bluuebunny/crossref_metadata_2025 huggingface dataset:
Bevacizumab Plus Interferon Alfa Compared With Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: CALGB 90206
Authors: Rini Brian I. , Halabi Susan , Rosenberg Jonathan E. , Stadler Walter M. , Vaena Daniel A. , Ou San-San , Archer Laura , Atkins James N. , Picus Joel , Czaykowski Piotr , Dutcher Janice , Small Eric J.
Published: October 2008

Purpose

Bevacizumab is an antibody that binds to vascular endothelial growth factor (VEGF) and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN) is a historic standard first-line treatment for RCC. A prospective, randomized phase III trial of bevacizumab plus IFN versus IFN monotherapy was conducted.

Patients and Methods

Patients with previously untreated, metastatic clear-cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN (9 million U subcutaneously three times weekly) or the same dose and schedule of IFN monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate (ORR), and safety.

Results

Between October 2003 and July 2005, 732 patients were enrolled. The prespecified stopping rule for OS has not yet been reached. The median PFS was 8.5 months in patients receiving bevacizumab plus IFN (95% CI, 7.5 to 9.7 months) versus 5.2 months (95% CI, 3.1 to 5.6 months) in patients receiving IFN monotherapy (log-rank P < .0001). The adjusted hazard ratio was 0.71 (95% CI, 0.61 to 0.83; P < .0001). Bevacizumab plus IFN had a higher ORR as compared with IFN (25.5% [95% CI, 20.9% to 30.6%] v 13.1% [95% CI, 9.5% to 17.3%]; P < .0001). Overall toxicity was greater for bevacizumab plus IFN, including significantly more grade 3 hypertension (9% v 0%), anorexia (17% v 8%), fatigue (35% v 28%), and proteinuria (13% v 0%).

Conclusion

Bevacizumab plus IFN produces a superior PFS and ORR in untreated patients with metastatic RCC as compared with IFN monotherapy. Toxicity is greater in the combination therapy arm.
Randomized Phase II Study of Vandetanib Alone or With Paclitaxel and Carboplatin as First-Line Treatment for Advanced Non–Small-Cell Lung Cancer
Authors: Heymach John V. , Paz-Ares Luis , De Braud Filippo , Sebastian Martin , Stewart David J. , Eberhardt Wilfried E.E. , Ranade Anantbhushan A. , Cohen Graham , Trigo Jose Manuel , Sandler Alan B. , Bonomi Philip D. , Herbst Roy S. , Krebs Annetta D. , Vasselli James , Johnson Bruce E.
Published: October 2008

Purpose

Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non–small-cell lung cancer (NSCLC).

Patients and Methods

All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P < .2) and to demonstrate noninferiority for vandetanib versus PC. Overall survival was a secondary assessment.

Results

The risk of progression was reduced for patients receiving VPC (n = 56) versus PC (n = 52; hazard ratio = 0.76, one-sided P = .098); median PFS was 24 weeks (VPC) and 23 weeks (PC). The vandetanib monotherapy arm (n = 73) was discontinued after a planned interim PFS analysis met the criterion for discontinuation (hazard ratio > 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention.

Conclusion

VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had shorter PFS.
A Decade of Tissue Microarrays: Progress in the Discovery and Validation of Cancer Biomarkers
Authors: Camp Robert L. , Neumeister Veronique , Rimm David L.
Published: October 2008

This year, 2008, marks the 10-year anniversary of the development of the modern tissue microarray (TMA). During the last decade, the use of TMAs has grown steadily and accounts for a small but increasing percentage of all cancer biomarker studies performed. The growing popularity of TMA-based studies attests to their benefits in the discovery and validation of new biomarkers. This review will focus on these benefits, but also on the faults of TMAs and the challenges of TMA studies that have been overcome in the last decade. We will also discuss the role of TMAs in the latest revolution in cancer treatment, the use of targeted drug therapy.
Circulating 25-Hydroxyvitamin D, VDR Polymorphisms, and Survival in Advanced Non–Small-Cell Lung Cancer
Authors: Heist Rebecca Suk , Zhou Wei , Wang Zhaoxi , Liu Geoffrey , Neuberg Donna , Su Li , Asomaning Kofi , Hollis Bruce W. , Lynch Thomas J. , Wain John C. , Giovannucci Edward , Christiani David C.
Published: October 2008

Purpose

We showed previously that in early-stage non–small-cell lung cancer (NSCLC), serum vitamin D levels and VDR polymorphisms were associated with survival. We hypothesized that vitamin D levels and VDR polymorphisms may also affect survival among patients with advanced NSCLC.

Patients and Methods

We evaluated the relationship between circulating 25-hydroxyvitamin D levels; VDR polymorphisms, including Cdx-2 G>A (rs11568820), FokI C>T (rs10735810), and BsmI C>T ( rs144410 ); and overall survival among patients with advanced NSCLC. Analyses of survival outcomes were performed using the log-rank test and Cox proportional hazards models, adjusting for sex, stage, and performance status.

