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Photon Counting Detectors (PCDs) open new opportunities in X-ray imaging. Pixie III is a PCD using simultaneously two energy thresholds. This enables to acquire images using two distinct energy bins in a single exposure and allows to perform K-Edge Subtraction (KES) imaging with laboratory sources. In that context, one has however to deal with an energy bin optimization: narrow energy bins lead to high KES signal at the expense of higher noise, while wider energy bins lead to poor KES signal but better statistics. This work presents a model that aims at finding the optimal energy thresholds and source voltage in order to retrieve the best Contrast to Noise Ratio (CNR) for a given sample. The model also optimizes the parameters for conventional absorption modality and compares both modalities. Since the input flux and the energy difference between the thresholds influence image noise, this is included in the model using phenomenological laws. The model is then compared to empirical optimization by experimental screening of the parameters using model materials composed of barium, iodine and water. Finally, it is explained how to model the influence of sample composition on the predicted CNR values.

Fracturing two-dimensional random fiber networks of different densities (porosities) were statistically analyzed using both high-resolution finite element models and image analysis algorithms. Under small strains, the finite element fracture models revealed that networks with high relative densities were able to localize evolving fractures to small cracks while surprisingly larger cracks were required to localize fractures in networks of lower density. Further, it is indicated that the pore size distribution in fiber networks is rather diverse and can be captured using two mixed Gamma distributions; one part describing the background size distribution containing the vast majority of pores, and a second part describing the size distribution of larger pores and open regions. The second part covers less than 5% of the total network area but seems to be of paramount importance for the network’s global fracture behavior. It seems as a fiber network’s crack sensitivity is related to the average pore size in the second part of the mixed Gamma distribution. The analysis is remarkably consistent with reported experiments.

Background Gastroparesis is a gastrointestinal motor disorder characterized by a delay in gastric emptying without evidence of mechanical obstruction. Data pertaining to the demographic and clinical characteristics of gastroparesis in the Canadian population is sparse. Aims To review the authors’ experience with gastroparesis. Methods This is a retrospective observational study conducted at the Hôpital Maisonneuve-Rosemont, a tertiary care center affiliated with the University of Montréal. We collected clinical data from all patients who had a diagnosis of gastroparesis confirmed by gastric emptying scintigraphy from January 2017 to December 2019. The authors reviewed medical records for details on gastroparesis etiologies, response to pharmacologic and non-pharmacologic treatment. Results 80 patients met the inclusion criteria. 66,8% of them were females. Average age was 62,4 ± 15,7 years. The most frequently identified etiologies of gastroparesis were idiopathic (36.3%), type 1 and 2 diabetes (40%) and medication-induced (23.8%). 82.8% of idiopathic cases were women. 56.6% of patients achieved complete resolution of symptoms with only one pharmacological agent. Response to pharmacologic treatment were mixed, with domperidone and prucalopride having the highest rates of complete resolution of symptoms. Simultaneous use of 2 pharmacologic agents was attempted in 14 patients, half of which achieved resolution of symptoms. All of these patients had at least partial amelioration of their symptoms with the addition of another pharmacologic treatment. Few patients were referred to a dietician, but 66,7% clinically improved with nutritional counselling. Non-pharmacologic approach alone (nutrition consultation, counselling from the physician, withdrawal of causal medication) leads to at least partial amelioration of symptoms in 77,8% of patients. Conclusions Diabetic gastroparesis represents the most frequent cause of gastroparesis in our study, with a significant female preponderance. Improvement in symptoms was associated with the use non-pharmacological interventions, as well as simultaneous use of two pharmacological agents. Funding Agencies None

