Search

There is a high demand and expectation for subseasonal to seasonal (S2S) prediction, which provides forecasts beyond 2 weeks, but less than 3 months ahead. To assess the potential benefit of artificial intelligence (AI) methods for S2S prediction through better postprocessing of ensemble prediction system outputs, the World Meteorological Organization (WMO) coordinated a prize challenge in 2021 to improve subseasonal prediction. The goal of this competition was to produce the most skillful forecasts of precipitation and 2-m temperature globally averaged over forecast weeks 3 and 4 and over weeks 5 and 6 for the year 2020 using artificial intelligence techniques. The top three submissions, described in this article, succeeded in producing S2S forecasts significantly more skillful than the bias-corrected ECMWF operational reference forecasts, particularly for precipitation, through improved calibration of the ECMWF raw forecast outputs or multimodel combination. These forecast improvements should benefit the use of S2S forecasts in applications. The authors thank the Swiss Data Science Center (SDSC) and the European Centre for Medium-Range Weather Forecasts (ECMWF) for their support to this competition. The CRIMS2S team acknowledges support from the Ministère de l’économie, innovation et exportation (MEIE) of Gouvernement du Québec. The UConn team would like to acknowledge contributions from Krishna Pattipati and Peter Willett from the University of Connecticut, Jason Nachamkin from the Naval Research Laboratory Marine Meteorology Division, and Paolo Braca and Leonardo Millefiori from the NATO STO CMRE. The authors thank the three anonymous reviewers for their suggestions and comments that helped improve the manuscript. Peer Reviewed "Article signat per 22 autors/es: F. Vitart, A. W. Robertson, A. Spring, F. Pinault, R. Roškar, W. Cao, S. Bech, A. Bienkowski, N. Caltabiano, E. De Coning, B. Denis, A. Dirkson, J. Dramsch, P. Dueben, J. Gierschendorf, H. S. Kim, K. Nowak, D. Landry, L. Lledó, L. Palma, S. Rasp, S. Zhou"

The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex is a structure consisting of nesprin, SUN, and lamin proteins. A principal function of the LINC complex is anchoring the nucleus to the actin, microtubule, and intermediate filament cytoskeletons. The LINC complex is present in nearly all cell types, including endothelial cells. Endothelial cells line the innermost surfaces of blood vessels and are critical for blood vessel barrier function. In addition, endothelial cells have specialized functions, including adaptation to the mechanical forces of blood flow. Previous studies have shown that depletion of individual nesprin isoforms results in impaired endothelial cell function. To further investigate the role of the LINC complex in endothelial cells we utilized dominant negative KASH (DN-KASH), a dominant negative protein that displaces endogenous nesprins from the nuclear envelope and disrupts nuclear-cytoskeletal connections. Endothelial cells expressing DN-KASH had altered cell-cell adhesion and barrier function, as well as altered cell-matrix adhesion and focal adhesion dynamics. In addition, cells expressing DN-KASH failed to properly adapt to shear stress or cyclic stretch. DN-KASH-expressing cells exhibited impaired collective cell migration in wound healing and angiogenesis assays. Our results demonstrate the importance of an intact LINC complex in endothelial cell function and homeostasis.

International audience; This paper introduces the use of the Proper Generalized Decomposition (PGD) method for the optical flow (OF) problem in a classical framework of Sobolev spaces, i.e. optical flow methods including a robust energy for the data fidelity term together with a quadratic penalizer for the regularisation term. A mathematical study of PGD methods is first presented for general regularization problems in the framework of (Hilbert) Sobolev spaces, and their convergence is then illustrated on OF computation. The convergence study is divided in two parts: (i) the weak convergence based on the Brézis-Lieb decomposition, (ii) the strong convergence based on a growth result on the sequence of descent directions. A practical PGD-based OF implementation is then proposed and evaluated on freely available OF data sets. The proposed PGD-based OF approach outperforms the corresponding non-PGD implementation in terms of both accuracy and computation time for images containing a weak level of information, namely low image resolution and/or low Signal-To-Noise Ratio (SNR).