Results

There were 294 patients and 233 deaths, with median follow-up of 42 months. We found no difference in survival by circulating vitamin D level. The C/C genotype of the FokI polymorphism was associated with improved survival: median survival for C/C was 21.4 months, for C/T was 12.1 months, and for T/T was 15.6 months (log-rank P = .005). There were no significant effects on survival by the Cdx-2 or BsMI polymorphism. However, having increasing numbers of protective alleles was associated with improved survival (adjusted hazard ratio for two or more v zero to one protective alleles, 0.57; 95% CI, 0.41 to 0.79; P = .0008). On haplotype analysis, the G-T-C (Cdx-2-FokI-BsmI) haplotype was associated with worse survival compared with the most common haplotype of G-C-T (adjusted hazard ratio, 1.61; 95% CI, 1.21 to 2.14; P = .001).

Conclusion

There was no main effect of vitamin D level on overall survival in the advanced NSCLC population. The T allele of the VDR FokI>T polymorphism and the G-T-C (Cdx-2-FokI-BsmI) haplotype were associated with worse survival.
Strain-Specific Effects of Rosiglitazone on Bone Mass, Body Composition, and Serum Insulin-Like Growth Factor-I
Authors: Ackert-Bicknell Cheryl L. , Shockley Keith R. , Horton Lindsay G. , Lecka-Czernik Beata , Churchill Gary A. , Rosen Clifford J.
Published: October 2008

Activation of peroxisome proliferator activated receptor-γ (PPARG) is required for the differentiation of marrow mesenchymal stem cell into adipocytes and is associated with the development of age-related marrow adiposity in mice. Thiazolidinediones are agonists for PPARG and have a heterogeneous effect on bone mineral density (BMD). We postulated that genetic determinants influence the skeletal response to thiazolidinediones. We examined the effects of rosiglitazone (3 mg/kg · d for 8 wk) on BMD, body composition, and serum IGF-I in adult female mice from four inbred strains. C3H/HeJ mice showed the most significant response to treatment, exhibiting decreased femoral and vertebral BMD, reduced distal femoral bone volume fraction and a decrease in serum IGF-I. In DBA/2J, there were no changes in femoral BMD or bone volume fraction, but there was a decrease in vertebral BMD. C57BL/6J mice showed increases in marrow adiposity, without associated changes in trabecular bone volume; the skeletal effects from rosiglitazone in A/J mice were minimal. No association between trabecular bone volume and marrow adiposity was found. The effect of rosiglitazone on gene expression in the femur was then examined in the C3H/HeJ and C57BL/6J strains by microarray. Increased gene expression was observed in the PPARG signaling pathway and fatty acid metabolism in both C3H/HeJ and C57BL/6J, but a significant down-regulation of genes associated with cell cycle was noted only in the C3H/HeJ strain. The divergent skeletal responses to rosiglitazone in this study suggest the existence of a strong genetic background effect.

Treatment of four inbred strains of mice with rosiglitazone results in very distinct skeletal and metabolic responses, suggesting an important genotype by drug interaction.
Identification of proSAAS Homologs in Lower Vertebrates: Conservation of Hydrophobic Helices and Convertase-Inhibiting Sequences
Authors: Kudo H. , Liu J. , Jansen E. J. R. , Ozawa A. , Panula P. , Martens G. J. M. , Lindberg I.
Published: October 2008

The prohormone convertases (PCs) 1/3 and 2 accomplish the major proteolytic cleavage events in neuroendocrine tissues; each of these convertases has a small associated binding protein that inhibits convertase action in the secretory pathway. The proSAAS protein binds to PC1/3, whereas the 7B2 protein binds to PC2. However, both convertase-binding proteins are more widely expressed than their cognate enzymes, suggesting that they may perform other functions as well. All known mammalian proSAASs are over 85% conserved; thus, identifying functionally important segments has been impossible. Here, we report the first identification of nonmammalian proSAAS molecules, from Xenopus and zebrafish (Danio rerio). Although these two proteins show an overall amino acid sequence identity of only 29 and 30% with mouse proSAAS, two 14–16 residue hydrophobic segments (predicted to form α-helices) and two, nine through 11 residue sequences containing basic convertase cleavage sites are highly conserved; therefore, these sequences may be of functional importance. Confidence that these nonmammalian molecules represent authentic proSAAS is supported by the finding that both inhibit mouse PC1/3 with nanomolar inhibition constants; human furin was not inhibited. In vitro, the two proteins were cleaved by PC2 and furin to three or more peptide products. Both zebrafish and Xenopus proSAAS exhibited neural and endocrine distributions, as assessed by in situ and PCR experiments, respectively. In summary, the identification of proSAAS molecules in lower vertebrates provides clues as to functional regions within this widely expressed neuroendocrine protein.

The identification of two proSAAS molecules in lower vertebrates provides clues as to functional regions within this widely-expressed neuroendocrine protein.
Development and validation of criteria to identify medication-monitoring errors in care home residents
Authors: Alldred David P , Standage Claire , Zermansky Arnold G , Jesson Barbara , Savage Imogen , Franklin Bryony Dean , Barber Nick , Raynor David K
Published: October 2008

Aim

The identification of medication-monitoring errors requires a validated definition. This paper describes the development and validation of a definition which includes criteria for specific medicines to determine whether a medication-monitoring error has occurred in the care home setting.

