bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Bilbao: Rethinking Flagship Cultural Development and Planning in Three California Cities
Authors: Grodach Carl
Published: December 2009

Since the widely publicized revitalization success story of the Guggenheim Museum Bilbao, local governments have been scrambling to create their own flagship cultural projects. Because of the broad public sponsorship of such projects, urban planners need a full understanding of the associated potentials and problems. However, little research specifically examines the localized complexities of the flagship cultural strategy. Examining projects in Los Angeles, San Francisco, and San Jose, California, the article illustrates that much more than impressive architecture influences their catalytic ability. Flagship cultural projects are highly dependent on a variety of contextual factors and, therefore, should be positioned to build on existing arts and related commercial activity rather than gamble that they will generate new development from scratch.
Intentional Practices in Supervision of Family Counseling: The Use of Supervisory Letters
Authors: Desmond Kimberly J. , Kindsvatter Aaron
Published: December 2009

Supervisors perform various roles in helping to guide the supervisee through the challenging process of family counseling. The use of letters in supervision helps to focus the supervisory processes in family counseling. Following the discrimination model of supervision, three types of supervisory letters are suggested for intentional supervision practices: letters of teaching, letters of counseling, and letters of consultation.
Effect of Atomoxetine on Executive Function Impairments in Adults With ADHD
Authors: Brown Thomas E. , Holdnack James , Saylor Keith , Adler Lenard , Spencer Thomas , Williams David W. , Padival Anoop K. , Schuh Kory , Trzepacz Paula T. , Kelsey Douglas
Published: December 2009

Objective: To assess the effect of atomoxetine on ADHD-related executive functions over a 6-month period using the Brown Attention-Deficit Disorder Scale (BADDS) for Adults, a normed, 40-item, self-report scale in a randomized, double-blind, placebo-controlled clinical trial. Method: In a randomized, double-blind clinical trial, adults with ADHD received either atomoxetine 25 to 100 mg/day or placebo for 6 months. Patients completed the BADDS to report their current daily functioning in 5 clusters of ADHD-related impairments of executive functioning: (1) Organizing and Activating to Work; (2) Focusing for Tasks; (3) Regulating Alertness and Effort; (4) Modulating Emotions; and (5) Utilizing Working Memory. Results: Mean scores were significantly more improved in the atomoxetine group compared to the placebo group: total score, -27.0 versus -19.0 ( p < .001); all 5 cluster scores, p < .01. Conclusions: Once-daily atomoxetine can improve executive function impairments in adults with ADHD as assessed by the BADDS. ( J. of Att. Dis. 2011; 15(2) 130-138)
Help-seeking for Mental Health Problems in Young Refugees: A Review of the Literature with Implications for Policy, Practice, and Research
Authors: de Anstiss Helena , Ziaian Tahereh , Procter Nicholas , Warland Jane , Baghurst Peter
Published: December 2009

The large and diverse bodies of literature on refugee child and adolescent mental health have not been matched by a commensurate interest in help-seeking. Most help-seeking research has centred on Western and, to a lesser extent, non-refugee ethnic minority adult populations. An emerging child and adolescent help-seeking literature consistently reports widespread underutilization of mental health services by children in the general population. Current research and opinion suggest a similar trend for refugee and other ethnic minority children. While service underutilization appears to be an issue for all children, those from refugee backgrounds may be at increased risk of mental health problems and have greater difficulty accessing mental health care. From a policy and practice perspective, the most important explanation for low uptake of services by refugee families concerns an overall failure of Western mental health systems to accommodate the needs of ethnically diverse populations in general and refugees in particular. In order to effectively plan for the mental health needs of refugee children and adolescents, Western host country governments need a clear understanding of help-seeking behaviour.
Methodological consideration of story telling in qualitative research involving Indigenous Peoples
Authors: Bird Susan , Wiles Janine L. , Okalik Looee , Kilabuk Jonah , Egeland Grace M.
Published: December 2009

Background: The use of storytelling in qualitative research involving Inuit compliments the oral tradition of Inuit culture. The objective of the research was to explore the use of qualitative methods to gain understanding of the experience of living with diabetes, with the ultimate goal of better formulating health care delivery and health promotion among Inuit. Methods : In-depth interviews were analyzed and interpreted using thematic analysis, open coding, and structured narrative analysis. Inuit community members acted as partners through all stages of the research. Results: ‘‘Because the more we understand, the more we’re gonna do a prevention on it … What I want is use my, use my diabetes, what I have … so that it can be used by other people for prevention because they’ll have understanding about it’’ — an Inuk storyteller speaks to the value of education in health promotion. Key methodological issues found relevant to improving qualitative research with Indigenous Peoples include: (i) participatory research methods, grounded in principals of equity, through all phases of research; (ii) the presentation of narratives rather than only interpretations of narratives; (iii) understanding of culture, language, and place to frame the interpretation of the stories in the context within which storytellers experience living with their diabetes, and (iv) the value of multiple methods of analyses. Interpretation: This article comments on the challenges of conducting rigorous research in a cross-cultural setting and outlines methodologies that can improve qualitative narrative analyses research. The research highlighted experiences of living with diabetes and the ways in which storytellers coped and negotiated social support. (Global Health Promotion, 2009; 16 (4): pp. 16—26)
Entre politiques nationales et initiatives locales, renforcer les synergies pour promouvoir la santé
Authors: Potvin Louise , Lamarre Marie-Claude
Published: December 2009

