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Les enjeux sériels épousent étroitement les grandes interrogations anthropologiques qu’une société se pose… ou est sur le point de se poser; ici se déploie « l’infinie possibilité des possibles », et nous verrons que peu à peu monte en puissance la thématique de l’humain prolongé, souvent sous l’angle d’un transhumanisme devenu fou. Ancrer la thématique de l’augmentation technologique dans l’imaginaire sexuel permet de focaliser immédiatement sur la fantasmatique intime de chaque lecteur/spectateur ; ce motif « situé » singularise aussi le sujet, voué pourtant à la stéréotypie du produit de genre, post-fordiste mais nécessairement soumis à des schémas identifiables. Le dissensus entre désirabilité obscure du processus et horreur des idéologies sous-jacentes formera donc la trame de ce propos ; la coloration dystopique affecte de fait l’essentiel du dispositif, mais sans que soit absente une forme de fascination honteuse pour cette « immortalité » technologique, ou même épistémocratique (voir note 3), que la science semble promettre — aux plus aisés en tout cas.

Abstract Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

BACKGROUND: The treatment of non-small cell lung cancer (NSCLC) has undergone changes that have improved the prognosis of patients. With the advent of immunotherapy, it has been possible to prolong significantly the overall and progression-free survival as well as quality of life. Nevertheless, its use represents clinical challenges which may turn into adverse events, such as progression and pseudo-progression, which are uncontrolled and often deleterious immune responses that simulate tumoral progression, generate worsening of symptoms and performance status of patients and even may lead to non-cancer related death of patients. MATERIALS AND METHODS: We assessed 128 records (clinical trials, reports, meta-analyses) in order to provide an updated review of the treatment of NSCLC, current definitions proposed for pseudo and hyperprogression (which are not homogeneous so far), incidence, theories about their physiopathogenesis, importance of making a judicious diagnostic workup, imaging criteria as well as biochemical markers in order to predict their appearance, concluding with a brief discussion about the topic addressed. CONCLUSIONS: Since there is no definition or standardized diagnostic and imaging criteria, these entities are a topic of major interest in the area of oncologic immunotherapy, for which the following review has been generated.

Introduction: Standard-of-care systemic chemotherapies for pancreatic ductal adenocarcinoma (PDAC) currently have limited clinical benefits, in addition to causing adverse side effects in many patients. One factor known to contribute to the poor chemotherapy response is the poor drug diffusion into PDAC tumors. Novel treatment methods are therefore drastically needed to improve targeted delivery of treatments. Here, we evaluated the efficacy of the 3DNA® Nanocarrier (3DNA) platform to direct delivery of therapeutics to PDAC tumors in vivo. Materials and Methods: A panel of PDAC cell lines and a patient tissue microarray were screened for established tumor-specific proteins to identify targeting moieties for active targeting of the 3DNA. NRG mice with or without orthotopic MIA PaCa-2-luciferase PDAC tumors were treated intraperitoneally with 100 μl of fluorescently labeled 3DNA. Results: Folic acid and transferrin receptors were significantly elevated in PDAC compared to normal pancreas. Accordingly, both folic acid- and transferrin-conjugated 3DNA treatments significantly increased delivery of 3DNA specifically to tumors in comparison to unconjugated 3DNA treatment. In the absence of tumors, there was an increased clearance of both folic acid-conjugated 3DNA and unconjugated 3DNA, compared to the clearance rate in tumor-bearing mice. Lastly, delivery of siLuciferase by folic acid-conjugated 3DNA in an orthotopic model of luciferase-expressing PDAC showed significant and prolonged suppression of luciferase protein expression and activity. Conclusion: Our study progresses the 3DNA technology as a reliable and effective treatment delivery platform for targeted therapeutic approaches in PDAC.