Setting

Criteria were developed for older people (aged 65 years or older) living in care homes.

Methods

Criteria were developed by two clinical pharmacists using published guidelines. The criteria were divided into those relating to initiation of therapy and maintenance monitoring. The study steering group, made up of clinical pharmacists, a general practitioner (GP) and pharmacy academics, then reviewed the criteria and a consensus was achieved. The criteria were then reviewed by a sample of 21 GPs and 11 clinical pharmacists. The threshold for acceptance for each criterion was set at 70% by agreement of all participants.

Key findings

The definition of a medication-monitoring error was accepted as ‘when a prescribed medicine is not monitored in the way which would be considered acceptable in routine general practice. It includes the absence of tests being carried out at the frequency listed in the criteria for each medicine, with tolerance of +50%’. Seventy per cent agreement was reached on all criteria for the initiation of therapy, except warfarin (69%), and on all criteria for maintenance monitoring, except penicillamine (63%) and potassium (63%).

Conclusions

To our knowledge, this is the first study to define a medication-monitoring error, and to determine and validate specific criteria to identify such errors in older people living in care homes.
An inverse method applied to the determination of deformation energy distributions in the presence of pre-hardening stresses
Authors: Latourte F , Samida A , Chrysochoos A , Pagano S , Wattrisse B
Published: October 2008

This paper presents an experimental procedure to estimate the deformation energy distribution within plane samples submitted to mechanical loading. This procedure combined a digital image correlation (DIC) technique giving in-plane displacement fields with an identification method that separately provided fields of material properties and stress distributions developed during the loading. The method was first applied to simulated data to characterize the capabilities of the image processing. Finite element computations were first performed on a complex structure using a standard linear kinematical hardening model to generate multistage loadings leading to heterogeneous displacements and distributions of deformation energy. Loads and displacements were then used as inputs to check the robustness of the image processing by comparing the identified deformation energy fields with the computed ones. The procedure was then applied to experimental data. Tests were conducted under conditions similar to the numerical tests. The identification of a linear kinematical hardening model gave deformation energy patterns showing a good agreement with the simulated results, even in the presence of residual stresses induced by a pre-hardening.
Spurious hyperkalaemia due to EDTA contamination: common and not always easy to identify
Authors: Cornes Michael P , Ford Clare , Gama Rousseau
Published: October 2008

Background

To study the detection and prevalence of spurious hyperkalaemia due to potassium ethylenediaminetetra-acetic acid (kEDTA) contamination.

Methods

In a one-month prospective study, serum EDTA, zinc, calcium, magnesium concentrations and alkaline phosphatase activity were measured in samples with serum potassium ≥6.0 mmol/L.

Results

Twenty-eight out of 117 hyperkalaemic samples were contaminated with EDTA. Only serum zinc values below the reference range had 100% sensitivity for indicating EDTA contamination, but even at an optimal specificity of 89% at least 12 potentially genuine hyperkalaemic samples would be rejected.

Conclusion

Spurious hyperkalaemia due to kEDTA contamination is common. Gross kEDTA contamination is obvious by marked unexpected hyperkalaemia, hypocalcaemia, hypomagnesaemia and hypozincaemia. Spurious hyperkalaemia due to low concentrations of kEDTA contamination can only be confidently detected by measurement of serum EDTA.
Measurement of cholesterol concentrations of major serum lipoprotein classes in haemodialysis patients by anion-exchange chromatography
Authors: Hirowatari Yuji , Yoshida Hiroshi , Fueki Yuriko , Ito Masayuki , Ogura Yutaka , Sakurai Nobuyuki , Miida Takashi
Published: October 2008

Background

Increased triglyceride (TG)-rich lipoproteins and decreased HDL that are implicated in the progression of atherosclerotic vascular diseases, are present in serum samples of patients undergoing haemodialysis (HD) therapy. Therefore, it is important to measure serum TG-rich lipoprotein concentrations to prevent the diseases.

Methods

The cholesterol concentrations of lipoprotein classes in serum samples from the HD patients ( n = 18) and healthy subjects ( n = 18) were analysed by our recently developed method of high-performance liquid chromatography (HPLC), in which the lipoprotein classes were separated using an anion-exchange column, and the cholesterol concentrations of each of those were measured enzymatically using a post-column reaction. The ability of fractionated lipoprotein cholesterol determination by this HPLC method is mostly equivalent to the determination ability of an ultracentrifugation (UC).

Results

HDL, LDL, and TG-rich lipoproteins, i.e. IDL, VLDL and chylomicrons, were well separated in the chromatograms. HDL cholesterol concentrations in the HD patients were significantly lower than in the healthy subjects ( P < 0.0001), and IDL cholesterol concentrations and VLDL cholesterol concentrations in the HD patients were significantly higher than in the healthy subjects ( P < 0.05). Profiles of these measured lipoprotein values were consistent with the previously reported lipoprotein values, measured ultracentrifugally characteristic of HD patients.