Tous les rapports qui se sont intéressés à l’articulation des politiques sanitaires nationales au niveau régional et local, à la rencontre des décideurs et des acteurs nationaux et locaux font tous ressortir la complexité de cette entreprise où se côtoient, s’enchevêtrent et se concurrencent de multiples niveaux décisionnels, et dispositifs de mise en œuvre des politiques et des actions. Cet intérêt pour le local comme lunette pour réfléchir et organiser l’action trouve aussi un écho dans la recherche. Depuis une vingtaine d’années, plusieurs équipes de disciplines variées ont tenté d’élucider comment les environnements sociaux façonnent la santé des individus et des populations et plus récemment, les inégalités sociales de santé. Dans cet article, les auteurs mettent en dialogue trois courants d’activités : 1) les efforts de réflexion des praticiens et des chercheurs de la francophonie ; 2) la recherche portant sur les lieux et la santé ; et 3) l’expérience globale concernant l’approche d’interventions sur les milieux de vie. Ce dialogue met en évidence le fait que dans beaucoup de pays l’approche territoriale de la programmation sanitaire en est encore à l’état d’expérimentation, quand, chez d’autres, elle est bien implantée. Cette approche reflète le souci de prendre en compte l’ensemble des déterminants de la santé, d’accorder une place importante aux environnements, d’être au plus proche de la préoccupation des personnes, de permettre une meilleure offre de service, d’optimiser les ressources disponibles et de lutter contre les inégalités. La décentralisation s’inscrit dans une culture dont il faut tenir compte avant d’en importer le modèle, car la diversité des acteurs d’horizon (santé, économique et social) et de culture (clinique, santé publique, planificateurs, professionnels de terrain, chercheurs) différents rend l’exercice riche mais extrêmement complexe. Ceci souligne l’importance de poursuivre des échanges entre différentes structures et différents pays. Le rôle de l’Union internationale de Promotion de la Santé et d’Éducation pour la Santé (UIPES) en tant que réseau mondial dont la mission est précisément de faciliter cette réflexion, la recherche, le partage et l’apprentissage des savoirs, des expériences et de l’expertise est à ce titre essentiel. (Global Health Promotion, 2009; 16 (4): pp. 75—82)
Single-agent arsenic trioxide in the treatment of children with newly diagnosed acute promyelocytic leukemia
Authors: Zhou Jin , Zhang Yingmei , Li Jinmei , Li Xiaoxia , Hou Jinxiao , Zhao Yanqiu , Liu Xiuhua , Han Xueying , Hu Longhu , Wang Shuye , Zhao Yanhong , Zhang Ying , Fan Shengjin , Lv Chengfang , Li Limin , Zhu Lingling
Published: December 2009

The aim of this study was to determine the efficacy and safety of treatment of pediatric acute promyelocytic leukemia (APL) with single-agent arsenic trioxide (ATO). A total of 19 children (≤ 15 years of age) with newly diagnosed APL were treated with single-agent ATO for remission induction and postremission therapy. Seventeen of the children (89.5%) achieved complete hematologic remission, and 2 early deaths occurred from intracranial hemorrhage. ATO-induced leukocytosis was observed in 13 (68.4%) patients. Other ATO-related toxicities were minimal and transient. Postremission ATO therapy continued for 3 years; the most common side effect was ATO-induced neutropenia. With a median follow-up of 53 months (range, 23-76 months), the calculated 5-year overall survival and event-free survival were 83.9% and 72.7%, respectively, which are comparable with results achieved by the use of ATRA plus chemotherapy, which is the standard therapy for APL. No chronic arsenic toxicity or second malignancies were found during the follow-up period, and arsenic retention was not significant in patients off treatment more than 24 months. ATO resistance was observed in only 1 patient with a complex karyotype. The results indicate the high efficacy and safety of single-agent ATO regimens in the treatment of children with de novo APL.
A new permutation strategy of pathway-based approach for genome-wide association study
Authors: Guo Yan-Fang , Li Jian , Chen Yuan , Zhang Li-Shu , Deng Hong-Wen
Published: December 2009

Background

Recently introduced pathway-based approach is promising and advantageous to improve the efficiency of analyzing genome-wide association scan (GWAS) data to identify disease variants by jointly considering variants of the genes that belong to the same biological pathway. However, the current available pathway-based approaches for analyzing GWAS have limited power and efficiency.

Results

We proposed a new and efficient permutation strategy based on SNP randomization for determining significance in pathway analysis of GWAS. The developed permutation strategy was evaluated and compared to two previously available methods, i.e. sample permutation and gene permutation, through simulation studies and a study on a real dataset. Results showed that the proposed permutation strategy is more powerful and efficient with greatly reducing the computational complexity.

Conclusion

Our findings indicate the improved performance of SNP permutation and thus render pathway-based analysis of GWAS more applicable and attractive.
Complete reversal of epithelial to mesenchymal transition requires inhibition of both ZEB expression and the Rho pathway
Authors: Das Shreyas , Becker Bryan N , Hoffmann F Michael , Mertz Janet E
Published: December 2009

Background

Epithelial to Mesenchymal Transition (EMT) induced by Transforming Growth Factor-β (TGF-β) is an important cellular event in organogenesis, cancer, and organ fibrosis. The process to reverse EMT is not well established. Our purpose is to define signaling pathways and transcription factors that maintain the TGF-β-induced mesenchymal state.

