Le Bras Research Articles

Personal CAPTCHA-based authentication protocol

In recent years, the number of personal accounts assigned to a single user has considerably increased. According recent study, the average employee had above 190 individual login credentials. The most important problems users face with such a large number of passwords are the strength of passwords and the user's ability to remember them. Researchers have shown that, in general, users are aware of what a secure password should look like, but may forgot these security measures in favour of more convenient passwords, depending largely on the type of account (le Bras, 2015). Repeating the same password across multiple platforms or creating it using dictionary words has also proven to be a common practice among many people. In this article, a new password reminder scheme will be presented. The goal was for the user to create a CAPTCHA-like image with a hidden meaning that only the user would be able to reveal. The image must have some connection to the person's experience and memory or unique knowledge. With such an image, presented each time the user logs in, he is asked to associate a password consisting of two or more words and a number. If the image is appropriately selected and associated with a strong association with the person's visual memory, the chances of recalling the long password he created in this way should not be a problem.

Integrative Study of a High-Grade B-Cell Lymphoma Cohort of 45 Patients: A Single Institution Real Life Study

Background :High grade B cell lymphoma (HGBL) either Not Otherwise Specified (NOS) or either Double Hit (DH MYC/BCL2 or DH MYC/BCL6) or Triple Hit (TH) have been considered as separate entities from Diffuse Large B-Cell Lymphoma (DLBCL) NOS in the 2016 WHO classification. Until now, treatment of these particularly aggressive histological sybtypes remains unclear and most of patients (pts) still have a poor outcome because of chemoresistance or early relapse. Except IPI score, prognosis factors are not completely clarified. Since few years, treatment with Chimeric Antigen Receptor T (CAR-T) cells has changed the prognosis of relapsed refractory DLBCL and could represent a promising therapeutic approach - early in the course of the disease - to improve survival of HGBL. The aim of the present study is to describe a « real life » cohort of pts treated in our institution and to evaluate the prognostic impact of clinical, histological, genetic and imaging characteristics and treatment.Methods :We collected data of 45 pts diagnosed between January 2009 and October 2020. BCL2, BCL6 and MYC break were analyzed by Interphase Fluorescence In Situ Hybridization (FISH) with break-apart probes. When MYC was rearranged, MYC partner gene was analyzed with double fusion probes (MYC/IgH, MYC/IgL, MYC/IgK). Total metabolic tumor volume (TMTV) was calculated using fully automatic segmentation of lymphoma lesions by an artificial intelligence (P. Blanc-Durand, Eur J Nucl Med Mol Imaging, 2021).All pts were treated with rituximab R-CHOP/CHOP-like regimens. Treatment was reinforced (intensive regimen) with high dose methotrexate (14 pts treated with RCOPADM and one with R-ACVBP) when they were considered fit enough. Autologous stem cell transplantation at 1st relapse was performed in 3 pts and 5 pts were treated with CAR-T cells at 2 nd relapse.Results :Baseline characteristics were as follows: median age 60 y (28-80), IPI 3-5 : n=33 (73%), CNS localization : n=8/42 (19%), bone marrow involvement : n=10/34 (22%).Twenty-seven pts were DH lymphoma (MYC/BCL2: 18; MYC/BCL6: 9), 8 patients were TH-lymphoma and 10 were HGBL-NOS.MYC rearrangement was detected in 40 cases with an immunoglobulin partner gene (IgH, IgL or IgK) in 14 (52%) of 27 evaluable cases.TMTV was calculated for 29 pts with a median TMTV of 1019 ml (2-4536 ml). Fifteen pts were treated with an intensive regimen. With a median follow-up of alive pts of 17 months, 2-y progression-free survival (PFS) and overall survival (OS) were 42% [26.4 ; 56.8] and 62% [43.7 ; 75.5] respectively.PFS and OS were significantly affected by IPI 3-5 (PFS: p= 0.006, HR=3.37 ; OS: p= 0.01, HR=3.71) and CNS involvement (PFS : p=0.006, HR=6.93 ; OS: p=0.006, HR=7.44). TMTV>1000ml (PFS: p=0.051, HR 2.99 ; OS: p=0.033, HR=4.13) was associated with a significantly inferior OS.Prognosis of HGBL DH/TH and HGBL-NOS was similar (PFS: p= 0.89, HR=0.93 ; OS: p=0.64, HR=1.32). Immunoglobulin as MYC partner gene had no significant impact on prognosis (PFS: p=0.47, HR=1.48 ; OS: p=0.32, HR=1.73). Intensive regimens did not improve significantly prognosis (PFS: p=0.26, HR=1.71 ; OS: p=0.08, HR=2.86).Conclusion:This monocentric study confirms previous reports on the poor prognosis of HGBL (DH/TH and NOS) especially for patients for both high IPI or high TMTV and in case of initial CNS involvement.We confirm that intensive regimen don't improve prognosis supporting the need of alternative strategies incorporating bispecific monoclonal antibodies or consolidative CAR-T cells in very high risk pts. DisclosuresRoulin: Janssen: Other: Travel and meetings. Lemonnier: Institut Roche: Research Funding; Gilead: Other: travel grant. Le Bras: Novartis: Honoraria; Takeda: Honoraria, Research Funding; Kite Gilead: Honoraria; Celgene BMS: Research Funding. Gaulard: Innate Pharma: Research Funding; Sanofi: Research Funding; Alderaan: Research Funding; Gilead: Consultancy; Takeda: Consultancy, Honoraria. Haioun: Miltenyi: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding.

