations according to consensus reports. Summarizing the use of plasma clearance of 51-Cr-EDTA after a single injection with one blood sample can be generally recommended, however with some modifications in special clinical situations, which are pointed out. Please note, that this paper is, for a significant part, an update of a previous paper published 2003 in “Der Nuklearmediziner” more...

The possibility of reduced cell kill following intensity-modulated radiation therapy (IMRT) compared to conventional radiation therapy has been debated in the literature. This potential reduction in cell kill relates to prolonged treatment times typical of IMRT dose delivery and consequently increased repair of sublethal lesions. While there is some theoretical support to this reduction in cell kill published in the literature, direct experimental evidence specific to IMRT dose delivery patterns is lacking. In this study we present cell survival data for three cell lines: Chinese hamster V79 fibroblasts, human cervical carcinoma, SiHa and colon adenocarcinoma, WiDr. Cell survival was obtained for 2.1 Gy delivered as acute dose with parallel-opposed pair (POP), irradiation time 75 s, which served as a reference; regular seven-field IMRT, irradiation time 5 min; and IMRT with a break for multiple leaf collimator (MLC) re-initialization after three fields were delivered, irradiation time 10 min. An actual seven-field dynamic MLC IMRT plan for a head and neck patient was used. The IMRT plan was generated for a Varian EX or iX linear accelerator with 120 leaf Millenium MLC. Survival data were also collected for doses 1X, 2X, 3X, 4X, and 5x 2.1 Gy to establish parameters of the linear-quadratic equation describing survival following acute dose delivery. Cells were irradiated inside an acrylic cylindrical phantom specifically designed for this study. Doses from both IMRT and POP were validated using ion chamber measurements. A reproducible increase in cell survival was observed following IMRT dose delivery. This increase varied from small for V79, with a surviving fraction of 0.8326 following POP vs 0.8420 following uninterrupted IMRT, to very pronounced for SiHa, with a surviving fraction of 0.3903 following POP vs 0.5330 for uninterrupted IMRT. When compared to IMRT or IMRT with a break for MLC initialization, cell survival following acute dose delivery was significantly different, p < 0.05, in three out of six cases. In contrast, when cell survival following IMRT was compared to that following IMRT with a break for MLC initialization the difference was always statistically insignificant. When projected to a 30 fraction treatment, dose deficit to bring cell survival to the same value as in POP was calculated as 4.1, 24.9, and 31.1 Gy for V79, WiDr, and SiHa cell lines, respectively. The dose deficit did not relate to the alpha/beta ratio obtained in this study for the three cell lines. Clinical data do not show reduction in local control following IMRT. Possible reasons for this are discussed. The obtained data set can serve as a test data set for models designed to explore the effect of dose delivery prolongation/fractionation in IMRT on radiation therapy outcome. more...

Background and purpose A subset of patients in a clinical study where sequential biopsies were to be obtained during multifraction radiotherapy received pimonidazole prior to initiating treatment, allowing a unique opportunity of following hypoxic cells in situ during therapy. Material and methods After institutional ethics review and with informed consent, women expecting to undergo radical treatment for cancer of the cervix received pimonidazole hydrochloride, with a biopsy approximately 24h later. Therapy was then started, and weekly biopsies were obtained. In the laboratory, the biopsies were reduced to single cell suspensions for flow cytometry analysis of DNA content, pimonidazole, and proliferation markers. Results Pre-treatment pimonidazole-positive cells were largely in G 0 /G 1 . Pimonidazole-labelled cells, though expected to be radioresistant, were markedly decreased even early into treatment, and continued to disappear with a half-time of about 3 days. Concurrently, the cell cycle distribution of the previously hypoxic cells changed from predominantly quiescent to mostly proliferating. Conclusions While a part of the rapid apparent loss of hypoxic cells was certainly due to loss of pimonidazole adducts through repair and dilution by cell division, the speed with which this occurred suggests that many labelled cells could rapidly re-enter the proliferative pool, a result consistent with many of those pimonidazole-labelled human cervix tumour cells being cyclically, rather than continuously, hypoxic. more...