Results

Inhibitors of five kinases implicated in EMT, TGF-β Type I receptor kinase (TβRI), p38 mitogen-activated protein kinase (p38 MAPK), MAP kinase kinase/extracellular signal-regulated kinase activator kinase (MEK1), c-Jun NH-terminal kinase (JNK), and Rho kinase (ROCK), were evaluated for reversal of the mesenchymal state induced in renal tubular epithelial cells. Single agents did not fully reverse EMT as determined by cellular morphology and gene expression. However, exposure to the TβRI inhibitor SB431542, combined with the ROCK inhibitor Y27632, eliminated detectable actin stress fibers and mesenchymal gene expression while restoring epithelial E-cadherin and Kidney-specific cadherin (Ksp-cadherin) expression. A second combination, the TβRI inhibitor SB431542 together with the p38 MAPK inhibitor SB203580, was partially effective in reversing EMT. Furthermore, JNK inhibitor SP600125 inhibits the effectiveness of the TβRI inhibitor SB431542 to reverse EMT. To explore the molecular basis underlying EMT reversal, we also targeted the transcriptional repressors ZEB1 and ZEB2/SIP1. Decreasing ZEB1 and ZEB2 expression in mouse mammary gland cells with shRNAs was sufficient to up-regulate expression of epithelial proteins such as E-cadherin and to re-establish epithelial features. However, complete restoration of cortical F-actin required incubation with the ROCK inhibitor Y27632 in combination with ZEB1/2 knockdown.

Conclusions

We demonstrate that reversal of EMT requires re-establishing both epithelial transcription and structural components by sustained and independent signaling through TβRI and ROCK. These findings indicate that combination small molecule therapy targeting multiple kinases may be necessary to reverse disease conditions.
Developmental dynamics of cone photoreceptors in the eel
Authors: Cottrill Phillippa B , Davies Wayne L , Semo Ma'ayan , Bowmaker James K , Hunt David M , Jeffery Glen
Published: December 2009

Background

Many fish alter their expressed visual pigments during development. The number of retinal opsins expressed and their type is normally related to the environment in which they live. Eels are known to change the expression of their rod opsins as they mature, but might they also change the expression of their cone opsins?

Results

The Rh2 and Sws2 opsin sequences from the European Eel were isolated, sequenced and expressed in vitro for an accurate measurement of their λmax values. In situ hybridisation revealed that glass eels express only rh2 opsin in their cone photoreceptors, while larger yellow eels continue to express rh2 opsin in the majority of their cones, but also have <5% of cones which express sws2 opsin. Silver eels showed the same expression pattern as the larger yellow eels. This observation was confirmed by qPCR (quantitative polymerase chain reaction).

Conclusions

Larger yellow and silver European eels express two different cone opsins, rh2 and sws2. This work demonstrates that only the Rh2 cone opsin is present in younger fish (smaller yellow and glass), the sws2 opsin being expressed additionally only by older fish and only in <5% of cone cells.
Phylogenomics of the oxidative phosphorylation in fungi reveals extensive gene duplication followed by functional divergence
Authors: Marcet-Houben Marina , Marceddu Giuseppe , Gabaldón Toni
Published: December 2009

Background

Oxidative phosphorylation is central to the energy metabolism of the cell. Due to adaptation to different life-styles and environments, fungal species have shaped their respiratory pathways in the course of evolution. To identify the main mechanisms behind the evolution of respiratory pathways, we conducted a phylogenomics survey of oxidative phosphorylation components in the genomes of sixty fungal species.

Results

Besides clarifying orthology and paralogy relationships among respiratory proteins, our results reveal three parallel losses of the entire complex I, two of which are coupled to duplications in alternative dehydrogenases. Duplications in respiratory proteins have been common, affecting 76% of the protein families surveyed. We detect several instances of paralogs of genes coding for subunits of respiratory complexes that have been recruited to other multi-protein complexes inside and outside the mitochondrion, emphasizing the role of evolutionary tinkering.

Conclusions

Processes of gene loss and gene duplication followed by functional divergence have been rampant in the evolution of fungal respiration. Overall, the core proteins of the respiratory pathways are conserved in most lineages, with major changes affecting the lineages of microsporidia, Schizosaccaromyces and Saccharomyces/Kluyveromyces due to adaptation to anaerobic life-styles. We did not observe specific adaptations of the respiratory metabolism common to all pathogenic species.
Phylogenetic analysis and temporal diversification of mosquitoes (Diptera: Culicidae) based on nuclear genes and morphology
Authors: Reidenbach Kyanne R , Cook Shelley , Bertone Matthew A , Harbach Ralph E , Wiegmann Brian M , Besansky Nora J
Published: December 2009

Background

Phylogenetic analyses provide a framework for examining the evolution of morphological and molecular diversity, interpreting patterns in biogeography, and achieving a stable classification. The generic and suprageneric relationships within mosquitoes (Diptera: Culicidae) are poorly resolved, making these subjects difficult to address.

Results

We carried out maximum parsimony and maximum likelihood, including Bayesian, analyses on a data set consisting of six nuclear genes and 80 morphological characters to assess their ability to resolve relationships among 25 genera. We also estimated divergence times based on sequence data and fossil calibration points, using Bayesian relaxed clock methods. Strong support was recovered for the basal position and monophyly of the subfamily Anophelinae and the tribes Aedini and Sabethini of subfamily Culicinae. Divergence times for major culicid lineages date to the early Cretaceous.

