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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
Clinical and experimental studies on the pathogenesis and the rol of bile salts
No full textChapter 1 provides a short introduction and the outline of this thesis. The aim of
the thesis was to identify clinical risk factors for non-anastomotic strictures (NAS),
by analyzing donor and patient characteristics, as well as surgical variables in relation
to postoperative outcome after orthotopic liver transplantation (OLT). Furthermore,
we have performed clinical studies and experimental studies in mice to unravel the
role of bile salt toxicity in the pathogenesis of hepatobiliary injury after OLT. The
thesis is divided in two parts.
The first part focuses on the clinical risk factors for the
development of NAS and in the second the part we investigate the role of toxic bile salts
and bile secretory function in the development of hepatobiliary injury after OLT.
Part I. Non-anastomotic biliary strictures after liver
transplantation
Chapter 2 provides an overview of the literature regarding the causes and consequences
of NAS, also called ischemic-type biliary lesions (ITBL). The aim of this chapter is to
describe the pathophysiological mechanisms, clinical presentation and the treatment
of NAS. NAS is a radiological diagnosis, characterized by intrahepatic strictures and
dilatations on cholangiography. NAS were first described after liver transplantation in
association with hepatic artery thrombosis (HAT). In case of early HAT the bile duct
becomes ischemic; resulting in a typical cholangiographic picture of biliary strictures,
dilatations and intraductal cast formation. However, these abnormalities can also be
seen in the absence of HAT, hence the term ischemic-type biliary lesions emerged. In
this thesis the term NAS was used to describe intrahepatic biliary strictures and dilations
of the bile duct in patients without HAT. The incidence of NAS varies around 15% in
different series reported in literature. Various risk factors for NAS have been identified,
strongly suggesting a multifactorial origin. The main categories include ischemia-related
injury, immune-mediated injury and toxic injury by bile salts. Nevertheless, in many
cases no specific risk factor can be identified. The clinical presentation of patients with
NAS is often not specific. Symptoms may include fever, abdominal complaints and
increased cholestatic liver function tests. The diagnosis is made by imaging studies of
the bile ducts. Treatment starts with relieving symptoms of cholestasis and dilation
of stenosed bile ducts via endoscopic retrograde cholangiopancreaticography (ERCP)
or percutaneous transhepatic cholangiodrainage (PTCD), if possible followed by
stenting. Eventually up to 50% of the patients with NAS may require retransplantation
or may die. In selected cases, retransplantation can be avoided or delayed by surgical
intervention.
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In the clinical study described in chapter 3 we aimed to determine whether Roux-Y
choledochojejunostomy is an independent risk factor for NAS after transplantation. A
total of 486 adult liver transplant recipients, transplanted between May 1992 and June
2006 with a median postoperative follow-up of 5.6 years, were included in this study.
One- and 5-year patient survival rates were 85.4 and 77.2%, respectively. Graft survival
rates at 1- and 5-years were 80.2% and 69.1%, respectively. NAS was observed in 80
of the 486 (16.5%) transplanted livers at a median time interval of 4.1 months after
OLT. A total of 18 potential risk factors for NAS were studied by comparing the group
of patients with NAS with those who did not develop NAS. Risk factors were grouped
as donor or recipient-related variables, surgical variables and postoperative outcome
variables. A univariate comparison of these demographic and clinical variables between
patients with and without NAS indicated primary sclerosing cholangitis (PSC), the
type of bile duct reconstruction and postoperative cytomegalovirus (CMV) infection as
risk factors for NAS. In patients who were transplanted for PSC, the incidence of NAS
was two-fold higher than in patients transplanted for other indications. In addition,
NAS were observed significantly more frequent when Roux-Y choledochojejunostomy
was used for biliary reconstruction, compared to patients with a duct-to-duct biliary
reconstruction. However, after multivariate regression analysis, including variables
previously reported in literature as important risk factors for the development of NAS,
Roux-Y choledochojejunostomy was not identified as independent risk factor for NAS.
Based on the results of this study, it was concluded that the association between Roux-Y
choledochojejunostomy and NAS that has been observed in previous studies can be
explained entirely by the more frequent use of Roux-Y reconstruction in patients with
PSC. Bacterial migration and (recurrent) ascending cholangitis as can be seen more
frequently in patients with a Roux-Y reconstruction, apparently do not play a role in the
pathogenesis of NAS after transplantation.
