bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of fire‐retardant intumescent mats for fire and heat protection of glass fibre‐reinforced polyester composites: Thermal barrier properties
Authors: Kandare Everson , Chukwudolue Christian , Kandola Baljinder K.
Published: March 2009

This study investigates the use of integral, hybrid intumescent thermal barriers (mats) to provide surface protection to the core fibre‐reinforced polyester composite structural integrity when exposed to a fire or heat source. Glass fibre‐reinforced composites protected by intumescent mats/fabrics containing silicate fibres, expandable graphite and in some cases borosilicate glass bounded together by an organic matrix have been evaluated for fire performance under a constant heat flux of 50kW/m2. The effect of insulative fabric thickness as well as chemical composition on the flammability of the resultant hybrid composites is evaluated. Glass fibre‐reinforced polyester (GRP) composites without any surface protection have a relatively higher time‐to‐ignition and peak heat release rate values when compared with core composites protected by insulative fabrics. Thermograms representing the variation of temperature on the reverse side of the hybrid composites with time when exposed to a constant heat flux show that the inclusion of intumescent surface barriers results in retarded temperature increments within the core GRP composites. Copyright © 2009 John Wiley & Sons, Ltd.
Cone calorimeter testing of S2 glass reinforced polymer composites
Authors: Morgan Alexander B. , Gagliardi Nicholas A. , Price William A. , Galaska Mary L.
Published: March 2009

With the ever increasing demand for fuel savings on vehicles, there is a strong push to replace metal with polymeric + fiber (carbon/glass) composites. However, the replacement of metal with polymeric composites can lead to additional fire risk. Our study focused on glass fiber reinforced polymer composites meant for vehicular structural applications, and flammability performance of these composites was studied by cone calorimetery. The effects of fiberglass loading, nanocomposite use (clay, carbon nanofiber) and polymer type (epoxy, phenolic) were studied under a heat flux of 50kW/m2 to better understand the potential effects that these variables would have on material flammability. It was found that as fiberglass loading increased, flammability decreased, but at a cost to structural integrity of the residual polymer + fiber char. The use of nanocomposites has little effect on reducing flammability in this set of samples, but the use of phenolic resins in comparison with epoxy resins was found to yield the greatest improvements in flammability performance. Further, the phenolic system yielded a higher level of structural integrity to the final polymer + fiberglass char when compared with the other polymer systems of low heat release. Copyright © 2009 John Wiley & Sons, Ltd.
Hiring for retention and performance
Authors: Barrick Murray R. , Zimmerman Ryan D.
Published: March 2009

This study evaluated the usefulness of several pre‐hire variables to predict voluntary turnover and job performance. Analyses showed that applicants who knew current employees, had longer tenure with previous employers, were conscientious and emotionally stable, were motivated to obtain the job, and were confident in themselves and their decision making were less likely to quit, and had higher performance within six months after hire. Results also indicated that pre‐hire attitudes (employment motivation and personal confidence) did not predict turnover and performance beyond biodata (pre‐hire embeddedness in the organization and habitual commitment) and the personality traits (conscientiousness and emotional stability). For all predictors but personality, the strength of the relationships weakened over time up to two years after hire. Nonetheless, organizations can avoid voluntary turnover and increase performance by basing hiring decisions on the set of predictors analyzed in this study. © 2009 Wiley Periodicals, Inc.
Employer‐supported volunteering benefits: Gift exchange among employers, employees, and volunteer organizations
Authors: Booth Jonathan E. , Park Kyoung Won , Glomb Theresa M.
Published: March 2009

Using gift exchange theory to explain the growing trend of employers offering employer‐supported volunteering (ESV) benefits, this article discusses the creation of exchange relationships between the employer and employee and between the volunteer organization and employee. Hypotheses derived from the employee's perspective are tested with a nationally representative sample of volunteers (n=3,658). Findings suggest that ESV benefits are positively related to hours volunteered by the employee. Volunteer hours predict employee perceptions of skill acquisition, and such perceptions are positively related to perceptions of job success and employer recognition. We discuss the implications of these findings for business, employees, and volunteer organizations, with an emphasis on human resource management policy and practice. © 2009 Wiley Periodicals, Inc.
Taking advantage of social comparisons in performance appraisal: The relative percentile method
Authors: Goffin Richard D. , Jelley R. Blake , Powell Deborah M. , Johnston Norman G.
Published: March 2009

Social comparison theory (Festinger, 1954) implies that it may be more efficacious for job performance raters to compare an employee to other employees rather than to use typical “absolute” rating standards. We assessed whether the incorporation of social comparisons into performance appraisals, using the relative percentile method (RPM), would predict criterion variance beyond that predicted by more traditional absolute ratings of performance. A sample (N=170) of managers involved in an assessment center was used, and the center provided criteria by which the relative criterion‐related validity of social‐comparative versus noncomparative (absolute) appraisals could be assessed. Overall, in consonance with a preponderance of earlier research, social‐comparative (RPM) performance appraisals showed incremental criterion‐related validity over traditional absolute performance appraisal methods. © 2009 Wiley Periodicals, Inc.
The effects of expatriate demographic characteristics on adjustment: A social identity approach
Authors: Olsen Jesse E. , Martins Luis L.
Published: March 2009