Conclusions

Deeper relationships within the family remain poorly resolved, suggesting the need for additional taxonomic sampling. Our results support the notion of rapid radiations early in the diversification of mosquitoes.
Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study
Authors: Sakhi Amrit K , Russnes Kjell M , Thoresen Magne , Bastani Nasser E , Karlsen Anette , Smeland Sigbjørn , Blomhoff Rune
Published: December 2009

Background

The purpose of this study was to compare plasma levels of antioxidants and oxidative stress biomarkers in head and neck squamous cell carcinoma (HNSCC) patients with healthy controls. Furthermore, the effect of radiotherapy on these biomarkers and their association with survival in HNSCC patients were investigated.

Methods

Seventy-eight HNSCC patients and 100 healthy controls were included in this study. Follow-up samples at the end of radiotherapy were obtained in 60 patients. Fifteen antioxidant biomarkers (6 carotenoids, 4 tocopherols, ascorbic acid, total antioxidant capacity, glutathione redox potential, total glutathione and total cysteine) and four oxidative stress biomarkers (total hydroperoxides, γ-glutamyl transpeptidase, 8-isoprostagladin F2α and ratio of oxidized/total ascorbic acid) were measured in plasma samples. Analysis of Covariance was used to compare biomarkers between patients and healthy controls. Kaplan-Meier plots and Cox' proportional hazards models were used to study survival among patients.

Results

Dietary antioxidants (carotenoids, tocopherols and ascorbic acid), ferric reducing antioxidant power (FRAP) and modified FRAP were lower in HNSCC patients compared to controls and dietary antioxidants decreased during radiotherapy. Total hydroperoxides (d-ROMs), a marker for oxidative stress, were higher in HNSCC patients compared to controls and increased during radiotherapy. Among the biomarkers analyzed, high levels of plasma carotenoids before radiotherapy are associated with a prolonged progression-free survival (hazard rate ratio: 0.42, 95% CI: 0.20-0.91, p = 0.03). Additionally, high relative increase in plasma levels of d-ROMs (hazard rate ratio: 0.31, 95% CI: 0.13-0.76, p = 0.01) and high relative decrease in FRAP (hazard rate ratio: 0.42, 95% CI: 0.17-0.998, p = 0.05) during radiotherapy are also positively associated with survival.

Conclusions

Biomarkers of antioxidants and oxidative stress are unfavourable in HNSCC patients compared to healthy controls, and radiotherapy affects many of these biomarkers. Increasing levels of antioxidant biomarkers before radiotherapy and increasing oxidative stress during radiotherapy may improve survival indicating that different factors/mechanisms may be important for survival before and during radiotherapy in HNSCC patients. Thus, the therapeutic potential of optimizing antioxidant status and oxidative stress should be explored further in these patients.
RNA degradation compromises the reliability of microRNA expression profiling
Authors: Ibberson David , Benes Vladimir , Muckenthaler Martina U , Castoldi Mirco
Published: December 2009

Background

MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression and their expression is frequently altered in human diseases, including cancer. To correlate clinically relevant parameters with microRNA expression, total RNA is frequently prepared from samples that were archived for various time periods in frozen tissue banks but, unfortunately, RNA integrity is not always preserved in these frozen tissues. Here, we investigate whether experimentally induced RNA degradation affects microRNA expression profiles.

Results

Tissue samples were maintained on ice for defined time periods prior to total RNA extraction, which resulted in different degrees of RNA degradation. MicroRNA expression was then analyzed by microarray analysis (miCHIP) or microRNA-specific real-time quantitative PCR (miQPCR). Our results demonstrate that the loss of RNA integrity leads to in unpredictability of microRNA expression profiles for both, array-based and miQPCR assays.

Conclusion

MicroRNA expression cannot be reliably profiled in degraded total RNA. For the profiling of microRNAs we recommend use of RNA samples with a RNA integrity number equal to or above seven.
Identification and verification of ultrafine particle affinity zones in urban neighbourhoods: sample design and data pre-processing
Authors: Harris Paul , Lindley Sarah , Gallagher Martin , Agius Raymond
Published: December 2009

A methodology is presented and validated through which long-term fixed site air quality measurements are used to characterise and remove temporal signals in sample-based measurements which have good spatial coverage but poor temporal resolution. The work has been carried out specifically to provide a spatial dataset of atmospheric ultrafine particle (UFP < 100 nm) data for ongoing epidemiologic cohort analysis but the method is readily transferable to wider epidemiologic investigations and research into the health effects of other pollutant species.
Comparative proteomic analysis of pathogenic and non-pathogenic strains from the swine pathogen Mycoplasma hyopneumoniae
Authors: Pinto Paulo M , Klein Cátia S , Zaha Arnaldo , Ferreira Henrique B
Published: December 2009

Background

Mycoplasma hyopneumoniaeis a highly infectious swine pathogen and is the causative agent of enzootic pneumonia (EP). Following the previous report of a proteomic survey of the pathogenic 7448 strain of swine pathogen,Mycoplasma hyopneumoniae, we performed comparative protein profiling of threeM. hyopneumoniaestrains, namely the non-pathogenic J strain and the two pathogenic strains 7448 and 7422.

