Electro-optical characterization of a CMOS image sensor optimized for soft x-ray astronomy

CIS221-X is a prototype complementary metal-oxide-semiconductor (CMOS) image sensor, optimized for soft x-ray astronomy and developed for the proposed ESA Transient High Energy Sky and Early Universe Surveyor (THESEUS) mission. The sensor features 40 μm pitch square pixels built on a 35 μm thick, high-resistivity epitaxial silicon that is fully depleted by reverse substrate bias. Backside illumination processing has been used to achieve high x-ray quantum efficiency, and an optical light-blocking filter has been applied to mitigate the influence of stray light. A comprehensive electro-optical characterization of CIS221-X has been completed. The median readout noise is 3.3 e− RMS with 90% of pixels reporting a value − RMS. At −40 ° C, the dark current is 12.4 ± 0.06 e− / pixel / s. The pixel photo-response is linear to within 1% for 0.3 to 5 keV photons (82 to 1370 e−) with 80 % quantum efficiency. With the exception of dark current, these results either meet or outperform the requirements for the THESEUS mission, strongly supporting the consideration of CMOS technology for soft x-ray astronomy

Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity

One approach to improving efficacy in MS therapy is to identify medications that provide additive or synergistic benefit in combination. Orally administered cholesterol-lowering HMG-CoA reductase inhibitors (known as statins), which exhibit immunomodulatory properties and are effective in treatment of the MS model EAE, are being tested in MS. As atorvastatin can enhance protective Th2 responses and has a different mechanism of action than glatiramer acetate (GA), a parenterally administered immunomodulatory agent approved for MS treatment, we tested whether the combination of these agents could be beneficial in EAE. Combination therapy using suboptimal doses of atorvastatin and GA prevented or reversed clinical and histologic EAE. Secretion of proinflammatory Th1 cytokines was reduced — and conversely Th2 cytokine secretion was increased — in these mice, but not in mice treated with each drug alone at the same doses. Monocytes treated with the combination of suboptimal doses of atorvastatin and GA secreted an antiinflammatory type II cytokine pattern and, when used as APCs, promoted Th2 differentiation of naive myelin-specific T cells. Our results demonstrate that agents with different mechanisms of immune modulation can combine in a synergistic manner for the treatment of CNS autoimmunity and provide rationale for testing the combination of atorvastatin and GA in MS

A multi-approach study to reveal eel life-history traits in an obstructed catchment before dam removal

International audienceRiver fragmentation is expected to impact not only movement patterns and distribution of eels within catchment, but also their life-history traits. Here, we used otolith multi-elemental signatures to reconstruct life sequences of European silver eels within an obstructed catchment, just before the removal of hydropower dams. Beyond providing an initial state, we hypothesized that otolith signatures can provide crucial information on the way eels use the watershed. Indeed, their spatial distribution is expected to shape life-history traits, including condition coefficient, trophic level, growth rate, or infection by metazoan parasites. While Sr:Ca and Ba:Ca ratios were complementary in tracing fish movements between freshwater and estuary, the Ba:Ca variations allowed to discriminate three freshwater sectors. The eels assigned to the midstream sector were more mobile and exhibited lower growth rates, probably in response to higher competition at the vicinity of dams. While most eels are currently produced by downstream and midstream sectors, eels assigned to upper reaches of connected tributaries generally display higher richness in native parasite and higher body condition and lipid reserve, known to promote the success of migration and reproduction. In the near future, the dam removals will represent an outstanding experimental framework for evaluating impacts of catchment reconnection

Prise en charge palliative des patients allogreffés : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