International audience

The COVID-19 pandemic has a pervasive effect on all aspects of family life. We can distinguish the collective societal and community effects of the global pandemic and the risk and disease impact for individuals and families. This paper draws on Rolland's Family Systems-Illness (FSI) model to describe some of the unique challenges through a multisystemic lens. Highlighting the pattern of psychosocial issues of COVID-19 over time, discussion emphasizes the evolving interplay of larger systems public health pandemic challenges and mitigation strategies with individual and family processes. The paper addresses issues of coping with myriad Covid-19 uncertainties in the initial crisis wave and evolving phases of the pandemic in the context of individual and family development, pre-existing illness or disability, and racial and socio-economic disparities. The discussion offers recommendations for timely family oriented consultation and psychoeducation, and for healthcare clinician self-care.La pandemia de la COVID-19 tiene un efecto generalizado en todos los aspectos de la vida familiar. Podemos distinguir los efectos comunitarios y sociales colectivos de la pandemia mundial, y el riesgo y el efecto de la enfermedad en las personas y en las familias. Este artículo hace uso del modelo de Sistemas Familiares y Enfermedad (Familly Systems Illness Model) de Rolland para describir algunos de los desafíos únicos que plantea la pandemia desde una perspectiva multisistémica. Destacando el patrón de problemas psicosociales de la COVID-19 conforme avanza el tiempo, el debate enfatiza la interacción emergente de los desafíos que plantea la pandemia en sistemas más grandes como la salud pública y las estrategias de mitigación con procesos familiares e individuales. El artículo aborda los problemas del afrontamiento con innumerables incertidumbres sobre la COVID-19 en la fase de crisis inicial y en las fases posteriores de la pandemia en el contexto del desarrollo individual y familiar, de discapacidades o enfermedades preexistentes, y de disparidades raciales y socioeconómicas. El debate ofrece recomendaciones para una consulta orientada a la familia y una psicoeducación oportunas, así como para el cuidado personal de los médicos de atención a la salud.COVID-19新冠肺炎疫情对家庭生活的各个方面都有普遍影响。我们可以区分全球性的疫病对作为整体的社会和社区的影响以及对个人和家庭的风险和疾病影响。本文借鉴了罗兰德的家庭系统疾病（FSI）模型，通过多系统视角描述了一些独特的挑战。本文突出强调了一段时期以来，COVID-19带来的心理社会问题的模式，讨论的内容也强调了更大系统的公共健康流行病挑战与缓解战略两者之间不断变化发展的相互作用，这种缓解策略关系到个人和家庭过程。本文讨论了在个人和家庭发展、既往疾病或残疾以及种族和社会经济差距的背景下，在危机初期和疫情演变阶段中应对大量新冠肺炎不确定性的问题。本讨论为适时进行家庭咨询、心理教育及医疗保健临床医生的自我保健提供了建议。.