Results

In 2DE comparisons, we were able to identify differences in expression levels for 67 proteins, including the overexpression of some cytoadherence-related proteins only in the pathogenic strains. 2DE immunoblot analyses allowed the identification of differential proteolytic cleavage patterns of the P97 adhesin in the three strains. For more comprehensive protein profiling, an LC-MS/MS strategy was used. Overall, 35% of theM. hyopneumoniaegenome coding capacity was covered. Partially overlapping profiles of identified proteins were observed in the strains with 81 proteins identified only in one strain and 54 proteins identified in two strains. Abundance analysis of proteins detected in more than one strain demonstrates the relative overexpression of 64 proteins, including the P97 adhesin in the pathogenic strains.

Conclusions

Our results indicate the physiological differences between the non-pathogenic strain, with its non-infective proliferate lifestyle, and the pathogenic strains, with its constitutive expression of adhesins, which would render the bacterium competent for adhesion and infection prior to host contact.
Race and ancestry in biomedical research: exploring the challenges
Authors: Caulfield Timothy , Fullerton Stephanie M , Ali-Khan Sarah E , Arbour Laura , Burchard Esteban G , Cooper Richard S , Hardy Billie-Jo , Harry Simrat , Hyde-Lay Robyn , Kahn Jonathan , Kittles Rick , Koenig Barbara A , Lee Sandra SJ , Malinowski Michael , Ravitsky Vardit , Sankar Pamela , Scherer Stephen W , Séguin Béatrice , Shickle Darren , Suarez-Kurtz Guilherme , Daar Abdallah S
Published: December 2009

The use of race in biomedical research has, for decades, been a source of social controversy. However, recent events, such as the adoption of racially targeted pharmaceuticals, have raised the profile of the race issue. In addition, we are entering an era in which genomic research is increasingly focused on the nature and extent of human genetic variation, often examined by population, which leads to heightened potential for misunderstandings or misuse of terms concerning genetic variation and race. Here, we draw together the perspectives of participants in a recent interdisciplinary workshop on ancestry and health in medicine in order to explore the use of race in research issue from the vantage point of a variety of disciplines. We review the nature of the race controversy in the context of biomedical research and highlight several challenges to policy action, including restrictions resulting from commercial or regulatory considerations, the difficulty in presenting precise terminology in the media, and drifting or ambiguous definitions of key terms.
Intensive Loading Dose of Trastuzumab Achieves Higher-Than-Steady–State Serum Concentrations and Is Well Tolerated
Authors: Leyland-Jones Brian , Colomer Ramon , Trudeau Maureen E. , Wardley Andrew , Latreille Jean , Cameron David , Cubedo Ricardo , Al-Sakaff Nedal , Feyereislova Andrea , Catalani Olivier , Fukushima Yumi , Brewster Michael , Cortés Javier
Published: December 2009

Purpose

Pharmacokinetics (PKs) and safety results from phase II/III trials suggest that, if high trastuzumab serum concentrations are reached early during treatment for human epidermal growth factor receptor 2 (HER2)–positive breast cancer, patients will gain clinical benefit, and the synergistic effects of trastuzumab and chemotherapy will be maximized. This phase I/II study evaluated the PKs, efficacy, and safety of a novel, intensive loading regimen of trastuzumab in women with HER2-positive metastatic breast cancer (MBC).

Patients and Methods

An intensive loading regimen of trastuzumab was given (6 mg/kg intravenously on days 1, 8, and 15 followed by 6 mg/kg every 3 weeks from day 22) to women age 18 years or older with HER2-positive MBC who may have received previous surgery, radiotherapy, and/or chemotherapy. Study medication was continued until disease progression or withdrawal occurred.

Results

All eligible women (N = 72) received at least one dose of trastuzumab. Median estimated trough concentration of trastuzumab at the end of 3 weeks of the intensive loading regimen (total of 18 mg/kg of trastuzumab administered) of cycle 1 was 119 mg/L, which is higher than steady-state trough concentrations with a conventional weekly or every-3-week regimen (64.9 or 47.3 mg/L, respectively). No new or unexpected adverse events or increased cardiotoxicity were reported during the study. In patients with measurable disease (n = 47), response rate was 23.4%. Median time to progression was 7.7 months (in all patients).

Conclusion

An intensive loading regimen of trastuzumab achieved higher-than-steady–state serum concentrations during cycle 1, was well tolerated, and had a good efficacy profile.
Pandemic influenza A (H1N1) 2009: the experience of the first six months
Authors: Maritz Jean , Maree Leana , Preiser Wolfgang
Published: December 2009

After a break of 41 years, 2009 saw the first influenza pandemic of the 21st century caused by a triple-reassortant influenza A (H1N1) virus. The current estimated case fatality rate is lower than that of previous influenza pandemics, but this may change as the pandemic evolves. Illness frequently occurs in previously healthy, young adults with a wide range of clinical presentations. The majority of circulating pandemic viruses remain susceptible to neuraminidase inhibitors, although all strains are intrinsically resistant to the adamantanes. Monovalent vaccines against the pandemic strain are available in both live attenuated and inactivated forms. This review aims to summarise important virological, epidemiological and clinical aspects of the pandemic influenza A (H1N1) virus for physicians and other clinical personnel.

