bluuebunny/crossref_metadata_2025 huggingface dataset:
Plant invaders and their novel natural enemies: who is naïve?
Authors: Verhoeven Koen J. F. , Biere Arjen , Harvey Jeffrey A. , Van Der Putten Wim H.
Published: October 2008

Introduced exotic species encounter a wide range of non‐coevolved enemies and competitors in their new range. Evolutionary novelty is a key aspect of these interactions, but who benefits from novelty: the exotic species or their new antagonists? Paradoxically, the novelty argument has been used to explain both the release from and the suppression by natural enemies. We argue that this paradox can be solved by considering underlying interaction mechanisms. Using plant defenses as a model, we argue that mismatches between plant and enemy interaction traits can enhance plant invasiveness in the case of toxin‐based defenses, whereas invasiveness is counteracted by mismatches in recognition‐based defenses and selective foraging of generalist herbivores on plants with rare toxins. We propose that a mechanistic understanding of ecological mismatches can help to explain and predict when evolutionary novelty will enhance or suppress exotic plant invasiveness. This knowledge may also enhance our understanding of plant abundance following range expansion, or during species replacements along successional stages.
Microbial diversity and activity through a permafrost/ground ice core profile from the Canadian high Arctic
Authors: Steven Blaire , Pollard Wayne H. , Greer Charles W. , Whyte Lyle G.
Published: October 2008

Culture‐dependent and culture‐independent methods were used in an investigation of the microbial diversity in a permafrost/massive ground ice core from the Canadian high Arctic. Denaturing gradient gel electrophoresis as well asBacteriaandArchaea16S rRNA gene clone libraries showed differences in the composition of the microbial communities in the distinct core horizons. Microbial diversity was similar in the active layer (surface) soil, permafrost table and permafrost horizons while the ground ice microbial community showed low diversity.BacteriaandArchaeasequences related to theActinobacteria(54%) andCrenarchaeota(100%) respectively were predominant in the active layer while the majority of sequences in the permafrost were related to theProteobacteria(57%) andEuryarchaeota(76%).The most abundant phyla in the ground ice clone libraries were theFirmicutes(59%) andCrenarchaeota(82%). Isolates from the permafrost were both less abundant and diverse than in the active layer soil, while no culturable cells were recovered from the ground ice. Mineralization of [1‐14C] acetic acid and [2‐14C] glucose was used to detect microbial activity in the different horizons in the core. Mineralization was detected at near ambient permafrost temperatures (−15°C), indicating that permafrost may harbour an active microbial population, while the low microbial diversity, abundance and activity in ground ice suggests a less hospitable microbial habitat.
Surveillance colonoscopy improves survival in a cohort of subjects with a single mismatch repair gene mutation
Authors: Stupart D. A. , Goldberg P. A. , Algar U. , Ramesar R.
Published: October 2008

Objective  Previous studies have shown a benefit for surveillance colonoscopy in heterogeneous groups of subjects with suspected or proven hereditary nonpolyposis colon cancer. The aim of this study was to investigate whether surveillance colonoscopy improves the survival in subjects who all carry a single mismatch repair gene defect.

Method  This is a prospective cohort study of 178 subjects who carry a mutation of the MLH1 gene in exon 13 (C1528T). They were offered surveillance colonoscopy between 1988 and 2006, and were followed up until September 2007.

Results  One hundred and twenty‐nine subjects underwent surveillance colonoscopy, and 49 declined. After a median follow up of 5 years, colorectal cancer was diagnosed in 14/129 (11%) subjects in the surveillance group and 13/49 (27%) in the nonsurveillance group (P = 0.019). Cancers in the surveillance group were at an earlier stage than in the nonsurveillance group (P = 0.032). Death from colorectal cancer occurred in three of 129 (2%) subjects in the surveillance group, and six of 49 (12%) in the nonsurveillance group (P = 0.021). The Kaplan–Meyer estimates for median survival from birth were 78 years in the surveillance group, and 55 years in the nonsurveillance group (P = 0.024). The Kaplan–Meyer estimates for median colorectal cancer‐free survival from birth were 73 years in the surveillance group and 47 years in the nonsurveillance group (P = 0.0089).

Conclusion  Surveillance colonoscopy was associated with improved overall and colorectal cancer‐related survival in subjects carrying a single mismatch repair gene mutation.
Subsidiary Strategy: The Embeddedness Component
Authors: Garcia‐Pont Carlos , Canales J. Ignacio , Noboa Fabrizio
Published: October 2008

abstract

This article develops the concept of internal subsidiary embeddedness as the canvas within which subsidiary strategy takes place. Developing an inductive model, we identify three hierarchical levels of embeddedness. The first level is operational embeddedness, which relates to interlocking day‐to‐day relations. The second level is capability embeddedness, which concerns the development of competitive capabilities for the multinational as a whole. The third level is strategic embeddedness, which concerns a subsidiary's participation in a multinational corporation's strategy setting. We derived our concept of embeddedness from an in‐depth case study. Embeddedness is not merely an outcome of the institutional setting in which a subsidiary is situated, but is a resource a subsidiary can manage by means of manipulating dependencies or exerting influence over the allocation of critical resources. A subsidiary can modify its embeddedness to change its strategic restraints. Therefore, the development of subsidiary embeddedness becomes an integral part of subsidiary strategy.
Measures for Dealing with Competence and Integrity Violations of Interorganizational Trust at the Corporate and Operating Levels of Organizational Hierarchy
Authors: Janowicz‐Panjaitan Martyna , Krishnan Rekha
Published: October 2008