Abstract Background To evaluate the impact of a nurse navigation program on treatment adherence and resolution of hepatitis C infection in patients with severe mental disorder. Methods An open, randomized, controlled trial with blinded outcome assessment. The intervention group will engage in a nurse navigation program designed by mental health nurses. The program involves active screening for patients with severe mental disorder. The patients and caregivers included in the program will receive information, training, support and guidance throughout the treatment and recovery process, which involves different healthcare professionals and units. The control group will receive the standard of care, which includes follow-up by a family physician, referral to the hepatologist, serological testing, new referral to the hepatologist, onset of treatment, and follow-up. Multidisciplinary care will be provided along a coordinated and seamless clinical pathway led by a nurse navigator. The primary endpoints are total recovery (hepatitis C cure) and treatment adherence. Occurrence of symptoms of schizophrenia and health-related quality of life will be also recorded. Follow-up of patients will be performed three and six months after the administration of antiviral treatment. The study was authorised by the Ethics Committee of Malaga in December 2021. Funding was approved in March 2021. Discussion If this intervention is proven to be effective in improving treatment access and adherence, it will represent a step forward in addressing a chronic health issue that is 16 times more prevalent in the population with severe mental disease. Finally, this intervention may lead to the detection of undertreated HCV infection in this population of patients. Trial registration This protocol has been registered in ClinicalTrials.gov with identifier code NCT04891445 on May 18, 2021.

Language functions are often used as fundamental guiding principles in ESL (English as a Second Language) textbooks especially now that focus on meaning has become crucial to ESL teaching and learning. This paper identifies general and specific language functions used in five beginner ESL textbooks to provide baseline data that will guide instructional material developers and teachers. It also examines language function content in relation to the objectives of each textbook to aide teachers in appropriately selecting materials for their students. Finally, the study analyzes the language function content of ESL textbooks "vis-à-vis" the needs of beginner ESL learners.

Deux sommes de littérature de jeunesse quasi contemporaines se répondent de part et d'autre de l'Atlantique : toutes deux ont pour héroïnes des fillettes partagées entre une expérience urbaine attristante et malheureuse, et une arrivée en pleine nature épanouissante et revigorante (on parlerait aujourd'hui de résilience) ; pourtant, entre la Canadienne Anne Shirley-Cuthbert (Anne des Pignons verts, Lucy Maud Montgomery) et la Suisse allemande Adélaïde/Heidi (Heidi, Johanna Spyri), que de différences ! Alors, campagne heureuse, villes toxiques ? Rien n'est simple, mais ces récits de jeunesse d'avant la première guerre mondiale supposent aussi que l'espoir est possible, et que le monde est ouvert aux âmes fortes. Mots-clés : amitié, Lucy Montgomery, nature, orphelines, Suisse alémanique.

Fidèle à la pensée benjaminienne, nous présenterons quelques aspects contemporains de la production « épique », principalement young adult, en en soulignant les aspects «pseudo-édifiants », puis nous montrerons en quoi ce legendarium réfère à une érotétique du mixte entre « chronos » et « kaïros » – entre le long temps du récit linéaire et l’exceptionnalité de l’instant foudroyant. Quant au « merveilleux noir » (formule empruntée à Denis Labbé), il s’appliquera davantage aux séries medfan, grandes porteuses de souffles et d’événements épiques ; il est de fait un préjugé bien ancré dans le champ culturel français de n’avoir pas, comme on dit, la « fibre épique » … Mais par un savoureux détour c’est la plus moderne fantasy qui va permettre à la littérature de revenir au « bel agir ». Mots-clés : épopée et jeunesse , high fantasy , médiévisme , cycles , quêtes.

Abstract We present a search for signatures of neutrino mixing of electron anti-neutrinos with additional hypothetical sterile neutrino flavors using the Double Chooz experiment. The search is based on data from 5 years of operation of Double Chooz, including 2 years in the two-detector configuration. The analysis is based on a profile likelihood, i.e. comparing the data to the model prediction of disappearance in a data-to-data comparison of the two respective detectors. The analysis is optimized for a model of three active and one sterile neutrino. It is sensitive in the typical mass range $${5 \times 10^{-3}}\,\mathrm{eV}^2 \lesssim \varDelta m^2_{41} \lesssim {3 \times 10^{-1}}\,\mathrm{eV}^2 $$ 5 × 10 - 3 eV 2 ≲ Δ m 41 2 ≲ 3 × 10 - 1 eV 2 for mixing angles down to $$\sin ^2 2\theta _{14} \gtrsim {0.02} $$ sin 2 2 θ 14 ≳ 0.02 . No significant disappearance additionally to the conventional disappearance related to $$\theta _{13} $$ θ 13 is observed and correspondingly exclusion bounds on the sterile mixing parameter $$\theta _{14} $$ θ 14 as a function of $$ \varDelta m^2_{41} $$ Δ m 41 2 are obtained.