More and more elderly people are hospitalised with myocardial infarction. Little is known on their pre-hospital management. In 2001 and 2002, 105 patients aged 80 years or more with suspected ST elevation infarction were managed by the mobile intensive care unit system of the SAMU de Paris-Necker. Diagnosis of infarction was confirmed in 92 (88%). Over 60% of the patients were women. Median time delay from symptom onset to call to the emergency service was 127 minutes, longer in nonagenarians (175 vs 101 minutes). Prehospital use of aspirin was 81% and 39% received an intravenous bolus of heparin. A reperfusion strategy was decided in only 30% (primary PCI: 23/26). One-month mortality was 21% and was related to older age, time when the call to the Samu was made, and absence of current smoking. Overall, the prehospital management of very elderly patients with suspected ST elevation infarction appears far from optimal. more...

Aim. This study aimed to determine whether third-trimester adipokines during gestational diabetes (GDM) are associated with higher metabolic risk.Methods. A total of 221 women with GDM (according to IADPSG criteria) were enrolled between 2011/11 and 2013/6 into a prospective observational study (IMAGE), and categorized as having elevated fasting blood glucose (FBG) or impaired fasting glucose (IFG, n=36) if levels were >= 92 mg/dL during a 75-g oral glucose tolerance test (OGTT), impaired glucose tolerance (IGT, n= 116) if FBG was = 92 mg/dL and 1-h or 2-h OGTT values were elevated.Results. - Pre-gestational body mass index (BMI) was higher in women with IFG or IFSG compared with JOT (P more...

In the past few years, 'perfusion-limited' hypoxia caused by intermittent decreases in tumour blood flow has received increasing attention. Little effort, however, has gone into characterizing the nature, magnitude or duration of these changes, or their functional significance other than as modifiers of radiotherapy. We have therefore undertaken multiple, quantitative analyses of tumour blood flow in human tumour xenograft systems, and rigorously examined the ramifications of transient blood flow changes. Tumour blood flow in these experimental tumours is much less constant than has previously been assumed, and not only impacts on response to radiotherapy and chemotherapy, but also on the more fundamental processes of tumour growth and repopulation. Notably, responses entirely consistent with the laboratory results have been seen in our initial studies of human tumours sequentially biopsied during treatment. more...

This paper reports observations of Ramsey fringes on a 10.6-$\ensuremath{\mu}\mathrm{m}$ two-photon transition of ${\mathrm{SF}}_{6}.$ We used two interaction zones separated by 8 cm and observed fringes of frequency 2.3 kHz. The experimental apparatus might be adapted to increase the resolution by an order of magnitude. The present 10-$\ensuremath{\mu}\mathrm{m}$ secondary frequency standards based on the ${\mathrm{CO}}_{2}$ laser locked onto a saturated absorption resonance of ${\mathrm{OsO}}_{4}$ reach an accuracy of a few ${10}^{\ensuremath{-}13}.$ This work contributes to the current attempts to build a new generation of frequency standards with a potential accuracy in the ${10}^{\ensuremath{-}14}\char21{}{10}^{\ensuremath{-}15}$ range. more...

We report the case of a motor impairment associated with bladder dysfunction several days after clopidogrel withdrawal in an arteriosclerotic woman scheduled for thoracotomy under general and thoracic epidural anaesthesia. Even if spinal artery syndrome may have a lot of aetiologies, we believe in a direct link between clopidogrel withdrawal and medulla ischaemia. more...

The comet assay is a single-cell gel electrophoresis technique that measures DNA damage in individual cells. Since radiation produces 3-4 times more DNA damage in well-oxygenated cells compared with hypoxic cells, this assay can quantify the fraction of radiation-resistant hypoxic cells found in many solid tumours. This paper summarizes our results with 73 accessible metastatic tumours irradiated with palliative intent. Hypoxic fractions ranged from 0.0 to 0.67 with a mean of 0.15; 62% of these advanced tumours showed a hypoxic fraction0.05. Comparisons between two sequential aspirates in 33 tumours gave a slope of 0.92 (r2 = 0.88), suggesting that a single aspirate is generally representative of the tumour. A limitation, however, is that the hypoxic fraction could not be measured in clinical samples given a conventional dose of 2 Gy. more...

