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1

Wilburn, Hugh. "The Kathmandu Valley Preservation Trust: a Nepal architecture archive at Harvard University". Art Libraries Journal 32, n.º 3 (2007): 11–16. http://dx.doi.org/10.1017/s0307472200014929.

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The papers of the Kathmandu Valley Preservation Trust are one result of the passion of Harvard University Professor Emeritus Eduard F. Sekler. In the 1960s he witnessed the encroachments of progress and the associated threat to buildings in the royal and religious centers of the Kathmandu Valley in Nepal, and co-founded the Trust in 1990 with others interested in documenting the sites and restoring the buildings. The Trust has restored numerous temples, guesthouses, townhouses and shrines in Kathmandu, Patan and Bhaktapur, and in the process has generated vital documentation including measured drawings, photographs, contextual materials, planning reports and feasibility studies. Threats to this material from the natural environment and political turmoil, as well as longstanding ties to Harvard of several of its members, led the Trust to approach the Frances Loeb Library at the University’s Graduate School of Design, where as a result the archive will be housed. The infrastructure developed by Harvard University Library will be used to create a virtual archive available worldwide on the web, as well as a parallel paper archive to be maintained by the Trust in Nepal.
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Balon, Jan. "O samotné myšlence jednotné sociologie: Harvard a Columbia". Teorie vědy / Theory of Science 33, n.º 3 (21 de novembro de 2011): 358–86. http://dx.doi.org/10.46938/tv.2011.123.

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On the Very Idea of Unified Sociology: Harvard and ColumbiaAbstract: The article concentrates on the historical context of American sociology's development in the period between 1930 and 1965, which is here associated with a specific project of the field's unification elaborated at Harvard University and Columbia University. It is argued that the idea of unified sociology is worked in the very project of American sociology as a science and found its genuine expression in the efforts to reach "objectivity and coherence" of sociological thought/knowledge. It also distinctly formed the professional identity of the discipline. It was expected that the scientific integrity would be achieved by means of securing the continuity of theory and practice, which was to provide a general methodological pillar for cumulative research. The historical contextualization of this formative period studies how the very idea of unified sociology affected both theoretical and methodological perspectives within the discipline and also the possibility of its integrated research agenda.O samotné myšlence jednotné sociologie: Harvard a ColumbiaAbstrakt: Článek se zaměřuje na historický kontext vývoje americké sociologie v období mezi lety 1930-1965, jež je spojeno se specifickým projektem sjednocení oboru rozpracovaným na Harvardské a Kolumbijské univerzitě. Samotná myšlenka jednotné sociologie je neoddělitelně vpletena do celého projektu americké sociologie jako vědy a své „čisté" vyjádření nalezla v úsilí prokázat „objektivitu a koherenci" sociologického myšlení/vědění. Zcela zřetelně také formovala profesní identitu oboru. Prostředkem zajištění vědecké integrity bylo především zajištění kontinuity teorie a praxe, ježby založilo a o něž by se mohlo opírat pevné metodologické „sebevědomí". Historická kontextualizace tohoto formativního období si klade za cíl sledovat, nakolik myšlenka sjednocené sociologie ovlivnila teoretické a metodologické perspektivy v rámci oboru i vlastní představy o možnosti jeho integrované výzkumné agendy.
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Rinaldo, Constance, Linda Ford e Joseph deVeer. "Museum, Library and Archives Partnership: Leveraging Digitized Data from Historical Sources". Biodiversity Information Science and Standards 2 (13 de junho de 2018): e25920. http://dx.doi.org/10.3897/biss.2.25920.

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The Museum of Comparative Zoology at Harvard University (MCZ), founded in 1859, has approximately 20 million extant and fossil invertebrate and vertebrate specimens. These historical collections continue to be a focus of research and teaching for the MCZ, Harvard and outside researchers. The Ernst Mayr Library/Archives (EMLA) of the MCZ is a founding member of the Biodiversity Heritage Library (BHL), an international consortium with a mission to make biodiversity literature openly available for use. Meeting the needs of the MCZ is a priority for EML Museum/library and achives collaboration One collaborative Museum/Library project was the digitization of approximately 81,000 MCZ specimen ledger pages/cards associated with various collections. These historical items, once digitized and deposited in the Harvard Digital Repository Service (DRS), were linked to the relevant specimen records in MCZbase, the museum-wide database. Over 1.2 million specimen records are now linked with digitized sources which benefit all users by adding to the provenance of the specimen data and allowing direct referral to the primary collection source. The EMLA holds an extensive collection of field notes, letters and manuscripts of researchers associated with the MCZ. Collector records are a gold mine of unpublished observations, notes, sketches, specimen lists and narratives. They are primary source data at its most personal, and may be the only documentation of a scientist’s thought processes and observations, particularly for unpublished materials. William Brewster was a prominent late 19th, early 20th century naturalist associated with the MCZ Ornithology Department until his death in 1919. Brewster provided authoritative and novel additions to the knowledge of birds, and his detailed, long-term observations are the key to his published contributions. Brewster’s unpublished scientific legacy is being digitized and deposited in the Harvard DRS and BHL by the EMLA. Transcribed notebook pages will be attached to images in BHL thus improving data discovery. Brewster deposited over 45,000 specimens in the MCZ Ornithology Collection. Combining specimens and unpublished notes is an opportunity to link hidden data and enhance research capabilities. Next steps for this collaborative project include finely grained cross-linking of specific pages, correspondence and photographs to and from the MCZ’s specimen database and BHL. We show how MCZ has leveraged data in digital repositories to enhance and directly relate to MCZbase, with citations to notes, transcriptions and published literature. These collaborations enhance discoverability of hidden data while promoting cross-discipline research to interrelated historical sources.
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Abouzid, Mohamed, Anna K. Główka e Marta Karaźniewicz-Łada. "Trend research of vitamin D receptor: Bibliometric analysis". Health Informatics Journal 27, n.º 4 (outubro de 2021): 146045822110431. http://dx.doi.org/10.1177/14604582211043158.

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Studies on vitamin D receptor (VDR) and its association with multiple disorders are expanding. This bibliometric study aims to find and summarize VDR-related publications, and compare them across various countries, organizations, and journals to demonstrate trends in VDR research. VOSviewer and Excel 2019 were used to classify and summarize Web of Science articles from 1900 to mid-2021. Total records of 8762 articles were analyzed, and maps of co-citations bibliometric keywords co-occurrence were designed. In conclusion, relative research interest and published papers related to VDR were growing in the past 30 years. The United States of America dominates the research regarding VDR. The highest quality of VDR research was achieved by the University of California System, University of Wisconsin System, and Harvard University. J Steroid Biochem Mol Biol, PLoS One, and J Biol Chem are the leading three productive journals on VDR. Various aspects of vitamin D deficiency associated disorders and genetic studies regarding VDR, including single nucleotide polymorphism, gene variants, epigenome, long non-coding ribonucleic acid (lncRNA), and small nucleolar RNA host gene 6 are potentially the recent research hotspot in this field. Moreover, coronavirus disease, polycystic ovary syndrome, non-alcoholic fatty liver disease, gut microbiota, gestational diabetes, systemic sclerosis, and chemoresistance are the trending medical conditions associated with VDR.
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Abouzid, Mohamed, Anna K. Główka e Marta Karaźniewicz-Łada. "Trend research of vitamin D receptor: Bibliometric analysis". Health Informatics Journal 27, n.º 4 (outubro de 2021): 146045822110431. http://dx.doi.org/10.1177/14604582211043158.

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Studies on vitamin D receptor (VDR) and its association with multiple disorders are expanding. This bibliometric study aims to find and summarize VDR-related publications, and compare them across various countries, organizations, and journals to demonstrate trends in VDR research. VOSviewer and Excel 2019 were used to classify and summarize Web of Science articles from 1900 to mid-2021. Total records of 8762 articles were analyzed, and maps of co-citations bibliometric keywords co-occurrence were designed. In conclusion, relative research interest and published papers related to VDR were growing in the past 30 years. The United States of America dominates the research regarding VDR. The highest quality of VDR research was achieved by the University of California System, University of Wisconsin System, and Harvard University. J Steroid Biochem Mol Biol, PLoS One, and J Biol Chem are the leading three productive journals on VDR. Various aspects of vitamin D deficiency associated disorders and genetic studies regarding VDR, including single nucleotide polymorphism, gene variants, epigenome, long non-coding ribonucleic acid (lncRNA), and small nucleolar RNA host gene 6 are potentially the recent research hotspot in this field. Moreover, coronavirus disease, polycystic ovary syndrome, non-alcoholic fatty liver disease, gut microbiota, gestational diabetes, systemic sclerosis, and chemoresistance are the trending medical conditions associated with VDR.
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Zhou, Bingrong, Yu Chen Zhao, Hongliang Liu, Sheng Luo, Christopher I. Amos, Jeffrey E. Lee, Xin Li, Hongmei Nan e Qingyi Wei. "Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival". Cancers 12, n.º 2 (24 de janeiro de 2020): 288. http://dx.doi.org/10.3390/cancers12020288.

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Because aberrant glycosylation is known to play a role in the progression of melanoma, we hypothesize that genetic variants of glycosylation pathway genes are associated with the survival of cutaneous melanoma (CM) patients. To test this hypothesis, we used a Cox proportional hazards regression model in a single-locus analysis to evaluate associations between 34,096 genetic variants of 227 glycosylation pathway genes and CM disease-specific survival (CMSS) using genotyping data from two previously published genome-wide association studies. The discovery dataset included 858 CM patients with 95 deaths from The University of Texas MD Anderson Cancer Center, and the replication dataset included 409 CM patients with 48 deaths from Harvard University nurse/physician cohorts. In the multivariable Cox regression analysis, we found that two novel single-nucleotide polymorphisms (SNPs) (ALG6 rs10889417 G>A and GALNTL4 rs12270446 G>C) predicted CMSS, with an adjusted hazards ratios of 0.60 (95% confidence interval = 0.44–0.83 and p = 0.002) and 0.66 (0.52–0.84 and 0.004), respectively. Subsequent expression quantitative trait loci (eQTL) analysis revealed that ALG6 rs10889417 was associated with mRNA expression levels in the cultured skin fibroblasts and whole blood cells and that GALNTL4 rs12270446 was associated with mRNA expression levels in the skin tissues (all p < 0.05). Our findings suggest that, once validated by other large patient cohorts, these two novel SNPs in the glycosylation pathway genes may be useful prognostic biomarkers for CMSS, likely through modulating their gene expression.
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Buckland, Warren. "Modern Enchantments: The Cultural Power of Secular Magic. By Simon During. Cambridge, MA: Harvard University Press, 2002; pp. 336 + illus. $35 cloth." Theatre Survey 45, n.º 1 (maio de 2004): 135–37. http://dx.doi.org/10.1017/s0040557404300086.

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Simon During's book presents a broad overview of European and North American magic and argues that magic influenced the formation of modern culture. During clearly delineates three types of magic: Supernatural Magic, or “real” spiritual magic associated with superstition, religion, and the occult; Natural Magic, which popularized scientific discoveries such as electricity, magnetism, X-rays, and optics; and Secular Magic, based on spectacle, skillful technique, illusion, and special effects. He successfully charts the complex relations among the three types of magic, and explains how they reinforce one another (as is the case with natural and secular magic), or work against one another (as when natural and secular magic gradually delegitimized the influence of supernatural magic in an increasingly secularized, modern culture).
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Liu, Jiangshan, Bote Qi, Lin Gan, Yanli Shen e Yu Zou. "A Bibliometric Analysis of the Literature on Irisin from 2012–2021". International Journal of Environmental Research and Public Health 19, n.º 10 (18 de maio de 2022): 6153. http://dx.doi.org/10.3390/ijerph19106153.

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Irisin is a hormone-like molecule mainly released by skeletal muscles in response to exercise, which is proposed to induce the ‘browning’ of white adipose tissue. Since its identification, irisin was reported to be closely associated with many metabolic diseases, including type 2 diabetes mellitus (T2DM), obesity, cardiovascular disease (CVD), and metabolic bone diseases. In recent years, irisin has attracted increasing research interest, and numerous studies have been published in this field. Thus, it is essential to identify the current research status of irisin and measure research hotspots and possible future trends. In this study, by utilizing two visualization software named CiteSpace and VOSviewer, we analyzed 1510 Web of Science publications on irisin published from 2012 to 2021. Our results show that the number of irisin-related articles published annually has increased significantly. China participates in the most studies, followed by the United States and Turkey. Firat University, Harvard University, and Shandong University are three major institutions with larger numbers of publications. The analysis of keywords co-occurrence indicates that insulin resistance, inflammation, and circulating irisin levels in serum are the research hotspots. Apoptosis, BDNF, and osteoporosis will likely become the focus of future research related to irisin. Overall, this study may provide helpful insights for researchers to understand the current research situation and identify the potential frontiers of irisin.
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Sur, Daniel, Cristina Lungulescu, Irina-Ioana Puscariu, Simona Ruxandra Volovat, Madalina Preda, Elena Adriana Mateianu e Cristian Virgil Lungulescu. "Immunotherapy-Related Publications in Colorectal Cancer: A Bibliometric Analysis". Healthcare 10, n.º 1 (31 de dezembro de 2021): 75. http://dx.doi.org/10.3390/healthcare10010075.

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Patients with microsatellite-instability-high (MSI-H) or mismatched repair-deficient colorectal cancer (CRC) appear to be responsive to checkpoint inhibitors. This study aimed to assess research trends in CRC immunotherapy. Publication patterns of articles covering immunotherapies in CRC in the Web of Science Core Collection database were retrospectively examined using VOS viewer software (version 1.6.16) prior to 25 May 2021. Ultimately, 3977 records were identified that were published between 1975 and 2021, which received a total of 128,681 citations (an average of 32.36 citations per item), with a noticeable rise in 2014. The majority of articles were published in the US (35.8%), China (17.7%), and Germany (9.4%). Publications mainly originated from the Institut National de la Santé Et De La Recherche Medicale Inserm, followed by the University of Texas System and Harvard University; however, Johns Hopkins University received the most citations (18,666 for 69 publications). The Journal of Clinical Oncology issued the most publications (n = 146), while the most referenced item (7724 citations) was published in the New England Journal of Medicine in 2012. The most common keywords were associated with tumors (expression and microsatellite instability) or immune system components (t-cells/dendritic cells). The findings demonstrate the scientific community’s interest in the MSI-H subtype of colorectal tumors and how immunotherapy may be employed more successfully to treat metastatic CRC.
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Hu, Suh-Woan, Jaw-Ji Yang e Yuh-Yih Lin. "Mapping the Scientific Landscape of Bacterial Influence on Oral Cancer: A Bibliometric Analysis of the Last Decade’s Medical Progress". Current Oncology 30, n.º 10 (5 de outubro de 2023): 9004–18. http://dx.doi.org/10.3390/curroncol30100650.