Abstract Background Malignant pleural mesothelioma is an infrequent neoplasia with a poor prognosis and the majority of patients already have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Mesothelioma is a neoplasia with a long preclinical stage that can span from 15 to 40 years. Methods This was a descriptive, observational, retrospective study of 136 patients with a confirmed diagnosis of mesothelioma, which compared histological subtypes, immunohistochemical biomarkers, concomitant chronic degenerative diseases, tobacco use, age at the time of diagnosis, clinical stage and chemotherapy agents used or other treatments such as radiotherapy and surgery to identify all the factors that impact in the prognosis of overall survival (OS) and progression‐free survival (PFS). Results A total of 136 patients were included in the study. In the total study population, 84 patients were male (61.8%) and 52 were female (38.2%). Median PFS was nine months (95% confidence interval [CI]: 8.4–9.5 months) and median OS was 12 months (95% CI: 11.3–12.6). The results indicated that the most determining prognostic factors for OS and PFS were cell differentiation measured by immunohistochemical biomarkers, the treatment chosen, and that RECIST was the most significant in the evaluation of patient response to treatment. Conclusions Malignant pleural mesothelioma is a cancer with a poor prognosis usually diagnosed at an advanced stage of disease. Our study revealed that the prognostic factors for OS and PS were cell differentiation, the treatment chosen and RECIST.

Abstract Introduction The aim of this study is to analyse different ways of participation during the development of a clinical guideline to improve the early detection of psychosis and to deploy a comprehensive treatment plan to improve prognosis and social integration. Materials and method The clinical guideline was developed using the ADAPTE method with the participation of 40 authors and 80 external reviewers. The process was divided into three major phases: set up, adaptation and finalization. During adaptation and completion, a total of 44 patients and 18 family caregivers were involved. Results and conclusions The different roles assumed by the patients and their family caregivers were described, depending on the panel in which they participated, with diverse grades of complexity: a user as author, integration of the results of qualitative research with the participation of local users and family caregivers, 13 users as individual external reviewers and the participation of users and caregiver organizations in the external review. In the guideline, contributions from patients during the qualitative research were included in an innovative way, placing them just behind the recommendations. On the other hand, the results of the family caregivers’ study were included in a specific area of uncertainty. Further, the expressed point of view was considered as the collective demands of users and family caregivers’ organizations in the cost‐benefit analysis made by the organizing committee. There were diverse ways to conduct direct patient participation during the guideline development, ensuring that their individual experiences contributed significantly to the final version.

Evidence shows that caring for a family member with a psychotic disorder generates a significant emotional impact and repercussions on social functioning. However, this caregiving experience can be influenced by cultural factors. The aim of this study is to explore the experience and perception of a group of family caregivers of patients with psychotic disorders of different durations regarding the emotional and social functioning repercussions of caregiving on them in Andalusia. Three focus groups (28 participants) were conducted. Data were subject to a thematic analysis. Three themes emerged from the data: 1) Emotional invasion; 2) Disruption in the caregiver's life project; and 3) Changes in the family system. Participants reported experiencing sadness, fear, overwhelm, hopelessness, and uncertainty. Caregivers' accounts reflected an interruption of their daily tasks, as well as the need to reformulate plans or goals outside the family life that require long-term commitment, such as professional development or even their residence. The narratives indicated an impact on all roles within the family system, particularly for the mother. The results are consistent with existing research. Healthcare professionals and programs should take into account the costs associated with caregiving in order to minimize them, given the impact it has on both the patient's and the caregivers' health. • Twenty-eight family caregivers participated in three focus groups. • Multiple negative emotions coexist within the emotional experience of caregivers. • Family relationships change, as well as the role that each member plays in the family. • Caregiving requires a review and reorganization of the caregiver's life plan. • These consequences are especially pronounced in the case of the mother. [ABSTRACT FROM AUTHOR]