Outcome of Relapsed/Refractory Aggressive B-Cell Lymphoma Patients Relapsing after Anti-CD19 CAR T-Cells and Enrolled in the Descar-T French National Registry

Outcome of Relapsed/Refractory Aggressive B-Cell Lymphoma Patients Relapsing after Anti-CD19 CAR T-Cells and Enrolled in the Descar-T French National Registry

Species Detection and Segmentation of Multi-specimen Historical Herbaria

Historically, herbarium specimens have provided users with documented occurrences of plants in specific locations over time. Herbarium collections have therefore been the basis of systematic botany for centuries (Younis et al. 2020). According to the latest summary report based on the data from Index Herbariorum, there are around 3400 active herbaria in the world containing 397 million specimens that are spread across 182 countries (Thiers 2021). Exponential growth in high quality image capturing devices induced by the enormous amount of uncovered collections has further led to rising interest in large scale digitization initiatives across the world (Le Bras et al. 2017). As herbarium specimens are increasingly becoming digitised and accessible in online repositories, an important need has also emerged to develop automated tools to process and enrich these collections to facilitate better access to the preserved archives. This rising number of digitised herbarium sheets provides an opportunity to employ computer-based image processing techniques, such as deep learning, to automatically identify species and higher taxa (Carranza-Rojas and Joly 2018, Carranza-Rojas et al. 2017, Younis et al. 2020) or to extract other useful information from the herbaria sheets, such as detecting handwritten text, color bars, scales and barcodes. The species identification task works well for herbarium sheets that have only one species in a page. However, there are many herbarium books that have multiple species on the same page (as shown in Fig. 1) for which the complexity of the identification problem increases tremendously. It also involves a great deal of time and effort if they are to be enriched manually. In this work, we propose a pipeline that can automatically detect, identify, and enrich plant species in multi-specimen herbaria. The core idea of the pipeline is to detect unique plant species and handwritten text around the plant species and map the text to the correct plant species. As shown in Fig. 2, the proposed pipeline begins with the pre-processing of the images. The images are rotated and aligned such that the longest edge is maintained as its height. In the case of herbarium books, the pages are detected and morphological transformations are performed to reduce occlusions (Thirukokaranam Chandrasekar and Verstockt 2020). A YOLOv3 (You Only Look Once version 3) object detection model (Zhao and Li 2020) is trained from scratch to detect plants and text. The model was trained on a dataset of single species herbarium sheets with a mosaic augmentation technique to extend the plants model to detect multiple species. The first results of the training shows impressive results although it could be further improved with more labelled data. We also plan to train an object segmentation model and contrast its performance with the plant detection model for multi-specimen herbarium sheets. After detecting both the plants and the text, the text will be recognized with a state-of-the-art handwritten text recognition (HTR) model. The recognized text can then be matched with a database of specimens, to identify each detected specimen. Furthermore, additional textual metadata (e.g. date, locality, collector's name, institution) visible on the sheet will be recognized and used to enrich the collection.

JEDI Events and Programming for OSM 2022

The biennial Ocean Sciences Meeting (OSM) is the most extensive opportunity for members of the global ocean sciences community to come together to share knowledge, network, build and strengthen collaborations, and grow ideas. In addition to sharing progress in research, technology, and education, these meetings are a valuable opportunity to advance diversity and inclusivity in the ocean sciences community. OSM 2020 featured several successful events and sessions with these themes, and reflection on them since then has been valuable for guiding further diversity, equity, and inclusion (DEI) efforts at our home institutions and for planning future conferences (Behl et al., 2021, in this issue; Le Bras, 2021).

Effect of a water, sanitation and hygiene program on handwashing with soap among household members of diarrhoea patients in healthcare facilities in Bangladesh: a cluster‐randomised controlled trial of the CHoBI7 mobile health program

The Cholera-Hospital-Based-Intervention-for-7-days (CHoBI7) is a water treatment and handwashing with soap intervention for diarrhoea patients and their household members which is initially delivered in a healthcare facility setting. This study evaluated the effectiveness of CHoBI7 program delivery in increasing handwashing with soap in a healthcare facility setting among diarrhoea patients and their household members. A randomised controlled trial of the CHoBI7 program was conducted among 404 diarrhoea patients and their accompanying household members in healthcare facilities in Dhaka, Bangladesh. The 'Standard Message' Arm received the standard message given in Bangladesh to diarrhoea patients on the use of oral rehydration solution. The 'Health Facility Visit+Soapy Water' Arm received the standard message, the CHoBI7 communication module delivered bedside to the patient; and a soapy water bottle in the healthcare facility. The 'Health Facility Visit+Handwashing Station' Arm received this same intervention plus a small plastic handwashing station. Within 24h of intervention delivery, three-hour structured observation of handwashing practices at stool/vomit- and food-related events (key events) was conducted in healthcare facilities of diarrhoea patients and their accompanying household members. Compared to the Standard Message Arm, there was significantly more handwashing with soap at key events in both the Health Facility Visit + Soapy Water Arm (51% vs. 25 %) (Odds Ratio: 3.02; (95% Confidence Interval (CI): 1.41, 6.45) and the Health Facility Visit+Handwashing Station Arm (58% vs. 25%) OR: 4.12; (95% CI: 1.86, 9.14). These findings demonstrate that delivery of the CHoBI7 communication module and provision of a soapy water bottle to diarrhoea patients and their accompanying household members presents a promising approach to increase handwashing with soap among this high risk population in a healthcare facility setting in Bangladesh.