Provides John S. Rolland's acceptance speech for the 2018 CFHA Don Bloch Award. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Introduction Les populations de sans domicile fixe ont un taux de mortalite superieur a celui de la population generale. Ceci est en partie en lien avec des maladies chroniques non suivis, des problemes d’addiction ainsi qu’une exposition plus forte aux maladies transmissibles, en particulier respiratoires. Nous avons realise une etude pour evaluer les taux d’attaque, d’hospitalisation et de mortalite lies a l’infection par le SARS-CoV-2 dans une population de residents de centres d’hebergement pour sans-abri et du personnel a leur contact. Materiels et methodes Une etude serologique retrospective a ete realisee sur l’ensemble des residents et des membres du personnel de trois centres d’hebergement pour sans-abri entre mars et mai 2020 : 2 centres de lits halte soins sante (LHSS) et un dortoir de femmes. Nous avons inclus tous les adultes presents dans les centres d’hebergement ou decedes d’une infection averee par le SARS-CoV-2. Les IgG anti-SARS-CoV-2 etaient detectes par le test ELISA « SARS-CoV-2 IgG Architect (Abbott) ». Un cas confirme de SARS-CoV-2 etait defini comme tout participant presentant une PCR ou une serologie positive. Des serologies de controle ont ete prelevees quatre mois apres la premiere serologie positive. Resultats Nous avons inclus 100 residents et 83 membres du personnel. Le taux de SARS-CoV-2 confirme par PCR ou serologie etait de 72/100 (72,0 %) pour les residents et de 17/83 (20,5 %) pour le personnel. Le taux d’hospitalisation chez les residents etait de 17/72 (25 %) et le taux de deces de 4/72 (5,6 %). Toutes les hospitalisations sauf une et tous les deces sont survenus chez des residents des LHSS. Trente-quatre sur 68 (50 %) des residents des LHSS presentaient au moins deux facteurs de risque de forme grave d’infection par le SARS-CoV-2. Les femmes hebergees dans le dortoir etaient plus jeunes, presentaient moins de comorbidite, avaient le taux d’attaque le plus eleve (90,6 %) et une morbidite-mortalite quasi nulle. Cinquante-deux sur 80 (63,4 %) des personnes ayant une premiere serologie positive ont eu une serologie de controle a 4 mois de la premiere serologie et 8 mois environ de leur infection. Parmi eux, 44 (84,6 %) avaient conserve des serologies positives. Conclusion Le taux d’attaque du SARS-CoV-2 etait extremement eleve chez les residents des centres d’hebergement pour sans-abri par rapport a la population generale. Le risque d’infection grave par le SARS-CoV-2 etait fortement associe a la presence de comorbidites a un plus jeune âge. Cette population a risque doit etre consideree comme prioritaire dans les campagnes de vaccination dans l’acces aux logements individuels pour les plus vulnerables.

During compression moulding, Sheet Moulding Compounds (SMCs) are subjected to tensile strains that yield detrimental tears. To understand these mechanisms, tensile experiments were performed with two uncured industrial SMC formulations with low and high pore and fibre contents. These experiments were coupled with Digital Image Correlation to estimate mesoscale strain fields on the sample surface. X-ray microtomography was used to obtain 3D ex situ evolutions of pores and fibre-bundle orientation. Both formulations behaved as porous, elastoviscoplastic, anisotropic and shear thinning fluids, showing strain hardening followed by softening and sample breakage. During stretching, SMCs dilated with anisotropic pore growth, whereas fibre bundles aligned along the tensile direction following the prediction of the modified Jeffery’s equation. In addition, the ductility of SMCs was largely altered both by the initial pore contents and fibre-bundle flocs/aggregates induced during the prepreg fabrication, the latter leading to undesirable strain localisation bands enhancing sample breakage.

When patients are incapacitated and face serious illness, family members must make medical decisions for the patient. Medical decision sciences give only modest attention to the relationships among patients and their family members, including impact that these relationships have on the decision-making process. A review of the literature reveals little effort to systematically apply a theoretical framework to the role of family interactions in proxy decision making. A family systems perspective can provide a useful lens through which to understand the dynamics of proxy decision making. This article considers the mutual impact of family systems on the processes and outcomes of proxy decision making. The article first reviews medical decision science's evolution and focus on proxy decision making and then reviews a family systems approach, giving particular attention to Rolland's Family Systems Illness Model. A case illustrates how clinical practice and how research would benefit from bringing family systems thinking to proxy decisions. We recommend including a family systems approach in medical decision science research and clinical practices around proxy decisions making. We propose that clinical decisions could be less conflicted and less emotionally troubling for families and clinicians if family systems approaches were included. This perspective opens new directions for research and novel approaches to clinical care. (PsycINFO Database Record

The properties of Sheet Moulding Compounds (SMCs) are altered by their porosity induced during the manufacturing or moulding of these prepregs. To characterise the pore scale mechanisms occurring during SMC flow, 3D synchrotron X-ray images were acquired during the compression of two uncured SMCs. For the high fibre content SMC ( 50 wt % ), with a high porosity, pores mainly decreased in size and disappeared during SMC consolidation. These mechanisms were related to the elasticity of the fibrous networks and to the permeability of the porous phase, estimated using pore scale CFD simulation. For the standard fibre content SMC ( 29 wt % ), with a lower porosity, the compressibility was limited and closed pores were transported towards the external surface of samples with non-affine motion, i.e., faster than the SMC flow and with tortuous trajectories. Besides, pores coalesced and decreased in size during compression. The size decrease was mainly related to the dissolution of pore gases.

