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The origin of high‐spatial‐frequency laser‐induced periodic surface structures, known as HSFLs, has always been a controversial topic. HSFLs of sub‐100 nm periodicity and sub‐20 nm amplitude are generated on tungsten by Ti:sapphire femtosecond laser irradiation under four different processing environments (ambient, air at 10 mbar, Ar at 10 mbar, and vacuum at 10−7mbar). The topography and subtopography analysis together with two‐temperature model–molecular dynamics simulations reveal that HSFLs formation originates from laser‐induced thermal stresses, implying both surface tension and tensile forces are involved. The experimental observation of subsurface cavitation confirms a hydrodynamics‐based origin for these nanostructures. The high‐spatial‐frequency laser‐induced nanostructures (HSFLs), of sub‐100 nm periodicity and sub‐20 nm amplitude are generated on tungsten by Ti:Sapphire femtosecond laser irradiation under four different processing environments. The topography and sub‐topography analysis together with two temperature model–molecular dynamics (TTM–MD) simulations reveal that their formation originates from laser‐induced thermal stresses, implying both surface tension and tensile forces.

Quantification of optical absorption gaps in nailfold capillaries has recently shown promise as a non-invasive technique for neutropenia screening. Here we demonstrate a low-cost, portable attachment to a mobile phone that can resolve optical absorption gaps in nailfold capillaries using a reverse lens technique and oblique 520nm illumination. Resolution <4μm within a 1mm^2 on-axis region is demonstrated, and wide field of view (3.5mm × 4.8mm) imaging is achieved with resolution <6μm in the periphery. Optical absorption gaps (OAGs) are visible in superficial capillary loops of a healthy human participant by an ∼8-fold difference in contrast-to-noise ratio with respect to red blood cell absorption contrast. High speed video capillaroscopy up to 240 frames per second (fps) is possible, though 60fps is sufficient to resolve an average frequency of 37 OAGs/minute passing through nailfold capillaries. The simplicity and portability of this technique may enable the development of an effective non-invasive tool for white blood cell screening in point-of-care and global health settings.

ABSTRACTTargeting transferrin receptor 1 (TfR1) with monoclonal antibodies is a promising therapeutic strategy in cancer as tumor cells often overexpress TfR1 and show increased iron needs. We have re-engineered six anti-human TfR1 single-chain variable fragment (scFv) antibodies into fully human scFv2-Fcγ1 and IgG1 antibodies. We selected the more promising candidate (H7), based on its ability to inhibit TfR1-mediated iron-loaded transferrin internalization in Raji cells (B-cell lymphoma). The H7 antibody displayed nanomolar affinity for its target in both formats (scFv2-Fcγ1 and IgG1), but cross-reacted with mouse TfR1 only in the scFv2-Fc format. H7 reduced the intracellular labile iron pool and, contrary to what has been observed with previously described anti-TfR1 antibodies, upregulated TfR1 level in Raji cells. H7 scFv2-Fc format elimination half-life was similar in FcRn knock-out and wild type mice, suggesting that TfR1 recycling contributes to prevent H7 elimination in vivo. In vitro, H7 inhibited the growth of erythroleukemia and B-cell lymphoma cell lines (IC500.1 µg/mL) and induced their apoptosis. Moreover, the Im9 B-cell lymphoma cell line, which is resistant to apoptosis induced by rituximab (anti-CD20 antibody), was sensitive to H7. In vivo, tumor regression was observed in nude mice bearing ERY-1 erythroleukemia cell xenografts treated with H7 through a mechanism that involved iron deprivation and antibody-dependent cytotoxic effector functions. Therefore, targeting TfR1 using the fully human anti-TfR1 H7 is a promising tool for the treatment of leukemia and lymphoma.

Une validation initiale d’un guide de consultation pharmaceutique standardisé a été réalisée dans un précédent travail pour optimiser l’adhésion médicamenteuse du patient au traitement du myélome multiple par anticancéreux oraux. L’objectif principal de ce travail était la validation finale de ce guide auprès de dix patients naïfs. Les principaux objectifs secondaires étaient d’évaluer pour le patient l’évolution des connaissances sur le traitement, la compréhension de l’objectif de la consultation pharmaceutique, l’adhésion aux outils. Chaque patient a complété un auto-questionnaire avant et après la première consultation pharmaceutique. Le critère de jugement principal était le taux moyen de réussite par question après la consultation pharmaceutique (une valeur ≥ 90 % validait l’acquisition des connaissances). Les critères de jugement secondaires étaient : évolution des taux moyens de réussite par patient et par question, taux de reformulation de l’objectif de la consultation pharmaceutique, taux de réponse aux questions sur la présentation, lisibilité et compréhension. Aucun taux moyen de réussite par question après la consultation pharmaceutique n’était statistiquement inférieur à 90 %. Les taux moyens de réussite par patient avant et après la consultation pharmaceutique étaient de 78,9±13,7 % vs 96,1±3,9 % (p=0,01). Les taux moyens de réussite par question étaient différents pour quatre questions. Tous les patients ont su reformuler l’objectif de la consultation pharmaceutique et ont validé la présentation, la lisibilité et la compréhension des documents. Cette étude a permis de réaliser la validation finale du guide de consultation pharmaceutique.

