747 research outputs found
The Adenosinergic Pathway in Non-Small Cell Lung Cancer
No full textSimple Summary Lung cancer remains the most important cause of cancer-related mortality worldwide. Immune checkpoint inhibitors revolutionized lung cancer care. These molecules restore the host's immune response against tumor cells and led to impressive results in non-small cell lung cancer patients. However, these benefits are only observed in a minority of patients. Extracellular adenosine is an immune checkpoint that contributes to immune evasion in tumor cells. Current research focuses on targeting this pathway with the aim of inducing durable treatment effects in a greater proportion of lung cancer patients.Abstract Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 and CTLA-4 have revolutionized the systemic treatment of non-small cell lung cancer (NSCLC), achieving impressive results. However, long-term clinical benefits are only seen in a minority of patients. Extensive research is being conducted on novel potential immune checkpoints and the mechanisms underlying ICI resistance. The tumor microenvironment (TME) plays a critical role in modulating the immune response and influencing the efficacy of ICIs. The adenosinergic pathway and extracellular adenosine (eADO) are potential targets to improve the response to ICIs in NSCLC patients. First, this review delves into the adenosinergic pathway and the impact of adenosine within the TME. Second, we provide an overview of relevant preclinical and clinical data on molecules targeting this pathway, particularly focusing on NSCLC
Diagnostic Validation of a Comprehensive Targeted Panel for Broad Mutational and Biomarker Analysis in Solid Tumors
No full textSIMPLE SUMMARY: The analysis of tumor-associated genetic variants and biomarkers is critical for therapy choice, as specific mutations allow for a personalized treatment. Because more and more mutation-treatment combinations become available, screening should be performed on many genes simultaneously. The use of large and comprehensive gene panel screenings in molecular diagnostics, however, requires an extensive and thorough validation to demonstrate the correctness of all clinically relevant data. Here, we describe such validation using a large number of samples and confirmed effective detection of several types of mutations for different validation parameters. Samples of tumor patients thus can be reliably tested with a comprehensive assay to maximize their personalized treatment regimen. ABSTRACT: The use of targeted Next Generation Sequencing (NGS) for the diagnostic screening of somatic variants in solid tumor samples has proven its high clinical value. Because of the large number of ongoing clinical trials for a multitude of variants in a growing number of genes, as well as the detection of proven and emerging pan-cancer biomarkers including microsatellite instability (MSI) and tumor mutation burden (TMB), the currently employed diagnostic gene panels will become vastly insufficient in the near future. Here, we describe the validation and implementation of the hybrid capture-based comprehensive TruSight Oncology (TSO500) assay that is able to detect single-nucleotide variants (SNVs) and subtle deletions and insertions (indels) in 523 tumor-associated genes, copy-number variants (CNVs) of 69 genes, fusions with 55 cancer driver genes, and MSI and TMB. Extensive validation of the TSO500 assay was performed on DNA or RNA from 170 clinical samples with neoplastic content down to 10%, using multiple tissue and specimen types. Starting with 80 ng DNA and 40 ng RNA extracted from formalin-fixed and paraffine-embedded (FFPE) samples revealed a precision and accuracy >99% for all variant types. The analytical sensitivity and specificity were at least 99% for SNVs, indels, CNVs, MSI, and gene rearrangements. For TMB, only values around the threshold could yield a deviating outcome. The limit-of-detection for SNVs and indels was well below the set threshold of 5% variant allele frequency (VAF). This validated comprehensive genomic profiling assay was then used to screen 624 diagnostic samples, and its success rate for adoption in a clinical diagnostic setting of broad solid tumor screening was assessed on this cohort
Motive und Motivationen als Grundlage menschlichen Verhaltens – Überlegungen zu einer integrativen Motivationstheorie