Suicide is a major public health problem, especially among the young population. Nurses are in a unique position to prevent it due to their constant contact with patients. However, addressing suicidal behaviour can be complicated by the emotional responses it elicits. Simulation has been shown to be an effective tool to increase the self-confidence of nursing students in dealing with these sensitive situations in a safe environment prior to dealing with real patients. To explore nursing students' perceptions, thoughts, and emotions about their performance in dealing with risk for suicidal behaviour through simulated scenarios. Qualitative descriptive study. Students of Mental Health and Psychiatric II in the third year of the Nursing course at the University of Málaga were invited to explain their experience by answering a questionnaire of three open-ended questions following their participation in the simulated scenarios of the course. A total of 72 students participated. Content analysis of the written responses identified three main themes: (i) Emotions experienced during the simulation; (ii) Self-criticism of the performance/intervention; (iii) Student evaluation of the learning experience. Most of the students indicated at some point during the clinical scenario, they had felt anxiety, proposing possible improvements in their own performance. The clinical scenario that elicited the most negative emotions was that of a person diagnosed with borderline personality disorder. Clinical simulations contribute to a better understanding of nursing practice with mental health patients and the need for training in emotional and therapeutic communication skills among students. • Students perceive simulation helpful to gain confidence in addressing suicide risk behaviour. • Nursing students need training in emotional and therapeutic communication skills. • Nursing students think simulation scenarios should be used more often during their studies. [ABSTRACT FROM AUTHOR]

This study aims to find the repertoire of aesthetic taste as a creative act and its relation to symbolic power in the arena of Indonesian cultural production of glass painting. The study used a qualitative approach with a phenomenological design. Data collection used in-depth interviews, participant observation, individual life’s history, and document examination. Data analysis used interpretive phenomenological analysis. The study finds five aesthetic taste repertoires that include: (1) the aesthetic taste of the palace which is characterized by the symbolic decorative visualization of calligraphy pictographs of petarekatan with wadasan and mega mendung ornaments; (2) the taste of strengthening cultural identity is marked by the symbolic decorative visualization of a traditional sourcebook for puppet shadow objects with wadasan and mega mendung ornaments; (3) the taste of traditional renewal is characterized by liberating expressive decorative visualizations; (4) the taste of cultural revitalization is characterized by decorative visualization of the superiority of tradition which is involute; and (5) the taste of marginalized community is characterized by the simplicity of traditional object visualizations. The five aesthetic tastes carry a decorative expression style with an interpretation of tradition based on the cultural capital of the artists. The production of aesthetic taste cannot fully be used to classify the social class structure of appreciators but is related to the identity of the cultural capital they have. The production of aesthetic taste is a creative education model that responds to the doxa of symbolic power in the form of orthodox or heterodox, resulting in defensive, subversive, defensive-subversive synthesis, and pseudo-subversive strategies, which are fought for legitimacy as symbolic power.

Tout propos critique tenu sur Fullmetal Alchemist s'adosse à l'énorme corps-toile vibrant d'une œuvre aux multiples supports, aux ramifications quasi-infinies, archétype de la culture jeune « mainstream ». Il n'en demeure pas moins qu'au cœur des récits serpente le fil rouge – le grand Chemin que chaque être doit suivre, de sa naissance à sa disparition, puis de sa disparition à son salut ; au « voyage inattendu » il n'est en effet pas de retour, le cheminement s'exerçant à l'intérieur de sa propre psyché au moins autant qu'en traversant les mondes – ou les temps – dans le grand chamboulement de la fantasy. C'est le voyage initiatique de deux frères, Edward et Alphonse Elric, qui semble le plus riche en interprétations : ayant essayé de ramener leur mère à la vie par une opération alchimique ratée, ils perdent leur intégrité corporelle... mais ne meurent pas ; ils partent, ils voyagent, ils font de leur mémoire un temps secret, une révolte. Leur quête ressemble au fond à la nôtre, elle est exemplaire : un jour ou l’autre, il faut mettre pied à terre et accepter la loi des autres, avant que les guetteurs ne fassent signe, que la nuit s’achève, et que le sens afflue. Mots-clés : alchimie ; résurrection ; fraternité ; dystopie ; fantasy

