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  • 1
    Keywords: Medicine ; Epidemiology ; Public Health ; Biostatistics ; Statistics  ; Artificial intelligence ; Biomedicine, general ; Epidemiology ; Public Health ; Biostatistics ; Statistics for Life Sciences, Medicine, Health Sciences ; Artificial intelligence ; Springer eBooks
    Description / Table of Contents: Foreword -- Preface -- Acknowledgements -- Essence of Clinical Medicine -- Essence of Clinical Research -- Clinical Research and Clinical Medicine at present -- Clinical Research Transformative of Clinical Medicine -- Core Concepts of Epidemiology and Epidemiological Research -- The Epidemiological Interface of Gnostic Clinical Research -- The Logistic Regression Model -- Statistics from the Model’s Fitting to Gnostic Data -- The Types of Diagnostic Challenge and Needs for Knowledge -- Harvesting Experts’ Diagnostic Probability Estimates -- Objects Design for a Diagnostic Probability Study -- Methods Design for a Diagnostic Probability Study -- The Bayes’ Theorem Framework for Diagnostic Research -- Research Focused on Diagnostic Tests -- Introduction to Etiognostic Research -- Objects Design for an Etiognostic Study -- Methods Design for an Etiognostic Study -- Introduction to Prognostic Research -- Example: Research on ‘Hormone Replacement Therapy’ -- Prognostic Probability Functions from Clinical-trial Data -- Non-experimental Intervention-prognostic Studies -- Intervention-prognostic Derivative Research -- Theory of Medicine Defining the Essential Missions for Clinical Research -- Theory of Clinical Research for Its Essential - Gnosis-serving - Missions -- Toward Worldwide Scientific Clinical Medicine -- Glossary -- Appendix 1: What about ‘Machine Learning’?- Appendix 2: On Excellence of Epidemiologic Academia -- Index
    Abstract: This book delineates the fundamental transformations that, according to its precepts, are now needed in the objects and methods of ́€˜patient-oriented́€™ clinical research, in order to make it genuinely patient-relevant. These transformations are presented as providing for transition from todaý€™s €˜évidence-based́€™ practices (advocated by ́€˜clinical epidemiologistś€™) to knowledge-based succedanea of these. While those existing practices vary according to doctorś€™ personal opinions about the burden of the available evidence, their knowledge-based succedanea will be essentially invariant across individual doctors, as theý€™ll be guided by €˜éxpert systemś€™ (imbedded in cyberspace). At issue in this is transformation in what the authors present as the very essence of clinical medicine, namely clinical doctorś€™ esoteric ad-hoc knowing: ́€œgnosis.́€ This is clinical doctorś€™ knowing ́€” probabilistic ́€” about relevant-but-hidden truths about their patientś€™ health, and constitutes the basis for their teaching (́€œdoctorinǵ€) the patients about these esoteric insights. The probabilities are ́€˜personalized́€™ in the meaning of their specificity to the caseś€™ gnostic profiles. Genuinely patient-relevant clinical knowledge this book presents as the requisite basis for three species of clinical doctorś€™ gnosis: diagnosis ́€” knowing about whether a particular type of illness is present (though hidden) in the patient; etiognosis ́€” knowing about whether the patient́€™s illness was caused by a particular antecedent of it; and prognosis ́€” knowing about the patient́€™s future health, including as to its dependence on the choice of treatment. Pivotal in gnostic clinical research this book presents to be the studieś€™ objects design in terms of a statistical model for the rate of occurrence of the entity of health in question, in a defined domain of case presentations. The essentials of the studieś€™ methods designs are deduced from their objects designs. Study of this book ́€” on the theory of ́€œmeta-epidemiological clinical research́€ ́€” is essential preparation for teaching ́€˜patient-oriented́€™ clinical research and for actual design & conduct of the studies and of their critical reviews. And by the same token, study of this book is essential preparation for the needed replacement of ́€˜case-based learninǵ€™ of clinical medicine, for suitably-learned teaching of the practice of clinical medicine ́€” focused on the status quo of the scientific knowledge-base for (gnoses in) the discipline (́€˜specialtý€™) at issue
    Pages: XXIV, 302 p. 2 illus. : online resource.
    Edition: 1st ed. 2019.