BACKGROUND: The low FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) diet has proven efficacy to reduce symptoms of irritable bowel syndrome (IBS). Whilst some mechanisms of action are known, our previous work has suggested that FODMAP-microbiota interactions change the metabolome which may modulate pain signaling in the gut, which may also be important. AIMS: The aim of this randomized cross-over study was to further characterize the effect of low and high FODMAP intake on symptoms and the metabolome. METHODS: In this longitudinal IBS (Rome IV) study, patients underwent 4 assessments: two non-intervention periods including a 1-week ‘baseline’ and 3-week ‘run-in’, followed by two dietary interventions, a low- and high-FODMAP diet, given in random order for 3-weeks each. Patients were provided detailed dietary instruction by a specialized dietitian at the start of each diet and advised that either diet may have therapeutic potential. At the end of each of the 4 periods, patients completed a 7-day food diary, the IBS Severity Scoring System (IBS-SSS), the quality-of-life (QOL) Nepean Dyspepsia index (SF-NDI), and provided fasting urine samples. Identification and quantification of 117 urine metabolites was performed using LC-MS. Questionnaires were analyzed by one-way ANOVA with Bonferroni, and metabolomics by multivariate analysis. RESULTS: Ten female patients completed the study for this interim analysis (7 IBS-D, 2 IBS-C, 1 IBS-M). Dietary data showed good compliance with the interventions (Table 1). Symptoms were stable between the non-intervention time points, significantly reduced with the low FODMAP diet (p=0.00), and a trend was seen between the low and high FODMAP diets (p=0.07). The urinary metabolite levels in patients on the low FODMAP diet differed significantly from baseline, the main metabolites responsible for the change were phosphatidylcholines (e.g. PC40:2AA, PC36:0AA, LYSOC18:2). There was also a shift in the metabolome between the low and high FODMAP diets, the most significantly changed metabolites were sphingomyelins (SM 20:2), phosphatidylcholines (LYSOC20:4, PC40:6AE), and acylcarnitines (C18:1OH). CONCLUSIONS: This study showed that IBS symptoms were stable over 3 weeks and lowering dietary FODMAPs significantly improved symptoms. The diets caused a shift in the metabolome, but greater numbers of patients are needed to determine the complete metabolomic profile and their potential physiological significance in symptom responses. FUNDING AGENCIES: CIHRCanadian Nutrition Society

Wood cells constitute the main building block in engineered wood-based materials, whose delimiting property frequently is moisture induced swelling. The hygroexpansion properties of wood cells, technically known as fibers, are used as input in predictive micromechanical models aimed for materials design. Values presented in the literature largely depend on the microfibrillar angle, the geometry of the fiber and limiting modelling assumptions. Synchrotron X-ray micro-computed tomography has recently prompted means for detailed measurements of the geometry of unconstrained individual fibers undergoing moisture-induced swelling, which makes it possible to directly quantify the hygroexpansion properties of the cell wall. In addition to a well-defined three-dimensional geometry, the present approach also accounts for large deformations and the fact that cell-wall stiffness depends on the presence of moisture. A mixed numerical-experimental approach is adopted where a finite-element updating scheme is used to simulate the swelling of an earlywood spruce fiber going from the experimental fiber geometry at 47 % relative humidity to the predicted geometry of the fiber in the wet state at 80 % relative humidity at equilibrium conditions. The hygroexpansion coefficients are identified by comparing the predicted and the experimental three-dimensional fiber geometry in the wet state. The obtained values are 0.17 strain per change in relative humidity transverse to the microfibrils in the cell wall, and 0.014 along the microfibrils.

