bluuebunny/crossref_metadata_2025 huggingface dataset:
Research Strategies: Lessons Learned From the Studies of Chinese Americans and Korean Americans
Authors: Lee Shih-Yu , Kim Eunjung , Chen Wei-Ti
Published: June 2010

Given the increasing population of Asian Americans in the United States, there is an urgent need for culturally and linguistically sensitive and appropriate research to validate research findings, particularly with respect to health care. Although increasing attention is being focused on ethnic minority-group studies, few research reports concentrate on research strategies with respect to Asian American populations. This article describes the importance of language in culturally informed research for ethnic minorities and explores the paradigm for Asian American research methods. Finally, this article makes use of six research projects to discuss practical issues that help produce culturally and linguistically appropriate research on Asian American populations. Cultural diversity issues in patient care need to be included in the health care—related curriculum. Cultural interpretation programs should be facilitated in hospital settings.
Multilevel Confirmatory Factor Analysis of a Scale Measuring Interagency Collaboration of Children’s Mental Health Agencies
Authors: Dedrick Robert F. , Greenbaum Paul E.
Published: June 2010

Multilevel confirmatory factor analysis was used to evaluate the factor structure underlying the 12-item, three-factor Interagency Collaboration Activities Scale (ICAS) at the informant level and at the agency level. Results from 378 professionals (104 administrators, 201 service providers, and 73 case managers) from 32 children’s mental health service agencies supported a correlated three-factor model at each level and indicated that the item loadings were not significantly ( p > .05) different across levels. Reliability estimates of the three factors (Financial and Physical Resource Activities, Program Development and Evaluation Activities, and Collaborative Policy Activities) at the agency level were .81, .60, and .72, respectively, whereas these estimates were .79, .82, and .85 at the individual level. These multilevel results provide support for the construct validity of the scores from the ICAS. When the ICAS was examined in relation to Level 1 and Level 2 covariates, results showed that participants’ characteristics (i.e., age, job role, gender, educational level, and number of months employed) and agency characteristics (i.e., state location and number of employees) were not significantly ( p > .05) related to levels of interagency collaboration.
Making the Best of Temporal Locality: Just-in-Time Renaming and Lazy Write-Back on the Cell/B.E
Authors: Bellens Pieter , Perez Josep M. , Badia Rosa M. , Labarta Jesus
Published: June 2010

Cell Superscalar (CellSs) provides a simple, flexible and easy programming approach for the Cell Broadband Engine (Cell/B.E.) that automatically exploits the inherent concurrency of applications at a function or task level. The CellSs environment is based on a source-to-source compiler that translates annotated C or Fortran code and a runtime library tailored for the Cell/B.E. that orchestrates the concurrent execution of the application. We introduce a technique called bypassing that allows CellSs to perform core-to-core Direct Memory Access (DMA) transfers for generic applications. In this review we concisely summarize the bypassing practice and introduce two improvements: just-in-time renaming and lazy write-back. These extensions come at no additional cost and potentially increase performance by improving the perceived bandwidth of the Element Interconnect Bus (EIB). Experiments on five fundamental linear algebra kernels demonstrate the applicability of these techniques and quantify the benefit that can be reaped. We also present performance results for a first prototype of CellSs with bypassing.
Analytical Performance Prediction for Iterative Reconstruction Techniques in Electron Tomography of Biological Structures
Authors: Fritzsche Paula Cecilia , Fernandez Jose-Jesus , Rexachs Dolores , Garcia Inmaculada , Luque Emilio
Published: June 2010

The problem of the three-dimensional reconstruction of structures from projection data occurs in a wide range of areas. Algebraic reconstruction techniques (ART) are iterative procedures for recovering the structure of three-dimensional objects from projection images. ART was dismissed during the seventies due to the high demands on computing resources. In the following years, computer algorithms for image reconstruction with fast convergence were designed, implemented, evaluated, and, finally, optimized. Nevertheless, the reported experimental data exceed computing potential for a single CPU as well as I/O capability. Interesting recent research aims at acquiring experience with parallelization strategies and at demonstrating the effectiveness of the massively parallel processing approach in biological environments. This makes the investigation of performance prediction for high-performance parallel computing of paramount importance. A performance prediction model for iterative reconstruction techniques (IRT) would provide additional knowledge of the parallel computer algorithm and predict its behavior under specific conditions or hardware configurations. Also, a goal of performance analysis is to find the set of parameter values that produces the best overall performance. Not only the end-users of these systems have a vested interest in predicting performance but also the computer designers and the professional engineers. This article addresses the derivation and evaluation of an analytical performance prediction model for a parallelization of IRT (block iterative version of the component averaging, BICAV) and emphasizes the essential role of parallel computers in image reconstruction. The techniques’ behavior is analyzed through specifics steps to create an analytical formulation of the problem. BPTomo is a parallel distributed application for tomographic reconstruction that uses IRT. The analytical performance prediction model is validated by comparison of the estimated times for representative datasets against BPTomo computation times measured on two PC clusters. The analytical model is shown to be quite accurate. The percentage deviation between estimated and measured times is less than 12%.
Measuring outcomes in outpatient child psychiatry: The contribution of electronic technologies and parent report
Authors: Murphy J. Michael , Masek Bruce , Babcock Rebecca , Jellinek Michael , Gold Joseph , Drubner Stacey , Sklar Ken , Hacker Karen
Published: June 2010

