bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcome of patients with major bleeding after venous thromboembolism
Authors: Nieto José , Camara Timoteo , Gonzalez-Higueras Elena , Ruiz-Gimenez Nuria , Guijarro Ricardo , Marchena Pablo , Monreal Manuel ,   for the RIETE Investigators
Published: October 2008

The natural history of patients with venous thromboembolism (VTE) who develop a major bleeding complication while on anticoagulant therapy is not well known. RIETE is a prospective registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. The clinical characteristics, treatment decisions and outcome of all VTE patients who had major bleeding during the first three months of anticoagulant therapy were retrospectively studied. As of January 2007, 17,368 patients were included in RIETE. Of these, 407 (2.3%) had major bleeding during the study period: 144 gastrointestinal, 119 haematoma, 51 intracranial, 43 genitourinary, 50 other. In 286 (69%) patients anticoagulant therapy was discontinued, in 74 (18%) not modified, in 38 (9.1%) a vena cava filter was inserted. During the first 30 days after bleeding, 24 (5.9%) patients re-bled, 20 (4.9%) had recurrent VTE, 133 (33%) died. Of these, 75 died of bleeding, 12 of recurrent pulmonary embolism. Most deaths occurred shortly after the bleeding episode (median:1 day).On multivariate analysis, insertion of a vena cava filter was the only variable independently associated with a lower incidence of fatal bleeding (odds ratio [OR]: 0.10; 95% confidence interval [CI]: 0.01–0.79) and all-cause mortality (OR: 0.21; 95%CI: 0.07–0.63). In conclusion, the occurrence of major bleeding in patients with VTE is outstanding in terms of overall mortality (33% within 30 days), fatal bleeding (18%) or re-bleeding (5.9%). However, these patients also have an increased incidence of recurrent VTE (4.9%) and fatal pulmonary embolism (1.2%).
High-Density Lipoproteins Affect Endothelial BMP-Signaling by Modulating Expression of the Activin-Like Kinase Receptor 1 and 2
Authors: Yao Yucheng , Shao Esther S. , Jumabay Medet , Shahbazian Ani , Ji Sheng , Boström Kristina I.
Published: October 2008

Objective—

High-density lipoproteins (HDL) have antiinflammatory effects on the vascular endothelium. Because bone morphogenetic proteins (BMPs) are known to be inflammatory mediators, we examined the effect of HDL on BMP signaling.

Methods and Results—

Increasing concentrations of HDL progressively enhanced expression of the activin-like kinase receptor (ALK)1 and ALK2 in human aortic endothelial cells as determined by real-time polymerase chain reaction and immunoblotting. Induction of ALK1 was a result of enhanced ALK2 expression as determined by siRNA interference, and was associated with increased levels of vascular endothelial growth factor (VEGF) and matrix Gla protein (MGP). The HDL-induction of ALK2 was dependent on BMP-signaling, and affected coregulation of the ALK2 gene by the homeodomain proteins MSX2, DLX3, and DLX5, as determined by reporter gene assays, siRNA interference, and chromatin immunoprecipitation. Apolipoprotein A-I transgenic mice, known to have high HDL and inhibition of atherogenesis, exhibited similar changes in aortic gene expression as seen in endothelial cells treated with HDL in vitro.

Conclusions—

We conclude that HDL benefits the arterial wall by allowing for enhanced ALK1 and ALK2 signaling, resulting in an increase of VEGF and MGP, essential for endothelial cell survival and prevention of vascular calcification, respectively.
Role of Junctional Adhesion Molecule-Like Protein in Mediating Monocyte Transendothelial Migration
Authors: Guo Ya-Lan , Bai Rui , Chen Celia X-J , Liu Dan-Qing , Liu Yuan , Zhang Chen-Yu , Zen Ke
Published: October 2008

Objective—

Monocyte migration across the vascular endothelium of blood vessels is a key early event in atherosclerosis. The mechanisms underlying monocyte transendothelial migration (TEM), however, are still not completely understood. Here we studied the role of junctional adhesion molecule-like protein (JAML) in regulating monocyte TEM.

Methods and Results—

Firstly, by Western blot and flow cytometry, we showed that JAML was strongly expressed in monocytes and monocyte surface expression of JAML was upregulated by monocyte chemotaxis protein-1 stimulation. Both monocyte adhesion to and migration across tumor necrosis factor-α (TNFα) preactivated human microvascular endothelial cell (HMEC-1) monolayers were dose-dependently reduced by anti-JAML antiserum or soluble extracellular JAML recombinant. Secondly, short-term exposure of human monocytes and THP-1 cells to advanced glycation end products increased cell surface JAML expression, which was correlated with enhanced cell adhesion and TEM. In contrast, knockdown of JAML in THP-1 monocytes decreased both adhesion and transmigration of THP-1 monocytes. Finally, direct binding assay of the soluble JAML to HMEC-1 monolayers suggested that endothelial coxsackie and adenovirus receptor (CAR) may serve as one of the ligands for JAML.

Conclusions—

Monocytic JAML plays a critical role in regulating monocyte TEM probably via binding to the endothelial CAR and other tight junction–associated adhesive molecules.
Genetic Modifier Loci Linked to Intima Formation Induced by Low Flow in the Mouse Carotid
Authors: Korshunov Vyacheslav A. , Berk Bradford C.
Published: October 2008

Objective—

Previously we found dramatic strain-dependent differences in a low flow model of vascular remodeling. Specifically, intima formation in the left common carotid artery was ≈30-fold greater in SJL compared to C3HeB/Fe (C3H/F) mice. We hypothesized that a few genes control intima formation in response to low flow. A C3H/F and SJL backcross resulted in broad range of N2 intima phenotypes.

