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1
Stewart-Knox, Barbara J., Gordon Rae, Ellen EA Simpson, Chris McConville, Jacqueline O’Connor, Angela Polito, Maud Andriollo-Sanchez, Charles Coudray, and JJ Strain. "Supplemented zinc does not alter mood in healthy older European adults – a randomised placebo-controlled trial: the Zenith study." Public Health Nutrition 14, no. 5 (January 28, 2011): 882–88. http://dx.doi.org/10.1017/s1368980010002764.
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AbstractObjectiveOlder people are vulnerable to zinc deficiency, which may impact upon their mood. This randomised, placebo-controlled, double-blind intervention study aimed to investigate the effect of oral zinc gluconate supplementation (15 mg/d; 30 mg/d; and placebo) on subjective mood (affect) in older Europeans.SubjectsHealthy volunteers (n 387) aged 55–87 years were recruited.SettingVolunteers in Rome (Italy; n 108) and Grenoble (France; n 91) were aged 70–87 years and those in Coleraine (Northern Ireland; n 93) and Clermont-Ferrand (France; n 95) were aged 55–70 years.DesignMood was measured using the Positive and Negative Affect Scale on four occasions per day over 4 d at baseline, 3 and 6 months post-intervention.ResultsMixed ANOVA indicated that neither positive nor negative affect altered in response to zinc (15 mg/d or 30 mg/d) compared to placebo in either the 55–70 years or the ≥70 years age group.ConclusionsThese results suggest that zinc does not benefit mood in healthy older people.
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Wanders, Niko, Stephan Thober, Rohini Kumar, Ming Pan, Justin Sheffield, Luis Samaniego, and Eric F. Wood. "Development and Evaluation of a Pan-European Multimodel Seasonal Hydrological Forecasting System." Journal of Hydrometeorology 20, no. 1 (January 1, 2019): 99–115. http://dx.doi.org/10.1175/jhm-d-18-0040.1.
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Abstract Hydrological forecasts with a high temporal and spatial resolution are required to provide the level of information needed by end users. So far high-resolution multimodel seasonal hydrological forecasts have been unavailable due to 1) lack of availability of high-resolution meteorological seasonal forecasts, requiring temporal and spatial downscaling; 2) a mismatch between the provided seasonal forecast information and the user needs; and 3) lack of consistency between the hydrological model outputs to generate multimodel seasonal hydrological forecasts. As part of the End-to-End Demonstrator for Improved Decision Making in the Water Sector in Europe (EDgE) project commissioned by the Copernicus Climate Change Service (ECMWF), this study provides a unique dataset of seasonal hydrological forecasts derived from four general circulation models [CanCM4, GFDL Forecast-Oriented Low Ocean Resolution version of CM2.5 (GFDL-FLOR), ECMWF Season Forecast System 4 (ECMWF-S4), and Météo-France LFPW] in combination with four hydrological models [mesoscale hydrologic model (mHM), Noah-MP, PCRaster Global Water Balance (PCR-GLOBWB), and VIC]. The forecasts are provided at daily resolution, 6-month lead time, and 5-km spatial resolution over the historical period from 1993 to 2012. Consistency in hydrological model parameterization ensures an increased consistency in the hydrological forecasts. Results show that skillful discharge forecasts can be made throughout Europe up to 3 months in advance, with predictability up to 6 months for northern Europe resulting from the improved predictability of the spring snowmelt. The new system provides an unprecedented ensemble of seasonal hydrological forecasts with significant skill over Europe to support water management. This study highlights the potential advantages of multimodel based forecasting system in providing skillful hydrological forecasts.
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Barrell, Ray, Julian Morgan, and Nigel Pain. "The World Economy." National Institute Economic Review 157 (July 1996): 28–57. http://dx.doi.org/10.1177/002795019615700104.
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It is now quite clear that growth slowed in Europe around the end of 1995, and that it remained low in the first quarter of 1996. However, the most recent information suggests that the slowdown is likely to prove temporary. Early indicators for the second quarter suggest that growth has begun to accelerate, much in line with our forecast published in May. We have made no further adjustment to our forecast for EU wide growth this year, with output still expected to rise by around 1½ per cent this year and around 2¾–3 per cent next year. Recent exchange rate developments should help support demand, as the D-mark, the French franc and other currencies within the D-mark bloc have all depreciated against the dollar in the last few months. A number of economies in Europe appear to have some spare capacity, and can increase output, whilst the US is operating at or above capacity, and a reduction in demand should ease incipient inflationary pressures rather more than it reduces output. The depreciation of the D-mark has been associated with a loosening of monetary policy, with short-term interest rates in Germany being a full point lower than they were a year ago. French short-term interest rates have fallen much more, reflecting the disappearance of a significant risk premium last year. The loosening of policy was timely, and should help offset the deflationary pressures that have come from a slowdown in stock accumulation in both France and Germany and from low investment, especially in Germany.
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Zhu, Yi, Yu Yue, Haobin Zhu, Jili Chen, and Jibo Zhou. "Influence of refractive error on pupil diameters in highly myopic eyes with implantable collamer lenses." European Journal of Ophthalmology 30, no. 6 (July 15, 2019): 1328–34. http://dx.doi.org/10.1177/1120672119863716.
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Purpose: To investigate the influence of refractive error on pupil diameters in highly myopic eyes with implantable collamer lenses. Setting: Shanghai, China. Design: A prospective consecutive observational study. Methods: Sixty-six eyes of 66 patients that underwent ICL V4c implantation were included. Pupil diameters before and 1 week, 1 month, and 3 months after surgery were measured using an automatic pupillometry system (MonCv3; Metrovision, Pérenchies, France) under four standardized illumination conditions: 0, 1, 10, and 100 cd/m2. The correlations between changes in pupil diameter and spherical equivalent values and patient age were investigated. Results: Based on preoperative spherical equivalent values, included eyes were divided into a high-myopia group (–6.3 to −9.9 D (diopters)) and a super-high-myopia group (–10 to −20 D). Pupil sizes remained unchanged after surgery in the high-myopia group and decreased at 1 and 10 cd/m2 in the super-high-myopia group. A between-group comparison showed that pupils were significantly smaller in the super-high-myopia group 1 week postoperatively under all illumination conditions and remained smaller at 1 month and 3 months under 1 and 10 cd/m2 lighting conditions. Preoperative spherical equivalent values were significantly correlated with the percent decrease in pupil diameter 1 week postoperatively under 0, 1, and 10 cd/m2 illumination conditions; the greater the degree of myopia, the greater the reduction in pupil diameter. Conclusion: Preoperative refractive error significantly affects pupil diameter in highly myopic eyes after implantable collamer lens implantation. Pupils of super highly myopic eyes remained smaller than preoperative levels under mesopic conditions after implantable collamer lens implantation.
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Bourdel-Marchasson, Isabelle, Rita Ostan, Sophie C. Regueme, Alessandro Pinto, Florence Pryen, Zoubida Charrouf, Patrizia A. d’Alessio, et al. "Quality of Life: Psychological Symptoms—Effects of a 2-Month Healthy Diet and Nutraceutical Intervention; A Randomized, Open-Label Intervention Trial (RISTOMED)." Nutrients 12, no. 3 (March 18, 2020): 800. http://dx.doi.org/10.3390/nu12030800.
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Depression symptoms and lower health-related quality of life (HRQoL) are associated with inflammation. This multicenter dietary intervention was shown to reduce inflammation in older people. This was the main outcome. Here, we describe the effects on HRQoL, anxiety, and depressive symptoms according to inflammation status. Overall, 125 healthy older subjects (65–80 year) were recruited (Italy, France, and Germany) and randomized into four arms (A, Healthy diet (HD); B, HD plus De Simone Formulation probiotic blend; C, HD plus AISA d-Limonene; D, HD plus Argan oil). The HD was weight maintaining, rich in antioxidant vitamins, polyphenols, polyunsaturated fatty acids (n6: n3 ratio = 3:1), and fiber. Data on inflammatory parameters, mental (MCS) and physical (PCS) component summaries of HRQoL (SF−36), anxiety symptoms (STAI state), and depressive symptoms (CES-D) were collected before and after 56 days of intervention. Body fat mass proportion (BFM) was considered a co-variable. A decrease of CES-D score was seen in the four arms (A: −40.0%, p = 0.001; B: −32.5%, p = 0.023; C: −42.8%, p = 0.004; and D: −33.3%, p = 0.21). Within the subgroups of subjects with medium/high inflammation a similar decrease in CES-D score occurred in all groups (A: −44.8%, p = 0.021; B, −46.7%, p = 0.024; C, −52.2%, p = 0.039; D, −43.8%, p = 0.037). The effect of interventions on CES-D was not related to baseline inflammation. MCS-HRQoL improved in A and C. There was no change in anxiety or PCS-HRQoL. In this trial with no control group, a decrease in depressive symptoms in healthy older volunteers was observed after a 2-month healthy diet intervention, independently of inflammation but with possible limitations due to participation.
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Semane, N., V. H. Peuch, S. Pradier, G. Desroziers, L. El Amraoui, P. Brousseau, S. Massart, B. Chapnik, and A. Peuch. "On the extraction of wind information from the assimilation of ozone profiles in Météo–France 4-D-Var operational NWP suite." Atmospheric Chemistry and Physics 9, no. 14 (July 22, 2009): 4855–67. http://dx.doi.org/10.5194/acp-9-4855-2009.
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Abstract. By applying four-dimensional variational data-assimilation (4-D-Var) to a combined ozone and dynamics Numerical Weather Prediction model (NWP), ozone observations generate wind increments through the ozone-dynamics coupling. The dynamical impact of Aura/MLS satellite ozone profiles is investigated using Météo-France operational ARPEGE NWP 4-D-Var assimilation system for a period of 3 months. A data-assimilation procedure has been designed and run on 6-h windows. The procedure includes: (1) 4-D-Var assimilating both ozone and operational NWP standard observations, (2) ARPEGE transporting ozone as a passive-tracer, (3) MOCAGE, the Météo–France chemistry and transport model re-initializing the ARPEGE ozone background at the beginning time of the assimilation window. Using observation minus forecast statistics, it is found that the ozone assimilation reduces the wind bias in the lower stratosphere. Moreover, the Degrees of Freedom for Signal diagnostics show that the MLS data covering the 68.1–31.6 hPa vertical pressure range are the most informative and their information content is nearly of the same order as tropospheric humidity-sensitive radiances. Furthermore, with the help of error variance reduction diagnostics, the ozone contribution to the reduction of the horizontal divergence background-error variance is shown to be better than tropospheric humidity-sensitive radiances.
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Blanc, Jean-frederic, Caroline Laurendeau, Nadia Kelkouli, and Philippe Mathurin. "Treatment patterns and survival in patients with late-stage hepatocellular carcinoma in France: A retrospective database analysis." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 288. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.288.
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288 Background: The prognosis for patients with late-stage hepatocellular carcinoma (HCC) is poor, with only one systemic treatment option available for patients until 2017. Aim: To describe treatment patterns and survival of French patients following diagnosis of late-stage HCC (Barcelona Clinic Liver Cancer classification B, C or D), using a comprehensive nationwide claims database, SNDS. Methods: The SNDS database was searched from 1 January 2015 to 31 December 2017 for patients with a diagnosis of HCC (ICD-10: C220) and late-stage disease, defined by the identification of transcatheter arterial chemoembolization (TACE) or radioembolization (TARE), HCC systemic therapy and/or best supportive care (BSC). Patients were followed up for a maximum of 2 years. Results: 17,298 patients (mean age: 68.7 years (SD: 11.3), 82.6% male) were identified, with 72.4% diagnosed at late stage. During follow-up, 29.6% of patients were treated with TACE or TARE, and 27.1% received systematic therapy (sorafenib in 99.5% of cases). The median duration of systemic treatment was 7.9 (95% CI: 7.4-8.5) months. In 62.5% of cases, this treatment was discontinued at 12 months; this proportion fell to 40.3% when using mortality as a competitive risk. Survival since diagnosis of late stage HCC differed according to the type of first treatment received. Median overall survival was 23.7, 11.9, 7.4 and 1 month in patients initially receiving TACE, TARE, systemic therapy or no treatment, respectively. Conclusions: These results confirm the high clinical burden of late-stage HCC over this period and the need for second-line systemic treatments to improve patient outcomes.
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Schlaich, Almut E., Willem Bouten, Vincent Bretagnolle, Henning Heldbjerg, Raymond H. G. Klaassen, Iben H. Sørensen, Alexandre Villers, and Christiaan Both. "A circannual perspective on daily and total flight distances in a long-distance migratory raptor, the Montagu's harrier, Circus pygargus." Biology Letters 13, no. 6 (June 2017): 20170073. http://dx.doi.org/10.1098/rsbl.2017.0073.
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Long-distance migrants are particularly recognized for the distances covered on migration, yet little is known about the distances they cover during the rest of the year. GPS-tracks of 29 Montagu's harriers from breeding areas in France, The Netherlands and Denmark showed that harriers fly between 35 653 and 88 049 km yr −1 , of which on average only 28.5% is on migration. Mean daily distances during migration were 296 km d −1 in autumn and 252 km d −1 in spring. Surprisingly, males' daily distances during breeding (217 km d −1 ) were close to those during migration, whereas breeding females moved significantly less (101 km d −1 ) than males. In terms of flight distance, the breeding season seemed nearly as demanding as migration periods for males. During the six winter months, both sexes moved less (114 and 128 km d −1 for females and males, respectively) than during migration. Harriers therefore covered shorter daily distances during winter which might allow birds to compensate for the more demanding phases of migration and breeding.
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Mentaverri, Romuald, Jean-Claude Souberbielle, Gilles Brami, Christelle Daniel, and Patrice Fardellone. "Pharmacokinetics of a New Pharmaceutical Form of Vitamin D3 100,000 IU in Soft Capsule." Nutrients 11, no. 3 (March 26, 2019): 703. http://dx.doi.org/10.3390/nu11030703.