No full textDie Untersuchungen der Autorin zur Motivation führen zu dem Schluss, dass Grundmotive im Menschen genetisch angelegt sind. Diese sind implizit in seinem Menschen- und Weltbild vorhanden und werden in situativen Motivationsprozessen aktualisiert. Das Motiv der Hilfeleistung, das in therapeutischen oder beraterischen Prozessen beim Therapeuten aktiviert ist, findet ein Gegenüber im Motiv der Suche nach Hilfe beim Klienten. Beide Seiten folgen einem, von der Autorin dargestellten intersubjektiven Motivationsprozess.The author’s research focuses on the origin and development of motives and moti¬vation with special emphasis on the motive of helpfulness in therapy or consulting. Helpfulness is an essential of the human character. It determines our concepts of the world and of mankind. From an integrative point of view the author discusses the origins of motives in man and develops a structural model of the process of motivation and behaviour of both, client and therapist.https://www.fpi-publikation.de/polyloge/13-2012-jaekel-brigitte-motive-und-motivationen-als-grundlage-menschlichen-verhaltens/peerReviewedpublishedVersio
Edgar and Brigitte Bodenheimer Collection 1897-1992, 2011 1920-1983
No full textThe Edgar and Brigitte Bodenheimer Collection documents the professional and personal life of law professor Edgar Bodenheimer as well as that of his wife, Brigitte Bodenheimer (née Levy). The collection contains documentation on their early legal work during the 1940s, Edgar's participation in the Nuremberg Trials, and postwar work as professors, as well as material on their daily lives and other family members. The collection includes a copious amount of correspondence, lecture texts, certificates and diplomas, diaries and notebooks, newspaper clippings, teaching material, poetry, a friendship album, and other papers.Original order in 5 boxes: Box 1: Edgar and Brigitte Bodenheimer: journals, poems, documents. Box 2: Edgar Bodenheimer: speeches & talks, CV, bibligraphies, teaching materials, reviews of E.B.'s books. Box 3: Edgar Bodenheimer professional correspondence. Box 4a: Edgar Bodenheimer personal correspondence. Box 4b: Edgar Bodenheimer personal correspondence.A book about Edgar and Brigitte Bodenheimer by their daughter Rosemarie Bodenheimer is available in the LBI Library: "Edgar and Brigitte: a German Jewish passage to America". This book was written using the documents in this collection.Two books by Edgar Bodenheimer with his extensive handwritten notes were removed to the LBI Library. Photocopies of these notes were retained in the collection and will be found in Series III.Edgar Bodenheimer was born in Berlin on March 14, 1908, the son of the bank director Siegmund Bodenheimer and his wife Rosa (called Rosi, née Maass). He studied law and political science at various German and Swiss universities, acquiring his Doctor of Laws from the University of Heidelberg in 1933. In 1934 Edgar Bodenheimer immigrated to the United States, where he found a position in a New York City law office.Brigitte M. Levy was the daughter of Ernst Levy, a professor and scholar of Roman Law at the University of Heidelberg, and Marie Levy (née Wolff). After studies at various German universities, she received her doctoral degree in jurisprudence from the University of Heidelberg in 1934 after have immigrating to New York, where she continued her studies at Columbia University. In 1935 Edgar Bodenheimer and Brigitte M. Levy married. (They eventually had three children: Peter became a professor of astrophysics at the University of California; Thomas became a physician; and Rosemarie became an author and professor of English literature at Boston College.In 1935 the couple moved to Seattle, Washington, where they both studied law at the University of Washington. Edgar Bodenheimer joined the Washington Bar Association in 1939 once he had become a citizen. The following year Edgar Bodenheimer received a Bachelor of Arts Degree in Law Librarianship. His book ‘Jurisprudence’ was published in 1940; many other books followed until 1962. In 1942 the Bodenheimers moved to Washington, D.C., working in various official positions. In 1945 Edgar joined the prosecuting team at the Nuremberg Trials.In 1946 Edgar Bodenheimer took a position