Resume Introduction L’infection urinaire (IU) constitue la deuxieme cause d’infection bacterienne communautaire chez le sujet âge. Ce diagnostic est difficile car les symptomes sont souvent atypiques. Nous presentons les caracteristiques des patients ayant une IU parmi une population geriatrique (signes fonctionnels urinaires et/ou syndrome infectieux). Nous avons egalement evalue la sensibilite et la specificite de la bandelette urinaire (BU) pour le diagnostic d’IU dans cette population. Patients et methode Nous avons realise une etude observationnelle, prospective, monocentrique, d’avril 2017 a janvier 2018, incluant tous les patients hospitalises en geriatrie, presentant des signes fonctionnels urinaires et/ou un syndrome infectieux sans point d’appel, pour lesquels un examen cytobacteriologique des urines (ECBU) a ete demande. Une BU etait systematiquement realisee pour tous ces patients. Les caracteristiques cliniques et biologiques des patients ont ete etudiees selon le diagnostic definitif. En outre, les resultats des BU ont ete compares a ceux des ECBU en cas de diagnostic final d’IU. Resultats Au total, 165 patients ont ete inclus. Parmi eux, 67 (40,6 %) avaient une IU et 98 (59,4 %) avaient un autre diagnostic. Il y avait significativement plus de femmes ( p p La BU presentait une sensibilite elevee (92 %) et une VPN elevee (91 %) interessantes dans notre population. Conclusion En cas d’IU chez le sujet âge, peu de criteres sont discriminants avec une autre origine. Par ailleurs, une BU negative suggere l’absence d’IU en raison de sa bonne valeur predictive negative.

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies., Clinical management of COVID-19 in resource-poor settings has distinct challenges and detailed patient characterisation is needed. Here, the authors describe the clinical and immunological profiles of patients at a hospital in Malawi with confirmed and suspected COVID-19.

Summary Introduction The Coronavirus disease-2019 outbreak (COVID-19) has been declared a pandemic by the World Health Organization. Studies report both a severe inflammatory syndrome and a procoagulant state in severe COVID-19 cases, with an increase of venous thromboembolism, including pulmonary embolism (PE) and deep vein thrombosis (DVT). In this context, we discuss the use of doppler ultrasonography (DUS) in the screening and diagnosis of DVT in ambulatory and hospitalized patients with, or suspected of having, COVID-19, outside the intensive care unit (ICU). Material and methods Non-systematic review of the literature. Results In patients hospitalized for or suspected of COVID-19 infection with the presence of either (a) DVT clinical symptoms, (b) a strong DVT clinical probability (Wells score > 2) or (c) elevated D-dimer levels without DVT clinical symptoms and without PE on lung CT angio-scan, DVT should be investigated with DUS. In the presence of PE diagnosed clinically and/or radiologically, additional systematic DVT screening using DUS is not recommended during the COVID-19 pandemic. The use of 4-points compression DUS for DVT screen and diagnosis is the most appropriate method in this context. Discussion Systematic DUS for DVT screening in asymptomatic COVID patients is not recommended unless the patient is in the ICU. This would increase the risk of unnecessarily exposing medical staff to SARS-CoV-2 and monopolizing limited resources during this period.

Accurate spatial dose delivery in radiotherapy is frequently complicated due to changes in the patient’s internal anatomy during and in-between therapy segments. The recent introduction of hybrid MRI radiotherapy systems allows unequaled soft-tissue visualization during radiation delivery and can be used for dose reconstruction to quantify the impact of motion. To this end, knowledge of anatomical deformations obtained from continuous monitoring during treatment has to be combined with information on the spatio-temporal dose delivery to perform motion-compensated dose accumulation (MCDA). Here, the influence of the choice of deformable image registration algorithm, dose warping strategy, and magnetic resonance image resolution and signal-to-noise-ratio on the resulting MCDA is investigated. For a quantitative investigation, four 4D MRI-datasets representing typical patient observed motion patterns are generated using finite element modeling and serve as a gold standard. Energy delivery is simulated intra-fractionally in the deformed image space and, subsequently, MCDA-processed. Finally, the results are substantiated by comparing MCDA strategies on clinically acquired patient data. It is shown that MCDA is needed for correct quantitative dose reconstruction. For prostate treatments, using the energy per mass transfer dose warping strategy has the largest influence on decreasing dose estimation errors.