abstract

We examine how partners in an interorganizational relationship can repair violated trust, and if that is impossible, how they can preserve the collaborative relationship. We also consider under what circumstances exit from the relationship is the only viable option. We propose that the effectiveness of legalistic and non‐legalistic measures in response to a trust violation is a function of the hierarchical level at which the violation occurred (corporate vs. operating), the character of the violation (competence vs. integrity), the frequency and severity with which it occurred, the organizational context in which boundary spanners are embedded, and the degree of dependence between the partners. Based on these factors, we explore how the way in which violation of trust is dealt with at one hierarchical level might affect trust at the other level. Our theoretical model reveals that prior findings on trust repair in inter‐personal context may not hold in the interorganizational context.
Managerial (In)attention to Competitive Threats
Authors: McMullen Jeffery S. , Shepherd Dean A. , Patzelt Holger
Published: October 2008

abstract

We integrate the Attention Based View of the firm and Regulatory Focus Theory to propose a model of managerial (in)attention that explains why appeals by middle managers for top managers to attend to specific threats of emerging rivals go unheeded. By acknowledging that different regulatory foci are elicited by different structural positions within the firm, we suggest that these differences in regulatory foci influence the allocation of attention to competitive intelligence warning of an emerging threat. We conclude by discussing how top managers might better evaluate whether threats of emerging rivals are worthy of deeper consideration.
Dietary Implications of Supermarket Development: A Global Perspective
Authors: Hawkes Corinna
Published: October 2008

Five decisions by supermarket operators have important dietary implications: the location of their outlets; the foods they sell; the prices they charge; the promotional strategies they use; and the nutrition‐related activities they implement. These decisions influence food accessibility, availability, prices and desirability, which in turn influence the decisions consumers make about food. Based on a comprehensive literature review, this article finds that the dietary implications are both positive – supermarkets can make a more diverse diet available and accessible to more people – and negative – supermarkets can reduce the ability of marginalised populations to purchase a high‐quality diet, and encourage the consumption of energy‐dense, nutrient‐poor highly‐processed foods. Overall, the most universally applicable dietary implication is that supermarkets encourage consumers to eat more, whatever the food.
Ontology‐based concept map for planning a personalised learning path
Authors: Chen Chih‐Ming
Published: October 2008

Developing personalised web‐based learning systems has been an important research issue in e‐learning because no fixed learning pathway will be appropriate for all learners. However, most current web‐based learning platforms with personalised curriculum sequencing tend to emphasise the learner preferences and interests in relation to personalised learning services but fail to consider the difficulty level of course materials, learning order of prior and posterior knowledge and learner abilities while constructing a personalised learning path. As a result, these ignored factors thus easily lead to the generation of poor quality learning paths. Generally, learners could generate cognitive overload or fall into cognitive disorientation owing to inappropriate curriculum sequencing during learning processes, thus, reducing the learning effect. With the advancement of artificial intelligence technologies, ontology technologies enable a linguistic infrastructure to represent conceptual relationships between course materials. Ontology can be served as a structured knowledge representation scheme, capable of assisting the construction of a personalised learning path. This study thus proposes a novel genetic‐based curriculum sequencing scheme based on a generated ontology‐based concept map, which can be automatically constructed by the pretest results of numerous learners, to plan appropriate learning paths for individual learners. The experimental results indicated that the proposed approach could create high‐quality learning paths for individual learners. The proposed approach thus can help learners to learn more effectively and to likely reduce learners' cognitive overloads during learning processes.
Svetovid—Interactive development and submission system with prevention of academic collusion in computer programming
Authors: Pribela Ivan , Ivanović Mirjana , Budimac Zoran
Published: October 2008

This paper discusses Svetovid, cross‐platform software that helps instructors to assess the amount of effort put into practical exercises and exams in courses related to computer programming. The software was developed as an attempt at solving problems associated with practical exercises and exams. This paper discusses the design and use of Svetovid system along with the advantages it brings to both students and instructors.
Use of three‐dimensional (3‐D) immersive virtual worlds in K‐12 and higher education settings: A review of the research
Authors: Hew Khe Foon , Cheung Wing Sum
Published: October 2008

In this paper, we review past empirical research studies on the use of three‐dimensional immersive virtual worlds in education settings such as K‐12 and higher education. Three questions guided our review: (1) How are virtual worlds (eg, Active Worlds, Second Life) used by students and teachers? (2) What types of research methods have been applied? (3) What research topics have been conducted on virtual worlds in teaching and learning, as well as their related findings? Overall, we found that virtual worlds may be utilised for the following uses: (1) communication spaces, (2) simulation of space (spatial), and (3) experiential spaces (‘acting’ on the world). Most of the studies reviewed were descriptive and conducted in polytechnic and university settings, and past virtual world research had been most frequently carried out in the media arts and health and environment disciplines. Three main research topics were found: participants' affective domain, learning outcomes and social interaction. We conclude by summarising some major findings and discussing three limitations of previous empirical studies. Several recommendations for future research related to virtual worlds in education settings are also provided.
Sure Independence Screening for Ultrahigh Dimensional Feature Space
Authors: Fan Jianqing , Lv Jinchi
Published: October 2008