Modular Synthesis of Diarylalkanes by Nickel-Catalyzed 1,1-Diarylation of Unactivated Terminal Alkenes

A nickel-catalyzed 1,1-diarylation of electronically unbiased alkenes has been developed, providing straightforward access to diarylalkanes from readily available materials. Importantly, both the e...

Rituximab Plus Gemcitabine and Oxaliplatin (R-GemOx) in Refractory/Relapsed (R/R) DLBCL. a Real Life Study in Patients Ineligible for Autologous Transplantation

Introduction: There is no standard treatment of refractory or relapsed (R/R) patients (pts) with DLBCL ineligible for autologous stem-cell transplantation (ASCT). However, R-GemOx is widely used in these circumstances. We here report the results of a retrospective analysis of a cohort of patient treated in two academic centers in France. The main objectives were to evaluate the activity and safety profile of this regimen in a large series of R/R DLBCL pts in a real life setting. Methods: Patients selected had to have de novo or transformed DLBCL, R/R after at least one line of treatment containing doxorubicin and rituximab, to be ineligible for ASCT and to have received at least one cycle of R-GEMOX. Rituximab 375 mg/m2 was administered on D1, gemcitabine 1000 mg/m2 on D2 and oxaliplatin 100 mg/m2 on D2 as previously described (Mounier N. et al. Haematologica 2013; 98:1726-31). Cycles were given every 2 weeks and 8 cycles were planned if at least a partial response (PR) was obtained after 4 cycles. Results: Between May 2002 and May 2017, 196 pts were treated. Baseline characteristics were: median age: 72 y (range, 24-89), international prognostic index (IPI) 3-5: 63%, refractory state to last treatment (tx): 42%, history of indolent lymphoma: 45%, prior ASCT: 16%. The median number of previous line was 1 (range 1-7) with 112 pts having received R-GemOx in second line. One hundred and thirty-six pts received at least 4 cycles, 86 pts completed 6 cycles and 61 pts 8 cycles. After 4 cycles, the overall response rate (ORR) according to IWC (Cheson 1999 or 2007) was 54 % and the complete response (CR) rate was 23 %. At the end of treatment, the ORR and CR rates were 38 % and 33 %, respectively. With a median follow-up of 22 months, median (m) progression-free survival (PFS) and overall survival (OS) were 5 and 10 months (mo), respectively. mOS was significantly longer in case of prior history of indolent lymphoma (21 vs 8 mo, p < 0.001), age<75y (16 v 7mo, p < 0.001), IPI <3 (p < 0.001), non-refractory status to last treatment (18 v 7mo, p < 0.001). The mOS of patients who attained a CR was 40 mo. Among pts who were treated with R-GemOx in second line, the CR rate was similar (32%), the same factors influenced the OS and duration of a first remission longer than 12 months was a favorable factor (p=0.006). Based on data collected from the population who received the first four cycles, (136 patients and 848 cycles) the median received dose intensities of oxaliplatin and gemcitabine were 73.1 %, and 75.8% of the theoretical dose, respectively. The most common toxicities during treatment were hematological and manageable. Grade 3-4 toxicities occurred in 30.6% of pts. Grade 1-2 peripheral neuropathy related to oxaliplatin was observed in 26% of the patients, with only 2 patients presenting a grade 3 peripheral neuropathy. Summary/Conclusion: This real life study of R/R DLBCL, confirms the activity and safety of R-GemOx. This combination represents a platform to be combined with targeted therapies as it is currently proposed with nivolumab in the phase 3 NIVEAU trial (NCT03366272) and planned with polatuzumab vedotin (POLARGO trial). However, facing this very high unmet medical need, new approaches including CAR T-cells should also be considered in this patient population. Disclosures Belhadj: Janssen: Honoraria; Celgene: Honoraria, Other: personal fees from Celgene, personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, outside the submitted work; Takeda: Honoraria; Amgen: Honoraria. Le Bras:Pfizer: Other: Travel grant; Takeda: Research Funding; Jansen: Other: Travel grant. Jardin:amgen: Honoraria; Servier: Honoraria; celgene: Honoraria; roche: Honoraria; janssen: Honoraria. Tilly:Roche: Consultancy; Celgene: Consultancy, Research Funding; Astra-Zeneca: Consultancy; Karyopharm: Consultancy; BMS: Honoraria; Janssen: Honoraria; Gilead: Honoraria; merck: Honoraria; servier: Honoraria; roche: Membership on an entity's Board of Directors or advisory committees. Haioun:F. Hoffmann-La Roche Ltd: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Servier: Honoraria; Miltenyi: Honoraria; Takeda: Honoraria.

Étendue du vocabulaire et compréhension écrite – le français à l'université en Suède

This paper investigates the amount of French vocabulary needed to read (with reasonable comprehension) three authentic novels used in a first semester course of French at a Swedish university. The analysis applies the concept of lexical coverage and uses the frequency lists of Lonsdale & Le Bras (2009). The counting unit is the lemma. This study also examines the common French word list used in all Swedish universities offering French degrees. The results show that 7 000 to 9 000 lemmas will provide the 98 % coverage needed for reasonable comprehension. This is at least twice the 4 000 lemmas contained in the university list. The results therefore point to the necessity of including a vocabulary component also in higher-level French courses.