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The research domain investigating bacterial factors in the development of oral cancer from January 2013 to December 2022 was examined with a bibliometric analysis. A bibliometric analysis is a mathematical and statistical method used to examine extensive datasets. It assesses the connections between prolific authors, journals, institutions, and countries while also identifying commonly used keywords. A comprehensive search strategy identified 167 relevant articles, revealing a progressive increase in publications and citations over time. China and the United States were the leading countries in research productivity, while Harvard University and the University of Helsinki were prominent affiliations. Prolific authors such as Nezar Al-Hebshi, Tsute Chen, and Yaping Pan were identified. The analysis also highlights the contributions of different journals and identifies the top 10 most cited articles in the field, all of which focus primarily on molecular research. The article of the highest citation explored the role of a Fusobacterium nucleatum surface protein in tumor immune evasion. Other top-cited articles investigated the correlation between the oral bacteriome and cancer using 16S rRNA amplicon sequencing, showing microbial shifts associated with oral cancer development. The functional prediction analysis used by recent studies has further revealed an inflammatory bacteriome associated with carcinogenesis. Furthermore, a keyword analysis reveals four distinct research themes: cancer mechanisms, periodontitis and microbiome, inflammation and Fusobacterium, and risk factors. This analysis provides an objective assessment of the research landscape, offers valuable information, and serves as a resource for researchers to advance knowledge and collaboration in the search for the influence of bacteria on the prevention, diagnosis, and treatment of oral cancer.
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Dratch, Gladys I. "SPECIAL COLLECTIONS FOR EDUCATION RESEARCH: CONTRIBUTIONS TO AN INFORMATION NETWORK". Education Libraries 22, n.º 1-2 (5 de setembro de 2017): 5. http://dx.doi.org/10.26443/el.v22i1-2.124.

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This article focuses on special collections in the United States which provide historical curriculum resources and other specialized materials for education research. An overview of the Special Collections at Monroe C. Gutman Library, Harvard University, Graduate School of Education provides background on their growth and development, descriptions of major collections, information about the preservation microfilming projects, and a discussion of the research use of the collections. Other sources of information about special collections are presented, including the author's annotated bibliographies of directories for locating special collections and selected World Wide Web sites. Various collections are featured in the descriptive entries for the print and online sources. The author concludes that promoting our institutions' special collections through various print and online sources, as well as formal and informal communication with colleagues and scholars, advances the work of researchers in the field, although there are challenges in addressing the associated issues of access, staffing, services, and preservation. It is suggested that Web sites have the greatest potential for enhancing the research process by disseminating in-depth information about special collections.
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Barness, Jessica, e Vince Giles. "Like a Letter, You". Matlit Revista do Programa de Doutoramento em Materialidades da Literatura 5, n.º 1 (27 de dezembro de 2017): 85–86. http://dx.doi.org/10.14195/2182-8830_5-1_15.

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Like a Letter, You is a collaborative investigation focused on the concept of ‘conversation as an object’. Originally recorded as part of a larger self-produced project titled hEar Pixels, this track manifests as an experimental soundbased reconfiguration of an original essay about handwritten correspondence: How might an analog essay be performed as a digital assemblage of sound? In what ways are the methods of a DJ tied to speech, literature, and dialog? The track is composed using a cut-and-paste process of ‘utterances’, which may be described as units of speech distinct from language that may be oral or written and are inevitably completed by a response[1] which inevitably forms a dialog. Further, these speech units may manifest through gestures associated with digital tools as a form of cultural production[2]. Like a Letter, You includes a reading of the essay aloud, snippets of informal spoken conversations between the authors, and musical bits generated with a touch-based audio mixing platform. In effect, Like a Letter, You embodies the concepts of writing, dialog, and gesture within the genre of sound literature, and it also speaks to the unpredictable nature of collaboration and human interaction. [1] BAKHTIN, Mikhail (1986). Speech Genres and Other Late Essays. Austin: University of Texas Press.[2] NOLAND, Carrie (2009). Agency and Embodiment: Performing Gestures/Producing Culture. Cambridge, MA: Harvard University Press.
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Müller, Liara De Oliveira, Jordana Marques Kneipp, Jaíne Pompeo Rodrigues e Rodrigo Reis Favarin. "Innovation of impact business models". Journal on Innovation and Sustainability RISUS 13, n.º 2 (15 de junho de 2022): 59–72. http://dx.doi.org/10.23925/2179-3565.2022v13i2p59-72.

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The business model innovation to insert sustainability has been approached as a strategic point of view about social and environmental concerns, integrating itself with the objectives of organizations. In this context, impact businesses represent the effective proposal to attract part of private capital to solutions that act directly on social, environmental, and technological challenges. Because of the relevance of the impact business model, this study aims to identify the main characteristics of international scientific production related to this theme in the last ten years. Therefore, a bibliometric investigation was developed, using the Web of Science database, integrating the terms “social impact”; “social entrepreneurship”; “impact business”; “innovation”; and “business models”. A significant increase in the production associated with the theme from 2015 can be highlighted, with a continuous evolution until 2020, which denotes the emergence of the theme. Concerning thematic areas, business and management presented the highest number of publications related to the researched topics, standing out with 395 and 251 publications, respectively. The United States of America leads the ranking of countries that publish the topics of impact and innovation business model. However, England and Spain also stand out in the surveys. Among the three institutions that publish the most on the topics, the University of London, the University of Groningen, and Harvard University published the most frequently. Yet, it was possible to determine, through a sociometric analysis, the words with the highest number of occurrences, the average number of citations per document of authors who have at least five articles published, and the documents that had the highest number of citations.
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Akdemir, Asuman, Aglaé Achechova, Benjamin Guichard, Andrey E. Guskov, Assel Lakhayeva, Anna Rakityanskaya, Natalya S. Redkina et al. "Libraries of the world during the pandemic: a new experience and the first conclusions". Bibliosphere, n.º 3 (24 de dezembro de 2020): 65–83. http://dx.doi.org/10.20913/1815-3186-2020-3-65-83.

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The main theme of 2020 for libraries around the world is organizing the work under the constraints associated with COVID-19, which was confirmed by the results of information searches for articles in the world’s largest databases (Google Scholar, Web of Science, Scopus, etc.), which discuss actual problems of libraries’ activity during this period. Their solution is achieved by developing common approaches to challenges at the global level, sharing best practices and methods of working in a pandemic. The purpose of the article is to present the key reports presented in the cycle of online meetings entitled “Life of the world’s libraries during a pandemic”, organized by the State Public Scientific and Technological Library of the Siberian Branch of Russian Academy of Science (SPSTL SB RAS). The article presents the experience of foreign and Russian libraries: Bibliothèque universitaire des langues et civilisations (France), the Libraries of New York University and Harvard Universities (USA), University of Tartu Library (Estonia), the National Library of the Republic of Turkey, the Scientific Library of the Belarusian National Technical University, Research Library of Tomsk State University and SPSTL SB RAS. The authors showed the activities of libraries to organize the work of employees and service users. As a result, it was determined that libraries choose different ways and methods of working with users, develop innovative services, expand the repertoire of information resources / products, take measures to ensure the safe work of employees, including remotely. It was emphasized that not all types of work could be transferred to a remote mode, and that required quick decisions on the redistribution of functions among employees and the мlaunch of new projects. It is concluded that librarians need to continue learning digital etiquette and gaining new skills and competencies for telecommuting.
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Song, Yaowen, Fangkun Zhao, Wei Ma e Guang Li. "Hotspots and trends in liver kinase B1 research: A bibliometric analysis". PLOS ONE 16, n.º 11 (4 de novembro de 2021): e0259240. http://dx.doi.org/10.1371/journal.pone.0259240.

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Introduction In the past 22 years, a large number of publications have reported that liver kinase B1 (LKB1) can regulate a variety of cellular processes and play an important role in many diseases. However, there is no systematic bibliometric analysis on the publications of LKB1 to reveal the research hotspots and future direction. Methods Publications were retrieved from the Web of Science Core Collection (WoSCC), Scopus, and PubMed databases. CiteSpace and VOSviewer were used to analysis the top countries, institutions, authors, source journals, discipline categories, references, and keywords. Results In the past 22 years, the number of LKB1 publications has increased gradually by year. The country, institution, author, journals that have published the most articles and cited the most frequently were the United States, Harvard University, Prof. Benoit Viollet, Journal of Biochemistry and Plos One. The focused research hotspot was the molecular functions of LKB1. The emerging hotspots and future trends are the clinical studies about LKB1 and co-mutated genes as biomarkers in tumors, especially in lung adenocarcinoma. Conclusions Our research could provide knowledge base, frontiers, emerging hotspots and future trends associated with LKB1 for researchers in this field, and contribute to finding potential cooperation possibilities.
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r, Selahattin. "Bibliometric Analysis of Chest Pain: A Holistic Approach from an Emergency Medicine Perspective (Chest Pain: A Holistic Bibliometric Analysis)". Annals of Medical Research 30, n.º 9 (2023): 1. http://dx.doi.org/10.5455/annalsmedres.2023.08.187.

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Objective: Chest pain is a very broad term and is the most common reason for admission to the emergency department (ED) after injury. This study aimed to present a medical perspective by examining scientific articles published on chest pain from a emergeny medicine perspective with statistical methods. Material and Methods: Exploratory and descriptive bibliometric study conducted in Ankara, Turkey. The source of our study is the Web of Science (WoS) database. The articles indexed between 1980-2022 were included in our research in the database, and the studies of 2023 were not included since the effect factors are not clear yet. While searching the database, the words “Chest Pain” were used as keywords. Results: We reached a total of 3329 publications by analyzing the WoS database using the term "chest pain". When the citations of the documents written about chest pain are evaluated, we found that the highest citation was made in 2021. Co-citation analysis has shown that there are 11310 authors investigating the issue of chest pain. Collaboration and citation collaboration was observed between Harvard University, the Duke University and the Mayo Clinic. Coronary artery disease and acute coronery syndrome were found the strongest relationship with chest pain. Conclusion: It is observed that the publications related to chest pain are associated with acute coronary syndrome (ACS) and this diagnosis has the highest publication, citation and impact power. The number of publications related to other fatal clinical conditions in the differential diagnosis of chest pain is relatively low.
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Fiorenza, Francis Schüssler. "Religion: A Contested Site in Theology and the Study of Religion". Harvard Theological Review 93, n.º 1 (janeiro de 2000): 7–34. http://dx.doi.org/10.1017/s0017816000016643.

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I first became acquainted with Richard Niebuhr's scholarship and thought in a German graduate seminar on Friedrich Schleiermacher and Ernst Troeltsch. Niebuhr's book, Schleiermacher on Christ and Religion, was a required text for the course and was regarded as the most significant study on Schleiermacher. My interest in Karl Rahner's theology had led me to go to Germany for doctoral studies. Once there, I discovered that much of what I had admired in Rahner had already been anticipated a century and a half earlier in Schleiermacher's work. Professor Niebuhr's study on Schleiermacher was the source of this insight. It influenced my decision later to translate into English Schleiermacher's On the Glaubenslehre: Two Letters to Dr. Lücke. My topic for this article, the theological retrieval of the category of religion, is obviously suggested by Niebuhr's study of Schleiermacher, which sought to overcome the dichotomies associated with the category of religion by the then-dominant Neo-orthodoxy. This topic is also a theme of Niebuhr's ensuing book, Experiential Religion, in which he elaborated his own constructive account of religion and experience. In addition, this topic appropriately relates to Niebuhr's activity at Harvard University, where he helped establish a program of studies in religion within the Committee on the Study of Religion.
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Hammad, Nour M., e Cindy W. Leung. "Food Insecurity Among Graduate Students and Postdoctoral Trainees". JAMA Network Open 7, n.º 2 (20 de fevereiro de 2024): e2356894. http://dx.doi.org/10.1001/jamanetworkopen.2023.56894.

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ImportanceFood insecurity on college campuses has emerged as an urgent public health priority; however, there has been a lack of studies focused on graduate students or postdoctoral trainees, particularly those enrolled at private academic institutions.ObjectiveTo estimate the prevalence of and factors associated with food insecurity among graduate students and postdoctoral trainees at a private academic university in Boston, Massachusetts.Design, Setting, and ParticipantsIn this cross-sectional survey study, a survey on food insecurity was sent to graduate students and postdoctoral trainees at 3 health-focused graduate schools at Harvard University during the end of the spring 2023 academic term (April to June). Participants were studying medicine, dental medicine, or public health. Data analysis was performed from July to September 2023.ExposureSociodemographic characteristics of graduate students and postdoctoral trainees.Main Outcomes and MeasuresThe primary outcome was food insecurity as assessed using the US Household Food Security Survey Module. Food insecurity also encompassed low and very low food security. Bidirectional stepwise logistic regression models were conducted to estimate the factors associated with food insecurity for graduate students and postdoctoral trainees.ResultsThe analytic sample included 1745 participants (response rate, 55%): 1287 were graduate students and 458 were postdoctoral trainees. The median age of respondents was 29.0 (IQR, 7.0) years, and more than half (1073 [61.5%]) identified as female. A total of 694 respondents (39.8%) identified as Asian, 625 (35.8%) as White, and 426 (24.4%) as being of other race or ethnicity. The prevalence of food insecurity was 17.4% (224 of 1287) among graduate students and 12.7% (58 of 458) among postdoctoral trainees. Among graduate students, factors associated with food insecurity included being Asian (OR, 1.06 [95% CI, 1.01-1.11]) or of other race or ethnicity (OR, 1.07 [95% CI, 1.02-1.13]), receiving financial aid (OR, 1.09 [95% CI, 1.05-1.13]), and having housing instability (OR, 1.53 [95% CI, 1.45-1.61]). Among postdoctoral trainees, factors associated with food insecurity included receiving Supplemental Nutrition Assistance Program benefits (OR, 1.59 [95% CI, 1.28-1.97]), having housing instability (OR, 1.33 [95% CI, 1.22-1.45]), and not owning a car (OR, 1.11 [95% CI, 1.04-1.18]).Conclusions and RelevanceIn this study, a substantial proportion of graduate students and postdoctoral trainees at a private academic institution experienced food insecurity during the academic year. These findings underscore the need for national and institutional interventions to address the complex, structural factors related to food insecurity in these distinct populations.
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Kelsey, Karl. "Epigenetics, environment and epidemiology: an interview with Karl Kelsey". Epigenomics 14, n.º 6 (março de 2022): 323–26. http://dx.doi.org/10.2217/epi-2022-0008.