Variable selection plays an important role in high dimensional statistical modelling which nowadays appears in many areas and is key to various scientific discoveries. For problems of large scale or dimensionality p, accuracy of estimation and computational cost are two top concerns. Recently, Candes and Tao have proposed the Dantzig selector using L1-regularization and showed that it achieves the ideal risk up to a logarithmic factor log(p). Their innovative procedure and remarkable result are challenged when the dimensionality is ultrahigh as the factor log(p) can be large and their uniform uncertainty principle can fail. Motivated by these concerns, we introduce the concept of sure screening and propose a sure screening method that is based on correlation learning, called sure independence screening, to reduce dimensionality from high to a moderate scale that is below the sample size. In a fairly general asymptotic framework, correlation learning is shown to have the sure screening property for even exponentially growing dimensionality. As a methodological extension, iterative sure independence screening is also proposed to enhance its finite sample performance. With dimension reduced accurately from high to below sample size, variable selection can be improved on both speed and accuracy, and can then be accomplished by a well-developed method such as smoothly clipped absolute deviation, the Dantzig selector, lasso or adaptive lasso. The connections between these penalized least squares methods are also elucidated.
The Cholinomimetic Agent Carbachol Induces Headache in Healthy Subjects
Authors: Schytz HW , Wieneckey T , Oturai PS , Olesen J , Ashina M
Published: October 2008

The parasympathetic nervous system is likely to be involved in migraine pathogenesis. We hypothesized that the cholinomimetic agonist carbachol would induce headache and vasodilation of cephalic and radial arteries. Carbachol (3 μg/kg) or placebo was randomly infused into 12 healthy subjects in a double-blind crossover study. Headache was scored on a verbal rating scale from 0–10. Velocity in the middle cerebral artery (Vmca) and diameter of the superficial temporal artery (STA) and radial artery (RA) were recorded. Nine participants developed headache after carbachol compared with three after placebo. The area under the curve for headache was increased after carbachol compared with placebo both during infusion (0–30 min) ( P = 0.042) and in the postinfusion period (30–90 min) ( P = 0.027). Carbachol infusion caused a drop in Vmca ( P = 0.003) and an increase in STA diameter ( P = 0.006), but no increase in the RA diameter ( P = 0.200). In conclusion, the study demonstrated that carbachol caused headache and dilation of cephalic arteries in healthy subjects.
Pre‐synaptic GABAB receptors inhibit glutamate release through GIRK channels in rat cerebral cortex
Authors: Ladera Carolina , Del Carmen Godino María , Cabañero María José , Torres Magdalena , Watanabe Masahiko , Luján Rafael , Sánchez‐Prieto José
Published: October 2008

Neuronal G protein‐gated inwardly rectifying potassium (GIRK) channels mediate the slow inhibitory effects of many neurotransmitters post‐synaptically. However, no evidence exists that supports that GIRK channels play any role in the inhibition of glutamate release by GABAB receptors. In this study, we show for the first time that GABAB receptors operate through two mechanisms in nerve terminals from the cerebral cortex. As shown previously, GABAB receptors reduces glutamate release and the Ca2+ influx mediated by N‐type Ca2+ channels in a mode insensitive to the GIRK channel blocker tertiapin‐Q and consistent with direct inhibition of this voltage‐gated Ca2+ channel. However, by means of weak stimulation protocols, we reveal that GABAB receptors also reduce glutamate release mediated by P/Q‐type Ca2+ channels, and that these responses are reversed by the GIRK channel blocker tertiapin‐Q. Consistent with the functional interaction between GABAB receptors and GIRK channels at nerve terminals we demonstrate by immunogold electron immunohistochemistry that pre‐synaptic boutons of asymmetric synapses co‐express GABAB receptors and GIRK channels, thus suggesting that the functional interaction of these two proteins, found at the post‐synaptic level, also occurs at glutamatergic nerve terminals.
Comparing Cost‐of‐Illness Estimates from Alternative Approaches: An Application to Diabetes
Authors: Honeycutt Amanda A. , Segel Joel E. , Hoerger Thomas J. , Finkelstein Eric A.
Published: October 2008

Objective. To compare disease cost estimates from two commonly used approaches.

Data Source. Pooled Medical Expenditure Panel Survey (MEPS) data for 1998–2003.

Study Design. We compared regression‐based (RB) and attributable fraction (AF) approaches for estimating disease‐attributable costs with an application to diabetes. The RB approach used results from econometric models of disease costs, while the AF approach used epidemiologic formulas for diabetes‐attributable fractions combined with the total costs for seven conditions that result from diabetes.

Data Extraction. We used SAS version 9.1 to create a dataset that combined data from six consecutive years of MEPS.