Source triangulation utilizing three-dimensional arrivals: Application to the search for the ARA San Juan submarine.

On Nov. 15, 2017, an intense acoustic event coincident with the disappearance of the Argentine navy submarine, ARA (Armada Argentina) San Juan, was recorded on the hydroacoustic network established to enforce compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT). Analysis by Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) scientists, based on two hydroacoustic and one seismic detection, provided a likely origin within an error ellipse of 19 km by 12 km; analysis based solely on the main arrival detected at the two hydroacoustic stations gave an error ellipse of ∼500 km by ∼25 km [Nielsen, Zampolli, Le Bras, Mialle, Bittner, Poplavskiy, Rozhkov, Haralabus, Tomuta, Bell, and Grenard, in European Geosciences Union General Assembly, Vol. 20, EGU2018-18559 (2018)]. The large major axis depends on uncertainty in establishing the event time, while the minor axis depends on precision in the ocean state estimate used to model propagation speed. This paper demonstrates how three-dimensional (3-D) propagation features can also be used in source triangulation, in particular when no seismic detection is available. A mode-based 3-D propagation model is implemented to reconstruct the propagation path of a 3-D arrival bathymetrically refracted from the continental slope. This additional arrival provides a third (virtual) station to decouple the location and time of the event and triangulate the event. This improvement is commensurate with the CTBTO analysis, but does not rely on the additional seismic station detection.

Historical Cartography of Confessions and Religions in the Polish-Lithuanian Commonwealth: Between Historical Geography and Spatial History

Historical thematic cartography devoted to confessional or, in yet broader terms, religious problematic enjoys a stable status in Poland. Religious issues have usually been treated in a two-fold way: 1. as the major subject of historical cartography, 2. as a component of historical cartography concerned with socio-cultural or historical-political problematic. The former embraces the tradition of the Centre for Research on (earlier Institute of ) Historical Geography of the Church in Poland (Catholic University of Lublin), whereas the latter – the works of the Historical Atlas of Poland (Institute of History of the Polish Academy of Sciences). Even though the Polish-Lithuanian Commonwealth was a multi-religious and multi-confessional country (including both Christian and non-Christian faiths), the majority of hitherto cartographic studies was predominantly preoccupied with institutions, peoples and religious practices of the Latin Church, which enjoyed a preferential systemic and socio-economic status in the Commonwealth. For decades, Polish historical cartography focused on the reconstruction of territorial structures and multi-level administrative divisions. The meticulousness and methodology of these approaches varied greatly, ranging from small-scale schematic maps of dioceses, to very detailed inventory maps of parochial borders (the “Historical Atlas of Poland” series). Its thematic development Polish cartography of confessions owes to professor Jerzy Kloczowski who made the geographical- historical method one of the pillars of studies into socio-religious history, strongly influenced by the French “Annales” school. The Centre for Research on Historical Geography of the Church in Poland at the Catholic University of Lublin is the only scientific institution in Poland whose research profile and methodology focus on geography and historical cartography of religions and confessions. The vast cartographic material collected over many decades forestalled a full development of cartographic research methodology and the subsequent evolution from cartographic presentation to analysis and interpretation, which had been advocated by Kloczowski already in the 1960s. The introduction of innovative technological devices to geographical-historical research, specifically databases and systems of spatial information, have opened anew the discussion on the opportunities for integrating data with methods of their analysis. Through its connection to other layers of the landscape of the past historical geography of confessions and religions is now becoming a crucial element of spatial history. Importantly, its inclusive and interdisciplinary character tallies well with the programme formulated by Le Bras and Kloczowski, within the framework of which institutions, peoples and religious practices should be presented alongside other elements of social, economic and cultural life. Only this may facilitate a proper assessment and description (both quantitative and qualitative) of religious practices, helping to properly interpret factors which have influenced the development of religious institutions and practices.

BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Prior to Autologous Stem Cell Transplant for Chemosensitive Relapses in Patients with Follicular Lymphoma: A Prospective Multicenter Phase II Study from Lymphoma Study Association (LYSA) Centers