Conclusion

These results suggest that the HPLC method may be sufficiently applied to the assessment of serum lipoprotein profile in HD patients in place of the other method including an UC.
Effect of delay in sampling on haemoglobin determined by faecal immunochemical tests
Authors: Brown Louise F , Fraser Callum G
Published: October 2008

Background

Faeces must be sampled directly onto guaiac-based faecal occult blood test (FOBT) cards since analysis of specimens collected in traditional faeces containers is inappropriate because degradation of haemoglobin continues after faeces have been passed. Newer faecal immunochemical tests (FIT) are replacing FOBT, but it is likely that the practice of obtaining specimens in traditional faeces collection containers for later analysis will continue. The aim of this study was to assess the effect of delay in stool sampling on FIT.

Methods

Five specimens of faeces from healthy volunteers, all qualitatively FIT negative, were supplemented with whole blood haemolysate to three different FIT positive concentrations. Each sample was analysed daily after 1–14 days delay using a quantitative latex immunoturbidimetric-based FIT and also after five and ten days delay using a qualitative FIT.

Results

Haemoglobin concentrations fell each day, the rate being generally proportional to the original haemoglobin concentration. After eight days delay, no sample had a haemoglobin concentration >100 ng/mL and, after nine days, no sample had a haemoglobin concentration >50 ng/mL. After five days delay, five of the 15 supplemented faeces with initially positive qualitative FIT had negative FIT; after 10 days, none had positive FIT.

Conclusion

False-negative results will occur if sampling of fresh faeces into or onto FIT collection devices is delayed. Laboratories that undertake FIT analyses on faeces collected into traditional containers are likely to miss significant neoplasia. FIT collection devices must be used for sampling fresh faeces.
A rapid rise in circulating pancreastatin in response to somatostatin analogue therapy is associated with poor survival in patients with neuroendocrine tumours
Authors: Stronge R L , Turner G B , Johnston B T , McCance D R , McGinty A , Patterson C C , Ardill J E S
Published: October 2008

Aim

To assess the value of pancreastatin as a predictive factor for identifying patients with neuroendocrine tumours (NETs) who respond poorly to somatostatin analogues.

Methods

A retrospective study of patients with NETs. Patient records from the Northern Ireland Neuroendocrine Tumour Register were interrogated. Those who had pancreastatin concentrations measured on two or more occasions, before and during somatostatin analogue therapy (within the set time-limits) were selected. Data relating to diagnosis, surgery, somatostatin analogue therapy and survival outcome were noted. Data were subjected to univariate and multivariate analysis using Cox proportional hazard model.

Results

Fifty-nine patients with gastroenteropancreatic NETs fulfilled the inclusion criteria. Factors associated with a poor survival outcome on univariate analysis were primary tumour site ( P = 0.006) and rapid rise in pancreastatin during somatostatin analogue treatment ( P < 0.001). In multivariate analysis, highly significant clinical prognostic indicators were: tumour location ( P < 0.001), pre-treatment pancreastatin ( P < 0.001) and pancreastatin change ( P < 0.001).

Conclusions

This study endorses the finding that pancreastatin is a useful prognostic indicator of neuroendocrine disease. On commencement of treatment, one-third of the subjects showed an immediate negative pancreastatin response to somatostatin analogues, which was associated with poor survival. This is the first study to document such an association. These findings have significant therapeutic consequences. In the presence of a rapidly rising pancreastatin alternative, treatment modalities should be sought.
Circulating markers for endocrine tumours of the gastroenteropancreatic tract
Authors: Ardill Joy E S
Published: October 2008

The diffuse endocrine system (DES) includes a wide range of secretory cells that may be the source of tumours. Gastroenteropancreatic endocrine (GEP) tumours arising within the DES secrete a variety of peptides and amines that are found in the circulation and are responsible for the syndromes associated with these tumours. In this review, the most common tumours of the GEP tract are outlined and the circulating products of these tumours identified. Where differential diagnosis is difficult these points are addressed. The peptides most commonly secreted by GEP neuroendocrine tumours are identified and described and their biological activities are discussed. Current methods available for measurement of these peptides are described. Attention is drawn towards molecular specificity where appropriate, as many pancreatic and gut peptides fall within families which show considerable homology, such as the tachykinin family or the glucagon family. Other peptides such as gastrin circulate in multiple molecular forms. This homology and diversity may cause difficulty in the interpretation of peptide measurements in the clinical situation if assays are not specific.
Determination of the reference range of endogenous plasma carnitines in healthy adults
Authors: Reuter Stephanie E , Evans Allan M , Chace Donald H , Fornasini Gianfranco
Published: October 2008

Background

l-carnitine is an endogenous substance, vital in the transport of fatty acids across the inner mitochondrial membrane for oxidation. Disturbances in carnitine homeostasis can have a significant impact on human health; therefore, it is critical to define normal endogenous concentrations for l-carnitine and its esters to facilitate the diagnosis of carnitine deficiency disorders. This study was conducted to determine the normal concentrations of a number of carnitines in healthy adults using three analytical methods. The impact of age and gender on carnitine concentrations was also examined.