    ISBN: 9783030061760
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  • 2
    Keywords: Medicine ; Neurosciences ; Behavioral Sciences ; Animal Physiology ; Biomedicine ; Neurosciences ; Behavioral Sciences ; Animal Physiology ; Springer eBooks
    Description / Table of Contents: Part I Evolution of the Brain -- 1 An overview of brain evolution: lobe-finned fish vs ray-finned fish -- 2 The Origins of the Bird Brain: Multiple Pulses of Cerebral Expansion in Evolution -- 3 The evolution of mammalian brains from early mammals to present-day primates -- 4 Developmental sequences predict multiple types of increased intra-connectivity in evolution: a comparative analysis of developmental timing, gene expression, neuron numbers, and diffusion MR tractography -- Part II Evolution of Cognition -- 5 The Evolution of Cognitive Brains in Non-mammals -- 6 Evolution of Cognitive Brains: Mammals -- 7 On the Matter of Mind: Neural Complexity and Functional Dynamics of the Human Brain -- 8 Behavioural, cognitive, and neuronal changes in the acquisition of tool use -- 9 Great ape social attention -- 10 Evolution of vocal communication: From animal calls to human speech -- 11 Integration Hypothesis: A Parallel Model of Language Development in Evolution -- Part III Evolution of Emotion -- 12 Evolution of the emotional brain -- 13 Evolutionary origin of empathy and inequality aversion
    Abstract: This book presents a new view on the evolution of the brain, cognition, and emotion. Around a half-century ago, Professor Harry Jerison published a seminal book entitled Evolution of the Brain and Intelligence. Since then, there has been a series of dramatic methodological and conceptual changes which have led to many new insights into the understanding of brain evolution and cognition. This book is particularly focused on three significant aspects of such changes. First, taking advantage of a new integrated approach called evolutionary developmental biology or Evo/Devo, researchers have started to look into vertebrate brain evolution from the developmental perspective. Second, comparative neuroanatomists have accumulated a large amount of information about the brains of diverse animal groups to refute the old-fashioned idea that vertebrate brains evolved linearly from non-mammals to mammals. Third, comparative behavioral studies have demonstrated that sophisticated cognition and emotion are not unique to some primates but are also found in many non-primate and even non-mammalian species. This work will appeal to a wide readership in such fields as neuroscience, cognitive science, and behavioral science
    Pages: X, 299 p. 76 illus., 25 illus. in color. : online resource.
    ISBN: 9784431565598
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  • 3
    Keywords: CANCER ; MONOCLONAL-ANTIBODY ; ACTIVATION ; IMPACT ; ASSOCIATION ; METASTATIC MELANOMA ; RECURRENCE ; CLINICAL-IMPLICATIONS ; TARGETED THERAPY ; BRAF V600E MUTATION
    Abstract: BACKGROUND: The aim of this study was to compare the detection of BRAF(V600E) by immunohistochemistry (IHC) using a mutation-specific antibody with molecular biology methods for evaluation of papillary thyroid carcinoma (PTC) patients. PATIENTS AND METHODS: This study concerned 198 consecutive conventional PTC patients, of which the majority were women (133/198; 67%), with a mean age of 56 years (range 19-79 years). BRAF mutation analysis was performed using DNA-based (direct sequencing, pyrosequencing, and SNaPshot) and IHC (VE1 antibody) methods. The sensitivity and specificity of IHC for BRAF(V600E) was compared with the molecular biology data. RESULTS: A BRAF mutational result was obtained in 194 cases. A BRAF(V600E) mutation was detected in 153/194 (79%) cases of PTC when using at least one molecular method, and in 151/194 (78%) cases with IHC. No false positive results were noted using IHC to detect the BRAF(V600E) mutation. Besides this mutation, other rare BRAF mutations (BRAF(V600K) and BRAF(K601E)), used as negative controls, were consistently negative with IHC. The sensitivity and specificity of IHC for the detection of this mutation were 98.7% and 100% respectively. The IHC test demonstrated excellent performance at a level equivalent to two DNA-based counterparts (pyrosequencing and SNaPshot). Failure to achieve a result was more frequent with the direct sequencing method than with the three other methods. CONCLUSION: IHC using the VE1 antibody is a specific and sensitive method for the detection of the BRAF(V600E) mutation in PTC. IHC may be an alternative to molecular biology approaches for the routine detection of this mutation in PTC patients.
    Type of Publication: Journal article published
    PubMed ID: 24417277
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  • 4
    Keywords: CANCER ; GENE ; FREQUENCY ; MELANOMA ; B-RAF ; EGFR ; KRAS ; molecular pathology ; HARBORING BRAF MUTATIONS ; ROUTINE PRACTICE
    Abstract: BackgroundNon-small-cell lung carcinoma (NSCLC) patients with a BRAF(V600E) mutation benefit from targeted therapy. The usefulness of immunohistochemistry (IHC) as an alternative approach for the detection of BRAF(V600E) in NSCLC patients has not been evaluated until now. This study compared the specificity and sensitivity of IHC with other methods for the detection of BRAF(V600E) in primary lung adenocarcinoma.Patients and methodsBRAF mutations were analysed by DNA sequencing of a Caucasian subpopulation of selected 450 of 1509 (30%) EGFR, KRAS, PI3KA, Her2 and EML4-ALK wild-type (wt) primary lung adenocarcinomas. Detection of the BRAF(V600E) mutation was carried out by IHC using the VE1 clone antibody and compared with the results of other molecular methodologies.ResultsOf 450 (9%) of tumours, 40 harboured a BRAF mutation, which corresponded to either a BRAF(V600E) or a non-BRAF(V600E) mutation in 21 of 450 (5%) and 19 of 450 (4%) cases, respectively. The IHC VE1 assay was positive in 19 of 21 (90%) BRAF(V600E)-mutated tumours and negative in all BRAF(nonV600E)-mutated tumours.ConclusionIHC using the VE1 clone is a specific and sensitive method for the detection of BRAF(V600E) and may be an alternative to molecular biology for the detection of mutations in NSCLC.
