1,721,077 research outputs found
Weighing up beta-cell mass in mice and humans: self-renewal, progenitors or stem cells? (In special issue: Stem cells and progenitors in organ maintenance, regeneration and replacement: the role of hormones and growth factors in health and disease)
No full textUnderstanding how beta-cells maintain themselves in the adult pancreas is important for prioritizing strategies aimed at ameliorating or ideally curing different forms of diabetes. There has been much debate over whether beta-cell proliferation, as a means of self-renewal, predominates over the existence and differentiation of a pancreatic stem cell or progenitor cell population. This article describes the two opposing positions based largely on research in laboratory rodents and its extrapolation to humans
Type 1 diabetes-associated antibodies during pregnancy and in infancy
Full text linkAbstractThere is evidence that the process leading to type 1 diabetes may start in early infancy or even in utero, with a prodrome of variable duration preceding clinical manifestation. The purpose of the present work was to learn more about the occurrence and significance of humoral beta-cell autoimmunity during pregnancy and in infancy, to search for possible signs of prenatal or early postnatal induction of beta-cell autoimmunity and to explore the role of enterovirus infections as potential triggers of such autoimmunity.The population comprised mothers and their newborn infants from families with type 1 diabetes who had entered the first (n=20) or the second pilot study (n=208) of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR). Almost 40% of the mothers with type 1 diabetes had antibodies to islet cells (ICA), 55% to glutamic acid decarboxylase (GADA) and 54% to the IA-2 protein (IA-2A) in the two samples taken during pregnancy, where the frequencies for the unaffected mothers were 5%, 5% and 3%, respectively. All autoantibody specificities were detected in the cord blood largely at the same frequencies as in the maternal circulation. In addition, ICA was found in 2.7%, GADA in 0.6%, IA-2A in 0.3% and insulin autoantibodies (IAA) in 0.1% out of a series of 1002 cord blood samples from infants representing the normal population. None of the infants of the autoantibody-negative mothers in these series had autoantibodies detectable in their cord blood.The rate of decline of transplacentally transferred autoantibodies during the first months of life was observed to be similar to that reported for the disappearance of maternally acquired IgG antibodies, the estimated mean elimination time ranging from 3.1–4.5 months. The higher the initial autoantibody level, the longer was the elimination time, and transplacentally transferred autoantibodies were occasionally detected up to the age of 9–12 months, and even at 15 months in a very few cases.The peak incidence of enterovirus RNA in serum was observed at the age of 6–12 months, while that of infections, based on changes in antibody titres, was seen at the age of 18 months. The frequency of enterovirus infections in the autoantibody-positive infants during the 6 months before the appearance of the first autoantibodies was almost three times higher than in age-matched infants testing negative for autoantibodies.These observations suggest that pregnancy does not have any strong modulating effect on the prevalence and titres of diabetes-associated autoantibodies. If such autoantibodies are present in the mother, most of them are transferred to the foetal circulation and are detectable in the cord blood. No signs of foetal induction of beta-cell autoimmunity were observed, indicating that such a phenomenon is extremely rare. Most of the transplacentally transferred autoantibodies disappear within the first 3–6 months of postnatal life, but they may persist even up to the age of 15 months in exceptional cases, suggesting that the optimal age for the initiation of large-scale screening in the general population is 18–24 months. The temporal association between enterovirus infections and the first signs of beta-cell autoimmunity supports the hypothesis that enteroviruses may induce a primary beta-cell insult.Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium of the Department of Paediatrics, on November 30th, 2001, at 12 noon.Abstract
There is evidence that the process leading to type 1 diabetes may start in early infancy or even in utero, with a prodrome of variable duration preceding clinical manifestation. The purpose of the present work was to learn more about the occurrence and significance of humoral beta-cell autoimmunity during pregnancy and in infancy, to search for possible signs of prenatal or early postnatal induction of beta-cell autoimmunity and to explore the role of enterovirus infections as potential triggers of such autoimmunity.