The objective of this study was to evaluate the impact of electronic technologies on the completion of a standardized rating form in an outpatient child psychiatry clinic, and the feasibility of adding a parent-report measure to the form. An electronic Outcomes Rating Form (e-ORF) was used in conjunction with a web-based patient tracking system and digital pens which allowed form data to be directly entered into a database. Clinician forms were collected for 87% of the 248 children seen for intake, a significant increase over the rate of 72% obtained in the same clinic with paper forms. Rating forms were also obtained from 85% of parents. Clinician- and parent-completed measures were moderately correlated with each other. This study showed that 1) the use of electronic technologies is associated with improved clinician completion rates; 2) it is possible to obtain rating forms from most parents; 3) clinician and parent measures provide related but distinct information; and 4) improvements in functioning found with clinician-report measures are corroborated by independent parent reports.
The clinical practice of Cognitive Behavioural Therapy for children and young people with a diagnosis of Asperger’s Syndrome
Authors: Donoghue Kate , Stallard Paul , Kucia Joanna
Published: June 2010

Children and young people diagnosed with Asperger’s Syndrome (AS) have significant social-communication difficulties and impaired empathy and theory of mind skills. These difficulties place them at risk of developing mental health problems, particularly anxiety, depression and obsessive compulsive disorder. Although Cognitive Behavioural Therapy (CBT) is recognised as an effective intervention for these problems in both child and adult populations, little research has specifically looked at the use of CBT with children and young people with an AS diagnosis. However, limited evidence suggests that CBT, if suitably adapted, is a feasible and potentially helpful treatment option. This paper focuses on the clinical practice of CBT and explores how the underpinning therapeutic relationship can be modified to meet the cognitive needs of this particular group of young clients.
Future Directions in the Sociology of Emotions
Authors: Stets Jan E.
Published: June 2010

In this article, I discuss how sociologists can advance the scientific study of emotions by broadening their work and approaching it more creatively. This requires sociologists to examine more closely the cultural, social structural, and biological aspects of emotions. It also requires them to investigate the rich array of emotions that individuals experience and the flow of these emotions within and across situations.
Show and Tell: The Role of Language in Categorizing Facial Expression of Emotion
Authors: Roberson Debi , Damjanovic Ljubica , Kikutani Mariko
Published: June 2010

We review evidence that language is involved in the establishment and maintenance of adult categories of facial expressions of emotion. We argue that individual and group differences in facial expression interpretation are too great for a fully specified system of categories to be universal and hardwired. Variations in expression categorization, across individuals and groups, favor a model in which an initial “core” system recognizes only the grouping of positive versus negative emotional expressions. The subsequent development of a rich representational structure may require the integration of a verbal categorization system with a perceptual processing system that is category-agnostic. Such a model may reconcile many strands of apparently conflicting behavioral, physiological, and neuroscience evidence concerning our understanding of facial expressions of emotion.
N, N, N′, N′-tetramethylethylenediamine on anticorrosion ability of micro-arc oxide coatings formed on magnesium alloy AZ91D
Authors: Bai A , Chen Z J
Published: June 2010

Oxide coatings on AZ91D alloy were prepared using micro-arc oxidation techniques at a low applied voltage in the Si–P electrolyte with the additive, hexamethylenetetramine or tetramethylethylenediamine (TMEDA). The additives in the Si–P electrolyte smoothed the cracks/pores on the oxide coatings. The 0·1M TMEDA in the Si–P electrolyte improved two orders of the magnitude of the anticorrosion ability from bare AZ91D alloy to the anodic coating, which was prepared by the Si–P electrolyte with 0·1M TMEDA. The surface roughness Ra was reduced from 10·2 to 1·1 μm, when the oxide coating was anodised in the low breakdown voltage and low thermal stress in the Si–P electrolyte with 0·1M TMEDA. In this work, the aforementioned additives in the Si–P electrolyte smoothed the surface of the oxide coating and modified the crystalline structure, resulting in a better anticorrosion ability.
Improved corrosion resistance of brush plated nanocrystalline Ni–Fe alloy coatings in 3·5 wt‐%NaCl solution
Authors: Dai P Q , Xiang Z N , Chen W Z
Published: June 2010