Methods and Results—

Using genome-wide scan we identified two highly significant quantitative trait loci (QTLs) for intima,
Im1
(
i
ntima
m
odifier
1
locus) on chromosome 2 (Chr2; 77.6 cM, LOD=6.4), and
Im2
on Chr11 (17 cM, LOD=5.3). One significant QTL
Im3
was found on Chr18 (6 cM, LOD=3.0), and two suggestive QTLs (LOD=1.5 and 1.8) were identified on Chr7 and Chr17, respectively. Interestingly, the intima/media ratio trait mapped to the same QTLs as the intima trait. Haplotype mapping predicted 40 candidate genes. Six of these genes contained SNPs that differed between C3H/F and SJL.

Conclusions—

We have successfully mapped 3 QTLs (
Im1
,
Im2
, and
Im3
) that are associated with carotid intima formation in response to low blood flow. These results may be important in identifying genes that influence carotid intima-media thickening and predict cardiovascular disease in humans.
Homozygous Missense N629D hERG (KCNH2) Potassium Channel Mutation Causes Developmental Defects in the Right Ventricle and Its Outflow Tract and Embryonic Lethality
Authors: Teng Guo Qi , Zhao Xian , Lees-Miller James P. , Quinn F. Russell , Li Pin , Rancourt Derrick E. , London Barry , Cross James C. , Duff Henry J.
Published: October 2008

Loss-of-function mutations in the human ERG1 potassium channel (hERG1) frequently underlie the long QT2 (LQT2) syndrome. The role of the ERG potassium channel in cardiac development was elaborated in an in vivo model of a homozygous, loss-of-function LQT2 syndrome mutation. The hERG N629D mutation was introduced into the orthologous mouse gene, mERG, by homologous recombination in mouse embryonic stem cells. Intact homozygous embryos showed abrupt cessation of the heart beat. N629D/N629D embryos die in utero by embryonic day 11.5. Their developmental defects include altered looping architecture, poorly developed bulbus cordis, and distorted aortic sac and branchial arches. N629D/N629D myocytes from embryonic day 9.5 embryos manifested complete loss of
I
Kr
function, depolarized resting potential, prolonged action potential duration (LQT), failure to repolarize, and propensity to oscillatory arrhythmias. N629D/N629D myocytes manifest calcium oscillations and increased sarcoplasmic reticulum Ca
+2
content. Although the N629D/N629D protein is synthesized, it is mainly located intracellularly, whereas +/+ mERG protein is mainly in plasmalemma. N629D/N629D embryos show robust apoptosis in craniofacial regions, particularly in the first branchial arch and, to a lesser extent, in the cardiac outflow tract. Because deletion of Hand2 produces apoptosis, in similar regions and with a similar final developmental phenotype, Hand2 expression was evaluated. Robust decrease in Hand2 expression was observed in the secondary heart field in N629D/N629D embryos. In conclusion, loss of
I
Kr
function in N629D/N629D cardiovascular system leads to defects in cardiac ontogeny in the first branchial arch, outflow tract, and the right ventricle.
Heat Shock Protein 20 Interacting With Phosphorylated Akt Reduces Doxorubicin-Triggered Oxidative Stress and Cardiotoxicity
Authors: Fan Guo-Chang , Zhou Xiaoyang , Wang Xiaohong , Song Guojie , Qian Jiang , Nicolaou Persoulla , Chen Guoli , Ren Xiaoping , Kranias Evangelia G.
Published: October 2008

Doxorubicin (DOX) is a widely used antitumor drug, but its application is limited because of its cardiotoxic side effects. Heat shock protein (Hsp)20 has been recently shown to protect cardiomyocytes against apoptosis, induced by ischemia/reperfusion injury or by prolonged β-agonist stimulation. However, it is not clear whether Hsp20 would exert similar protective effects against DOX-induced cardiac injury. Actually, DOX treatment was associated with downregulation of Hsp20 in the heart. To elucidate the role of Hsp20 in DOX-triggered cardiac toxicity, Hsp20 was first overexpressed ex vivo by adenovirus-mediated gene delivery. Increased Hsp20 levels conferred higher resistance to DOX-induced cell death, compared to green fluorescent protein control. Furthermore, cardiac-specific overexpression of Hsp20 in vivo significantly ameliorated acute DOX-triggered cardiomyocyte apoptosis and animal mortality. Hsp20 transgenic mice also showed improved cardiac function and prolonged survival after chronic administration of DOX. The mechanisms underlying these beneficial effects were associated with preserved Akt phosphorylation/activity and attenuation of DOX-induced oxidative stress. Coimmunoprecipitation studies revealed an interaction between Hsp20 and phosphorylated Akt. Accordingly, BAD phosphorylation was preserved, and cleaved caspase-3 was decreased in DOX-treated Hsp20 transgenic hearts, consistent with the antiapoptotic effects of Hsp20. Parallel ex vivo experiments showed that either infection with a dominant-negative Akt adenovirus or preincubation of cardiomyocytes with the phosphatidylinositol 3-kinase inhibitors significantly attenuated the protective effects of Hsp20. Taken together, our findings indicate that overexpression of Hsp20 inhibits DOX-triggered cardiac injury, and these beneficial effects appear to be dependent on Akt activation. Thus, Hsp20 may constitute a new therapeutic target in ameliorating the cardiotoxic effects of DOX treatment in cancer patients.
Mutation in EGFP Domain of LDL Receptor-Related Protein 6 Impairs Cellular LDL Clearance
Authors: Liu Wenzhong , Mani Sheida , Davis Nicole R. , Sarrafzadegan Nizal , Kavathas Paula B. , Mani Arya
Published: October 2008