Methods

Blood samples were collected from 60 healthy subjects of both genders and various ages. Plasma samples were analysed for endogenous carnitine concentrations by radioenzymatic assay, high-performance liquid chromatography and electrospray tandem mass spectrometry.

Results

Precision and accuracy of results obtained for each assay were within acceptable limits. Average endogenous concentrations obtained from the three analytical methods in this study were in the range of 38–44, 6–7 and 49–50 μmol/L for l-carnitine, acetyl-l-carnitine and total carnitine, respectively. Comparison of results between the genders indicated that males had significantly higher endogenous plasma l-carnitine and total carnitine concentrations than females. Age was found to have no impact on plasma carnitine concentrations.

Conclusion

These results are useful in the evaluation of biochemical or metabolic disturbances and in the diagnosis and treatment of patients with carnitine deficiency.
Standardization of the IMMULITE systems growth hormone assay with the recombinant IS 98/574
Authors: Barth Julian H , Sibley Paul E C
Published: October 2008

Background

The diagnosis of disorders of growth hormone (GH) secretion is based on the measurement of GH before and after dynamic stimulation or suppression tests. Over the years, specific cut-off values have been proposed without taking account of the considerable variation in results obtained using different methods for analysing GH. Recent publications have recommended the standardization of GH assays using IS 98/574, which is calibrated in mass and units (U). The IMMULITE range of GH assays have been recalibrated using this standard.

Methods

We analysed 745 samples using the current and the restandardized GH assay kits. This series of samples contained 90 stimulation tests and seven suppression tests.

Results

The data comparing the current and restandardized assays show a similar relationship for both basal and stimulated GH values for all IMMULITE platforms. There is a negative bias by the restandardized assay above approximately 20 μg/L. A conversion can be derived from this study which would mean that patient GH results expressed in milliunits per litre of IMMULITE in-house derived standard will be approximately three-fold of that expressed in micrograms per litre of IS 98/574.

Conclusion

Use of IS 98/574 offers standardized reporting in microgram per litre IS 98/574. This will permit compliance with the consensus recommendations and the development of a firm evidence base for defining decision-making GH values.
Acute intermittent porphyria presenting with a subarachnoid haemorrhage
Authors: van Heyningen Charles , Simms David M
Published: October 2008

A 47-year-old man presented with abdominal pain, neck stiffness, severe transient hypertension and unusually dark urine. Cerebrospinal fluid investigations and angiography confirmed the diagnosis of a subarachnoid haemorrhage. Porphyrin studies on the patient and his family demonstrated that the family has acute intermittent porphyria. This is the second case report of an acute hepatic porphyria presenting with a subarachnoid haemorrhage. Acute transient hypertension during the attack of porphyria caused the rupture of an intracranial arterial aneurysm.
Reinventing Westminster: how public executives reframe their world
Authors: Rhodes R.A.W. , Wanna John , Weller Patrick
Published: October 2008

The rise of the new public management in the 1980s led to recurring challenges to the administrative traditions of the public service in Australia, Canada and the UK. This article analyses how the heads of the public service articulate the traditions of ‘constitutional bureaucracy’ found in Westminster systems of parliamentary government and selectively draws on past understandings to understand present-day changes. We describe traditions under challenge that reshape reforms as reforms reshape them. We conclude that the heads of public services have found ‘space’ or ‘voice’ to articulate innovative ways of combining past traditions with new organising principles of governance. In each case, it is not a question of ‘in with the new, out with the old’, but of ‘in with the new alongside key components of the old’. The myths and legends of yore remain germane to the modern public service.
The Spanish model of devolution and regional governance: evolution, motivations and effects on policy making
Authors: Colino César
Published: October 2008

The Spanish model of decentralisation was originally devised to achieve cultural-political recognition for some regions and democracy and economic development for all. This article examines how this approach has evolved since the 1970s and the effectiveness of Spain's regional governance institutions. It concludes that regionalisation has been managed relatively well. Nonetheless, ambiguities surround the relations between tiers of government and questions remain about the institutional capacity of regional bodies and the extent of their discretion over decision making and the allocation of resources.
Response to Susan Castillo Interesting Times
Authors: Bak Hans
Published: October 2008

Offering a pragmatic, experiential and personal response to Susan Castillo's Interesting Times, Hans Bak argues that American exceptionalism, rather than being dead as the legendary dodo, seems a phoenix that continues to rise from its own ashes, and that the transnational or internationalist
perspective in American Studies called for by Susan Castillo has in effect been central to the reconfigurations of many European American Studies programs for some years, both in theory and pedagogical practice. He pleads for a firmer methodological and institutionalized grounding, so that
European Americanists can fully avail themselves of their unique positioning to implement a transnational, comparative, multilingual approach to American Studies.
Documenting children's dialogue: a hermeneutic phenomenological approach
Authors: Oh Jhong Sook
Published: October 2008