Nanocrystalline Ni and Ni–Fe alloy coatings were synthesised by brush plating using soluble anode, and the corrosion characteristics of nanocrystalline Ni, Ni–5·84%Fe and Ni–13·49%Fe were investigated by soak method and electrochemical polarisation method respectively. The nanocrystalline Ni–Fe alloy coatings showed higher hardness and smaller grain size than that of Ni coating. Ni–13·49%Fe alloy coating exhibited better corrosion resistance in 3·5 wt‐% NaCl solution than the nanocrystalline Ni coating and the Ni–5·84%Fe coating, which indicats that the corrosion resistant of nanocrystalline Ni coating can be improved by adding appropriate amount of Fe.
Muscle-derived Gr1dimCD11b+ cells enhance neovascularization in an ischemic hind limb mouse model
Authors: Kim Jeong A. , March Keith , Chae Hee-Don , Johnstone Brian , Park Su-Jung , Cook Todd , Merfeld-Clauss Stephanie , Broxmeyer Hal E.
Published: June 2010

Gr1+CD11b+ cells are characterized as myeloid-derived suppressor cells potentially involved in angiogenesis. We demonstrate that Gr1+CD11b+ cells isolated from ischemic muscle in a hind-limb ischemic C57BL/6 mouse model play a role in vessel formation after ischemic injury. Gr1dimCD11b+ cells, a subpopulation of Gr1+CD11b+ cells, within skeletal muscle were increased in context of ischemia. Strikingly, astrocyte-plexus formed from muscle-derived Gr1dimCD11b+ cells in Matrigel culture, followed by formation of isolectin and von Willebrand Factor–expressing cells, similar to that reported for angiogenesis in retina. When isolated muscle-derived Gr1dimCD11b+ cells were injected into ischemic muscles, recovery of blood flow was significantly enhanced and these cells were incorporated into vessel walls. This suggests that Gr1dimCD11b+ cells are recruited into ischemic regions after ischemia and may be involved in angiogenesis by their capacity to generate vascular cells.
IVIg modulates BCR signaling through CD22 and promotes apoptosis in mature human B lymphocytes
Authors: Séïté Jean-François , Cornec Divi , Renaudineau Yves , Youinou Pierre , Mageed Rizgar A. , Hillion Sophie
Published: June 2010

Among various mechanisms for interactions with B cells, intravenous immunoglobulin (IVIg) may operate through the insertion of its Fc part into the Fc-γ receptor, or the binding of its sialic acid (SA)–bearing glycans to the negatively regulating CD22 lectin. It appeared that IVIg reduces B lymphocyte viability in a dose- and time-dependent manner. Furthermore, we show by confocal microscopy that SA-positive IgG, but not SA-negative IgG bind to CD22. This interaction reduces the strength of B-cell receptor–mediated signaling trough down-regulating tyrosine phosphorylation of Lyn and the B-cell linker proteins, and up-regulating phospholipase Cγ2 activation. This cascade resulted in a sustained activation of Erk 1/2 and arrest of the cell cycle at the G1 phase. These changes may be accounted for the efficacy of IVIg in autoimmune diseases.
Role of 2-month sputum smears in predicting culture conversion in pulmonary tuberculosis
Authors: Su W-J. , Feng J-Y. , Chiu Y-C. , Huang S-F. , Lee Y-C.
Published: June 2010

Sputum smears and culture conversion are frequently used to evaluate treatment response in pulmonary tuberculosis patients. Limited data are available on the evaluation of the correlation between under-treatment sputum smear results and culture conversion.

This prospective study included sputum culture-proven pulmonary tuberculosis patients at six hospitals in Taiwan. At least two sets of sputum were collected at the completion of 8 weeks of TB treatment. The sensitivities and specificities of 2-month sputum smears were estimated based on culture conversion status.

A total of 371 patients were enrolled for analysis. Factors associated with culture conversion included having a smear positive before treatment, presence of a cavity on radiography, rifampicin resistance and usage of the DOTS (directly observed therapy, short course) strategy. The sensitivities of 2-month sputum smears for culture conversion among all patients, initially smear-positive patients and initially smear-negative patients were 64.3, 71.4 and 38%, respectively, and the specificities were 81.6, 69.9 and 92.8%, respectively. In patients who were 2-month sputum smear-positive, the 2-month culture conversion rate was 80% if the patients were under DOTS and without cavitary lesions in radiograms.