Mutation in the EGFP domain of LDL receptor-related protein 6 (LRP6
R611C
) is associated with hypercholesterolemia and early-onset atherosclerosis, but the mechanism by which it causes disease is not known. Cholesterol uptake was examined in cells from LRP6
+/−
mice and LRP6
R611C
mutation carriers. Splenic B cells of LRP6
+/−
mice have significantly lower LRP6 expression and low-density lipoprotein (LDL) uptake than those of the wild-type littermates. Although similar levels of total LRP6 were found in lymphoblastoid cells (LCLs) of LRP6
R611C
mutation carriers and those of the unaffected family member, LDL uptake was significantly lower in the mutant cells. Mutant and wild-type receptors show similar affinities for apolipoprotein B at neutral pH. LRP6 colocalized with LDL and was coimmunoprecipitated with NPC1 (Niemann–Pick disease type C1), an endocytic regulator of LDL trafficking. However, the cellular localization of LRP6 in the mutant cells shifted from cell surface to late endosomes/lysosomes. Plasma membrane expression levels of LRP6
R611C
was lower compared to wild-type receptor and declined to a greater extent in LDL-rich medium. Further examinations revealed lower efficacy of apolipoprotein B dissociation from LRP6
R611C
compared to wild-type receptor at an acidic pH. These studies identify LRP6 as a receptor for LDL endocytosis and imply that R611C mutation results in reduced LRP6 membrane expression and decreased LDL clearance. Based on our findings, we conclude that the increased affinity of the mutant receptor for LDL in acidic pH leads to their impaired dissociation in late endosomes, which compromises their recycling to the plasma membrane.
IGF-1–Overexpressing Mesenchymal Stem Cells Accelerate Bone Marrow Stem Cell Mobilization via Paracrine Activation of SDF-1α/CXCR4 Signaling to Promote Myocardial Repair
Authors: Haider Husnain Kh , Jiang Shujia , Idris Niagara M. , Ashraf Muhammad
Published: October 2008

We hypothesized that mesenchymal stem cells (MSCs) overexpressing insulin-like growth factor (IGF)-1 showed improved survival and engraftment in the infarcted heart and promoted stem cell recruitment through paracrine release of stromal cell–derived factor (SDF)-1α. Rat bone marrow–derived MSCs were used as nontransduced (
Norm
MSCs) or transduced with adenoviral-null vector (
Null
MSCs) or vector encoding for IGF-1 (
IGF-1
MSCs).
IGF-1
MSCs secreted higher IGF-1 until 12 days of observation (
P
<0.001 versus
Null
MSCs). Molecular studies revealed activation of phosphoinositide 3-kinase, Akt, and Bcl.xL and inhibition of glycogen synthase kinase 3β besides release of SDF-1α in parallel with IGF-1 expression in
IGF-1
MSCs. For in vivo studies, 70 μL of DMEM without cells (group 1) or containing 1.5×10
6
Null
MSCs (group 2) or
IGF-1
MSCs (group 3) were implanted intramyocardially in a female rat model of permanent coronary artery occlusion. One week later, immunoblot on rat heart tissue (n=4 per group) showed elevated myocardial IGF-1 and phospho-Akt in group 3 and higher survival of
IGF-1
MSCs (
P
<0.06 versus
Null
MSCs) (n=6 per group). SDF-1α was increased in group 3 animal hearts (20-fold versus group 2), with massive mobilization and homing of ckit
+
, MDR1
+
, CD31
+
, and CD34
+
cells into the infarcted heart. Infarction size was significantly reduced in cell transplanted groups compared with the control. Confocal imaging after immunostaining for myosin heavy chain, actinin, connexin-43, and von Willebrand factor VIII showed extensive angiomyogenesis in the infarcted heart. Indices of left ventricular function, including ejection fraction and fractional shortening, were improved in group 3 as compared with group 1 (
P
<0.05). In conclusion, the strategy of IGF-1 transgene expression induced massive stem cell mobilization via SDF-1α signaling and culminated in extensive angiomyogenesis in the infarcted heart.
Glycemic Index, Retinal Vascular Caliber, and Stroke Mortality
Authors: Kaushik Shweta , Wang Jie Jin , Wong Tien Y. , Flood Victoria , Barclay Alan , Brand-Miller Jennie , Mitchell Paul
Published: October 2008

Background and Purpose—

It is unclear whether diets with high glycemic index (GI) and low cereal fiber (CF) are associated with greater risk of stroke. We aimed to assess the relationship between dietary GI and CF content, retinal microvasculature changes, and stroke-related mortality.

Methods—

The study consisted of a population-based cohort, 49+ years, examined at baseline (1992 to 1994). At baseline, participants completed validated food frequency questionnaires. Mean GI was calculated using an Australian database. Retinal arteriolar and venular diameters were measured from photographs. Mortality data were derived using the Australian National Death Index.

