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Renal osteodystrophy : Bone histomorphometric studies in dialysis patients and kidney transplant recipients
Get PDFAims
This study’s first aim was to observe the evolution of bone turnover in waitlisted patients on dialysis and after kidney transplantation. An additional aim was to investigate the role of bone biopsy in transplant recipients with persistent hyperparathyroidism and to evaluate whether bone biomarkers can recognize high bone turnover disease. The final aim was to define the prevalence of low bone volume and incident fractures in kidney transplant recipients.
Methods
Two patient cohorts were studied to accomplish these aims. The evolution of bone turnover in dialysis patients and after kidney transplantation was investigated in a cohort of 61 patients who had been on maintenance dialysis for at least one month and were planned or waitlisted for kidney transplantation from a deceased donor. Patients were treated and followed up in the Hospital District of Helsinki and Uusimaa during the study. Iliac crest bone biopsy, dual energy x-ray absorptiometry scans, and bone biomarkers were obtained at baseline in this prospective, longitudinal study and repeated after two years in patients who continued on maintenance dialysis. The second biopsy was taken two years after engraftment in kidney transplant recipients. Demographic characteristics and data on immunosuppressive and mineral metabolism therapy were obtained from electronic patient charts (Study I and II).
Bone histomorphometric findings of 114 bone biopsies obtained from kidney transplant recipients due to the clinical suspicion of high bone turnover were retrospectively analyzed to investigate the role of bone biomarkers in recognizing increased bone turnover after kidney transplantation. Electronic patient charts were concurrently reviewed for demographics, medication, and laboratory findings (Study III).
The histomorphometric findings of 109 bone biopsies obtained from transplant recipients were retrospectively evaluated to study the prevalence of low bone volume and incident fractures after kidney transplantation. Relevant demographics and data on mineral metabolism therapy at the time of biopsy, laboratory findings, the results of dual-energy x-ray absorptiometry scans, and incident fractures were concurrently collected from electronic patient records, including surgery reports
and documents of imaging examinations (Study IV).
Results
Fifty-two specimens were qualified for the histomorphometric analysis at baseline. Thirty-seven out of 56 participants received a kidney transplant during the two-year follow-up. Twenty-seven transplant recipients underwent successful repeat bone biopsy. The proportion of high bone turnover in these patients declined from 63% at baseline to 19%, whereas the proportion of those with low bone turnover increased from 26% to 52%. Of 19 participants remaining on maintenance dialysis after two years, 13 were successfully re-biopsied. The proportion of patients continuing on dialysis with high bone turnover decreased from 69% to 31%, while low bone turnover increased from 8% to 38%. The proportion of abnormal bone mineralization increased in transplant recipients from 33% to 44% but decreased in patients remaining on dialysis from 46% to 15%. The proportion of patients with low trabecular bone volume was unchanged in transplant recipients but increased in patients remaining on dialysis. Bone biomarkers did not predict bone turnover in either transplant recipients or dialysis patients. Bone mineral density at the femoral neck correlated with bone volume in dialysis patients, but no correlation between bone mineral density and bone volume was found in Study II.
High bone turnover was identified in Study III in approximately 10% of all the patients who had received a kidney transplant between 2000 and 2015. Seventy percent of the patients had high turnover in bone biopsy despite this study solely including patients with bone biopsies performed due to the clinical suspicion of high bone turnover. A logistic regression model combining three variables (alkaline phosphatase, natural logarithmic parathyroid hormone, and ionized calcium) recognized the presence of high bone turnover in a reasonably accurate manner.
Bone turnover was classified in Study IV as high in 78 (72%) and normal or low in 31 (28%) patients. The prevalence of low bone volume was 43%. Patients with low/normal turnover had a higher prevalence of low volume compared to patients with high turnover [18 (58%) vs. 29 (37%), P = 0.047]. Thirty-seven fragility fractures occurred in 23 (21%) transplant recipients corresponding to a fracture incidence of 15 per 1000 person-years during a median follow-up of 9.1 (interquartile range, 6.3-12.1) years. Bone mineral density at the lumbar spine correlated with trabecular bone volume but not with incident fractures. Trabecular bone volume accordingly did not correlate with incident fractures. The cumulative corticosteroid dose was an important determinant of low bone volume but not of incident fractures (Study IV).
Conclusions
Bone turnover decreased over time both in patients continuing on dialysis and in kidney transplant recipients. Bone biomarkers were not associated with bone metabolism changes detected in bone biopsy specimens.
High bone turnover was verified in approximately 10% of all transplant recipients and in 70% of patients biopsied due to the clinical suspicion of high bone turnover. The presented logistic regression model discriminated high bone turnover from non-high in a moderately accurate manner among transplant recipients with increased prevalence of high bone turnover. This model may serve as a non-invasive tool in recognizing high bone turnover after engraftment if bone biopsy is not readily available.
Post-transplantation bone loss affects almost half of kidney transplant recipients, and the incidence of fractures is considerable compared to the general population. A bone biopsy is an important tool for determining bone turnover and mineralization, but it is presumably not the best measure of bone volume. The lack of association between bone trabecular volume and fractures suggests that bone microarchitecture and bone cortical component have crucial roles in the fractures of kidney transplant recipients.