Abstract Background While the European Union is striving to become the ‘Innovation Union’, there remains a lack of quantifiable indicators to compare and benchmark regional innovation clusters. To address this issue, a HealthTIES (Healthcare, Technology and Innovation for Economic Success) consortium was funded by the European Union’s Regions of Knowledge initiative, research and innovation funding programme FP7. HealthTIES examined whether the health technology innovation cycle was functioning differently in five European regional innovation clusters and proposed regional and joint actions to improve their performance. The clusters included BioCat (Barcelona, Catalonia, Spain), Medical Delta (Leiden, Rotterdam and Delft, South Holland, Netherlands), Oxford and Thames Valley (United Kingdom), Life Science Zürich (Switzerland), and Innova Észak-Alföld (Debrecen, Hungary). Methods Appreciation of the ‘triple helix’ of university–industry–government innovation provided the impetus for the development of two quantifiable innovation indexes and related indicators. The HealthTIES H-index is calculated for disease and technology platforms based on the h-index proposed by Hirsch. The HealthTIES Innovation Index is calculated for regions based on 32 relevant quantitative and discriminative indicators grouped into 12 categories and 3 innovation phases, namely ‘Input’ (n = 12), ‘Innovation System’ (n = 9) and ‘Output’ (n = 11). Results The HealthTIES regions had developed relatively similar disease and technology platform profiles, yet with distinctive strengths and weaknesses. The regional profiles of the innovation cycle in each of the three phases were surprisingly divergent. Comparative assessments based on the indicators and indexes helped identify and share best practice and inform regional and joint action plans to strengthen the competitiveness of the HealthTIES regions. Conclusion The HealthTIES indicators and indexes provide useful practical tools for the measurement and benchmarking of university–industry–government innovation in European medical and life science clusters. They are validated internally within the HealthTIES consortium and appear to have a degree of external prima facie validity. Potentially, the tools and accompanying analyses can be used beyond the HealthTIES consortium to inform other regional governments, researchers and, possibly, large companies searching for their next location, analyse and benchmark ‘triple helix’ dynamics within their own networks over time, and to develop integrated public–private and cross-regional research and innovation strategies in Europe and beyond.

Abstract Biodistribution studies are essential in drug carrier design and translation, and radiotracing provides a sensitive quantitation for this purpose. Yet, for biodegradable formulations, small amounts of free‐label signal may arise prior to or immediately after injection in animal models, causing potentially confounding biodistribution results. In this study, we refined a method to overcome this obstacle. First, we verified free signal generation in animal samples and then, mimicking it in a controllable setting, we injected mice intravenously with a radiolabeled drug carrier formulation (125I‐antibody/3DNA) containing a known amount of free radiolabel (125I), or free 125I alone as a control. Corrected biodistribution data were obtained by separating the free radiolabel from blood and organs postmortem, using trichloroacetic acid precipitation, and subtracting the confounding signal from each tissue measurement. Control free 125I‐radiolabel was detected at ≥85% accuracy in blood and tissues, validating the method. It biodistributed very heterogeneously among organs (0.6–39 %ID/g), indicating that any free 125I generated in the body or present in an injected formulation cannot be simply corrected to the free‐label fraction in the original preparation, but the free label must be empirically measured in each organ. Application of this method to the biodistribution of 125I‐antibody/3DNA, including formulations directed to endothelial target ICAM‐1, showed accurate classification of free 125I species in blood and tissues. In addition, this technique rendered data on the in vivo degradation of the traced agents over time. Thus, this is a valuable technique to obtain accurate measurements of biodistribution using 125I and possibly other radiotracers.