Results—

Over 13 years, 95 of 2897 participants (3.5%) died from stroke. Increasing GI (hazard ratio, 1.91; 95% CI, 1.01 to 3.47, highest versus lowest tertile) and decreasing CF (hazard ratio, 2.13; 95% CI, 1.19 to 3.80, lowest versus highest tertile) predicted greater risk of stroke death adjusting for multiple stroke risk factors. Persons consuming food in the highest GI tertile and lowest CF tertile had a 5-fold increased risk of stroke death (hazard ratio, 5.06; 95% CI, 1.67 to 15.22). Increasing GI and decreasing CF were also associated with retinal venular caliber widening (
P
trend
<0.01). Adjustment for retinal venular caliber attenuated stroke death risk associated with high GI by 50% but did not affect the risk associated with low CF consumption.

Conclusions—

High-GI and low-CF diets predict greater stroke mortality and wider retinal venular caliber. The association between a high-GI diet and stroke death was partly explained by GI effects on retinal venular caliber, suggesting that a high-GI diet may produce deleterious anatomic changes in the microvasculature.
Effect of Raloxifene on Stroke and Venous Thromboembolism According to Subgroups in Postmenopausal Women at Increased Risk of Coronary Heart Disease
Authors: Mosca Lori , Grady Deborah , Barrett-Connor Elizabeth , Collins Peter , Wenger Nanette , Abramson Beth L. , Paganini-Hill Annlia , Geiger Mary Jane , Dowsett Sherie A. , Amewou-Atisso Messan , Kornitzer Marcel
Published: October 2008

Background and Purpose—

Raloxifene, a selective estrogen receptor modulator, reduces risk of invasive breast cancer and osteoporosis, but the effect on risk for stroke and venous thromboembolism in different patient subgroups is not established. The purpose of this analysis was to evaluate the effect of raloxifene on the incidence of all strokes, stroke deaths, and venous thromboembolic events according to participant subgroups.

Methods—

This was a secondary end point analysis of an international, randomized, placebo-controlled clinical trial of 10 101 postmenopausal women with or at increased risk of coronary heart disease followed a median of 5.6 years. Strokes, venous thromboembolic events, and deaths were adjudicated by expert centralized committees. Strokes were categorized as ischemic, hemorrhagic, or undetermined and venous thromboembolic events were subclassified.

Results—

The incidences of all strokes did not differ between raloxifene (incidence rate per 100 woman-years=0.95) and placebo (incidence rate=0.86) treatment groups (
P
=0.30). In women assigned raloxifene versus placebo, there was a higher incidence of fatal strokes (incidence rates=0.22 and 0.15, respectively,
P
=0.0499) and venous thromboembolic events (incidence rates=0.39 and 0.27, respectively,
P
=0.02). No significant subgroup interactions were found except that there was a higher incidence of stroke associated with raloxifene use among current smokers.

Conclusions—

In postmenopausal women at increased risk for coronary events, the incidences of venous thromboembolism and fatal stroke but not all strokes were higher in those assigned raloxifene versus placebo. Raloxifene’s effect did not differ across subgroups, except that the risk of stroke differed by smoking status. Treatment decisions about raloxifene should be based on a balance of projected absolute risks and benefits.
C
linical- and
I
maging-Based
P
rediction of Stroke Risk After Transient Ischemic Attack
Authors: Ay Hakan , Arsava E. Murat , Johnston S. Claiborne , Vangel Mark , Schwamm Lee H. , Furie Karen L. , Koroshetz Walter J. , Sorensen A. Gregory
Published: October 2008

Background and Purpose—

Predictive instruments based on clinical features for early stroke risk after transient ischemic attack suffer from limited specificity. We sought to combine imaging and clinical features to improve predictions for 7-day stroke risk after transient ischemic attack.

Methods—

We studied 601 consecutive patients with transient ischemic attack who had MRI within 24 hours of symptom onset. A logistic regression model was developed using stroke within 7 days as the response criterion and diffusion-weighted imaging findings and dichotomized ABCD
2
score (ABCD
2
≥4) as covariates.

Results—

Subsequent stroke occurred in 25 patients (5.2%). Dichotomized ABCD
2
score and acute infarct on diffusion-weighted imaging were each independent predictors of stroke risk. The 7-day risk was 0.0% with no predictor, 2.0% with ABCD
2
score ≥4 alone, 4.9% with acute infarct on diffusion-weighted imaging alone, and 14.9% with both predictors (an automated calculator is available at http://cip.martinos.org). Adding imaging increased the area under the receiver operating characteristic curve from 0.66 (95% CI, 0.57 to 0.76) using the ABCD
2
score to 0.81 (95% CI, 0.74 to 0.88;
P
=0.003). The sensitivity of 80% on the receiver operating characteristic curve corresponded to a specificity of 73% for the CIP model and 47% for the ABCD
2
score.

Conclusions—

Combining acute imaging findings with clinical transient ischemic attack features causes a dramatic boost in the accuracy of predictions with clinical features alone for early risk of stroke after transient ischemic attack. If validated in relevant clinical settings, risk stratification by the CIP model may assist in early implementation of therapeutic measures and effective use of hospital resources.
Risk Factors for Perioperative Death and Stroke After Carotid Endarterectomy
Authors: Halm Ethan A. , Tuhrim Stanley , Wang Jason J. , Rockman Caron , Riles Thomas S. , Chassin Mark R.
Published: October 2008

Background and Purpose—

The benefit of carotid endarterectomy is heavily influenced by the risk of perioperative death or stroke. This study developed a multivariable model predicting the risk of death or stroke within 30 days of carotid endarterectomy.