As demand increases for expatriates to manage far‐flung operations in a global economy, scholars and practitioners are focusing their attention on the factors that contribute to expatriate success. One such factor is the support that expatriates receive from host country nationals (HCNs) with whom they work. Researchers interested in understanding expatriate success have not closely examined the phenomenon from an HCN perspective, however. At the same time, although we have gained a significant understanding of the roles of psychological, organizational, and contextual variables in the international assignment, there is still much to be understood about how expatriates' demographic characteristics affect their experiences in international assignments. Current findings regarding the effects of demographic characteristics often are inconsistent, highlighting the need for more complex theorizing. This article reviews recent research on the effects of expatriate demographic characteristics and proposes a social identity approach to understanding how these characteristics affect HCN support for the expatriate. It also seeks to develop a theory that addresses discrepancies in extant empirical findings, provides propositions to guide future research in the study of expatriates, and discusses implications for both researchers and practitioners. © 2009 Wiley Periodicals, Inc.
Human colon fibroblasts induce differentiation and proliferation of intestinal epithelial cells through the direct paracrine action of keratinocyte growth factor
Authors: Visco Vincenzo , Bava Felice A. , d'Alessandro Federica , Cavallini Marco , Ziparo Vincenzo , Torrisi Maria Rosaria
Published: March 2009

The effects exerted by the keratinocyte growth factor (KGF) on intestinal epithelial cells cultured in vitro are influenced by cell confluence and differentiation through the modulation of keratinocyte growth factor receptor (KGFR) expression. In order to better define the contribution of KGF on the intestinal epithelial cell differentiation and proliferation, here we developed a coculture model, able to mimick in vitro the epithelial–mesenchymal interactions of the bowel. In consequence of its ability to produce KGF, demonstrated by real‐time PCR and Western blot analysis, the human colon fibroblast cell line CCD‐18 has been selected as coculture partner for the intestinal epithelial Caco‐2 cell line. Analysis of the expression of the differentiation and proliferation markers CEA and Ki67, through double immunofluorescence assays, showed that either the coculture with CCD‐18 cells or the incubation with primary colon fibroblast‐derived conditioned media (CM‐F and CM‐F2) induced an increase in differentiation and proliferation of confluent intestinal epithelial Caco‐2 or HT29 cells, parallel to that obtained by KGF treatment. Use of anti‐KGF blocking antibodies and of a tyrosine kinase KGFR inhibitor demonstrated the contribution of KGF and the direct role of its receptor in the regulation of epithelial growth and differentiation, indicating that KGF is a crucial paracrine factor involved in promoting these effects. J. Cell. Physiol. 220: 204–213, 2009. © 2009 Wiley‐Liss, Inc.
The Cdk5 inhibitor roscovitine strongly inhibits glucose uptake in 3T3‐L1 adipocytes without altering GLUT4 translocation from internal pools to the cell surface
Authors: Muruáis Gemma , Lalioti Vassiliki , Sandoval Ignacio V.
Published: March 2009

Glucose entry into mammalian cells is facilitated by a family of glucose transport proteins known as GLUTs. Treatment of 3T3‐L1 adipocytes with the Cdk5 inhibitor roscovitine strongly inhibits insulin‐stimulated/GLUT4‐mediated glucose transport. Inhibition of glucose uptake occurs within 2–6 min of the addition of roscovitine and is slowly reversed. The roscovitine treatment interferes with neither the translocation nor the insertion of GLUT4 into the plasma membrane. These studies support recent evidence showing that insulin‐stimulated Cdk5 is implicated in the regulation of GLUT4‐mediated glucose uptake in 3T3‐L1 adipocytes. J. Cell. Physiol. 220: 238–244, 2009. © 2009 Wiley‐Liss, Inc.
An optimized extended DNA kappa B site that enhances plasmid DNA nuclear import and gene expression
Authors: Gonçalves Cristine , Ardourel Marie‐Yvonne , Decoville Martine , Breuzard Gilles , Midoux Patrick , Hartmann Brigitte , Pichon Chantal
Published: March 2009

Background

The nuclear factor kappa B (NFκB) transcription factor, which shuttles between the cytoplasm and the nucleus under specific conditions, is a suitable intracellular target to increase the nuclear import of plasmid DNA. We report the design of an optimized and extended NFκB DNA binding sequence that promotes an efficient plasmid nuclear import.

Methods

On the basis of structural studies, the 5′‐CTGGGGACTTTCCAGCTGGGGACTTTCCAGCTGGGGACTTTCCAGG‐3′ segment (termed 3NF) comprising three 10‐bp κB sites (GGGACTTTCC) separated by a 5‐bp optimized spacer (AGCTG) was selected for its capacity to ensure the best structural fit with NFκB and to fix simultaneously three proteins. Plasmids encoding luciferase and bearing this sequence (3NF‐plasmids) were constructed and their nuclear import and gene expression efficiencies compared with that of plasmids containing classical κB motifs.

Results

A high luciferase expression was associated with plasmids containing one (p3NF‐luc) or two (p3NF‐luc‐3NF) 3NF sequences. In situ hybridization experiments and quantitative measurement of the number of plasmid copies demonstrated that the nuclear delivery of 3NF‐plasmids was more efficient than that of 3NF‐free plasmids. Cross‐linked immunoprecipitation showed that 3NF‐plasmids were recognized by NFκB inside cells upon transfection. The nuclear delivery was inhibited with BAY 11‐7085, an inhibitor of NFκB activation. Finally, p3NF‐luc‐3NF, the most efficient construct for in vitro transfection, had a long‐lived luciferase expression in vivo.