Background: Trauma-related symptoms are often experienced after a first psychotic episode. Objective: In this study, we conduct a qualitative analysis of referred traumatic experiences of outpatients diagnosed with psychotic disorders. Method: Focus groups were formed and in-depth interviews conducted with 30 participants, focusing on their experience with the disorder and the health care received. Given the frequency with which trauma and psychosis have been associated in the scientific literature, the nature of this relation is addressed as a secondary objective, via a qualitative analysis. Results: Analysis revealed two main themes in the patients’ discourse. On many occasions, traumatic experiences were related to the development of the disorder. Although most participants referred to traumatic experiences during childhood, episodes during adult life were also reported, which may have triggered the disorder. The second theme was that of the interlocking relationship between the psychotic experience and certain coercive practices undergone during the provision of health care for psychosis, and the traumatic effects thus generated. Conclusions: The participants considered both themes to be highly important. Accordingly, these issues should be carefully assessed and managed in order to provide appropriate person-centred care.

This study used short-term longitudinal data to examine the contributions of democratic teaching practices (e.g., the Developmental Designs approach) and equitable school climate to civic engagement attitudes, beliefs, and behaviors among 515 Black and Latino middle school students (47.9% male). Concurrent experiences of democratic homeroom and classroom practices, and equitable school climate were associated with higher scores on each civic engagement component. The relation between classroom practices and civic attitudes was more robust when school climate was seen as more equitable. Longitudinally, homeroom practices and equitable school climate predicted higher civic attitudes 1 year later. Discussion focuses on civic attitudes and future research on school experiences that support civic engagement among youth of color.

The Myo/Nog cell lineage was discovered in the chick embryo and is also present in adult mammalian tissues. The cells are named for their expression of mRNA for the skeletal muscle specific transcription factor MyoD and bone morphogenetic protein inhibitor Noggin. A third marker for Myo/Nog cells is the cell surface molecule recognized by the G8 monoclonal antibody (mAb). G8 has been used to detect, track, isolate and kill Myo/Nog cells. In this study, we screened a membrane proteome array for the target of the G8 mAb. The array consisted of >5,000 molecules, each synthesized in their native confirmation with appropriate post-translational modifications in a single clone of HEK-293T cells. G8 mAb binding to the clone expressing brain-specific angiogenesis inhibitor 1 (BAI1) was detected by flow cytometry, re-verified by sequencing and validated by transfection with the plasmid construct for BAI1. Further validation of the G8 target was provided by enzyme-linked immunosorbent assay. The G8 epitope was identified by screening a high-throughput, site directed mutagenesis library designed to cover 95-100% of the 954 amino acids of the extracellular domain of the BAI1 protein. The G8 mAb binds within the third thrombospondin repeat of the extracellular domain of human BAI1. Immunofluorescence localization experiments revealed that G8 and a commercially available BAI1 mAb co-localize to the subpopulation of Myo/Nog cells in the skin, eyes and brain. Expression of the multi-functional BAI1 protein in Myo/Nog cells introduces new possibilities for the roles of Myo/Nog cells in normal and diseased tissues.

Autoimmune diseases such as rheumatoid arthritis are caused by immune system recognition of self-proteins and subsequent production of effector T cells that recognize and attack healthy tissue. Therapies for these diseases typically utilize broad immune suppression, which can be effective, but which also come with an elevated risk of susceptibility to infection and cancer. T cell recognition of antigens is driven by binding of T cell receptors to peptides displayed on major histocompatibility complex proteins (MHCs) on the cell surface of antigen-presenting cells. Technology for recombinant production of the extracellular domains of MHC proteins and loading with peptides to produce pMHCs has provided reagents for detection of T cell populations, and with the potential for therapeutic intervention. However, production of pMHCs in large quantities remains a challenge and a translational path needs to be established. Here, we demonstrate a fusion protein strategy enabling large-scale production of pMHCs. A peptide corresponding to amino acids 259–273 of collagen II was fused to the N-terminus of the MHC_II beta chain, and the alpha and beta chains were each fused to human IgG4 Fc domains and co-expressed. A tag was incorporated to enable site-specific conjugation. The cytotoxic drug payload, MMAF, was conjugated to the pMHC and potent, peptide-specific killing of T cells that recognize the collagen pMHC was demonstrated with tetramerized pMHC-MMAF conjugates. Finally, these pMHCs were incorporated into MMAF-loaded 3DNA nanomaterials in order to provide a biocompatible platform. Loading and pMHC density were optimized, and peptide-specific T cell killing was demonstrated. These experiments highlight the potential of a pMHC fusion protein-targeted, drug-loaded nanomaterial approach for selective delivery of therapeutics to disease-relevant T cells and new treatment options for autoimmune disease.

Cholangiocarcinoma (CCA) comprises a group of heterogeneous biliary cancers with dismal prognosis. The etiologies of most CCAs are unknown, but primary sclerosing cholangitis (PSC) is a risk factor. Non-invasive diagnosis of CCA is challenging and accurate biomarkers are lacking. We aimed to characterize the transcriptomic profile of serum and urine extracellular vesicles (EVs) from patients with CCA, PSC, ulcerative colitis (UC), and healthy individuals. Serum and urine EVs were isolated by serial ultracentrifugations and characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting. EVs transcriptome was determined by Illumina gene expression array [messenger RNAs (mRNA) and non-coding RNAs (ncRNAs)]. Differential RNA profiles were found in serum and urine EVs from patients with CCA compared to control groups (disease and healthy), showing high diagnostic capacity. The comparison of the mRNA profiles of serum or urine EVs from patients with CCA with the transcriptome of tumor tissues from two cohorts of patients, CCA cells in vitro, and CCA cells-derived EVs, identified 105 and 39 commonly-altered transcripts, respectively. Gene ontology analysis indicated that most commonly-altered mRNAs participate in carcinogenic steps. Overall, patients with CCA present specific RNA profiles in EVs mirroring the tumor, and constituting novel promising liquid biopsy biomarkers.

This study documents the vicarious psychological impact of the 2010 earthquake in Haiti on Haitians living in the United States. The role of coping resources--family, religious, and community support--was explored. The results highlight the importance of family and community as coping strategies to manage such trauma.

Ce genre « trouble » les anciennes taxies, en instaure d’autres, ludiques, car jouant toujours aux limites du sérieux et du bouffon, de l’ellipse et de l’indicible. La notion de marge, de frontière, de transgression, semble à la fois essentielle et largement folklorisée par les auteurs en général, comme peuvent en témoigner, entre mille autres, les réécritures — surtout anglo-américaines — du Fantôme de l'opéra” de Gaston Leroux. Les romans policiers — encore que dans ce cas précis il s’agisse plus d’amour fou et d’onirisme à demi-fantastique — échangent intrigues, casting, allusions, dans une perpétuelle intertextualité où les aficionados s’amusent à saluer tel ou tel clin d’œil, coup de chapeau ou discret coup de patte qui nervurent les œuvres d’un palimpseste secret.

This work aimed at combining different segmentation approaches to produce a robust and accurate segmentation result. Three to five segmentation results of the left ventricle were combined using the STAPLE algorithm and the reliability of the resulting segmentation was evaluated in comparison with the result of each individual segmentation method. This comparison was performed using a supervised approach based on a reference method. Then, we used an unsupervised statistical evaluation, the extended Regression Without Truth (eRWT) that ranks different methods according to their accuracy in estimating a specific biomarker in a population. The segmentation accuracy was evaluated by estimating six cardiac function parameters resulting from the left ventricle contour delineation using a public cardiac cine MRI database. Eight different segmentation methods, including three expert delineations and five automated methods, were considered, and sixteen combinations of the automated methods using STAPLE were investigated. The supervised and unsupervised evaluations demonstrated that in most cases, STAPLE results provided better estimates than individual automated segmentation methods. Overall, combining different automated segmentation methods improved the reliability of the segmentation result compared to that obtained using an individual method and could achieve the accuracy of an expert.