Methods—

The New York Carotid Artery Surgery (NYCAS) Study is a population-based cohort of 9308 carotid endarterectomies performed on Medicare patients from January 1998 through June 1999 in New York State. Detailed clinical data were abstracted from medical charts to assess sociodemographic, neurological, and comorbidity risk factors. Deaths and strokes within 30 days of surgery were confirmed by physician overreading. Multivariable logistic regression was used to identify independent patient risk factors.

Results—

The 30-day rate of death or stroke was 2.71% among asymptomatic patients with no history of stroke/transient ischemic attack (TIA), 4.06% among asymptomatic ones with a distant history of stroke/TIA, 5.62% among those operated on for carotid TIA, 7.89% of those with stroke, and 13.33% in those with crescendo TIA/stroke-in-evolution. Significant multivariable predictors of death or stroke included: age ≥80 years (OR, 1.30; 95% CI, 1.03 to 1.64), nonwhite (OR, 1.83; 1.23 to 2.72), admission from the emergency department (OR, 1.95; 1.50 to 2.54), asymptomatic but distant history of stroke/TIA (OR, 1.40; 1.02 to 1.94), TIA as an indication for surgery (OR, 1.81; 1.39 to 2.36), stroke as the indication (OR, 2.40; 1.74 to 3.31), crescendo TIA/stroke-in-evolution (OR, 3.61; 1.15 to 11.28), contralateral carotid stenosis ≥50% (OR, 1.44; 1.15 to 1.79), severe disability (OR, 2.94; 1.91 to 4.50), coronary artery disease (OR, 1.51; 1.20 to 1.91), and diabetes on insulin (OR, 1.55; 1.10 to 2.18). Presence of a deep carotid ulcer was of borderline significance (OR, 2.08; 0.93 to 4.68).

Conclusions—

Several sociodemographic, neurological, and comorbidity risk factors predicted perioperative death or stroke after carotid endarterectomy. This information may help inform decisions about appropriate patient selection, assessments about the impact of different surgical processes of care on outcomes, and facilitate comparisons of risk-adjusted outcomes among providers.
Does Study Enrollment Delay Treatment With Intravenous Thrombolytics for Acute Ischemic Stroke?
Authors: Martin-Schild Sheryl , Albright Karen C. , Hallevi Hen , Barreto Andrew D. , Grotta James C. , Savitz Sean I.
Published: October 2008

Background and Purpose—

Enrollment in acute stroke trials at a stroke center with multiple study protocols may delay the initiation of intravenous thrombolytics in patients who present within 3 hours of symptom onset.

Methods—

We studied all patients presenting with acute ischemic stroke over the past 3.5 years who qualified for thrombolysis within 3 hours of symptom onset. We collected demographics, baseline National Institutes of Health Stroke Scale scores, CT findings, and arrival-to-treatment times and compared patients treated with intravenous thrombolytics in a clinical trial with patients who received standard of care intravenous tissue plasminogen activator.

Results—

Of 290 treated patients, 19 were enrolled in prelytic studies, 46 were enrolled in postlytic studies, and 225 were treated with standard intravenous tissue plasminogen activator. There was no significant difference in age, gender, National Institutes of Health Stroke Scale score, admission glucose, or changes on CT. There was no difference in onset-to-arrival time or arrival-to-treatment time between patients enrolled in clinical studies and those who received standard treatment. However, among study patients, prelytic randomization led to a significantly longer arrival-to-treatment time by 13 minutes (
P
=0.028).

Conclusion—

We found that trials requiring prethrombolytic randomization can lead to a delay in the initiation of treatment. Future studies are needed to determine if such a delay is clinically significant and can be shortened by improved enrollment strategies.
A hidden Markov model-based text classification of medical documents
Authors: Yi Kwan , Beheshti Jamshid
Published: October 2008

The purpose of the study is to test the application of the hidden Markov model (HMM) using prior knowledge in medical text classification (TC). HMM has been applied to a wide range of applications in information processing, but not so much in TC applications. The Medical Subject Heading (MeSH) is utilized for prior knowledge in the model. A prototype for an HMM-based TC model is designed, and an experimental model based on the prototype is implemented so as to categorize medical documents into MeSH. A subset of OHSUMED is used for the experiments. Our results show that the performance of our model is comparable to those reported in the literature.
Examining the dimensionality and measurement of user-perceived knowledge and information quality in the KMS context
Authors: Wang Yu-Min , Wang Yi-Shun
Published: October 2008

While several knowledge management systems' (KMS) success measures have been developed in previous studies, most of them focus on the measurement of knowledge use and performance of KMS. Little research has been conducted to develop specific instruments for measuring KMS success from the perspective of KMS knowledge production. Thus, the objective of this study was to develop an instrument for measuring user-perceived knowledge and information quality (KIQ) of KMS from the side of knowledge production. In this study, the characteristics of KMS were firstly analysed, and previous instruments for measuring information quality and KMS success then reviewed. Finally, an instrument for measuring the construct of KIQ in the KMS context was developed and validated in terms of its psychometric properties. The proposed instrument will be of value to researchers and practitioners interested in designing, implementing, researching, and managing KMS.
The knowledge pyramid: a critique of the DIKW hierarchy
Authors: Frické Martin
Published: October 2008