Background and purpose : The objective of the present study was to evaluate the predictive potential of cell kinetic parameters and repopulation rates determined by flow cytometry during multifraction irradiation of spheroids, a system in which the fate of all cells can be determined with high precision. Ultimately, similar analytical techniques should provide a reproducible and prognostically significant clinical predictive assay. Materials and methods : Multicellular spheroids of Chinese hamster V79 lung cells were irradiated with 2.5 Gy of 250 kVp X-rays twice daily to a total dose of 25 Gy. Repopulation parameters and cell kinetic parameters were followed throughout the irradiation period and for 5 days after completion of exposure. Results : (1) Regrowth (RG) took place early during multifraction irradiation. (2) Potential doubling time ( T pot ) decreased steadily from the early part of treatment, remaining of short duration until the spheroids almost attained the pre-treatment number of clonogenic cells. (3) Accelerated repopulation was mainly due to a decreased cell loss factor ( Φ ) and increased growth fraction (GF), although a modest decrease in cell cycle time ( t c ) was suggested. (4) Φ decreased during exponential RG. (5) Other parameters such as observed doubling time ( t d ) and labelling index (LI) paralleled these findings. Conclusions : Clonogen repopulation that began early in the irradiation scheme and accelerated rapidly is not consistent with the prevailing view that accelerated repopulation begins several weeks into clinical protocols. Also, pre-treatment T pot did not adequately estimate the repopulation speed in the spheroids. Equivalent studies in animal tumour systems, and then in the clinic, are consequently indicated and of some urgency. more...

International audience; Purpose Neovascular age-related macular degeneration (AMD) is the main cause of central vision loss among individuals aged 50 years or older in developed countries. The aim of this study was to review systematically the effect of bevacizumab compared to ranibizumab in patients with AMD at 1 year. Methods A systematic review was performed on Medline, Embase, and the Cochrane Library and Trial registers to October 2013. Eligibility criteria for selecting studies were randomised controlled trials (RCT) comparing bevacizumab with ranibizumab in patients with neovascular AMD. Odds ratio (OR) and mean difference (MD) estimates were synthesized under fixed-and random-effects models. Heterogeneity was assessed using the Q statistic and I-2. Results Five RCTs were included, representing 2,686 randomised patients. The meta-analysis confirmed the non-inferiority of bevacizumab compared to ranibizumab for change in visual acuity at 1 year (MD 0.57 letters, -1.80 to 0.66, p = 0.37, I-2 = 0 %). Better anatomical results were found for ranibizumab. Bevacizumab was associated with a 34 % increase in the number of patients with at least one serious systemic adverse event (OR 1.34, 1.08 to 1.66, p = 0.01, I-2 = 0 %). Conclusions The pooled evidence confirmed that, compared with ranibizumab, bevacizumab was associated with equivalent effects on visual acuity at 1 year and with a higher risk of systemic serious adverse events. The current available data do not show which types of adverse events occur more frequently. In practice, bevacizumab should be used under a risk-management plan until further studies have been carried out to assess accurately the increased risk of systemic adverse events. more...

Purpose: Accelerated repopulation has generated considerable recent interest. Our purpose in this study was to determine whether flow cytometry measurements like those used for classical T pot determinations could be used to quantify the rate of repopulation, and the time of its initiation in irradiated human tumor xenografts. Methods and Materials: Two human tumor cell lines (SiHa, a squamous cell cervix carcinoma, and WiDr, an adenocarcinoma of the colon) were grown as subcutaneous xenografts in SCID mice. T pot was measured in a conventional manner using flow cytometry, for control tumors and for tumors exposed to five fractions of 4 Gy twice daily over a 2-day interval. For the irradiated tumors, T pot measurements were conducted 48 h following the final exposure. Results: Active proliferation even after irradiation was observed in both the radiosensitive SiHa and more radioresistant WiDr tumors, and the estimated repopulation rate was at least as fast as would have been predicted by the pre-treatment T pot estimates. Conclusions: Our data clearly indicate tumor cell proliferation after only a few fractions of radiation exposure in these human tumor xenografts. Additionally, the data suggest that pretreatment T pot values may underestimate the actual regrowth rate. more...