Real-time MR-imaging has been clinically adapted for monitoring thermal therapies since it can provide on-the-fly temperature maps simultaneously with anatomical information. However, proton resonance frequency based thermometry of moving targets remains challenging since temperature artifacts are induced by the respiratory as well as physiological motion. If left uncorrected, these artifacts lead to severe errors in temperature estimates and impair therapy guidance. In this study, we evaluated deep learning for on-line correction of motion related errors in abdominal MR-thermometry. For this, a convolutional neural network (CNN) was designed to learn the apparent temperature perturbation from images acquired during a preparative learning stage prior to hyperthermia. The input of the designed CNN is the most recent magnitude image and no surrogate of motion is needed. During the subsequent hyperthermia procedure, the recent magnitude image is used as an input for the CNN-model in order to generate an on-line correction for the current temperature map. The method's artifact suppression performance was evaluated on 12 free breathing volunteers and was found robust and artifact-free in all examined cases. Furthermore, thermometric precision and accuracy was assessed for in vivo ablation using high intensity focused ultrasound. All calculations involved at the different stages of the proposed workflow were designed to be compatible with the clinical time constraints of a therapeutic procedure., 21 pages, 9 figures, 1 table

Objectives Environmental contamination by patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through respiratory droplets suggests that surfaces and equipment could be a medium of transmission. We aimed to assess the surface and equipment contamination by SARS-COV-2 of an emergency department (ED) during the coronavirus infectious disease-2019 (COVID-19) outbreak. Methods We performed multiple samples from different sites in ED patients care and non-patient care areas with sterile premoistened swabs and used real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect the presence of SARS-CoV-2 ribonucleic acid (RNA). We also sampled the personal protective equipment (PPE) from health care workers (HCWs). Results Among the 192 total samples, 10 (5.2%) were positive. In patient care areas, 5/46 (10.9%) of the surfaces directly in contact with COVID-19 patients revealed the presence of SARS-CoV-2 RNA, and 4/56 (7.1%) of the surfaces that were not directly in contact with COVID-19 patients were positive. SARS-CoV-2 RNA was present only in the patients’ examination and monitoring rooms. Before decontamination SARS-CoV-2 RNA was present on the saturation clip, the scuff for blood pressure measurement, the stretcher, the plastic screens between patients and the floor. After decontamination, SARS-CoV-2 RNA remained on the scuff, the stretcher and the trolleys. All samples from non-patient care areas or staff working rooms were negative. Only one sample from the PPE of the HCWs was positive. Conclusions Our findings suggest that surfaces and equipment contamination by SARS-CoV-2 RNA in an ED during the COVID-19 outbreak is low and concerns exclusively patients’ examination and monitoring rooms, preserving non-patient care areas.

Introduction Les etudes anterieures sur la mucormycose du systeme nerveux central (SNC) sont basees sur des cas rapportes ou des cohortes de petits effectifs. Elles manquent de donnees cliniques et biologiques precises. Des etudes supplementaires sont necessaires pour guider les cliniciens, car la mucormycose du SNC necessite un diagnostic rapide. Materiels et methodes Nous avons mene une etude observationnelle retrospective multicentrique dans 24 hopitaux francais. Tous les patients diagnostiques avec une mucormycose du SNC prouvee, probable ou putative de 2005 a 2020 – selon des criteres EORTC modifies – ont ete inclus dans cette etude. Resultats Sur 42 patients inclus (21 mucormycoses du SNC prouvees, 17 probables et 4 putatives), 69 % etaient des hommes. L’âge median etait de 60 ans [EIQ = 49-64]. Vingt-huit (67 %) avaient une infection pluri-organes par dissemination hematogene, 14 (33 %) avaient une mucormycose orbito-rhino-cerebrale (MORC). Les 2 principales pathologies sous-jacentes etaient les hemopathies malignes (n = 26) et le diabete (n = 11). Il n’y avait pas de difference significative en termes de maladies sous-jacentes entre la dissemination hematogene et la MORC, mais parmi 2 patients n’ayant aucun facteur predisposant aux infections fongiques invasives, tous deux avaient une MORC (p = 0,04). Les signes cliniques frequemment observes comprenaient la fievre (74%) et l’alteration de la conscience (49 %). Cependant, 28% des patients avaient un examen neurologique normal. Des proportions importantes de lymphopenie (87 %), d’hypoalbuminemie (75 %) et de neutropenie (58 %) ont ete observees au diagnostic. L’analyse du liquide cephalo-rachidien (LCR) effectuee chez 14 patients a revele 4 meningites biologiques et 7 cas d’hyperprotenorachies. En termes de biomarqueurs, la PCR serique etait frequemment positive (87 %) et la PCR dans le LCR etait positive dans 50 % des cas. La mortalite globale a un mois etait de 68 % (dont 16 patients (40 %) decedes a une semaine). En analyse univariee, le deces a un mois etait significativement associe a la dissemination hematogene (OR = 12,94) et a la neutropenie au diagnostic (PNN Conclusion Cette etude souligne que la mucormycose du SNC est rapidement mortelle, notamment en cas de dissemination hematogene et de neutropenie. Ainsi, l’infection du SNC doit etre traquee lorsqu’une mucormycose invasive est identifiee ou suspectee. Un examen neurologique normal ne doit pas exclure le diagnostic et une analyse du LCR doit etre effectuee lorsque cela est possible. Dans les cas confirmes, les experts recommandent des doses elevees d’amphotherine-B liposomale et un traitement chirurgical, ce dernier etant associe a une diminution de la mortalite a un mois dans notre etude, bien qu’un biais de selection puisse intervenir.