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In this interview, Professor Karl Kelsey speaks with Storm Johnson, Commissioning Editor for Epigenomics, on his work to date in the field of environmental epigenomics and epidemiology. Dr Karl Kelsey, MD, MOH is a Professor of Epidemiology and Pathology and Laboratory Medicine at Brown University. He is the Founding Director of the Center for Environmental Health and Technology and Head of the Environmental Health Section at the Department of Epidemiology. Dr Kelsey is interested in the application of laboratory-based biomarkers in environmental disease, with experience in chronic disease epidemiology and tumor biology. The goals of his work include a mechanistic understanding of individual susceptibility to exposure-related cancers. In addition, his laboratory is interested in tumor biology, investigating somatic alterations in tumor tissue from the patients who have developed exposure-related cancers. This work involves the use of an epidemiologic approach to characterize epigenetic and genetic alteration of genes in the causal pathway for malignancy. Active work includes several studies of individual susceptibility to cancer. Dr Kelsey's laboratory mainly investigates susceptibility to smoking-related lung cancer and studies multi-racial and ethnic populations. In addition, the laboratory is also involved with the study of inherited susceptibility to brain tumors and pancreatic cancer. Major case control studies that are ongoing in the laboratory include studies designed to understand inherited and acquired susceptibility in head and neck cancers. The laboratory is also involved in a case control study of asbestos-associated mesothelioma, arsenic exposure, cigarette smoking and bladder cancer. Considerable work is being devoted to understanding the mechanisms of action of both asbestos and arsenic including their ability to affect promoter methylation and gene silencing in carcinogenesis. Recent laboratory studies includes an interest in using newly developed DNA methylation biomarkers to probe immune profiles from archived blood. Dr Kelsey received his MD from the University of Minnesota and Masters of Occupational Health from Harvard University.
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Al-Hemiary, Nesif J. "Exposure to violence and academic achievement in Iraq". Journal of the Faculty of Medicine Baghdad 57, n.º 3 (1 de outubro de 2015): 218–20. http://dx.doi.org/10.32007/jfacmedbagdad.573366.

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Background: Iraqis were exposed to wars, widespread violence and civil war. Post-traumatic stress disorder develops after exposure to trauma and violence. It has a negative effect on academic achievement of the students.Objective: This report was carried out to study the effect of exposure to violence on academic achievement of youths in Iraq.Methods: A total of 319 university students from Baghdad were included in the study. Their age ranged between 18 and 24 years with male to female ratio of 0.6:1. A questionnaire was filled for each participant. Requested data were demographic information, data on school achievement and Harvard Trauma questionnaire (exposure to war trauma, posttraumatic stress disorder “PTSD”). Chi square was used to examine the association between PTSD and poor academic achievement. Student’s t test was used to demonstrate the difference in exposure between students with poor and good academic achievement. P value < 0.5 was considered as significant.Results: Post- traumatic stress disorder was observed in 21.9% of students. Poor academic achievement was noticed in 32.9% of students with post-traumatic stress disorder. Academic achievement was not significantly associated with post-traumatic stress disorder (p=0.8). Significant difference was found in score of exposure to violence between students with poor and good academic achievement (p= 0.001).Conclusion: Exposure to violence had a negative effect on academic achievement
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Bottary, Ryan, Eric Fields, Elizabeth Kensinger e Tony Cunningham. "235 Age and Chronotype Associated with Sleep Timing Changes During COVID-19-Related Lockdowns in the US". Sleep 44, Supplement_2 (1 de maio de 2021): A94. http://dx.doi.org/10.1093/sleep/zsab072.234.

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Abstract Introduction Global lockdowns implemented to reduce spread of the Coronavirus Disease 2019 (COVID-19) have offered unique insight into how sleep patterns change when typical social obligations are significantly reduced. Here, we aimed to replicate findings of sleep timing delays and reduced social jetlag during lockdown using a large, regionally-diverse sample of participants from the United States (US). Further, we conducted exploratory analyses to determine if observed sleep changes were associated with age and self-reported chronotype. Methods A sample of 691 US adults (age 18-89) completed the Ultrashort Munich Chronotype Questionnaire twice during the same assessment: once querying retrospective memory for sleep patterns in the 6-weeks prior to February 1, 2020 (Pre-Lockdown) and a second time for sleep patterns in the 6-weeks prior to ~May 20th (Peak-Lockdown in the US). Participants also completed the abbreviated Morningness-Eveningness Questionnaire to assess chronotype. We compared sleep duration (SDur), sleep onset time (SO), sleep end time (SEnd), social jetlag (SJL; difference between work-day and free-day sleep midpoint) and social sleep restriction (SSR; difference between work-day and free-day sleep duration) Pre- to Peak-Lockdown. We conducted exploratory analyses to determine whether Pre- to Peak-Lockdown changes in these sleep metrics were associated with age or chronotype. Main analyses were preregistered with Open Science Framework (https://osf.io/4a3fx). Results During the Peak-Lockdown period, participants, on average, reported significantly later SO and SEnd times and significantly reduced SJL and SSR compared with the Pre-Lockdown period. Change in SJL and SSR Pre- to Peak-Lockdown was significantly positively associated with age and chronotype such that SJL and SSR decreased more during lockdown in younger participants and those with an evening chronotype. Conclusion Our results support lockdown-associated sleep timing delays and reduced SJL and SSR. Younger age and evening chronotype were associated with greater reductions in SJL and SSR during lockdown. These findings suggest that individuals, particularly young individuals and those with an evening chronotype, experience greatest desynchrony between intrinsic and social sleep timing when conforming to typical pre-pandemic social schedules. Support (if any) Harvard Medical School Division of Sleep Medicine T32 HL007901 (RB and TJC); Brandeis University NIH NRSA T32 NS007292 (ECF)
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Hutchins-Wiese, Heather. "Mediterranean Diet and Lifestyle Index Development for Older Adults". Current Developments in Nutrition 5, Supplement_2 (junho de 2021): 413. http://dx.doi.org/10.1093/cdn/nzab038_025.

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Abstract Objectives The Mediterranean diet is associated with many health benefits, yet it is typically only the food pattern that is assessed without consideration for lifestyle attributes that accompany a Mediterranean way of life. The Mediterranean diet pyramid includes lifestyle activities at the base of the pyramid such as regular physical activity (PA), adequate rest, conviviality, biodiversity and seasonality, traditional local and eco-friendly products, and culinary activities. The purpose of this study was to design and pilot test a Mediterranean diet and lifestyle index for older adults in the U.S. Methods The Harvard Food Frequency Questionnaire was used to determine the alternative Mediterranean Diet Score (aMed). The short version of the Minnesota Leisure Time PA questionnaire and additional Mediterranean diet-related dietary habit and lifestyle questions were piloted in 75 older adults attending senior centers. Results Participants were primarily women (80.6%) and Caucasian (68%) with an average age of 71.89+/−7.60 years. A 27-item index including the aMed food groups, dietary habits, PA, culinary activities, purchasing of local and seasonal foods, and adequate rest resulted in a reliable score (α = 0.75). Individual index factors correlated with the overall Mediterranean diet and lifestyle score. Conclusions While this Mediterranean diet and lifestyle index resulted in good internal consistency; assessment of conviviality, especially for older adults in the time of Covid-19, need be re-evaluated as a lifestyle measure that can impact dietary intake and overall health. Funding Sources Eastern Michigan University Faculty Research Fellowship Award.
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STAFFORD, WILLIAM. "SHALL WE TAKE THE LINGUISTIC TURN? BRITISH RADICALISM IN THE ERA OF THE FRENCH REVOLUTION". Historical Journal 43, n.º 2 (junho de 2000): 583–94. http://dx.doi.org/10.1017/s0018246x99001028.

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Intertextual war: Edmund Burke and the French Revolution in the writings of Mary Wollstonecraft, Thomas Paine, and James Mackintosh. By Steven Blakemore. Cranbury, NJ: Associated University Presses, 1997. Pp. 256. ISBN 0-8386-3751-5. £32.Radical expression: political language, ritual, and symbol in England, 1790–1850. By James Epstein. Oxford: Oxford University Press, 1994. Pp. xi+233. ISBN 0-19-506550-6. £30.Tom Paine: a political life. By John Keane. London: Bloomsbury, 1996. Pp. xxii+644. ISBN 0-7475-2543-9. £8.99.Gothic images of race in nineteenth-century Britain. By H. L. Malchow. Stanford, CA: Stanford University Press, 1996. Pp. xii+335. ISBN 0-8047-2664-7. £35 (hb). ISBN 0-8047-2793-7. £12.95 (pb).Popular contention in Great Britain, 1758–1834. By Charles Tilly. Cambridge, MA: Harvard University Press, 1995. Pp. xvii+476. ISBN 0-674-68980-1. £31.50.Radical culture: discourse, resistance and surveillance, 1790–1820. By David Worrall. Hemel Hempstead: Harvester Wheatsheaf, 1992. Pp. ix+236. ISBN 0-7450-0960-3. £40.Most of these books are influenced by current philosophical or methodological concerns which might be labelled, according to taste, as poststructuralism, postmodernism, or the linguistic turn; but they are influenced to very varying degrees. At one end of the spectrum stands Tilly's substantial study, essentially modernist, rejecting the latest fashions. At the other stand the books by Blakemore and Malchow, their colours firmly nailed to the mast of deconstruction. Blakemore teaches in a department of English, and although Malchow's institutional affiliation is as an historian, his book is a hermeneutic of literary texts. The great majority of ‘postmodern’ analyses of texts from this period have come from the stable of literary studies, perhaps especially from scholars concerned, as Malchow is, with the construction of gender, that great growth area of the present time. None of these books subscribes in practice to a postmodern relativism, declaring itself to be merely a construction or representation of the past: all arrive at some kind of closure, explicitly or implicitly asserting the truth of their interpretations. Historians concerned to justify their subject to funding bodies may judge this to be prudent; nevertheless a greater degree of reflexivity, of self-doubt, would have been welcome in some instances, as we shall see.
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Abouzid, Mohamed, Marta Karaźniewicz-Łada, Basel Abdelazeem e James Robert Brašić. "Research Trends of Vitamin D Metabolism Gene Polymorphisms Based on a Bibliometric Investigation". Genes 14, n.º 1 (14 de janeiro de 2023): 215. http://dx.doi.org/10.3390/genes14010215.

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Vitamin D requires activation to show its pharmacological effect. While most studies investigate the association between vitamin D and disease, only a few focus on the impact of vitamin D metabolism gene polymorphisms (vitDMGPs). This bibliometric study aims to provide an overview of current publications on vitDMGPs (CYP27B1, CYP24A1, CYP2R1, CYP27A1, CYP2R1, DHCR7/NADSYN1), compare them across countries, affiliations, and journals, and inspect keywords, co-citations, and citation bursts to identify trends in this research field. CiteSpace© (version 6.1.R3, Chaomei Chen), Bibliometrix© (R version 4.1.3 library, K-Synth Srl, University of Naples Federico II, Naples, Italy), VOSviewer© (version 1.6.1, Nees Jan van Eck and Ludo Waltman, Leiden University, Leiden, Netherlands) and Microsoft® Excel 365 (Microsoft, Redmond, Washington, USA) classified and summarized Web of Science articles from 1998 to November 2022. We analyzed 2496 articles and built a timeline of co-citations and a bibliometric keywords co-occurrence map. The annual growth rate of vitDMGPs publications was 18.68%, and their relative research interest and published papers were increasing. The United States of America leads vitDMGPs research. The University of California System attained the highest quality of vitDMGPs research, followed by the American National Institutes of Health and Harvard University. The three productive journals on vitDMGPs papers are J. Steroid. Biochem. Mol. Biol., PLOS ONE, and J. Clin. Endocrinol. Metab. We highlighted that the vitDMGPs domain is relatively new, and many novel research opportunities are available, especially those related to studying single nucleotide polymorphisms or markers in a specific gene in the vitamin D metabolism cycle and their association with disease. Genome-wide association studies, genetic variants of vitDMGPs, and vitamin D and its role in cancer risk were the most popular studies. CYP24A1 and CYB27A1 were the most-studied genes in vitDMGPs. Insulin was the longest-trending studied hormone associated with vitDMGPs. Trending topics in this field relate to bile acid metabolism, transcriptome and gene expression, biomarkers, single nucleotide polymorphism, and fibroblast growth factor 23. We also expect an increase in original research papers investigating the association between vitDMGPs and coronavirus disease 2019, hypercalcemia, Smith–Lemli–Opitz syndrome, 27-hydroxycholesterol, and mendelian randomization. These findings will provide the foundations for innovations in the diagnosis and treatment of a vast spectrum of conditions.
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Koutsogiannaki, Sophia, e Koichi Yuki. "Elucidating the mechanism of neutrophil-mediated lung injury in sepsis and the role of CD11d/CD18 integrin on this process". Journal of Immunology 208, n.º 1_Supplement (1 de maio de 2022): 105.21. http://dx.doi.org/10.4049/jimmunol.208.supp.105.21.

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Abstract Sepsis is the leading cause of death in intensive care unit (ICU) and the most expensive condition treated in the US, without a specific therapy yet available. Acute lung injury (ALI) is one of the most significant organ injuries in sepsis, resulting from massive migration of neutrophils to the lung, but the exact mechanism is not known. β2 (CD18) integrin family [consisting of αLβ2 (CD11a/CD18), αMβ2 (CD11b/CD18), αXβ2 (CD11c/CD18) and αDβ2 (CD11d/CD18)] and its counter-receptor on the endothelium, ICAM-1 (CD54), are critical for neutrophil migration, but their role in ALI is not yet delineated. Using a murine model of sepsis induced by cecal ligation and puncture (CLP) surgery, we showed decreased neutrophil levels and attenuated injury in the lung of β2−/− and ICAM-1−/− mice at 12h post-CLP, suggesting the importance of β2 integrins in this process. In addition, we observed decreased neutrophil levels and attenuated injury in the lung of αDβ2−/− mice but not in the lung of αLβ2−/− and αMβ2−/− mice, suggesting that αDβ2 has an orchestrating role in sepsis-induced ALI. In support, we found increased αDβ2 expression levels on neutrophils both in the lung and blood of WT mice as sepsis progressed. RNAseq analysis in neutrophils from blood and lung of WT and αDβ2−/− mice showed that αDβ2 mediates neutrophil migration to the lung through pathways associated with antigen presentation, apoptosis and NOD-like receptor signaling. αDβ2−/− neutrophils had also less Cxcr2, Ltb4r1 and Dhrs9 expression, associated with neutrophil migration and the retinoic acid pathway. Taken together, our results suggest a mechanism for ALI in sepsis in which αDβ2 integrin has a major role and could be a novel target for therapeutic intervention. The Anesthesia Research Distinguished Trailblazer Award, Boston Children's Hospital The William F. Milton Fund, Harvard University
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Slominski, Andrzej, Jacobo Wortsman, Andrew J. Carlson, Lois Y. Matsuoka, Charles M. Balch e Martin C. Mihm. "Malignant Melanoma". Archives of Pathology & Laboratory Medicine 125, n.º 10 (1 de outubro de 2001): 1295–306. http://dx.doi.org/10.5858/2001-125-1295-mm.