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Vitamin D deficiency is frequent in the general population and both subjects and health professionals could benefit from a broader range of vitamin D3 formulations. We conducted a single-dose, open-label, parallel-group, randomized bioequivalence study to compare a single dose of a newly developed vitamin D3 100,000 IU in a soft capsule (Group 1) with the reference drug vitamin D3 100,000 IU oral solution in ampoule (Group 2) in healthy volunteers over a four-month period. The primary endpoint was the area under the curve (AUC) of serum 25-hydroxyvitamin-D (25(OH)D) concentrations on Day 112. This study was conducted in France from February to June 2014 in 53 young adults with a mean age of 26.9 years. At baseline, low mean serum 25(OH)D levels were observed in both groups (10.6 ng/mL in Group 1 and 9.0 ng/mL in Group 2). On Day 112, the AUC of serum 25(OH)D concentration was 2499.4 ± 463.8 nmol/mL (7.8 ± 0.2 for LogAUC) for Group 1 and 2152.3 ± 479.8 nmol/mL (7.6 ± 0.2 for LogAUC) for Group 2. Bioequivalence of the two treatments was not demonstrated. Superiority of vitamin D3 100,000 IU soft capsule was observed with p = 0.029 for AUC and p = 0.03 for LogAUC using a non-parametric Wilcoxon test. The profile of the serum 25(OH)D concentration showed a significant difference in favor of Group 1 on Days 1, 3, 7, 14 and 90. Mean serum 25(OH)D concentrations in Group 1 were between 20 and 30 ng/mL during the four-month period and under 20 ng/mL throughout the study in Group 2, except on Day 112. Mean Cmax for Group 1 was significantly higher (p = 0.002). Fourteen days were needed to reach Tmax by more than half the subjects in Group 1 compared to 45 days in Group 2. Both treatments were well tolerated, with no severe or related adverse events reported. In conclusion, the pharmacokinetic profile of the new formulation of vitamin D3 100,000 IU soft capsule is superior to that of the oral solution in ampoule. The new formulation increased serum 25(OH)D levels to above 20 ng/mL and maintained levels from 20 ng/mL to 30 ng/mL for four months in late winter and spring.
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Mota, Tounian, Guillou, Pierre, and Membré. "Estimation of the Burden of Iron Deficiency Anemia in France from Iron Intake: Methodological Approach." Nutrients 11, no. 9 (September 1, 2019): 2045. http://dx.doi.org/10.3390/nu11092045.
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: Dietary iron deficiency (ID) is the first nutritional deficiency in the world, in terms of disability adjusted life years (DALY). This nutritional deficiency may lead to anemia, especially among children, adolescents, and adult women. The aim of this study was to build an original probabilistic model to quantitatively assess the ID, the iron deficiency anemia (IDA) and the subsequent health burden in France expressed in DALY, per age class and gender. The model considered the distribution of absorbed iron intake, the iron requirement distribution established by the European Food Safety Authority and the iron status in France. Uncertainty due to lack of data and variability due to biological diversity were taken into account and separated using a second-order Monte Carlo procedure. A total of 1290 (95% CI = 1230–1350) IDA cases corresponding to 16 (95% CI = 11–20) DALY were estimated per 100,000 individuals per year. The major contributors to IDA burden were menstruating females aged from 25 to 44 years old. Then, a consumption scenario was built with ground beef as intake, an increase in red meat consumption to 100 g/d would not eliminate entirely the IDA burden. The quantitative methodology applied here for France could be reused for other populations.
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Pitlick, Jamie M., Ginelle A. Bryant, Michael W. Daly, Carrie F. Koenigsfeld, Nicholas Lehman, Kaitlin Brueggen, Alex McCormick, and Katlynn Wellington. "Real-World Evaluation of Dosing in Patients Converted From Insulin Glargine (Lantus) to Insulin Glargine (Basaglar)." Annals of Pharmacotherapy 54, no. 9 (February 10, 2020): 846–51. http://dx.doi.org/10.1177/1060028020903816.
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Background: Basaglar, insulin glargine (BGlar; Eli Lilly, Indianapolis, IN), a follow-on biologic, was developed after the patent for Lantus, insulin glargine (LGlar; Sanofi-Aventis, Paris, France) expired. Objective: To compare the dosing and hemoglobin A1C (A1C)-lowering effects of BGlar compared with LGlar in a real-world setting. Methods: Adult patients, at 5 clinics, with type 1 (T1DM) or type 2 diabetes mellitus (T2DM) who were converted from LGlar to BGlar were included in this retrospective observational study. The primary outcome compared mean basal insulin dose (U/d) from the date of conversion to 6 months. Basal insulin and total daily insulin doses were also compared from baseline to 3- and 12-months postconversion, as also change in A1C, body weight, and estimated monthly acquisition costs of basal insulin. Results: Of the 225 patients included, 56% were male, and 81% had T2DM. The mean conversion dose (U/d) of LGlar was 46.3 ± 32.7. There was no significant difference in the mean BGlar dose (U/d) at 6 months (45.9 ± 33.5; P = 0.52), nor was there a statistical difference at 3 or 12 months. There were no significant differences in change in A1C at any time point. The estimated monthly acquisition cost of BGlar was significantly less than that for LGlar at conversion ($286 vs $341, P < 0.001) and 6 months ($290 vs $351, P < 0.001) respectively. Conclusion/Relevance: The results of this retrospective study suggest that BGlar resulted in similar glycemic outcomes compared with LGlar in a real-world setting and may be a preferable option in a value-based health care environment.
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Keckhut, P., A. Hauchecorne, S. Bekki, A. Colette, C. David, and J. Jumelet. "Evidences of thin cirrus clouds in the stratosphere at mid-latitudes." Atmospheric Chemistry and Physics Discussions 5, no. 3 (June 21, 2005): 4037–55. http://dx.doi.org/10.5194/acpd-5-4037-2005.
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Abstract. This study is devoted to the possible presence of cirrus clouds in the stratosphere. Three months of lidar data collected in the south of France (44° N) for detection of stratospheric cirrus are carefully analyzed. Most of the cirrus clouds appear to be located in the troposphere below the dynamical tropopause even when the cloud top is close to the thermal tropopause. Two cirrus are found to be unambiguously located well above the local dynamical tropopause. According to high-resolution PV advection calculations, these two clouds are observed inside air masses that originate from the tropical regions and are then transported rapidly to mid-latitudes through isentropic transport. The air mass history for one case is investigated with a 3-D trajectory model. The back-plumes indicate that the air mass, moist with respect to typical stratospheric air, was transported from the subtropical troposphere to the lowermost stratosphere in 4 days before detection above France. A continuous cooling of 5–10° along the trajectory took place during its transit. This cooling could have been partly responsible for the thin cirrus layer detected.
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Faure, Ghislain, Philippe Chambon, and Pierre Brousseau. "Operational Implementation of the AROME Model in the Tropics: Multiscale Validation of Rainfall Forecasts." Weather and Forecasting 35, no. 2 (March 16, 2020): 691–710. http://dx.doi.org/10.1175/waf-d-19-0204.1.
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Abstract Météo-France runs operationally, for the needs of several overseas regions in the tropical belt, five numerical weather prediction configurations, based on the convection-permitting model AROME and called the AROME-OM system. These configurations use the high-resolution model [Integrated Forecasting System (IFS)] from the European Centre for Medium-Range Weather Forecasts (ECMWF) for both initialization and lateral forcing. In this study, the performance of the AROME-OM system for rainfall forecasting is compared to the one of ECMWF IFS. The validation uses spatialized rainfall estimates over a 24-h time period at two time scales (daily and annual), from both satellite and ground-based instruments. It has been performed over a 10-month period and across five tropical domains. The intercomparison demonstrates consistent signals across domains and scales. The added value of the AROME-OM system compared to ECMWF IFS is shown for rain/no-rain discrimination and for rain accumulations larger than 10 mm day−1. The AROME-OM system also shows a better ability to forecast realistic rain patterns over these tropical regions. The main weakness found is for an intermediate range of rain accumulations, from 1 to 10 mm day−1, for which the ECMWF IFS forecasts slightly outperform the AROME-OM system forecasts.
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Morgan, Julian, and Nigel Pain. "The World Economy." National Institute Economic Review 156 (May 1996): 28–54. http://dx.doi.org/10.1177/002795019615600103.
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Economic growth slowed in most of the major industrialised countries over the course of last year. The slowdown has been particularly apparent in continental Europe, with GDP falling in the fourth quarter in Germany, France and Italy. Early indications suggest that activity has been subdued in the first quarter of this year, with industrial production declining in Germany, Spain and Sweden, the provisional UK figures recording the lowest per quarter growth since 1992, and a continued deterioration apparent in indicators of the general business climate in Europe. We have made a significant downward adjustment to our previous forecasts for Europe, with EU-wide GDP now projected to rise by only 1½ per cent this year, after growth of 2½ per cent in 1995. We expect growth to pick-up over the course of the year as the contractionary effects of ongoing inventory adjustment come to an end and as the effects from a more relaxed monetary stance begin to outweigh those from ongoing fiscal consolidation. Recent currency movements should help to stimulate external demand in Germany and France, with the D-mark having depreciated against the US dollar by around 7 per cent over the past four months. Private sector expenditure is also likely to benefit from the recent sustained appreciation of equity prices in most national stockmarkets, with prices at the end of April having risen by over 11 per cent in Germany, France, Italy and Spain since the beginning of the year.
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Keckhut, P., A. Hauchecorne, S. Bekki, A. Colette, C. David, and J. Jumelet. "Indications of thin cirrus clouds in the stratosphere at mid-latitudes." Atmospheric Chemistry and Physics 5, no. 12 (December 16, 2005): 3407–14. http://dx.doi.org/10.5194/acp-5-3407-2005.
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Abstract. This study is devoted to the possible presence of cirrus clouds in the stratosphere. Three months of lidar data collected in the south of France (44° N) for detection of stratospheric cirrus are carefully analyzed. Most of the cirrus clouds appear to be located in the troposphere below the dynamical tropopause even when the cloud top is close to the thermal tropopause. Ten cirrus cases are found to be unambiguously located above the local dynamical tropopause according to high-resolution PV advection calculations. The highest cloud detected above the local tropopause (nearly 3 km above) is observed inside air masses that originate from the sub-tropical regions and are then transported rapidly to mid-latitudes through isentropic transport. The details of the air mass history is described with a 3-D trajectory model. The back-plumes indicate that the air mass, moist with respect to typical stratospheric air, was transported from the subtropical troposphere to the lowermost stratosphere in 4 days before detection above France. A continuous cooling of 5–10° along the trajectory took place during its transit. This cooling could have been partly responsible for the thin cirrus layer detected.
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Auriacombe, Marc, Perrine Roux, Laélia Briand Madrid, Sébastien Kirchherr, Charlotte Kervran, Carole Chauvin, Marie Gutowski, et al. "Impact of drug consumption rooms on risk practices and access to care in people who inject drugs in France: the COSINUS prospective cohort study protocol." BMJ Open 9, no. 2 (February 2019): e023683. http://dx.doi.org/10.1136/bmjopen-2018-023683.
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IntroductionThe high prevalence of hepatitis C and the persistence of HIV and hepatitis C virus (HCV) risk practices in people who inject drugs (PWID) in France underlines the need for innovative prevention interventions. The main objective of this article is to describe the design of the COSINUS cohort study and outline the issues it will explore to evaluate the impact of drug consumption rooms (DCR) on PWID outcomes. Secondary objectives are to assess how DCR (a) influence other drug-related practices, such as the transition from intravenous to less risky modes of use, (b) reduce drug use frequency/quantity, (c) increase access to treatment for addiction and comorbidities (infectious, psychiatric and other), (d) improve social conditions and (e) reduce levels of violence experienced and drug-related offences. COSINUS will also give us the opportunity to investigate the impact of other harm reduction tools in France and their combined effect with DCR on reducing HIV-HCV risk practices. Furthermore, we will be better able to identify PWID needs.Methods and analysisEnrollment in this prospective multi-site cohort study started in June 2016. Overall, 680 PWID in four different cities (Bordeaux, Marseilles, Paris and Strasbourg) will be enrolled and followed up for 12 months through face-to-face structured interviews administered by trained staff to all eligible participants at baseline (M0), 3 month (M3), 6 month (M6) and 12 month (M12) follow-up visits. These interviews gather data on socio-demographic characteristics, past and current drug and alcohol consumption, drug-use related practices, access to care and social services, experience of violence (as victims), offences, other psychosocial issues and perception and needs about harm reduction interventions and services. Longitudinal data analysis will use a mixed logistic model to assess the impact of individual and structural factors, including DCR attendance and exposure to other harm reduction services, on the main outcome (HIV-HCV risk practices).Ethics and disseminationThis study was reviewed and approved by the institutional review board of the French Institute of Medical Research and Health (opinion number: 14–166). The findings of this cohort study will help to assess the impact of DCR on HIV-HCV risk practices and other psycho-social outcomes and trajectories. Moreover, they will enable health authorities to shape health and harm reduction policies according to PWID needs. Finally, they will also help to improve current harm reduction and therapeutic interventions and to create novel ones.
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Papakostas, Konstantinos, Ioannis Tiganitis, and Agis Papadopoulos. "Energy and economic analysis of an auditorium’s air conditioning system with heat recovery in various climatic zones." Thermal Science 22, Suppl. 3 (2018): 933–43. http://dx.doi.org/10.2298/tsci170916026p.
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In many heating, ventilation and air-conditioning (HVAC) applications, heat recovery devices are installed, aiming at reducing energy consumption. Especially in buildings requiring a high percentage of outside air for ventilation, there is a high potential for heat recovery from exhaust air. Climatic conditions are an important parameter which affects the recovered heat and the payback period of the heat recovery device. In this paper, a 250 person auditorium is used as a model to estimate the applicability of an air-to-air fixed-plate heat exchanger installed in the air handling unit of the HVAC system. The application is considered for four cities, representative of climatic zones A, B, C, D of Greece, which also represent typical Mediterranean climate conditions. Zone A, Crete and Southern Greece, is similar to Nicosia (Cyprus) and Palermo (Sicily), Zone B, with Athens, corresponds to Rome (Italy) and coastal Spain, Zone C with Thessaloniki is similar to the Toulon (France) and Split (Croatia) and Zone D, with its continental climate is more like Milan (Italy) and Lyon (France). An energy analysis with the modified bin method energy calculation was performed to calculate (a) the heating and cooling energy that can be recovered, (b) the reduction in HVAC equipment, and (c) the expected payback period. For the specific climatic conditions examined, it was proven that: heating energy consumption decreased by 31 to 40%, depending on occupancy, while electric energy consumption didn?t change notably; the payback period does not exceed 24 months, depending on climate zone and occupancy.