Clin Chem Lab Med 2010;48:11–21.
Natural Variation in Odorant Recognition Among Odorant-Binding Proteins in Drosophila melanogaster
Authors: Wang Ping , Lyman Richard F , Mackay Trudy F C , Anholt Robert R H
Published: December 2009

Chemical recognition is essential for survival and reproduction. Adaptive evolution has resulted in diverse chemoreceptor families, in which polymorphisms contribute to individual variation in chemosensation. To gain insights into the genetic determinants of individual variation in odorant recognition, we measured olfactory responses to two structurally similar odorants in a population of wild-derived inbred lines of Drosophila melanogaster. Odorant-binding proteins (OBPs) are the first components of the insect olfactory system to encounter odorants. Previously four single-nucleotide polymorphisms (SNPs) in the Obp99 group were associated with variation in olfactory responses to benzaldehyde. Here, we identify six different SNPs that are associated with variation in responses to a structurally similar odorant, acetophenone, in the same Obp genes. Five SNPs are in coding regions of Obp99b and Obp99d and one SNP is in the 3′-untranslated region of Obp99a (A610G). We found that the 610G allele is associated with higher response scores to acetophenone than the 610A allele, but with lower expression of Obp99a, suggesting that binding of acetophenone to Opb99a might limit rather than facilitate access to odorant receptors. Our results show that overlapping sets of OBPs contribute to odorant recognition for structurally similar odorants, but that different SNPs are associated with odorant-specific individual variation. Thus, dual olfactory recognition where OBPs regulate odorant access to receptors may enhance olfactory discrimination.
Streptococcus pneumoniae–Associated Hemolytic Uremic Syndrome: Classification and the Emergence of Serotype 19A
Authors: Copelovitch Lawrence , Kaplan Bernard S.
Published: December 2009

Streptococcus pneumoniae–associated hemolytic uremic syndrome (HUS) is an underrecognized condition that mainly occurs in young children. Early diagnosis is important because of the potential to improve morbidity and mortality rates. The purposes of this report are to review the clinical and laboratory features of 14 patients with pneumococcal HUS and present a modified classification to capture cases that may not have been documented with a diagnosis of pneumococcal HUS. We thereby provide a rationale for including patients with concurrent disseminated intravascular coagulopathy and/or those whose culture results were negative, and we highlight the emergence of serotype 19A subsequent to the introduction of 7-valent pneumococcal protein conjugate vaccine (Prevnar). This is the largest series of such subjects (to our knowledge) from a single center. Sixty-four percent of the patients recovered without any long-term sequelae. Three patients developed chronic kidney disease, 1 developed end-stage renal failure, and 1 died in the acute phase. The greatest risk factor for the development of chronic kidney disease is the need for acute dialysis for >20 days, and death in the acute phase is rare unless meningitis is the primary infection.
(E)pistemological Awareness, Instantiation of Methods, and Uninformed Methodological Ambiguity in Qualitative Research Projects
Authors: Koro-Ljungberg Mirka , Yendol-Hoppey Diane , Smith Jason Jude , Hayes Sharon B.
Published: December 2009

This article explores epistemological awareness and instantiation of methods, as well as uninformed ambiguity, in qualitative methodological decision making and research reporting. The authors argue that efforts should be made to make the research process, epistemologies, values, methodological decision points, and argumentative logic open, accessible, and visible for audiences. To these ends, they discuss two ways of conceptualizing the role of epistemological awareness and instantiation of methods, including (a) a series of decision junctures and (b) a spatial conceptualization of epistemological decision making. Through an analysis of researchers’ decision junctures drawn from studies published in high-impact education journals in 2006, the authors illustrate current methodological awareness and instantiation of methods in the field of education research.
Thermal Conductivity of Diamond Composites
Authors: Kidalov Sergey   V. , Shakhov Fedor  M.
Published: December 2009

A major problem challenging specialists in present-day materials sciences is the development of compact, cheap to fabricate heat sinks for electronic devices, primarily for computer processors, semiconductor lasers, high-power microchips, and electronics components. The materials currently used for heat sinks of such devices are aluminum and copper, with thermal conductivities of about 250 W/(m·K) and 400 W/(m·K), respectively. Significantly, the thermal expansion coefficient of metals differs markedly from those of the materials employed in semiconductor electronics (mostly silicon); one should add here the low electrical resistivity metals possess. By contrast, natural single-crystal diamond is known to feature the highest thermal conductivity of all the bulk materials studied thus far, as high as 2,200 W/(m·K). Needless to say, it cannot be applied in heat removal technology because of high cost. Recently, SiC- and AlN-based ceramics have started enjoying wide use as heat sink materials; the thermal conductivity of such composites, however, is inferior to that of metals by nearly a factor two. This prompts a challenging scientific problem to develop diamond-based composites with thermal characteristics superior to those of aluminum and copper, adjustable thermal expansion coefficient, low electrical conductivity and a moderate cost, below that of the natural single-crystal diamond. The present review addresses this problem and appraises the results reached by now in studying the possibility of developing composites in diamond-containing systems with a view of obtaining materials with a high thermal conductivity.
Real Time Imaging of Biomarkers in the Parkinson's Brain Using Mini-Implantable Biosensors. II. Pharmaceutical Therapy with Bromocriptine
Authors: Broderick Patricia  A. , Kolodny Edwin  H.
Published: December 2009