Purpose Tracking of the internal anatomy by means of a motion model that uses the MR-derived motion fields and noise covariance matrix (NCM) dynamic as a surrogate signal. Methods A 2D respiratory motion model was developed based on the MR-derived motion fields and the NCM of a receive array used in MRI. Temporal dynamics of the NCM were used as a motion surrogate for a linear correspondence motion model. The model performance was tested on five healthy volunteers with a liver as the target. The motion fields were calculated from the cineMR frames with an optical flow registration tool. Results The model estimated the liver motion with an average residual error of 2.3 mm (13% of the motion amplitude). The model formation takes 3 min and the model latency was 0.5 s in the current implementation. The limiting factor for the latency is the current update time of the NCM (0.48 s), which in principle can be reduced to 0.004 s with an alternative way to determine the NCM. Conclusions The 2D respiratory motion of the liver can be effectively estimated with the linear motion model that uses the temporal behavior of the NCM as motion surrogate. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The proposed needle insertion sequencing can therefore assist in delivering an optimal dose in HDR prostate brachytherapy.

INTRODUCTION: Cell stretch is a method which can rapidly apply mechanical force through cell-matrix and cell-cell adhesions and can be utilized to better understand underlying biophysical questions related to intracellular force transmission and mechanotransduction. METHODS: 3D printable stretching devices suitable for live-cell fluorescent imaging were designed using finite element modeling and validated experimentally. These devices were then used along with FRET based nesprin-2G force sensitive biosensors as well as live cell fluorescent staining to understand how the nucleus responds to externally applied mechanical force in cells with both intact LINC (linker of nucleoskeleton and cytoskeleton) complex and cells with the LINC complex disrupted using expression of dominant negative KASH protein. RESULTS: The devices were shown to provide a larger strain ranges (300% uniaxial and 60% biaxial) than currently available commercial or academic designs we are aware of. Under uniaxial deformation, the deformation of the nucleus of NIH 3T3 cells per unit of imposed cell strain was shown to be approximately 50% higher in control cells compared to cells with a disrupted LINC complex. Under biaxial deformation, MDCK II cells showed permanent changes in the nuclear morphology as well as actin organization upon unloading, indicating that failure, plastic deformation, or remodeling of the cytoskeleton is occurring in response to the applied stretch. CONCLUSION: Development and open distribution of low-cost, 3D-printable uniaxial and biaxial cell stretching devices compatible with live-cell fluorescent imaging allows a wider range of researchers to investigate mechanical influences on biological questions with only a minimal investment of resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12195-019-00579-y) contains supplementary material, which is available to authorized users.