We have developed a frequency stabilization scheme for CO/sub 2/ lasers using only external modulation via an electrooptic modulator (EOM). One of the two laser sidebands which are generated by the EOM and frequency-modulated is set in resonance with a Fabry-Perot cavity, itself filled with OsO/sub 4/ as an absorber. The saturation signal of an OsO/sub 4/ line detected in transmission of the Fabry-Perot cavity is used for stabilization. We obtained a stability of 0.1 Hz (/spl Delta//spl nu///spl nu/=3.5 10/sup -15/) on a 100-s time scale, and a reproducibility up to 10 Hz with the strongest OsO/sub 4/ reference lines. These results largely improve the performance of our previous setup for which modulation was applied through piezoelectric transducers. Further, the stabilized laser is not frequency-modulated and is easily tunable. more...

Summary form only given. This work deals with high energy eye-safe lasers for long-distance active imagery purpose. Direct resonant pumping of erbium appears as a very promising technique, either at 1530 nm with fibre lasers or at 1470 nm with laser-diodes [1-3]. Indeed, the long lifetime (5-10 ms) of the upper laser level ensure a favourable energy storage capability and the resonant scheme leads to a reduced thermal loading if compared with usual pumping at 980 nm in codoped Er-Yb materials. It is worth noting that only the summary is available for the ref [2] claiming the same energy than presented here. Our laser system rely on Er:YAG crystals and fibre coupled laser diode bars. The doping level of the gain medium is 0.5%. Each pump fibre (400μm diameter, 0.2 numerical aperture) delivers 120W at 1470nm. Each crystal is end-pumped on its two faces. The laser system (see Fig. 1) consists in an oscillator and to single pass amplifiers. Each pump fibre is imaged with a magnification of 4 (3) in the oscillator (amplifier) crystal. Dichroic mirrors (DM) ensure efficient laser reflection and good pump transmission. The output coupler (OC) has a 40% transmission coefficient and the Q-Switching is performed with an acousto-optic cell (QS). The pump are driven with 6ms pulses at 30Hz. Pair of lenses (PL) are used between the oscillator and each amplifiers to adjust the laser beam size and compensate for thermal lensing in the gain medium. Main results are reported in Fig. 2.To avoid damages of the dichroic mirrors, the Q-Switch was activated with a delay after the end of the pump pulse. Reducing this delay increases the output energy and thus the laser fluence. A delay shorter than 0.2ms usually damages the dichroic mirror. We demonstrated an oscillator output energy of 50mJ and a gain of 40-45% for each amplifier, leading to 100mJ output energy for the laser system. The pulse width is 100ns. The beam quality slightly degrades along the amplifier from M2x=2.5 / M2y=2.0 at the oscillator output to M2x=3.7 / M2y=3.1 at the laser system output. more...

Ultra-high-resolution spectroscopy and metrology require very stable lasers with a high-spectral purity. For spectroscopy with a resolution in the range 10-100 Hz at 30 THz, we are developing a new stabilization scheme which acts separately on the long and short term stabilities. We present the results achieved with the first part of our new scheme, which is based upon the stabilization on a saturation signal detected in transmission of an active Fabry-Perot cavity. With a laser linewidth of 3.4 Hz (FWHM) and a flicker plateau of 0.7 Hz (/spl Delta//spl nu///spl nu/=2.10/sup -14/) obtained using a strong OsO/sub 4/ line as reference, this stabilization system already improves the both short and long-term stabilities obtained by our previous setup which involved an external cell instead of a Fabry-Perot cavity. We present also the results using a CO/sub 2/ laser line as frequency reference. > more...

International audience; ChemCam is a remote sensing instrument suite on board the "Curiosity" rover (NASA) that uses Laser-Induced Breakdown Spectroscopy (LIBS) to provide the elemental composition of soils and rocks at the surface of Mars from a distance of 1.3 to 7 m, and a telescopic imager to return high resolution context and micro-images at distances greater than 1.16 m. We describe five analytical capabilities: rock classification, quantitative composition, depth profiling, context imaging, and passive spectroscopy. They serve as a toolbox to address most of the science questions at Gale crater. ChemCam consists of a Mast-Unit (laser, telescope, camera, and electronics) and a Body-Unit (spectrometers, digital processing unit, and optical demultiplexer), which are connected by an optical fiber and an electrical interface. We then report on the development, integration, and testing of the Mast-Unit, and summarize some key characteristics of ChemCam. This confirmed that nominal or better than nominal performances were achieved for critical parameters, in particular power density (>1 GW/cm2). The analysis spot diameter varies from 350 μm at 2 m to 550 μm at 7 m distance. For remote imaging, the camera field of view is 20 mrad for 1024×1024 pixels. Field tests demonstrated that the resolution (˜90 μrad) made it possible to identify laser shots on a wide variety of images. This is sufficient for visualizing laser shot pits and textures of rocks and soils. An auto-exposure capability optimizes the dynamical range of the images. Dedicated hardware and software focus the telescope, with precision that is appropriate for the LIBS and imaging depths-of-field. The light emitted by the plasma is collected and sent to the Body-Unit via a 6 m optical fiber. The companion to this paper (Wiens et al. this issue) reports on the development of the Body-Unit, on the analysis of the emitted light, and on the good match between instrument performance and science specifications. more...