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Cardin, L., B. Delecolle, and B. Moury. "First Report of Cucumber mosaic virus and Turnip vein-clearing virus in Dichondra repens in France, Italy, and China." Plant Disease 93, no. 2 (February 2009): 201. http://dx.doi.org/10.1094/pdis-93-2-0201b.
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During surveys of Dichondra repens (kidneyweed, family Convolvulaceae) turfs in public gardens of the Franco-Italian Riviera from 1993 to 2003, leaf mosaic and yellow ringspot symptoms have been observed in Antibes, Menton, Nice, and Vallauris (France) and San Remo and La Mortola (Italy). Isolates from these six locations and from two locations in China (Shanghai and Kunming) have revealed the presence of Cucumber mosaic virus (CMV) based on the behavior of a range of manually inoculated plants (1), the observation of 30 nm isometric particles in semipurified extracts of inoculated Nicotiana tabacum ‘Xanthi’ plants with the electron microscope, and positive reactions in double antibody sandwich (DAS)-ELISAs with specific polyclonal antibodies. All isolates were shown to belong to group II of CMV isolates (3) by double-immunodiffusion analysis. CMV was previously identified in D. repens in California in 1972 (4). Following isolation from local lesions on Vigna unguiculata and multiplication in ‘Xanthi’ tobacco plants, two of the isolates were used to inoculate seedlings of D. repens manually or by Aphis gossypii aphids. Two months later, all inoculated plants showed symptoms similar to those previously observed and were positive in DAS-ELISA. In 2000, a D. repens sample collected in Antibes showing similar symptoms as above, induced necrotic local lesions in inoculated ‘Xanthi’ plants in 48 h, followed by systemic mosaic symptoms typical of CMV, therefore revealing the presence of a second virus. That virus was separated from CMV in apical, noninoculated leaves of Chenopodium quinoa and then used to inoculate a range of test plants. It was infectious in most plants of the families Solanaceae (including Cyphomandra betacea) and Brassicaceae, together with in Chenopodium amaranticolor, C. quinoa, Claytonia perfoliata, Convolvulus spp. ‘Belle de jour’, Digitalis purpurea, Gomphrena globosa, Ocimum basilicum, Plantago lanceolata, and Valerianella olitoria. It induced asymptomatic systemic infections in D. repens. Numerous, rod-shaped, 300 nm long particles were observed in sap extracts of infected plants with the electron microscope, suggesting the presence of a tobamovirus. A set of primers polyvalent for tobamoviruses (2) allowed the amplification of a DNA product of approximately 800 bp through reverse transcription-PCR performed with total RNA extracts from inoculated ‘Xanthi’ plants. The DNA product was cloned and sequenced (GenBank Accession No. EU927306) revealing that the virus belonged to a tobamovirus lineage including Ribgrass mosaic virus and viruses infecting cruciferous plants (Turnip vein-clearing virus [TVCV] and Youcai mosaic virus) and was closest to TVCV (95% amino acid identity; GenBank Accession No. NC_001873). To our knowledge, this is the first report of TVCV in D. repens. References: (1) L. Cardin et al. Plant Dis. 87:200, 2003. (2) A. Gibbs et al. J. Virol. Methods 74:67, 1998. (3) M. J. Roossinck. J. Virol. 76:3382, 2002. (4) L. G. Weathers and D. J. Gumpf. Plant Dis. Rep. 56:27, 1972.
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Ghanima, Waleed, Vibeke Almaas, Saad Aballi, Dorje Christina, and Per Morten Sandset. "A Fast Track Strategy for Managing Suspected Pulmonary Embolism (PE) in Outpatients." Blood 104, no. 11 (November 16, 2004): 1766. http://dx.doi.org/10.1182/blood.v104.11.1766.1766.
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Abstract Background: Several strategies for managing patients with suspected PE have been validated. However, most of these strategies are complicated, involving multiple rounds of tests, and are thus, time consuming, costly and difficult to apply in clinical practice. Aiming to introduce a simple, fast and cost-effective strategy, we adopted a new diagnostic approach combining clinical probability assessment, D-Dimer and multi-slice spiral CT (MSSCT) scanning. Aims: The aim of this study was to assess the safety and efficacy of this management strategy by a prospective outcome study with 3-month follow-up. Methods: 495 consecutive patients referred to the Emergency Department at Østfold Hospital, Fredrikstad, Norway, for suspected PE, between Feb 2002 and Dec 2003, were considered for inclusion. 63 (12.7%) patients were excluded and the final cohort consisted of 432 patients. Patients were managed by serial non-invasive testing starting with D-Dimer test. Normal plasma D-Dimer (Liatest, latex agglutination assay, Stago-France, cut-off <0.4 mg/L) was deemed to rule out PE in patients with low-intermediate clinical probability (CP). CP for PE was assessed according to the categories proposed by Hyers. Patients with normal D-Dimer, but with high CP, and patients with elevated D-Dimer proceeded to MSSCT scan. A 4-row detector spiral CT scan was used in the study (scans were done with 2.5 mm collimation, pitch of 1.25). If MSSCT diagnosis was inconclusive, bilateral compression ultrasonography was recommended followed by a perfusion scan and eventually pulmonary angiography if further verification was necessary. Patients with verified PE received anticoagulation according to the hospitals guidelines. The entire cohort were followed-up for 3 months. Results: Normal D-Dimer and low-intermediate CP ruled out PE in 100 patients (23.1%). Twenty patients had normal D-Dimer but high CP and proceeded to MSSCT. All proved negative for PE. A total of 332 patients underwent MSSCT examination. PE was diagnosed in 95 patients (22%) and was ruled out by negative MSSCT in 221 patients. In 16 patients (4.8%), MSSCT was inconclusive due to suboptimal contrast filling (n=7), artefacts (n=2), or uncertain peripheral emboli (n=7). In ten, interpretation was inconclusive but decision to anticoagulate was made by the attending physician. Compression ultrasonography was performed in three of those; two had positive findings for DVT. In the remaining six, anticoagulation was withheld. Five had undergone further examination with ultrasound; none had DVT. Pulmonary angiography was carried out in one and perfusion lung scan in another patient; both examinations were negative. The diagnostic algorithm yielded a definite diagnosis in 96.3% of the patients. Follow-up was successfully completed in 321 (98.1%) of the patients in whom anticoagulation was withheld. Five of 321 patients (1.5%) in whom the diagnostic algorithm ruled out PE died during the follow-up period. The cause of death was adjudicated as not related to PE in three and possibly related to PE in two. No patient developed venous thromboembolism during the 3 month follow-up period, resulting in a 3-month thromboembolic rate of 0%, 95%CI (0–1.1%). Conclusions: Our results compare favorably to the results reported in previous outcome studies, and confirm the safety and efficacy of this management strategy combining D-Dimer as a first step test followed by MSSCT as a single imaging test in patients with elevated D-Dimer.
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Gerotziafas, Grigorios T., Despina Fotiou, Patrick Van Dreden, Theodoros N. Sergentanis, Ismail Elalamy, Loula Papageorgiou, Matthieu Grusse, et al. "In Newly Diagnosed Multiple Myeloma Patients, Longer Procoagulant Phospholipid-Dependent Clotting Time, Higher Levels of P-Selectin, D-Dimers and Thrombin Generation Peak Are Associated with Increased Risk of Resistance to Treatment: Results of the Prospective Roadmap-MM Study." Blood 132, Supplement 1 (November 29, 2018): 2014. http://dx.doi.org/10.1182/blood-2018-99-114871.
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Abstract Background:Despite an increasing number of approved therapies, multiple myeloma (MM) remains an incurable disease with frequent drug resistsance. Resistance-mediating alterations are preexisting in early disease, and it is the selective pressure of antitumor therapy that promotes their clonal expansion from baseline tumor heterogeneity. Cross-talk between monoclonal plasma cells, platelets and endothelial cells enhances hypercoagulability. The prospective, longitudinal observational study ROADMAP-MM CAT (PROspective Risk Assessment anD bioMArkers of hyPercoagulability for the identification of patients with Multiple Myeloma at risk for Cancer Associated Thrombosis) was designed to explore alternative strategies for the development of risk stratification tools in patients with MM. Aim: We explored cellular and plasma hypercoagulability in newly diagnosed chemotherapy naïve MM (NDMM) patients to identify relevant biomarkers that can be used to classify patients at high risk of resistance to anti-myeloma treatment. Methods: Symptomatic NDMM were enrolled. Patients on anticoagulant treatment were excluded from the study. Study end-point was response to treatment at 3 months (T1) according the the International Myeloma Working Group response criteria. "Resistance to antimyeloma treatment" was defined as progressive disease (PD), stable disease (SD) or minor response (MR) at 3 months post treatment initiation. Blood samples were collected at inclusion. Procoagulant phospholipid-dependent clotting time (Procoag-PPL®), tissue factor activity (TFa), thrombomodulin activity (TMa), factor VIIa, factor V (FV), antithrombin (AT), fibrin monomers (FM) and D-Dimers were measured with respective assays from Diagnostica Stago (Asnieres, France) on a STA-R® analyzer (Diagnostica Stago). Plasma levels of P-Selectin and heparanase were measured with ELISA Kits from Cusabio Biotech (from CliniSciencies, France) and R&D Systems (Lille France), respectively. Samples of platelet-poor plasma (PPP) were assessed for thrombin generation (TG) with the TF 5 pM PPP-Reagent® on Calibrated Automated Thrombogram (Stago, France). Univariate logistic regression analysis examined the associations between biomarkers and treatment resistance. The cut-off values for studied biomarkers were selected based on ROC analysis. Results A total of 144 patients were enrolled (age 66.0±12.0 yrs; 53% male). Distribution of disease stage was as follows: 32% ISS I, 23% ISS II, 45% ISS III. Bone disease was present in 71% of patients and 19% of patients had high risk cytogenetic lesions. Proteasome inhibitor (PI) based therapy was given to 64% of patients, immunomodulatory drug (IMiD) based therapy in 32% and 4% received other regimens. At 3 months, 64% of patients showed treatment "resistance". At the univariate logistic regression "resistance to treatment" was associated with longer Procoag-PPL (32.4% in patients with Procoag-PPL ≥41.7 sec vs. 12.3% in patients with Procoag-PPL <41.7 sec; OR=3.41, 95%CI: 1.45-8.03, p=0.005), higher levels of D-dimers (36.0% in patients with D-dimers ≥1.44 μg/ml vs. 14.9% in patients with D-dimers <1.44 μg/ml; OR=3.21, 95%CI: 1.43-7.22, p=0.005) and higher Peak in the thrombogram (28.1% in patients with Peak ≥181.66 nM vs. 12.5% in patients with Peak <181.66 nM; OR=2.73, 95%CI: 1.03-7.23, p=0.043). On the other hand, PD/SD/MR rate was inversely associated with P-selectin levels (14.5% in patients with ≥23477 pg/ml vs. 42.3% in patients with P-selectin <23477 pg/ml; OR=0.23, 95%CI: 0.08-0.65, p=0.005). Conclusion. The prospective ROADMAP-CAT multiple myeloma study demonstrates for the first time that biomarkers of hypercoagulablity may also be useful to identify patients likely to display resistance to treatment. Among a large number of hypercoagulability biomarkers PPL-ct, that reflects the amount of procoagulant microparticles present in plasma, thrombin generation and the levels P-Selectine and D-Dimers were found to be significant predictors of poor treatment response. A prospective trial is required to evaluate the potential role of these biomarkers in anti-myeloma treatment optimization. Disclosures Terpos: Novartis: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Genesis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding. Dimopoulos:Celgene: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Amgen: Honoraria.
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Sonneborn, George, and H. Warren Moos. "First Results from the FUSE Mission." Highlights of Astronomy 12 (2002): 545–91. http://dx.doi.org/10.1017/s1539299600014313.
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AbstractThe Far Ultraviolet Spectroscopic Explorer (FUSE) provides high-resolution spectroscopy at far ultraviolet (FUV) wavelengths (905–1187Å) of many astronomical objects in order to address fundamental questions related to the origin of the universe. FUSE, a cooperative project of the United States, Canada, and France, was launched in June 1999 for a three-year primary mission. The instrument sensitivity permits studies of many extragalactic sources at high spectral resolution. The key science drivers for the mission design are absorption-line spectroscopy of the ISM and IGM to investigate D/H, O VI, and molecular hydrogen abundances and distribution in the Galaxy and beyond to z ~ 0.3. Most of the observing time is available to Guest Investigators. This Joint Discussion summarizes some of the scientific results determined primarily from the first several months of FUSE observations.
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Motelay-Massei, A., D. Ollivon, B. Garban, and M. Chevreuil. "Atmospheric deposition of toxics onto the Seine Estuary, France: example of polycyclic aromatic hydrocarbons." Atmospheric Chemistry and Physics Discussions 2, no. 5 (September 17, 2002): 1351–69. http://dx.doi.org/10.5194/acpd-2-1351-2002.
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Abstract. Concentrations of Polycyclic Aromatic Hydrocarbons (PAH) were measured in precipitation samples on a weekly basis between March and October 2001, at four sites in the Seine Estuary (France). Mean concentrations of total PAHs (S 14 PAHs) ranged from 38 to 141 ng L-1. Fluoranthene, phenanthrene and pyrene were the dominant PAH compounds and were detected in each sample. The six potential carcinogenic PAHs accounted for 20 to 25% of the total PAH concentration in bulk deposition. The PAH signatures in bulk (wet and dry) deposition and surface water were also compared to investigate source/sink relationships. Seasonal patterns were observed with maximum loading occurring during the colder months of the studied period (March and April). Mean values of daily flux reported for S 14 PAHs ranged from 108 to 267 ng m-2 d-1. Spatial influences were also observed, indicating both localized and long-range atmospheric source inputs (controlled by hydroclimatic parameters).
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Walther, Regis, Julien Schaguene, Luc Hamm, and Eric David. "COUPLED 3D MODELING OF TURBIDITY MAXIMUM DYNAMICS IN THE LOIRE ESTUARY, FRANCE." Coastal Engineering Proceedings 1, no. 33 (December 14, 2012): 22. http://dx.doi.org/10.9753/icce.v33.sediment.22.