Introduction: high dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) is an effective treatment in relapsed follicular lymphoma (FL). Alternative regimens including bendamustine based conditioning (BeEAM) had been developed to improve lymphoma outcome. Visani et al. showed in a phase I/II for relapsed aggressive lymphomas and relapsed Hodgkin lymphomas that bendamustine used at a dose of 200mg/m2, 2 days in combination with cytarabine (400 mg/m2, day-5 to day-2), etoposide (200 mg/m2, day-5 to day-2) and melphalan (140 mg/m2, day-1) was well tolerated with promising efficacy results. We designed a single arm, multicenter, phase II study for first and second chemosensitive relapses in FL patients (pts) evaluating this conditioning regimen.Methods: The primary endpoint is the efficacy of BeEAM by measuring the 2-year event-free survival (2-year EFS) rate defines by relapse, progression, death from any cause and initiation of a new therapy. The hypothesis was the improvement of 2-year EFS rate from 70% (H0) to 85% (H1). Based on a Fleming-A'Hern single-stage design, 50 pts are needed. Secondary endpoints are: overall response rate (ORR) at day 100 according to 2007 Cheson criteria; progression-free survival (PFS); overall survival (OS) and safety profile of BeEAM. Main eligible criteria are: histologically confirmed FL relapsed (WHO grade 1, 2, 3a); aged 18-65 years; first or second chemosensitive relapses after salvage immunochemotherapy based on 2007 Cheson criteria with a complete (CR) or a partial response (PR) before the BeEAM; eligibility for ASCT; signed informed consent. This trial was funded by the French government PHRC program 2012.Results: Twenty-one pts were included between July 2014 and November 2016 in 7 LYSA centers. One patient did not receive the treatment. The final analysis was based on 20 pts. Inclusion were performed for 16 (80%) and 3 (15%) pts at 1st and 2nd relapses, respectively. One patient (5%) was included at 3rd relapse and is considered as protocol minor deviation. The median time between the initial diagnostic and the 1st relapse was 3.6 years (0.7-12.9). In first-line therapy, 17/20 pts (85%) were treated with immunochemotherapy. At the relapse allowing inclusion, the FLIPI score were 0-1, 2, ≥3 for 6 (32%), 7 (36%), 6 (32%) pts, respectively. Salvage treatments were rituximab (R) associated with, dexamethasone, cytarabine, and platin in 19 pts and R-CHOP in one patient. The median age at inclusion was 57 years (range, 39-63); 16 (80%) and 4 (20%) pts were in CR and PR before BeEAM. After 18 included pts, the protocol was amended due to unexpected toxicities especially two hepatic veino-occlusive diseases (VOD), leading to the reduction of bendamustine dosage. Finally, 17 and 3 pts were respectively treated at 200mg/m2, 2 days and 160mg/m2, 2 days. The median time for neutrophil>0.5 G/L and platelet recoveries>20 G/L were 7.5 (0-11) and 7 (2-18) days. Patients received a median of 4 (0-12) packed red blood cell units and 6 (3-21) platelet units until J100. The median duration of hospital stay duration was 27 days (20-50). Response evaluation at J100 showed 19 CR pts and one patient in progressive disease. The ORR was 95.0% (95%CI, 75.1-99.9). Six pts progressed with two deaths of the FL (Figure 1A). With a median follow-up of 31 months (16-42), the 2-year EFS rate was 59.6% (95%CI, 35.1-77.4) but two events correspond to unplanned rituximab maintenance in two CR pts (Figure 1B). The PFS and OS rates were 69.6% (95%CI, 44.5-85.1) and 90% (95%CI, 65.6-97.4), respectively (Figure 1C). Fifteen pts (75%) had infectious complications until J100 that needed treatments for more than 7 days. Grade ≥3 toxicities were infections (N=18, 90%), gastrointestinal disorders (N=14, 70%), mucositis (N=12, 60%); atrial flutter (N=1, 5%); acute renal failure (N=2, 10%); HHV6 reactivation (N=3, 15%). In total, 29 serious adverse events (SAE) were declared for 16 pts. Two pts experienced VOD classified as unexpected SAE; one of them needed a hepatic transplantation. No patient presented toxic death.Conclusions: the prospective evaluation of BeEAM conditioning in FL pts with a chemosensitive relapses showed excessive toxicities especially infectious complications, cases of VOD leading to premature termination of the trial. Based on the 20 treated pts, the outcome seems not improve with the use of BeEAM. Our study does not encourage the use of BeEAM conditioning in relapsed FL pts. DisclosuresGhesquieres:Sanofi: Consultancy; Gilead: Consultancy; Celgene: Consultancy. Le Bras:Amgen: Consultancy. Le Gouill:Roche: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria. Cartron:Celgene: Consultancy, Honoraria; Gilead Sciences: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Roche: Consultancy, Honoraria.

French Immigration—Demography Meets Politics: A Review Essay

French Immigration—Demography Meets Politics: A Review Essay

Europe in the Age of Reformations: The Modern State and Confessionalization

The End of Confessional History or History Writing?As the 500th anniversary of the Reformation approaches, we are A reminded that history is one long transition. As with all civilizations handing over the baton, it is not outside agencies that are killing the West but the West killing itself. But what is specific to our times is that we have lost sight of the shore from which we set out: at most, through a thick fog we glimpse heaps of rubble that we have shed in the last century or so, from the Decalogue to the atomic bomb and the Shoah. On a lighter note, you will smile to hear (if it does not make you weep) how a third-year university student of colleague Claudia Pancino answered a question on the distinction between depraesenti marriage and de futuro marriage (a contractual promise to celebrate a wedding at some other date):Even after the Council of Trent and its attempt to regulate marriage, people failed to observe the distinction between verbs in the future and those in the present. This was partly because people were poor and ignorant and didn't know their tenses.But all joking aside, the problem may be that today's millennial youth-not just students but those in Western society as a whole-don't do past tense and future tense but only see and understand a timeless present of 2.0 images.In a previous publication I tried to show how we have been involved these last few decades in the anthropological crisis of Homo europaeus,1 far more than just another passing transition. The historical argument I wish to develop here is that, as the strands linking confessional Churches and modern states unravel after a five-century cycle dating from Martin Luther's 1517 protest, our whole surroundings are changing, not just in terms of religion but politically and institutionally as well.Much has been said in recent decades as to where institutions are heading, most of the time seeing it as a one-way process of secularization. It has been argued that modernity is basically just that, for politics and society as much as for science and culture at large: throwing off the theological, and donning the human and worldly. By contrast, the point I have been laboring to make is that modernity stems from dialogue and osmosis between the two poles-call it dialectic, dualism, or what you will-and in various ways this has hinged on the process of confessionalization (that is, the changeover from a single creed, central to the liturgy and common faith of all the Churches of Europe, to professions of faith that differ across European regions). Churches and states are tied in life and death to this common process. Historians-and still more analysts and political commentators-go very wrong when they overlook this point in tackling the present-day aspects of crisis: the issue of secularism, of multiculturalism, of our daily tragedy of migration and uprooted peoples. The problem is that their analysis is boxed inside the modern period and its time frame. What changes with this century is not that our view of history is better than our forefathers', but simply that now-as 2017 approaches-we can see this pattern from outside and above the viewpoint of the masters who came before us.The claim I start from and intend vigorously to uphold is that, over the last fifty years, the historian's perspective has altered enormously, just as daily historical events have changed with globalization and mushrooming technology. We now stand outside the long historical cycle that generated the Europe into which my own generation was born. We have thrown off confessional-ecclessiastical historiography but are far from acquiring a historically appropriate awareness to guide our research and divulge its insights.As for the unfolding of historical events these last fifty years, everything has changed around us. In the 1950s the panorama in which Western man grew up had been splendidly captured by Gabriel Le Bras in a short study that I hail as one of the best things written in our field: L'Eglise et le village (Paris, 1976). …