We used Neuromolecular Imaging (NMI) and trademarked BRODERICK PROBE® mini-implantable biosensors, to selectively and separately detect neurotransmitters in vivo, on line, within seconds in the dorsal striatal brain of the Parkinson’s Disease (PD) animal model. We directly compared our results derived from PD to the normal striatal brain of the non-Parkinson’s Disease (non-PD) animal. This advanced biotechnology enabled the imaging of dopamine (DA), serotonin (5-HT), homovanillic acid (HVA) a metabolite of DA, L-tryptophan (L-TP) a precursor to 5-HT and peptides, dynorphin A 1-17 (Dyn A) and somatostatin (somatostatin releasing inhibitory factor) (SRIF). Each neurotransmitter and neurochemical was imaged at a signature electroactive oxidation/half-wave potential in dorsal striatum of the PD as compared with the non-PD animal. Both endogenous and bromocriptine-treated neurochemical profiles in PD and non-PD were imaged using the same experimental paradigm and detection sensitivities. Results showed that we have found significant neurotransmitter peptide biomarkers in the dorsal striatal brain of endogenous and bromocriptine-treated PD animals. The peptide biomarkers were not imaged in dorsal striatal brain of non-PD animals, either endogenously or bromocriptine-treated. These findings provide new pharmacotherapeutic strategies for PD patients. Thus, our findings are highly applicable to the clinical treatment of PD.
Flow Injection Chemiluminescent Immunoassay for Carcinoembryonic Antigen Using Boronic Immunoaffinity Column
Authors: Ma Xiaoling , Li Huihui , Wu Min , Sun Chong , Li Laifa , Yang Xiaodi
Published: December 2009

A flow injection chemiluminescence immunoassay for rapid and sensitive detection of carcinoembryonic antigen (CEA) by using a phenylboronic acid-based immunoaffinity column as a glycoprotein collector was proposed in this paper. The column was prepared by coupling of 3-aminophenylboronic acid on the glass beads through a γ-glycidoxypropyltrimethoxysilane (GPMS) linkage. Based on an indirect competitive immunoreaction, the mixture of CEA sample and enzyme conjugated CEA antibody (HRP-anti-CEA) was incubated in advance, followed by direct injection to the column to capture free HRP-labeled CEA antibody in the column. The trapped HRP-labeled antibody was detected by flow inject chemiluminescence in the presence of luminol and hydrogen peroxide. The decreased chemiluminescent signal was proportional to the concentration of CEA in the range of 3.0–30.0 ng/mL with a correlation coefficient of 0.998. The column showed an acceptable reproducibility and stability and is potentially used for practical clinical detection of the serum CEA level.
A New Experimental Method for in Situ Corrosion Monitoring Under Alternate Wet-Dry Conditions
Authors: Fu Xinxin , Dong Junhua , Han Enhou , Ke Wei
Published: December 2009

A new experimental method was applied in in situ corrosion monitoring of mild steel Q235 under alternate wet-dry conditions. The thickness of the electrolyte film during the wet cycle was monitored by a high-precision balance with a sensibility of 0.1 mg. At the same time, an electrochemical impedance technique was employed to study the effect of film thickness on corrosion rates. Experimental results showed that there was a critical electrolyte film condition for which the corrosion rate reached a maximum during wet-dry cycles. For the substrate, the critical condition could be described by a film thickness of about 17 μm. For the rusted specimen, the critical condition could be described by an electrolyte amount of about 0.038 g, which is equivalent to a film thickness of 38 μm. This monitoring system was very useful for studying atmospheric corrosion of metals covered by corrosion products.
An Algebraic Approach to Weakly Symmetric Finsler Spaces
Authors: Deng Shaoqiang
Published: December 2009

In this paper, we introduce a new algebraic notion, weakly symmetric Lie algebras, to give an algebraic description of an interesting class of homogeneous Riemann-Finsler spaces, weakly symmetric Finsler spaces. Using this new definition, we are able to give a classification of weakly symmetric Finsler spaces with dimensions 2 and 3. Finally, we show that all the non-Riemannian reversible weakly symmetric Finsler spaces we find are non-Berwaldian and with vanishing S-curvature. Thismeans that reversible non-Berwaldian Finsler spaces with vanishing S-curvaturemay exist at large. Hence the generalized volume comparison theorems due to Z. Shen are valid for a rather large class of Finsler spaces.
Exploring Spatial and Multitype Assemblages of Species Abundances
Authors: Georgescu Vera , Soubeyrand Samuel , Kretzschmar André , Laine Anna‐Liisa
Published: December 2009

The ecological theory of the existence of multiple stable states between species, or the spatial heterogeneity of some unobserved environmental factor, supports the idea of multitype interactions between species. These multitype interactions can lead to different assemblages of species abundances. An exploratory tool for the detection of these species assemblages and for their spatial analysis is presented in this article. A two‐stage analysis is proposed. First, a classification into types of species assemblages using only the species abundances at each site, regardless of their spatial location, is performed. The clustering procedure is based on multivariate normal mixtures and provides a measure of the classification uncertainty. Second, some tools for the study of the spatial structure of these types of assemblages are presented. We transfer the classification uncertainty to the spatial analysis of the classes in order to draw more accurate conclusions. This classification and spatial analysis method is used to point out a spatial gradient of infection in a host–pathogen system in the Åland Islands in Finland. It can be a useful preliminary tool for ecological studies involving the spatial distributions of several species.
The effects of Nigella sativa on bile duct ligation induced‐liver injury in rats
Authors: Coban Sacid , Yildiz Fahrettin , Terzi Alpaslan , Al Behcet , Aksoy Nurten , Bitiren Muharrem , Celik Hakim
Published: December 2009