The paper evaluates the data—information—knowledge—wisdom (DIKW) hierarchy. This hierarchy, also known as the `knowledge hierarchy', is part of the canon of information science and management. Arguments are offered that the hierarchy is unsound and methodologically undesirable. The paper identifies a central logical error that DIKW makes. The paper also identifies the dated and unsatisfactory philosophical positions of operationalism and inductivism as the philosophical backdrop to the hierarchy. The paper concludes with a sketch of some positive theories, of value to information science, on the nature of the components of the hierarchy: that data is anything recordable in a semantically and pragmatically sound way, that information is what is known in other literature as `weak knowledge', that knowledge also is `weak knowledge' and that wisdom is the possession and use, if required, of wide practical knowledge, by an agent who appreciates the fallible nature of that knowledge.
Agricultural Information Sources Used by Farmers in Imo State, Nigeria
Authors: Opara Umunna Nnaemeka
Published: October 2008

This study investigated the sources of agricultural information available to farmers in Imo State, Nigeria as well as the farmers' preferred sources. The ex-post facto research design was used for the study. A stratified proportionate sampling technique was used to select a sample of 1386 farmers across the existing 34 farm blocks and 63 farm cells in the Agricultural Development Programme (ADP) zones of the state. A self-developed and validated structured questionnaire was used for data collection. Two research questions were formulated to find answers to the sources of agricultural information to the farmers as well as the sources they preferred. A reliability co-efficient of 0.83 was obtained for the instrument using the Crombach apha. Descriptive statistics were used to analyze the data. The results showed that 88.1 percent of the farmers indicated agricultural extension agents as their source of information, 71.2 percent indicated fellow farmers, 63.2 percent indicated radio, 43.3 percent indicated television, etc. The results further showed that majority (70.0 percent ) preferred the extension agent to the other media (radio 28.4 percent, friends and relatives 27.2 percent, television 19.1 percent, etc.) The results emphasize the need for the extension agency to regularly identify those sources of information that farmers prefer, or use most, as this will enable them deliver agricultural information effectively to the farmers.
Relationship between Records Management, Public Service Delivery and the Attainment of the United Nations Millennium Development Goals in Kenya
Authors: Kemoni Henry , Ngulube Patrick
Published: October 2008

The paper discusses the relationship between records management, public service delivery and the attainment of the United Nations (UN) Millennium Development Goals (MDGs) in Kenya. It defines the concept of records management and provides an overview of the current socio-political and economic environment in Kenya. The concept of public service delivery is defined, including the application of the concept in Kenya. The link between records management, public service delivery and the attainment of UN MDGs is explored. Recent research findings regarding current recordkeeping practices in the Kenyan public sector and their effect on service delivery and attainment of UN MDGs are presented. The paper concludes by positing that poor records management practices would have adverse consequences for public service delivery in Kenya and hamper the attainment of the UN MDGs. Thus, to achieve economic development in line with the UN MDGs, public offices need to have in place good recordkeeping systems.
Cost-Effectiveness of Rotavirus Vaccination: Exploring Caregiver(s) and ``No Medical Care'' Disease Impact in Belgium
Authors: Bilcke Joke , Van Damme Pierre , Beutels Philippe
Published: October 2008

Aim . To estimate the cost-effectiveness of universal childhood rotavirus vaccination in Belgium, taking into account the impact of caregiver burden and the burden of sick children for whom no medical care is sought (``no medical care''). Methods . A cohort of newborns is modeled in relation to costs and health outcomes for rotavirus disease, distinguishing episodes leading to consultations, hospitalizations, and deaths from no medical care episodes. Fully funded universal vaccination is compared with no vaccination as well as with the current situation in Belgium, whereby the 2-dose Rotarix or the 3-dose RotaTeq vaccine can be bought at market prices, which are partially reimbursed. Results . Compared with no vaccination, fully funded universal rotavirus vaccination would cost 51,030 per quality-adjusted life year (QALY) gained with Rotarix and 65,767 with RotaTeq (for society, 7572 and 30,227 per QALY, respectively). However, there is considerable uncertainty due to some analytical choices: the proportion of simulations with an acceptable incremental cost-effectiveness ratio (given a willingness to pay 50,000 for an additional QALY), increases from 2%/0.6% (Rotarix/RotaTeq) to 86%/59% when considering no medical care, and including 2 caregivers to estimate QALY loss instead of zero. Uncertainty is greater still under the societal than under the health care payer perspective. Conclusion . For the Belgian health care payer, at current vaccine prices, universal childhood rotavirus vaccination is unlikely to be judged cost-effective versus no vaccination but would be a more efficient and equitable choice than continuing with current practice.
Imaging of Central Nervous System Tumors in Children: Advances and Limitations
Authors: Vézina Louis-Gilbert
Published: October 2008

Magnetic resonance technology is continually improving. Functional imaging techniques such as magnetic resonance spectroscopy, perfusion imaging, diffusion imaging, and diffusion tensor imaging are increasingly used in the diagnosis and treatment of brain tumors in children. However, estimate of tumor size remains the primary imaging endpoint in the evaluation of response to treatment, and validation across institutions and vendor platforms of magnetic resonance imaging functional parameters is necessary given the relatively uncommon occurrence of brain tumors in children. Pediatric neuroimaging can be challenging, and the optimal way to image children with tumors of the central nervous system is not uniformly applied across all centers. Application of proper scanning techniques and validation of functional imaging techniques should lead to improved care of children with central nervous system tumors.
IGFBP2 Is Overexpressed by Pediatric Malignant Astrocytomas and Induces the Repair Enzyme DNA-PK
Authors: Becher Oren J. , Peterson Katia M. , Khatua Soumen , Santi Maria R. , MacDonald Tobey J.
Published: October 2008

