Le couple et la contractualisation de la rupture

La contractualisation de la rupture impose peu à peu l’arasement des différences entre les trois formes de vie en couple que consacre la loi. La composante institutionnelle du mariage est ébranlée. Déjà, en droit français, la protection assurée par l’entremise du juge est atténuée dans le divorce par consentement mutuel dans la mesure où ni une réelle volonté commune de divorcer ni un règlement juste et équilibré des conséquences de la rupture ne sont effectivement imposés. Néanmoins, le recours obligatoire au juge joue un rôle préventif et symbolique qui rappelle que le mariage est non seulement un contrat mais aussi une institution qui donne statut. Un projet récurrent de divorce par consentement mutuel par déclaration commune devant le notaire menace la spécificité du mariage. En effet, la rupture de l’union ne procéderait alors que de la simple déclaration des époux ; l’aménagement de ses conséquences pour les époux sans enfant serait exclusivement assuré sur un mode consensuel, à l’instar du pacte civil de solidarité (PACS). Cette extension du modèle contractuel n’est cependant pas justifiée par une meilleure protection de ceux qui n’ont que l’arme du contrat pour gérer leur rupture. Dans le PACS comme dans le concubinage, les difficultés liées au coup de force et au partage des richesses ne peuvent être ignorées. Les tribunaux en sont de plus en plus souvent saisis. Elles ne pourront être surmontées que par l’instauration de règles destinées à protéger le membre le plus fragile du couple, en particulier celui qui est délaissé sans ressources.Contractual settlement of failed unions has gradually lessened the differences between the three types of conjugal relations sanctioned by law. The institutional component of marriage has been destabilized. In French law, the protection afforded by the magistrate is attenuated in divorce proceedings by mutual consent insofar as neither a true common resolve to divorce, nor a reasonable and balanced settlement of the consequences resulting from the failed union are ascertained. Nonetheless, the mandatory recourse to a judge plays a preventive and symbolic role that calls to mind that marriage is not merely a contract but also an institution that brings about a change in status. Hence, a recurrent project to implement divorce by mutual consent before a notary threatens the specificity of marriage. Indeed, the dissolution of the marital bond would then be effected by a simple statement made by the spouses ; the arrangement of resulting consequences amongst childless spouses would be exclusively based upon common agreement, somewhat similar to the PACS (pacte civil de solidarité or civil union agreement). The extension of the contractual model cannot be justified by enhanced protection of those whose only defence is a contract to oversee the dissolution of their union. In the French PACS as in concubine unions, difficulties resulting from one party overpowering the other or the inequitable sharing of wealth cannot be overlooked. These issues are increasingly taken to court. They will not be resolved until rules are implemented to protect the weaker party, specifically the one who is left destitute

Les aménagements consensuels que les couples appliquent à leur rupture sont-ils d’essence contractuelle ?

En droit français, il est fréquemment fait appel à des aménagements consensuels pour régler le principe et les conséquences des ruptures de couple. La doctrine qualifie de « contractuels » ces accords et de « contractualisation progressive du droit de la famille » cette tendance. Or la confrontation de ces accords avec les principes qui gouvernent le contrat conduit à douter de cette qualification. Pour ce qui est de la formation de ces accords, dans le cadre institutionnel du divorce comme dans celui réellement contractuel du pacte civil de solidarité (PACS), l’insanité et les vices du consentement ne sont pas pris en considération. En ce qui a trait à leur exécution, ils ne bénéficient ni de la force obligatoire des conventions ni de leur effet relatif lorsque, au-delà du couple, des enfants sont touchés. De même, leur inexécution ne peut être sanctionnée par de simples dommages-intérêts. La qualification habituellement retenue de contractualisation n’est pas seulement erronée. Elle se révèle en outre trompeuse en ce qu’elle cache ce qui se joue derrière cette évolution : le passage d’un gouvernement de la famille par la loi à un gouvernement de la famille par les hommes.Under French law, there is frequent recourse to consensual agreements in order to resolve the consequences of failed unions. Doctrine characterizes such agreements as “contractual” and describes this trend as the “contractualization” of family law. Yet the incompatibility of these agreements with the principles governing contracts raises doubts regarding such an inference. When one observes the formation of agreements both within the institutional context of divorce and in the truly contractual context of the PACS (pacte civil de solidarité or civil union agreement), one notes that neither insanity nor defects of consent are taken into account. As for their performance, they benefit neither from the binding force nor from the relative effect of contracts when, beyond the estranged couple, the fate of their children is at stake. Furthermore, non-performance cannot be sanctioned by mere damages. The often used inference of “contractualization” is not only a misnomer, but is deceitful owing to the real nature of the evolution taking place : namely the transition from a family regime governed by law to a family regime governed by interested individuals