    Type of Publication: Journal article published
    PubMed ID: 23131393
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  • 5
    Keywords: COMBINATION ; MODEL ; MODELS ; FOLLOW-UP ; INFORMATION ; DISEASE ; DISEASES ; RISK ; HEART ; TIME ; MARKER ; ASSOCIATION ; ASSAY ; DESIGN ; PLASMA ; NUMBER ; AGE ; meta-analysis ; smoking ; DATABASE ; C-REACTIVE PROTEIN ; MYOCARDIAL-INFARCTION ; HEART-DISEASE ; vascular disease ; REGRESSION ; ASSOCIATIONS ; ISCHEMIC-STROKE ; CORONARY-HEART-DISEASE ; METAANALYSIS ; LEVEL ; methods ; EXTENT ; ARTERY-DISEASE ; MIDDLE-AGED MEN ; ACTIVATING-FACTOR-ACETYLHYDROLASE ; ATHEROSCLEROSIS RISK ; lipoprotein-associated phospholipase A(2) ; LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE-A2 ; REPEAT
    Abstract: Background A large number of observational epidemiological studies have reported generally positive associations' between circulating mass and activity levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA(2) markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. Objectives By combination of data from individual participants from all relevant observational studies in a systematic,meta-analysis, with correction for regression dilution (using available data on serial measurements of Lp-PLA(2)), the Lp-PLA(2) Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA(2) with coronary heart disease (and, where data are sufficient with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA(2) and cardiovascular outcomes. Methods A central database is being established containing data on circulating Lp-PLA(2) values, sex and other potential confounding factors, age at baseline Lp-PLA(2) Measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA(2) will yield information on a total of about 15 000 cardiovascular disease endpoints
    Type of Publication: Journal article published
    PubMed ID: 17301621
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  • 6
    ISSN: 1434-4726
    Keywords: Pediatric thyroid neoplasms ; Spindle epithelial tumor ; Thymoma ; Ectopic thymus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An intrathyroid primary epithelial spindle-cell tumor with mucous cysts is described in a 9-year-old child. Histologically, this well-circumscribed tumor exhibited a nodular pattern, a prominent spindle cell component with minimal pleomorphism, and well-differentiated mucinous glands within fibrous bands. The spindle cells demonstrated diffuse immunopositivity for cytokeratin and vimentin. Electron microscopy of tissue sections demonstrated that cells contained bundles of cytoplasmic tonofilaments and numerous desmosomes. The light and electron microscopic features and immunohistochemical profile of this tumor were similar to those of recently described thyroid tumors that have been called “SETTLE” tumors (i.e., spindle epithelial tumor with thymus-like differentiation). These uncommon tumors can be considered intrathyroid thymoblastomas and must be regarded as potentially malignant lesions.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0047-2484
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0047-2484
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1523-5378
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Research in the last year has provided new insights into the function of the the cag-associated type IV secretion system and the vacuolating toxin VacA. A quite new aspect was disclosed by the finding that Helicobacter pylori in Mongolian gerbils colonizes a very distinct topology in the gastric mucous layer, obviously providing optimal conditions for long-term survival. Further research activities focused on H. pylori ammonia and metal metabolism as well as on bacterial stress defence mechanisms. Differential expression of approximately 7% of the bacterial genome was found at low pH suggesting that H. pylori has evolved a multitude of acid-adaptive mechanisms. VacA was shown to interrupt phagosome maturation in macrophage cell lines as well as to modulate and interfere with T lymphocyte immunological functions. Gastric mucosa as well as the H. pylori-infected epithelial cell line AGS strongly express IL-8 receptor A and B, which might contribute to the augmentation of the inflammatory response. Accumulating evidence implicates genetic variation in the inflammatory response to H. pylori in the etiology of the increased risk of gastric cancer after H. pylori infection. The chronic imbalance between apoptosis and cell proliferation is the first step of gastric carcinogenesis. In this regard, it was demonstrated that coexpression of two H. pylori proteins, CagA and HspB, in AGS cells, caused an increase in E2F transcription factor, cyclin D3, and phosphorylated retinoblastoma protein.Taken together, we now have a better understanding of the role of different virulence factors of H. pylori. There is still a lot to be learned, but the promising discoveries summarized here, demonstrate that the investigation of the bacterial survival strategies will give novel insights into pathogenesis and disease development.
    Type of Medium: Electronic Resource
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