Introduction Depuis l’emergence du SARS-CoV-2, la pandemie COVID-19 est responsable de 376 427 deces (ECDC). Les personnes precaires, sujettes aux comorbidites multiples et desequilibrees, presentent des facteurs de risque pour des formes graves de COVID-19 et peu d’etudes les concernant ont ete publiees. Les lits haltes soins sante (LHSS) accueillent des personnes en situation de precarite et sans domicile fixe, necessitant des soins aigus sans justifier d’une hospitalisation. Il s’agit d’etablissements medico-sociaux permettant une prise en charge pluridisciplinaire ne pouvant exceder 30 lits. Notre objectif est de decrire les clusters de cas COVID-19 et leur gestion dans 3 de nos LHSS. Materiels et methodes Etude descriptive d’une cohorte dans 3 LHSS. L’ensemble des heberges majeurs de ces structures, ont ete inclus entre le 8 mars (date du premier cas diagnostique) et le 4 mai 2020 (dernier cas diagnostique) et categorises COVID-19 positif ou negatif selon des criteres cliniques ou virologiques ou radiologiques. Les donnees sociodemographiques, cliniques, paracliniques et therapeutiques sont recueillies a partir des dossiers medicaux. Resultats Soixante-dix-huit heberges ont ete inclus, d’âge moyen 53 ans dont 19 individus avec un âge superieur a 65 ans et 74 hommes (94,9 %). Sept (9 %) presentaient un diabete insulinodependant non equilibre, 6 (8 %) une immunodepression, 12 (19,7 %) une pathologie respiratoire chronique et 8 (10,3 %) une obesite. Trente-trois ont eu un diagnostic COVID-19 confirme par PCR (taux d’attaque 42,3 %) et 11 sont des cas possibles, suspectes sur la clinique sans realisation de PCR soit un taux d’attaque probable a 56,4 %. Parmi ces cas probables, 22 (50 %) ont necessite une hospitalisation, et 4 sont decedes, soit une letalite de 9,1 %. Parmi les cas diagnostiques, la fievre isolee etait le symptome le plus frequent (40 individus, 90,9 %) souvent associee a des signes respiratoires (13 individus, 29,6 %). Les defis dans les centres ont ete la mise en place des protocoles d’hygiene avec repartition des cas, contacts et individus sains sur des etages distincts, isolement des cas probables et confirmes, formation du personnel, formation des heberges aux gestes barriere, adaptation des soins habituels et reductions des risques de sevrage notamment. Malgre ces mesures exceptionnelles pour nos structures, l’impact psychique et somatique a ete reel chez le personnel comme les heberges, dont le suivi medicosocial prevu a ete modifie, pouvant majorer l’impact indirect du COVID-19 chez ces personnes vulnerables. Conclusion Dans ces clusters de cas, le taux d’attaque apparait eleve lies aux conditions d’hebergement collectif et au confinement responsables d’une promiscuite prolongee. La letalite apparait elevee, vraisemblablement en lien avec l’âge des individus et les comorbidites. Ces donnees confirment la grande vulnerabilite de nos publics face au SARS-COV-2.

Introduction Au 13 juin 2020, la pandémie COVID-19 est responsable d’au moins 425 931 décès dans le monde dont 29 354 en France. Sans traitement spécifique efficace ni recommandation au début de l’épidémie en France, les attitudes thérapeutiques ont évolué en fonction des publications scientifiques et des recommandations officielles. Ainsi, l’intérêt de l’hydroxychloroquine (HCQ), du tocilizumab ou des corticoïdes a été particulièrement controversé. L’objectif de notre étude est de décrire les attitudes thérapeutiques pour la prise en charge des COVID-19 et leur évolution au cours de la période épidémique en France. Matériels et méthodes Un questionnaire court anonymisé en ligne a été diffusé par la société de pathologie infectieuse de langue française (SPILF) les 22 mars, 23 avril et 10 juin 2020. Il recueillait les caractéristiques d’exercice des répondants, les références utilisées pour la prise en charge des patients COVID-19 et les prescriptions réalisées ou privilégiées (molécules et indications). Résultats Nous avons analysé 144 réponses issues de 115 médecins. Cinquante-trois (46 %) exercent en centre hospitalier universitaire, 79 (69 %) dans un service de maladies infectieuses. Dix-neuf médecins (32 %) de la première étude participaient à au moins un protocole de recherche (5 études différentes), contre 40 (74 %) d’entre eux lors de la deuxième étude (18 protocoles, p