Impact of blood storage and sample handling on quality of high dimensional flow cytometric data in multicenter clinical research

Obtaining reliable and reproducible high quality data in multicenter clinical research settings requires design of optimal standard operating procedures. While the need for standardization in sample processing and data analysis is well-recognized, the impact of sample handling in the pre-analytical phase remains underestimated. We evaluated the impact of sample storage time (approximate to transport time) and temperature, type of anticoagulant, and limited blood volume on reproducibility of flow cytometric studies. EDTA and Na-Heparin samples processed with the EuroFlow bulk lysis protocol, stained and stored at 4 degrees C showed fairly stable expression of cell surface markers and distribution of the major leukocyte populations for up to 72 h. Additional sample fixation (1% PFA, Fix & Perm) did not have any beneficial effects. Blood samples stored for < 24 h at room temperature before processing and staining seemed suitable for reliable immunophenotyping, although losses in absolute cell numbers were observed. The major losses were observed in myeloid cells and monocytes, while lymphocytes seemed less affected. Expression of cell surface markers and population distribution were more stable in Na-Heparin blood than in EDTA blood. However, storage of Na-Heparin samples was associated with faster decrease in leukocyte counts over time. Whole blood fixation strategies (Cyto-Chex, TransFix) improved long-term population distribution, but were detrimental for expression of cellular markers. The main conclusions from this study on healthy donor blood samples were successfully confirmed in EDTA clinical (patient) blood samples with different time delays until processing. Finally, we recognized the need for adjustments in bulk lysis in case of insufficient blood volumes. Despite clear overall conclusions, individual markers and cell populations had different preferred conditions. Therefore, specific guidelines for sample handling should always be adjusted to the clinical application and the main target leukocyte population

Cell therapy for bone fracture repair: A comparative preclinical review of mesenchymal stromal cells from bone marrow and from adipose tissue

Over the last decade, there has been an increasing interest among researchers for human mesenchymal stromal cells (MSC). Their regenerative properties, multilineage differentiation capacity and immunomodulatory properties make them promising candidates for treatment in various conditions. Emerging biotechnology companies specialized in cellular and regenerative therapies have been focusing their interest on MSC-based therapies, and their use in clinical trials has steadily increased. Notably, MSC are currently tested in clinical trials addressing unmet medical needs in the field of bone fracture repair and more specifically in non-union and delayed union fractures where the bone repair process is impaired. Although MSC can be isolated from various tissues, the most commonly studied sources are bone marrow (BM) and adipose tissue (Ad). In this article, we reviewed the literature directly comparing BM- and Ad-MSC for their in vitro characteristics and in vivo osteogenic potential to determine which source of MSC would be more appropriate for bone fracture repair. As considerable variations in experimental settings between studies were found, our review was based on studies meeting specific sets of criteria, notably regarding donors’ age and gender. This review of side-by-side comparisons suggests that while BM-and Ad-MSC share common general characteristics, BM-MSC have a higher intrinsic osteogenic capacity in vitro and bone repair potential in vivo

Improved standardization of flow cytometry diagnostic screening of primary immunodeficiency by software-based automated gating