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Abstract Context.—The rapidly developing fields of melanoma research are revolutionizing the current concepts on melanoma etiology and pathogenesis and are introducing newer diagnostic techniques and potential therapeutic approaches. Objectives.—To present the most current concepts on the etiology and pathogenesis of melanoma and to introduce the recent diagnostic techniques and the potential therapeutic approaches. Methods.—Data sources were reports on melanoma published in the English language literature and observations made using specimens available at Harvard University, Johns Hopkins Medical Center, Albany Medical College, Loyola University Medical Center, and University of Tennessee Health Science Center. Results.—Studies on melanoma containing chromosomal or genetic evaluation were selected for further analysis. Current clinical and pathologic categories with the reported genetic abnormalities were related to the latest information on pigment biology. The data extracted were used to develop a conceptual framework on the pathogenesis of melanoma; the generated model was then evaluated and used to suggest potential therapeutic approaches. Conclusions.—(1) Melanoma is not genetically homogenous, and the existing differences between the pathologic categories, particularly in areas such as type of growth phase (radial vs vertical growth), total vertical dimension, ulceration of primary tumor, and metastatic process, have profound prognostic and therapeutic implications. (2) Chromosomal aberrations and gene mutations are found in sporadic and familial melanomas; among the most important are those affecting the 9p21, which contains the p16 locus, a site known to be critical for normal progression of the cell cycle. Aberrant p16 expression is associated with more aggressive behavior. (3) Melanoma cells possess a remarkable repertoire of biosynthetic capacities represented by the production of hormones, growth factors, and their receptors that may sustain and accelerate tumor development and progression. For example, expression of the tumoral products α-melanocyte-stimulating hormone and adrenocorticotropic hormone is regulated in vitro by ultraviolet light, a known carcinogen. (4) Melanomas differ from other tumors in their intrinsic capability to express melanogenic enzymes with the corresponding structural proteins to actually synthesize melanin. Melanogenesis-related proteins are rapidly entering the clinical arena, being used not only as diagnostic markers, but also as potential targets for melanoma therapy.
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Yip, Ka-che. "Trust in Troubled Times: Money, Banks, and State-Society Relations in Republican Tianjin. By BRETT SHEEHAN. [Cambridge, MA: Harvard University Press, 2003. 269 pp. £30.00. ISBN 0-674-01080-9.]". China Quarterly 181 (março de 2005): 189–90. http://dx.doi.org/10.1017/s0305741005320108.

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Trust in Troubled Times is an important addition to the still relatively small body of literature on banking and finance in Republican China. In this careful and thoughtful study of the development of banking and paper money in Tianjin from late Qing to the eve of the Sino-Japanese War in 1937, Brett Sheehan analyses the rise of modern banks and the growth of social trust in such financial institutions, and examines their relations to the process of state-building. The work is solidly based on a wealth of primary sources including newspapers published in Tianjin, Beijing and Shanghai, archival materials in China, Taiwan and the United States, as well as interviews with individuals who had worked in Tianjin banks in the 1920s and 1930s. Indeed, one of the main contributions of this book is the tremendous amount of data amassed by the author that illuminates the complexity of the problems associated with banking and finance in the pre-1949 period.Drawing on Western theories on banking and social trust, Sheehan begins his study with a discussion of a theoretical framework which provides not only a foundation for the analysis of developments in Tianjin, but also the basis for comparative studies of institution and state-building in different political, social and economic milieus. He then examines a series of financial crises, from the moratorium on exchange in 1916, the bank runs under the warlord governments, the financial instability created by the Japanese attack on Shanghai in 1932, and the monetary reforms of the Nationalist government in 1935. The responses of government officials, bankers and the local elites to the crises, the strategies they used to establish and promote impersonal trust in Tianjin banks, and the impact of these crises on the elites, the banking profession and state-society relations constitute the main body of the study. The story is both encouraging and disheartening: encouraging because by 1937, trust in Chinese-owned and operated banks was indeed established; disheartening because the banks failed to gain the autonomy that could have shielded them from the abuses of the government.
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Lee, Ellen, Helmet Karim, Ipsit Vahia e Andrea Iaboni. "100 - Artificial Intelligence in Geriatric Mental Health: Recent Advances in Clinical Research". International Psychogeriatrics 33, S1 (outubro de 2021): 1. http://dx.doi.org/10.1017/s1041610221001307.

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SynopsisWith the rise of wearable sensors, advancement in comprehensible artificial intelligence (AI) algorithms, and growing acceptance of AI in medicine, AI has great potential to more reliably diagnose, prognose, and treat mental illnesses. The rapidly rising number of older adults worldwide presents a unique challenge for clinicians due to increased mental health needs in the setting of a dwindling clinical workforce. AI has enabled researchers to better understand mental illnesses by taking advantage of ‘big data.’This symposium will present an overview of novel research leveraging AI (machine learning, natural language processing) to better track, understand, and support mental health and cognitive functioning in older adults.Helmet Karim, PhD will present on prediction of treatment response in late-life major depressive disorder and the implications of those models.Ellen Lee, MD will present on using natural language processing to understand psychosocial functioning in older adults.Ipsit Vahia, MD will present on radio-based sensors to phenotype changes in behavior patterns that may correlate with a range of geropsychiatric symptoms.Andrea Iaboni, MD DPhil FRCPC will present on multimodal wearable and vision-based sensors for the detection and categorization of behavioural symptoms of dementia.The symposium includes three physician-scientists (Iaboni, Lee, Vahia), two women (Iaboni, Lee), and two early career faculty (Lee, Karim – co-chairs). The symposium represents four different institutions across the country (McLean/Harvard, Toronto Rehabilitation Institute/University of Toronto, UC San Diego, University of Pittsburgh) and four very different approaches using AI technology to improve understanding and outcomes in the field of geriatric mental health.The symposium seeks to address the underutilization of AI in psychiatric research, especially in the field of aging research. The increased individual-level heterogeneity associated with aging; complex trajectories of decline in cognitive, mental, and physical health; and lack and slow adoption of older adult-centered technologies present great challenges to advancing the field. However, advances in the field of explainable AI and transdisciplinary development of AI approaches can address the unique challenges of aging research.
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Gudkov, Maxim M. "Red Rust vs Yellow Rust: Metamorphoses of the Soviet Play on Broadway". Literature of the Americas, n.º 14 (2023): 141–88. http://dx.doi.org/10.22455/2541-7894-2023-14-141-188.

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The study focuses on the adaptation of a politically engaged dramaturgical work from Bolshevik Russia — Vladimir Kirshon’s and Andrey Uspensky’s play Konstantin Terekhin (Rust) — to the specific requirements of Broadway, the commercial theater of the USA, and the textual changes of the Soviet original associated with it. The basic principles of the Broadway theater creative and organizational model, drastically different from the repertory theater of post-revolutionary Russia, are defined — the primacy of commerce over artistry, the absence of state support and censorship, a respectable audience that does not accept radical political ideas. On the American stage the Soviet play was produced in 1929, with the changed title (Red Rust), and the text subjected to changes and distortions. The paper considers these changes in the context of American socio–economic life of the Red Thirties. The discrepancy between the original dramaturgical material and the specific requirements of the American commercial theater is analyzed. The free handling of the text from Bolshevik Russia in the US theater is due to the absence of copyright regulations between the two countries. The process of exporting the play to the United States — via Paris and London — is being reconstructed. Three sources that have carried out the textual transformation of the Soviet original are characterized: the authors of the French-language adaptation from Russian (Fernand Nozière and Vladimir Bienstock), British translators from French into English (Virginia and Frank Vernon) and Broadway stage director who previously visited Moscow and sought to introduce into the text what, in his opinion, Soviet censorship would not allow (Herbert Biberman). The study is based on the materials from the Beinecke Library of Rare Books and Manuscripts collections (Yale University), as well as documents from the Houghton Library (Harvard University), the New York Public Library for Performing Arts, the Russian State Archive of Literature and Art (Moscow), and the museum of the Mossovet State Academic Theater (Moscow). The study is aimed at expanding the understanding of the stage history of the Russian drama in America.
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Schram, C. "30. Abortion and the fall of midwifery in 19th Century North America". Clinical & Investigative Medicine 30, n.º 4 (1 de agosto de 2007): 43. http://dx.doi.org/10.25011/cim.v30i4.2790.

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The 19th Century in North America was a time of many social and scientific changes that impacted the field of medicine. A result of one such change was the medicalization of childbirth, as the primary care of women during labour shifted from midwives to physicians. While there is ample discourse on the many factors that contributed to this shift, there is very little discussion on the role played by abortion. Studying abortion in the 19th Century is often limited by a paucity of primary sources from the physicians who performed abortions and women who obtained them. Although most authors who discuss the midwifery shift do not make any mention of a role played by the issue of abortion, it has been addressed and supported by primary sources. This raises the question, why is abortion not discussed in histories on the medicalization of childbirth by other authors? The objectives of this paper are historical and histographic. First, it will present the evidence on the use of abortion as a political tool employed by some policy makers, physicians and the media to discourage women from choosing midwives for their childbirth care. Second, it will analyze possible reasons why this topic is not addressed by the majority of historians of childbirth in 19th Century North America. Are the authors concerned about the varying social views of abortion, the associated politics, the lack of primary sources, or are they personally uncomfortable with the subject? Only the authors themselves can truly know their reasons for neglecting the subject of abortion in their work, but this analysis will show how issues that influence historians determine the version of the past that is produced and propagated into the present and the future. Borst CG. Catching Babies: the Professionalization of Childbirth, 1870-1920. Cambridge, Mass.: Harvard University Press, 1995. Bourgeault B, Davis-Floyd R, eds. Reconceiving Midwifery. Montreal & Kingston: McGill-Queen’s University Press, 2004. Dodd DE, Gorham D, eds. Caring and Curing: Historical Perspectives on Women and Healing in Canada. Ottawa: University of Ottawa Press, 1994. Wertz DC, Wertz RW. Lying In; a History of Childbirth in America (expanded edition published 1989 by Richard W. Wertz and Dorothy C. Wertz) New York: Free Press; London: Macmillan, 1977. Reagan LJ. Linking midwives and abortion in the Progressive Era. Bulletin of the History of Medicine 1995; 69(4):569-98. Reagan LJ. When Abortion Was a Crime, Women, Medicine, and Law in the United States, 1867-1973. London: University of California Press, 1997.
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Wang, Dongqing, Leonard Kamanga Katalambula, Andrea R. Modest, Tara Young, Abbas Ismail, Mary Mwanyika-Sando, Amani Tinkasimile et al. "Meals, Education, and Gardens for In-School Adolescents (MEGA): study protocol for a cluster randomised trial of an integrated adolescent nutrition intervention in Dodoma, Tanzania". BMJ Open 12, n.º 7 (julho de 2022): e062085. http://dx.doi.org/10.1136/bmjopen-2022-062085.

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IntroductionSecondary schools have the transformative potential to advance adolescent nutrition and provide a unique entry point for nutrition interventions to reach adolescents and their families and communities. Integrated school nutrition interventions offer promising pathways towards improving adolescent nutrition status, food security and building sustainable skill sets.Methods and analysisThe Meals, Education, and Gardens for In-School Adolescents (MEGA) project aims to implement and evaluate an integrated, school-based nutrition intervention package among secondary schools in the Chamwino District of Dodoma, Tanzania. MEGA is a cluster-randomised controlled trial, including six public secondary schools assigned to three different arms. Two schools will receive the full intervention package, including school meals, school gardens, nutrition education and community workshops. Two schools will receive the partial intervention package, including the school garden, nutrition education and community workshops. Two schools will serve as the controls and will not receive any intervention. The intervention will be implemented for one academic year. Baseline and end-line quantitative data collection will include 750 adolescents and 750 parents. The domains of outcomes for adolescents will include haemoglobin concentrations, anthropometry, educational outcomes and knowledge, attitudes and practices regarding nutrition, agriculture and health. The domains of outcomes for parents will include knowledge, attitudes and practices of nutrition, agriculture and health. End-line focus group discussions will be conducted among selected adolescents, parents and teachers to assess the facilitators and barriers associated with the intervention.Ethics and disseminationThis study was approved by the Institutional Review Board at Harvard T.H. Chan School of Public Health (approval number: IRB20-1623), the Institutional Research Review Committee at the University of Dodoma (approval number: MA.84/261/02) and the Tanzania National Institute for Medical Research (approval number: NIMR/HO/R.8a/Vol. IX/3801). A manuscript with the research findings will be developed for publication. Local dissemination meetings will be held with key stakeholders.Trial registration numberNCT04788303.; ClinicalTrials.gov Identifier.
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Zhao, Weijie, e Kevin T. Zhao. "An exciting time for genome editing: an interview with David R. Liu". National Science Review 6, n.º 3 (23 de novembro de 2018): 452–54. http://dx.doi.org/10.1093/nsr/nwy146.

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Abstract In 1987, several Osaka University researchers discovered a special kind of clustered DNA repeats in bacteria. Within a few years, two other groups independently discovered the same phenomenon but no one knew its function at the time. Only a small handful of scientists studied this property from its discovery in 1987 to 2005. It was then that the function of these DNA repeats, which were named Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), was finally elucidated. Researchers found that CRISPR, when combined with its CRISPR-associated partner (Cas), is crucial for the functioning of the bacterial adaptive immune system against viral phage infection. CRISPR sequences can be transcribed into targeting RNA molecules, and Cas enzymes are guided by these RNAs to cut specific viral DNA loci, rendering resistance against the viral infection. Scientists realized that this natural bacterial immune response system could be engineered to become a powerful genome editing tool. Prior to CRISPR, existing genome editing tools such as Zinc Finger Nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs) relied solely upon protein–DNA interactions to target an enzyme to specific DNA sequences. The design, engineering and evolution of proteins for various DNA sequences is difficult and time-consuming. In contrast, the CRISPR-Cas system uses Watson–Crick base pairing between a guide RNA and the target DNA to localize the complex to specific DNA sequences. This feature enables users to simply change an RNA sequence to match a DNA target to reposition the whole complex. Since then, numerous talented scientists have headed into this field. Within a single decade, they have developed the CRISPR-Cas system into a powerful genome editing tool and applied it to the editing of microorganisms, plants, animals and even human embryos. David R. Liu, Professor of Harvard University and the Broad Institute, and an investigator of the Howard Hughes Medical Institute, is one of them. One of his major contributions to the field is the development of ‘base editing’. His group engineered the CRISPR system to transform it from being DNA scissors that cut DNA into specific DNA base pair rewriters that directly convert one base pair to a different base pair. This development opens the door to precision genome editing, raising the possibility of treating thousands of genetic diseases that are caused by single point mutations in the human genome. Here, David talks about this exciting time for genome editing.
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Rosen, Alan. "Return from the vanishing point: a clinician's perspective on art and mental illness, and particularly schizophrenia". Epidemiologia e Psichiatria Sociale 16, n.º 2 (junho de 2007): 126–32. http://dx.doi.org/10.1017/s1121189x00004747.