Conclusions

The results obtained in the present study demonstrate the NFκB‐mediated nuclear delivery of 3NF‐plasmids. Due to its high affinity for fixing several NFκB, the 3NF sequence is a very promising helper for a nonviral gene delivery system. Copyright © 2009 John Wiley & Sons, Ltd.
Profiling RNA interference (RNAi)‐mediated toxicity in neural cultures for effective short interfering RNA design
Authors: Read Martin L. , Mir Sohaib , Spice Rachel , Seabright Ruth J. , Suggate Ellen L. , Ahmed Zubair , Berry Martin , Logan Ann
Published: March 2009

Background

A promising strategy to enhance axon regeneration is to employ short interfering (si)RNA targeting either RhoA or p75NTR, which are components of a signalling cascade triggered by growth inhibitory ligands. However, it is important to profile the biological impact of siRNA on cell homeostasis in order to develop safe and effective therapies.

Methods

We used microarray and quantitative reverse transcriptase‐polymerase chain reaction techniques to analyse the transcriptional effects of siRNA against p75NTR and RhoA in neuronal cell line and primary cultures.

Results

Expression analysis showed that primary rat dorsal root ganglion cells were up to 279‐fold more sensitive than nerve growth factor‐differentiated PC12 cells in detecting innate immune responses to siRNA. The sequence and method of synthesis of siRNA critically influenced the magnitude of the innate immune response. Importantly, siRNA sequences were identified that efficiently silenced RhoA and p75NTR mRNA with attenuated induction of the interferon‐responsive gene mx1. Moreover, microarray analysis identified genes related to RhoA function, such as tgfβ2, plod2 and mmp3, with implications for interpretating the ability of RhoA siRNA to promote axon regeneration.

Conclusions

These findings demonstrate the importance of screening the biological impact of different siRNA sequences not only for their silencing efficacy, but also for potential toxicity. The results of the present study suggest that the toxicity observed was sequence‐dependent because only two out of five siRNA sequences targeting RhoA were identified that did not induce a significant innate immune response. Copyright © 2009 John Wiley & Sons, Ltd.
Environmental variability and vulnerable livelihoods: Minimising risks and optimising opportunities for poverty alleviation
Authors: K. Assan Joseph , Caminade Cyril , Obeng Frances
Published: March 2009

This paper presents an analysis that explores theoretical and policy debates on environmental variability, sustainable livelihood strategies, household well‐being and development policy. The paper focuses on communities in vulnerable environments with limited well‐being and poor assets. The study examines the changing livelihood strategies and livelihood options of households located within ecosystems perceived to be experiencing environmental change in Northeastern Ghana. Livelihood diversification as a poverty reduction strategy has been argued to result in improved well‐being or perpetuates a cycle of impoverishment. On‐farm and non‐farm diversification and migration as livelihood strategies are considered as survival strategies in environments experiencing rising temperatures and erratic rainfall patterns. It is argued that diversified livelihoods are operated within a cycle of impoverishment. The paper calls for geographically and locally sensitive policy intervention approaches that can sustainably expand the livelihood options of the poor in changing environments. Copyright © 2009 John Wiley & Sons, Ltd.
Introduction: Livelihood options for the poor in the changing environment
Authors: Assan Joseph K. , Kumar Pushpam
Published: March 2009

Environmental variability and climate change has become an enormous challenge of our time. Policy approaches to find sustainable strategies and interventions have become more and more important by the day. Whilst it is difficult to predict the current and future impacts of a phenomenon with such diverse impact streams, it is evident that the livelihood options of the poor and marginal societies in the global south are more likely to experience a significant shift. Again, their environment and the availability of the resources they depend on for their sustenance are predicted to be dwindling. This editorial seeks to bring together diverse approaches and experience from some of the different geographical regions in the global south identified to be most likely to be affected by environmental variability and to examine the various policy options that could facilitate the livelihood options of the poor, enhance their adaptation and reduce poverty. Copyright © 2009 John Wiley & Sons, Ltd.
The effect of a promoter polymorphism on the transcription of nitric oxide synthase 1 and its relevance to Parkinson's disease
Authors: Rife Terrie , Rasoul Bareza , Pullen Nicholas , Mitchell David , Grathwol Kristen , Kurth Janice
Published: March 2009

Transcriptional changes of the enzyme nitric oxide synthase I (NOS1) are believed to play a role in the development of many diseases. The gene for NOS1 has 12 alternative first exons (1A–1L). The 1F exon is one of the most highly utilized first exons in the brain and has a polymorphism ((TG)mTA(TG)n) located in its promoter region. The polymorphism's length has been suggested to affect NOS1 transcription and play a role in Parkinson's disease (PD); however, the actual influence of the polymorphism on NOS1 transcription has not been studied. To better characterize the links of the polymorphism with PD, a genotyping study was done comparing polymorphism length among 170 PD patients and 150 age‐matched controls. The pattern of changes between the two group's allele frequencies shows statistical significance (P = 0.0359). The smallest polymorphism sizes are more predominant among PD patients than controls. To study the effects of this polymorphism on NOS1 gene transcription, reporter gene constructs were made by cloning the NOS1 1F promoter with polymorphism lengths of either 42, 54, or 62 bp in front of the luciferase gene and transfecting them into HeLa or Sk‐N‐MC cells. NOS1‐directed reporter gene constructs with the 62‐bp polymorphism increased transcription of luciferase 2.2‐fold in HeLa and 1.8‐fold in Sk‐N‐MC cells compared with reporter gene constructs with the 42‐bp polymorphism. These data suggest that if smaller polymorphism size contributes to the higher NOS1 levels in PD patients, an as yet unknown transcriptional mechanism is required. © 2009 Wiley‐Liss, Inc.
Synergistic effect of low‐frequency ultrasound and low‐dose bradykinin on increasing permeability of the blood–tumor barrier by opening tight junction
Authors: Zhang Zhen , Xia Chunyi , Xue Yixue , Liu Yunhui
Published: March 2009