Purpose: To apply the alkaline comet assay to the detection of radiobiologically hypoxic cells in solid tumors and normal tissues of mice, and to examine the influence of strand break repair on the oxygen enhancement ratio measured using the alkaline comet assay. Methods and Materials: In previous studies, we found that hypoxic fraction in squamous cell carcinomas growing in C3H mice could be reliably and easily measured using the alkaline comet assay. The comet assay applies fluorescence microscopy and image analysis to examine patterns of migration of deoxyribonucleic acid from individual cells embedded in agarose and exposed to an electric field. This method has sufficient resolution to detect subpopulations of hypoxic cells which show about 3 × fewer strand breaks than aerobic cells after irradiation. Results: Fast rejoining kinetics in vitro are comparable to those measured in vivo , and rejoining of strand breaks in hypoxic tumor cells occurs at a similar rate as rejoining in aerobic cells. Little residual damage was detectable using the comet assay in tumors 4–24 h following 15 Gy, allowing repeat measurements to be performed. Bone marrow and testis, but not liver, spleen, or jejunum contained a small fraction of hypoxic cells when mice breathed 10% oxygen during irradiation. Conclusion: The comet assay confirms that some normal tissues may border on hypoxia. Rejoining of strand breaks occurs rapidly in both oxic and hypoxic cells so that the oxygen enhancement ratio remains relatively constant with time after irradiation. Interestingly, a smaller oxygen enhancement ratio was observed in tumors than was expected, probably as a result of the presence of acutely hypoxic cells. more...

This study analyses differences and similarities in information technology (IT) resource, practice and perceived success across firms in the USA, France and Korea. Results are framed within the context of cultural characteristics and their influence on business practice as developed in international business, cultural anthropology and social psychology literature. Our findings indicate similarities in resource use across these varying cultures. Specifically, IT budget and deployment policies seem fairly consistent among the countries examined. In contrast, very distinct differences in IT practice are observed. Specifically, the role of IT, integration of strategic and IT planning, and risk taking in information systems (IS) projects varied among the countries examined. Korean entities, unlike their US and French counterparts, seem to view IT in a more traditional, operational vein with little tolerance for risk taking. Interestingly, perceived benefits of IT use also varied among countries. Consistent with their cultural profile, US firms seem positively to associate market level impact with the measured dimensions of IT practice and use. The results of this study, along with the cultural context in which they are presented, should aid both corporate planners and researchers in recognizing and explaining cultural differences and their potential influence on IT policy and use. more...