La sécurisation du traitement par anticancéreux oraux ambulatoires est une thématique forte du plan cancer 2014–2019. L’objectif de cette étude a été d’élaborer un guide de consultation pharmaceutique en vue d’améliorer l’adhésion médicamenteuse chez les patients traités pour un myélome multiple par anticancéreux oral. Un groupe de travail professionnel pluridisciplinaire a retenu une liste d’items pertinents en lien avec l’adhésion médicamenteuse qui ont servi de trame pour la conception des documents supports de la consultation pharmaceutique dans un langage accessible au patient. La lisibilité, compréhension et mémorisation des informations ont ensuite été validées auprès de dix patients traités pour un myélome. Douze items ont été retenus relatifs à l’information sur le traitement (5 items), à l’organisation de la prise du traitement (5 items) et aux effets indésirables (2 items). Un guide pharmacien, un guide patient, un agenda de prise, 3 autoquestionnaires permettant d’évaluer les connaissances et la compréhension des patients au cours des consultations pharmaceutiques ont été élaborés. Le test auprès des patients a entraîné des modifications sur le guide pharmacien, le guide patient, l’agenda de prise et les questions/réponses. Cette étude a permis de réaliser la validation initiale de documents pour protocoliser la démarche de consultation pharmaceutique destinée aux patients traités pour un myélome afin qu’elle soit reproductible d’un patient à l’autre quel que soit le pharmacien, par la standardisation des informations délivrées. Cette étude nécessite d’être complétée par une validation finale auprès de patients atteints de myélome, naïfs de traitement par anticancéreux oraux.

The article focuses on the implementation of use case-driven health information technology (HIT) solutions and a collaborative approach for stakeholders involved, to enable interoperability in healthcare. Topics discussed include stakeholders involved such as IT personnel and health information managers, understanding user needs documented in the business process and functional standards, and examination of the HIT project in terms of business needs and workflow management.

The article focuses on the application of the concept hierarchy in the domain of electronic-prescribing and medication dispensing in the U.S. It provides the approach and standards for creating use cases and realization scenarios for healthcare information exchange. Also discussed is the use of the technical interoperability infrastructure in information sharing between an electronic health record (EHR) system and a picture archiving and communication system (PACS).

Innovation in IT solutions introduces new usages in ehealth that allows the patient to be more active in his (her) health care and well-being. Strong expectations on electronic exchanges or shared medical documents from healthcare professionals and patients are pushing decision makers and stakeholders to develop quickly efficient and structured data enabled health IT infrastructures. One of the challenges of this paradigm shift is to provide at the point of care interoperable solutions in full compliance with regulations, ethics, organizational and technical states of the art. This paper describes this approach developed as a four steps process and defines the basic concepts for designing an interoperability infrastructure. For each of the steps, examples will be provided and discussed accordingly with the different interoperability layers (legal, policy, process, information and technical) developed in the Refined eHealth European Interoperability Framework (ReEIF) (eHealth Network, 2015).

The article presents the hierarchy between concepts of business cases that define user needs for the adoption of health information technology (HIT) to support HIT systems interoperability and information sharing across systems. It illustrates the hierarchy by using the examples of assembling the artifacts in the domain of clinical imaging. It also describes the approach and standards for building the business cases in eHealth setting.

In mammals, neuroepithelial cells play an essential role in embryonic neurogenesis, whereas glial stem cells are the principal source of neurons at postembryonic stages. By contrast, neuroepithelial‐like stem/progenitor (NE) cells have been shown to be present throughout life in teleosts. We used three‐dimensional (3D) reconstructions of cleared transgenic wdr12:GFP medaka brains to demonstrate that this cell type is widespread in juvenile and to identify new regions containing NE cells. We established the gene expression profile of optic tectum (OT) NE cells by cell sorting followed by RNA‐seq. Our results demonstrate that most OT NE cells are indeed active stem cells and that some of them exhibit long G2 phases. We identified several novel pathways (e.g., DNA repair pathways) potentially involved in NE cell homeostasis. In situ hybridization studies showed that all NE populations in the postembryonic medaka brain have a similar molecular signature. Our findings highlight the importance of NE progenitors in medaka and improve our understanding of NE‐cell biology. These cells are potentially useful not only for neural stem cell studies but also for improving the characterization of neurodevelopmental diseases, such as microcephaly. StemCells2017;35:1505–1518 We performed an enhancer screen in a locus composed of two medaka genes in tandem having a preferential expression in neuroepithelium. Thus, we isolated a driver for cells that we demonstrated to have cytological features of neuroepithelial cells. (A) Analysis of histological sections and 3D images from clarified brains of transgenic fish indicated that neuroepithelial‐based neurogenesis may be present in almost all the proliferation zones of the fish brain. Our study almost also points to the intriguing possibility that neuroepithelial cells exhibit long G2 phases. (B) RNA seq from optic tectum GFP+ sorted cells revealed neuroepithelium marker genes, some of which are orthologous to mammalian neuroepithelium markers. Many genes are associated to ribosome biogenesis, proliferation or DNA repair.

The article provides definitions for the use case concepts of health information technology (HIT) or ehealth. These include the business case, interoperability use case, realization scenario and technical use cases. Also mentioned are the examples of business cases, use cases and realization scenarios by project such as biosurveillance, emergency response and referral from primary to secondary care.

Évaluer la faisabilité en routine clinique de la tomoscintigraphie de perfusion pulmonaire couplée au scanner pour prédire la fonction pulmonaire postopératoire avant lobectomie.