Low‐frequency ultrasound (LFU) and bradykinin (BK) have been shown separately to increase the permeability of the blood–tumor barrier (BTB) in the rat model of C6 glioma. This study examined the hypothesis that the combination of LFU and low‐dose BK has a synergistic effect on increasing the permeability of BTB and explored the possible underlying mechanism including the involvement of tight junction (TJ). The rats were divided into six groups: control group, LFU group, BK group, 2/3LFU + 1/2BK group, 5/6LFU + 2/3BK group, and LFU + BK group. The BTB permeability was assessed by Evans blue extravasation. The mRNA and protein expressions of TJ‐related proteins ZO‐1, occludin, and claudin‐5 were determined by reverse transcriptase–polymerase chain reaction, immunohistochemistry, immunolocalization, and Western blot test. BTB permeability increased in all the experimental groups, accompanied by opening of local TJ of the BTB, observed by transmission electron microscopy, and decreased mRNA and protein expressions of ZO‐1, occludin, and claudin‐5. In addition, there was a further increase in BTB permeability and a further reduction in the expressions of TJ‐related proteins in 5/6LFU + 2/3BK and LFU + BK groups, compared with LFU or BK group. These results indicate that LFU and low‐dose BK applied in combination act in a synergistic manner to increase BTB permeability. The down‐regulation of TJ‐related proteins ZO‐1, occludin, and claudin‐5 may be one of the underlying mechanisms of the increase in BTB permeability induced by LFU and BK. © 2009 Wiley‐Liss, Inc.
NMDA receptors mediate an early up‐regulation of brain‐derived neurotrophic factor expression in substantia nigra in a rat model of presymptomatic Parkinson's disease
Authors: Bustos Gonzalo , Abarca Jorge , Bustos Victor , Riquelme Eduardo , Noriega Viviana , Moya Catherine , Campusano Jorge
Published: March 2009

The clinical symptoms of Parkinson's disease (PD) appear late and only when the degenerative process at the level of the nigrostriatal dopamine (DA) pathway is quite advanced. An increase in brain‐derived neurotrophic factor (BDNF) expression may be one of the molecular signals associated to compensatory and plastic responses occurring in basal ganglia during presymptomatic PD. In the present study, we used in vivo microdialysis, semiquantitative reverse transcriptase–polymerase chain reaction, and immunohistochemistry to study N‐methyl‐D‐aspartic acid (NMDA) receptor regulation of BDNF expression in substantia nigra (SN) of adult rats after partial lesioning of the nigrostriatal DA pathway with unilateral striatal injections of 6‐hydroxydopamine (6‐OHDA). A time‐dependent partial decrease of striatal DA tissue content as well as parallel and gradual increases in extracellular glutamate and aspartate levels in SN were found 1 to 7 days after unilateral 6‐OHDA intrastriatal injection. Instead, the number of tyrosine hydroxylase–immunoreactive (IR) cells in the ipsilateral SN pars compacta remained statistically unchanged after neurotoxin injection. Intrastriatal administration of 6‐OHDA also produced an early and transient augmentation of pan‐BDNF, exon II–BDNF, and exon III–BDNF transcripts in the ipsilateral SN. The pan‐BDNF and exon II–BDNF transcript increases were completely abolished by the prior systemic administration of MK‐801, a selective antagonist of NMDA receptors. MK‐801 also blocked the increase in BDNF‐IR cells in SN observed 7 days after unilateral 6‐OHDA intrastriatal injections. Our findings suggest that a coupling between glutamate release, NMDA receptor activation, and BDNF expression may exist in the adult SN and represent an important signal in this midbrain nucleus triggered in response to partial DA loss occurring in striatal nerve endings during presymptomatic PD. © 2009 Wiley‐Liss, Inc.
Interaction of estrogen receptor‐α ligand binding domain with nuclear proteins of aging mouse brain
Authors: Ghosh Swati , Thakur M.K.
Published: March 2009

After the interaction of estrogen with the ligand binding domain (LBD) of mouse estrogen receptor‐α (mERα) and hormone‐responsive elements of target genes, many nuclear proteins are recruited to regulate the expression of specific genes. Because it is not known which brain proteins interact with LBD or whether these proteins vary with age and sex, we used pull‐down assay and far Western blotting to detect five nuclear proteins of 160, 140, 87, 60, and 46 kD in the mouse brain. These interacting proteins were identified as PELP1, RIP140, PGC1α, BAF60, and ADA3, respectively. The level of PELP1, RIP140, PGC1α, and BAF60 decreased drastically in old compared with adult male mice, whereas the ADA3 level showed no significant change. PELP1, PGC1α, and BAF60 levels were lower in old male compared with female mice. Thus we report the identification and interaction of five nuclear proteins with mERα‐LBD, indicating their role in estrogen signaling and brain functions during aging. © 2009 Wiley‐Liss, Inc.
Opposite role of infralimbic and prelimbic cortex in the tachycardiac response evoked by acute restraint stress in rats
Authors: Tavares R.F. , Corrêa F.M.A. , Resstel L.B.M.
Published: March 2009