Réforme catholique, religion des prêtres et “foi des simples”. Études d’anthropologie religieuse (XVI e –XVIII e siècles) by Dominique Julia (review)

Reviewed by: Réforme catholique, religion des prêtres et “foi des simples”. Études d’anthropologie religieuse (XVIe–XVIIIe siècles) by Dominique Julia Joseph Bergin Réforme catholique, religion des prêtres et “foi des simples”. Études d’anthropologie religieuse (XVIe–XVIIIe siècles). By Dominique Julia. [Cahiers d’Humanisme et Renaissance, Vol. 118; Sous-collection Ad Deum nfl 2.] (Geneva: Librairie Droz. 2014. Pp. 525. €75,00/$98.40 paperback. ISBN 978-2-600-01753-4.) Now that the quarante glorieuses of postwar French historiography are themselves becoming an object of increasing historical curiosity, several scholars who are little known to a wider public have been gaining the recognition they deserve. The golden age of the French historical sociology of religion, as it was called, was inspired primarily by the distinguished medievalist Gabriel Le Bras; the subsequent shift toward religious anthropology was the work of an early modernist who was the radical opposite of Le Bras, Alphonse Dupront. Dominique Julia managed the feat of being a disciple of both men! It was Dupront, who published scarcely anything during his lifetime, that founded an influential research institute, the Centre d’Anthropologie Religieuse Européenne (CARE), of which Julia, an indefatigable researcher and participant in collective projects, has been a pillar over the years. The essays in this collection cover only part of his oeuvre, as Julia has been active in several other major fields of research without ever abandoning his earlier terres d’élection. These include the history of schooling, literacy, reading habits, universities, colleges, teaching orders, pedagogical credos, childhood, pilgrimages, miracles, and historiography. Nor is this all: from the outset, his publications have been accompanied by the hard-graft of inventorying and editing extant sources. Hardly any of this enormously varied output, which runs to approximately 200 items, has been in book form, apart two early forays—one with Michel de Certeau and Jacques Revel on language politics during the French Revolution, another with Roger Chartier on education in early-modern France. This reviewer has long considered Julia a master of the extended and thoroughly researched monographic article, which has become so rare in any language today. Indeed, the volume under review contains two such publications—“La Réforme post-tridentine en France” (pp. 137–231) and “Un miracle à Paris en 1725” (pp. 343–410)—both of which have hitherto been available only in Italian publications that can be difficult to find. The first of them dates from 1973 and remains the most comprehensive and lucid synthesis of the research done by Le Bras’s disciples on pastoral visitations as a source for the history of popular religious practices. It is supported here by two further essays on the Tridentine reform’s campaign to separate popular “profane” culture from authorized religion and on the culture of the French clergy in Champagne, one of whom, the famous Jean Meslier, was a secret atheist. A major debate of the 1970s concerned the subject of de-Christianization before 1789. Julia’s long essay on that question deals with the evolution of the eighteenth-century Diocese of Auxerre, where the religious culture [End Page 639] imposed by a Jansenist bishop and clergy led to bitter divisions by the 1760s, prefiguring similar changes elsewhere in France. A third essay examines the political questions—an unusual subject for Julia—which produced an ever-widening gap between church and monarchy under Louis XV. By contrast, the essay on the 1725 miracle in Paris, which dates from 2007 and arose from more recent research inspired by Dupront on pilgrimages and miracles at the CARE, is unfortunately the most isolated of the collection and would have benefited from being flanked by one or more essays from Julia’s pen on this subject. Finally, as Julia is also a learned and astute guide to historians’ methodology, with an impressively wide range of interdisciplinary reference, it is no surprise that the volume opens with three essays on historiography, but with a characteristic focus on sources and their relative value. One of the essays reprinted here was first published in the celebrated 1970s collection Faire de l’Histoire. In 1995, Julia coedited Passés recomposés...