at the University of Utah in Salt Lake City; in 1951 he was made full professor and held the position until his departure in 1966. Brigitte Bodenheimer worked primarily in the fields of divorce, marriage, and juvenile court legislation. In 1964 she also became a full-time professor at the University of Utah.In 1966 Edgar Bodenheimer became professor of law at the University of California at Davis. In 1975 he became Professor Emeritus. Brigitte Bodenheimer became a full professor at Davis in 1972; in 1979 she became Professor Emeritus. She died in 1981 at the age of 69.Edgar Bodenheimer held visiting professorships at several universities in Germany and in the U.S. In 1975 he was named an Outstanding Educator of America. He died in 1991 in Davis, California, survived by his second wife, Brigitte née Schoenberg.Finding aid available onlineProcesseddigitize
Ambivalenzen des Alltags : Neuorientierungen fur eine Theorie des Politischen /
No full textDie politische Theorie ist gegenwärtig - nicht zuletzt in Reaktion auf veränderte gesellschaftliche Verhältnisse - durch eine angeregte Diskussion über das Politische geprägt. Brigitte Bargetz greift diese aktuellen Debatten auf und schlägt mit dem Konzep.Political theory is currently marked by lively discussion, not least in response to changing social conditions. Brigitte Bargetz siezes on these current debates and puts forward a new direction of political thought using the concept of the everyday: Following Henri Lefebvre, Agnes Heller, and Lawrence Grossberg, she outlines a complex theory of everyday life which allows the perception of the everyday as an ambivalent political battleground between domination and resistance, providing the starting point for a practical theory of politics beyond the state.Die politische Theorie ist gegenwärtig - nicht zuletzt in Reaktion auf veränderte gesellschaftliche Verhältnisse - durch eine angeregte Diskussion über das Politische geprägt. Brigitte Bargetz greift diese aktuellen Debatten auf und schlägt mit dem Konzep.Political theory is currently marked by lively discussion, not least in response to changing social conditions. Brigitte Bargetz siezes on these current debates and puts forward a new direction of political thought using the concept of the everyday: Following Henri Lefebvre, Agnes Heller, and Lawrence Grossberg, she outlines a complex theory of everyday life which allows the perception of the everyday as an ambivalent political battleground between domination and resistance, providing the starting point for a practical theory of politics beyond the state.Includes bibliographical references.JSTO
Liquid Biopsy in Early-Stage Lung Cancer: Current and Future Clinical Applications
No full textLung cancer remains the leading cause of cancer death worldwide, with the majority of cases diagnosed in an advanced stage. Early-stage disease non-small cell lung cancer (NSCLC) has a better outcome, nevertheless the 5-year survival rates drop from 60% for stage IIA to 36% for stage IIIA disease. Early detection and optimized perioperative systemic treatment are frontrunner strategies to reduce this burden. The rapid advancements in molecular diagnostics as well as the growing availability of targeted therapies call for the most efficient detection of actionable biomarkers. Liquid biopsies have already proven their added value in the management of advanced NSCLC but can also optimize patient care in early-stage NSCLC. In addition to having known diagnostic benefits of speed, accessibility, and enhanced biomarker detection compared to tissue biopsy, liquid biopsy could be implemented for screening, diagnostic, and prognostic purposes. Furthermore, liquid biopsy can optimize therapeutic management by overcoming the issue of tumor heterogeneity, monitoring tumor burden, and detecting minimal residual disease (MRD), i.e., the presence of tumor-specific ctDNA, post-operatively. The latter is strongly prognostic and is likely to become a guidance in the postsurgical management. In this review, we present the current evidence on the clinical utility of liquid biopsy in early-stage lung cancer, discuss a selection of key trials, and suggest future applications.This research received no external funding
Le travail du coton chez les Ema de Timor portugais