Background Multiparameter flow cytometry (FC) is essential in the diagnostic work-up and classification of primary immunodeficiency (PIDs). The EuroFlow PID Orientation tube (PIDOT) allows identification of all main lymphocyte subpopulations in blood. To standardize data analysis, tools for Automated Gating and Identification (AG&I) of the informative cell populations, were developed by EuroFlow. Here, we evaluated the contribution of these innovative AG&I tools to the standardization of FC in the diagnostic work-up of PID, by comparing AG&I against expert-based (EuroFlow-standardized) Manual Gating (MG) strategy, and its impact on the reproducibility and clinical interpretation of results. Methods FC data files from 44 patients (13 CVID, 12 PID, 19 non-PID) and 26 healthy donor (HD) blood samples stained with PIDOT were analyzed in parallel by MG and AG&I, using Infinicyt (TM) software (Cytognos). For comparison, percentage differences in absolute cell counts/mu L were calculated for each lymphocyte subpopulation. Data files showing differences >20% were checked for their potential clinical relevance, based on age-matched percentile (p5-p95) reference ranges. In parallel, intra- and inter-observer reproducibility of MG vs AG&I were evaluated in a subset of 12 samples. Results The AG&I approach was able to identify the vast majority of lymphoid events (>99%), associated with a significantly higher intra- and inter-observer reproducibility compared to MG. For most HD (83%) and patient (68%) samples, a high degree of agreement (<20% numerical differences in absolute cell counts/mu L) was obtained between MG and the AG&I module. This translated into a minimal impact (<5% of observations) on the final clinical interpretation. In all except three samples, extended expert revision of the AG&I approach revealed no error. In the three remaining samples aberrant maturation and/or abnormal marker expression profiles were seen leading in all three cases to numerical alarms by AG&I. Conclusion Altogether, our results indicate that replacement of MG by the AG&I module would be associated with a greater reproducibility and robustness of results in the diagnostic work-up of patients suspected of PID. However, expert revision of the results of AG&I of PIDOT data still remains necessary in samples with numerical alterations and aberrant B- and T-cell maturation and/or marker expression profiles

In-depth blood immune profiling of Good syndrome patients

[Introduction]: Good syndrome (GS) is a rare adult-onset immunodeficiency first described in 1954. It is characterized by the coexistence of a thymoma and hypogammaglobulinemia, associated with an increased susceptibility to infections and autoimmunity. The classification and management of GS has been long hampered by the lack of data about the underlying immune alterations, a controversy existing on whether it is a unique diagnostic entity vs. a subtype of Common Variable Immune Deficiency (CVID).[Methods]: Here, we used high-sensitive flow cytometry to investigate the distribution of up to 70 different immune cell populations in blood of GS patients (n=9) compared to age-matched CVID patients (n=55) and healthy donors (n=61).[Results]: All 9 GS patients displayed reduced B-cell counts -down to undetectable levels (<0.1 cells/μL) in 8/9 cases-, together with decreased numbers of total CD4+ T-cells, NK-cells, neutrophils, and basophils vs. age-matched healthy donors. In contrast, they showed expanded TCRγδ+ T-cells (p ≤ 0.05). Except for a deeper B-cell defect, the pattern of immune cell alteration in blood was similar in GS and (age-matched) CVID patients. In depth analysis of CD4+ T-cells revealed significantly decreased blood counts of naïve, central memory (CM) and transitional memory (TM) TCD4+ cells and their functional compartments of T follicular helper (TFH), regulatory T cells (Tregs), T helper (Th)2, Th17, Th22, Th1/Th17 and Th1/Th2 cells. In addition, GS patients also showed decreased NK-cell, neutrophil, basophil, classical monocyte and of both CD1c+ and CD141+ myeloid dendritic cell counts in blood, in parallel to an expansion of total and terminal effector TCRγδ+ T-cells. Interestingly, those GS patients who developed hypogammaglobulinemia several years after the thymoma presented with an immunological and clinical phenotype which more closely resembled a combined immune humoral and cellular defect, with poorer response to immunoglobulin replacement therapy, as compared to those in whom the thymoma and hypogammaglobulinemia were simultaneously detected.[Discussion]: Our findings provide a more accurate definition of the immune cell defects of GS patients and contribute to a better discrimination among GS patients between those with a pure B-cell defect vs. those suffering from a combined immunodeficiency with important consequences on the diagnosis and management of the disease.AT-V is supported by a grant from the Junta de Castilla y León (Fondo Social Europeo, Orden EDU/601/2020, Valladolid, Spain). This study has been founded by the Instituto de Salud Carlos III (ISCIII) through the project “PI20/01712” and co-founded by the European Union.Peer reviewe