Developmental expression of vascular endothelial growth factor receptor 3 and vascular endothelial growth factor C in forebrain

Increased understanding of the neurovascular niche suggests that development of the central nervous system (CNS) and its vasculature is coordinated through shared regulatory factors. These include the vascular endothelial growth factor (VEGF) family, reported to promote neuroproliferation and neuroprotection in addition to angiogenesis via its receptors VEGFR1–3. VEGFR3, a mediator of lymphangiogenesis, is expressed in murine and rat brain from early gestation, has been associated with neural progenitors and neurons (Choi et al., 2010) and oligodendroglia (Le Bras et al., 2006) in the developing cortex and is reported to mediate adult neurogenesis in the subventricular zone (SVZ) (Calvo et al., 2011). The early expression pattern of VEGFR3 protein and its cellular associations has not as yet been comprehensively reported. We describe the temporal expression of VEGFR3 protein at a cellular level and its close association with its VEGFC ligand, determined by double-labeling immunohistochemistry in the developing rat brain from embryonic day (E) 13 to postnatal day (P) 23. We found high expression of VEGFR3 in the ventricular zone and along radial glia in early gestation in association with neural stem cells and neuroblasts. Similar expression patterns were seen in the immature olfactory bulb and optic cup. In later development we found less expression by neural progenitors in proliferative regions including the SVZ and dentate gyrus of the hippocampus. In contrast, VEGFR3 expression increased with development in the cortex in neurons and astrocytes, and appeared in the emerging population of oligodendroglial progenitors. High expression in ventricular ependyma, choroid plexus and pigmented retinal epithelium was noted from E18. VEGFC ligand was found in association with VEGFR3 throughout development, with highest expression in embryonic stages. Our findings suggest an important role for VEGFC/VEGFR3 signaling in neuronal proliferation in early forebrain development, and ongoing functions with niche neurogenesis, glial and ependymal function in the maturing postnatal brain.

Vascular endothelial growth factor receptor 3 controls neural stem cell activation in mice and humans.

SUMMARYNeural stem cells (NSCs) continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR) 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs), VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

Metabarcoding analysis of European hake diet in the Mediterranean Sea

Event Abstract Back to Event Metabarcoding analysis of European hake diet in the Mediterranean Sea Giulia Riccioni1*, Marco Stagioni1, Fausto Tinti1, 2, Corrado Piccinetti1 and Simone Libralato3 1 University of Bologna, Department of Biological, Geological and Environmental Sciences, Italy 2 University of Bologna, Department of Biological, Geological and Environmental Sciences, Italy 3 National Institute of Oceanography and Experimental Geophysics, Italy European hake (EH), Merluccius merluccius, is a demersal fish distributed from the North Sea and Atlantic to the Levantine Sea in the Mediterranean. EH is an important predator of deep Mediterranean upper shelf slope communities and it is currently characterised by growth overexploitation. EH adults feed mainly on fish and squids whereas the young (<16 cm) feed on crustaceans. All current EH diet studies relied on the morphological identification of prey remains in stomach content, however this method is labour intensive and it precludes the identification of strongly digested food. The development of High-Throughput Sequencing (HTS) approaches provide more accurate methods for dietary studies revealing many consumed species simultaneously (DNA metabarcoding). The aim of this study is to use a HTS approach based on COI amplification, contextually to classic microscopic morphological identification, to analyse EH stomach content and to evaluate the efficiency of the molecular method. HTS sequencing has been carried out on the amplicons obtained by PCR amplification (Leray et al. 2013) of stomach remains and all the Miseq Illumina paired-end reads have been analysed by using bioinformatic tools (Boyer et al. 2015) for taxonomic assignment. The selected sequences clustered in OCTUs (Operational Clustered Taxonomic Units) and taxonomically assigned, will be used in diversity analyses to compute distance matrices among samples, to compare taxa summaries from different samples, to create networks and perform PCA and PcoA analysis. Classic microscopic morphological analyses on stomach content remains have been carried out contextually to compare the results of the two methods. The molecular approach has proven a promising method to study marine fish dietary habits. All the data will be summarized to reconstruct EH trophic dynamics in the Mediterranean Sea. Acknowledgements This study has been conducted in the framework of the “progetto bandiera RITMARE” (Ricerca Italiana per il Mare). References Leray, M., Yang, J. Y. , Meyer, C.P., Mills, S.C., Agudelo, N., Ranwez,V., Boehm, J.T., and Machida, R.J. (2013) A new versatile primer set targeting a short fragment of the mitochondrial COI region for metabarcoding metazoan diversity: application for characterizing coral reef fish gut contents. Front. Zool., 10:34 Boyer, F., Mercier, C., Bonin, A., Le Bras, Y., Taberlet, P., and Coissac, E. (2015). obitools: a unix‐inspired software package for DNA metabarcoding. Mol. Ecol. Resour. Keywords: metabarcoding, European Hake, Diet, Illumina, Mediterranean Sea Conference: XV European Congress of Ichthyology, Porto, Portugal, 7 Sep - 11 Sep, 2015. Presentation Type: Poster Presentation Topic: Phylogeny, Systematics and Genetics Citation: Riccioni G, Stagioni M, Tinti F, Piccinetti C and Libralato S (2015). Metabarcoding analysis of European hake diet in the Mediterranean Sea. Front. Mar. Sci. Conference Abstract: XV European Congress of Ichthyology. doi: 10.3389/conf.FMARS.2015.03.00160 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Oct 2015; Published Online: 28 Nov 2015. * Correspondence: PhD. Giulia Riccioni, University of Bologna, Department of Biological, Geological and Environmental Sciences, Fano, 61032, Italy, giulia.riccioni@unibo.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Giulia Riccioni Marco Stagioni Fausto Tinti Corrado Piccinetti Simone Libralato Google Giulia Riccioni Marco Stagioni Fausto Tinti Corrado Piccinetti Simone Libralato Google Scholar Giulia Riccioni Marco Stagioni Fausto Tinti Corrado Piccinetti Simone Libralato PubMed Giulia Riccioni Marco Stagioni Fausto Tinti Corrado Piccinetti Simone Libralato Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Abstract 335: A genetic mouse model of head-and-neck squamous cell carcinoma using targeted deletion of E-cadherin and TGFβ receptor II.