In chapter 4, outcome after transplantation is compared for livers from brain death
(DBD) or cardiac death (DCD) donors performed in The Netherlands between January
2001 and December 2006. Of a total of 526 transplant procedures performed in this
time period, in 55 cases a liver from a DCD donor was used and in 471 cases a liver
from a DBD donor was used. A national protocol was introduced for multiorgan
donation (MOD) of organs from controlled DCD donors. All three participating
Dutch liver transplant centers agreed to allocate livers from DCD donors according
159
to the national waiting list. There were no significant differences in the overall 1- and
3-year patient survival rates after DCD and DBD liver transplantation (84.6% versus
80.4%, and 86.3% versus 80.8%, respectively). Overall 1- and 3- year graft survival did
also not differ between DCD and DBD liver transplantation (74.0% versus 67.9%, and
80.5% versus 74.7%, respectively), although significant differences in the rate of graft
loss were observed between centers. NAS was observed significantly more frequently
after DCD liver transplantation (23.6% versus 7.9%, DCD versus DBD, respectively),
requiring significantly more retransplantations (10.9% versus 2.5%, DCD versus
DBD). Risk factors for graft loss and NAS were grouped as donor and recipients related
variables, surgical, and postoperative outcome variables. Multivariate regression analysis
revealed transplant center, first warm ischemic and cold ischemic time as independent
risk factors for 1-year graft survival in DCD liver transplantation. In a multivariate
regression analysis the following independent risk factors for NAS were identified:
DCD liver grafts, donor age, and PSC.
Part II . The role of bile salts in the pathogenesis of
hepatobiliary injury after liver transplantation
In chapter 5 we investigated the role of endogenous bile salts in the origin of bile duct
injury after OLT in a mouse model of arterialized liver transplantation. Previously,
Geuken et al. suggested that an increased biliary bile salt/phospholipid ratio early after
OLT, leading to toxic bile composition, may result in increased intrahepatic bile duct
injury (1). However, formal evidence for a cause-effect relationship between toxic bile
formation and bile duct injury after OLT could not be established by this observational
clinical study. In fact, it could not be ruled out that toxic bile composition and bile
duct injury both resulted from the same underlying factor. By comparing outcome after
transplantation of livers from wild-type mice or mice heterozygous for the disruption of
the Mdr2 gene (Mdr2+/-), we demonstrated that endogenous bile salts act synergistically
to ischemia/reperfusion in the origin of bile duct injury. This study provided evidence
that bile salt toxicity is an important factor that may contribute to hepatobiliary injury
after OLT.
In chapter 6 the involvement of bile secretory function in the pathogenesis of
hepatobiliary injury after the occurrence of HAT was investigated. In contrast to the
liver parenchyma, the bile ducts have a single blood supply that comes entirely from
160
the hepatic artery. HAT is a well known risk factor for the development of ischemic
bile duct strictures after OLT. Although ischemic injury of the bile ducts is a key
mechanism, it was unknown whether changes in bile composition may contribute
to the development of biliary injury in this situation as well. Previous studies have
indicated that hepatic arterial blood flow is critical for the recovery of hepatocyte
bile secretory function after OLT (2). In the absence of bile secretion, bile salts can
accumulate and act cytotoxic on hepatocytes and cholangiocytes. To study whether
changes in bile secretion could play a role in the pathogenesis of hepatobiliary injury
in the event of HAT, we developed a mouse model of impaired arterial perfusion
of the liver induced by ligation of either the hepatic artery or the peribiliary plexus,
or a combination of the two. Ligation of either the hepatic artery or the peribiliary
plexus did not result in marked histological, biochemical or molecular changes. This
means that the hepatic artery and peribiliary plexus both have the capacity to provide
sufficient blood supply to the biliary tree in this model. The combination of hepatic
artery ligation and interruption of the peribiliary plexus (complete loss of arterial
blood supply to the liver), however, resulted in severe injury of the bile ducts and liver
parenchyma, with two out of five animals dying after 14 days. As early as 24 hours
after complete dearterialization, in the absence of hepatobiliary injury, liver ATP-levels
were significantly decreased, and gene expression for the bile salt transporter Ntcp
and Bsep decreased and serum conjugated bile salt levels increased, subsequently.
Pro-inflammatory cytokine release was slowly induced and intrahepatic cholestasis
progressed in the following weeks. This study demonstrated that the expression of
hepatobiliary transporters is dysregulated early after complete loss of arterial blood
supply to the liver, leading to intrahepatic cholestasis and bile salt-mediated injury.
These data suggest that hepatobiliary injury frequently seen when HAT occurs after
OLT, may not only be due to a direct ischemic injury, but is also related to bile saltmediated
injury.