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SUMMARYAims - To examine earlier uses and abuses of artworks by individuals living with severe mental illnesses, and particularly schizophrenia by both the psychiatric and arts communities and prevailing stereotypes associated with such practices. Further, to explore alternative constructions of the artworks and roles of the artist with schizophrenia and other severe mental illnesses, which may be more consistent with amore contemporary recovery orientation, encompassing their potentials for empowerment, social inclusion as citizens and legitimacy of their cultural role in the community. Results - Earlier practices with regardto the artworks of captive patients of psychiatrists, psychotherapists, art therapists, occupational and diversional therapists, often emphasised diagnostic or interpretive purposes, or were used to gauge progress or exemplify particular syndromes. As artists and art historians began to take an interest in such artworks, they emphasised their expressive, communicative and aesthetic aspects, sometimes in relation to primitive art. These efforts to ascribe value to these works, while well-meaning, were sometimes patronising and vulnerable to perversion by totalitarian regimes, which portrayed them as degenerate art, often alongside the works of mainstream modernist artists. This has culminated in revelations that the most prominent European collection of psychiatric art still contains, and appears to have only started to acknowledge since these revelations, unattributed works by hospital patients who were exterminated in the so-called “euthanasia” program in the Nazi era. Conclusions - Terms like Psychiatric Art, Art Therapy, Art Brut and Outsider Art may be vulnerable to abuse and are a poor fit with the aspirations of artists living with severe mental illnesses, who are increasingly exercising their rights to live and work freely, without being captive, or having others controlling their lives, or mediating and interpreting their works. They sometimes do not mind living voluntarily marginal lives as artists, but they prefer to live as citizens, without being involuntarily marginalised by stigma. They also prefer to live with culturally valued roles which are recognised as legitimate in the community, where they are also more likely to heal and recover.Declaration of Interest: This paper was completed during a Visiting Fellowship, Department of Social Medicine, School of Public Health, & Department of Medical Anthropology, Faculty of Arts & Sciences, Harvard University, Cambridge, Mass, USA. A condensed version of this paper is published in “For Matthew & Others: Journeys with Schizophrenia”, Dysart, D, Fenner, F, Loxley, A, eds. Sydney, University of New South Wales Press in conjunction with Campbelltown Arts Centre & Joan Sutherland Performing Arts Centre, Penrith, 2006, to accompany with a large exhibition of the same name, with symposia & performances, atseveral public art galleries in Sydney & Melbourne, Australia. The author is also a printmaker, partly trained at Ruskin School, Oxford, Central St. Martin's School, London, and College of Fine Arts, University of New South Wales, Sydney.
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Bradner, James. "Common Gene Deletions and Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation." Blood 110, n.º 11 (16 de novembro de 2007): 37. http://dx.doi.org/10.1182/blood.v110.11.37.37.

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Abstract Graft-versus-host disease (GVHD) is a serious and common complication of allogeneic hematopoetic stem cell transplantation (HSCT). GVHD results from genetic incompatibilities between donor and host. Although matching of donor and recipient human leukocyte antigens (HLA) is critical to transplant outcomes, GVHD is common even in transplants involving HLA-identical sibling donors. The additional determinants of graft compatibility are poorly understood, though a small number of minor histocompatibility antigens have been reported. The human genome has recently been found to show large-scale structural variation, including large gene deletions sufficiently common to appear as homozygous gene deletions in many patients. We investigated whether donor-recipient disparity for common gene deletion polymorphisms (homozygous gene deletion in donor but not in recipient) was associated with GVHD following allogeneic HSCT in 821 HLA-identical sibling donor-recipient pairs. Patient samples and clinical outcomes data were assembled collaboratively from institutions in Finland and North America, in strict compliance with ethical standards and IRB-approved protocols. Donors and patients were typed for the presence of six common gene deletions using real-time PCR. Donor-recipient disparities were then assessed for association with acute and chronic GVHD. Donor-recipient disparities in the expected direction (-/- in donor, +/- or +/+ in recipient) for two common gene deletions, UGT2B28 and UGT2B17, were associated with chronic GVHD (OR &gt; 4, P=0.001; and OR=2.0, P=0.05 respectively). Donor-recipient disparity for UGT2B17 was also associated with acute GVHD (OR=2.0, P=0.05). In the cohorts assembled for this study, we also observed an expected robust association for sex mismatch with chronic GVHD (OR=1.6, p=0.001) and a non-significant trend toward association with acute GVHD (OR=1.1, p=0.30). No significant association with acute or chronic GVHD was observed for the other four common gene deletion polymorphisms (GSTT1, GSTM1, OR51A2, and LCE3C). Consistent with prior studies of minor histocompatibility antigens on the Y-chromosome, we observed evidence of serologic immunoreactivity to a nine residue peptide on UGT2B17 in an HSCT recipient with mismatch at this locus. Because disparities for UGT2B17 and UGT2B28 occur in fewer than 6% of sibling-donor transplants in populations with European ancestry, they can explain only a fraction of the genetically attributable risk of GVHD. Of note, deletion of UGT2B28 appears to be more common in individuals with African and Latin American ancestry (allele frequency of 25–35%), and therefore merits investigation as a potential contributor to transplant outcome in those populations. We conclude that variation in genome structure associates with graft-versus-host disease and merits further investigation as a cause of minor histocompatibility barriers to hematopoietic stem cell transplantation. For the Transplant Structural Genetics Consortium: David Altshuler, Shannon Chilewski, Steven McCarroll (Broad Institute of Harvard and MIT, Cambridge, MA); Joseph Antin, James Bradner, Stephanie Lee, Jerome Ritz, Robert Soiffer (Dana-Farber Cancer Institute, Boston, MA); Aarno Palotie (Finnish Genome Center, Helsinki, Finland); Jukka Partanen, Hannu Turpeinen (Finnish Red Cross, Helsinki, Finland); Tapani Ruutu, Liisa Volin (Helsinki University Central Hospital, Helsinki, Finland); David Ginsburg, David Siemeniak (University of Michigan, Ann Arbor, MI).
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Kakani, Pragya. "Physician-pharmacy integration and oral cancer drug use and quality." Journal of Clinical Oncology 39, n.º 28_suppl (1 de outubro de 2021): 39. http://dx.doi.org/10.1200/jco.2020.39.28_suppl.39.

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39 Background: Public reports suggest increasing integration of in-house specialty pharmacies by independent and system-based oncology practices. Understanding the impact of such integration has important implications for state-level regulations limiting physicians’ ability to launch pharmacies in certain states and policies governing pharmacy network design. In this analysis, I document the growth of in-house pharmacies and estimate the impact of this growth on oral cancer drug use and quality. Methods: I used 2006-2017 data from Medicare Fee-for-Service and Part D claims, pharmacy names and characteristics from health plan pharmacy network lists and the National Plan and Provider Enumeration System, and a unique Health System and Practice Dataset, developed by National Bureau of Economic Research and Harvard University researchers, that tracks practice ownership relationships. I first linked physician organizations and pharmacies that they operate using a novel claims-based algorithm combining information on pharmacy characteristics, similarities in names of practices and pharmacies, and the share of total pharmacy spending attributable to a single practice or system. I then used an event study approach to compare oral oncolytic use and quality at practices launching a pharmacy between 2009 to 2014 compared with matched controls. Outcomes included total spending on oral oncolytics, use of oral drugs when an intravenous equivalent exists (capecitabine and 5-fluoruracil), timeliness of new prescription fills (# days from first fill to last office visit), medication adherence, and early discontinuation of lenalidomide, tyrosine kinase inhibitors, aromatase inhibitors, tamoxifen, enzalutamide, and abiraterone. Results: The number of independent or system-based oncology practices with an in-house pharmacy filling any oncology prescriptions increased from 135 in 2006 to 442 in 2017. In that time, the share of Medicare Part D spending on oral oncolytics filled at in-house pharmacies increased from 4% in 2006 to 27% in 2017. The launch of an in-house pharmacy was not associated with an overall increase in spending on oral oncolytics, but was associated with a 4.5 percentage point (p =.01) increase in the use of capecitabine relative to 5-fluorouracil, within 2 years of launch. In-house pharmacies were associated with a modest decrease in the time to fill an initial prescription (2.4 days, p <.001) within 2 years of launch, but no improvements in adherence or reductions in early discontinuation. Conclusions: There has been substantial growth in the use of in-house pharmacies in oncology in recent years. Having an in-house pharmacy only had modest effects on cost and quality. Policymakers should therefore approach claims that in-house pharmacies meaningfully impact cost and quality with caution.
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Akanbi, Maxwell Oluwole, Lucy Bilaver, Chad Achenbach, Lisa Hirschhorn, Oche Agbaji, Robert Murphy e Samuel O. Adekolujo. "Kaposi sarcoma among adults enrolling for HIV care in a large HIV clinic in Nigeria: 2006-2017." Journal of Clinical Oncology 39, n.º 15_suppl (20 de maio de 2021): e18539-e18539. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e18539.

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e18539 Background: Expanded access to antiretroviral therapy (ART) has led to a dramatic decline in Kaposi sarcoma (KS) among people initiating HIV care globally. In Nigeria, the country with the second-largest global HIV population, ART coverage increased from 11% in 2006 to 57% by 2017. The impact of Nigeria’s ART expansion of KS risk is unclear. We examined trends in KS risk among patients enrolled for HIV care in a large clinic in Nigeria from 2006-2017. Methods: We analyzed data of 16,431 adults (age ≥18 years) enrolled for HIV care from January 1, 2006, to December 31, 2017, in a large clinic in Jos, Nigeria. KS at enrollment was defined as KS recorded in the electronic health record within 30 days of clinic enrollment. Time trends were compared among three periods: 2006-2009, 2010-2013, and 2014-2017 (Mean national ART coverage 16%, 33%, and 50% respectively), using the Chi-test trend test and logistic regression models to identify factors independently associated with KS. The study was approved by the local institutional Institutional Review Board (IRB) and ruled exempt by the IRBs of Northwestern University and Harvard School of Public Health. Results: The study population had a mean age 35.1 (standard deviation, SD 9.5) years, and were 65.7% female (n= 10,788). The median first CD4 cell count was 192 (IQR 84-320), 215 (IQR 98-344), and 222 (IQR 94-353) in 2006-2009, 2010-2013, and 2014-2017, respectively. The overall KS prevalence at entry was 0.59 % (95% CI 0.48-0.72). KS prevalence was lowest for patient entering care during 2006-2009 (0.39%, 95% CI 0.29-0.53), increased to 1.12% (95% CI 0.82-1.52) in 2010-2013 and declined to 0.72% (95% CI 0.42-1.20) from 2014-2017 (Chi2 for trend, 12.14, p<0.01). Adjusting for age, sex, and CD4 T-cell count KS prevalence was significantly higher in 2010-2013 compared to 2006-2009 (Table). Conclusions: Despite ART expansion, KS at enrollment showed no significant decline. The low CD4+ cell count, across all periods, indicates delay in enrollment for HIV care, which increases KS risk. Interventions aimed at early HIV diagnosis and linkage to ART are critical to KS risk reduction in this population. Factors associated with Kaposi sarcoma at HIV care enrollment in Jos, Nigeria (2006-2017).[Table: see text]
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Discenza, Nicole Guenther. "Susan Irvine and Malcolm R. Godden, eds. and trans., The Old English Boethius: With Verse Prologues and Epilogues Associated with King Alfred. (Dumbarton Oaks Medieval Library 19.) Cambridge: Harvard University Press, 2012. Pp. xxiv, 451. $29.95. ISBN: 978-0-674-05558-2." Speculum 89, n.º 3 (julho de 2014): 785–86. http://dx.doi.org/10.1017/s0038713414001055.

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Woolf, Michael. "Marcelline Krafchick, World Without Heroes: The Brooklyn Novels of Daniel Fuchs (London, Cranbury, N.J. & Toronto: Associated University Presses, 1988 £13) Pp 120. ISBN 0 8386 3312 9. - Ruth R. Wisse, A Little Love in Big Manhattan: Two Yiddish Poets (London & Cambridge, MA: Harvard University Press, 1988, £19.95). Pp. 279. ISBN 0 674 53659 2." Journal of American Studies 24, n.º 3 (dezembro de 1990): 445–46. http://dx.doi.org/10.1017/s002187580003396x.

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Stahnisch, Frank W. "Urbanization, Bourgeois Culture, and the Institutionalization of the Frankfurt Neurological Institute by Ludwig Edinger (1855–1918)". Histories 4, n.º 1 (7 de fevereiro de 2024): 107–24. http://dx.doi.org/10.3390/histories4010007.

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Ludwig Edinger (1855–1918) is often perceived as a functional neuroanatomist who primarily followed traditional lines of microscopic research. That he was a rather fascinating innovator in the history of neurology at the turn from the nineteenth to the twentieth century has, however, gone quite unnoticed. Edinger’s career and his pronounced hopes for future investigative progress in neurological work mark an important shift, one away from traditional research styles connected to department-based approaches towards a multi-perspective and quite advanced form of interdisciplinary scientific work. Being conceptually influenced by the Austrian neuroanatomist Heinrich Obersteiner (1847–1922) and his foundation of the Neurological Institute in Vienna in 1882, Edinger established a multi-faceted brain research program. It was linked to an institutional setting of laboratory analysis and clinical research that paved the way for a new type of interdisciplinarity. After completion of his medical training, which brought him in working relationships with illustrious clinicians such as Friedrich von Recklinghausen (1810–1879) and Adolf Kussmaul (1822–1902), Edinger settled in 1883 as one of the first clinically working neurologists in the German city of Frankfurt/Main. Here, he began to collaborate with the neuropathologist Carl Weigert (1845–1904), who worked at the independent research institute of the Senckenbergische Anatomie. Since 1902, Edinger came to organize the anatomical collections and equipment for a new brain research laboratory in the recently constructed Senckenbergische Pathologie. It was later renamed the “Neurological Institute”, and became an early interdisciplinary working place for the study of the human nervous system in its comparative, morphological, experimental, and clinical dimensions. Even after Edinger’s death and under the austere circumstances of the Weimar Period, altogether three serviceable divisions continued with fruitful research activities in close alignment: the unit of comparative neurology, the unit of neuropsychology and neuropathology (headed by holist neurologist Kurt Goldstein, 1865–1965), and an associated unit of paleoneurology (chaired by Ludwig Edinger’s daughter Tilly, 1897–1967, who later became a pioneering neuropaleontologist at Harvard University). It was especially the close vicinity of the clinic that attracted Edinger’s attention and led him to conceive a successful model of neurological research, joining together different scientific perspectives in a unique and visibly modern form.
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Lee, Jin-Seong. "Measuring the value of apartment density?" International Journal of Housing Markets and Analysis 9, n.º 4 (3 de outubro de 2016): 483–501. http://dx.doi.org/10.1108/ijhma-08-2015-0047.