This paper reports on the author's experiments with the Reggio Emilia approach to pedagogy in an informal learning context in Korea. It explicates a hermeneutic study method she has developed over time as a means for interpreting young children's dialogue and determining the study themes
and expressive modes teachers might use to build on their life experience and extend their meaning making abilities.
The Narikiri Emaki (picture scroll) project
Authors: Mogi Kazuji , Shimohara Miho
Published: October 2008

In this article we introduce Narikiri Emaki, a practical workshop featuring emaki (picture scrolls) from which Japanese animation is said to derive. Our aim is to demonstrate the validity of this kind of workshop as a new way of learning in an information society; and to show
how some theories that social constructivist and situated learning scholars suggest can benefit art education. We have already conducted Narikiri Emaki workshops several times in Japan and Italy for cross-cultural research purposes. This article centres on workshops organized on 24
May 2006, for students at the Centro Linguisticai Ateneo Universita degli Studi Firenze (a Language Centre at the University of Florence), and on 19 August 2006, for primary school students at the Echigo-Tsumari Art Triennial, Japan. Because we wanted the students to learn the basic characteristics
of emaki and come to appreciate it as an art form, we asked them to perform a favourite emaki character using their bodies as a means of expression. There was evidence of global visual influences derived from animation and cartoons in the emaki they created together with
local cultural characteristics. Asking students to act out emaki characters resulted in dynamic, multimodal artistic expressions.
Art Work by primary-age children from St Petersburg taught by Natalia Novikova
Authors: Degtyareva Tatiana
Published: October 2008

Natalia Novikova is an art teacher from St Petersburg, Russia. She teaches students aged seven to fourteen who have one 45-minute art lesson per week. She offers additional lessons for fee-paying students as an after-school activity on the school premises. Natalia graduated from St
Petersburg Herzen Pedagogical University to become a primary school teacher specializing in art. Her approach to teaching is psychological. Her goal is to understand the student's imagery and teach them the skills they need to help them fulfil their own artistic aims. These lessons focused
on favourite fairy-tale characters and folk mythology.
Film Reviews: FilmClash: a blitz review of five recently released theatrical films
Authors: Belile C. Tyler
Published: October 2008

The Strangers
(2008) Rogue Pictures Director Bryan Bertino Screenplay Bryan Bertino Producers Doug Davison, Nathan Kahane, Roy Lee Cinematographer Peter Sova Art Director Linwood Taylor Edited by Kevin Greutert Starring
Liv Tyler (Kristen McKay), Scott Speedman (James Hoyt), Glenn Howerton (Mike) Runtime 90 minutes

Kung Fu Panda
(2008) Dreamworks Animation Director Mark Osborne, John Stevenson Screenplay Jonathan Aibel, Glenn Berger Producer Melissa Cobb Cinematographer
Yong Duk Jhun Art Director Tang Kheng Heng Voiced by Jack Black (Po), Dustin Hoffman (Shifu), Ian McShane (Tai Lung), Angelina Jolie (Tigress), Seth Rogen (Mantis), Lucy Liu (Viper), Jackie Chan (Monkey) Runtime 92 minutes

My Blueberry Nights
(2007) Block
2 Pictures Director Kar Wai Wong Screenplay Kar Wai Wong Producers Stphane Kooshmanian, Jean-Louis Piel, Wang Wei Cinematographer Darius Khondji Art Director Judy Rhee Starring Norah Jones (Elizabeth), Jude Law (Jeremy), David Straitharn (Arnie Copeland),
Rachel Weisz (Sue Lyne Copeland), Natalie Portman (Leslie) Runtime 90 minutes

Young@Heart
(2007) Walker Geroge Films Director Stephen Walker Producers Hannah Beckerman, Sally George, Jane Villiers Cinematographer Ed Marritz Starring An incredible
group of senior citizens Runtime 107 minutes

Don't Mess With the Zohan
(2008) Happy Madison Productions Director Dennis Dugan Screenplay Adam Sandler, Robert Smigel Producers Barry Bernardi, Jack Giarraputo, Daryl Kass, Alrdic La'Auli Porter Cinematographer
Michael Barrett Art Directors Toni Barton, John Collins, Marco Niro Starring Adam Sandler (Zohan), John Turturro (The Phantom), Emmanuelle Chriqui (Dalia), Nick Swardson (Michael), Rob Schneider (Salim) Runtime 113 minutes
Designing Effective Health Communications: A Meta-Analysis
Authors: Keller Punam Anand , Lehmann Donald R.
Published: October 2008

A meta-analysis of health communications examines the influence of 22 tactics and six individual characteristics on intentions to comply with health recommendations. The analysis indicates that message tactics have a significant influence on intentions toward health-related recommendations even after the authors account for individual differences. In addition, the authors examine when message tactics interact with individual characteristics to determine intentions. The results, which are based on 60 studies involving nearly 22,500 participants, show that there is significant opportunity to tailor health communications more efficiently to different market segments.
Reaching Parents to Prevent Adolescent Risky Behavior: Examining the Effects of Threat Portrayal and Parenting Orientation on Parental Participation Perceptions
Authors: Tanner John F. , Carlson Les A. , Raymond Mary Anne , Hopkins Christopher D.
Published: October 2008