Principal Findings. The RB approach produced higher estimates of diabetes‐attributable medical spending ($52.9 billion in 2004 dollars) than the AF approach ($37.1 billion in 2004 dollars). RB model estimates may in part be higher because of the challenges of implementing the two approaches in a similar manner, but may also be higher because they capture the costs of increased treatment intensity for those with the disease.

Conclusions. We recommend using the RB approach for estimating disease costs whenever individual‐level data on health care spending are available and when the presence of the disease affects treatment costs for other conditions, as in the case of diabetes.
Hemicrania Continua Evolving From Cluster Headache Responsive to Valproic Acid
Authors: Lambru Giorgio , Castellini Paola , Bini Annamaria , Evangelista Andrea , Manzoni Gian Camillo , Torelli Paola
Published: October 2008

Hemicrania continua (HC) is a rare type of primary headache characterized by a prompt and enduring response to indomethacin. We describe a patient who suffered from cluster headache evolving into ipsilateral HC, who does not tolerate a long‐term indomethacin therapy. The case was complex in terms of diagnosis, associated comorbidity, and choice of treatment; after several trials with different therapeutic regimens, we started the patient on a therapy with valproic acid and obtained an improvement of her HC.
Refractory Migraine and Chronic Migraine: Pathophysiological Mechanisms
Authors: Goadsby Peter J. , Hargreaves Richard
Published: October 2008

Despite increased understanding of primary headaches and their treatment, the underlying causes of refractory migraine remain unknown. This note considers potential genetic, structural, functional and pharmacological factors that could contribute to this relatively intractable condition. Further understanding of refractory migraine will require the use of medical imaging technologies, clinical experimental medicine studies on novel pharmacological agents and astute observations in clinical practice to direct potential novel therapeutic approaches.
“Outside‐In” vs “Inside‐Out”: Revisiting Migraine's Vascular Hypothesis
Authors: Rothrock John F.
Published: October 2008

The neurovascular contribution to migraine biogenesis should not be overlooked in the rush to embrace a central “generator.”
The Neurogenic Basis of Migraine
Authors: Cutrer F. Michael , Charles Andrew
Published: October 2008

There is accumulating evidence of a neurogenic basis of migraine. This evidence arises from both the clinical and experimental domains. Many of the well known clinical features of migraine attacks including the prodrome are not explained by changes in vascular caliber. Despite the fact that ergotamines and triptans are vasoactive does not provide substantive proof that vasoconstriction is their most important mechanism of action. Several effective treatments for migraine, both old and new, do not affect vascular caliber. Experimental evidence from investigation of both the aura and headache phases of migraine clearly supports a neural basis of migraine. All genes thus far conclusively associated with hemiplegic migraine code for neural proteins.
Sodium, hypertension, and an explanation of the “lag phenomenon” in hemodialysis patients
Authors: TWARDOWSKI Zbylut J.
Published: October 2008

Sodium balance is precisely regulated by intake and output. The kidneys are responsible for adjusting sodium excretion to maintain balance at varying intakes. Our distant ancestors were herbivores. Their diet contained little sodium, so they developed powerful mechanisms for conserving sodium and achieving low urinary excretion. About 10,000 years ago, early humans became villagers and discovered that food could be preserved in brine. This led to increased consumption of salt. High salt intake increases extracellular volume (ECV), blood volume, and cardiac output resulting in elevation of blood pressure. High ECV induces release of a digitalis‐like immunoreactive substance and other inhibitors of Na+‐K+‐ATPase. As a consequence, intracellular sodium and calcium concentrations increase in vascular smooth muscles predisposing them to contraction. Moreover, high ECV increases synthesis and decreases clearance of asymmetrical dimethyl‐l‐arginine leading to inhibition of nitric oxide (NO) synthase. High concentration of sodium and calcium in vascular smooth muscles, and decreased synthesis of NO lead to an increase in total peripheral resistance. Restoration of normal ECV and blood pressure are attained by increased glomerular filtration and decreased sodium reabsorption. In some individuals, the kidneys have difficulty in excreting sodium, so the equilibrium is achieved at the expense of elevated blood pressure. There is some lag time between reduction of ECV and normalization of blood pressure because the normal levels of Na+‐K+‐ATPase inhibitors and asymmetrical dimethyl‐l‐arginine are restored slowly. In dialysis patients, all mechanisms intended to increase renal sodium removal are futile but they still operate and elevate blood pressure. The sodium balance must be achieved via dialysis and ultrafiltration. Blood pressure is normalized a few weeks after ECV is returned to normal, i.e., when the patient reaches dry body weight. This is called the “lag phenomenon.”
Fatal cerebritis and brain abscesses following a nontraumatic subdural hematoma in a chronic hemodialyzed patient
Authors: MESQUITA Maria , DAMRY Nasroolla , GAZAGNES Marie D.
Published: October 2008