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Purpose The primary purpose of this study is to identify whether there is a price premium and consumers’ preferences for higher housing density, and whether there is a relationship between housing densities and sales prices. The second purpose was to identify if there is a non-linear relationship between housing density and prices even though housing density is directly associated with housing prices. Design/methodology/approach This paper applies hedonic modeling techniques to measure the value of development density of apartments in the metropolitan area of Seoul, South Korea. The regression of the sale price is a function of different types of variables such as density, market, location and other control variables. Findings For the first question, this paper concludes that the higher densities cause housing prices to decrease in Seoul. The summary of the results presents that housing density, floor area ratio (FAR), building coverage ratio and floor level are all important components affecting housing prices. Generally, consumers tend to buy housing with central heating systems, more parking spaces, smaller portion of rental housing within an apartment and buildings that have more of a mixed-use function. Consumers are also found to pay higher premiums for housing in areas with high population growth and less housing supply. It is conclusive that people are inclined to live in populated areas but do not want more density. For the second question, the results show that generally FAR has quadratic effects, but most housing density variables tend to have a non-linear relationship depending on the different quantile groups. Originality/value There is a knowledge gap in the area of estimating development density of apartments. Generally, studies investigating property value impacts of multifamily housing focus on external effects of the multifamily housing on home values to examine whether high density development could result in a decrease in nearby property values. These studies found that there are some positive effects. A study found that high-density housing increases property values of existing single-family homes (Joint Center for Housing Studies, 2011). More specifically, developments that are of a high design quality and superior landscaping increase values of single-family homes as well. Also, those residents who live in these high-density apartments can be good potential buyers for the existing single-family homes. The greater the number of buyers, the greater the housing market becomes. Similarly, according to a report by the Joint Center for Housing Studies (2011) at Harvard University, the presence of multifamily residents correlates with higher home values in “working communities”. Indeed, density can be an important factor determining value of apartments because of its unique characteristics. However, no empirical evidence has been provided in the literature with regard to the value of the development density. This study contributes toward improving this knowledge gap.
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González, P., S. Alaniz, M. J. Montelongo, L. Rauduviniche, J. Rebellato, E. Silvera-Pérez e P. Mondino. "First Report of Pestalotiopsis clavispora Causing Dieback on Blueberry in Uruguay". Plant Disease 96, n.º 6 (junho de 2012): 914. http://dx.doi.org/10.1094/pdis-12-11-1070-pdn.

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During the last 10 years, blueberry (Vaccinium corymbosum) production in Uruguay has increased to more than 850 ha. From 2005, symptoms of dieback characterized by the death of twigs and branches have been frequently observed in blueberry plants cv. O'Neal in orchards located in Uruguay. Symptomatic 4-year-old plants (cv. O'Neal) were collected and small pieces of necrotic tissues were surface disinfected and plated onto potato dextrose agar (PDA) with 0.2 g liter–1 of streptomycin sulfate. Plates were incubated at 25°C in the dark. All affected tissues consistently developed colonies with white and cottony mycelium, turning slightly yellow after 7 to 10 days. Black acervuli distributed in concentric circles were observed after 10 days. Conidia were fusiform, straight, and had five cells. Basal and apical cells were colorless while the three median cells were dark brown. Conidia (n = 50) had an average of 22.1 (16.5 to 28.2) × 6.6 (5.6 to 7.7) μm. All conidia had one basal appendage of 6.1 (3.9 to 14.3) μm and two to four (usually three) apical appendages of 22.8 (17.4 to 42.9) μm. According to colony and conidia morphology, the isolates were initially identified as Pestalotiopsis clavispora (G.F. Atk.) Steyaert (1). To identify, the internal transcribed spacers (ITS1, 5.8S, ITS2) region of rDNA of a representative isolate (Ara-1) was amplified with ITS1/ITS4 primers (4), sequenced, and compared with those deposited in GenBank. The isolate Ara-1 (Accession No. JQ008944) had 100% sequence identity with P. clavispora (Accession Nos. FJ517545 and EU342214). To confirm pathogenicity, isolate Ara-1 was inoculated onto asymptomatic 1-year-old blueberry plants (cv. O'Neal). Mycelial plugs (4 mm in diameter) from an actively growing colony on PDA were applied to same-size bark wounds made with a cork borer in the center of the stems previously disinfected with 70% ethanol and covered with Parafilm. Control plants were inoculated with sterile PDA plugs. Inoculated plants (five per treatment) were randomly distributed in a greenhouse and watered as needed. After 2 weeks, all stems inoculated with P. clavispora showed brown necrotic lesions 2 to 3 cm in length and 1 to 2 mm deep. White mycelium was observed over lesions. Control plants remained symptomless. The pathogen was reisolated from all necrotic lesions, thus fulfilling Koch's postulates. P. clavispora has been reported as associated with blueberry in Hawaii (3) and Chile (2). To our knowledge, this is the first report of P. clavispora causing dieback disease on blueberry in Uruguay. References: (1) E. F. Guba, Monograph of Pestalotia and Monocheatia. Harvard University Press, Cambridge, MA, 1961. (2) J. G. Espinoza et al. Plant Dis. 92:1407, 2008. (3) L. M. Keith et al. Plant Dis. 90:16, 2006. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.
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Handayani, Diah. "Political Identity, Popular Culture, and Ideological Coercion: The Discourses of Feminist Movement in the Report of Ummi Magazine". Jurnal Pemberdayaan Masyarakat: Media Pemikiran dan Dakwah Pembangunan 5, n.º 1 (18 de junho de 2021): 185–210. http://dx.doi.org/10.14421/jpm.2021.051-08.

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This research examines the rise of Islamic populism in Indonesia and understands it as an instrument to clear a new pathway for populism movement into popular culture. Ummi magazine is one of the religious media used to be political vehicles of stablishing constituencies, especially for the Tarbiyah movement in the Soeharto era to the current tendency to popularize the Tarbiyah identity as a new lifestyle. Historically, The Tarbiyah movement in Indonesia is a social and political movement among Indonesian Muslimah students, especially activists in the Suharto period. Muslim middle class entrepreneurs launched a campaign of ‘economic jihad. This research uses a qualitative approach by interpreting and studying the data contained in Ummi Magazine. Media studies were carried out in the January 2017 to 2018 editions. The data obtained were described and associated with the magazine's transformation as an ideological medium and Muslim women's lifestyle today. The result shows that the magazine's transformation from ideology magazine to lifestyle magazine can influence readers because there are more new readers. Whether Ummi as a media for da'wah and a women's magazine, it is still perceived by the readers to apply ideological coercion or simply provide an alternative lifestyle or consumption where religious independence is the main characteristic of the magazine. We argue that Islamic populism is mainly a medium for coercion ideology to gain tracks to power, while the poor remain as ‘floating mass’, and entrapped in many so-called 'empowerment' projects. Populism can be interpreted as a communication style in which a group of politicians considers themselves to represent the people’s interests contrasted with elite interests. Nevertheless, the populism approach is gaining momentum. Abdullah, I. (1996). Tubuh, Kesehatan, dan Struktur yang Melemahkan Wanita. Kumpulan Makalah Seminar Bulanan. Pusat Penelitian Kependudukan UGM.Al-Abani, S. M. N. (1999). Jilbab Wanita Muslimah. Pustaka At-Tibyan.Ahmed, L. (1992). Women and Gender in Islam: Historical Roots of Modern Debate. Yale University Press.Al-Ghifari, A. (2005). Kerudung Gaul, Berjilbab Tapi Telanjang. Mujahid Press.Armbrust, W. (2000). ‘Introduction’, Mass Mediation: New Approaches to Popular Culture In The Middle East and Beyond. University California Press.Askew, K. (2002). ‘Introduction’, The Anthropology of Media: A Reader.Blackwell.Astuti, S. N. A. . (2005). Membaca Kelompok Berjilbab Sebagai Komunitas Sub Kultur. Universitas Gadjah Mada.BPS. (2017). Statistika Pendapatan. BPS Publication. Banet-Weiser, S. (2006). “I just want to be me again!”: Beauty pageants, reality television and post-feminism. Feminist Theory, 7(2), 255–272. https://doi.org/10.1177/1464700106064423Banna, H. (2011). Majmu’ah Rasail Al Iman As Syahid (Risalah Pergerakan Ikhawanul Muslimin. Era Intermedia. Barthel, D. (1976) . 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Television and Sex Role Acquisition I: Content’. British Journal of Social Psycology, 24, 102-113.Effendi, B. (2003). ‘Islam Politik Pasca Suharto’. Refleksi, 5(2).El-Guindi, F. (1991). Veil, Modesty, Privacy, and Resistance. Berg.Frederick, W. H. (1982). Rhoma Irama and The Dangdut Style: Aspects of Contemporary Indonesian Popular Culture. Indonesia, 34, 103-130.Featherstone, M. (2001). The Body in Consumer Culture. In The Body: Social Process and Cultural Theory. SAGE Publication.Foucault, M. (1981). The Order of Discourse. Routledge and Keagon Paul.Fukuyama, F. (2018). Against Identity Politics. Foreign Affairs, Sptember/October, 1-25.Gough, Y. A. (2003). Understanding Women Magazine. Routledge.Gautlett, D. (2002). Media, Gender, and Identity: An Introduction. Routledge.Geetzt, C. (1973). The Interpretation of Culture. Verso.Gill, R. (2009). Mediated Intimacy and Post Feminism: a Discourse Analytic Examination of Sex and Relationship advice in Woman’s Magazine. Discourse and Communication Journal, 3(4), 345-369. https://doi.org/10.1177/1750481309343870Gramsci, A. (1992). Selection from The Prison on Notebooks. International Publisher.Gorham, B. W. (2004). The Social Psychology of Stereotypes: Implications for Media Audiences. In Race/Gender/Media: Considering Diversity Across Audiences, Content, and Producers. Pearson.Hall, S. (1997). The Work Of Representation. In Representation: Cultural Representations and Signifying Practices. SAGE Publication.Handayani, D. (2014). Performatifitas Muslimah dalam Majalah Ummi. At-Tabsyir. Jurnal Komunikasi Penyiaran Islam, 2(1), 73-98. http://doi.org/10.21043/at-tabsyir.v2i1.461.Hanifah, U. (2011). Konstruksi Ideologi Gender pada Majalah Wanita (Analisis Wacana Kritis Majalah Ummi). KOMUNIKA: Jurnal Dakwah dan Komunkasi, 5(2), 199-220. https://doi.org/10.24090/komunika.v5i2.170Imdadun, R. (2005). Arus Baru Iislam Radikal: Transmisi, Revivalisme Islam Timur Tengah ke Indonesiaan. Erlangga.Itzin, C.(1986). Media Images of Women: The Social Construction of Ageism and Sexism. In Feminist Social Psycology: Developing Theory and Practice. Milton Keynes. Open University Press.Kailani, N. (2008). Budaya Populer Islam di Indonesia: Jaringan Dakwah Foru Lingkar Pena. Jurnal Sosiologi Reflektif, 2(3). Kellner, D. (1995). Cultural Studies, Identities and Politics Between The Modern and Postmodern. Routledge.Machmudi, Y. (2006). Islamizing Indonesia: The Rise of Jamaah Tarbiyah and The Presperous Justice Party (PKS). PhD Dissertation, Australia National University.Maulidiyah, L. (2014). Wacana Relasi Gender Suami Istri dalam Keluarga Muslim di Majalah Wanita Muslim Indonesia. Universitas Airlangga.Parihatin, A. (2004). Ideologi Revivalisme Islam dalam Majalah Perempuan Islam (Analisis Wacana pada Majalah Ummi). Universitas Indonesia. Qadarawi, Y. (2004). Al Islamu wal Fannu. Islam Bicara Seni. Era Intermedia. Qutb, S. (1980). Ma’alim fi Al Tariq (Petunjuk Jalan-Milestone). Media Dakwah.Rozak, A. (2008). Citra Perempuan dalam Majalah Wanita Islam UMMI. Jurnal Penelitian Agama. VXII(2), 332-354.Storey, J. (2010). Culture and Power in Cultural Studies: The Politics of Signification. Edinburg University Press.Ulfa, N. M. (2016). Dakwah Melalui Media Cetak (Analisis Isi Rubrik Mutiara Islam Majalah Ummi). Islamic Communication Journal, 1(1), 73-89.
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Zhang, Jiajia, Justina Caushi, Boyang Zhang, Zhicheng Ji, Taibo Li, Hongkai Ji, Andrew Pardoll e Kellie Smith. "665 Transcriptional landscape of tumor-reactive TIL in lung cancer and melanoma". Journal for ImmunoTherapy of Cancer 9, Suppl 2 (novembro de 2021): A693. http://dx.doi.org/10.1136/jitc-2021-sitc2021.665.

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BackgroundMelanoma and lung cancers have two of the highest response rates to immune checkpoint inhibitors (ICIs).1 However, patients may respond unpredictably, partly due to heterogeneity in the quantity and quality of tumor-specific T cells. In this study, we performed an integrated transcriptomic analysis of anti-tumor CD8+ TIL from non-small cell lung cancer (NSCLC) and melanoma. Our goal was to study the global transcriptomic landscape of tumor-specific T cells and to compare their functional programming in lung cancer vs. melanoma.MethodsTIL from 19 patients (15 NSCLC and 3 melanoma) were sequenced using combined single-cell (sc) RNA-seq/TCR-seq. All NSCLC patients received neoadjuvant anti-PD-1 (nivolumab, NCT02259621) whereas melanoma patients received a personal neoantigen vaccine (NCT01970358). Neoantigen-, tumor-associated antigen-, and viral-specific CD8+ T cell clonotypes were identified using functional assays and were validated by TCR cloning as previously described.2 3 Transcriptional profiles of antigen-specific T cells were identified using the TCRβ CDR3 as a barcode to link with the antigen specificity output from the functional assays. The prevalence, phenotype, and differentiation trajectory of tumor-specific T cells were compared between the two cancer types.ResultsA total of 175,826 CD8+ TIL were analyzed, of which 30,174 single cells were from the melanoma cohort and 145,652 were from the NSCLC cohort. Tumor-specific T cells were detected at variable frequencies among CD8+ TIL (median=1.2%, range 0.01%–35.8%) across nine patients, with melanoma having more clonal tumor-specific T cells as compared to NSCLC. CD8+ TIL from melanoma were more enriched in an activated tissue resident T cell (TRM) cluster characterized by upregulated expression of CXCL13, CRTAM, 4-1BB, XCL1/2, and FABP5, whereas those from NSCLC have a greater representation of a cytotoxic TRM cluster with an exhaustion signature (coexpression of GZMB, GZMH, PDCD1, and CTLA4). Distinct from EBV-specific T cells and flu-specific T cells, tumor-specific T cells primarily resided in TRM clusters in both cancers. More MANA-specific TIL from melanoma presented with an effector phenotype and were more proliferative as compared to those from NSCLC. To reveal the differentiation trajectory and regulatory programs of tumor-specific T cells upon tumor recognition and association with response to ICIs, pseudotime/velocity analysis of tumor-specific TIL is underway.ConclusionsThis is the first analysis to inform on the global transcriptomic landscape of tumor-specific CD8+ TIL in lung cancer and melanoma at single cell resolution. This provides a useful framework to study the underlying mechanisms of T cell exhaustion and dysfunction in human cancer.Trial RegistrationNCT02259621,NCT01970358ReferencesYarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. The New England Journal of Medicine 2017;377(25):2500.Caushi JX, et al. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature 2021;1–7.Oliveira G, et al. Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma. Nature 2021;1–7.Ethics ApprovalThe melanoma clinical trial was approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board (IRB) (NCT01970358). The NSCLC clinical trial was approved by the Institutional Review Boards (IRB) at Johns Hopkins University (JHU) and Memorial Sloan Kettering Cancer Center (NCT02259621). All participants gave informed consent before taking part.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
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Zhang, Jiajia, Justina Caushi, Giacomo Oliveira, Boyang Zhang, Zhicheng Ji, Jarushka Naidoo, Kristen Marrone et al. "327 Development and validation of a neoantigen-specific T cell gene signature to identify antitumor T cells in lung cancer and melanoma". Journal for ImmunoTherapy of Cancer 9, Suppl 2 (novembro de 2021): A353. http://dx.doi.org/10.1136/jitc-2021-sitc2021.327.