With more than two million teens affected, adolescents are the most at-risk group for unwanted pregnancies and sexually transmitted diseases. Parents, who teens cite as their most influential resource for making decisions about premarital sex, receive little consideration from federal initiatives. However, promoting more active parenting to parents to reduce risky behavior among teenagers seems to be an appropriate strategy. This study examines parents’ reactions to advertisements that promote abstinence education programs. The results indicate that “warm” parents (i.e., those who indicate concern about children's interactions with the marketplace) are more likely to intend to communicate with their children about sex and have a more favorable attitude toward the ad when the advertisement is clear about the consequences of teens engaging in sex. The findings have implications for how public policy officials and agencies can influence parents as key socialization agents in efforts to prevent adolescents from engaging in risky sexual behavior.
Why New Tobacco “Harm-Reduction” Products should be Regulated
Authors: Goldberg Marvin E.
Published: October 2008

“Snus” consist of loose ground tobacco in a very small tea bag–like pouch, placed behind the upper gum for up to 30 minutes. With a different curing process and in the absence of combustion, several carcinogens are reduced, if not eliminated. Epidemiological studies in Sweden, where snus were developed and adopted by approximately 20% of males, have found few, if any, increases in oral/head cancers or cardiovascular risks. Although snus are considerably safer than cigarettes from the perspective of an individual smoker, from a broader societal perspective, at least three problems suggest the need for regulatory oversight: (1) Snus could serve as a “gateway” product for adolescents; (2) snus could serve as a temporary bridge/replacement product for smokers in situations in which cigarettes cannot be used, thus dampening their motivation to quit smoking; and (3) studies have found potentially heightened risks of pancreatic cancer, premature birth, dental disease, and oral lesions among users.
Le Mieux Est L'ennemi Du Bien
Authors: Ringold Debra Jones
Published: October 2008

The controversy associated with promoting smokeless tobacco as a safer alternative to smoking is a case in which the perfect (i.e., abstaining from tobacco) is the enemy of the good, or at least of the better (i.e., consuming smokeless tobacco). In contrast to the putative objectives of the public health community, the current regulatory regimen deters the innovation, sale, and consumption of more healthful tobacco products. If the desire for perfect information and perfect solutions can be avoided, if consumers can be trusted to understand risk information and its relevance to them, and if the marketplace is allowed to work, consumers will be better off.
An Exploration of Marketing's Impacts on Society: A Perspective Linked to Democracy
Authors: Jocz Katherine E. , Quelch John A.
Published: October 2008

The authors propose a political theory perspective for examining the impact of the modern aggregate marketing system on consumer welfare and society. Specifically, they suggest that the benefits marketing delivers to consumers are similar to the conditions required for representative democracy. This perspective encompasses a broader range of benefits than is usually considered in the marketing literature and could provide a possible template for evaluating marketing actions. Viewing marketing as democratic is consistent with the historical evolution of marketing and with existing definitions of marketing. Linking marketing to political science begins to connect individual-level outcomes with societal outcomes. The approach also lends itself to policy discussions and further research on the relationships among the three primary actors in the marketing system: consumers, marketers, and government. It raises several questions about optimal marketing systems.
Ethics and Public Policy Implications of Research on Consumer Well-Being
Authors: Sirgy M. Joseph
Published: October 2008

This essay provides an overview of research programs related to consumer well-being (CWB) and discusses the ethics perspectives and public policy implications of the programs. The author groups CWB research programs into five ethics perspectives: (1) ethics of consumer sovereignty, (2) duty ethics of nonmaleficence, (3) ethics of stakeholder theory, (4) ethics of social justice, and (5) ethics of human development and quality of life. Ethical guidelines and public policy implications are then logically deduced to assist professional and industry associations in setting CWB standards, to train member organizations to develop and implement programs to enhance CWB, and to monitor the extent to which the entire profession or industry is contributing to society through CWB. These ethical guidelines can also help government institutions and nongovernmental organizations create public policies to ensure that institutions deliver higher levels of CWB.
Active immunisation against gastric inhibitory polypeptide (GIP) improves blood glucose control in an animal model of obesity-diabetes
Authors: Irwin Nigel , McClean Paula L. , Patterson Steven , Hunter Kerry , Flatt Peter R.
Published: October 2008