The ventral medial prefrontal cortex (vMPFC) comprises the prelimbic cortex (PL) and the infralimbic cortex (IL). Conflicting results have been reported from studies aiming to investigate the role played by the vMPFC in behavioral and autonomic responses evoked in rodents exposed to experimental protocols that promote defense responses. Acute restraint is an unavoidable stress situation that evokes marked and sustained cardiovascular changes, which are characterized by elevated blood pressure (BP) and intense heart rate (HR) increases. We report here a comparison between the effects of pharmacological inhibition of IL and PL neurotransmission on BP and HR responses evoked by acute restraint in rats. Bilateral microinjection of 200 nl of the unspecific synaptic blocker CoCl2 (1 mM) into the PL increased HR response associated with restraint, without affecting the restraint‐induced BP response. However, when local synapses in the IL were inhibited by bilateral injection of CoCl2 into that area, the restraint‐induced HR increases were significantly reduced, without a significant effect on the concomitant BP response. No responses were observed when CoCl2 was microinjected into structures surrounding the vMPFC, such as the cingulate cortex area 1, the corpus callosum, or the tenia tecta. The present results confirm the involvement of the vMPFC in modulation of the tachycardiac response evoked by acute restraint but not of the restraint‐evoked blood pressure response. They also indicate that the IL and PL areas have opposite roles in the cardiac response, facilitating and reducing, respectively, restraint‐evoked tachycardiac responses. © 2009 Wiley‐Liss, Inc.
Increased levels of proinflammatory cytokines in the aged rat brain attenuate injury‐induced cytokine response after excitotoxic damage
Authors: Campuzano O. , Castillo‐Ruiz M. M. , Acarin L. , Castellano B. , Gonzalez B.
Published: March 2009

In order to evaluate proinflammatory cytokine levels and their producing cell types in the control aged rat brain and after acute excitotoxic damage, both adult and aged male Wistar rats were injected with N‐methyl‐D‐aspartate in the striatum. At different survival times between 6 hr and 7 days after lesioning, interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor alpha (TNF‐α) were analyzed by enzyme‐linked immunosorbent assay and by double immunofluorescence of cryostat sections by using cell‐specific markers. Basal cytokine expression was attributed to astrocytes and was increased in the normal aged brain showing region specificity: TNF‐α and IL‐6 displayed age‐dependent higher levels in the aged cortex, and IL‐1β and IL‐6 in the aged striatum. After excitotoxic striatal damage, notable age‐dependent differences in cytokine induction in the aged vs. the adult were seen. The adult injured striatum exhibited a rapid induction of all cytokines analyzed, but the aged injured striatum showed a weak induction of cytokine expression: IL‐1β showed no injury‐induced changes at any time, TNF‐α presented a late induction at 5 days after lesioning, and IL‐6 was only induced at 6 hr after lesioning. At both ages, in the lesion core, all cytokines were early expressed by neurons and astrocytes, and by microglia/macrophages later on. However, in the adjacent lesion border, cytokines were found in reactive astrocytes. This study highlights the particular inflammatory response of the aged brain and suggests an important role of increased basal levels of proinflammatory cytokines in the reduced ability to induce their expression after damage. © 2009 Wiley‐Liss, Inc.
Killer cell immunoglobulin-like receptor genotype and killer cell immunoglobulin-like receptor–human leukocyte antigen C ligand compatibility affect the severity of hepatitis C virus recurrence after liver transplantation
Authors: de Arias Alejandro Espadas , Haworth Simone Elizabeth , Belli Luca Saverio , Burra Patrizia , Pinzello Giovambattista , Vangeli Marcello , Minola Ernesto , Guido Maria , Boccagni Patrizia , De Feo Tullia Maria , Torelli Rosanna , Cardillo Massimo , Scalamogna Mario , Poli Francesca
Published: March 2009

In 20% to 30% of infected individuals, hepatitis C virus (HCV) can cause cirrhosis and hepatocellular carcinoma, for which liver transplantation is the best treatment available. HCV re-infection is universal, and hepatitis disease recurrence occurs in most cases with a 30% probability of progression to graft cirrhosis at 5 years post-transplant. The immunological response to HCV involves natural killer (NK) cells and killer cell immunoglobulin-like receptors (KIRs), which specifically recognize human leukocyte antigen (HLA) class I antigens present on target cells. The effector functions of NK cells are influenced by inhibitory KIR interaction with self-HLA class I ligands, with HLA-C being the most predominant. This study examines the roles of KIR genotypes and their HLA ligands in both HCV disease recurrence and its progression. A total of 151 patients were included in the cohort, and their clinical details were recorded. Liver biopsies were used to define the absence/presence of recurrent hepatitis, the degree of fibrosis, and the progression to cirrhosis over a 10-year period. Mismatching of KIR–HLA-C ligands between donor-recipient pairs was associated with the recurrence of hepatitis (P = 0.008). The presence of KIR2DL3 in the recipient correlated with progression to liver fibrosis (P = 0.04). The mismatching of HLA-KIR ligands favored the progression of the recurrent hepatitis to fibrosis only in the presence of KIR2DL3 (P = 0.04). These preliminary results indicate that the KIR genotype and KIR–HLA-C ligand compatibility play roles in the recurrence and progression of hepatitis C disease in liver transplant recipients.
Post–liver transplant survival in hepatitis C patients is improving over time
Authors: O'Leary Jacqueline G. , Randall Henry , Onaca Nicholas , Jennings Linda , Klintmalm Göran B. , Davis Gary L.
Published: March 2009