Abstract We previously observed that 70% of esophageal tumors demonstrated coordinated loss of E-cadherin and TGFβRII. When grown in three-dimensional organotypic reconstruct cultures, cells lacking E-cadherin and TGFβRII demonstrate fibroblast-dependent invasion into the underlying matrix. Therefore, we hypothesized that coordinated loss of CDH1 (E-cadherin) and TGFBR2 (TGFβRII) will induce tumorigenesis in vivo. We developed a mouse model targeting CDH1 and TGFBR2 loss in the oral-esophageal epithelium using the Epstein-Barr virus L2 promoter, ED-L2. For spatio-temporal control of CDH1- and TGFBR2 gene expression, we also generated an inducible mouse model using Cre-ERT(tam) under the control of the keratin 14 promoter. Few mouse models focusing on genetic alterations of oral and head-and-neck cancer exist. We show that the loss of E-cadherin and TGFβ receptor II without carcinogen treatment is sufficient to induce invasive HNSCC and forestomach tumors. Double knock-out animals succumb to the disease between 1 and 1.5 years of age and show invasive tumors in the oral cavity and tongue, as well as the forestomach. Advanced tumors metastasize to the lung. The tumors are characterized by Ki67-positive and p63-positive staining and show disruption of adherens junctions with loss of β-catenin and mislocalisation of p120 to the cytoplasm. Additional genetic modifications frequently described for HNSCC are the upregulation of c-myc and cyclin D1. We could show that the oral mouse tumors are positive for these markers allowing us to conclude that this animal model recapitulates HNSCC at the pathologic and molecular levels. Furthermore, the forestomach is an extension of the squamous epithelium of the esophagus in the mouse. Known genetic alterations causing esophageal squamous cancer are amplification of EGFR, cyclin D1 and mutations in p53 in addition to the loss of E-cadherin and TGFβRII. The analysis of the forestomach tumors recapitulates these events in the mouse model as a result of CDH1 and TGFBR2 loss. This tumor model will provide us with a unique tool for testing therapeutic approaches. Citation Format: Thomas Andl, Gregoire F. Le Bras, Nicole F. Richards, Gillian L. Allison, M. Kay Washington, R. Katie Lee, Claudia D. Andl. A genetic mouse model of head-and-neck squamous cell carcinoma using targeted deletion of E-cadherin and TGFβ receptor II. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 335. doi:10.1158/1538-7445.AM2013-335

Canon Law and the Letters of Ivo of Chartres. By Christof Rolker. Cambridge Studies in Medieval Life and Thought, 4th series. Cambridge: Cambridge University Press, 2010, xiii + 396 pp. £65.00 cloth.

(ProQuest: ... denotes non-US-ASCII text omitted.)One of the most influential studies of the development of the western church and of its canon law between the ninth and the twelfth centuries has been the Histoire des collections canoniques en Occident: depuis les Fausses Decretales jusqu'au Decret de Gratien of P. Fournier and G. Le Bras (2 vols. [Paris: Recueil Sirey, 1931-2]). Fournier and Le Bras put forward the case for seeing the great reform of the church in the eleventh and twelfth centuries being carried forward by new collections of law intended to promote papal primacy and to eradicate clerical marriage and lay investiture. Whereas the monumental collection of church law made between 1012 and 1022 by Burchard, bishop of Worms, clarified the responsibilities of bishops, some of the collections made in the eleventh century radically promoted papal primacy and "Gregorian" reforms. The Decretum of Ivo, bishop of Chartres from 1090 to 1115, together with his Panormia and Prologue , also promoted reform and entered the mainstream of academic and practical life in the twelfth century as the "investiture contest" drew to an end. Finally the great Concordance of Discordant Canons produced by Gratian of Bologna in about 1140, which built upon the work of Ivo, closed a long period during which "scholastic" methods for interpreting church doctrine and law had been forged, largely by promoters of reform.In the present book Rolker mounts a sustained assault on this powerful account. This may not have been his original intention when he embarked upon a study of the canon law content of Ivo's letters. But the results of his studies have catapulted him into a position where the grand narrative of Fournier and Le Bras had to be further reconsidered once it became clear to him that Ivo was not a reformer in the way in which Fournier and Le Bras had represented him nor was he the author of the Panormia nor was the earlier work of Burchard displaced by new legislation. The result is a fine book on at least three levels. The first is the tunneling for sources utilized by Ivo in his correspondence. In a concordance that fills over thirty-five pages, he lists the parallels between quotations found in the letters and in Ivonian collections. The second level is that of Ivo's participation as bishop of Chartres in the great affairs of the French kingdom and church, including his principled but rather isolated resistance to the re-marriage of king Philip I. The third level is one on which a fresh look is taken at the broad outlines of the history of church reform and the stimulus it gave to scholasticism. These seem less linear than they did to Fournier and Le Bras, very great though their achievement was and remains. The key is Rolker's finding that Ivo is not only not the author of the very successful Panormia but also that he never used it and that it was probably completed later than is usually thought, in about 1115. …