Nigella sativa (NS) has been shown to have antioxidant and antiinflammatory activities in different conditions. The goal of this study was to evaluate the effects of NS on cholestatic liver injury in rats. Thirty rats were recruited in the study as follows: Group 1, Bile duct ligation (BDL) (n = 10); Group 2, BDL plus NS (n = 10); and Group 3, Sham (n = 10). Bile duct ligated group received 0.2 mL kg−1 dose of NS intraperitoneally daily throughout 14 days. Liver damage and cholestasis were determined by the biochemical and the pathologic examination. Data showed a decrease in gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities of the NS treated rats when compared with BDL group (p < 0.001 for GGT and p < 0.05 for others). The NS treated rats' tissue levels of total oxidant status (TOS), oxidative stress index (OSI), and myeloperoxidase (MPO) were significantly lower than that of the BDL group (p < 0.01 for all). Increases in total antioxidant capacity (TAC) and catalase (CAT) levels were statistically significant in the NS treated rats compared to BDL group (p < 0.01 for both). On the other hand, administration of NS in the rats with biliary obstruction resulted in inhibition of necro‐inflammation. These results indicate that NS exerts a therapeutic effect on cholestatic liver injury in bile duct ligated rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. Copyright © 2009 John Wiley & Sons, Ltd.
Thermal‐ and Light‐Induced Spin Crossover in a Guest‐Dependent Dinuclear Iron(II) System
Authors: Amoore Jarrod J. M. , Neville Suzanne M. , Moubaraki Boujemaa , Iremonger Simon S. , Murray Keith S. , Létard Jean‐François , Kepert Cameron J.
Published: December 2009

We previously reported the dinuclear material [FeII2(ddpp)2(NCS)4]⋅4 CH2Cl2 (1⋅4 CH2Cl2; ddpp=2,5‐di(2′,2′′‐dipyridylamino)pyridine) and its partially desolvated analogue (1⋅CH2Cl2), which undergo two‐ and one‐step spin‐crossover (SCO) transitions, respectively. Here, we manipulate the type and degree of solvation in this system and find that either a one‐ or two‐step spin transition can be specifically targeted. The chloroform clathrate 1⋅4 CHCl3 undergoes a relatively abrupt one‐step SCO, in which the two equivalent FeII sites within the dinuclear molecule crossover simultaneously. Partial desolvation of 1⋅4 CHCl3 to form 1⋅3 CHCl3 and 1⋅CHCl3 occurs through single‐crystal‐to‐single‐crystal processes (monoclinic C2/c to P21/n to P21/n) in which the two equivalent FeII sites become inequivalent sites within the dinuclear molecule of each phase. Both 1⋅3 CHCl3 and 1⋅CHCl3 undergo one‐step spin transitions, with the former having a significantly higher SCO temperature than 1⋅4 CHCl3 and the latter, and each has a broader SCO transition than 1⋅4 CHCl3, attributable to the overlap of two SCO steps in each case. Further magnetic manipulation can be carried out on these materials through reversibly resolvating the partially desolvated material with chloroform to produce the original one‐step SCO, or with dichloromethane to produce a two‐step SCO reminiscent of that seen for 1⋅4 CH2Cl2. Furthermore, we investigate the light‐induced excited spin state trapping (LIESST) effect on 1⋅4 CH2Cl2 and 1⋅CH2Cl2 and observe partial LIESST activity for the former and no activity for the latter.
Enantioseparation of benzazoles and benzanilides on polysaccharide‐based chiral columns
Authors: Kubota Takateru , Sawada Naotaka , Zhou Lili , Welch Christopher J.
Published: December 2009

The chiral recognition ability of the polysaccharide‐based chiral columns (Chiralpak AD‐RH, Chiralpak AS‐RJ, Chiralpak IC, Chiralcel OD‐RH, and Chiralcel OJ‐RH) for the benzazoles and the benzanilides was evaluated under reversed phase conditions. The columns showed the high chiral recognition ability for a wide range of benzazoles and benzanilides. Twenty‐one racemates were used for the evaluation, and 20 racemates were completely separated on at least one of the columns. In particular, AS‐RH and OJ‐RH showed the high chiral recognition ability for the benzazoles, and the AD‐RH, IC, and OJ‐RH were effective for the benzanilides. Chirality 2010. © 2009 Wiley‐Liss, Inc.
Can Copper(II) Mediate Hoogsteen Base‐Pairing in a Left‐Handed DNA Duplex? A Pulse EPR Study
Authors: Santangelo Maria Grazia , Antoni Philipp M. , Spingler Bernhard , Jeschke Gunnar
Published: December 2009

Pulse EPR spectroscopy is used to investigate possible structural features of the copper(II) ion coordinated to poly(dG‐dC)⋅poly(dG‐dC) in a frozen aqueous solution, and the structural changes of the polynucleotide induced by the presence of the metal ion. Two different copper species were identified and their geometry explained by a molecular model. According to this model, one species is exclusively coordinated to a single guanine with the N7 nitrogen atom forming a coordinative bond with the copper. In the other species, a guanine and a cytosine form a ternary complex together with the copper ion. A copper crosslink between the N7 of guanine and N3 of cytosine is proposed as the most probable coordination site. Moreover, no evidence was found for an interaction of either copper species with a phosphate group or equatorial water molecules. In addition, circular dichroism (CD) spectroscopy showed that the DNA of the CuII‐poly(dG‐dC)⋅poly(dG‐dC) adducts resembles the left‐handed Z‐form. These results suggest that metal‐mediated Hoogsteen base pairing, as previously proposed for a right‐handed DNA duplex, can also occur in a double‐stranded left‐handed DNA.