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Comprehensive 3D modeling efforts to understand salt intrusion and fine sediment dynamics in the Loire estuary started in 2006 and first results about the role of fluid mud on the hydrodynamic circulation through the bottom roughness was reported by Hamm and Walther during ICCE 2008. Recent progress since 2008 includes a) the coupling between the three modules (hydrodynamic, salinity, fine sediment transport) in order to let the fluid mud control the bottom roughness, b) the improvement of the vertical turbulence model enabling to reproduce strong stratifications observed during neap tides, c) a new empirical consolidation model calibrated against lab measurements and including the quantification of the erosion rate over a large range of bed dry densities and d) a new parameterization of the settling velocity function of the turbulence level of the flow. These developments have been validated over a period of five months in winter against field measurements of salinity and turbidity acquired through a permanent network of fixed sub-surface turbidimeters established in 2007. Additional validation against bathymetric measurements of the position of the fluid mud layer in the navigation channel is also presented.
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Salah-Mabed, Imene, Sarah Moran, Emmanuelle Perez, Guillaume Debellemanière, and Damien Gatinel. "Anatomical and Visual Outcomes after LASIK Performed in Myopic Eyes with the WaveLight® Refractive Suite (Alcon® Laboratories Inc., USA)." Journal of Ophthalmology 2020 (October 5, 2020): 1–18. http://dx.doi.org/10.1155/2020/7296412.
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Purpose. To evaluate changes in corneal anatomy and quality of vision following LASIK refractive surgery for mild to high myopia using the WaveLight® Refractive Suite (Alcon® Laboratories Inc., USA). Setting. Rothschild Foundation, Paris, France. Design. Prospective interventional case series. Methods. We examined 60 myopic eyes (average SE −4.5 D, from −9.3 to −0.75 D) of 30 patients from 21.3 to 38.7 years old. Pachymetry, keratometry, Q factor, corneal aberrations, visual acuity (VA), contrast sensitivity, dry eye assessment, and quality of vision were measured preoperatively, one day (D1), and 1, 3, and 6 months postoperatively. Results. 6 months postoperatively, keratometry became flatter, and the Q factor became more oblate (from −0.18 ± 0.08 to +0.19 ± 0.06). Pachymetry decreased by 117.9 ± 62.2 µm at D1 and increased by 37.87 ± 32.6 µm between D1 and M6. Refraction was emmetropic at D1 and remained stable thereafter. Six months after surgery, VA was slightly but nonsignificantly improved (<0.05 log MAR), whereas contrast sensitivity remained unchanged. Quality of vision was not affected by surgery and was more related to dry eye symptoms than to corneal HOAs (r2 = 0.49; p<0.001 vs. r2 = 0.03; p<0.001). Conclusions. LASIK surgery for moderate to high myopia, performed with the WaveLight® Refractive Suite, showed good postoperative outcomes, with demonstrated safety, predictability, efficiency, and stability. This is probably due to well-controlled spherical aberration and the use of large optical zones. Besides, we can assume that the patients’ quality of vision depends more on the postoperative dry eye disease generated by the laser than on the induced HOAs.
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Gao, Ya, Huijun Wang, and Dong Chen. "The Capability of ENSEMBLES Models in Predicting the Principal Modes of Pan-Asian Monsoon Precipitation." Journal of Climate 28, no. 21 (October 30, 2015): 8486–510. http://dx.doi.org/10.1175/jcli-d-15-0010.1.
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Abstract The predictability of the dominant modes of summer (June–September) precipitation in the pan-Asian monsoon region is evaluated based on 1-month-lead retrospective forecasts in five state-of-the-art coupled models from the ENSEMBLES project for the period 1979–2005. The results show that the models and their multimodel ensemble mean (MME) perform well in reproducing the interannual variability of the climatology and the spatiotemporal distribution of the first mode of summer precipitation in the pan-Asian monsoon region. The associated oceanic and atmospheric circulation indicators are also well captured, such as the spatiotemporal structures of the simultaneous El Niño–Southern Oscillation (ENSO) and Antarctic Oscillation in the Pacific Ocean (AAOSP). Moreover, the interannual variation of the preceding AAOSP can also be captured by some of the coupled models. For individual models, the ECMWF, Météo-France, and Met Office models exhibit better skill with respect to the first mode of summer precipitation in the pan-Asian monsoon region, which displays a tripole pattern from north to south over 80°–140°E. In addition, these models can successfully predict the intensity and location of the associated ENSO, as well as the simultaneous summer AAOSP distributions. By contrast, the prediction capabilities of the Leibniz Institute of Marine Sciences (IFM-GEOMAR) and Euro-Mediterranean Center for Climate Change (CMCC-INGV) models are relatively weaker. Furthermore, the predictions of the second mode of the summer precipitation in the pan-Asian monsoon region are investigated. Some of the ENSEMBLES models show good capability in predicting the spatiotemporal distribution of the second mode, owing to the successful prediction of the atmospheric convection activities over the tropical Indian Ocean.
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Pétré, Marie-Amélie, Bernard Ladouche, Jean-Luc Seidel, Romain Hemelsdaël, Véronique de Montety, Christelle Batiot-Guilhe, and Claudine Lamotte. "Hydraulic and geochemical impact of occasional saltwater intrusions through a submarine spring in a karst and thermal aquifer (Balaruc peninsula near Montpellier, France)." Hydrology and Earth System Sciences 24, no. 11 (November 27, 2020): 5655–72. http://dx.doi.org/10.5194/hess-24-5655-2020.
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Abstract. Submarine springs are a common discharge feature of the karst aquifers along the Mediterranean coast. In some instances, occasional and localized saltwater intrusions can occur through the submarine spring and negatively impact the quality of the groundwater resource. The hydraulic and geochemical behaviour of a submarine spring discharging into the Thau Lagoon just offshore of the Balaruc peninsula near Montpellier, France, has been characterized to determine the impacts of such phenomena to better understand the dynamics of a regional karst aquifer and improve its groundwater management. This work is based on both historical and new hydrogeological and geochemical data, illustrating six occasional saltwater intrusion events (from 1967 to 2014) in the Thau Lagoon area (southern France). Hydraulic perturbation of the aquifer is propagated instantly within the Balaruc-les-Bains peninsula and reaches a distance of about 5 km upgradient within 9 d. Comparison of hydraulic heads during seawater intrusion events in 2010 and 2014 indicates an aggravation of the phenomenon with an increase in hydraulic head variations. In contrast, isotopic tracers (87Sr∕86Sr, D/H, 18O∕16O) and rare earth elements (REEs) demonstrate that the geochemical impact of these inversac events is only observed at the local scale but is still perceptible several years after the event. For example, some of the thermal wells had not recovered their initial geochemical state 20 and 40 months after the last two inversac events (2010 and 2014, respectively), suggesting a geochemical legacy of this phenomenon within the complex karst system. By contrast, an adjacent deep karst compartment located south of the study area is not affected by the saltwater intrusion and is characterized by distinctly different hydrodynamic behaviour. Overall, this work on occasional and localized saltwater intrusions constitutes a key step in understanding the dynamics of this complex karstic and thermal aquifer and will support the management of the groundwater resource.
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Ádám, Zoltán, László Csaba, András Bakács, and Zoltán Pogátsa. "Book Reviews." Acta Oeconomica 56, no. 4 (December 1, 2006): 455–68. http://dx.doi.org/10.1556/aoecon.56.2006.4.5.
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István Csillag - Péter Mihályi: Kettős kötés: A stabilizáció és a reformok 18 hónapja [Double Bandage: The 18 Months of Stabilisation and Reforms] (Budapest: Globális Tudás Alapítvány, 2006, 144 pp.) Reviewed by Zoltán Ádám; Marco Buti - Daniele Franco: Fiscal Policy in Economic and Monetary Union. Theory, Evidence and Institutions (Cheltenham/UK - Northampton/MA/USA: Edward Elgar Publishing Co., 2005, 320 pp.) Reviewed by László Csaba; Piotr Jaworski - Tomasz Mickiewicz (eds): Polish EU Accession in Comparative Perspective: Macroeconomics, Finance and the Government (School of Slavonic and East European Studies, University College of London, 2006, 171 pp.) Reviewed by András Bakács; Is FDI Based R&D Really Growing in Developing Countries? The World Investment Report 2005. Reviewed by Zoltán Pogátsa
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Cardin, L., J. P. Onesto, and B. Moury. "First Report of Cucumber mosaic virus in Helleborus foetidus in France and Italy." Plant Disease 87, no. 10 (October 2003): 1263. http://dx.doi.org/10.1094/pdis.2003.87.10.1263b.
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Helleborus foetidus L. (bear's foot) is a perennial plant from the family Ranunculaceae that is common in chalky soils of southern and western Europe. It is grown in gardens for its palm-shaped leaves and early flowers. In 1995, yellow-to-white oak leaf and line patterns in leaves of H. foetidus plants were observed in Hunawihr (Alsace, France). The same symptoms were observed in plants in Entrevaux, Biot, and Gourdon (Provence-Alpes-Côte d'Azur, France) in 2000 and 2001, in Triora (Liguria, Italy) in 2002, and on cv. Western Flisk in a nursery in Nice (Provence-Alpes-Côte d'Azur, France) in 2002. Samples collected from these six locations contained six isolates that were further characterized. Sap extracted from symptomatic plants was mechanically inoculated onto Nicotiana tabacum cvs. Xanthi-nc and Samsun, Chenopodium quinoa, C. amaranticolor, Vigna unguiculata cv. Black, and Cucumis sativus cv. Poinsett. Symptoms exhibited by the inoculated plants indicated infection by Cucumber mosaic virus (CMV). Sap extracted from symptomatic plants reacted positively in double-antibody sandwich-enzyme-linked immunosorbent assays (DAS-ELISA) to antibodies raised against CMV (2). Isometric particles (approximately 30 nm) were observed with an electron microscope in crude sap preparations from infected plants. Following purification of the suspect virus from infected N. tabacum (2) and treatment with formaldehyde (1), each isolate was shown to belong to group II of CMV strains (1,3) by double-immunodiffusion analysis. Following isolation from local lesions on V. unguiculata, the Hunawihr isolate was grown in cv. Xanthi-nc plants and back-inoculated to 2-year-old uninfected seedlings of H. foetidus by aphids (Myzus persicae) or mechanical transmission. Mechanical transmissions were also performed with sap extracted from cv. Xanthi-nc plants infected with the D strain, which belongs to group I of CMV strains (3). Three months postinoculation, symptoms previously described in the original plants were observed in 3 of 10 mechanically inoculated plants and in 2 of 14 aphid-inoculated plants (Hunawihr isolate), whereas no symptoms could be seen in any of the six plants inoculated with the D strain. On the basis of DAS-ELISA, 7 of 10 plants mechanically inoculated and 7 of 14 plants aphid inoculated with the Hunawihr isolate were infected with CMV, whereas 3 of the 6 plants inoculated with the D strain were infected with CMV. To our knowledge, this is the first report that H. foetidus is a natural host for CMV. Beyond the direct impact of the disease induced by CMV on H. foetidus, this perennial and widespread plant species can be an important reservoir of CMV. References: (1) J. C. Devergne and L. Cardin. Ann. Phytopathol. 7:225, 1975. (2) J. C. Devergne et al. Ann. Phytopathol. 10:233, 1978. (3) M. J. Roossinck. J. Virol. 76:3382, 2002.
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Brenot, H., A. Walpersdorf, M. Reverdy, J. van Baelen, V. Ducrocq, C. Champollion, F. Masson, E. Doerflinger, P. Collard, and P. Giroux. "A GPS network for tropospheric tomography in the framework of the Mediterranean hydrometeorological observatory Cévennes-Vivarais (southeastern France)." Atmospheric Measurement Techniques 7, no. 2 (February 19, 2014): 553–78. http://dx.doi.org/10.5194/amt-7-553-2014.
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Abstract. The Mediterranean hydrometeorological observatory Cévennes-Vivarais (OHM-CV) coordinates hydrometeorological observations (radars, rain gauges, water level stations) on a regional scale in southeastern France. In the framework of OHM-CV, temporary GPS measurements have been carried out for 2 months in autumn 2002, when the heaviest rainfall are expected. These measurements increase the spatial density of the existing permanent GPS network, by adding three more receivers between the Mediterranean coast and the Cévennes-Vivarais range to monitor maritime source of water vapour flow feeding the precipitating systems over the Cévennes-Vivarais region. In addition, a local network of 18 receivers covered an area of 30 by 30 km within the field of view of the meteorological radar. These regional and local networks of permanent and temporary stations are used to monitor the precipitable water vapour (PWV) with high temporal resolution (15 min). Also, the dense local network provided data which have been inverted using tomographic techniques to obtain the 3-D field of tropospheric water vapour content. This study presents methodological tests for retrieving GPS tropospheric observations from dense networks, with the aim of assessing the uncertainties of GPS retrievals. Using optimal tropospheric GPS retrieval methods, high resolution measurements of PWV on a local scale (a few kilometres) are discussed for rain events. Finally, the results of 3-D fields of water vapour densities from GPS tomography are analysed with respect to precipitation fields derived from a meteorological radar, showing a good correlation between precipitation and water vapour depletion areas.
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LARSEN, M. "Prospects for controlling animal parasitic nematodes by predacious micro fungi." Parasitology 120, no. 7 (May 2000): 121–31. http://dx.doi.org/10.1017/s0031182099005739.
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Resistance against anthelmintics is widespread, particularly in parasitic nematode populations of small ruminants. Several new techniques or supplements have been developed or are under investigation. Biological control (BC) is one of these new methods. The net-trapping predacious fungus Duddingtonia flagrans produces thick walled resting spores, chlamydospores, which are able to survive passage through the gastrointestinal tract of cattle, horses, sheep and pigs. Under Danish climatic conditions it has been shown that the number of parasite larvae on pasture and the worm burden of the grazing animals is significantly reduced when animals are fed spores during the initial 2–3 months of the grazing season. Work with D. flagrans in France, Australia, USA, and Mexico has confirmed the strong BC potential of this fungus. Today much work is going into development of suitable delivery systems for grazing livestock worldwide. Ultimately, BC should be implemented in integrated parasite control strategies, both in conventional and organic livestock production.