The study described in chapter 7 provides new insights in the role of cholangiocyte
bile salt transporters in biliary injury after OLT in mice. Cholangiocytes express various
bile salt transporters such as Asbt and heteromeric Ost-alpha/beta, responsible for the
uptake and secretion of bile salts, respectively. We analyzed gene and protein expression
for these transporters in our previously established mouse OLT model. To determine
the impact of biliary bile salts and the bile salt/phospholipid ratio on the expression
161
of these transporters, we compared livers transplanted from Mdr2+/- mice with livers
from wild-type donors. Since changes in cholangiocyte transporter expression are
associated with hepatic pro-inflammatory cytokine release, we also assessed the hepatic
expression for TNF-alpha and IL1-beta in the donor livers and correlated this with the
expression levels of the cholangiocyte transporters. Transplantation of Mdr2+/- livers
resulted in down-regulation of mRNA expression for Asbt, Ost-beta and Ost-alpha
after OLT. Asbt expression appeared to be regulated in direct proportion to the biliary
bile salt/phospholipid ratio, whereas Ost-alpha/beta expression correlated negatively
with the expression for TNF-alpha and IL1-beta. The unbalanced reduction of Asbt
and Ost-alpha/beta expression after OLT therefore, may result in bile salt retention in
cholangiocytes, cytotoxicity and aggravate bile duct injury.
In chapter 8 we have examined changes in the expression of cholangiocyte bile
transporters and the cholehepatic shunt in patients after OLT in humans. Expression
of ASBT, OST-alpha/beta and CFTR was determined in liver transplant biopsies and
levels of expression were correlated with biliary bile salt secretion and the development
of microscopic bile duct injury at one week after transplantation. OST-alpha transcript
levels were significantly down-regulated at the end of cold storage and immediately
after graft reperfusion, but levels had restored to normal values at one week after OLT.
OST-beta mRNA expression was more than 8-fold up-regulated at the end of cold
preservation and after graft reperfusion and increased further during the first week after
OLT. Overall the immunofluorescence staining pattern of these two transporters was
similar. The observed changes in the expression of the bile salt transporters OST-alpha
and OST-beta correlate with biliary bile salt secretion, but not with the degree of bile
duct injury. Although increased uptake of bile salts through cholangiocytes has been
linked with an increased expression for CFTR, we found no major changes in CFTR
mRNA expression. Altogether, these data suggest that the cholehepatic shunt does not
play a major role in the development of bile salt induced bile duct injury after OLT.
162
Collectively, the studies described in Part II of this thesis indicate that bile salt toxicity
and intrahepatic cholestasis are key events contributing to hepatobiliary injury after
OLT. Therapeutic strategies to prevent hepatobiliary injury after OLT therefore
should focus on options to alter bile composition and to maintain choleresis. Drugs
that could potentially reduce this type of injury should target at bile composition and
the affected bile duct epithelium itself, and ideally should also have anti-cholestatic,
anti-inflammatory and anti-fibrotic properties. Ursodeoxycholic acid (UDCA) is
known to improve cholestatic disorders and is widely used in the treatment of patients
with cholestatic liver diseases. Several mechanisms may potentially contribute to the
beneficial effect of UDCA after human OLT. Under cholestatic conditions, UDCA
stimulates hepatocyte secretion of bile salts, inhibits bile salt induced hepatocyte (and
cholangiocyte) apoptosis, protects injured cholangiocytes against the toxic effects of
endogenous bile salts, and/or stimulates Cl- and HCO3- secretion into bile via CFTR
(3). In contrast to UDCA, its side chain-shortened homologue nor-UDCA undergoes
cholehepatic shunting leading to a bicarbonate-rich hypercholeresis. Nor-UDCA has
anti-inflammatory, anti-proliferative and anti-fibrotic effects, and stimulates bile salt
detoxification. This drug may be potentially of benefit in patients undergoing OLT and
may reduce the incidence and severity of biliary injury leading to NAS. Finally, drugs
that can affect biliary phospholipid and bile salt excretion via nuclear receptors (FXR,
PPAR-alpha) could theoretically be of benefit as a prophylactic approach to prevent
bile salt-induced biliary injury after OLT. Time has come to design and initiate clinical
studies. An attractive fist option to study will be the potential benefits of UDCA or nor-
UDCA in liver transplant recipients. Since NAS is frequently observed after DCD liver
transplantation, this category of patients could be an attractive focus for future research.
The efficacy of UDCA or nor-UDCA should ideally be evaluated in a large-scale
multicenter placebo-controlled randomized trial in DCD liver transplant recipients.
Initiatives for such a multicenter study have recently been taken.
163
References
1. Geuken E, Visser D, Kuipers F, Blokzijl H, Leuvenink HG, de Jong KP, Peeters
PM, et al. Rapid increase of bile salt secretion is associated with bile duct injury
after human liver transplantation. J Hepatol 2004;41:1017-1025.
2. Wheatley AM. Hepatic artery and post-transplantation hemodynamics and
function. Am J Transplant 2004;4:290; author reply 291.
3. Beuers U. Drug insight: Mechanisms and sites of action of ursodeoxycholic acid
in cholestasis. Nat Clin Pract Gastroenterol Hepatol 2006;3:318-328.
164status: Publishe
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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