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BackgroundMutation-associated neoantigen (MANA)-specific T cells play a key role in tumor control and response to immune checkpoint inhibition (ICI).1 2 However, the majority of tumor-infiltrating lymphocytes (TIL) are not specific for the tumor.3 Herein, we developed and validated MANAscore, a bioinformatic scoring algorithm based on the transcriptional programs of MANA-specific T cells to isolate antitumor T cells from bystander T cells in lung cancer and melanoma.MethodsCombined single-cell (sc) RNA-seq/TCR-seq was performed on TIL obtained from 15 resectable non-small cell lung cancer (NSCLC) patients receiving neoadjuvant anti-PD-1 (NCT02259621). MANA-specific clonotypes were identified by coculturing autologous T cells with predicted MANA, and were validated by cloning the full TCR alpha and beta chain as previously described.1 Using the TCRβ CDR3 as a barcode, antigen-specific T cells were linked with their intratumoral sc expression profile. Using the first two patients enrolled in the clinical trial as a discovery cohort, MANAscore was developed to identify gene programs that best distinguish MANA-specific vs viral-specific T cells from NSCLC. Prediction performance was assessed in independent patients from the NSCLC and melanoma cohort.2 Seven MANAscore< sup >hi</sup > TCRs were cloned and queried for reactivity to peptide libraries of putative MANA derived from whole-exome sequencing of the respective tumor. Association of MANAscorehi clones with response to ICIs among all patients was assessed.ResultsA total of 890 MANA- and 542 viral-specific T cells were identified in sc TIL from six NSCLC patients. MANA- and viral-specific TIL presented with unique transcriptional profiles. Particularly, MANA-specific CD8 TIL expressed a partially activated cytolytic program with co-expression of multiple immune checkpoints and upregulated transcriptional regulators of T cell dysfunction. MANAscore showed high prediction accuracy and outperformed CD39 in identifying tumor-reactive T cells in independent NSCLC patients, as well as in an external validation cohort of melanoma patients (3936 MANA-specific T cells and 626 viral-specific T cells from 4 patients). Of seven MANAscore< sup >hi</sup > clones tested for reactivity, three were confirmed as MANA-specific. The pseudobulk expression profile of MANAscore< sup >hi</sup > clones showed a significant correlation with response to ICI, which is not observed in total CD8+ TIL.ConclusionsMANA-specific TIL demonstrated a distinct gene signature that enabled us to identify de novo antitumor TIL in NSCLC and melanoma. MANAscore may serve as a useful tool in facilitating mechanistic studies of ICI response and resistance.Trial RegistrationNCT01970358,NCT02259621ReferencesSimoni, Yannick, et al. “Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates.” Nature 557.7706 (2018):575–579.Caushi, Justina X, et al. “Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers.” Nature (2021):1–7.Oliveira, Giacomo, et al. “Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma.” Nature (2021):1–7.Ethics ApprovalThe melanoma clinical trial was approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board (IRB) (NCT01970358). The NSCLC clinical trial was approved by the Institutional Review Boards (IRB) at Johns Hopkins University (JHU) and Memorial Sloan Kettering Cancer Center (NCT02259621)ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal
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Venturas, Marta, Jaimin S. Shah, Xingbo Yang, Tim H. Sanchez, William Conway, Denny Sakkas e Dan J. Needleman. "Metabolic state of human blastocysts measured by fluorescence lifetime imaging microscopy". Human Reproduction 37, n.º 3 (6 de janeiro de 2022): 411–27. http://dx.doi.org/10.1093/humrep/deab283.

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Abstract STUDY QUESTION Can non-invasive metabolic imaging via fluorescence lifetime imaging microscopy (FLIM) detect variations in metabolic profiles between discarded human blastocysts? SUMMARY ANSWER FLIM revealed extensive variations in the metabolic state of discarded human blastocysts associated with blastocyst development over 36 h, the day after fertilization and blastocyst developmental stage, as well as metabolic heterogeneity within individual blastocysts. WHAT IS KNOWN ALREADY Mammalian embryos undergo large changes in metabolism over the course of preimplantation development. Embryo metabolism has long been linked to embryo viability, suggesting its potential utility in ART to aid in selecting high quality embryos. However, the metabolism of human embryos remains poorly characterized due to a lack of non-invasive methods to measure their metabolic state. STUDY DESIGN, SIZE, DURATION We conducted a prospective observational study. We used 215 morphologically normal human embryos from 137 patients that were discarded and donated for research under an approved institutional review board protocol. These embryos were imaged using metabolic imaging via FLIM to measure the autofluorescence of two central coenzymes, nicotinamide adenine (phosphate) dinucleotide (NAD(P)H) and flavine adenine dinucleotide (FAD+), which are essential for cellular respiration and glycolysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Here, we used non-invasive FLIM to measure the metabolic state of human blastocysts. We first studied spatial patterns in the metabolic state within human blastocysts and the association of the metabolic state of the whole blastocysts with stage of expansion, day of development since fertilization and morphology. We explored the sensitivity of this technique in detecting metabolic variations between blastocysts from the same patient and between patients. Next, we explored whether FLIM can quantitatively measure metabolic changes through human blastocyst expansion and hatching via time-lapse imaging. For all test conditions, the level of significance was set at P &lt; 0.05 after correction for multiple comparisons using Benjamini–Hochberg’s false discovery rate. MAIN RESULTS AND THE ROLE OF CHANCE We found that FLIM is sensitive enough to detect significant metabolic differences between blastocysts. We found that metabolic variations between blastocyst are partially explained by both the time since fertilization and their developmental expansion stage (P &lt; 0.05), but not their morphological grade. Substantial metabolic variations between blastocysts from the same patients remain, even after controlling for these factors. We also observe significant metabolic heterogeneity within individual blastocysts, including between the inner cell mass and the trophectoderm, and between the portions of hatching blastocysts within and without the zona pellucida (P &lt; 0.05). And finally, we observed that the metabolic state of human blastocysts continuously varies over time. LIMITATIONS, REASONS FOR CAUTION Although we observed significant variations in metabolic parameters, our data are taken from human blastocysts that were discarded and donated for research and we do not know their clinical outcome. Moreover, the embryos used in this study are a mixture of aneuploid, euploid and embryos of unknown ploidy. WIDER IMPLICATIONS OF THE FINDINGS This work reveals novel aspects of the metabolism of human blastocysts and suggests that FLIM is a promising approach to assess embryo viability through non-invasive, quantitative measurements of their metabolism. These results further demonstrate that FLIM can provide biologically relevant information that may be valuable for the assessment of embryo quality. STUDY FUNDING/COMPETING INTEREST(S) Supported by the Blavatnik Biomedical Accelerator Grant at Harvard University. Becker and Hickl GmbH and Boston Electronics sponsored research with the loaning of equipment for FLIM. D.J.N. is an inventor on patent US20170039415A1. TRIAL REGISTRATION NUMBER N/A.
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Marra, R. E., e D. W. Li. "First Report of Pestalotiopsis paeoniicola Causing Twig Blight on Paeonia suffruticosa in North America". Plant Disease 93, n.º 9 (setembro de 2009): 966. http://dx.doi.org/10.1094/pdis-93-9-0966c.

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Native to China, tree peony (Paeonia suffruticosa Andrews) is a perennial valued for its showy, often fragrant flowers. In May 2007, samples received from two field-grown tree peonies from Torrington, CT exhibited twig blight characterized by small, black spots on the bark of living or dead branches, and associated with subsequent death and loss of the branches. Colonies on potato dextrose agar (PDA) attained 5.5 to 6.5 cm in diameter in 9 days at 25°C and produced abundant, white, aerial mycelium, later turning pink and forming scattered, wet, black, acervular conidiomata containing abundant conidia that were five-celled, fusiform, smooth, straight, or slightly curved, and 24.0 ± 1.8 × 7.1 ± 0.5 μm (n = 20); three intermediate cells were dark brown and end cells were hyaline; two to four hyaline whip-like appendages on the apical cell, 26.6 ± 4.1 μm long, and one appendage on the basal cell, 6.7 ± 1.1 μm long. We identified the fungus as Pestalotiopsis paeoniicola (Tsukam. & T. Hino) J.G. Wei & T. Xu (= Pestalotia paeoniicola Tsukam. & T. Hino) based on morphology and host and have deposited a culture with CBS (CBS 124745). Originally described from Paeonia suffruticosa in Japan (1,3), the fungus is also found in China on Paeonia lactiflora (Pall.) (2). To confirm pathogenicity, two 5-year-old potted plants of Paeonia suffruticosa cv. Shichifukujin were inoculated with the fungus as follows: a 2-week-old PDA culture was used to produce a conidial spore suspension in sterile water; incisions (5 mm) were made with a sterile scalpel; 4 μl of either the conidial suspension or water were applied; and the wounds were wrapped with Parafilm. Each plant received three replicates each of the treatment and the control. Plants were loosely covered with plastic bags, kept on laboratory benches with ambient light for 1 month, and transferred to a greenhouse for an additional 2 months. Subsequent inspection revealed irregular or elongate, grayish brown lesions at the treatment inoculations, while the controls remained symptom free. Lesions gradually girdled the branches and the infected cortex turned dark brown. At advanced stages, small, black acervuli developed. Treatment and control tissues were cut into four pieces, surface sterilized, and placed on malt extract agar in petri dishes, four per dish. These were incubated for 9 days at 25°C under ambient light. Reisolation of P. paeoniicola only from tissues that had been treated with the pathogen, not from control inoculations, confirmed that the causal agent was P. paeoniicola. DNA sequences were obtained from the β-tubulin gene (1,512 bp) and the internal transcribed spacer (ITS1 and ITS2) and 5.8S regions of the rDNA (550 bp) and were deposited in GenBank (Nos. FJ975603 and FJ997645, respectively). Neither ITS nor β-tubulin sequences distinguished this P. paeoniicola isolate from Pestalotiopsis spp. whose sequences are deposited in GenBank. Morphological characteristics identify the fungus as P. paeoniicola, constituting, to our knowledge, the first report of this pathogen in North America. Discovery of P. paeoniicola in field-grown plants warrants further monitoring by growers because of the uncertain level of threat this pathogen may pose to the tree peony industry. References: (1) E. F. Guba. Monograph of Monochaetia and Pestalotia: 224. Harvard University Press, Cambridge, MA, 1961. (2) F. Tai. Sylloge Fungorum Sinicorum: 1021. Sci. Acad. Sin, Peking, 1979. (3) E. Tsukamoto et al. Ann. Phytopathol. Soc. Jpn. 4:183, 1956.
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Lu, Hongyan, Shicheng Yang, Xiao Huang, Harun El Masri, Paul C. Trampont, Amandeep Salhotra, James G. Farmar, Alexander J. Wendling e Mary J. Laughlin. "Nuclear Factor of Activated T-Cells (NFAT1): Potential Novel Target in T-Cell Acute Lymphocytic Leukemia (T-ALL)". Blood 118, n.º 21 (18 de novembro de 2011): 4634. http://dx.doi.org/10.1182/blood.v118.21.4634.4634.

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Abstract Abstract 4634 Background. T-cell transcription factor NFAT1 (NFATc2) has been reported to regulate cell cycle regulatory proteins including cyclins, cyclin-dependent kinases (CDKs), and p21. MicroRNA-184 (miR-184) has been noted to have close sequence homology to the 3’ UTR of NFAT1 and to regulate NFAT1 mRNA translation in human adult and umbilical cord blood (UCB) CD3+CD4+ T-cells. In this study, we are characterizing the functional role of NFAT1 in T-ALL cells to determine whether its dysregulation may alter normal cell cycle regulation and thereby may contribute to T-ALL leukemogenesis. Materials/Methods. In this study we used MOLT-4 cell line to investigate the role of NFAT1 in T-ALL, since MOLT-4 represents early stage of human T-ALL (CD4+CD8+ double positive) compared with other T-cell lines including Jurkat. We developed two distinct approaches to explore NFAT1 signalling, either by manipulating the expression level of NFAT1 protein by blocking miR-184, or by overexpressing a constitutively active form of NFAT1 (caNFAT1) holding a HA-tag (Addgene plasmid 11792, A. Rao, PhD, Harvard University). caNFAT1 was introduced into gateway system expression vector pEF-DEST51. MOLT-4 cells were maintained in complete RPMI 1640 medium according to ATCC guidelines. Electroporation transfection was performed on Amaxa Nucleofector I using program C-05. 200 nM of anti-miR-184 miRNA inhibitor (Dharmacon) or 2 μ g of plasmid containing caNFAT1 was transfected into 2×10e6 MOLT-4 cells in each sample. Transfection efficiency was tested using pmaxGFP (Lonza). Proteins were extracted at various time points after transfection using RIPA buffer (PIERCE) with protease inhibitor cocktail and tested for the expression of NFAT1 (BD Biosciences), phosphorylated NFAT1 (Santa Cruz Biotechnology), HA (Roche), and beta-actin (Sigma-Aldrich). Cell cycle was measured at various time points by pelleting down 0.5–1 X10e6 cells, followed by ethanol fixation, and incubation in propidium iodide (PI) (10 μ g/ml) staining solution and flow cytometric measurement for PI incorporation. Cell apoptosis was measured by PE-conjugated annexin V staining (BD Biosciences) in transfected MOLT-4 cells including empty plasmid controls. Results/Discussion. The over-expression of caNFAT1 in MOLT-4 led to increased proportion of cells in G2 phase than in controls (10.8% vs. 7.3% on day5, and 11.8% vs. 8.1% on day6). In addition to these cell cycle changes in MOLT-4 treated with caNFAT1 plasmid, higher rates of apoptosis were noted on day 2 (28.3% vs. 15.5%), which notably leveled off from day 3 to day 6 potentially attributed to compensatory cellular responses. Previous work by this group has shown higher expression of miR-184 in MOLT-4 by 56 fold compared with normal human CD4/8 double positive T-cells. Here, miR-184 knockdown was also notable for a larger proportion of MOLT-4 cells in G2 cell cycle phase and higher apoptosis, albeit modest changes compared with that exerted by caNFAT1. Conclusion. In MOLT-4 cell line, this preliminary data suggests that increasing active non-phosphorylated NFAT1 is associated with enhanced proportion of cells in G2 phase as well as enhanced resultant apoptosis. Taken together, regulation of NFAT1 may be exploited as potential T-ALL targeted therapy. Disclosures: No relevant conflicts of interest to declare.
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Proctor, Jennifer L., Sharon L. Hyzy, Hillary L. Adams, Melissa L. Brooks, Andrew D. Gabros, Sean M. McDonough, Lena Kien et al. "Single Doses of Antibody Drug Conjugates (ADCs) Targeted to CD117 or CD45 Have Potent In Vivo Anti-Leukemia Activity and Survival Benefit in Patient Derived AML Models". Blood 132, Supplement 1 (29 de novembro de 2018): 3316. http://dx.doi.org/10.1182/blood-2018-99-112726.