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Yam, Kai Chi, Joshua Conrad Jackson, Christopher M. Barnes, Jenson Lau, Xin Qin, and Hin Yeung Lee. "The rise of COVID-19 cases is associated with support for world leaders." Proceedings of the National Academy of Sciences 117, no. 41 (September 24, 2020): 25429–33. http://dx.doi.org/10.1073/pnas.2009252117.
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COVID-19 has emerged as one of the deadliest and most disruptive events in recent human history. Drawing from political science and psychological theories, we examine the effects of daily confirmed cases in a country on citizens’ support for the political leader through the first 120 d of 2020. Using three unique datasets which comprise daily approval ratings of head of government (n= 1,411,200) across 11 world leaders (Australia, Brazil, Canada, France, Germany, Hong Kong, India, Japan, Mexico, the United Kingdom, and the United States) and weekly approval ratings of governors across the 50 states in the United States (n= 912,048), we find a strong and significant positive association between new daily confirmed and total confirmed COVID-19 cases in the country and support for the heads of government. These analyses show that political leaders received a boost in approval in the early months of the COVID-19 pandemic. Moreover, these findings suggest that the previously documented “rally ‘round the flag” effect applies beyond just intergroup conflict.
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Zhao, Zhanlin, Sylvain Michée, Jean-François Faure, Christophe Baudouin, and Antoine Labbé. "Effects of SMILE Surgery on Intraocular Pressure, Central Corneal Thickness, Axial Length, Peripapillary Retinal Nerve Fiber Layer, and Macular Ganglion Cell Complex Thickness." Journal of Ophthalmology 2020 (November 27, 2020): 1–6. http://dx.doi.org/10.1155/2020/4934196.
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Purpose. To evaluate the change in intraocular pressure (IOP), central corneal thickness (CCT), axial length, peripapillary retinal nerve fiber layer (RNFL) thickness, and macular ganglion cell complex (GCC) thickness after small incision lenticule extraction (SMILE) surgery. Methods. This prospective observational study was conducted in Espace Nouvelle Vision, Ophthalmological Clinic, Paris, France. Fifty eyes of 25 patients were enrolled in this study and underwent SMILE surgeries. IOP, central corneal thickness (CCT), axial length (AL), peripapillary RNFL thickness, and macular GCC thickness were measured before and at 3 months after SMILE. Results. The mean preoperative spherical equivalent was −3.15 ± 1.50 diopters (D), and the mean postoperative value was 0.15 ± 0.28 D. After SMILE surgery, IOP decreased from 15.03 ± 2.79 mmHg to 11.02 ± 2.73 mmHg and 10.02 ± 2.21 mmHg at 1 and 3 months, respectively ( P < 0.01 for both comparisons). The mean decrease in measured IOP as a function of ablation depth was 0.065 ± 0.031 mmHg/μm. CCT decreased from 545.98 ± 26.61 μm to 478.40 ± 30.26 μm after SMILE surgery ( P < 0.01 ). AL decreased from 24.80 ± 0.84 mm to 24.70 ± 0.83 mm ( P < 0.01 ). There was no statistically significant change in mean peripapillary RNFL or mean GCC thickness after SMILE surgery. Conclusions. SMILE surgery modified IOP measurement, CCT, and AL but did not change peripapillary RNFL and macular GCC thicknesses. The postoperative drop in measured IOP might be explained by the decreased CCT. An accurate re-evaluation of AL should be performed before cataract surgery among post-SMILE patients.
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Chaari, Mourad, Grigoris T. Gerotziafas, Lilia Ghorbal, Vassiliki Galea, Ines Ayadi, Patrick Van Dreden, Mariette Adam, et al. "Hypercoagulability Linked to Breast Cancer Depends On the Stage and the Duration of the Tumor Evolution." Blood 120, no. 21 (November 16, 2012): 3396. http://dx.doi.org/10.1182/blood.v120.21.3396.3396.
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Abstract Abstract 3396 Introduction The risk of venous thromboembolic event (VTE) in patients with cancer is particularly increased compared to normal population. It seems that this risk depends largely on the characteristics of the tumor, such as its site or its stage of evolution, and the anti-neoplasic treatment. The capacity of thrombin generation and D-dimers levels are two biological markers proposed for the stratification of the risk of VTE. We have analyzed thrombin generation and D-dimers levels in patients with breast cancer as markers of a hypercoagulable state, depending on the stage and the period of the tumor evolution. Materials and methods It is a prospective study carried out at the day hospital of the carcinology department of the University Hospital H. Bourguiba in Sfax-Tunisia, including patients with breast cancer at different stages of evolution and different period elapsed since cancer diagnosis. At the time of inclusion, a venous citrated blood sampling (3.2%) was made. The test of thrombin generation was carried out according to the technique of Calibrated Automated Thrombogram assay (CAT®, Diagnostica Stago, Asnières, France). The parameters of the thrombogram were analyzed: endogenous thrombin potential (ETP), peak of thrombin (peak) and mean rate index (MRI). D-dimers were measured using the STA®- Liatest® D-Di assay (Diagnostica-Stago). Results Sixty one patients were included. Their average age is 51.8 ± 10.9 years old. Depending on the stage of cancer disease, 3 sub-groups of patients were distinguished: early local stage (T1, n=16), advanced local stage (T2-T4; n=25) and metastatic stage (M; n=20). Considering the time passed since diagnosis, we have different periods : inferior to 6 months (n=26), 6 to 12 months (n=7), 12 to 36 months (n=15) and more than 36 months (n=13). The analysis of the different parameters of the thrombogram depending on the cancer stage revealed that patients with an advanced local stage and a period elapsed since cancer diagnosis inferior to 6 months had significantly higher values of ETP and thrombin peak (1708±247 nM.min and 379±80 nM) compared to those with an older cancer (1404±308 nM.min, p<0.05 and 321±52, p<0.05 respectively). The study of D-dimers levels depending on the stage of cancer revealed an increase of this marker according to the severity of the cancer. Patients with metastatic stages have the highest levels (1937 ± 2468 μg/l) compared to patients with an early local stage (615±456 μg/l, p<0.05 ). In addition, the period of time since cancer diagnosis does not have any influence on D-dimers levels. Conclusion The evaluation of the capacity of thrombin generation and D-dimers levels showed that these biological parameters are indeed linked to the stage of evolution and the severity of breast cancer. Therefore, these biological tests underlying an hypercoagulable state have a potential and complementary importance to stratify the risk of VTE in this context. This should be confirmed by the prospective follow-up of the thromboembolic risk existing in the patients with breast cancer. Disclosures: No relevant conflicts of interest to declare.
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Noltie, H. J. "Notes relating to the Flora of Bhutan: XXI. Carex (Cyperaceae)." Edinburgh Journal of Botany 50, no. 2 (July 1993): 185–206. http://dx.doi.org/10.1017/s0960428600002560.
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The following new species and subspecies are described: Carex burttii Noltie, C. griersonii Noltie, C. nigra (L.) Reich, subsp. drukyulensis Noltie, C. schlagintweitiana Boeck. subsp. deformis Noltie, C. speciosa Kunth subsp. dilatata Noltie, C. speciosa subsp. pinetorum Noltie, C. laeta Boott subsp. gelongii Noltie. The new combination C. fusiformis Nees subsp. finitima (Boott) Noltie is made. C. sikkimensis C.B. Clarke is reduced to the synonymy of C. fucata Boott ex C.B. Clarke, and C. praelonga C.B. Clarke to that of C. teres Boott. Notes are provided on C. notha Kunth, C. inclinis C.B. Clarke, C. inanis C.B. Clarke and C. alopecuroides D. Don ex Tillooh & Taylor. C. fastigiata Franch. and C. radicatis Boott are reported new to Bhutan and C. montis-everestii Kük. new to Sikkim. Lectotypes are designated for C. fucata, C. sikkimensis, C. teres, C. praelonga, C. setigera γ humilis, C. inanis. C. fusiformis, C. finitima, C. alopecuroides, C. chlorostachys D. Don ex Tilloch & Taylor and C. alopecuroides var. chlorostachya C.B. Clarke. A phytogeographical checklist is provided for species occurring in the Flora of Bhutan area.
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Brenot, H., A. Walpersdorf, M. Reverdy, J. van Baelen, V. Ducrocq, C. Champollion, F. Masson, E. Doerflinger, P. Collard, and P. Giroux. "A GPS network for tropospheric tomography in the framework of the Mediterranean hydrometeorological observatory Cévennes-Vivarais (South-Eastern France)." Atmospheric Measurement Techniques Discussions 6, no. 6 (November 6, 2013): 9513–78. http://dx.doi.org/10.5194/amtd-6-9513-2013.
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Abstract. The Mediterranean hydrometeorological observatory Cévennes-Vivarais (OHM-CV) coordinates hydrometeorological observations (radars, rain gauges, water level stations) on a regional scale in South-Eastern France. In the framework of OHM-CV, temporary GPS measurements have been carried out for 2 months in autumn 2002, when the heaviest rainfall are expected. These measurements increase the spatial density of the existing permanent GPS network, by adding three more receivers between the Mediterranean coast and the Cévennes-Vivarais range to monitor maritime source of water vapour flow feeding the precipitating systems over the Cévennes-Vivarais region. In addition, a local network of 18 receivers covered an area of 30 by 30 km within the field of view of the meteorological radar. These regional and local networks of permanent and temporary stations are used to monitor the precipitable water vapour (PWV) with high temporal resolution (15 min). Also, the dense local network provided data which have been inversed using tomographic techniques to obtain the 3-D field of tropospheric water vapour content. This study presents methodological tests for retrieving GPS tropospheric observations from dense networks, with the aim of assessing the uncertainties of GPS retrievals. Using the optimal tropospheric GPS retrieval methods, high resolution measurements of PWV on a local scale (a few kilometres) are discussed for rain events. Finally, the results of 3-D fields of water vapour densities from GPS tomography are analysed with respect to precipitation fields derived from a meteorological radar, showing a good correlation between precipitation and water vapour depletion areas.
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Demirkan, H. B., O. Yilmaz, C. Çoker, M. Gümüstekin, J. Batu, M. Bülbül, T. Canda, and M. Alakavuklar. "The influence of partial hepatectomy (PH) on pharmacokinetics of docetaxel (D) in sprague-dawley rats (SDR) with experimental mammary neoplasm models (EMNM)." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 12021. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.12021.
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12021 Background: Docetaxel (Taxotere-Aventis) is used in the treatment of breast, lung, head and neck, prostate and ovarian cancers. Recently, PH for isolated hepatic metastases of breast cancer has been reported in Japan and France. PH is an experimental model of hepatic insufficiency. Therefore we aimed to study the influence of PH on pharmacokinetics of D in SDR with EMNM. Methods: After the approval of Local Ethical Commitee on Laboratory Animal Researches, 40 female 50-day-old SDR were injected with 50 mg/kg body weight N-nitroso-N-methylurea (NMU) in 09% NaCL solution intraperitoneally. 5 female 50-day-old SDR were only injected with 09% NaCL solution intraperitoneally. After 6-months follow-up period for the formation of EMNM, 8 rats in the Group D+H were hepatectomized partially. Baseline venous blood samples were taken. 24 hours after PH, 6 rats were alive. There were 8 rats in the Group D (without hepatectomy). Before chemotherapy and 1 hour after intravenous infusion of 5 mg/kg body weight D, blood samples were taken for biochemical analyses from both groups. 5., 15., 30. minutes and 1., 2., 4., 5. hours after D infusion, arterial blood samples were taken for pharmacokinetic analyses. Biochemical and Pharmacokinetic tests (BPT) were done by auto-analyzer Hitachi Modular Analytic and HPLC (High Performance Liquid Chromatography) respectively. Area under the concentration-time curve [AUC (0–60)] was determined for each group. Statistical analyses were done by SPSS 11.0 for Windows at the 5% significance level. Results: PH affected liver functions and serum albumin levels negatively (p = 0.028). Although D infusion didn’t affect serum ALT and bilirubine levels, low serum albumin was detected 1 hour after chemotherapy in both groups (p= 0.028 and p= 0.030). AUC(0–60) of plasma D in hepatectomized rats were greater than the other group (p = 0.015). Conclusion: During the treatment of cancer patients in posthepatectomy period with taxanes (D), dose adjustment must be done. In both groups, statistically significant low serum albumin after D infusion may be as a result of decreased intertitial fluid pressure, albumin extravasation and edema formation caused by taxanes. Physiological and preventive studies are needed. No significant financial relationships to disclose.
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Cardin, L., and B. Moury. "First Report of Alfalfa mosaic virus on Rhamnus alaternus in France." Plant Disease 90, no. 8 (August 2006): 1115. http://dx.doi.org/10.1094/pd-90-1115c.
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Rhamnus alaternus L. (evergreen buckthorn), family Rhamnaceae, is a small, hardy shrub from Mediterranean regions grown for its ornamental persistent green or variegated foliage. Chlorotic oak leaf or ringspot symptoms on R. alaternus leaves have been observed in southern France (Bellegarde, Gard department in 1998; Fanjaux, Aude department in 2000; and Saint-Jean-Cap-Ferrat, Alpes-Maritimes department in 2002). Samples from these three localities revealed the presence of Alfalfa mosaic virus (AMV) due to (i) the symptoms observed in an inoculated diagnostic host range previously described (1), (ii) observation of typical bullet-shaped virion particles of different sizes with transmission electron microscopy, (iii) nonpersistent transmission to Nicotiana tabacum cv. Xanthi-nc by Myzus persicae, and (iv) positive reaction in double-antibody sandwich-enzyme-linked immunosorbent assays (DAS-ELISA) to antibodies raised against AMV (gift of G. Marchoux). In addition, in Fanjaux, Viburnum tinus L. plants located close to the infected R. alaternus plants were also infected by AMV and exhibited typical intense calico mosaics (3). The close species, R. frangula L., was previously identified as a natural host for AMV in Italy (2). Following isolation from local lesions on Vigna unguiculata, the Fanjaux isolate was grown in cv. Xanthi-nc plants, where it induced a severe mosaic and stunting of the plants, and inoculated to 2-year-old virus-free R. alaternus plants either mechanically or with M. persicae (10 plants each). Plants were subsequently kept in an insect-proof greenhouse. At 8 and 12 months postinoculation, only one aphid-inoculated plant showed symptoms on young leaves and was AMV-positive in DAS-ELISA, while no mechanically infected plants were infected. This low infection level together with the rare observation of symptoms in natural conditions suggest that R. alaternus is not frequently infected by AMV. References: (1) L. Cardin and B. Moury. Plant Dis. 84:594, 2000. (2) F. Marani and L. Giunchedi. Acta Hortic. 59:97, 1976. (3) N. Plese and D. Milicic. Phytopathol. Z. 72:219, 1971.