To identify targets critical to malignant childhood astrocytoma, we compared the expression of receptor tyrosine kinase— associated genes between low-grade and high-grade pediatric astrocytomas. The highest differentially overexpressed gene in high-grade astrocytoma is insulin-like growth factor— binding protein-2 (P = .0006). Immunohistochemistry confirmed overexpression of insulin-like growth factor—binding protein-2 protein (P = .027). Insulin-like growth factor— binding protein-2 stimulation had no effect on astrocytoma cell growth and migration, and minimally inhibited insulin-like growth factor-1—mediated migration, but not insulin-like growth factor-2—mediated migration. However, insulin-like growth factor—binding protein-2 stimulation significantly upregulated the major DNA repair enzyme gene, DNA-PKcs, and induced DNA-dependent protein kinase catalytic subunit protein expression in a time-dependent and dose-dependent manner, whereas insulin-like growth factor-1 had no effect. DNA-PKcs is also highly overexpressed by high-grade astrocytomas. These findings suggest insulin-like growth factor—binding protein-2 plays a role in astrocytoma progression by promoting DNA-damage repair and therapeutic resistance.
Tumors of the Central Nervous System: Clinical Aspects, Molecular Mechanisms, Unanswered Questions, and Future Research Directions
Authors: Babcock Michael A. , Kostova Felina V. , Guha Abhijit , Packer Roger J. , Pollack Ian F. , Maria Bernard L.
Published: October 2008

Central nervous system tumors are the most common solid tumors in children. Many histological subtypes and biological variants exist. The 2007 Neurobiology of Disease in Children Symposium, held in conjunction with the 36th annual meeting of the Child Neurology Society, aimed to define current knowledge in the field and to develop specific aims for future clinical, translational, and fundamental science. Because of advances in structural and metabolic imaging, surgical technique, and combination therapies, the life expectancy of children with some of the most common tumors, such as cerebellar astrocytomas and medulloblastomas, has improved. Other common tumor types, including diffuse pontine gliomas and malignant embryonal tumors, still have a dismal prognosis. As novel therapies are identified for pediatric central nervous system tumors, long-term survival may be associated with considerable disability. A cooperative effort is crucial to early diagnosis and to translating basic research findings into safe, effective new treatments.
Initial Management of Childhood Brain Tumors: Neurosurgical Considerations
Authors: Nejat Farideh , El Khashab Mostafa , Rutka James T.
Published: October 2008

Intracranial tumors are the most common solid tumors in children. The infratentorial compartment will be the primary site for 60% to 70% of these tumors, including astrocytomas, medulloblastomas, and ependymomas. Several technological advancements have increased our knowledge of the cell biology of pediatric brain tumors, facilitated earlier diagnosis, and improved neurosurgical resections while minimizing neurological deficits. These in turn have not only improved the survival of children with brain tumors but also their quality of life. Current management strategies in most cases rely on surgery coupled with adjuvant therapies, including radiation therapy and chemotherapy. The vulnerability of the immature brain to adjuvant therapies creates many challenges for the treating physician. We review current diagnostic and therapeutic approaches and outcome for children harboring the most common pediatric brain tumors: astrocytomas (low-grade and high-grade glioma), ependymoma, medulloblastoma, and craniopharyngioma. The emphasis will be on the neurosurgical management of children with these tumors.
Aggressive Infantile Embryonal Tumors
Authors: MacDonald Tobey J.
Published: October 2008

Embryonal tumors are the most common brain tumors in infants less than 36 months. Histologically characterized as undifferentiated small, round cell tumors with divergent patterns of differentiation, these include medulloblastoma, the most common form of embryonal tumor, as well as supratentorial primitive neuroectodermal tumor, medulloepithelioma, ependymoblastoma, medullomyoblastoma, melanotic medulloblastoma, and atypical teratoid/rhabdoid tumor. All are similarly aggressive and have a tendency to disseminate throughout the central nervous system. Because of efforts to avoid craniospinal irradiation in an attempt to lessen treatment-related neurotoxicity, management of these tumors in infants is unique. Outcomes remain similarly poor among all the tumor types and, therefore, identification of specific molecular targets that have prognostic and therapeutic implications is crucial. The molecular and clinical aspects of the 3 most common aggressive infantile embryonal tumors, medulloblastoma, supratentorial primitive neuroectodermal tumor, and atypical teratoid/rhabdoid tumor, are the focus of this review.
Diagnostic and Therapeutic Stratification of Childhood Brain Tumors: Implications for Translational Research
Authors: Pollack Ian F.
Published: October 2008

Recent advances in the categorization of childhood brain tumors have improved risk-based treatment planning. In several instances, new therapeutic strategies that incorporate these advances have resulted in meaningful improvements in progression-free and overall survival. Current studies are directed at further refining therapy based on clinical, biological, and molecular data; testing the effectiveness of a number of novel therapeutic strategies for high-risk tumors; and examining approaches to reduce sequelae of treatment among more favorable-risk tumor subsets. Because multiple tumor subtypes are individually relatively uncommon, most such studies are being conducted by large co-operative groups, such as the Children's Oncology Group, or by smaller brain tumor-focused consortia, such as the Pediatric Brain Tumor Consortium.
Targeting Hyaluronan Interactions in Spinal Cord Astrocytomas and Diffuse Pontine Gliomas
Authors: Maria Bernard L. , Gupta Nalin , Gilg Anne G. , Abdel-Wahab May , Leonard Anthony P. , Slomiany Mark , Wheeler William G. , Tolliver Lauren B. , Babcock Michael A. , Lucas John T. , Toole Bryan P.
Published: October 2008