The predictive value of 2-month sputum smears in culture conversion was limited and highly influenced by clinical factors in pulmonary tuberculosis patients.
Diaphragm electromyogram in infants with abdominal wall defects and congenital diaphragmatic hernia
Authors: Kassim Z. , Jolley C. , Moxham J. , Greenough A. , Rafferty G.F.
Published: June 2010

Measurement of the diaphragm electromyogram (EMGdi) elicited by phrenic nerve stimulation could be useful to assess neonates suffering from respiratory distress due to diaphragm dysfunction, as observed in infants with abdominal wall defects (AWD) or congenital diaphragmatic hernia (CDH). The study aims were to assess the feasibility of recording EMGdi using a multipair oesophageal electrode catheter and examine whether diaphragm muscle and/or phrenic nerve function was compromised in AWD or CDH infants.

Diaphragm compound muscle action potentials elicited by magnetic phrenic nerve stimulation were recorded from 18 infants with surgically repaired AWD (n = 13) or CDH (n = 5), median (range) gestational age 36.5 (34–40) weeks. Diaphragm strength was assessed as twitch transdiaphragmatic pressure (TwPdi).

One AWD patient had prolonged phrenic nerve latency (PNL) bilaterally (left 9.31 ms, right 9.49 ms) and two CDH patients had prolonged PNL on the affected side (10.1 ms and 10.08 ms). There was no difference in left and right TwPdiin either group. PNL correlated significantly with TwPdiin CDH (r = 0.8; p = 0.009).

Oesophageal EMG and magnetic stimulation of the phrenic nerves can be useful to assess phrenic nerve function in infants. Reduced phrenic nerve conduction accompanies the reduced diaphragm force production observed in infants with CDH.
Smoking strongly predicts disability retirement due to COPD: the Finnish Twin Cohort Study
Authors: Koskenvuo K. , Broms U. , Korhonen T. , Laitinen L.A. , Huunan-Seppälä A. , Keistinen T. , Autti-Rämö I. , Kaprio J. , Koskenvuo M.
Published: June 2010

No previous studies on the association of smoking behaviour with disability retirement due to register verified chronic obstructive pulmonary disease (COPD) exist. This 30-yr follow-up study examined how strongly aspects of cigarette smoking predict disability retirement due to COPD.

The study population consisted of 24,043 adult Finnish twins (49.7% females) followed from 1975 to 2004. At baseline the participants had responded to a questionnaire. Information on retirement was obtained from the Finnish pension registers.

Smoking strongly predicted disability retirement due to COPD. In comparison to never-smokers, age adjusted hazard ratio (HR) for current smokers was 22.0 (95% CI 10.0–48.5) and for smokers with ≥12 pack-yrs was 27.3 (95% CI 12.6–59.5). Similar estimates of risk were observed in within-pair analyses of twin pairs discordant for disability retirement due to COPD. Among discordant monozygotic pairs those with disability pension due to COPD were more often current smokers. The effect of early smoking onset (<18 yrs) on the risk of disability retirement due to COPD remained after adjustment for the amount smoked (HR 1.70, 95% CI 1.08–2.68).

Smoking strongly predicts disability retirement due to COPD. Preventive measures against disability retirement and other harmful consequences of tobacco smoking should receive greater emphasis.
EPHX1polymorphisms, COPD and asthma in 47,000 individuals and in meta-analysis
Authors: Lee J. , Nordestgaard B.G. , Dahl M.
Published: June 2010

We tested the hypothesis that two well-characterised functional polymorphisms of the microsomal epoxide hydrolase gene (EPHX1),T113CandA139G, may influence susceptibility to chronic obstructive pulmonary disease (COPD) and asthma.

We genotyped participants from the Copenhagen City Heart Study (n = 10,038) and the Copenhagen General Population Study (n = 37,022) for theT113CandA139Gvariants in theEPHX1gene and measured lung function and recorded COPD hospitalisation and asthma and smoking history. Finally, we meta-analysed results from 19 studies including 7,489 COPD cases and 42,970 controls.

The OR for spirometry-defined COPD or COPD hospitalisation did not differ from 1.0 for any of theEPHX1genotypes or phenotypes overall, or in smokers or nonsmokers separately (p-value for trend 0.18–0.91). Likewise,EPHX1genotypes or phenotypes did not associate with risk of asthma (p-value for trend 0.46–0.98). In meta-analysis, random effects OR for COPD inT113Cheterozygotes and homozygotesversusnon-carriers were 1.17 (0.99–1.38) and 1.38 (1.09–1.74), respectively. Corresponding values forA139Gwere 0.93 (0.83–1.05) and 0.89 (0.78–1.02).