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Abstract Background. Allogeneic bone marrow transplant (BMT) is a potentially curative approach in patients with refractory or high risk hematologic malignancies, such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Prior to transplant, patients are prepared with non-specific, high dose chemotherapy alone or in combination with total body irradiation, which are associated with early and late morbidities, including organ toxicities, infertility, secondary malignancies, and substantial risk of mortality. As a result, many eligible patients do not consider transplant and of those transplanted, 2/3 can only tolerate reduced intensity conditioning, which is associated with increased relapse rates (Scott et al. Journal of Clinical Oncology 2017, 1154-1161). Thus, safer and more effective conditioning agents with improved disease control are urgently needed. To meet this need, we developed two novel antibody drug conjugates (ADCs) conjugated to amanitin (AM) targeting CD117 (C-KIT, Pearse 2018), which is expressed on hematopoietic stem and progenitor cells and AML and MDS cells in >60% of patients (Ludwig et al. Haematologica 1997, 617-621), and CD45 (Palchaudhuri 2018) which is expressed on all lympho-hematopoietic cells and nearly all hematologic malignancies except multiple myeloma. The aim of the project was to design an agent with the dual benefit of depleting primary human hematopoietic stem progenitor cells (HSPCs) while reducing disease burden in leukemia models. Methods. ADCs were tested in xenograft murine models inoculated with human AML cells from immortalized cell lines (Kasumi-1, a CD117 expressing leukemia cell line, and REH-Luc, a CD45 expressing AML cell line tagged with luciferase), and three patient-derived xenografts (PDX) developed from FLT-3+NPM1+ AML samples (J000106132 [prior treatment with Allogeneic BMT, Sorafenib, Hydroxyurea, and Decitabine], J000106565 [M4/5, prior treatment with Induction chemotherapy, Consolidation HiDAC, Allogeneic BMT], J000106134 [M4, no prior treatment reported]) with varying growth kinetics (median survival of vehicle treated groups was 43, 63, 82 days post inoculation) that express both CD117 and CD45 (Jackson Laboratories). Results. In the Kasumi model, a single injection of 0.3 mg/kg anti-CD117-AM administered on day 7 or 42 after AML inoculation resulted in a marked increase in survival (median >240 days) compared to vehicle treated controls (median 76 days) or unconjugated anti-CD117 antibody (median 86.5 days) (n=6-8 mice/group, p<0.0001). In the REH-Luc model, a single injection of 1 mg/kg anti-CD45-AM on day 5 after AML inoculation resulted in longer survival by a median of 15 days compared to vehicle treated controls or unconjugated anti-CD45 antibody (n=10 mice/group, p<0.0001). For the three PDX, a single intravenous dose of ADCs (anti-CD117-AM, anti-CD45-AM, isotype-AM (ISO-AM), unconjugated anti-CD117 antibody, or vehicle PBS) were administered to AML-PDX animals when 2-5% blasts were observed in the blood. With 4-5 mice/group/AML-PDX model, survival was significantly increased in recipients of 1 mg/kg anti-CD117-AM, and 1 mg/kg anti-CD45-AM as compared to vehicle controls (Figure 1 and Table 1). Conclusions. Anti-CD117-AM and anti-CD45-AM are potent anti-leukemia agents based on these data in humanized murine models with established AML. Together with prior reports on the potency of anti-CD117-AM and anti-CD45-AM as conditioning agents, these non-genotoxic ADCs may be useful to reduce disease burden in patients with active disease and in recipients of reduced dose conditioning who are at high risk of disease relapse. Disclosures Proctor: Magenta Therapeutics: Employment, Equity Ownership. Hyzy:Magenta Therapeutics: Employment, Equity Ownership. Adams:Magenta Therapeutics: Employment, Equity Ownership. Brooks:Magenta Therapeutics: Employment, Equity Ownership. Gabros:Magenta Therapeutics: Employment, Equity Ownership. McDonough:Magenta Therapeutics: Employment, Equity Ownership. Kien:Magenta Therapeutics: Employment, Equity Ownership. Aslanian:Magenta Therapeutics: Employment, Equity Ownership. Pearse:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Palchaudhuri:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties; Harvard University: Patents & Royalties. Li:Magenta Therapeutics: Employment, Equity Ownership. Kallen:Magenta Therapeutics: Employment, Equity Ownership. Sarma:Magenta Therapeutics: Employment, Equity Ownership. McShea:Magenta Therapeutics: Employment, Equity Ownership. Ladwig:Magenta Therapeutics: Employment, Equity Ownership. Dushime:Magenta Therapeutics: Employment, Equity Ownership. Panwar:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. McDonagh:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Boitano:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Cooke:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties.
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Palchaudhuri, Rahul, Borja Saez, Jonathan Hoggatt, Amir Schajnovitz, David B. Sykes, Michael K. Mansour e David T. Scadden. "Immunotoxin Enables Non-Genotoxic Conditioning for Hematopoietic Stem Cell Transplantation". Blood 126, n.º 23 (3 de dezembro de 2015): 32. http://dx.doi.org/10.1182/blood.v126.23.32.32.

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Abstract Hematopoietic stem cell transplantation (HSCT) can cure non-malignant hemoglobinopathies, congenital immunodeficiencies and, perhaps, AIDS, diseases that affect millions of people worldwide; yet, it's use is limited outside of malignancies largely because allogeneic transplantation can be complicated by serious conditioning-related toxicities and graft-versus-host disease (GVHD). The advent of highly efficient gene editing technology promises to enable autologous HSCT while avoiding GVHD. However, conditioning-related toxicities will remain a significant barrier to patient accrual unless addressed. Current conditioning approaches rely on genotoxic methods such as total body irradiation (TBI) and/or chemotherapy. These non-targeted methods induce cytopenias, adversely affect niche cells and may damage other organ systems including germ cells. To fully realize the curative potential of HSCT, the development of mild-conditioning methods that preserve immunity while enabling efficient donor engraftment is essential. Efforts to develop mild non-genotoxic approaches (e.g. CD117 antagonist ACK2 antibody) have thus far been met with efficacy limited to immunocompromised animals with very poor engraftment in immunocompetent settings. While extensively explored in cancer therapy, protein-based internalizing immunotoxins (ITs) that induce cell death by inhibiting protein synthesis have not been explored as a conditioning strategy. By creating saporin-based ITs against various antigens present on HSCs, we identified an immunotoxin against CD45 receptor (CD45-IT) that potently depleted hematopoietic cells in vitro (40-70 picomolar IC50) and achieved efficient HSC depletion (>98% depletion in vivo)in fully immunocompetent mice when administered as a single dose. Following CD45-IT administration, transplantation of whole bone marrow donor cells enabled efficient donor engraftment (>90% chimerism). A wide engraftment window was tolerated as transplantation anywhere between 2-12 days post CD45-IT resulted in equivalent engraftment. Immune reconstitution was multi-lineage, durable (maintained for >15 months) and transferrable to secondary recipients, indicative of true stem cell engraftment. Using sickle cell disease mice, we demonstrated CD45-IT conditioning enabled >90% healthy donor cell engraftment resulting in complete disease correction (n=18 sickle mice). We next compared the toxicities induced by CD45-IT and conventional TBI (sub-lethal) in non-transplanted mice over a 120-day period. CD45-IT was non-lethal as mice survived long-term without requiring transplantation (n=12 mice). In contrast to TBI, CD45-IT had significantly less adverse effects on marrow hematopoietic progenitors, vascular integrity and overall marrow cellularity, which recovered faster than in TBI-treated mice. While peripheral B and T-cells were efficiently depleted by both CD45-IT and TBI immediately after treatment, unusually rapid lymphocyte recovery was observed following CD45-IT (12-18 days for T- and B-cell recovery) in comparison to TBI (48 days for recovery). Histology of thymi revealed CD45-IT does not induce thymic atrophy (unlike TBI) as the cortical region continued to support T-cell development as confirmed by T-cell receptor excision circle (TREC) analysis. Whereas TBI reduced peripheral neutrophil counts versus control, CD45-IT induced a rapid expansion of neutrophils (3-fold higher than naïve control). To test innate immunity, we performed a systemic challenge of candida albicans (a clinically relevant fungal strain). Candida challenge in TBI-conditioned mice proved lethal (100% death in 3 days, p value < 0.0001, n=10 mice). In contrast, CD45-IT treated mice were significantly immune to candida challenge with comparable survival to naïve controls (60% survival for CD45-IT, n=10 mice per group). To summarize, a protein-based immunotoxin targeting CD45 enables efficient HSCT in fully immunocompetent animals. The targeted immunotoxin avoids numerous toxicities associated with current genotoxic conditioning approaches and preserves innate immunity, thymic integrity and enables quicker recovery of adaptive immune cells while avoiding loss of vascular integrity, undesirable anemia, and prolonged cytopenias. Given these advantages, CD45-IT may be useful for conditioning of non-malignant transplant patients. Disclosures Hoggatt: Harvard University: Patents & Royalties.
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Nolan, James L. "Atomic Doctors: Conscience and Complicity at the Dawn of the Nuclear Age". Perspectives on Science and Christian Faith 73, n.º 1 (março de 2021): 54–55. http://dx.doi.org/10.56315/pscf3-21nolan.

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ATOMIC DOCTORS: Conscience and Complicity at the Dawn of the Nuclear Age by James L. Nolan Jr. Cambridge, MA: The Belknap Press of Harvard University Press, 2020. 294 pages, plus index. Hardcover; $29.95. ISBN: 9780674248632. *This book ends with a tragic photograph. The reader will see a young boy carrying a sleeping infant on his back. However, the infant is not asleep but instead is dead as his brother waits his turn to have his brother's body thrown into a giant pyre at Nagasaki in the days following the atomic bomb blast. This picture is symbolic of the tragedy of war and provides a provocative statement regarding the involvement of US physicians in the development of the atomic weapons program toward the end of World War II. The author, James L. Nolan Jr., PhD (Professor of Sociology, Williams College), provides an excellent historical vignette of this period through a written biography of his grandfather, James F. Nolan, MD. *Dr. Nolan, as well as Louis Hempelmann, MD and Stafford Warren, MD, were intricately involved with the Trinity testing in New Mexico as well as with the development of the atomic bomb as part of the Manhattan Project. Dr. Nolan met and collaborated with such famous people associated with the Manhattan Project, including J. Robert Oppenheimer, Edward Teller, and General Leslie Groves. The entire group of physicians oversaw determining radiation risks during atomic bomb development and testing. This placed them in a difficult situation which "linked the arts of healing and war in ways that had little precedent" (p. 166) especially regarding the Hippocratic Oath.1 *Dr. Nolan was involved with setting up the hospital at Los Alamos as well as providing medical care for the Los Alamos staff and families. However, the job of these clinicians also had other aspects. Radiation exposure to workers was observed and recorded at Los Alamos leading to some of the initial descriptions of radiation poisoning. Additionally, the physicians were involved in determining radiation hazards associated with Los Alamos and in the setting of Trinity with most of their findings either being ignored or hidden from the public, sometimes with the complicity of these individuals. It is fascinating to consider that Dr. Nolan was one of the military personnel chosen to accompany Little Boy (the bomb that exploded over Hiroshima) to the Pacific Front at Tinian Island on the famous and later tragic USS Indianapolis. I cannot imagine, in our present time, that a physician would be charged with transporting and reporting the safety of a technologically advanced weapons system. *The book contains many fascinating stories, including how military physicians as well as other personnel were told to assert there was no significant radiation after the bombing in Japan (despite obvious radiation injury being noted in thousands of individuals), how the military allowed reporters at the Trinity test site after the bomb test with no protection except for "protective" booties, how US military physicians were told to not treat Japanese civilians after the bombing in order to circumvent moral responsibility of the bombing (this was ignored), how the inhabitants of the Bikini Atoll and Enewetak Atoll were forced to abandon their ancestral homes so that further atomic bomb testing could occur (with subsequent deleterious effects in their sociologic and health outcomes), and how patients in the United States (many who were already terminally ill) were secretly injected with plutonium to determine the effects of radiation injury. *Besides being a biography and history of a physician and his colleagues, this book also goes in some philosophical directions, including considering what is the goal of technology. Oppenheimer himself stated that "It's amazing ... how the technology tools trap one" (p. 33). The "trap" leads to a myriad of issues. Dr. Nolan believed radiation should be considered under the paradigm of an "instrumentalist view of technology" in which new technology could be used for the advancement or decline of our species. In his case, he began experimenting with radiation to treat gynecologic cancer in his patients. The book then explores "technological determinism," both optimistic and pessimistic, which is still an issue permeating our culture today. The author states that humans appear to always choose technologic advances even before fully knowing downstream economic, political, or cultural effects. Such examples cited by the author include the internet, social media, and genetic engineering. *A Christian will find this book unsettling when one considers what one prioritizes in his (her) faith. For example, one of the physicists who worked at Los Alamos was a Quaker. The Trinity test was named after the Christian Trinity (based on a John Donne sonnet). These facts are sobering when the author provides reports of "downwinders" who suffered catastrophic disease after the Trinity test as well as going into detail about the thousands of Japanese who suffered radiation poisoning after the nuclear bombing. In addition, the bombing of Nagasaki was close to the Christian part of the city resulting in the killing of most of the Christians living there. Indeed, the pursuit of science is a fascinating human endeavor, but the point of science is to objectively determine facts. Science does not necessarily provide subjectivity by itself which allows it to be influenced by meaning, moral values, and responsibility.2 In the moral arena, people with religious beliefs, including Christians, are required to influence the idea of technologic determinism in a positive direction. I highly recommend this book not only to learn about an interesting part of world history but also to appreciate the tragedy of the human condition in the setting of war. *Notes *1Michael North, translator, "Greek Medicine," History of Medicine Division, National Library of Medicine, National Institutes of Health, last updated February 7, 2012, https://www.nlm.nih.gov/hmd/greek/greek_oath.html. *2Mehdi Golshani, "Science Needs a Comprehensive Worldview," Theology and Science 18, no. 3 (2020): 438-47. *Reviewed by John F. Pohl, MD, Professor of Pediatrics, Department of Pediatrics, University of Utah, Salt Lake City, UT 84113.
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