Although significant advances have been made in treating malignant pediatric central nervous system tumors such as medulloblastoma, no effective therapy exists for diffuse pontine glioma or intramedullary spinal astrocytoma. Biology of these 2 tumors is poorly understood, in part because diffuse pontine gliomas are not treated surgically, and tumor specimens from intramedullary spinal astrocytomas are rare and minuscule. At the 2007 Neurobiology of Disease in Children Symposium, we presented evidence that malignant glioma behaviors, including antiapoptosis, invasiveness, and treatment resistance, are enhanced by hyaluronan, an extracellular glycosaminoglycan. We review the clinical course of pediatric intramedullary spinal astrocytoma and diffuse pontine glioma, and show expression of membrane proteins that interact with hyaluronan: CD44, extracellular matrix metalloproteinase inducer, and breast cancer resistance protein (BCRP/ABCG2). Furthermore, we describe novel animal models of these tumors for preclinical studies. These findings suggest that hyaluronan antagonism has potential therapeutic value in malignant central nervous system tumors.
The Anticult Initiative and Hong Kong Christianity's Turn from Religious Privilege
Authors: Nedilsky Lida V.
Published: October 2008

Excluding others from membership tends to reveal the instability of anyone's terms of belonging in society. Hong Kong's Anticult Initiative of 2001 sought to establish the legal difference between cult and religion and to exclude some from the protections offered by freedom of religion. In the context of Hong Kong's own renegotiation of political authority with China this initiative prompted Protestant and Catholic leaders to reflect on the peculiarities of their own faith and reassess their position in a post-1997 polity. This article analyzes public discourse, both newspaper editorials and interviews, to document a turn in self-perception away from privilege and toward vulnerability. Now that Christians can imagine themselves, like the assumed target of the anticult initiative, Falun Gong, vulnerable to restrictions on their freedom of religion, they indicate an acceptance of their unstable position and an emerging willingness to take on new concerns and allies. In the face of exclusivity, liberal Christians manage a shift toward greater inclusiveness whose extent is yet uncharted.
Utilizing Satire in Post-Deng Chinese Politics
Authors: Gao Jia , Pugsley Peter C .
Published: October 2008

Although China's institutional campaign against the Falun Gong has been closely observed and analyzed, researchers have failed to take note of the subversive power of satire utilized in the comic theatrical skits ( xiaopin) of popular comedian Zhao Benshan to ridicule the Falun Gong. This exemplifies the Chinese Communist Party's long-established political practice of “educating the masses.” Based on an analysis of what are now commonly referred to as “Zhao Benshan xiaopin” and their perceived impact on the Falun Gong issue, this article examines how satirical power in post-Deng Chinese politics has been employed, and it outlines the key features of the practice. This article reviews the use of satire as a political weapon in contemporary Chinese politics, before turning to focus on four relevant Zhao Benshan xiaopin and the way in which they create popular metaphors for propagating official views in the anti-Falun Gong campaign.
Ensuring Cross-Cultural Equivalence in Translation of Research Consents and Clinical Documents
Authors: Lee Cheng-Chih , Li Denise , Arai Shoshana , Puntillo Kathleen
Published: October 2008

The aim of this article is to describe a formal process used to translate research study materials from English into traditional Chinese characters. This process may be useful for translating documents for use by both research participants and clinical patients. A modified Brislin model was used as the systematic translation process. Four bilingual translators were involved, and a Flaherty 3-point scale was used to evaluate the translated documents. The linguistic discrepancies that arise in the process of ensuring cross-cultural congruency or equivalency between the two languages are presented to promote the development of patient-accessible cross-cultural documents.
Recidivism Rates for Registered and Nonregistered Juvenile Sexual Offenders
Authors: Letourneau Elizabeth J. , Armstrong Kevin S.
Published: October 2008

The primary purpose of this study is to examine the effects of South Carolina's comprehensive registration policy on recidivism of juveniles who sexually offend. Registered and nonregistered male youth are matched on year of index offense, age at index offense, race, prior person offenses, prior nonperson offenses, and type of index sexual offense, for a total of 111 matched pairs. Recidivism is assessed across a mean 4.3-year follow-up ( SD = 2.5). The sexual offense reconviction rate is too low (2 events) to support between-group analyses. Cox regression results indicate no significant between-group differences with respect to new nonsexual person offense convictions but significant between-group differences with respect to new nonperson offense convictions. Specifically, registered youth are more likely than nonregistered youth to have new nonperson offense convictions across follow-up. Public policy implications of these findings are discussed.
Agency, Relatedness, Inner Peace, and Problem Solving in Sexual Offending
Authors: Barnett Georgia , Wood Jane L.
Published: October 2008

Untreated imprisoned sexual offenders ( N = 42) completed interviews and questionnaires to establish the priority they assigned, at the time of their offending, to three “goods” from the good lives model and to gain insight into how they operationalized these goods at that time. The relationship between the priorities offenders assigned to the goods of (a) agency, (b) relatedness, and (c) inner peace at the time of offending and their problem-solving ability was also explored. A measure of problem-solving ability was obtained with the Social Problem-Solving Inventory—Revised, and a measure of functional and dysfunctional problem solving was obtained from its scales. The results suggest that sexual offenders tend to experience problems in prioritizing, rather than operationalizing, inner peace, as this good is not related to problem-solving ability but tends to be assigned lower priority than agency and relatedness. Although agency and relatedness tend to be given higher importance, and this is related to better problem-solving ability, there appear to be problems with scope in some offenders' good lives conceptions and problems with the capacity, means, and conflict among the means used to achieve these goods. Directions for future research are suggested.