Our results indicate that genetically reduced microsomal epoxide hydrolase activity is not a major risk factor for COPD or asthma in the Danish population; however, meta-analysis cannot completely exclude a minor effect on COPD risk.
Prognostic factors in pathological stage IB nonsmall cell lung cancer greater than 3 cm
Authors: Hung J-J. , Jeng W-J. , Hsu W-H. , Lin S-F. , Hsieh C-C. , Huang B-S. , Huang M-H. , Liu J-S. , Chou T-Y. , Wu Y-C.i
Published: June 2010

Significant heterogenity of stage IB (sixth edition of the TNM staging system) nonsmall cell lung cancer (NSCLC) has been identified, and further subclassification according to tumour size has been proposed. The aim of this study is to evaluate the prognostic factors in patients with resected stage IB NSCLC >3 cm.

From January 1980 to December 2000, 525 patients underwent surgical resection for stage IB NSCLC >3 cm at Taipei Veterans General Hospital, Taipei, Taiwan. The clinicopathological characteristics of these patients were retrospectively reviewed.

The 5- and 10-yr overall survival rates were 44.9% and 27.3%, respectively. Age (p<0.001), tumour size (p = 0.002), extent of pulmonary resection (p = 0.002), histological type (p = 0.005) and number of mediastinal lymph nodes dissected/sampled (p = 0.004) were significant predictors for overall survival in multivariate analysis. Patients with tumour size >7 cm, or >5 to ≤7 cm, had a worse survival than those with tumour size >3 to ≤5 cm. However, visceral pleural invasion did not influence overall survival.

Stage IB NSCLC with a diameter >3 cm may be subclassified according to tumour size regardless of visceral pleural invasion.
Ongoing tuberculosis transmission to children in Greenland
Authors: Soborg B. , Koch A. , Thomsen V.Ø. , Ladefoged K. , Andersson M. , Wohlfahrt J. , Melbye M. , Andersen A.B.
Published: June 2010

Inuit in the Arctic are experiencing an increase in tuberculosis cases, reaching levels in Greenland comparable to high-incidence countries. This prompted us to study the level of tuberculosis transmission to Greenlandic children. Specifically, we estimated the current prevalence ofMycobacterium tuberculosisinfection (MTI) and the underlying annual risk of MTI.

2,231 Greenlandic school children aged 5–17 yrs (∼25% of the Greenlandic population in the relevant age group) were tested for MTI using the tuberculin skin test and the QuantiFERON®-TB Gold in-tube test. Subjects with dual-positive results were considered infected and subjects with dual-negative results uninfected. The children with discordant test results were classified as probably having MTI and analysed separately.

8.1% of the children had dual-positive test results. The annual risk of MTI was estimated as 0.80% (95% CI 0.67–0.92%) giving a cumulative risk at the 18th birthday of 13.4%. The annual risk of MTI varied substantially by ethnicity (0.87% in Inuit children, 0.02% in non-Inuit children; p<0.001) and by location (0.13% on the west coast, 1.68% on the south coast; p<0.001).

M. tuberculosistransmission occurs at a very high level in Inuit children with pronounced geographic differences emphasising the need for immediate public health interventions.
Systems genetics analysis of body weight and energy metabolism traits in Drosophila melanogaster
Authors: Jumbo-Lucioni Patricia , Ayroles Julien F , Chambers Michelle Moses , Jordan Katherine W , Leips Jeff , Mackay Trudy FC , De Luca Maria
Published: June 2010

Background

Obesity and phenotypic traits associated with this condition exhibit significant heritability in natural populations of most organisms. While a number of genes and genetic pathways have been implicated to play a role in obesity associated traits, the genetic architecture that underlies the natural variation in these traits is largely unknown. Here, we used 40 wild-derived inbred lines ofDrosophila melanogasterto quantify genetic variation in body weight, the content of three major metabolites (glycogen, triacylglycerol, and glycerol) associated with obesity, and metabolic rate in young flies. We chose these lines because they were previously screened for variation in whole-genome transcript abundance and in several adult life-history traits, including longevity, resistance to starvation stress, chill-coma recovery, mating behavior, and competitive fitness. This enabled us not only to identify candidate genes and transcriptional networks that might explain variation for energy metabolism traits, but also to investigate the genetic interrelationships among energy metabolism, behavioral, and life-history traits that have evolved in natural populations.