Staphylococcus aureus is the leading cause of bacteremia in hemodialysis‐dependent patients that can lead to metastatic abscesses with poor outcome. We report a case of a 65‐year‐old chronic hemodialyzed male patient who developed cerebritis and brain abscesses complicating a spontaneous subdural hematoma, following Staphylococcus aureus bacteremia related to infected arteriovenous fistula. In spite of adequate antibiotherapy and several surgical brain drainages, our patient did not survive. Prevention of S. aureus is highly important in hemodialysis patients.
Heparin leak from a hemodialysis catheter causing major bleeding, ultimately leading to transplant rejection and death
Authors: DREYER Gavin , LAWTON Paul , JOSE Matthew
Published: October 2008

Leakage of hemodialysis catheter‐locking solutions into the circulation has been reported in in vitro and in vivo studies, although there have been few reports of serious clinical adverse events. We describe a case of heparin leak from a hemodialysis catheter, which caused significant clinical bleeding requiring multiple transfusions and may have ultimately been responsible for the patient's death after transplantation.
Cultural comparison of symptoms in patients on maintenance hemodialysis
Authors: WEISBORD Steven D. , BOSSOLA Maurizio , FRIED Linda F. , GIUNGI Stefania , TAZZA Luigi , PALEVSKY Paul M. , ARNOLD Robert M. , LUCIANI Giovanna , KIMMEL Paul L.
Published: October 2008

Although symptoms are common and frequently severe in patients on maintenance hemodialysis, little is known about the relationship between cultural background and symptom burden. The aim of this study was to explore differences in the prevalence and severity of symptoms between American and Italian hemodialysis patients. We administered the 30‐item Dialysis Symptom Index to American and Italian patients receiving maintenance hemodialysis during routine dialysis sessions. The prevalence and severity of individual symptoms were compared between patient populations, adjusting for multiple comparisons. Multivariable logistic regression and ordinal logistic regression were used to assess the independent associations of cultural background with the prevalence and severity of symptoms, respectively. We enrolled 75 American and 61 Italian patients. American patients were more likely to be black (36% vs. 0%, P<0.001) and diabetic (53% vs. 13%, P<0.001). Italian patients were more likely to report decreased interest in sex, decreased sexual arousal, feeling nervous, feeling irritable, and worrying (P<0.001, respectively). Adjustment for demographic and clinical variables had no impact on these cultural differences in symptom prevalence. The median severity of 11 symptoms including muscle soreness, muscle cramps, and itching was greater among Americans (P<0.001, respectively), although nearly all of these differences were rendered nonstatistically significant with adjustment for race, diabetes, and/or Kt/V. Italian patients receiving chronic hemodialysis report a greater burden of symptoms than American patients, particularly those related to sexual dysfunction and psychosocial distress. These findings suggest that cultural background may affect adaptation to chronic hemodialysis therapy.
Costs of managing anemia with erythropoiesis‐stimulating agents during hemodialysis: A time and motion study
Authors: SCHILLER Brigitte , DOSS Sheila , DE COCK Erwin , DEL AGUILA Michael A. , NISSENSON Allen R.
Published: October 2008

Use of erythropoiesis‐stimulating agents (ESAs) presents a significant time and cost burden in the management of anemia of chronic kidney disease (CKD). We conducted a prospective, observational, activity‐based costing study to estimate the health care personnel time and resulting direct medical costs associated with administering epoetin 3 times weekly to patients with end‐stage renal disease on dialysis. The study was conducted at 5 US hemodialysis centers. The personnel time and costs were derived from time and motion observations. Predicted time and cost savings were modeled for switching patients to once‐monthly ESA therapy. Patients also completed a survey questionnaire to assess their level of CKD knowledge and information needs. Total per‐patient‐per‐year (PPPY) time expended on anemia management with epoetin averaged 608 minutes (range 512–915 minutes), with an average PPPY cost of $548 (range $342–$651). Use of a once‐monthly ESA, compared with epoetin, could decrease average PPPY time expenditure by 79% (127 minutes [range 96–173 minutes]) and reduce PPPY costs by 81% ($104 [range $79–$136]). The patient questionnaire reported insufficient education on CKD. Use of a once‐monthly ESA to correct anemia in dialysis patients may provide substantial time, resource, and cost savings compared with current treatment practices.
Correlates affecting survival in chronic hemodialysis patients: The combined impact of albumin and high hemoglobin levels on improving outcomes, local and national results
Authors: CAPELLI John P. , KUSHNER Harvey
Published: October 2008