The population comprised mothers and their newborn infants from families with type 1 diabetes who had entered the first (n=20) or the second pilot study (n=208) of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR). Almost 40% of the mothers with type 1 diabetes had antibodies to islet cells (ICA), 55% to glutamic acid decarboxylase (GADA) and 54% to the IA-2 protein (IA-2A) in the two samples taken during pregnancy, where the frequencies for the unaffected mothers were 5%, 5% and 3%, respectively. All autoantibody specificities were detected in the cord blood largely at the same frequencies as in the maternal circulation. In addition, ICA was found in 2.7%, GADA in 0.6%, IA-2A in 0.3% and insulin autoantibodies (IAA) in 0.1% out of a series of 1002 cord blood samples from infants representing the normal population. None of the infants of the autoantibody-negative mothers in these series had autoantibodies detectable in their cord blood.
The rate of decline of transplacentally transferred autoantibodies during the first months of life was observed to be similar to that reported for the disappearance of maternally acquired IgG antibodies, the estimated mean elimination time ranging from 3.1–4.5 months. The higher the initial autoantibody level, the longer was the elimination time, and transplacentally transferred autoantibodies were occasionally detected up to the age of 9–12 months, and even at 15 months in a very few cases.
The peak incidence of enterovirus RNA in serum was observed at the age of 6–12 months, while that of infections, based on changes in antibody titres, was seen at the age of 18 months. The frequency of enterovirus infections in the autoantibody-positive infants during the 6 months before the appearance of the first autoantibodies was almost three times higher than in age-matched infants testing negative for autoantibodies.
These observations suggest that pregnancy does not have any strong modulating effect on the prevalence and titres of diabetes-associated autoantibodies. If such autoantibodies are present in the mother, most of them are transferred to the foetal circulation and are detectable in the cord blood. No signs of foetal induction of beta-cell autoimmunity were observed, indicating that such a phenomenon is extremely rare. Most of the transplacentally transferred autoantibodies disappear within the first 3–6 months of postnatal life, but they may persist even up to the age of 15 months in exceptional cases, suggesting that the optimal age for the initiation of large-scale screening in the general population is 18–24 months. The temporal association between enterovirus infections and the first signs of beta-cell autoimmunity supports the hypothesis that enteroviruses may induce a primary beta-cell insult
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Beta-cell autoimmunity and assessment of the risk of progression to type 1 diabetes
Full text linkAbstractThe purpose of this work was to assess the value of humoral and genetic risk markers in the prediction of type 1 diabetes in siblings of children with type 1 diabetes, to characterise preclinical course of beta-cell autoimmunity in siblings, and to investigate the frequency of autoantibodies and their relations to genetic markers, beta-cell function and progression to type 1 diabetes in a schoolchild population.The prevalence and predictive value of autoantibodies was studied in 755 initially unaffected siblings, and the combination of genetic markers and autoantibodies in 701 of these siblings. Islet cell autoantibodies (ICA), insulin autoantibodies (IAA), glutamic acid decarboxylase antibodies (GADA) and IA-2 antibodies (IA-2A) were all shown to be of value in the prediction of type 1 diabetes in siblings initially tested at or close to the diagnosis of type 1 diabetes in the index case in the family. The risk of progression to type 1 diabetes was related to the number of autoantibodies detected, and the PPV of multiple autoantibodies was 55% over a period of 8 years. Autoantibodies were closely associated with HLA risk markers. A combination of the genetic markers and autoantibodies increased the PPVs of all autoantibodies substantially but also markedly reduced the sensitivity. The preclinical course of type 1 diabetes was investigated in 39 initially unaffected siblings who progressed to clinical disease during the follow-up. These individuals were characterised by the high-risk genetic markers, decreased beta-cell function and humoral autoimmunity against multiple beta-cell targets. However, all measures implied a remarkable individual variation in the rate of the disease process and the pattern of humoral beta-cell autoimmunity. Furthermore, the autoimmune process resulting in clinical presentation of type 1 diabetes could not be unambiguously distinguished from autoimmunity not leading to clinical disease within almost 10 years of follow-up.The frequencies of ICA, IA-2A, GADA and IAA in 3652 healthy Finnish schoolchildren were 2.8%, 0.6%, 0.5% and 0.9%, respectively, and multiple antibodies