Results

We found significant genetically based variation in all traits. Using a genome-wide association screen for single feature polymorphisms and quantitative trait transcripts, we identified 337, 211, 237, 553, and 152 novel candidate genes associated with body weight, glycogen content, triacylglycerol storage, glycerol levels, and metabolic rate, respectively. Weighted gene co-expression analyses grouped transcripts associated with each trait in significant modules of co-expressed genes and we interpreted these modules in terms of their gene enrichment based on Gene Ontology analysis. Comparison of gene co-expression modules for traits in this study with previously determined modules for life-history traits identified significant modular pleiotropy between glycogen content, body weight, competitive fitness, and starvation resistance.

Conclusions

Combining a large phenotypic dataset with information on variation in genome wide transcriptional profiles has provided insight into the complex genetic architecture underlying natural variation in traits that have been associated with obesity. Our findings suggest that understanding the maintenance of genetic variation in metabolic traits in natural populations may require that we understand more fully the degree to which these traits are genetically correlated with other traits, especially those directly affecting fitness.
Overexpression of S100A4 in human cancer cell lines resistant to methotrexate
Authors: Mencía Nuria , Selga Elisabet , Rico Isabel , de Almagro M Cristina , Villalobos Xenia , Ramirez Sara , Adan Jaume , Hernández Jose L , Noé Véronique , Ciudad Carlos J
Published: June 2010

Background

Methotrexate is a chemotherapeutic drug that is used in therapy of a wide variety of cancers. The efficiency of treatment with this drug is compromised by the appearance of resistance. Combination treatments of MTX with other drugs that could modulate the expression of genes involved in MTX resistance would be an adequate strategy to prevent the development of this resistance.

Methods

The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. A global comparison of all the studied cell lines was performed in order to find out differentially expressed genes in the majority of the MTX-resistant cells. S100A4 mRNA and protein levels were determined by RT-Real-Time PCR and Western blot, respectively. Functional validations of S100A4 were performed either by transfection of an expression vector for S100A4 or a siRNA against S100A4. Transfection of an expression vector encoding for β-catenin was used to inquire for the possible transcriptional regulation of S100A4 through the Wnt pathway.

Results

S100A4 is overexpressed in five out of the seven MTX-resistant cell lines studied. Ectopic overexpression of this gene in HT29 sensitive cells augmented both the intracellular and extracellular S100A4 protein levels and caused desensitization toward MTX. siRNA against S100A4 decreased the levels of this protein and caused a chemosensitization in combined treatments with MTX. β-catenin overexpression experiments support a possible involvement of the Wnt signaling pathway in S100A4 transcriptional regulation in HT29 cells.

Conclusions

S100A4 is overexpressed in many MTX-resistant cells. S100A4 overexpression decreases the sensitivity of HT29 colon cancer human cells to MTX, whereas its knockdown causes chemosensitization toward MTX. Both approaches highlight a role for S100A4 in MTX resistance.
Functional mapping of genotype-environment interactions for soybean growth by a semiparametric approach
Authors: Li Qin , Huang Zhongwen , Xu Meng , Wang Chenguang , Gai Junyi , Huang Youjun , Pang Xiaoming , Wu Rongling
Published: June 2010

Background

Functional mapping is a powerful approach for mapping quantitative trait loci (QTLs) that control biological processes. Functional mapping incorporates mathematical aspects of growth and development into a general QTL mapping framework and has been recently integrated with composite interval mapping to build up a so-called composite functional mapping model, aimed to separate multiple linked QTLs on the same chromosomal region.

Results

This article reports the principle of using composite functional mapping to estimate the effects of QTL-environment interactions on growth trajectories by parametrically modeling the tested QTL in a marker interval and nonparametrically modeling the markers outside the interval as co-factors. With this new model, we can characterize the dynamic patterns of the genetic effects of QTLs governing growth trajectories, estimate the global effects of the underlying QTLs during the course of growth and development, and test the differentiation in the shapes of QTL genotype-specific growth curves between different environments. By analyzing a real example from a soybean genome project, our model detects several QTLs that cause significant genotype-environment interactions for plant height growth processes.

Conclusions

The model provides a basis for deciphering the genetic architecture of trait expression adjusted to different biotic and abiotic environments for any organism.
Phase III Study of the Value of Thalidomide Added to Melphalan Plus Prednisone in Elderly Patients With Newly Diagnosed Multiple Myeloma: The HOVON 49 Study
Authors: Wijermans Pierre , Schaafsma Martijn , Termorshuizen Fabian , Ammerlaan Rianne , Wittebol Shulamiet , Sinnige Harm , Zweegman Sonja , van Marwijk Kooy Marinus , van der Griend René , Lokhorst Henk , Sonneveld Pieter
Published: June 2010

Purpose

For several decades, the treatment of elderly patients with multiple myeloma (MM) has consisted of melphalan and prednisone (MP). The Dutch-Belgium Hemato-Oncology Cooperative Group (HOVON) investigated the efficacy of thalidomide added to MP (MP-T) in a randomized phase III trial. The objective of this study was to investigate the efficacy, toxicity, and effects on quality of life of MP-T.