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Angelergues, Antoine, Denis Maillet, Aude Flechon, Mustafa Ozguroglu, Florence Mercier, Aline Guillot, Sylvestre Le Moulec, et al. "Prognostic factors of survival in patients with metastatic castration resistant prostate cancer (mCRPC) treated with cabazitaxel: Sequencing might matter." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 5063. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.5063.
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5063 Background: Recently, several new drugs have demonstrated an overall survival (OS) benefit in patients (pts) with mCRPC. Their use must be optimized to maximize patient outcomes. We evaluated prognostic factors of OS in mCRPC pts treated with cabazitaxel (C), a new taxane developed to overcome docetaxel (D) resistance. Methods: Records of 125 consecutive mCRPC pts (median 67 yrs) treated with C (after D) were retrospectively collected in 9 centers (France, n=8; Turkey, n=1). Baseline characteristics, disease history, PSA response, OS and radiological and/or clinical progression-free survival (PFS) were collected. The influence of selected variables on OS was analyzed by multivariate logistic regression. Results: At C initiation, 83.3% of pts were ECOG 0-1, 50.8% had an initial Gleason score of 8-10, 62.9% had pain and 84.8% had radiological or clinical progression. Median duration of response to first-line androgen deprivation therapy was 20 months (mo) and 22% received ≥2 prior D lines. New hormonal agents (abiraterone or enzalutamide) were given before C in 33% of pts and after C in 16%. Median number of C cycles received was 6 (range 2-14). A PSA decrease of ≥50% and ≥30% was reached in 41.3% and 48.8% of patients treated with C. Median OS from first C cycle was 13.3 mo and median clinical and/or radiological PFS was 6.5 mo. In multivariate analysis, OS was significantly reduced in pts with ECOG 2 (HR: 6.05), alkaline phosphatase ≥1.5 ULN (HR: 2.64), lymph node involvement (HR: 1.89). Conversely, OS was significantly prolonged in pts with ≥2 prior D lines (HR: 0.35), prior curative therapy (HR: 0.55), a PSA decrease ≥30% with C (HR: 0.21) and in pts treated with abiraterone/enzalutamide after C (HR: 0.37). Median OS from the first D dose was 65 mo in pts treated with abiraterone or enzalutamide after C versus 39 mo in pts receiving these agents before C. Conclusions: Patients with ≥ 2 prior D lines, PSA response ≥30% with C and treated with new hormonal agents after C experienced a prolonged OS. Conversely, intake of new hormonal agents before C rather than after was associated with a reduced OS from the first D dose. Prospective randomized trials are needed to confirm these results.
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Tourani, J. M., R. Levy, P. Colonna, B. Desablens, P. Y. Leprise, F. Guilhot, S. Brahimi, M. Belhani, N. Ifrah, and L. Sensebe. "High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin's disease." Journal of Clinical Oncology 10, no. 7 (July 1992): 1086–94. http://dx.doi.org/10.1200/jco.1992.10.7.1086.
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PURPOSE For patients with Hodgkin's disease (HD) who do not achieve complete response (CR), who experience a relapse within the first year of CR, and for those who have two or more relapses, the outcome is poor. Salvage chemotherapy regimens at conventional doses produce a CR rate that ranges from 10% to 50% and a 5-year disease-free survival (DFS) between 10% and 25%. On the other hand, high-dose chemotherapy regimens given in combination with bone marrow transplantation (BMT) produce a CR rate that ranges from 40% to 80% and a 3-year DFS of approximately 40%. We report the 5-year results of a prospective study in patients with refractory HD who were treated with three courses of intensive chemotherapy without BMT. PATIENTS AND METHODS Thirty-nine adult patients with refractory HD were treated with three courses of intensive chemotherapy. Each cycle of chemotherapy comprised vindesine 1 mg/m2/d in continuous intravenous (IV) infusion from day 1 to day 5; Adriamycin (doxorubicin; Roger Bellon Laboratories, Neuilly, France) 40 mg/m2/d in continuous IV infusion from day 1 to day 3; carmustine 140 mg/m2/d at day 3; etoposide 200 mg/m2/d from day 3 to day 5; and methylprednisolone 120 mg/m2/d from day 1 to day 5. After the third cycle of chemotherapy, irradiation (20 Gy) was performed whenever possible and depended on previous irradiation. RESULTS At the end of the treatment, 31 patients (79%) were in CR. Among these patients, 10 relapsed after a median time of 3 months. The overall 5-year survival rate was 46%. The freedom from progression (FFP) and the freedom from treatment failure (FFTF) rates were 48% and 43%, respectively. The main toxicities were hematologic (neutropenia and thrombocytopenia) and digestive. Four patients died due to treatment-related complications (two from septic shocks, one from respiratory insufficiency, and one from posttransfusional AIDS). CONCLUSION The results of this study seem to be comparable to those results obtained with high-dose chemotherapies with autologous BMT.
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Cardin, L., J. P. Onesto, and B. Moury. "First Report of Cucumber mosaic virus in Paeonia lactifera in France." Plant Disease 94, no. 6 (June 2010): 790. http://dx.doi.org/10.1094/pdis-94-6-0790c.
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Chinese peony (Paeonia lactiflora Pall.), a hardy ornamental plant of the family Paeoniaceae cultivated in gardens and for cut flower production, is frequently infected by Tobacco rattle virus (TRV) in the field. The virus usually induces severe mosaic and chlorotic ringspot symptoms in the leaves, decreasing the commercial value of cut flowers. TRV is routinely detected by mechanical inoculation onto Nicotiana tabacum cv Xanthi, where it induces typical necrotic local ringspots in 3 to 7 days, followed by a reverse transcription (RT)-PCR test (2). In 2004, Xanthi test plants inoculated with sap extracts from 4 of 36 P. lactiflora cv. Odile plants grown in a field plot in the region of Hyères (southeast France) showed systemic mosaic symptoms in addition to the TRV-typical response. In each case, Cucumber mosaic virus (CMV) was detected by the reactions of a range of inoculated plants (1), the observation of 30 nm isometric particles in crude leaf extracts with the electron microscope, and by positive reactions in double antibody sandwich (DAS)-ELISAs with specific polyclonal antibodies. In double-immunodiffusion analysis, these isolates were shown to belong to the group II of CMV isolates (3). ELISA of the peony plants confirmed the presence of CMV and revealed two additional infected plants in the spring of 2006. Following isolation from local lesions on Vigna unguiculata and multiplication in Xanthi tobacco plants, one of the isolates was used to inoculate manually or with Myzus persicae aphids 10 CMV-free plants of P. lactiflora cv. Odile obtained from meristem culture. Three months postinoculation, only three of the aphid-inoculated plants were CMV positive by DAS-ELISA. No change was observed at 1 year postinoculation and no symptoms have been observed, even in CMV-infected plants. CMV appears to be latent in P. lactiflora, therefore detection of CMV before vegetative propagation of the plants is advised because of the risks of synergism for symptoms with other viruses such as TRV. To our knowledge this is the first report of CMV in peony. References: (1) L. Cardin et al. Plant Dis. 87:1263, 2003. (2) D. J. Robinson J. Virol. Methods 40:55, 1992. (3) M. J. Roossinck. J. Virol. 76:3382, 2002.
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Hansen, E. M., Jean-Claude Streito, and Claude Delatour. "First Confirmation of Phytophthora lateralis in Europe." Plant Disease 83, no. 6 (June 1999): 587. http://dx.doi.org/10.1094/pdis.1999.83.6.587b.
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Phytophthora lateralis, a pathogen of Chamaecyparis lawsoniana (Port-Orford cedar or Lawson's cypress), was confirmed in France, but isolates from Germany identified as P. lateralis or “similar to” P. lateralis proved to be P. gonapodyides. Previously, P. lateralis was known only from western North America, where it has been destructive in nurseries, ornamental plantings, and the forest since its introduction about 1920 (1). Reports from other locations have proved to be misidentifications or impossible to confirm. In France, P. lateralis was isolated and identified from C. lawsoniana on two occasions (1996 and 1998) in different parts of the country, probably stemming from a single original infestation of young, potted, greenhouse-propagated cedars in a commercial nursery. German isolates were from an old culture collection and from irrigation water in a nursery growing a wide range of woody ornamentals. Identifications were confirmed by comparison (2) with authentic isolates. P. lateralis isolates from France and Oregon formed laterally proliferating, elongated obpyriform sporangia that under the conditions of our tests could be dislodged by agitation, leaving a short pedicel. Also, brown chlamydospores formed laterally on the hyphae or terminally on a short stalk and oospores were not formed on standard media. Radial growth was about 2 mm per day. In contrast, sporangia of German isolates and known P. gonapodyides isolates were similar. They exhibited nested pro liferation, were broader than P. lateralis sporangia, and were not readily dehiscent. Some P. gonapodyides isolates, including those from Germany, formed chlamydospores, but these were nearly all catenulate and not lateral, and isolates grew faster (3 to 4 mm per day). Pathogenicity was tested by stem inoculation of C. lawsoniana. P. lateralis from France and Oregon produced lesions averaging 4.7 cm after 2 months (range 2.0 to 8.1 cm, six replicates per isolate, five isolates) while the six replicates of the two German isolates averaged 1.2- and 1.6-cm lesion lengths. Furthermore, sequences of internal transcribed spacer (ITS) DNA from French and Oregon P. lateralis isolates were identical, while sequences of German isolates were similar to P. gonapodyides (J. Duncan and D. Cooke, personal communiation). P. lateralis is a dangerous pathogen of C. lawsoniana and is also pathogenic to Taxus spp. (1), although less aggressive on this host. If established, it would be a serious threat to the widespread ornamental plantings and scattered forest plantations of C. lawsoniana in Europe. References: (1) E. M. Hansen and K. J. Lewis. Compendium of Conifer Diseases. American Phytopathological Society, 1997. (2) C. M. Tucker and J. A. Milbrath. Mycologia 34:94, 1942.
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Lok, Anne, jean-Come Meniane, Clarisse Joachim, Jacqueline Baudin, Jonathan Macni, Jean-Pierre Marolleau, Nicolas Blin, and Philippe Moreau. "Myeloma in Martinique; Characteristics and Overall Survival." Blood 124, no. 21 (December 6, 2014): 5772. http://dx.doi.org/10.1182/blood.v124.21.5772.5772.
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Abstract Introduction African Americans (AA) are twice as likely to be diagnosed with multiple myeloma (MM) as Caucasian Americans (CA). Differences in overall survival have also been shown between those two populations with no consistent explanation with regard to social status or genetic profile given by gene expression profiling. In Martinique, where most of the population has African or French Caribbean ethnic origin with similar increased incidence in MM, we lack data about disease characteristics and survival as compared to French Caucasian patients. Material and methods The aim of this single center retrospective study was to evaluate characteristics, progression free and overall survival of this population. We analyzed 54 MM elderly patients consecutively treated in Fort de France Hematology department from March 2007 to March 2012. All patients received first line treatment with melphalan 0.2 mg/kg/d, prednisone 2 mg/kg/d and thalidomide 400 mg/d every 6 weeks according to French IFM guidelines. Disease characteristics and survival data were analyzed and compared to French Caucasian elderly MM patients included in first line IFM published trials. Results Population had a median age of 80 years (66 to 93). Concerning prognostic markers, International Scoring System (ISS) was of 3 (high) in 52% of patients and cytogenetic analysis showed rearrangements with translocation 14q32 in 22% with 7% of t(4;14). When considering deletion 13q, it was found in 41% and deletion 17p in 6%. With a median follow up of 35 months, survival features showed median overall survival (OS) of 48.6 months and progression free survival (PFS) of 28.9 months. Discussion Compared to French Caucasian patients, our series showed that Martinique’s population was older and presented more aggressive disease based on ISS. Moreover, almost half patients presented with MDRD clearance lower than 60ml/min which conferred higher B2m and worse prognosis. We also confirmed results recently published by Weiss and all who described lower rate of IgH translocation in African American population with MM. Despite higher median age and ISS, median overall survival of our population was unexpectedly similar to French published studies with IFM 99 06 trial showing median OS and PFS in MPT arm of 51.6 and 27.5 months respectively. In IFM 01/01 trial where patients were aged more than 75 with lower doses of melphalan and thalidomide, survival data showed median OS of 44 months and median PFS of 24.1 months. In meta analysis published by European Myeloma Network, median OS was even lower with 39.3 months. Our data tend to show that French Caribbean patients with first line MM treated in Martinique appear to have similar overall survival as compared to French Caucasian patients despite higher median age and more adverse prognostic features which has not been reported so far. We plan to confirm those data with new analysis with longer median follow up and extensive clinical and biological disease characteristics evaluation. Disclosures Moreau: celgene: Consultancy.
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Cardin, L., A. Poupet, and J. P. Onesto. "First Report of Cucumber mosaic virus in Teucrium fruticans." Plant Disease 87, no. 2 (February 2003): 200. http://dx.doi.org/10.1094/pdis.2003.87.2.200c.