were detected in 0.6% of these children. GADA and multiple antibodies were related to the DQB1*0302 allele and the DQB1*02/0302 genotype. A reduced first-phase insulin reponse (FPIR) was associated with IA-2A, GADA, IAA and multiple antibodies, but not with ICA or any specific DQB1 allele or genotype. Four subjects progressed to type 1 diabetes, all of them having multiple autoantibodies and those two who underwent an intravenous glucose tolerance test had also a reduced FPIR. None of the progressors carried the high risk DQB1*0302 allele and two of them even carried the protective DQB1*0602 or *0603 allele.In conclusion, autoantibodies alone are recommended as first-line screening in siblings, whereas subsequent determination of HLA-DQB1 markers and their combination with autoantibodies provides a valuable tool for more precise risk assessment. Wide heterogeneity in the course of preclinical type 1 diabetes complicates an accurate estimation of the individual risk of progression to type 1 diabetes among siblings of children with type 1 diabetes. Combined screening for autoantibodies is recommended for the assessment of the risk of progression to type 1 diabetes in schoolchild populations, whereas the present observations challenge the value of current genetic risk markers in predictive strategies targeting schoolchildren.Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in Auditorium 12 of the University Hospital of Oulu, on June 14th, 2000, at 12 noon.Abstract
The purpose of this work was to assess the value of humoral and genetic risk markers in the prediction of type 1 diabetes in siblings of children with type 1 diabetes, to characterise preclinical course of beta-cell autoimmunity in siblings, and to investigate the frequency of autoantibodies and their relations to genetic markers, beta-cell function and progression to type 1 diabetes in a schoolchild population.
The prevalence and predictive value of autoantibodies was studied in 755 initially unaffected siblings, and the combination of genetic markers and autoantibodies in 701 of these siblings. Islet cell autoantibodies (ICA), insulin autoantibodies (IAA), glutamic acid decarboxylase antibodies (GADA) and IA-2 antibodies (IA-2A) were all shown to be of value in the prediction of type 1 diabetes in siblings initially tested at or close to the diagnosis of type 1 diabetes in the index case in the family. The risk of progression to type 1 diabetes was related to the number of autoantibodies detected, and the PPV of multiple autoantibodies was 55% over a period of 8 years. Autoantibodies were closely associated with HLA risk markers. A combination of the genetic markers and autoantibodies increased the PPVs of all autoantibodies substantially but also markedly reduced the sensitivity.
The preclinical course of type 1 diabetes was investigated in 39 initially unaffected siblings who progressed to clinical disease during the follow-up. These individuals were characterised by the high-risk genetic markers, decreased beta-cell function and humoral autoimmunity against multiple beta-cell targets. However, all measures implied a remarkable individual variation in the rate of the disease process and the pattern of humoral beta-cell autoimmunity. Furthermore, the autoimmune process resulting in clinical presentation of type 1 diabetes could not be unambiguously distinguished from autoimmunity not leading to clinical disease within almost 10 years of follow-up.
The frequencies of ICA, IA-2A, GADA and IAA in 3652 healthy Finnish schoolchildren were 2.8%, 0.6%, 0.5% and 0.9%, respectively, and multiple antibodies were detected in 0.6% of these children. GADA and multiple antibodies were related to the DQB1*0302 allele and the DQB1*02/0302 genotype. A reduced first-phase insulin reponse (FPIR) was associated with IA-2A, GADA, IAA and multiple antibodies, but not with ICA or any specific DQB1 allele or genotype. Four subjects progressed to type 1 diabetes, all of them having multiple autoantibodies and those two who underwent an intravenous glucose tolerance test had also a reduced FPIR. None of the progressors carried the high risk DQB1*0302 allele and two of them even carried the protective DQB1*0602 or *0603 allele.
In conclusion, autoantibodies alone are recommended as first-line screening in siblings, whereas subsequent determination of HLA-DQB1 markers and their combination with autoantibodies provides a valuable tool for more precise risk assessment. Wide heterogeneity in the course of preclinical type 1 diabetes complicates an accurate estimation of the individual risk of progression to type 1 diabetes among siblings of children with type 1 diabetes. Combined screening for autoantibodies is recommended for the assessment of the risk of progression to type 1 diabetes in schoolchild populations, whereas the present observations challenge the value of current genetic risk markers in predictive strategies targeting schoolchildren
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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