We used three-dimensional (3-D) images of snow microstructure to carry out numerical estimations of the full tensor of the intrinsic permeability of snow (K). This study was performed on 35 snow samples, spanning a wide range of seasonal snow types. For several snow samples, a significant anisotropy of permeability was detected and is consistent with that observed for the effective thermal conductivity obtained from the same samples. The anisotropy coefficient, defined as the ratio of the vertical over the horizontal components of K, ranges from 0.74 for a sample of decomposing precipitation particles collected in the field to 1.66 for a depth hoar specimen. Because the permeability is related to a characteristic length, we introduced a dimensionless tensor K*=K/res2, where the equivalent sphere radius of ice grains (res) is computed from the specific surface area of snow (SSA) and the ice density (ρi) as follows: res=3/(SSA×ρi. We define K and K* as the average of the diagonal components of K and K*, respectively. The 35 values of K* were fitted to snow density (ρs) and provide the following regression: K = (3.0 ± 0.3) res2 exp((−0.0130 ± 0.0003)ρs). We noted that the anisotropy of permeability does not affect significantly the proposed equation. This regression curve was applied to several independent datasets from the literature and compared to other existing regression curves or analytical models. The results show that it is probably the best currently available simple relationship linking the average value of permeability, K, to snow density and specific surface area.

BACKGROUND: Lowering dietary FODMAPs in IBS patients reduces symptom severity in many cases yet the mechanism is poorly understood. It has been proposed that FODMAPs may activate mast cells in some patients. Mast cell mediators in turn could sensitize nociceptors innervating the gut, leading to exaggerated pain signalling. AIMS: To determine if altering FODMAP intake modulates the excitability of nociceptors. METHODS: Three IBS patients (Rome IV; 12 wk longitudinal crossover study) followed a low- and high-FODMAP diet. Mucosal sigmoid biopsies were collected during sigmoidoscopy and symptoms recorded using the IBS symptom severity score (IBS-SSS) at four 3 week intervals: 1) baseline, 2) after a run-in period and 3, 4) after each dietary intervention period; patients reporting score reductions of ≥50 after intervention were defined as responders. Mouse nociceptive dorsal root ganglia (DRG) neurons were cultured overnight with biopsy supernatants. Excitability of the neurons was assessed using perforated patch-clamp techniques and a decrease in rheobase was equated with increased excitability. RESULTS: Patients 1 and 2 (high FODMAP diet 1(st)) responded only to the low FODMAP diet compared to run-in (Table 1). Patient 3 (low FODMAP diet 1(st)) responded to both diets. Rheobases at the different time points did not differ in any patient (Table 1). The baseline rheobase of the IBS patients did not differ from control supernatants, in contrast to that seen previously with many patients. CONCLUSIONS: Low FODMAP dietary intervention reduced symptoms in this patient subset yet colonic biopsy supernatants had no effect on DRG neuron excitability. Thus, this pilot study suggests sigmoid mucosal immune activation may not underlie increased nociceptive signalling in this small subset of IBS patients. Further studies of other IBS patients is needed where baseline immune activation is present as well as studies of other sources of active metabolites e.g. the microbiota. FUNDING AGENCIES: CIHR