Objetivo: proponer un sistema de indicadores como instrumento de dirección para el laboratorio clínico, desde la perspectiva de gestión interna de un cuadro de mando integral. Material y métodos: los indicadores se obtienen de distintas fuentes, a través de registros internos del sistema informático del laboratorio, control externo de calidad de la Generalitat Valenciana. Se muestran los resultados de los indicadores de proceso analítico (proporción) de un año. Resultados: se proponen indicadores de gestión interna (divididos en proceso, adecuación y control de calidad). Los indicadores de proceso muestran una progresiva mejora desde su establecimiento. Conclusión: tras un año de utilización de los indicadores de proceso analítico de un cuadro de mando integral en el laboratorio, los resultados obtenidos validan su utilidad como instrumento para la gestión del laboratorio.Objective: to propose a set of indicators as a management tool for a clinical laboratory, by using the balanced scorecard internal business processes perspective. Material and methods: indicators proposed are obtained from different sources; external proficiency testing of the Valencia Community Government, by means of internal surveys and laboratory information system registers. One year testing process proportion indicators results are showed. Results: internal management indicators are proposed (process, appropriateness and proficiency testing). The process indicators results show gradual improvement since its establishment. Conclusion: after one years of using a conceptually solid Balanced Scorecard Internal business processes perspective indicators, the obtained results validate the usefulness as a laboratory management tool.

”Mobilis in mobile”... Les trains fous, cirques ambulants, déplacement erratiques et sentiments exacerbés qui sont de règle dans Fantômas portent tous le signe de la vitesse, de l’abolition des computs antérieurs, de l’irruption toujours métamorphique de l’altérité radicale : la victime est une maîtresse cachée, l’ennemie une fille ignorée, le mort un vivant cataleptique...Ces voltes constantes de la fiction nous arrachent à nos habitudes réalistes ancrées, et nous amènent à un tout autre type de posture lectrice - flottant quelque part entre volonté fossile d’un psychologisme impossible, et griserie coupable d’une matière imageante plasmatique.

Malaria transmission blocking vaccines (TBVs) are considered an effective means to control and eventually eliminate malaria. The Pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of Plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for TBV. It has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (VLPs). We engineered VLPs (Pfs25-CP VLP) comprising Pfs25 fused to the Alfalfa mosaic virus coat protein (CP) and produced these non-enveloped hybrid VLPs in Nicotiana benthamiana plants using a Tobacco mosaic virus-based 'launch' vector. Purified Pfs25-CP VLPs were highly consistent in size (19.3±2.4 nm in diameter) with an estimated 20-30% incorporation of Pfs25 onto the VLP surface. Immunization of mice with one or two doses of Pfs25-CP VLPs plus Alhydrogel® induced serum antibodies with complete transmission blocking activity through the 6 month study period. These results support the evaluation of Pfs25-CP VLP as a potential TBV candidate and the feasibility of the 'launch' vector technology for the production of VLP-based recombinant vaccines against infectious diseases.

In order to model squamous cell carcinoma development in vivo, researchers have long preferred hairless mouse models such as SKH-1 mice that have traditionally been classified as 'wild-type' mice irrespective of the genetic factors underlying their hairless phenotype. The work presented here shows that mutations in the Hairless (Hr) gene not only result in the hairless phenotype of the SKH-1 and Hr(-/-) mouse lines but also cause aberrant activation of NFκB and its downstream effectors. We show that in the epidermis, Hr is an early UVB response gene that regulates NFκB activation and thereby controls cellular responses to irradiation. Therefore, when Hr expression is decreased in Hr mutant animals there is a corresponding increase in NFκB activity that is augmented by UVB irradiation. This constitutive activation of NFκB in the Hr mutant epidermis leads to the stimulation a large variety of downstream effectors including the cell cycle regulators cyclin D1 and cyclin E, the anti-apoptosis protein Bcl-2, and the pro-inflammatory protein Cox-2. Therefore, Hr loss results in a state of uncontrolled epidermal proliferation that promotes tumor development, and Hr mutant mice should no longer be considered merely hairless 'wild-type' mice. Instead, Hr is a crucial UVB response gene and its loss creates a permissive environment that potentiates increased tumorigenesis.