International audienceAllogeneic hematopoietic cell transplantation (allo-HCT), the only curative therapy for numerous hematological malignancies, carries a significant risk of morbidity and mortality. The patients and families’ expectations regarding the procedure, the prognosis uncertainties, as well as the existence of potential new therapeutic possibilities, lead to frequent use of intensive care. Even though the transplant physicians are highly skilled in acute care, their knowledge of palliative approach is limited, making the use of palliative care insufficient and often late. By promoting reflection on the proportionality of care and the patients’ quality of life, palliative care may contribute to the allo-HCT patients management. Nevertheless, obstacles to this approach remain. The objective of this work is to propose recommendations to promote the implementation of palliative care into transplant units.L’allogreffe de cellules hématopoïétiques, seule perspective curative pour certaines hémopathies malignes, comporte des risques de morbi-mortalité importants. Les attentes des patients et de leurs proches vis-à-vis de la procédure, les incertitudes pronostiques, ainsi que l’existence de nouvelles possibilités thérapeutiques, engendrent un recours fréquent, onéreux aux soins intensifs. Si les médecins greffeurs maîtrisent parfaitement les soins actifs, leur connaissance en ce qui concerne les soins palliatifs est limitée, rendant l’accès à ces soins très restreint et souvent tardif. Favorisant une réflexion sur la proportionnalité des soins et sur la qualité de vie des patients, les soins palliatifs peuvent contribuer à la prise en charge des patients allogreffés et à l’accompagnement de leurs proches. Néanmoins, des obstacles à cette approche demeurent. Cet article a pour objectif de proposer des recommandations pour favoriser l’intégration de la démarche palliative au sein des unités d’allogreffe

Molecular profiling of rheumatoid arthritis patients reveals an association between innate and adaptive cell populations and response to anti-tumor necrosis factor

Background The goal of this study is to use comprehensive molecular profiling to characterize clinical response to anti-TNF therapy in a real-world setting and identify reproducible markers differentiating good responders and non-responders in rheumatoid arthritis (RA). Methods Whole-blood mRNA, plasma proteins, and glycopeptides were measured in two cohorts of biologic-naïve RA patients (n = 40 and n = 36) from the Corrona CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory coNditions) registry at baseline and after 3 months of anti-TNF treatment. Response to treatment was categorized by EULAR criteria. A cell type-specific data analysis was conducted to evaluate the involvement of the most common immune cell sub-populations. Findings concordant between the two cohorts were further assessed for reproducibility using selected NCBI-GEO datasets and clinical laboratory measurements available in the CERTAIN database. Results A treatment-related signature suggesting a reduction in neutrophils, independent of the status of response, was indicated by a high level of correlation (ρ = 0.62; p < 0.01) between the two cohorts. A baseline, response signature of increased innate cell types in responders compared to increased adaptive cell types in non-responders was identified in both cohorts. This result was further assessed by applying the cell type-specific analysis to five other publicly available RA datasets. Evaluation of the neutrophil-to-lymphocyte ratio at baseline in the remaining patients (n = 1962) from the CERTAIN database confirmed the observation (odds ratio of good/moderate response = 1.20 [95% CI = 1.03–1.41, p = 0.02]). Conclusion Differences in innate/adaptive immune cell type composition at baseline may be a major contributor to response to anti-TNF treatment within the first 3 months of therapy

MHC class II–dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies

Whether B cells serve as antigen-presenting cells (APCs) for activation of pathogenic T cells in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) is unclear. To evaluate their role as APCs, we engineered mice selectively deficient in MHC II on B cells (B-MHC II-/-), and to distinguish this function from antibody production, we created transgenic (Tg) mice that express the myelin oligodendrocyte glycoprotein (MOG)-specific B cell receptor (BCR; IgH(MOG-mem)) but cannot secrete antibodies. B-MHC II-/- mice were resistant to EAE induced by recombinant human MOG (rhMOG), a T cell-and B cell-dependent autoantigen, and exhibited diminished Th1 and Th17 responses, suggesting a role for B cell APC function. In comparison, selective B cell IL-6 deficiency reduced EAE susceptibility and Th17 responses alone. Administration of MOG-specific antibodies only partially restored EAE susceptibility in B-MHC II-/- mice. In the absence of antibodies, IgH(MOG-mem) mice, but not mice expressing a BCR of irrelevant specificity, were fully susceptible to acute rhMOG-induced EAE, also demonstrating the importance of BCR specificity. Spontaneous opticospinal EAE and meningeal follicle-like structures were observed in IgH(MOG-mem) mice crossed with MOG-specific TCR Tg mice. Thus, B cells provide a critical cellular function in pathogenesis of central nervous system autoimmunity independent of their humoral involvement, findings which may be relevant to B cell-targeted therapies