Patients and Methods

A randomized phase III trial compared standard MP with MP-T (thalidomide 200 mg/d) in newly diagnosed patients with multiple myeloma older than age 65 years. Maintenance therapy with thalidomide 50 mg/d was administered to patients after MP-T until relapse. The primary end point was event-free survival (EFS); response rate, overall survival (OS), and progression-free survival (PFS) were secondary end points.

Results

An intent-to-treat analysis of 333 evaluable patients showed significantly higher response rates in MP-T–treated patients compared with MP-treated patients a response (≥ partial response: 66% v 45%, respectively; P < .001; and ≥ very good partial response [VGPR]: 27% v 10%, respectively; P < .001). EFS was 13 months with MP-T versus 9 months with MP (P < .001). OS was 40 months with MP-T versus 31 months with MP (P = .05).

Conclusion

This study demonstrates that thalidomide improves the response rate and VGPR in elderly patients with newly diagnosed MM. MP-T also results in a better EFS, PFS, and OS.
Immune Regulation of Cancer
Authors: Disis Mary L.
Published: June 2010

Innate and adaptive immune system cells play a major role in regulating the growth of cancer. Although it is commonly thought that an immune response localized to the tumor will inhibit cancer growth, it is clear that some types of inflammation induced in a tumor may also lead to cancer proliferation, invasion, and dissemination. Recent evidence suggests, however, that some patients with cancer can mount an antitumor immune response that has the potential to control or eliminate cancer. Indeed, a so-called “immune response” signature has been described in malignancy that is associated with improved outcomes in several tumor types. Moreover, the presence of specific subsets of T cells, which have the capability to penetrate tumor stroma and infiltrate deep into the parenchyma, identifies patients with an improved prognosis. Immune-based therapies have the potential to modulate the tumor microenvironment by eliciting immune system cells that will initiate acute inflammation that leads to tissue destruction.
Capecitabine, Bevacizumab, and Mitomycin in First-Line Treatment of Metastatic Colorectal Cancer: Results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study
Authors: Tebbutt Niall C. , Wilson Kate , Gebski Val J. , Cummins Michelle M. , Zannino Diana , van Hazel Guy A. , Robinson Bridget , Broad Adam , Ganju Vinod , Ackland Stephen P. , Forgeson Garry , Cunningham David , Saunders Mark P. , Stockler Martin R. , Chua YuJo , Zalcberg John R. , Simes R. John , Price Timothy J.
Published: June 2010

Purpose

To determine whether adding bevacizumab, with or without mitomycin, to capecitabine monotherapy improves progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) in an open-label, three-arm randomized trial.

Patients and Methods

Overall, 471 patients in Australia, New Zealand, and the United Kingdom with previously untreated, unresectable mCRC were randomly assigned to the following: capecitabine; capecitabine plus bevacizumab (CB); or capecitabine, bevacizumab, and mitomycin (CBM). We compared CB with capecitabine and CBM with capecitabine for progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, response rate (RR), and quality of life (QOL).

Results

Median PFS was 5.7 months for capecitabine, 8.5 months for CB, and 8.4 months for CBM (capecitabine v CB: hazard ratio [HR], 0.63; 95% CI, 0.50 to 0.79; P < .001; C v CBM: HR, 0.59; 95% CI, 0.47 to 0.75; P < .001). After a median follow-up of 31 months, median OS was 18.9 months for capecitabine and was 16.4 months for CBM; these data were not significantly different. Toxicity rates were acceptable, and all treatment regimens well tolerated. Bevacizumab toxicities were similar to those in previous studies. Measures of overall QOL were similar in all groups.

Conclusion

Adding bevacizumab to capecitabine, with or without mitomycin, significantly improves PFS without major additional toxicity or impairment of QOL.
The Euro-Mediterranean Parliamentary Assembly, 2004 – 2008: Assessing the First Years of the Parliamentary Dimension of the Barcelona Process
Authors: Pace Roderick , Stavridis Stelios
Published: June 2010

Parliamentarization is an under-studied dimension of Euro-Mediterranean relations. A preliminary assessment of the Euro-Mediterranean Parliamentary Assembly shows that the parliamentary process is not unique to the Mediterranean. The origins, aims, and objectives of the EMPA are presented, as are its structure and functions during its first four years of existence. Despite many weaknesses and limitations, the EMPA can play an important role in Euro-Mediterranean relations, but in order for it to do so, both its structures and functions need to be strengthened.
From the Border of the City to the Shore of the Island: The Angolan Artist António Ole
Authors: Siegert Nadine
Published: June 2010