Improved standardization of flow cytometry diagnostic screening of primary immunodeficiency by software-based automated gating

BackgroundMultiparameter flow cytometry (FC) is essential in the diagnostic work-up and classification of primary immunodeficiency (PIDs). The EuroFlow PID Orientation tube (PIDOT) allows identification of all main lymphocyte subpopulations in blood. To standardize data analysis, tools for Automated Gating and Identification (AG&I) of the informative cell populations, were developed by EuroFlow. Here, we evaluated the contribution of these innovative AG&I tools to the standardization of FC in the diagnostic work-up of PID, by comparing AG&I against expert-based (EuroFlow-standardized) Manual Gating (MG) strategy, and its impact on the reproducibility and clinical interpretation of results.MethodsFC data files from 44 patients (13 CVID, 12 PID, 19 non-PID) and 26 healthy donor (HD) blood samples stained with PIDOT were analyzed in parallel by MG and AG&I, using Infinicyt (TM) software (Cytognos). For comparison, percentage differences in absolute cell counts/mu L were calculated for each lymphocyte subpopulation. Data files showing differences >20% were checked for their potential clinical relevance, based on age-matched percentile (p5-p95) reference ranges. In parallel, intra- and inter-observer reproducibility of MG vs AG&I were evaluated in a subset of 12 samples.ResultsThe AG&I approach was able to identify the vast majority of lymphoid events (>99%), associated with a significantly higher intra- and inter-observer reproducibility compared to MG. For most HD (83%) and patient (68%) samples, a high degree of agreement (<20% numerical differences in absolute cell counts/mu L) was obtained between MG and the AG&I module. This translated into a minimal impact (<5% of observations) on the final clinical interpretation. In all except three samples, extended expert revision of the AG&I approach revealed no error. In the three remaining samples aberrant maturation and/or abnormal marker expression profiles were seen leading in all three cases to numerical alarms by AG&I.ConclusionAltogether, our results indicate that replacement of MG by the AG&I module would be associated with a greater reproducibility and robustness of results in the diagnostic work-up of patients suspected of PID. However, expert revision of the results of AG&I of PIDOT data still remains necessary in samples with numerical alterations and aberrant B- and T-cell maturation and/or marker expression profiles.Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Bone Tissue Response to Porous and Functionalized Titanium and Silica Based Coatings

Background: Topography and presence of bio-mimetic coatings are known to improve osseointegration. The objective of this study was to evaluate the bone regeneration potential of porous and osteogenic coatings. Methodology: Six-implants [Control (CTR); porous titanium coatings (T1, T2); thickened titanium (Ti) dioxide layer (TiO2); Amorphous Microporous Silica (AMS) and Bio-active Glass (BAG)] were implanted randomly in tibiae of 20-New Zealand white rabbits. The animals were sacrificed after 2 or 4 weeks. The samples were analyzed histologically and histomorphometrically. In the initial bone-free areas (bone regeneration areas (BRAs)), the bone area fraction (BAF) was evaluated in the whole cavity (500 mm, BAF-500), in the implant vicinity (100 mm, BAF-100) and further away (100–500 mm, BAF-400) from the implant. Bone-to-implant contact (BIC-BAA) was measured in the areas where the implants were installed in contact to the host bone (bone adaptation areas (BAAs)) to understand and compare the bone adaptation. Mixed models were used for statistical analysis. Principal Findings: After 2 weeks, the differences in BAF-500 for different surfaces were not significant (p.0.05). After 4 weeks, a higher BAF-500 was observed for BAG than CTR. BAF-100 for AMS was higher than BAG and BAF-400 for BAG was higher than CTR and AMS. For T1 and AMS, the bone regeneration was faster in the 100-mm compared to the 400-mm zone. BIC-BAA for AMS and BAG was lower after 4 than 2 weeks. After 4 weeks, BIC-BAA for BAG was lower than AMS and CTR. Conclusions: BAG is highly osteogenic at a distance from the implant. The porous titanium coatings didn’t stimulate bone regeneration but allowed bone growth into the pores. Although AMS didn’t stimulate higher bone response, it has a potential of faster bone growth in the vicinity compared to further away from the surface. BIC-BAA data were inconclusive to understand the bone adaptation.status: publishe