While national mortality rates for end‐stage renal disease (ESRD) patients remain high, for the past 4 years, lower than expected local mortality rates have been consistently seen in our facilities. Because of these progressive improvements in mortality rates, a study of 687 hemodialysis patients over a 4‐year period, 2003 through 2006, was undertaken to analyze which factors may be contributing to the enhanced survival rates. We also examined the partially overlapping United States Renal Data System clinical performance measures national data sets of hemodialysis patients for 2001 to 2004. Proportional hazards and logistic regression models were used to determine significant predictors of short‐term survival. Variables tested included hemoglobin (Hb), albumin, calcium, phosphorus, infections, hospitalizations, URR, Kt/V, erythropoietic stimulating agents (epoetin‐α) use, and comorbid conditions. The local and national models identified albumin, Hgb, and hospitalization as statistically significant predictors of survival. Local models also found years of dialysis as a significant predictor. Locally, there was a 69‐fold increase from 16.1 deaths/1000 patient years for albumin ≥4.0 with Hgb≥14.0 to 1115.9 deaths/1000 patient‐years for albumin <3.5 with Hgb<11.0. The increase nationally is a 4‐fold increase from 96 deaths/1000 patient‐years for albumin ≥4.0 with Hgb≥14.0 to 406 deaths/1000 patient‐years for albumin <3.5 with Hgb<11.0. There was no evidence that higher erythropoietic stimulating agents dose levels were associated with higher mortality rates, independent of the other significant factors. In conclusion, the findings indicate that individually higher Hgb and albumin levels are associated with increased survival, and when higher Hgb levels are in association with high albumin levels, the survival rates and hospitalizations are synergistically improved.
Infective spondylodiscitis in patients on high‐flux hemodialysis and on‐line hemodiafiltration
Authors: ABID Saima , DE SILVA Shamila , WARWICKER Paul , FARRINGTON Ken
Published: October 2008

Infective spondylodiscitis (ISD) is a rare but potentially devastating condition in hemodialysis (HD) patients. Reports are limited especially in patients receiving high‐flux HD and hemodiafiltration (HDF). In a retrospective analysis, 13 patients on our maintenance high‐flux HD/HDF program were identified as having has infective spondylodiscitis over a 10‐year period (1997–2006), an incidence of approximately 1 episode every 215 patient‐years. The incidence was around 3 times higher in patients dialyzing with tunnelled central venous catheters (TCVC) than in those with arteriovenous fistulae. Affected patients were elderly (mean age 70 years) and had multiple comorbidities. Access problems, particularly TCVC infection, were common in the months preceding it's onset. Tunnelled central venous catheter removal during these episodes did not necessarily prevent it. Diagnosis was based on a history of back pain, raised C‐reactive protein, positive blood cultures, and characteristic magnetic resonance findings. Many patients were apyrexial and had normal white cell counts. In our patients on high‐flux HD/hemodiafiltration, its incidence appears comparable to that in conventional HD settings. No patients had infection with waterborne organisms. Blood cultures were positive in 77%. Gram‐positive organisms predominated, particularly Staphylococcus aureus. The major route of infection was hematogenous, with the most likely source the venous access. All received antibiotics for 6 to 12 weeks or until death. Only 2 patients underwent surgical drainage. Mortality was high (46%) and predicted by the development of complications, and by pre‐existing cardiovascular comorbidity. Prevention, using strategies to reduce the prevalence of bacteremia, including limiting the use of TCVC, should be an overriding aim.
Paraoxonase‐1 (PON1) activity as a risk factor for atherosclerosis in chronic renal failure patients
Authors: SAEED Saeed Abdelwhab , ELSHARKAWY Magdy , ELSAEED Kadry , FOODA Osman
Published: October 2008

Paraoxonase is a high‐density lipoprotein‐associated enzyme and has been shown to reduce the susceptibility to low‐density lipoprotein peroxidation. This study aimed to investigate the activity of serum paraoxonase in uremic patients on hemodialysis (HD) and in the predialysis period, and to evaluate the correlations of vascular disease with paraoxonase activity. Thirty patients with chronic renal failure (CRF) undergoing HD (group 1), 30 patients with CRF under conservative treatment (group 2), and 30 healthy controls (group 3) were included. Basal, salt‐stimulated, and arylesterase activity were tested by UV spectrophotometry. Serum lipid parameters were determined. B‐Mode Doppler ultrasound was used to assess common carotid intima‐media thickness (IMT). Basal paraoxonase, salt‐stimulated, and arylesterase activity showed no significant difference between group 1 and group 2. However, it was significantly lower in group 1 and in group 2 than controls. Carotid IMT was significantly higher in group 1 than group 2 and both were significantly higher than controls. Basal paraoxonase‐1 (PON1), salt‐stimulated PON1, and arylesterase activity correlate with BUN, but only basal PON1 and salt‐stimulated PON1 correlate with serum albumin. Linear regression showed that the most significant determinant of carotid IMT was PON1 arylesterase activity in group 1 and arylesterase activity and basal PON1 activity in group 2. Patients with CRF, whether under HD or conservative treatment, have reduced basal and stimulated paraoxonase activities, and this could be an important factor causing increased vascular disease in those patients. Modifying this factor can be of great value to protect against this common complication.
Linking Centers for Medicare & Medicaid Services data with prospective DCOR trial data: Methods and data comparison results
Authors: St. PETER Wendy L. , LIU Jiannong , WEINHANDL Eric D. , FAN Qiao
Published: October 2008