Outcomes after orthotopic liver transplantation for chronic hepatitis C have been reported to be worsening over the last 2 decades. We analyzed our center's experience over 15 years to identify trends in post–orthotopic liver transplantation survival in patients with and without hepatitis C virus infection. Patient survival and graft survival among adult primary orthotopic liver transplantation recipients who survived more than 90 days from January 1991 to June 2006 at the Baylor Regional Transplant Institute (n = 1901) were evaluated by Kaplan-Meier analysis. Those with or without hepatitis C virus infection were analyzed by era: era 1, 1991-1994 (n = 473); era 2, 1995-1998 (n = 421); era 3, 1999-2002 (n = 498); and era 4, 2003-2006 (n = 512). Differences in eras with disparate survivals were assessed by univariate and multivariable analysis. Overall, patient survival and graft survival were significantly lower among hepatitis C virus infection recipients compared to those without hepatitis C virus infection (P < 0.001). This difference was dependent on the era of transplantation, with progressive improvement in hepatitis C virus patient (P < 0.001) and graft (P < 0.001) survival in sequential eras. Several factors accounted for this improvement, notably better selection of hepatocellular carcinoma patients and fewer late cytomegalovirus infections. Improvement occurred despite an increase in the ages of both donors and recipients. In conclusion, posttransplant survival after orthotopic liver transplantation for chronic hepatitis C has improved significantly over the last 15 years despite demographic changes in patients and grafts that have been previously shown to impair survival. A major reason for this improvement is better selection of patients with concurrent hepatocellular carcinoma and fewer late cytomegalovirus infections, although other factors may play a role as well.
Technique and outcome of autologous portal Y-graft interposition for anomalous right portal veins in living donor liver transplantation
Authors: Hwang Shin , Lee Sung-Gyu , Ahn Chul-Soo , Kim Ki-Hun , Moon Deok-Bog , Ha Tae-Yong , Song Gi-Won , Jung Dong-Hwan , Ryu Je-Ho , Ko Kyung-Hoon , Choi Nam-Kyu , Kim Kwan-Woo
Published: March 2009

This study was intended to describe in detail the surgical technique and long-term outcome of autologous portal vein (PV) Y-graft interposition for adult living donor liver transplantation (LDLT). We assessed the outcome of 841 patients who underwent right lobe LDLT from January 2002 to December 2007 with respect to the reconstruction of double-graft PVs. PV anatomy of the donor livers was classified as type I in 796 patients (94.6%), type II in 15 patients (1.8%), and type III in 30 patients (3.6%). Seven type II grafts and all type III PV grafts had double PV orifices. Autologous PV Y-graft interposition was used in 31 patients, and complications occurred in only 1 patient during a median follow-up of 27 months. Overall, the 1- and 3-year graft survival rates were 87.5% and 80.6%, respectively. Use of a Y-graft was not a risk factor for biliary complications, but the liver anatomy of anomalous PV per se seems to be associated with a higher occurrence of biliary complications, especially during the early posttransplant period. The favorable outcome and technical feasibility of autologous portal Y-graft interposition imply that this technique could be the standard procedure for reconstruction of right lobe grafts with double PV orifices.
Decision analysis model for hepatitis B prophylaxis one year after liver transplantation
Authors: Saab Sammy , Ham Maggie Y. , Stone Michael A. , Holt Curtis , Tong Myron
Published: March 2009

In patients receiving orthotopic liver transplantation, hepatitis B recurrence rates have decreased significantly with the use of various methods for prophylaxis. At present, a combination of hepatitis B immunoglobulin (HBIG) and lamivudine is the standard of care, resulting in recurrence rates of 0% to 11%. Recent data suggest that the addition of adefovir to lamivudine is successful in treating patients with recurrent hepatitis B infection. A Markov model was used to compare costs and outcomes of 2 strategies for hepatitis B prophylaxis 1 year after transplantation. The first consisted of prophylaxis with lamivudine and adefovir (strategy 1), whereas the second consisted of intramuscular HBIG and lamivudine (strategy 2) with the addition of adefovir in patients who subsequently developed hepatitis B recurrence. Patients who failed with adefovir and lamivudine were then treated with tenofovir and entecavir. 16.8% of liver transplant recipients had hepatitis B recurrence after 10 years of treatment with lamivudine and HBIG. The medical costs for strategy 1 and strategy 2 after 10 years of therapy were $151,819 and $166,246, respectively, and this resulted in cost savings of $14,427. The decision analysis model began 1 year after liver transplantation. A 1-way sensitivity analysis demonstrated that the model was most sensitive to cost changes of adefovir and HBIG injections as well as variations in the hepatitis B virus recurrence rate. The model was robust to costs of lamivudine, laboratory costs, administrative fees, and office visit fees. Our decision analysis model resulted in marked savings in costs with strategy 1 (lamivudine and adefovir), providing pharmacoeconomic support for the use of this strategy as first-line therapy in hepatitis B prophylaxis in liver transplant recipients 1 year after liver transplantation.
Pulmonary hypertension after liver transplantation: Case presentation and review of the literature
Authors: Koch David G. , Caplan Michael , Reuben Adrian
Published: March 2009