.Tausta ja tavoitteet
Tutkimuksen ensimmäisenä tavoitteena oli arvioida, miten luun aineenvaihdunta muuttuu dialyysihoidon aikana munuaissiirtolistalla olevilla potilailla ja millaisia muutokset ovat siirron jälkeen. Muina tutkimustavoitteina oli arvioida, voidaanko munuaissiirtopotilaan kiihtynyt luun aineenvaihdunta tunnistaa poikkeavien laboratoriokokeiden perusteella sekä arvioida matalan hohkaluutilavuuden esiintyvyyttä ja murtumien ilmaantuvuutta munuaissiirron jälkeen.
Aineisto ja menetelmät
Ensimmäisessä ja toisessa osatyössä luun aineenvaihduntaa tarkasteltiin Helsingin ja Uudenmaan sairaanhoitopiirissä hoidetuilla 61 munuaissiirtolistalla olevilla dialyysipotilaalla. Tässä etenevässä pitkittäistutkimuksessa potilaista otettiin luubiopsia, luun aineenvaihduntaa kuvastavia merkkiaineita ja tehtiin luuntiheysmittaus kaksienergiaisella röntgenabsorptiometrialla. Tutkimukset otettiin seurannan alussa ja toistettiin kahden vuoden seuranta-ajan jälkeen niillä potilailla, jotka olivat edelleen dialyysihoidossa. Munuaissiirron saaneilla potilailla tutkimukset uusittiin kaksi vuotta munuaissiirron jälkeen.
Osatyössä III tarkasteltiin retrospektiivisesti munuaissiirtopotilailta otettujen luubiopsioiden histomorfometrisiä tuloksia. Biopsian ottosyy oli kliininen epäily kiihtyneestä luun aineenvaihdunnasta.
Osatyössä IV tarkasteltiin matalan hohkaluutilavuuden esiintyvyyttä ja murtumien ilmaantuvuutta 109 munuaissiirtopotilaasta otetuissa luubiopsianäytteissä.
Osatöissä I-IV potilaiden luubiopsialöydöksiä verrattiin samanaikaisesti otettuihin laboratoriokokeisiin, demografisiin tietoihin sekä hyljinnänestolääkityksen ja mineraaliaineenvaihduntaan vaikuttavien lääkkeiden käyttöön.
Tulokset ja johtopäätökset
Tutkimuksen alussa histomorfometrinen analyysi tehtiin 52 teknisesti onnistuneesta biopsiasta. Kahden vuoden seuranta-aikana 37:sta munuaissiirron saaneesta potilaasta 27:lle sekä 13 dialyysipotilaalle tehtiin uusintaluubiopsia. Kiihtynyttä luun aineenvaihduntaa sairastavien potilaiden osuus väheni munuaissiirtopotilailla 63 %-->19 % ja dialyysipotilailla 69 %--> 31 %. Munuaissiirtopotilailla epänormaalin luuston mineralisaation osuus lisääntyi hieman, kun taas dialyysipotilailla epänormaali mineralisaatio hieman korjaantui. Matalan hohkaluun tilavuuden osuus ei juurikaan muuttunut munuaissiirtopotilailla, mutta dialyysipotilailla matala luun tilavuus yleistyi. Luuntiheysmittaus reisiluun kaulassa korreloi luun tilavuuteen dialyysipotilailla, mutta seurantatutkimuksessa luuntiheysmittauksen ja matalan hohkaluutilavuuden välillä ei havaittu yhteyttä. Luun aineenvaihduntaa kuvaavat laboratorioparametrit eivät korreloineet biopsialöydöksiin dialyysi- tai munuaissiirtopotilailla.
Osatyössä III kiihtynyt luun aineenvaihdunta varmistui 70 %:lla biopsoiduista potilaista. Kolmeen muuttujaan (alkalinen fosfataasi, logaritminen lisäkilpirauhashormoni ja ionisoitu kalsium) perustuva logistinen regressioanalyysi tunnisti kiihtyneen luun aineenvaihdunnan varsin luotettavasti.
Neljännessä osatyössä luun hohkaluutilavuus oli alentunut 43 %:lla munuaissiirtopotilaista. Seuranta-aikana (mediaani 9.1, vaihteluväli 6.3–12.1 vuotta) 23 (21 %) munuaissiirtopotilaalla ilmeni yhteensä 37 murtumaa, mikä vastasi ilmaantuvuutta 15 murtumaa/1000 potilasvuotta. Vaikka hohkaluutilavuus korreloi lannerangan luuntiheysmittaukseen, luuntiheysmittaus tai hohkaluutilavuus eivät korreloineet murtumien ilmaantuvuuteen. Luunmurtumien ja hohkaluun tilavuuden välisen yhteyden puuttuminen viittaa luun mikroarkkitehtuurin ja kortikaalisen luun merkittävään asemaan munuaissiirtopotilaiden luunmurtumissa.ei saavutettav
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Variations on the Author
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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