The Dialysis Clinical Outcomes Revisited (DCOR) trial was a large randomized, multicenter 3‐year trial comparing the effects of sevelamer with calcium‐based binders on mortality, hospitalization, morbidity, and medical costs in hemodialysis subjects. Dialysis Clinical Outcomes Revisited was prospectively designed to link subjects to the Centers for Medicare & Medicaid Services End‐Stage Renal Disease (CMS ESRD) database to collect additional baseline characteristic data and to enhance outcome evaluation. Subjects were linked to the CMS ESRD database by means of an algorithm using several patient identifiers. Some baseline characteristic data were collected exclusively from the CMS ESRD database. Mortality and hospitalization end points were obtained from the CMS ESRD database and compared with similar data collected prospectively into a case‐report form (CRF) database. Of the 2103 patients who participated in the DCOR study, 2101 were successfully linked to the CMS ESRD database. Patient baseline data showed that treatment groups were well‐balanced, except that a higher proportion of subjects in the calcium‐based binder group had atherosclerotic heart disease. Calculated mortality rates were similar between databases, but more deaths were identified in the CMS than in the CRF database. These additional deaths were verified through several sources. More hospitalizations were also detected in the CMS than in the CRF database. The CMS database was a good source of death end points and hospitalization occurrence. Linking patients to the data‐rich CMS ESRD database allowed assessment of additional important secondary end points at a relatively low cost compared with prospective data collection.
Design and Fabrication of a Novel Electrode‐Supported Honeycomb SOFC
Authors: Yamaguchi Toshiaki , Shimizu Sota , Suzuki Toshio , Fujishiro Yoshinobu , Awano Masanobu
Published: October 2008

We report the design and fabrication of a novel electrode‐supported honeycomb solid oxide fuel cell (SOFC), that can generate high volumetric power density. Among various cell designs, honeycomb SOFCs are suitable for compact SOFC modules because they have a large surface electrode area per unit volume. We have succeeded in fabricating a cathode‐supported honeycomb SOFC via extrusion of a LaSrMnO3 honeycomb monolith and through the use of a new slurry injection method for the channel surface coating using electrolyte/anode bi‐layers. The fabricated honeycomb SOFCs exhibited high volumetric power densities of approximately 1.2 W/cm3 at 600°C under a wet H2 fuel flow.
Calponin control of cerebrovascular reactivity: therapeutic implications in brain trauma
Authors: Kreipke Christian W. , Rafols Jose A.
Published: October 2008

A role for Calponin (Cp) in mediating smooth muscle (SM) contraction

Cp phosphorylation and vascular contractility

Cp localization and function in the brain

Does Cp play a role in pathologic states?

Cp and TBI

Endothelin (ET)‐1, its receptors (ETrA, ETrB) and Cp‐mediated vasoreactivity: Therapeutic implications

Conclusion

Calponin (Cp) is an actin‐binding protein first characterized in chicken gizzard smooth muscle (SM). This review discusses the role of Cp in mediating SM contraction, the biochemical process by which Cp facilitates SM contraction and the function of Cp in the brain. Recent work on the role of Cp in pathological states with emphasis on traumatic brain injury is also discussed. Based on past and present data, the case is presented for targeting Cp for novel genetic and pharmacological therapies aimed at improving outcome following traumatic brain injury (TBI).
Women and Shakespeare in the Restoration and Eighteenth Century
Authors: Ritchie Fiona
Published: October 2008

This article examines the role of gender in the popularisation of Shakespeare in the long eighteenth century, providing an overview of scholarship on three groups of women: actresses (the first women on the stage and later performers such as Catherine Clive, Susannah Cibber and Hannah Pritchard), women in the theatre audience (including Elizabeth Pepys and the Shakespeare Ladies Club) and female critics (notably Charlotte Lennox and Elizabeth Montagu). In addition to suggesting further reading on the topic of women and Shakespeare and highlighting directions for subsequent research, the essay demonstrates that women were instrumental in shaping the Bard's reputation in the period from the reopening of the theatres in 1660 to David Garrick's Shakespeare Jubilee of 1769, the height of the period's adulation of Shakespeare.
Representations of the Devil in Fin‐de‐Siècle Literature
Authors: White Lizzie
Published: October 2008

This article makes the case for a critical consideration of representations of the devil in fin‐de‐siècle literature. Surveying the field of critical material relating to representations of the devil, it argues that texts from the fin de siècle receive little attention. In addition, it suggests that discussion of religious issues is often quite limited in critical treatments of fin‐de‐siècle writers. By using six texts published between 1880 and 1920 as examples, it encourages a reconsideration of the literature of the period in relation to the religious controversies of the mid‐nineteenth century.
Victorian Detective Fiction
Authors: Radford Andrew
Published: October 2008

This essay traces the principal currents in scholarship on Victorian detective fiction over the last century. Starting with a survey of the key critical perspectives established in the first half of the twentieth century, it moves into a more detailed discussion of prominent trends since the turn of the millennium. It suggests a number of directions in which future work might go and draws attention to the Victorian detective narrative's diversity in terms of form and subject matter, indicating that the genre is not as straightforward to label as it first seems. Charting lines of influence between distinctive theoretical and historical approaches to this genre reveals key scholarly trends and areas of recurrent formal and thematic interest in detective fiction studies. Through the discussion of these interlinking approaches I will argue that recent critical modes afford a productive new language with which to comprehend this immensely popular genre. Each grappling in various ways with the problem of how to locate and specify this genre, commentators address the detective narrative as, for example, a cryptic commentary on the nature of discipline; an expose of imperialism and its discontents; and as a fraught reaction to the teeming profusion of the modern metropolis.
A novel gene, fad49, plays a crucial role in the immediate early stage of adipocyte differentiation via involvement in mitotic clonal expansion
Authors: Hishida Tomoaki , Eguchi Tsuyoshi , Osada Shigehiro , Nishizuka Makoto , Imagawa Masayoshi
Published: October 2008