Monitoring the time evolution of snow microstructure in 3-D is crucial for a better understanding of snow metamorphism. We, therefore, designed a cryogenic cell that precisely controls the experimental conditions of a sample while it is scanned by X-ray tomography. Based on a thermoelectrical regulation and a vacuum insulation, the cell operates at room temperature. It is, thus, adaptable to diverse scanners, offering advantages in terms of imaging techniques, resolution, and speed. Three-dimensional time-lapse series were obtained under equitemperature and temperature gradient conditions at a 7.8 μm precision. The typical features of each metamorphism and the anisotropic faceting behavior between the basal and prismatic planes, known to occur close to −2°C, were observed in less than 30 h. These results are consistent with the temperature fields expected from heat conduction simulations through the cell. They confirm the cell's accuracy and the interest of relatively short periods to study snow metamorphism.

We carried out a study to monitor the time evolution of microstructural and physical properties of snow during temperature gradient metamorphism: a snow slab was subjected to a constant temperature gradient in the vertical direction for 3 weeks in a cold room, and regularly sampled in order to obtain a series of three-dimensional (3-D) images using X-ray microtomography. A large set of properties was then computed from this series of 3-D images: density, specific surface area, correlation lengths, mean and Gaussian curvature distributions, air and ice tortuosities, effective thermal conductivity, and intrinsic permeability. Whenever possible, specific attention was paid to assess these properties along the vertical and horizontal directions, and an anisotropy coefficient defined as the ratio of the vertical over the horizontal values was deduced. The time evolution of these properties, as well as their anisotropy coefficients, was investigated, showing the development of a strong anisotropic behavior during the experiment. Most of the computed physical properties of snow were then compared with two analytical estimates (self-consistent estimates and dilute beds of spheroids) based on the snow density, and the size and anisotropy of the microstructure through the correlation lengths. These models, which require only basic microstructural information, offer rather good estimates of the properties and anisotropy coefficients for our experiment without any fitting parameters. Our results highlight the interplay between the microstructure and physical properties, showing that the physical properties of snow subjected to a temperature gradient cannot be described accurately using only isotropic parameters such as the density and require more refined information. Furthermore, this study constitutes a detailed database on the evolution of snow properties under a temperature gradient, which can be used as a guideline and a validation tool for snow metamorphism models at the micro- or macroscale.

Conditions involving neurocognitive impairment pose enormous challenges to couples and families. However, research and practice tend to focus narrowly on immediate issues for individual caregivers and their dyadic relationship with the affected member. A broad family systems approach with attention to family processes over time is needed in training, practice, and research. In this paper, Rolland's Family Systems Illness model provides a guiding framework to consider the interaction of different psychosocial types of neurocognitive conditions and their evolution over time with individual, couple, and family life-course development. Discussion addresses key family and couple issues with mild-to-severe cognitive impairment and progressive dementias, including: communication, multigenerational legacies, threatened future neurocognitive disability, ambiguous loss, decisional capacity, reaching limits, placement decisions, issues for adult children and spousal caregivers, and the transformation of intimate bonds. Principles and guidelines are offered to help couples and families master complex challenges, deepen bonds, and forge positive pathways ahead.

Clinicians often assume that patients vaccinated for hepatitis B virus (HBV) have immunity. We report three cases of acute HBV infection in HBV-vaccinated HIV patients. These cases illustrate that patients at an elevated risk of HBV exposure presenting with acute hepatitis should be tested for HBV infection regardless of previous vaccination status.