Recent research suggests that long-term ablation of gastric inhibitory polypeptide (GIP) receptor signalling can reverse or prevent many of the metabolic abnormalities associated with dietary and genetically induced obesity-diabetes. The present study was designed to assess the sub-chronic effects of passive or active immunisation against GIP in ob/ob mice. Initial acute administration of GIP antibody together with oral glucose in ob/ob mice significantly increased the glycaemic excursion compared to controls (p<0.05). This was associated with a significant reduction (p<0.05) in the overall glucose-mediated insulin response. However, sub-chronic passive GIP immunisation was not associated with any changes in body weight, food intake or metabolic control. In contrast, active immunisation against GIP for 56 days in young ob/ob mice resulted in significantly (p<0.05) reduced circulating plasma glucose concentrations on day 56 compared to controls. There was a tendency for decreased circulating insulin in GIP immunised mice. The glycaemic response to intraperitoneal glucose was correspondingly improved (p<0.05) in mice immunised against GIP. Glucose-stimulated insulin levels were not significantly different from controls. Furthermore, insulin sensitivity was similar in mice immunised against GIP and respective controls. Overall, the results reveal that active, as opposed to passive, immunisation against GIP improves blood glucose control ob/ob mice.
Biochemical characterization of the catalytic domains of three different clostridial collagenases
Authors: Eckhard Ulrich , Schönauer Esther , Ducka Paulina , Briza Peter , Nüss Dorota , Brandstetter Hans
Published: October 2008

Clostridial collagenases are used for a broad spectrum of biotechnological applications and represent prime target candidates for both therapy and diagnosis of clostridial infections. In this study, we biochemically characterized the catalytic domains of three clostridial collagenases, collagenase G (ColG) and H (ColH) from Clostridium histolyticum, and collagenase T (ColT) from C. tetani. All protein samples showed activity against a synthetic peptidic substrate (furylacryloyl-Leu-Gly-Pro-Ala, FALGPA) with ColH showing the highest overall activity and highest substrate affinity. Whereas the K
m values of all three enzymes were within the same order of magnitude, the turnover rate k
cat of ColG decreased 50- to 150-fold when compared to ColT and ColH. It is noteworthy that the protein N-terminus significantly impacts their substrate affinity and substrate turnover as well as their inhibition profile with 1,10-phenanthroline. These findings were complemented with the discovery of a strictly conserved double-glycine motif, positioned 28 amino acids upstream of the HEXXH zinc binding site, which is critical for enzymatic activity. These observations have consequences with respect to the topology of the N-terminus relative to the active site as well as possible activation mechanisms.
Characterization of Local Strain Distribution in Zircaloy-4 and M5® Alloys
Authors: Elbachiri Kamal , Doumalin Pascal , Crépin Jérôme , Bornert Michel , Barberis Pierre , Rebeyrolle Véronique , Bretheau Thierry
Published: October 2008

Zirconium alloys with low alloying content are mainly used in the nuclear industry as structural materials because of their superior properties in terms of neutron transparency, mechanical strength, and corrosion resistance. In order to further improve the corrosion resistance as well as the integrity of Zr based cladding tubes under severe thermomechanical loading, the M5® alloy was developed to replace stress-relieved Zircaloy-4. An experimental study conducted at the macroscopic scale between 20 and 500°C shows that the mechanical behavior of the studied Zr based alloys depends on the metallurgical state (stress-relieved or recrystallized) rather than on the chemical composition. To try to understand these mechanical differences, an experimental multiscale investigation was devised at ambient temperature (20°C) in order to characterize the strain distribution at the scale of the grains and at that of the representative volume element. Local strain fields were measured by means of a microscale digital image correlation technique, based on microgrid deposits and scanning electronic microscopy (SEM). Tensile tests were performed inside the SEM chamber. Here, the original method of strain distribution quantification based on statistical strain field analysis is used. First, this analysis reveals a particular strain distribution consisting of bands with an orientation greater that 45° with regards to the direction of macroscopic tension, and second, shows that these interaction lengths are much greater than the average size of the grains, which clearly demonstrates that local investigations cannot be limited to a few grains. Therefore, the macroscopic mechanical response of these materials is not only governed by intragranular heterogeneities but by the local deformations which become organized between the grains in a pattern of bands at a mesoscale, which is determined by medium to long-range interactions. The difference of values in the band characteristics could partly explain the anisotropic global behavior of these materials linked with their microstructure.
Condensation Damage Behind Self-Adhering Membrane Flashing and Interior Furnishings on Exterior Residential Walls
Authors: Ofori-Amanfo Collins , Spink Matthew J.
Published: October 2008

This paper will present case studies of condensation damage behind self-adhering membranes installed around windows and other penetrations in exterior walls, as well as case studies of condensation damage behind large interior furnishings installed on the interior surfaces of exterior walls, and in unventilated spaces in Minnesota. The self-adhering membranes that are often used to integrate water-resistive barriers with residential doors and windows can, under certain conditions, lead to condensation and subsequent damage. While wider membranes help prevent inward movement of liquid water to the sheathing and stud framing, they also inhibit outward movement of interior water vapor. By increasing the distance that outward moving vapor must travel, wide membrane flashings trap moisture that can condense in cold climates and cause deterioration of degradable materials. In cold climate regions, condensation damage can also occur in exterior walls behind furnishings such as large mirrors and large cabinets. These interior decorations act as thermal reflectors and prevent interior heat from migrating into the exterior walls. When moisture behind these thermal reflectors is cooled below the dew point, condensation and related deterioration of the wall framing can occur. This paper discusses suggestions for the width of applied self-adhered membranes in cold climate regions and recommends locations for thermally reflecting interior furnishings.