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Teucrium fruticans (shrubby germander), family Lamiaceae, is a hardy shrub. Being drought tolerant, it is widespread in the Mediterranean area. Because it is readily propagated through cuttings, it is also planted in hedges. In 1997 and 2000, respectively, yellow chlorotic areas were observed on the foliage of T. fruticans in Saint Jean Cap Ferrat (France) and San Remo (Italy). These symptoms were distinct from those produced by a rust that frequently affects T. fruticans in these areas. Viruses from both locations were identified as Cucumber mosaic virus (CMV) based on the following: (i) symptoms after mechanical inoculation of Nicotiana tabacum cv. Xanthi nc, N. tabacum cv. Samsum, Chenopodium quinoa, C. amaranticolor, Vigna unguiculata cv. Black, and Cucumis sativus cv. Poinsett; (ii) the morphology of particles observed in electron microscopy of uranyl acetate stained leaf dips from tobacco; and (iii) positive result from leaves of diseased T. fruticans and mechanically inoculated host plants cited above based on enzyme-linked immunosorbent assay (ELISA) using CMV antisera. On tobacco cv. Xanthi nc, the French (F) and Italian (I) isolates first induced essentially necrotic rings on the inoculated leaves followed by the same systemic symptoms as described above. The two isolates were cloned from local lesions after two successive inoculations in V. unguiculata cv. Black, multiplied in tobacco, purified with the citrate-chloroform method, and stabilized with formaldehyde (1). The serotype determination was made by double immunodiffusion in agar gel with the CMV-D and CMV-To strains and homologous antisera (1,2). The formation of spurs and antigen-antibody lines indicated that both isolates belonged to the ToRS serotype (1). Thirty plants of T. fruticans cv. Azureum, first tested negative for CMV using ELISA, were mechanically inoculated with the F isolate (25 plants) and the CMV-D strain (five plants) and cultivated in a hydroponic system. Three months later, plants inoculated with the F isolate were positive for CMV using ELISA and displayed clear symptoms with chlorotic spots, which were sometimes ring-shaped. As plants mature, symptoms tend to disappear on young shoots. For the CMV-D strain, three plants of five were ELISA positive, but did not show any typical symptoms. This report demonstrates the infection of T. fruticans by CMV and the symptom induction by some CMV isolates. In September 2002, two CMV isolates were collected from T. fruticans in public gardens in Menton (France) and Genoa (Italy). These new isolates have the same characteristics as those described in this report. References: (1) J. C. Devergne and L. Cardin. Ann. Phytopathol. 7:225, 1975. (2) M. H. V. van Regenmortel. Adv. Virus Res. 12:207, 1966.
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Botticella, G., M. Pizzonia, B. Cossu, R. Bruno, D. Camellino, G. Girasole, A. Giusti, et al. "POS1105 EFFECTS OF CHOLECALCIFEROL AND CALCIFEDIOL IN OSTEOPOROTIC WOMEN WITH SECONDARY HYPERPARATHYROIDISM DUE TO SEVERE VITAMIN D DEFICIENCY UNDERGOING ZOLEDRONIC ACID TREATMENT: A RANDOMIZED-CONTROLLED TRIAL." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 833.1–833. http://dx.doi.org/10.1136/annrheumdis-2021-eular.809.
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Background:Secondary hyperparathyroidism (sHPTH) due to vitamin D deficiency impairs the bone mineral density (BMD) response to alendronate,1-2 but the optimal strategy for its correction in postmenopausal osteoporotic women (PMO) about to start zoledronic acid (ZOL) therapy is still unknown.Objectives:To evaluate the effects of cholecalciferol (D3) and calcifediol (25OHD) on serum 25-OH-vitamin D (s25OHD), parathyroid hormone (PTH) and BMD in PMO presenting with sHPTH due to vitamin D deficiency.Methods:PMO with s25OHD <20 ng/ml, sHPTH (PTH >65 pg/ml) and BMD T-score at the lumbar spine (LS), femoral neck (FN) or total hip (TH) < -2.5, or between -1 and -2.5 plus one vertebral/femoral fracture, were randomly assigned to receive a therapeutic dose of D3 (300.000 IU bolus) followed by 175 mcg/weekly of D3, or 175 mcg/weekly of 25OHD alone, 2 months before receiving a single intravenous infusion of ZOL (5 mg). BMD at the LS, FN and TH was assessed at baseline and after one year from ZOL. Serum calcium, PTH and s25OHD were measured at baseline, and 6- and 12-month after ZOL. Adverse and clinical events were ascertained by 3-and 9-month telephone interviews, and by 6- and 12-month clinical evaluation.Results:45 PMO (25OHD N=23, D3 N=22) were enrolled over one year and 32 subjects (mean age ±SD 75±10 years, range 51-91) completed the 1-year of treatment/follow-up (25OHD N=17, D3 N=15). Most PMO discontinued for protocol violation, while three deceased before study ending (25OHD N=1, D3 N=2) for reasons not related to the agents investigated. The baseline characteristics were comparable in both groups. At baseline mean s25OHD (±SE) was 8±1 ng/ml in the 25OHD group and 8±1 ng/ml in the D3 group. The corresponding figures for PTH were 111±6 pg/ml (25OHD) and 117±5 pg/ml (D3). Mean s25OHD (±SE) increased in both groups at 6- and 12-month, being significantly greater in the 25OHD group (12-month, 56±2 ng/ml) compared to the D3 group (12-month, 34±2 ng/ml, P<.001) at both time points (Figure 1). PTH (mean ±SE) decreased in both groups, being significantly lower in the 25OHD group at 12-month (25OHD 46±6 pg/ml versus D3 70±6 pg/ml, P=.007), as shown in Figure 1. BMD at the LS, FN and TH increased in both groups (with significant increases versus baseline only at the FN) without significant differences between s25OHD and D3. In PMO receiving D3 serum calcium remained stable over time, while those receiving s25OHD demonstrated a significant increase of serum calcium, with 2 PMO presenting a value close to the upper limit of the reference range at 12-month. No patient reported incident fractures or adverse events.Conclusion:Calcifediol 175 mcg weekly appears more potent in improving s25OHD and decreasing PTH concentrations compared to cholecalciferol therapeutic dose (300’000 IU) plus 175 mcg weekly in PMO presenting with sHPTH due to severe vitamin D deficiency about to start ZOL therapy. Further studies are warranted to clarify implications on BMD improvements on the long-term of similar 25OHD and D3 regimens.References:[1]Barone A et al., J Am Geriatr Soc 2007.[2]Kincse G et al., BMC Musculoskelet Disord 2012.Disclosure of Interests:Giulia Botticella: None declared, Monica Pizzonia: None declared, Barbara Cossu: None declared, Roberta Bruno: None declared, Dario Camellino Speakers bureau: AbbVie, Celgene, Janssen-Cilag, Eli Lilly, Medac, Mylan, Novartis, and Sanofi, outside the submitted work, Giuseppe Girasole Speakers bureau: Abiogen Pharma and Novartis, outside the submitted work, Andrea Giusti Speakers bureau: UCB, Amgen, Kyowa Kirin, Abiogen Pharma, and Eli Lilly, outside the submitted work, Consultant of: EffRx and Abiogen Pharma, outside the submitted work, Mario Pedrazzoni: None declared, Simona Alexovits: None declared, Franco Pleitavino: None declared, Federico Santolini: None declared, Alessio Nencioni: None declared, Gerolamo Bianchi Speakers bureau: Abbvie, Abiogen Pharma, Amgen, BMS, Celgene, Eli Lilly, GSK, Janssen-Cilag, Medac, MSD, Novartis, Pfizer, Roche, Sanofi, Genzyme, and Servier, outside the submitted work.
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Putnam, M. L. "First Report of Leaf Blight and Stem Dieback of St. John's-Wort Caused by Diploceras hypericinum in Oregon." Plant Disease 84, no. 11 (November 2000): 1250. http://dx.doi.org/10.1094/pdis.2000.84.11.1250b.
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St. John's-wort, Hypericum perforatum L., was formerly considered a noxious weed in the Pacific Northwest and is now grown commercially for its medicinal properties. In May 1999, plants from a 5-ha field in Jefferson County, OR, were observed with yellowing leaves and stem dieback. Lower leaves showed marginal necrosis or circular, expanding, uniformly brown, unremarkable leaf lesions that appeared randomly over the lamina and consumed from a quarter to nearly the entire leaf area. Remaining leaf tissue was chlorotic, and affected leaves eventually abscised. Infection of the stems resulted in girdling lesions 0.5 to 1.0 cm in length that caused chlorosis, wilting, and eventual dieback of tissues distal to the lesion. Diploceras hypericinum (Cesati) Diedicke was sporulating on affected stems and leaves. The fungus was isolated from surface-disinfested tissue onto 1.5% water agar. A single-spore isolate was used to inoculate 10-month-old plants raised from seed in sand. Spores from 6-week-old cultures grown on 50% potato-dextrose agar were harvested, suspended in phosphate buffer with 0.2% gelatin (PBG), and sprayed onto three plants using a DeVilbiss atomizer. Inoculum concentration was 7 × 103 and 3 ml per plant were used (plants were 8 to 10 cm tall). Three control plants were sprayed with sterile PBG. Inoculated and control plants were separately bagged to retain moisture and maintained at 22 to 25°C. Four days later, inoculated plants exhibited leaf spots similar to those originally observed, followed by stem dieback. D. hypericinum was isolated from all inoculated plants but not from control plants. The known distribution of D. hypericinum is France, Germany, Portugal, Sweden, Greece, and Ontario, Canada (1,2). This is the first report of D. hypericinum causing leaf blight and stem dieback of St. John's-wort in the United States. References: (1) D. F. Farr et al. 1989. Fungi on Plants and Plant Products in the United States. American Phytopathological Society, St. Paul, MN. (2) T. R. Nag Raj. 1993. Coelomycetous Anamorphs with Appendage-bearing Conidia. Mycologue Publications, Waterloo, Canada.
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Donadieu, Jean, C. Thomas, V. Barlogis, C. Galambrun, A. Robert, V. Gandemer, Y. Bertrand, et al. "Langerhans Cell Histiocytosis with Hematological Dysfunction, Refractory to Standard Therapy Could Be Cured by an Association of 2-CdA and Ara-C: Concordant Results from the Observational Survey of Treated Patients and from a Nation Wide Registry." Blood 110, no. 11 (November 16, 2007): 2412. http://dx.doi.org/10.1182/blood.v110.11.2412.2412.
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Abstract In Children’s Langerhans cell histiocytosis, hematological dysfunction refractory to standard regimen, is the major cause of death until recently. In 2005, (Eur J Cancer, Bernard F et al, 2005) we have reported the results of a pilot study of 2-CdA and Ara-C in this extremely rare subset of patients. Among 10 patients enrolled between 1996 and 2004 (group 1), seven were cured, but three died, two of toxicity, and one after subsequent bone marrow transplantation. We report here A) the results of the 9 additional patients treated in France between mid 2004 and july 2007 (group 2) and B) the results of the national registry which had collected at the national level all cases of LCH in france since 1983. A) The group 2 comprised 9 patients who have all received at least two courses of Ara-C (1000 mg/m2/d) and 2-CdA (9 mg/m2/d) administered for 5 days. Maintenance therapy usually involved 6 courses of 2-CdA (5mg/m2 for 3 days every 3 weeks). Group 2 was comparable to group 1 for median diagnosis age (group 1: 0.78 years vs group 2: 0.73 years), as well as the number of organs involved. The delay between LCH diagnosis and 2-CdA Ara-C onset was shorter in the group 2 (group 1: 0.98 years- group 2: 0.35 years). The initial regimen to treat LCH was the same in the two groups (Vinblastine + steroid +- Methotrexate = LCH III protocol). Group 1 had received several second line therapies before 2-CdA Ara-C, while group 2 had received only the 2-Cda Ara-C as a second line therapy. Grade IV WHO haematological toxicities were observed in all patients, but no toxic death was observed in the group 2. One patient in group 2 underwent a 2-CdA overdose (injection at 10-fold the dose) but no major side effect was observed and latter the protocol was completed. After 2 courses, a decrease in disease activity was observed in all patients, but none had achieved a complete remission status after 2 courses. One patient had received a subsequent HSCT with an attenuated conditioning regimen with a very short hematological recovery at day 15, while the other patients had received only standard chemotherapy regimen as maintenance. Complete remission was achieved in the 8 assessable patients (including the patient who had received HSCT) and one patient had still an active disease but only 2 months after 2-Cda Arac onset. B) In the national French LCH register, 103 cases with hematological dysfunction, among 827 patients (<18 years), were registered from 1983 to 2007. In the same period, 45 deaths were observed, 34 (75%) with haematological dysfunction. In the latter group, the death rate dramatically decreased since the recommendation of 2-Cda Arac as salvage therapy for patients haematological dysfunction refractory to standard chemotherapy in France (1996) as 28 deaths were observed in the 54 patients diagnosed before 1996 (51%) and 6 among 49 patients since 1996 (12%) (p<0.001). In conclusion, 2-CdA and Ara-C combined chemotherapy has major activity to treat refractory LCH with haematological dysfunction, despite a high toxicity. This promising results warrant confirmation in the phase II open labelled study LCHS2005, officially open in France, and in Canada and in few centers in USA.
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Rea, Delphine, Gabriel Etienne, Franck Emmanuel Nicolini, Pascale Cony-Makhoul, Hyacinthe Johnson-Ansah, Laurence Legros, Francoise Huguet, et al. "Front-Line Imatinib Mesylate (IM) in Patients with Newly Diagnosed Accelerated Phase (AP)-Chronic Myeloid Leukemia (CML), a Study From the FILMC Group (France Intergroupe Leucemie Myeloide Chronique)." Blood 114, no. 22 (November 20, 2009): 3288. http://dx.doi.org/10.1182/blood.v114.22.3288.3288.