No full text2. Brigitte Clamagirand (C.N.R.S., Paris) telah dua kali tinggal dalam watu jang lama di daerah penduduk Kemak, Timor Portugis, untuk mengadakan penjelidikan. Penulis memaparkan berbagai tahap pengerdjaan kapas, jang hanja dikerdjakan oleh kaum wanita; untuk tiap tahap jang penting, mulai dari membersihkan kapas dari bidji2-nja sampai memberi warna (proses ikai) dan waktu penenunan, penulis memberikan semua istilah tehniknja beserta photo dan skemanja.(2) Brigitte Clamagirand (CRNS, Paris) has made two field trips of long duration among the Ema (Kemak) of Portuguese Timor; she presents us with the diverse phases of working of cotton, which, there, is exclusively the work of women. For each of the principal phases, from the gining of the wad, to the tinting (ikat process), to the weaving (with a back strap loom), the author gives us the technical terms with photographs and schémas.Clamagirand Brigitte. Le travail du coton chez les Ema de Timor portugais. In: Archipel, volume 3, 1972. pp. 55-80
Recenzja: Wiedeński okres w życiu Adolfa Hitlera w ujęciu Brigitte Hamann i Augusta Kubizka
No full text THE VIENNESE PERIOD IN ADOLF HITLER’S LIFE AS PRESENTED BY BRIGITTE HAMANN AND AUGUST KUBIZEKThe article discusses the literature and the findings concerning the relatively least explored questions concerning Adolf Hitler, namely those of his youth. As the author stresses, just over a dec­ade ago Polish readers interested in the Hitler phenomenon knew much less than they do now. Thanks to several books recently published in Poland they have had a chance to considerably expand their knowledge. The present author points to two figures, Brigitte Hamann and August Kubizek, focusing on the similarities and differences in their approach to this period of Hitler’s life. THE VIENNESE PERIOD IN ADOLF HITLER’S LIFE AS PRESENTED BY BRIGITTE HAMANN AND AUGUST KUBIZEKThe article discusses the literature and the findings concerning the relatively least explored questions concerning Adolf Hitler, namely those of his youth. As the author stresses, just over a dec­ade ago Polish readers interested in the Hitler phenomenon knew much less than they do now. Thanks to several books recently published in Poland they have had a chance to considerably expand their knowledge. The present author points to two figures, Brigitte Hamann and August Kubizek, focusing on the similarities and differences in their approach to this period of Hitler’s life
Les paradoxes de Linguet
No full textBrigitte Burmeister : Linguet's paradoxes.
The social theories of Linguet (1736-1794) combine lucid criticism of 18th-century capitalism with pessimistic, even reactionary conclusions. In his Theory of Civil laws (1767), a critique of the Esprit des lois, Linguet begins with a description of the suffering caused by social inequality, to finish with a plan of reform which rejects any social change. Taking as a starting-point two " paradoxes " of Linguet — his apologies for slavery and for oriental despotism — the author demonstrates how these theories reveal the limitations of Enlightenment ideology by reflecting the contradictions of capitalistic society, insoluble within the framework of bourgeois emancipation. This results in the case of Linguet, not in a communistic Utopia but in an equally utopie, and yet reactionary, rejection of Enlightenment thought.Burmeister Brigitte. Les paradoxes de Linguet. In: Dix-huitième Siècle, n°7, 1975. pp. 147-155
Immune checkpoint inhibition in early-stage non-small cell lung cancer
No full textThe introduction of immune checkpoint inhibitors significantly advanced outcomes in both metastatic and locally advanced non-small cell lung cancer. Despite these advancements, the 5-year survival rate remains suboptimal. Even in early-stage disease a significant portion of patients relapse and die from metastatic progression. The integration of immunotherapy in the management of early-stage NSCLC demonstrated promising results, supported by a plethora of positive clinical trials conducted in recent years. Nonetheless, numerous questions persist. In this manuscript we comprehensively review the currently available data on adjuvant, neoadjuvant, and perioperative treatment strategies. We also address the challenges inherent to these approaches from different stakeholders' perspective
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