Hepatopulmonary syndrome and portopulmonary hypertension are the most common pulmonary vascular complications in patients with cirrhosis. Usually but not universally mutually exclusive, they each may present prior to liver transplantation and, if severe enough, may be a contraindication to transplant. However, there have been a number of case reports describing patients developing pulmonary hypertension de novo after liver transplantation. This report describes one such patient from our institution and reviews the medical literature describing this unusual clinical entity.
The mechanisms of collisional activation of ions in mass spectrometry
Authors: Mayer Paul M. , Poon Clement
Published: March 2009

This article is a review of the mechanisms responsible for collisional activation of ions in mass spectrometers. Part I gives a general introduction to the processes occurring when a projectile ion and neutral target collide. The theoretical background to the physical phenomena of curve‐crossing excitation (for electronic and vibrational excitation), impulsive collisions (for direct translational to vibrational energy transfer), and the formation of long‐lived collision intermediates is presented. Part II highlights the experimental and computational investigations that have been made into collisional activation for four experimental conditions: high (>100 eV) and intermediate (1–100 eV) center‐of‐mass collision energies, slow heating collisions (multiple low‐energy collisions) and collisions with surfaces. The emphasis in this section is on the derived post‐collision internal energy distributions that have been found to be typical for projectile ions undergoing collisions in these regimes. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 28:608–639, 2009
Frequent occurrence of RASSF1A promoter hypermethylation and merkel cell polyomavirus in merkel cell carcinoma
Authors: Helmbold Peter , Lahtz Christoph , Enk Alexander , Herrmann‐Trost Peter , Marsch Wolfgang Ch. , Kutzner Heinz , Dammann Reinhard H.
Published: March 2009

Merkel cell carcinoma (MCC) is one of the most aggressive cancers of the skin. It has recently been reported that integration of a Merkel cell polyomavirus (MCPyV) in receptor tyrosine phosphates type G (PTPRG) gene occurs in MCC, and that viral infections are associated with epigenetic silencing of tumor suppressor genes (TSG) in cancer. To examine whether a correlation between TSG inactivation and viral infection can be found in MCC, we investigated the promoter hypermethylation of RASSF1A, TP73, PTPRG, FHIT, and CDKN2A and the presence of MCPyV and SV40 in 98 MCC by PCR. Hypermethylation of RASSF1A was frequently found in 42 of 83 (51%) of MCC. Methylation of CDKN2A was present in 9 of 41 (22%) of MCC. Hypermethylation of TP73 (0%), PTPRG (4%), and FHIT (0%) was infrequent in MCC. Interestingly, MCPyV was found in 90 of 98 (92%) MCC, however, no SV40 signal was detected. No correlation between TSG hypermethylation and viral infection was found. Our results show frequent hypermethylation of RASSF1A and the presence of MCPyV in primary MCC, and that these events may contribute to the pathogenesis of MCC. © 2009 Wiley‐Liss, Inc.
Generalized finite element method using proper orthogonal decomposition
Authors: Aquino W. , Brigham J. C. , Earls C. J. , Sukumar N.
Published: March 2009

A methodology is presented for generating enrichment functions in generalized finite element methods (GFEM) using experimental and/or simulated data. The approach is based on the proper orthogonal decomposition (POD) technique, which is used to generate low‐order representations of data that contain general information about the solution of partial differential equations. One of the main challenges in such enriched finite element methods is knowing how to choose, a priori, enrichment functions that capture the nature of the solution of the governing equations. POD produces low‐order subspaces, that are optimal in some norm, for approximating a given data set. For most problems, since the solution error in Galerkin methods is bounded by the error in the best approximation, it is expected that the optimal approximation properties of POD can be exploited to construct efficient enrichment functions. We demonstrate the potential of this approach through three numerical examples. Best‐approximation studies are conducted that reveal the advantages of using POD modes as enrichment functions in GFEM over a conventional POD basis. Copyright © 2009 John Wiley & Sons, Ltd.
A combined finite volume–finite element scheme for the discretization of strongly nonlinear convection–diffusion–reaction problems on nonmatching grids
Authors: Eymard Robert , Hilhorst Danielle , Vohralík Martin
Published: March 2009

We propose and analyze in this paper a numerical scheme for nonlinear degenerate parabolic convection–diffusion–reaction equations in two or three space dimensions. We discretize the time evolution, convection, reaction, and source terms on a given grid, which can be nonmatching and can contain nonconvex elements, by means of the cell‐centered finite volume method. To discretize the diffusion term, we construct a conforming simplicial mesh with the vertices given by the original grid and use the conforming piecewise linear finite element method. In this way, the scheme is fully consistent and the discrete solution is naturally continuous across the interfaces between the subdomains with nonmatching grids, without introducing any supplementary equations and unknowns or using any interpolation at the interfaces. We allow for general inhomogeneous and anisotropic diffusion–dispersion tensors, propose two variants corresponding respectively to arithmetic and harmonic averaging, and use the local Péclet upstream weighting in order to only add the minimal numerical diffusion necessary to avoid spurious oscillations in the convection‐dominated case. The scheme is robust, efficient since it leads to positive definite matrices and one unknown per element, locally conservative, and satisfies the discrete maximum principle under the conditions on the simplicial mesh and the diffusion tensor usual in the finite element method. We prove its convergence using a priori estimates and the Kolmogorov relative compactness theorem and illustrate its behavior on a numerical experiment. © 2009 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2010
Who benefits from demand‐driven distribution of HIV/AIDS services? An analysis of the emerging CBO sector in Malawi
Authors: Schou Arild
Published: March 2009