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Abstract Abstract 3288 Poster Board III-1 IM is approved for the treatment of AP-CML at 600mg daily. Clinical trials in which IM was evaluated in this setting have mainly enrolled patients (pts) who have failed prior therapies and the efficacy of the drug in newly diagnosed AP-CML has never been specifically studied. We collected data from 43 de novo pts with disease acceleration at diagnosis and treated with first-line IM. Thirty-three showed hematological acceleration (HEMAP) according to WHO 2002 or ELN 2006 criteria and 10 had cytogenetic acceleration only (CYAP), defined as the presence of chromosomal abnormalities additional (ACA) to the Philadelphia (Ph) chromosome. Ph variant translocations, loss of the Y chromosome and constitutional cytogenetic abnormalities were excluded from ACA definition. Ten out of 33 HEMAP pts (30%) had also ACA. ACA included Ph duplication (n=4), trisomy 8 (n=5), add(6) (n=3), monosomy 7 (n=1), del(5q) (n=1), t(3;21)(q26;q22) (n=1) and others (n=7). Median age at diagnosis was 51 years (19–67), 32 pts were males (75%) and 11 were females (25%). The median time from diagnosis to IM initiation was 15 days (0–140). The initial IM dose was 600mg/d (n=32) or 400mg/d (n=11). The median duration of IM therapy was 20 months (1–90). A sustained complete hematologic response (CHR) for at least 4 weeks was achieved in 38/43 pts (88.4%, 95% CI 78.4–99.3), including 29 HEMAP and 9 CYAP pts (87.9% versus 90%, not significant (ns)). The median time to achievement of CHR was 42 days (0–97). CHR was lost in 3 pts after 4, 6 and 10 months. Pts with lack or loss of CHR were initially classified as HEMAP (n=5) or CYAP (n=3), all except one harboured ACA at diagnosis. In addition, 4/7 screened pts had a BCR-ABL mutation (E255K n=3, E355G n=1) at the time of IM failure. A major cytogenetic response (MajCR) was observed in 31/43 patients (72.1%, 95% CI 58.1–86.1), and a complete cytogenetic response (CCR) was obtained by 27/43 pts (62.8 %, 95% CI 44.7–78.8), with 22 HEMAP pts and 5 CYAP pts (66.6% versus 50%, ns). The median time to reach CCR was 6 months (3–23). The rate of CCR in HEMAP pts with ACA was significantly lower than that in HEMAP pts without ACA (36.4% vs 80%, p=0.023). Eighteen pts with CCR (16 HEMAP pts and 2 CYAP pts) also gained a major molecular response (MMR: BCR-ABL/ABL ratio % IS ≤ 0.1%). The median time to MMR was 9 months (5–34). Seven pts subsequently lost their MajCR (CCR n=3, partial CR n=4) 3 to 31 months after first achieving it, 2 due to a poor compliance to IM and 5 due to acquired resistance. Of the latter, 4/5 had ACA at diagnosis and a BCR-ABL mutation emerged in 3/5 (E355G n=1, E255K n=1 and T315I n=1). Four pts (2 HEMAP and 2 CYAP) who failed to achieve CHR or CCR evolved toward blast crisis (BC) while on IM, after 1 to 11 months of treatment. The event-free survival (EFS) rate on IM was 57.1% (95% CI 41.4–72.7) at 24 months, events being defined as lack/loss of response, BC or death, whichever came first. The progression-free survival (PFS) rate on IM was 89.7% (95% CI 80–99.4) at 24 months, progression being defined as BC or death. EFS and PFS and did not significantly differ between HEMAP and CYAP pts but EFS at 24 months was significantly poorer in HEMAP pts with ACA at diagnosis than that in HEMAP pts without ACA (26% vs 74.7%, p=0.0055). Twenty-three out of 43 (53.5%) pts discontinued IM after a median duration of treatment of 11 months (1–90), because of treatment failure/progression (n=14), intolerance (n=8) or undetectable molecular residual disease (UMRD, n=1). For those on continuous IM therapy, the median observation time was 32 months (3–76). Following IM discontinuation, 15 pts were switched to second generation tyrosine kinase inhibitors (TKI) and 2 of them evolved toward BC and died, 3 pts underwent allogeneic hematopoietic stem cell transplantation, 4 pts received intensive chemotherapy with or without TKI and 1 was further transplanted, and the last pt with UMRD remained treatment-free. To conclude, although IM front-line induces substantial and durable responses in de novo AP-CML, our results suggest that there may be room for further improvement, especially in case of HEMAP together with ACA. The potential of other front-line therapies such as second generation TKI may be evaluated in this setting. Disclosures: No relevant conflicts of interest to declare.
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Guilhot, Francois, Francoise Rigal-Huguet, Joelle Guilhot, Agnès Guerci-Bresler, Franck E. Nicolini, Frédéric Maloisel, Delphine Rea, et al. "Long Term Outcome of Chronic Phase Chronic Myeloid Leukemia (CP CML) Patients (pts) from the French Spirit Study Comparing Imatinib (IM) 400 Mg to Higher Dose Imatinib or Combination with Peg-interferonα2a (PegIFN) or Cytarabine (Ara-C) : A Trial of the FI LMC (France intergroupe de la leucemie myéloïde chronique)." Blood 124, no. 21 (December 6, 2014): 1793. http://dx.doi.org/10.1182/blood.v124.21.1793.1793.
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Abstract Although they produce high rate of molecular response second generation tyrosine kinase inhibitors or imatinib cannot eradicate CML primitive progenitors. Interferon has been shown to modulate gene expression, inhibits leukemic cell growth and induces an immunomodulatory response. In vitro studies support the use of combination of IM plus interferon. We designed a phase III randomised multicenter open-label prospective trial comparing IM 400 mg/d (n=223) with 3 experimental arms: IM 600 mg/d (n=171), IM 400 mg/d combined to s/c Peg-IFN2a (90 µg/wk) (n=221) and IM 400 mg/d combined to s/c Ara-C, (20 mg/m2/d, d15-28 of 28-day cycles)(n=172). Pts were allocated at a 1.1.1.1 ratio, stratified by Sokal risk groups. Molecular assessments were centralised, blinded and calculated according to the international standardised ratio (IS) As of December 31st 2010, date for closing accrual, 787 pts have been included. We first demonstrated that the addition of PegIFN increased the molecular responses. The planned molecular analysis after 1 year based on the outcome of 636 pts resulted in a highly significant superiority of MR4 (≤0.01 % Bcr-Abl/Abl on IS) of the combination IM 400mg-PegIFN (Preudhomme et al. N Engl J Med, 2010). The protocol was also amended after the demonstration that a lower dose of PegIFN (45 µg/week) resulted in less toxicity and similar molecular responses as compared with 90 µg/week. Of interest, a 3-months BCR-ABL transcript level of ≤10% IS was associated with PFS (Accelerated phase, blast crisis, deaths) and time to progression (TTP) improvement overall. However, results which were observed with the addition of PegIFN or an increased dose of IM frontline do not confirm the relevance of the 10% BCR-ABL cut-off level as a strong surrogate marker for progression. After a median observation time of 60 months, 5-year overall survival (OS) was 94%, and 5-year PFS was 93%. Overall 70 pts died because of blastic (n=24) or accelerated phases (n = 1). Out of the 35 pts who progressed to AP and BC, 11 are alive. A blastic phase was recorded in 27 pts (myeloid 20, lymphoid 6, biphenotypic 1), of these 4 are alive (2 myeloid, 2 lymphoid). Main causes of deaths in CP (n = 46) were infections (IM 400 n=4,IM 600 n=0, IM PegIFN n=4, IM Ara-c n=0 ), vascular events (IM 400 n=1,IM 600 n=2,IM PegIFN n=1, IM Ara-c n=1) malignancies (IM 400 n=3, IM 600 n=2 ,IM PegIFN n=4, IM Ara-c n=7 ). In addition, the following causes of death were recorded: suicide (n=2), GVHD (n=2), miscellaneous (n=13). Cumulative incidence of progression, PFS and OS by arms are shown in the table: Table 1 IM 400 (n = 223) IM 600 (n = 171) IM PegIFN (n = 221) IM Ara-c (n 172) Cumulative incidence of progression (p: 0.43)(a) N progressions 11 11 7 6 N competing events (deaths in CP) 9 7 15 15 At 60 months % (95%CI) 5% (3-8) 5% (3-9) 2% (1-4) 4% (2-8) PFS (p:0.92)(b) N (progressions and deaths) 20 18 22 21 At 60 months 93% 93% 94% 91% (95%CI) (89-96) (88-96) (90-97) (85-94) OS (p: 0.64)(b) N (deaths) 15 16 19 20 At 60 months 95% 94% 95% 91% (95%CI) (91-98) (89-97) (91-97) (86-95) Gray’s test Log-rank test Conclusions:The French SPIRIT trial demonstrated that the combination of imatinib with Peg-IFNα2a was associated with deeper molecular responses at 12 months and was able to counteract the risk of early progression in newly diagnosed CML-CP patients. The dose of 45µg/week is well tolerated and sufficient for achieving molecular responses and should be used in further trials. The risk of progression to blastic or accelerated phase, although currently non-significant, is lower with this combination. An update of outcomes will be presented. Disclosures Maloisel: Hospira: Consultancy; Sandoz: Research Funding; Pfizer: Research Funding. Gardembas:BMS: Honoraria. Legros:Novartis, BMS: Honoraria.
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Novak-Marcincin, Jozef, Daniela Gîfu, and Mirela Teodorescu. "Florentin Smarandache: Law of Included Multiple-Middle - Book Review." International Letters of Social and Humanistic Sciences 40 (September 2014): 29–34. http://dx.doi.org/10.18052/www.scipress.com/ilshs.40.29.
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Florentin Smarandache is known as scientist and writer. He writes in three languages: Romanian, French, and English. He graduated the Department of Mathematics and Computer Science at the University of Craiova in 1979 first of his class, earned a Ph. D. in Mathematics from the State University Moldova at Kishinev in 1997, and continued postdoctoral studies at various American Universities such as University of Texas at Austin, University of Phoenix, etc. after emigration. He did post-doctoral researches at Okayama University of Science (Japan) between 12 December 2013 - 12 January 2014; at Guangdong University of Technology (Guangzhou, China), 19 May - 14 August 2012; at ENSIETA (National Superior School of Engineers and Study of Armament), Brest, France, 15 May - 22 July 2010; and for two months, June-July 2009, at Air Force Research Laboratory in Rome, NY, USA (under State University of New York Institute of Technology). In U.S.A. he worked as a software engineer for Honeywell (1990-1995), adjunct professor for Pima Community College (1995-1997), in 1997 Assistant Professor at the University of New Mexico, Gallup Campus, promoted to Associate Professor of Mathematics in 2003, and to Full Professor in 2008. Between 2007-2009 he was the Chair of Math & Sciences Department.
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Ghesquieres, Herve, Caroline Houillier, Olivier Chinot, Sylvain Choquet, Cecile Molucon-Chabrot, Patrick Beauchene, Remy Gressin, et al. "Rituximab-Lenalidomide (REVRI) in Relapse or Refractory Primary Central Nervous System (PCNSL) or Vitreo Retinal Lymphoma (PVRL): Results of a "Proof of Concept" Phase II Study of the French LOC Network." Blood 128, no. 22 (December 2, 2016): 785. http://dx.doi.org/10.1182/blood.v128.22.785.785.
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Abstract Background Primary CNS lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL), predominantly of non-germinal center (non-GC) subtype. Despite improvement of therapeutic results since the introduction of high-dose methotrexate (MTX) in first-line treatment, improvements of therapeutic results are needed in PCNSL, both in first-line treatment and at relapse. The roles of consolidation and maintenance therapy need to be addressed as well. The association of Rituximab and Lenalidomide has shown activity in non-CNS non-GC DLBCL, but its activity in PCNSL was unknown. Methods In this prospective, multicenter open-label phase II study, we enrolled patients over 18 with a refractory or relapse PCNSL or primary vitreo-retinal lymphoma (PVRL) of DLBCL type. The treatment consisted in an induction phase with 8 cycles of 28 days with R2 (Rituximab 375/m2 IV D1; Lenalidomide 20 mg/D D1-D21 for the first cycle then 25 mg/D D1-D21 for the subsequent cycle in the absence of hematologic toxicity), followed, in responder patients by a maintenance phase with 12 cycles of 28 days with Lenalidomide alone (10 mg/D, D1-D21). Corticosteroids were allowed during the first induction cycle in case of a threatening or symptomatic edema. Deep vein thrombosis prophylaxis was mandatory. Patient who received a complete month of treatment were evaluable for response. The primary end-point was the objective response rate (ORR) at the end of the induction phase, according to the international primary CNS lymphoma collaborative group (IPCG) criteria. The analysis was based of a Fleming's two-step design (P0 = 10 %; P1= 30%). A pilot exploration of circulating NK and T cells before and after treatment and correlation with therapeutic response was conducted. This study is registered with ClinicalTrials.gov, number NCT01956695 Results Between September 17, 2013 and September 29, 2015, fifty patients (median age: 69, range 46-86) were recruited from 10 centers. All the patients had previously received high-dose (HD) MTX. Median number of previous lines of chemotherapy was 2 (range, 1-4). Nine patients had previous received an HD chemotherapy followed by hematopoetic stem cell rescue. Initial diagnoses were PCNSL (n = 42) and PVRL (n = 8). At time of inclusion in the study, diagnoses were PCNSL (n = 41) and PVRL or isolated intra-ocular (IO) relapse of PCNSL (n=9). Seven patients had concomitant involvement of the cerebrospinal fluid (CSF). Patients were included either for a relapse after last treatment (80 %; median time to relapse = 5.5 months), or for a refractory disease (20 %). Thirty-four patients received concomitant corticosteroids during the first month of treatment. Forty-five patients were evaluable for response after the first cycle of treatment. Median number of induction cycles was 7 (range, 1-8). Grade 3 or 4 adverse events were reported in 11 patients (infection: n = 10, cutaneous rash: n =1). A second cancer (melanoma) occurred in one patient. Two patients withdrew their consent. During the induction phase, best observed responses were CR (n = 16), PR (n = 11), stable disease (n = 5) and progressive disease (n = 11) for an ORR of 63% (27/43). . At the end of the induction phase, 43 patients were evaluable for the primary objective. ORR was 39 % (17/43) including 13 CR (30%). A response has been observed in patients included for a PCNSL (n = 13, 32%) and for an IO relapse or PVRL (n = 4, 44%). Seventeen patients started the maintenance phase. With a median follow-up of 9 months (range, 1.1-15.4), median overall and progression-free survivals of the whole population were 15.3 months (95 % CI, 9.6 - non reached) and 8.1 months (95 % CI, 4.2 - non reached) respectively. Median duration of response in the responder patients was 8.9 months (95 % CI, 7.6- non reached). The results of the maintenance phase are pending. Results will be further updated. Conclusion This phase II study demonstrates a significant activity of the rituximab-lenalidomide regimen in relapse or refractory PCNSL or PVRL. Updated results with a longer follow-up are awaited to better evaluate the PFS and the median duration of response. This regimen warrants to be added in the armamentarium drugs for PCNSL and further explored in combination with other chemotherapies in first-line treatment, as maintenance therapy, or as a chemo-free regimen for patients unfit for high-dose methotrexate. Funding: Celgne, Roche Figure. Figure. Disclosures Ghesquieres: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche France: Research Funding; Mundipharma: Consultancy. Choquet:Celgene: Consultancy; Janssen: Consultancy. Morschhauser:Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Janssen: Honoraria; Servier: Consultancy, Honoraria. Soussain:Roche: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding.