80 research outputs found

    Measurement of recall with and without text.

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    Thesis (Ed.M.)--Boston Universit

    Cytosolic 5'-triphosphate ended viral leader transcript of measles virus as activator of the RIG I-mediated interferon response.

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    International audienceBACKGROUND: Double stranded RNA (dsRNA) is widely accepted as an RNA motif recognized as a danger signal by the cellular sentries. However, the biology of non-segmented negative strand RNA viruses, or Mononegavirales, is hardly compatible with the production of such dsRNA. METHODOLOGY AND PRINCIPAL FINDINGS: During measles virus infection, the IFN-beta gene transcription was found to be paralleled by the virus transcription, but not by the virus replication. Since the expression of every individual viral mRNA failed to activate the IFN-beta gene, we postulated the involvement of the leader RNA, which is a small not capped and not polyadenylated RNA firstly transcribed by Mononegavirales. The measles virus leader RNA, synthesized both in vitro and in vivo, was efficient in inducing the IFN-beta expression, provided that it was delivered into the cytosol as a 5'-trisphosphate ended RNA. The use of a human cell line expressing a debilitated RIG-I molecule, together with overexpression studies of wild type RIG-I, showed that the IFN-beta induction by virus infection or by leader RNA required RIG-I to be functional. RIG-I binds to leader RNA independently from being 5-trisphosphate ended; while a point mutant, Q299A, predicted to establish contacts with the RNA, fails to bind to leader RNA. Since the 5'-triphosphate is required for optimal RIG-I activation but not for leader RNA binding, our data support that RIG-I is activated upon recognition of the 5'-triphosphate RNA end. CONCLUSIONS/SIGNIFICANCE: RIG-I is proposed to recognize Mononegavirales transcription, which occurs in the cytosol, while scanning cytosolic RNAs, and to trigger an IFN response when encountering a free 5'-triphosphate RNA resulting from a mislocated transcription activity, which is therefore considered as the hallmark of a foreign invader

    Existential Loneliness and end-of-life care: A Systematic Review

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    Contains fulltext : 88662.pdf (publisher's version ) (Closed access)Patients with a life-threatening illness can be confronted with various types of loneliness, one of which is existential loneliness (EL). Since the experience of EL is extremely disruptive, the issue of EL is relevant for the practice of end-of-life care. Still, the literature on EL has generated little discussion and empirical substantiation and has never been systematically reviewed. In order to systematically review the literature, we (1) identified the existential loneliness literature; (2) established an organising framework for the review; (3) conducted a conceptual analysis of existential loneliness; and (4) discussed its relevance for end-of-life care. We found that the EL concept is profoundly unclear. Distinguishing between three dimensions of EL-as a condition, as an experience, and as a process of inner growth-leads to some conceptual clarification. Analysis of these dimensions on the basis of their respective key notions-everpresent, feeling, defence; death, awareness, difficult communication; and inner growth, giving meaning, authenticity-further clarifies the concept. Although none of the key notions are unambiguous, they may function as a starting point for the development of care strategies on EL at the end of life.1 april 201

    Convergent genetic and expression data implicate immunity in Alzheimer's disease

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    Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

    Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

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    Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

    La relation soignants/soignĂ©s Ă  l’épreuve de l’image

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    À en juger par le nombre croissant des productions audiovisuelles et cinĂ©matographiques sur les thĂšmes de la santĂ©, de la maladie ou de la mĂ©decine, force est de constater que les pratiques mĂ©dicales occupent de nos jours une place importante sur la scĂšne mĂ©diatique. Du cĂŽtĂ© de la fiction, la figure d'autoritĂ© du soignant, personnage hĂ©roĂŻque au savoir biomĂ©dical spĂ©cialisĂ©, recĂšle des ressources scĂ©naristiques inĂ©puisables comme en tĂ©moignent, par exemple, les Ă©pisodes de la sĂ©rie Dr House (D. Shore, 2004-2012). Mais les failles personnelles du soignant, ses doutes, qu’il soit mĂ©decin gĂ©nĂ©raliste (La maladie de Sachs, M. Deville, 1990) ou psychanalyste (In Treatement, H. Levy, 2008-2010) travaillent Ă©galement les reprĂ©sentations sociales, annonçant en creux une image inversĂ©e et critique de la toute puissance du savoir mĂ©dical, de ses limites techniques et scientifiques et des crises identitaires plus profondes qui traversent le milieu mĂ©dical actuel. Les mises en scĂšnes d'intrigues autour de la question de la maladie et du soin (Le bruit des glaçons, Blier, 2010) ne manquent pas d’alimenter les prĂ©occupations sociales des patients, dĂ©sormais rĂ©currentes, autour du droit Ă  l’information mĂ©dicale, des valeurs et de l’éthique mĂ©dicale, du traitement des corps dans leurs dimensions biologique, sociale et politique. Au-delĂ  de cette dramaturgie de l’intime (Remillet 2013), prĂ©sente dans le cinĂ©ma de fiction comme dans de nombreux documentaires – La consultation (De Crecy 2009), Hospital (F. Wiseman, 1970), Les patients (C. Simon, 1989) et Ils ne mourraient pas tous, mais tous Ă©taient frappĂ©s (M.A. Roudil, S. Bruneau, 2006) –, rares sont les films rĂ©alisĂ©s dans une perspective anthropologique et accordant une place centrale aux soins du corps (Michau 2007), Ă  la parole du malade, Ă  celle du mĂ©decin ou du thĂ©rapeute (Candelise 2013, Remillet 2014). Cependant, que nous apprend de plus que les analyses dĂ©sormais classiques de l'anthropologie de la maladie et de l’anthropologie mĂ©dicale un acte mĂ©dical observĂ©, filmĂ© ou photographiĂ©, alors que certaines notions clĂ©s telles que illness et sickness (Young 1982, Kleinman 1988 et 1997) ont dĂ©jĂ  largement contribuĂ© Ă  asseoir ces deux disciplines sur le plan thĂ©orique ? Qu’en est-il lorsque les chercheurs en sciences sociales tentent d'approcher la « rĂ©alitĂ© » des soins Ă  travers des prises de vues, qu'elles soient photographiques ou filmiques

    Integrating Multidisciplinary Observations in Vent Environments (IMOVE): Decadal Progress in Deep-Sea Observatories at Hydrothermal Vents

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    The unique ecosystems and biodiversity associated with mid-ocean ridge (MOR) hydrothermal vent systems contrast sharply with surrounding deep-sea habitats, however both may be increasingly threatened by anthropogenic activity (e.g., mining activities at massive sulphide deposits). Climate change can alter the deep-sea through increased bottom temperatures, loss of oxygen, and modifications to deep water circulation. Despite the potential of these profound impacts, the mechanisms enabling these systems and their ecosystems to persist, function and respond to oceanic, crustal, and anthropogenic forces remain poorly understood. This is due primarily to technological challenges and difficulties in accessing, observing and monitoring the deep-sea. In this context, the development of deep-sea observatories in the 2000s focused on understanding the coupling between sub-surface flow and oceanic and crustal conditions, and how they influence biological processes. Deep-sea observatories provide long-term, multidisciplinary time-series data comprising repeated observations and sampling at temporal resolutions from seconds to decades, through a combination of cabled, wireless, remotely controlled, and autonomous measurement systems. The three existing vent observatories are located on the Juan de Fuca and Mid-Atlantic Ridges (Ocean Observing Initiative, Ocean Networks Canada and the European Multidisciplinary Seafloor and water column Observatory). These observatories promote stewardship by defining effective environmental monitoring including characterizing biological and environmental baseline states, discriminating changes from natural variations versus those from anthropogenic activities, and assessing degradation, resilience and recovery after disturbance. This highlights the potential of observatories as valuable tools for environmental impact assessment (EIA) in the context of climate change and other anthropogenic activities, primarily ocean mining. This paper provides a synthesis on scientific advancements enabled by the three observatories this last decade, and recommendations to support future studies through international collaboration and coordination. The proposed recommendations include: i) establishing common global scientific questions and identification of Essential Ocean Variables (EOVs) specific to MORs, ii) guidance towards the effective use of observatories to support and inform policies that can impact society, iii) strategies for observatory infrastructure development that will help standardize sensors, data formats and capabilities, and iv) future technology needs and common sampling approaches to answer today’s most urgent and timely questions

    Integrating Multidisciplinary Observations in Vent Environments (IMOVE): Decadal Progress in Deep-Sea Observatories at Hydrothermal Vents

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    The unique ecosystems and biodiversity associated with mid-ocean ridge (MOR) hydrothermal vent systems contrast sharply with surrounding deep-sea habitats, however both may be increasingly threatened by anthropogenic activity (e.g., mining activities at massive sulphide deposits). Climate change can alter the deep-sea through increased bottom temperatures, loss of oxygen, and modifications to deep water circulation. Despite the potential of these profound impacts, the mechanisms enabling these systems and their ecosystems to persist, function and respond to oceanic, crustal, and anthropogenic forces remain poorly understood. This is due primarily to technological challenges and difficulties in accessing, observing and monitoring the deep-sea. In this context, the development of deep-sea observatories in the 2000s focused on understanding the coupling between sub-surface flow and oceanic and crustal conditions, and how they influence biological processes. Deep-sea observatories provide long-term, multidisciplinary time-series data comprising repeated observations and sampling at temporal resolutions from seconds to decades, through a combination of cabled, wireless, remotely controlled, and autonomous measurement systems. The three existing vent observatories are located on the Juan de Fuca and Mid-Atlantic Ridges (Ocean Observing Initiative, Ocean Networks Canada and the European Multidisciplinary Seafloor and water column Observatory). These observatories promote stewardship by defining effective environmental monitoring including characterizing biological and environmental baseline states, discriminating changes from natural variations versus those from anthropogenic activities, and assessing degradation, resilience and recovery after disturbance. This highlights the potential of observatories as valuable tools for environmental impact assessment (EIA) in the context of climate change and other anthropogenic activities, primarily ocean mining. This paper provides a synthesis on scientific advancements enabled by the three observatories this last decade, and recommendations to support future studies through international collaboration and coordination. The proposed recommendations include: i) establishing common global scientific questions and identification of Essential Ocean Variables (EOVs) specific to MORs, ii) guidance towards the effective use of observatories to support and inform policies that can impact society, iii) strategies for observatory infrastructure development that will help standardize sensors, data formats and capabilities, and iv) future technology needs and common sampling approaches to answer today’s most urgent and timely questions
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