En 2017, le Canada célèbre son 150e anniversaire et mettra sans doute l'accent sur le succès de son modèle de fédéralisme, de sa dualité linguistique, de sa diversité multiculturelle et de son récent traitement plus favorable des Premières nations, entre autres. Derrière ce visage se cachent beaucoup de tensions historiques et de luttes sociales incarnées dans la Charte canadienne des droits et libertés, adoptée en 1982. Au sujet de la dualité linguistique, l'article 23 de la Charte garantit aux minorités des deux langues officielles l'accès à l'éducation dans leur langue maternelle. Sans une mise en application vigoureuse, une telle garantie demeure lettre morte. De fait, il existe six régimes linguistiques au Canada et le respect de l'article 23 s'obtient souvent de gouvernements récalcitrants à force de recours judiciaires. Ceux-ci ont généré 156 jugements depuis l'adoption de la Charte, dont 15 de la Cour suprême du Canada. Nous analysons le cas d'un gouvernement particulièrement réticent à mettre en application l'article 23, c'est-à-dire celui du territoire du Yukon, afin d'expliquer comment toute cette jurisprudence n'arrive pas à régler définitivement et avec une certaine finalité la question des droits de l'article 23. Au-delà des différences de régime linguistique, les jugements pertinents de cette cause yukonnaise manifestent aussi une confrontation des paradigmes idéologiques des intervenants, entre une idéologie majoritaire dominante et restrictive versus une idéologie large et libérale fondée sur le principe de la dualité linguistique.

Urinary tract infections (UTI) are the second cause of community-acquired bacterial infections in the elderly. Distinguishing symptomatic UTI from asymptomatic bacteriuria is problematic, as older adults are less likely to present with localized urinary symptoms. We evaluated characteristics of patients presenting UTI among elderly with sepsis. Moreover, we aimed to evaluate the sensibility and specificity of urine dipstick tests in the diagnosis of UTI in geriatric population.We led a prospective, monocentric, observational study between April 2017 and January 2018. We included patients hospitalized in geriatric wards, who were prescribed urine culture for UTI symptoms or/and infection without primary sites for which a urine culture was prescribed. Dipstick urinalyses were performed for all patients. Clinical and biological characteristics of all patients were compared according to the final diagnosis of UTI. Moreover, results of dipstick tests were evaluated for the diagnosis of UTI in this population.Among 165 patients, 67 (40.6 %) had a UTI and 98 (59.4 %) had another diagnosis. These two groups were comparable for age and daily-living activities. In the UTI group, the proportion of women was higher than in the other group (P0.05), and mean MMSE score was lower (P0.05). Positive urine dipstick test for leukocytes and/or nitrites had high sensitivity (92 %), but low specificity (50 %). Negative predictive value of this test was high (91 %).For suspicion of UTI among elderly, few criteria are specific. Negative dipstick tests can suggest an absence of UTI due to its high negative predictive value.

Abundant literature has focused on the phenomenon called "the curse of natural resources". So far, all authors who have studied the resource curse have focused on the relationship between the endowment of natural resources and macroeconomic growth. We empirically test the existence of this phenomenon using the data of 6581 private enterprises from twenty-four African countries that are rich and poor in natural resources. The data show that enterprises that are set up in countries extracting huge quantities of energizing natural resources are inefficient compared to those in countries poor in natural resources. The extent of the harmful effect of the richness in natural resources on enterprises’ productivity is still more important in countries where share of natural resources in exportation income is very high.

International audience; For the successful completion of medical interventional procedures, several concepts, such as daily positioning compensation, dose accumulation or delineation propagation, rely on establishing a spatial coherence between planning images and images acquired at different time instants over the course of the therapy. To meet this need, image-based motion estimation and compensation relies on fast, automatic, accurate and precise registration algorithms. However, image registration quickly becomes a challenging and computationally intensive task, especially when multiple imaging modalities are involved. In the current study, a novel framework is introduced to reduce the computational overhead of variational registration methods. The proposed framework selects representative voxels of the registration process, based on a supervoxel algorithm. Costly calculations are hereby restrained to a subset of voxels, leading to a less expensive spatial regularized interpolation process. The novel framework is tested in conjunction with the recently proposed EVolution multi-modal registration method. This results in an algorithm requiring a low number of input parameters, is easily parallelizable and provides an elastic voxel-wise deformation with a subvoxel accuracy. The performance of the proposed accelerated registration method is evaluated on cross-contrast abdominal T1/T2 MR-scans undergoing a known deformation and annotated CT-images of the lung. We also analyze the ability of the method to capture slow physiological drifts during MR-guided high intensity focused ultrasound therapies and to perform multi-modal CT/MR registration in the abdomen. Results have shown that computation time can be reduced by 75% on the same hardware with no negative impact on the accuracy.