International audience; Thermoforming allows the manufacture of structural parts for the automotive and aeronautical domains using long fiber thermoplastic prepregs with short cycle times. During this operation, several sheets of molten prepregs are stacked and subjected to large macroscale strains, mainly via in-plane shear, out-of-plane consolidation or dilatation, and bending of the fibrous reinforcement. These deformation modes and the related meso and microstructure evolutions are still poorly understood. However, they can drastically alter the end-use macroscale properties of fabricated parts. To better understand these phenomena, bias extension tests were performed using specimens made of several stacked layers of glass woven fabrics and polyamide matrix. The macroscale shear behavior of these prepregs was investigated at various temperatures. A multiscale analysis of deformed samples was performed using X-ray microtomography images of the deformed specimens acquired at two different spatial resolutions. The low-resolution images were used to analyze the deformation mechanisms and the structural characteristics of prepregs at the macroscale and bundle scales. It was possible to analyze the 3D shapes of deformed samples and, in particular, the spatial variations of their thickness so as to quantify the out-of-plane dilatancy or consolidation phenomena induced by the in-plane shear of prepregs. At a lower scale, the analysis of the high-resolution images showed that these mechanisms were accompanied by the growth of pores and the deformation of fiber bundles. The orientation of the fiber bundles and its through-thickness evolution were measured along the weft and warp directions in the deformed samples, allowing the relevance of geometrical models currently used to analyze bias extension tests to be discussed. Results can be used to enhance the current rheological models for the prediction of thermoforming of thermoplastic prepregs.

Background Cabozantinib (C), a tyrosine kinase inhibitor against VEGFR2, RET, MET and Axl, has demonstrated clinical activity in RCC and 2L HCC, and has been shown to promote an immune-permissive environment. C is being investigated in clinical trials in combination with immune checkpoint inhibitors (ICI). This preclinical study aimed to determine systemic cytokine profile changes induced by the combination of C + αPD1 and assess cooperativity in anti-tumoral effects. Methods Syngeneic colon (CT26, Colon38) and bladder (MBT2) tumour models were established in BALB/C, C57Bl6 or C3H/HEJ mice. C (10 or 30 mg/kg po qd) and αPD1 (10 mg/kg ip 2x weekly) were administered either simultaneously for up to 30 days or with a 14-day delay for αPD1, and serum was collected. Results After 30 days' coadministration of C (30 mg/kg) and αPD1, serum cytokines and chemokines (VEGFA, IL3, GM-CSF, MIP1beta, IL17, CCL5, IFNγ, IL10, IL5) were elevated with a median of 72x (range 39–1207x), as compared to 30-days' single administration of αPD1 or C with a median of 3.7x (1.4–135x) and 1.0x (0.5–1.9x), respectively, relative to vehicle-treated animals. Delayed treatment with αPD1 did not result in the same increase in analyte levels as coadministration (median of 1.74x [1–9.9x]). For anti-tumour efficacies, two C doses were explored in CT26 (T/C10/30 67/38% - tumour growth inhibition T/C ratios at 10 or 30 mg/kg), MBT2 (T/C10/30 37/14%) and Colon38 (T/C10/30 21/12%) models. C at 30 mg/kg led to strong anti-tumour efficacy in MBT2 and Colon38, limiting any ICI combinatorial impact to the post-treatment tumour expansion. For CT26 (30 mg/kg) and MBT2 (10 mg/kg), simultaneous dosing of C and αPD1 showed greater anti-tumour effects than single agents despite only limited effects of αPD1 alone. C + αPD1 more than doubled the treatment-specific time that tumours required to reach 1000mm3 compared to C alone. Conclusions The results indicate that simultaneous treatment of C + αPD1 leads to strong systemic increases in key cytokines and chemokines and can result in robust anti-tumour efficacy. Our results support the clinical exploration of C + ICI combinations and the potential of this TKI for use in further clinical settings. Editorial acknowledgement Isabelle Kaufmann, PhD of Oxford PharmaGenesis, Oxford, UK for provided medical writing support, which was sponsored by Ipsen, Abingdon, UK. Legal entity responsible for the study Ipsen. Funding Ipsen. Disclosure R. Sparks: Full / Part-time employment: Ipsen. S. Rolland: Full / Part-time employment: Ipsen. S. Klinz: Full / Part-time employment: Ipsen. F. Meyer-Losic: Full / Part-time employment: Ipsen. J. Nakhle: Full / Part-time employment: Ipsen. R. Delille: Full / Part-time employment: Ipsen. M. Hillairet de Boisferonc: Research grant / Funding (institution), Contractual obligation: Ipsen.