Community‐based organisations (CBOs) play a key role in Malawi's multi‐sector programme for responding to the HIV/AIDS pandemic. In this programme they are funded in a demand‐driven manner—which means that only those areas that apply for funds to CBO services are blessed with programme benefits. This paper argues that this funding mechanism is not conducive to either distributing CBO services to areas most in need or enhancing downward accountability. Because areas most in need of services generally also lacked the capacity to attract project funding, the programme did not reach them. Instead, it tended to reach those areas with the greatest capacity to attract funding, though not necessarily the greatest need for it. Furthermore, those CBOs that were funded were unable to facilitate collective action in their communities because of elite capture of decision making. The programme, however, was relatively responsive to the communities' thematic demands. Thus, all in all, the elites were relatively more successful in representing the communities' wishes than in caring for all geographical areas in their constituencies. Copyright © 2009 John Wiley & Sons, Ltd.
Dealing with sectoral corruption in Bangladesh: Developing citizen involvement
Authors: Knox Colin
Published: March 2009

Bangladesh has had a troubled political history since gaining independence in 1971 and is also beleaguered by poverty and natural environmental disasters. In particular however, corruption is blighting its prospects for economic growth, undermining the rule of law and damaging the legitimacy of the political process. This article adopts a sectoral approach to the study of corruption by examining people's experiences of using health and education services in Bangladesh through a large scale quantitative survey. It also presents case study research which assesses the impact of anti‐corruption work by Transparency International Bangladesh (TIB) in the areas of health and education. The article concludes that: the poorest in Bangladesh are most penalised by corruption; there are significant benefits for health and education service users resulting from TIB's interventions and there is a need for committed political leadership if ongoing efforts to tackle corruption are to be effective and sustainable. Copyright © 2009 John Wiley & Sons, Ltd.
Modes of influence: Participation in publicly administered development programmes
Authors: Parkinson Sarah
Published: March 2009

This article considers the way that farmers within a national agricultural advisory programme in Uganda were able to exert influence over that programme's policy and practice. Although the literature has tended to focus on engagement within formal programme structures as a major mode of participation, the analysis of the NAADS case reveals that farmers were able to exert an important influence over programme policy through their roles as political constituents. The brokerage role of supportive programme staff also worked to allow farmers' views to influence the programme, as did the collective weight of decisions commonly made by farmers, and to a lesser extent, the lobbying efforts of national NGOs. Copyright © 2009 John Wiley & Sons, Ltd.
False‐photosensitivity and transient hemiparesis following high‐dose intravenous and intrathecal methotrexate for treatment of acute lymphoblastic leukemia
Authors: Shah Nilay , Zambidis Elias T.
Published: March 2009

We describe a patient who was treated with high‐dose intravenous and intrathecal methotrexate for acute lymphoblastic leukemia, and who manifested a false photosensitivity reaction with no prior evidence of sun exposure. This patient later experienced delayed transient hemiparesis following methotrexate administration, although without long‐term sequelae. The etiology of these events is obscure, but suggestive of a vasculitic or immune‐mediated reaction to methotrexate. Pediatr Blood Cancer 2009;53:103–105. © 2009 Wiley‐Liss, Inc.
Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib
Authors: Janeway Katherine A. , Albritton Karen H. , Van Den Abbeele Annick D. , D'Amato Gina Z. , Pedrazzoli Paolo , Siena Salvatore , Picus Joel , Butrynski James E. , Schlemmer Marcus , Heinrich Michael C. , Demetri George D.
Published: March 2009

Background

Sunitinib inhibits KIT and other members of the split‐kinase‐domain family of receptor tyrosine kinases. Sunitinib prolongs survival in adult patients with imatinib‐resistant gastrointestinal stromal tumor (GIST). We report the experience with sunitinib in pediatric patients with advanced GIST following failure of imatinib.

Procedure

Sunitinib therapy was provided through a treatment‐use protocol. Patients were 10–17 years old at enrollment. All patients had GIST resistant to imatinib therapy. Sunitinib was administered daily for 4 weeks in 6‐week treatment cycles. KIT and platelet‐derived growth factor receptor alpha (PDGFRA) genotyping of tumor tissue were performed.

Results

One patient achieved a partial response, five patients had stable disease and one patient had progressive disease on sunitinib. The duration of disease stabilization was between 7 and 21+ months, with a mean of 15 months. Time to tumor progression was longer on sunitinib than on prior imatinib treatment for five of six patients. Two patients experienced grade 3 adverse events. All other adverse events were grade 1–2. None of the five patients tested had mutations in KIT or PDGFRA.

Conclusion

Sunitinib treatment was associated with substantial initial antitumor activity and acceptable tolerability in this group of pediatric patients with imatinib‐resistant GIST. Pediatr Blood Cancer 2009;52:767–771. © 2009 Wiley‐Liss, Inc.