T here seems to be little question that development of a predictive assay that could reliably forecast the response of individual tumors to treatment would be of tremendous value to practicing oncologists. However, exactly what type of information is needed in such an assay is less certain. For example, is the determinant of success the inherent sensitivity of the majority, or that of a minority of the tumor cells? Because treatment "failure" is typically recognized by the regrowth or continued growth of the tumor mass, what is the role of cell kinetics in that process? Perhaps of most pressing importance, can predictive assays lead to alternate, hopefully superior, forms of treatment? While measuring tumor cell sensitivity to both radiation and drugs has become fashionable in recent years, correlations between in vitro sensitivity analyses and eventual patient outcome have generally been found only between tumor types, but not between individual tumors of a certain type. This suggests that factors in addition to inherent sensitivity must be considered. Analyzing patterns of failure can often be useful in this regard; in a provocative article analyzing outcomes for patients with head and neck cancer, Withers et al I reached the rather alarming conclusion that treatments lasting more than 4 weeks required a dose escalation of 0.6 Gy/extension day to retain the same probability of cure. More general reviews 2-4 similarly argue for a dose increase of 0.3 to 0.7 Gy/day of treatment for treatment extensions beyond 4 weeks. These results strongly' implicate time as a critical factor for successful treatments. However, identifying a clinical problem is considerably easier than resoMng it. For example, does the repopulation seen at later times during therapy indicate that cells are cycling more rapidly, that more cells are in cycle, that fewer clonogenic cells are "lost," or combinations of the above? When does repopulation actually"accelerate"? Perhaps of greater immediate importance, can reliable and unambiguous methods of measurement be developed for tumor cell kinetics, and when should they be used? Alternatively, can repopulation rate or potential be predicted? Clearly', several philosophical and practical limitations combine to inhibit addressing these questions in the most relevant system, the human cancer patient. At least one tumor model system is available, however, in which many relevant and highly detailed studies can be pursued: the multicell spheroid model. 5,6 It is of particular note that the spheroid system can be easily maintained in long-term culture, allowing large numbers of virtually identical "tumors" to be propagated and reproducibly tested, without host factors complicating the response. 7,8 Every cell of the system potentially contributes to the net response, and of particular importance, each cell can be recovered and assessed. The intent of this article is to examine the role of cell kinetics when spheroids are treated with multifraction protocols. In addition to multifraction radiation treatments, multiple drug exposures will be briefly explored. From the design of these studies, we have been able to address not only the role of pretreatment cell kinetics, but also factors controlling changes of those kinetic properties during, and in response to, the therapeutic manipulations. more...

Contrary to expectations, a study of creativity enhancing software showed that user creativity declined when using the software on an analysis task. Software increased the number of alternatives, but independent judges determined that these were less original or inventive than those produced without the software. These findings were consistent for both ‘highly creative’ and ‘less creative’ groups. Computer technology is an added variable that can interact to inhibit creativity in a moderately complex case analysis task. Creativity inducing software appears to need further development before it can contribute meaningfully to improving decision support systems. more...

The therapeutic potential of a variety of bioreductive agents, including misonidazole, RSU-1069, NFVO, mitomycin C, porfiromycin, and SR-4233 was evaluated using Chinese hamster V79 multicell spheroids in vitro. Fluorescence-activated cell sorting techniques were used to selectively recover cells from various depths within the spheroids to measure the differential cytotoxicity in the cells near the hypoxic core of the spheroid relative to the well oxygenated peripheral cells. At the high cell density found in spheroids (as in tissues in vivo) the differential toxicity observed was typically much less than expected, based on data from single cell systems. In some cases, this was due to lack of sufficient hypoxia in the spheroids; in other cases, drug treatment itself produced reoxygenation through metabolic or toxic effects during treatment. An unexpected observation of considerable concern was rapid bioreduction of the more active agents; this sometimes occurred at rates that exceeded drug delivery, resulting in considerably less efficacy when large hypoxic fractions were present (e.g. mitomycin C, NFVO, and SR-4233). This suggests that induction of hypoxia prior to bioreductive agent therapy may not be the most productive approach. Though none of the agents showed "ideal" properties, porfiromycin was judged to give the best combination of differential toxicity, longevity in situ, and ability to reach the entire hypoxic cell subpopulation. more...

A numerical model predicts the beam profile of solid-state variable-reflectivity resonators, taking into account diffraction, gain saturation, and stored energy depletion. An experimental analysis of propagation effects shows that the beam profile in the intermediate field is extremely sensitive to residual diffraction effects in the resonator. more...

