Progress of the European Metrology Network for Advanced Manufacturing

The European Metrology Network (EMN) for Advanced Manufacturing has been established in June 2021. Currently nine EMNs focussing on different important topics of strategic importance for Europe exist and form an integral part of EURAMET, the European Association of National Metrology Institutes (NMI). All EMNs are tasked to develop a high-level coordination of the metrology community in Europe in a close dialogue with the respective stakeholders. The development of a Strategic Research Agenda (SRA) is a key task for all EMNs in their thematic areas as important input for the European Partnership on Metrology programme in alignment with other relevant European Partnerships. This task will be based on an analysis of the existing metrology infrastructure and capabilities of the NMIs, the metrology research needs for advanced manufacturing identified in close cooperation with industrial stakeholders and a resulting gap analysis. Here we report on the progress of the EMN for Advanced Manufacturing

Prévalence et caractéristiques des effets indésirables des antihypertenseurs chez les patients suivis en ambulatoire au Centre Hospitalier Universitaire Yalgado Ouédraogo

La prise en charge médicamenteuse de l'hypertension artérielle (HTA) entraine des effets indésirables qui peuvent être gênants et ainsi influencer l'observance du patient. Nous avons étudié ces effets indésirables dans le service de cardiologie du Centre hospitalier universitaire Yalgado Ouédraogo afin de déterminer leurs fréquences et leurs caractéristiques. Il s'agissait d'une étude transversale de juillet à septembre 2015 chez les patients suivis en ambulatoire pour HTA. Les données ont été obtenues à partir de l'interrogatoire, des carnets de suivi des patients et des fiches de consultations. Au total 278 patients ont été inclus. La population d'étude incluait 69,1% de femmes. L'âge moyen était de 52,2 ans avec des extrêmes de 23 et 86 ans. Quatre vingt et sept virgule huit pourcent (87,8%) vivaient en milieu urbain. Le tabagisme, la dyslipidémie et les antécédents familiaux d'HTA représentaient respectivement 9%, 35,6% et 57,2%. Au plan thérapeutique, 43,2% étaient sous monothérapie, 35,6% sous bithérapie à l'initiation du traitement. Les inhibiteurs calciques (59,7%) étaient la classe thérapeutique la plus utilisée. La prévalence globale des effets indésirables était de 60,1%. Les inhibiteurs calciques étaient impliqués dans 53,6% suivis des diurétiques (48,6%) dans la survenue de l'effet indésirable. La prévalence spécifique par molécule était 28,1% pour l'amlodipine et 24,5% pour l'hydrochlorothiazide. La diurèse excessive (13,7%), la toux (12,9%) et les vertiges (11,5%) étaient les effets indésirables les plus fréquemment évoqués par les patients. Le système nerveux central et périphérique et le système ostéo-musculaire étaient les systèmes les plus atteints. Les effets indésirables sont un déterminant majeur de l'adhésion aux traitements antihypertenseur, car leur impact sur la vie quotidienne des patients peut s'avérer significatif

Equal Expansion of Endogenous Transplant-Specific Regulatory T Cell and Recruitment Into the Allograft During Rejection and Tolerance

Despite numerous advances in the definition of a role for regulatory T cells (Tregs) in facilitating experimental transplantation tolerance, and ongoing clinical trials for Treg-based therapies, critical issues related to the optimum dosage, antigen-specificity, and Treg-friendly adjunct immunosuppressants remain incompletely resolved. In this study, we used a tractable approach of MHC tetramers and flow cytometry to define the fate of conventional (Tconvs) and Tregs CD4+ T cells that recognize donor 2W antigens presented by I-Ab on donor and recipient antigen-presenting cells (APCs) in a mouse cardiac allograft transplant model. Our study shows that these endogenous, donor-reactive Tregs comparably accumulate in the spleens of recipients undergoing acute rejection or exhibiting costimulation blockade-induced tolerance. Importantly, this expansion was not detected when analyzing bulk splenic Tregs. Systemically, the distinguishing feature between tolerance and rejection was the inhibition of donor-reactive conventional T cell (Tconv) expansion in tolerance, translating into increased percentages of splenic FoxP3+ Tregs within the 2W:I-Ab CD4+ T cell subset compared to rejection (~35 vs. <5% in tolerance vs. rejection). We further observed that continuous administration of rapamycin, cyclosporine A, or CTLA4-Ig did not facilitate donor-specific Treg expansion, while all three drugs inhibited Tconv expansion. Finally, donor-specific Tregs accumulated comparably in rejecting tolerant allografts, whereas tolerant grafts harbored <10% of the donor-specific Tconv numbers observed in rejecting allografts. Thus, ~80% of 2W:I-Ab CD4+ T cells in tolerant allografts expressed FoxP3+ compared to ≤10% in rejecting allografts. A similar, albeit lesser, enrichment was observed with bulk graft-infiltrating CD4+ cells, where ~30% were FoxP3+ in tolerant allografts, compared to ≤10% in rejecting allografts. Finally, we assessed that the phenotype of 2W:I-Ab Tregs and observed that the percentages of cells expressing neuropilin-1 and CD73 were significantly higher in tolerance compared to rejection, suggesting that these Tregs may be functionally distinct. Collectively, the analysis of donor-reactive, but not of bulk, Tconvs and Tregs reveal a systemic signature of tolerance that is stable and congruent with the signature within tolerant allografts. Our data also underscore the importance of limiting Tconv expansion for high donor-specific Tregs:Tconv ratios to be successfully attained in transplantation tolerance

Vitalism and the Resistance to Experimentation on Life in the Eighteenth Century

There is a familiar opposition between a ‘Scientific Revolution’ ethos and practice of experimentation, including experimentation on life, and a ‘vitalist’ reaction to this outlook. The former is often allied with different forms of mechanism – if all of Nature obeys mechanical laws, including living bodies, ‘iatromechanism’ should encounter no obstructions in investigating the particularities of animal-machines – or with more chimiatric theories of life and matter, as in the ‘Oxford Physiologists’. The latter reaction also comes in different, perhaps irreducibly heterogeneous forms, ranging from metaphysical and ethical objections to the destruction of life, as in Margaret Cavendish, to more epistemological objections against the usage of instruments, the ‘anatomical’ outlook and experimentation, e.g. in Locke and Sydenham. But I will mainly focus on a third anti-interventionist argument, which I call ‘vitalist’ since it is often articulated in the writings of the so-called Montpellier Vitalists, including their medical articles for the Encyclopédie. The vitalist argument against experimentation on life is subtly different from the metaphysical, ethical and epistemological arguments, although at times it may borrow from any of them. It expresses a Hippocratic sensibility – understood as an artifact of early modernity, not as some atemporal trait of medical thought – in which Life resists the experimenter, or conversely, for the experimenter to grasp something about Life, it will have to be without torturing or radically intervening in it. I suggest that this view does not have to imply that Nature is something mysterious or sacred; nor does the vitalist have to attack experimentation on life in the name of some ‘vital force’ – which makes it less surprising to find a vivisectionist like Claude Bernard sounding so close to the vitalists