Adipogenesis is accomplished via a complex series of steps, and the events at the earliest stage remain to be elucidated. To clarify the molecular mechanisms of adipocyte differentiation, we previously isolated 102 genes expressed early in mouse 3T3‐L1 preadipocyte cells using a PCR subtraction system. About half of the genes isolated appeared to be unknown. After isolating full‐length cDNAs of the unknown genes, one of them, named factor for adipocyte differentiation 49 (fad49), appeared to be a novel gene, as the sequence of this clone showed no identity to known genes. FAD49 contains a phox homology (PX) domain and four Src homology 3 (SH3) domains, suggesting that it may be a novel scaffold protein. We found that the PX domain of FAD49 not only has affinity for phosphoinositides, but also binds to its third SH3 domain. Expression of fad49 was transiently elevated 3 h after differentiation was induced, and diminished 24 h after induction. Induction of the fad49 gene was observed in adipocyte differentiable 3T3‐L1 cells, but not in non‐adipogenic NIH‐3T3 cells. RNAi‐mediated knockdown of fad49 significantly impaired adipocyte differentiation. Moreover, the knockdown of fad49 by RNAi inhibited mitotic clonal expansion, and reduced the expression of CCAAT/enhancer‐binding protein β (C/EBPβ) and C/EBPδ at the immediate early phase. Taken together, these results show that fad49, a novel gene, plays a crucial role in the immediate early stage of adipogenesis.
Soluble recombinant CD69 receptors optimized to have an exceptional physical and chemical stability display prolonged circulation and remain intact in the blood of mice
Authors: Vaněk Ondřej , Nálezková Monika , Kavan Daniel , Borovičková Ivana , Pompach Petr , Novák Petr , Kumar Vinay , Vannucci Luca , Hudeček Jiří , Hofbauerová Kateřina , Kopecký Jr Vladimír , Brynda Jiří , Kolenko Petr , Dohnálek Jan , Kadeřávek Pavel , Chmelík Josef , Gorčík Lukáš , Žídek Lukáš , Sklenář Vladimír , Bezouška Karel
Published: October 2008

We investigated the soluble forms of the earliest activation antigen of human leukocyte CD69. This receptor is expressed at the cell surface as a type II homodimeric membrane protein. However, the elements necessary to prepare the soluble recombinant CD69 suitable for structural studies are a matter of controversy. We describe the physical, biochemical and in vivo characteristics of a highly stable soluble form of CD69 obtained by bacterial expression of an appropriate extracellular segment of this protein. Our construct has been derived from one used for CD69 crystallization by further optimization with regard to protein stability, solubility and easy crystallization under conditions promoting ligand binding. The resulting protein is stable at acidic pH and at temperatures of up to 65 °C, as revealed by long‐term stability tests and thermal denaturation experiments. Protein NMR and crystallography confirmed the expected protein fold, and revealed additional details of the protein characteristics in solution. The soluble CD69 refolded in a form of noncovalent dimers, as revealed by gel filtration, sedimentation velocity measurements, NMR and dynamic light scattering. The soluble CD69 proved to be remarkably stable in vivo when injected into the bloodstream of experimental mice. More than 70% of the most stable CD69 proteins is preserved intact in the blood 24 h after injection, whereas the less stable CD69 variants are rapidly taken up by the liver.
Directed evolution of a histone acetyltransferase – enhancing thermostability, whilst maintaining catalytic activity and substrate specificity
Authors: Leemhuis Hans , Nightingale Karl P. , Hollfelder Florian
Published: October 2008

Histone acetylation plays an integral role in the epigenetic regulation of gene expression. Transcriptional activity reflects the recruitment of opposing classes of enzymes to promoter elements; histone acetyltransferases (EC 2.3.1.48) that deposit acetyl marks at a subset of histone residues and histone deacetylases that remove them. Many histone acetyltransferases are difficult to study in solution because of their limited stability once purified. We have developed a directed evolution protocol that allows the screening of hundreds of histone acetyltransferase mutants for histone acetylating activity, and used this to enhance the thermostability of the human P/CAF histone acetyltransferase. Two rounds of directed evolution significantly stabilized the enzyme without lowering the catalytic efficiency and substrate specificity of the enzyme. Twenty‐four variants with higher thermostability were identified. Detailed analysis revealed twelve single amino acid mutants that were found to possess a higher thermostability. The residues affected are scattered over the entire protein structure, and are different from mutations predicted by sequence alignment approaches, suggesting that sequence comparison and directed evolution methods are complementary strategies in engineering increased protein thermostability. The stabilizing mutations are predominately located at surface of the enzyme, suggesting that the protein’s surface is important for stability. The directed evolution approach described in the present study is easily adapted to other histone modifying enzymes, requiring only appropriate peptide substrates and antibodies, which are available from commercial suppliers.