Medical imaging is currently employed in the diagnosis, planning, delivery and response monitoring of cancer treatments. Due to physiological motion and/or treatment response, the shape and location of the pathology and organs-at-risk may change over time. Establishing their location within the acquired images is therefore paramount for an accurate treatment delivery and monitoring. A feasible solution for tracking anatomical changes during an image-guided cancer treatment is provided by image registration algorithms. Such methods are, however, often built upon elements originating from the computer vision/graphics domain. Since the original design of such elements did not take into consideration the material properties of particular biological tissues, the anatomical plausibility of the estimated deformations may not be guaranteed. In the current work we adapt two existing variational registration algorithms, namely Horn-Schunck and EVolution, to online soft tissue tracking. This is achieved by enforcing an incompressibility constraint on the estimated deformations during the registration process. The existing and the modified registration methods were comparatively tested against several quality assurance criteria on abdominal in-vivo MR and CT data. These criteria included: the Dice Similarity Coefficient (DSC), the Jaccard index, the target registration error (TRE) and three additional criteria evaluating the anatomical plausibility of the estimated deformations. Results demonstrated that both the original and the modified registration methods have similar registration capabilities in high-contrast areas, with DSC and Jaccard index values predominantly in the 0.8 - 0.9 range and an average TRE of 1.6 - 2.0 mm. In contrast-devoid regions of the liver and kidneys, however, the three additional quality assurance criteria have indicated a considerable improvement of the anatomical plausibility of the deformations estimated by the incompressibility-constrained methods. Moreover, the proposed registration models maintain the potential of the original methods for online image-based guidance of cancer treatments.

Background Impact of comedications and comorbidities upon OS isn’t well described in cancer patients (pts). We aimed to evaluate their impacts on DFS and OS on pts resected from a stage III colon cancer and treated by adjuvant FOLFOX-4 +/- cetuximab in the PETACC8 study. Methods Treatments (trts) categories were defined according to the WHO ATC classification system. We focused on 4 medication classes: anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts. We classified the 2559 pts in each category if they took trt at baseline or during study whatever the duration was. Kaplan-Meier method and Cox model were used to compare survival curves. Multivariate analyses were performed on the overall population and according to trt arm. Results Only 1% of pts had no comedications. Comedications with anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts were observed respectively in 18%, 40%, 30% and 9% of the cases. Patients with antidiabetic or cardiovascular trts had more comorbidities. For each other comedication categories, baseline characteristics were balanced between pts treated or not. All comedication categories, except antidiarrheals, were associated with a significant decrease of DFS and OS (Table). Dose-intensity was balanced and may not explain survival differences. For pts treated with at least one cardiac, diabetic or anticoagulant trts, severe events were more frequently reported, including 9 early deaths. The use of antidiarrheals is maybe associated to a better exposure to chemotherapy as reflected by a higher rate of grade ≥3 adverse events but also a potential better efficacy. Table. Comedications impact on DFS and OS. Table . 549P Overall analysis DFS OS HR [95%CI] p HR [95%CI] p Anticoagulants Intake vs no 1.33 [1.10–1.62] .003 1.34 [1.07–1.67] .01 Antidiarrheals Intake vs no 0.87 [0.73–1.04] .12 0.78 [0.63–0.96] .02 Cardiovascular trts Intake vs no 1.20 [1.03–1.41] .02 1.28 [1.07–1.54] .01 Antidiabetics Intake vs no 1.37 [1.07–1.76] .01 1.45 [1.09–1.92] .01 Conclusions Comorbidities related to analyzed ATC classes negatively impact OS and DFS in PETACC8 pts, except antidiarrheal agents which positively impact OS and DFS. Clinical trial identification PETACC8; 2005-003463-23. Legal entity responsible for the study Federation Francophone de Cancerologie Digestive, Dijon. Funding Merck and Sanofi. Disclosure J. Taieb: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.