Background and purpose The possibility of using γH2AX foci as a marker of DNA damage and as a potential predictor of tumour response to treatment was examined using biopsies from 3 sets of patients with advanced carcinoma of the cervix. The relation between endogenous γH2AX expression and hypoxia was also examined. Materials and methods Set 1 consisted of 26 biopsies that included pre-treatment and 24 h post-radiation treatment samples. Pre-treatment biopsies from 12 patients in Set 2 were used to develop image analysis software while pre-treatment biopsies from 33 patients in Set 3 were examined for the relation between staining for the hypoxia marker pimonidazole and endogenous γH2AX expression. Formalin-fixed paraffin-embedded sections were analyzed after antigen retrieval and fluorescence antibody labeling for the hypoxia markers CAIX or pimonidazole in combination with γH2AX staining. Results Before treatment, 24 ± 19% of cells contained γH2AX foci, with most positive cells containing fewer than 5 foci per nucleus. Twenty-four hours after exposure to the first fraction of 1.8–2.5 Gy, 38 ± 19% contained foci. CAIX positive cells were 1.4 times more likely to exhibit endogenous γH2AX foci, and pimonidazole-positive cells were 2.8 times more likely to contain γH2AX foci. For 18 patients for whom both pre-treatment and 24 h post-irradiation biopsies were available, local control was unrelated to the fraction of cells that retained γH2AX foci. However, 24 h after irradiation, tumours that had received 2.5 Gy showed a significantly higher fraction of cells with residual γH2AX foci than tumours given 1.8 Gy. Conclusions Endogenous γH2AX foci are enriched in hypoxic tumour regions. Small differences in delivered dose can produce quantifiable differences in residual DNA damage that can overshadow inter-tumour differences in response. more...

The inherent radio- and chemosensitivity of tumor cells clearly affects their response to treatment. Accumulating evidence, however, suggests that the biochemical and physiological status of the cell during treatment is at least as important. In this review, a critique of the current evidence for, and extent of, microenvironmental heterogeneity in tumors is presented, emphasizing human tumor cells in situ. The expected consequences of those changes on cellular response to radiation and chemotherapy is then briefly reviewed. Finally, the continuing interest in developing new therapeutic strategies for which the tumor microenvironment is an asset (as opposed to a liability) is discussed in the context of the dynamic nature of tumors, and the complexity of adequately analyzing combination treatments. more...

Managers spend about two-thirds of their time communicating, but little IS research has considered technology's effect on the communication process. Earlier findings indicated that communications composed at a keyboard differ structurally and stylistically from traditionally produced communications. Measuring eleven communication dimensions, the experimental study found that managers rated keyboard composed documents more positively than traditionally produced communications (using paper and pencil). Importantly, managers expressed more confidence in conclusions presented by writers using word processing tools than from those composed by traditional means. Thus, communication persuasiveness and effectiveness (from the writer's perspective) was enhanced by using the technology. more...

A large-scale investigation of fracture flow was recently conducted in a granite uranium mine at Fanay-Augeres, France. Its aim was to develop a methodology for the investigation of possible nuclear waste repository sites in crystalline environments, and thus to determine what measurements to make and what models to use in order to predict the flow and transport properties of the medium, i.e., their average behaviors and spatial variabilities at different scales. Four types of data were collected: (1) geometry of the fracture network; (2) local hydraulic properties measured by injection tests in boreholes; (3) global hydraulic behavior from flow rate and piezometric head distribution at a 106 m3 scale; and (4) tracer tests performed at a scale of up to 40 m. A stochastic fracture network model assuming negligible matrix permeability was developed and calibrated essentially on data 1 and 2 above; this was then used to predict data 3 and 4 in an attempt to validate both the parameters and the structure of the model. In this first part, only the flow problem (data 1) is discussed. more...

Background and purpose: Antiprotons travel through tissue in a manner similar to that for protons until they reach the end of their range where they annihilate and deposit additional energy. This makes them potentially interesting for radiotherapy. The aim of this study was to conduct the first ever measurements of the biological effectiveness of antiprotons. Materials and methods: V79 cells were suspended in a semi-solid matrix and irradiated with 46.7 MeV antiprotons, 48 MeV protons, or Co-60 gamma-rays. Clonogenic survival was determined as a function of depth along the particle beams. Dose and particle fluence response relationships were constructed from data in the plateau and Bragg peak regions of the beams and used to assess the biological effectiveness. Results: Due to uncertainties in antiproton dosimetry we defined a new term, called the biologically effective dose ratio (BEDR), which compares the response in a minimally spread out Bragg peak (SOBP) to that in the plateau as a function of particle fluence. This value was similar to 3.75 times larger for antiprotons than for protons. This increase arises due to the increased dose deposited in the Bragg peak by annihilation and because this dose has a higher relative biological effectiveness (RBE). Conclusion: We have produced the first measurements of the biological consequences of antiproton irradiation. These data substantiate theoretical predictions of the biological effects of antiproton annihilation within the Bragg peak, and suggest antiprotons warrant further investigation. (c) 2006 Elsevier Ireland Ltd. All. rights reserved. more...