Introduction Les traitements par CAR-T ont depuis peu une AMM dans les leucemies aigues lymphoblastiques refractaires (LAL) et les lymphomes B a diffus a grandes cellules en rechute/refractaire, et se developpent dans le myelome et certaines tumeurs solides. Ces therapies s’adressent actuellement a des sujets lourdement pretraites et immunodeprimes. De plus, l’injection de CAR-T se complique frequemment d’un syndrome de relargage cytokinique (CRS), proche d’un syndrome d’activation macrophagique dans les formes severes et necessitant la prescription d’immunomodulateurs comme le tocilizumab ou une corticotherapie. Materiels et methodes Nous rapportons les infections chez 9 cas de LAL B refractaire traites par CAR-T tisagenlecleucel (Kymriah®) dans notre centre depuis 07/2017. Resultats Sept/9 (78 %) etaient de sexe masculin, d’âge median 21 ans (18 a 30), atteints de LAL-B en rechute/refractaire, en mediane apres 2 lignes de traitement (1 a 6), dont 5/9 (56 %) en rechute d’une allogreffe de moelle, 5/9 (56 %) en aplasie pre-CAR-T. Trois (33 %) etaient colonises a BMR/BHR, 2 avaient un antecedent d’infection a Clostridium difficile, 1 d’aspergillose invasive (AI) possible. Apres l’injection de CAR-T, 2 ne sont jamais sortis d’aplasie, la mediane de sortie etant de 13 jours pour les 7 autres patients (0 a 20 j). Parmi les 7/9 (78 %) ayant eu un CRS, 6/7 (86 %) etaient de grade 2 ou plus avec un passage en reanimation dans 5/7 (71 %) cas, 3/7 (43 %) ont recu du tocilizumab, 4/7 (57 %) une corticotherapie. Sur le plan infectieux, ont ete documentes apres l’injection de CAR-T : une colite a Clostridium difficile, des bacteriemies a Klebsielle,Providencia,une infection de catheter a Staphylocoque haemolyticus, une AI pulmonaire probable, une infection invasive sinusienne mixte a alternaria et mucorale, une infection invasive fongique pulmonaire possible, des reactivations a CMV, adenovirus, une cystite hemorragique a BK virus et une infection respiratoire a rhinovirus. Parmi les 4/9 (44 %) patients decedes, 1 etait en echec, 2 avaient une rechute de leur LAL et 1 un CRS de grade 5. Conclusion Les CAR-T s’adressent actuellement a des patients tres immunodeprimes, en rechute de leur maladie, qui vont developper apres l’injection de CAR-T des reactivations virales, des septicemies et infections invasives fongiques parfois tres severes. Ces episodes infectieux constituent le diagnostic differentiel principal des CRS qui necessitent, dans leur forme grave, un traitement rapide par tocilizumab et une corticotherapie. La mise en place d’un observatoire infectieux parait necessaire afin de mieux apprehender l’incidence de ces evenements et de preciser les liens entre CRS et infection apres traitement par CAR-T.

Resume Deux portees (I et II) de chiots Corgi gallois Pembroke, respectivement 7 et 6 sujets, ainsi que leur mere commune et leurs peres differents ont subi un examen oculaire complet. Les geniteurs etaient apparentes. A l’exception de l’un d’entre eux (pere de la portee no II), tous les sujets examines presentaient une persistance de la membrane pupillaire (PMP) sans deficit visuel invalidant pour aucun d’entre eux. Quatre chiots de la portee II montraient des opacites corneennes endotheliales focales unilaterales, deux de la portee I des opacites corneennes endotheliales plus etendues ainsi que des lesions de dermoides conjonctivo-corneen et corneen unilaterales. Ces dernieres ont ete traitees avec succes par keratectomie superficielle. Les modes de transmission autosomique recessif, mais aussi polygenique, etaient compatibles avec la distribution et le phenotype des cas de PMP observes.

We reviewed Canadian federal, provincial, and territorial policies related to the health of official language minorities (OLMs) and found important provincial and territorial differences as well as policies penalizing OLMs, which thus contribute significantly to health disparities and to the low vitality of OLM communities. These findings suggest the need for more aggressive, hands-on, and concerted federal and provincial/territorial government efforts to address social inequities and health disparities. Increased policy coherence between these levels of government will not only increase the health and vitality of these populations but also help close the disparity gap and lead to better health and well-being for all Canadians.