Angola, a blank spot on the map of the international art world due to its long-lasting civil war, has carved out an outstanding position for itself as a metropolis of the future; it is sometimes referred to as the Dubai of Africa. The reflection of memory and violence in Angolan history is one of the main topics in António Ole’s artwork. The artist was born into a mixed Angolan and Portuguese family in 1951. His first exhibitions in Luanda took place at the end of the 1960s, before independence. After finishing his film studies in Los Angeles in the early 1980s, Ole returned to Angola, and today he is one of the country’s most important artists. Even though he has exhibited in important venues like the biennales of Venice, São Paulo, and Havana, one of his main concerns is the establishment of better connections within the African continent. Thus he aims to work and exhibit more within African networks and has recently changed the focus of his artistic projects to new and intriguing topics. This article offers an overview of his artistic life and most important exhibitions and an analysis of his major artworks.
Whitfield Lovell: Autour Du Monde
Authors: McGee Julie L.
Published: June 2010

This essay examines recent work by the American artist Whitfield Lovell, who has been collecting and using vintage accoutrements—the material culture of late-nineteenth- and early-twentieth-century African American life, including photographs—for many years. He is best known for his installations and tableaux, combinations of superb charcoal and Conté crayon drawings, on weathered wooden planks or cream paper, and found objects. As an artist who draws inspiration from history and the material culture of a bygone era, Lovell doesn’t set out to teach us history, but the subjects and objects he brings together necessarily encourage us to deepen our knowledge of African and American history and culture. Works discussed include Lovell’s 2008 Kith and Kin exhibition at D. C. Moore Gallery in New York and his Kin Series, an ongoing sequence of images and tableaux dedicated to African Americans in the military. An endeavor that has not yet reached its conclusion, Lovell’s Kin Series takes us autour du monde. Grounded in the source materials of his immediate and personal ancestry, the American South, the Caribbean, and the Bronx, and drawing on the relational currents of the Black Atlantic, Lovell’s work is both rooted and expansive. Perhaps no other exhibition of Lovell’s recent work has linked “home” and “away” so clearly as Kith and Kin.
A Land of Signs
Authors: Garb Tamar
Published: June 2010

This essay looks at the way in which the history of South Africa is imprinted in representations of place. It examines images of the land as sites of inscription, exploring the residue of deep colonial history as well as the more immediate past of apartheid on the signs and signifiers that we encounter in the landscape. The works of seven contemporary South African artists are discussed in this context, including the photography of David Goldblatt, Guy Tillim, and Santu Mofokeng, video work and anamorphic drawings by William Kentridge, film by Berni Searle, painting by Vivienne Koorland, and installation by Nicholas Hlobo. The examples therefore cross generations and media in an attempt to understand the ongoing challenge of history for contemporary representations of place in the context of postapartheid South Africa.
Integrating one-dimensional and three-dimensional maps of genomes
Authors: Naumova Natalia , Dekker Job
Published: June 2010

Genomes exist in vivo as complex physical structures, and their functional output (i.e. the gene expression profile of a cell) is related to their spatial organization inside the nucleus as well as to local chromatin status. Chromatin modifications and chromosome conformation are distinct in different tissues and cell types, which corresponds closely with the diversity in gene-expression patterns found in different tissues of the body. The biological processes and mechanisms driving these general correlations are currently the topic of intense study. An emerging theme is that genome compartmentalization – both along the linear length of chromosomes, and in three dimensions by the spatial colocalization of chromatin domains and genomic loci from across the genome – is a crucial parameter in regulating genome expression. In this Commentary, we propose that a full understanding of genome regulation requires integrating three different types of data: first, one-dimensional data regarding the state of local chromatin – such as patterns of protein binding along chromosomes; second, three-dimensional data that describe the population-averaged folding of chromatin inside cells and; third, single-cell observations of three-dimensional spatial colocalization of genetic loci and trans factors that reveal information about their dynamics and frequency of colocalization.
Plk4 trans-autophosphorylation regulates centriole number by controlling βTrCP-mediated degradation
Authors: Guderian Gernot , Westendorf Jens , Uldschmid Andreas , Nigg Erich A.
Published: June 2010

Centrioles are the main constituents of the mammalian centrosome and act as basal bodies for ciliogenesis. Centrosomes organize the cytoplasmic microtubule network during interphase and the mitotic spindle during mitosis, and aberrations in centrosome number have been implicated in chromosomal instability and tumor formation. The centriolar protein Polo-like kinase 4 (Plk4) is a key regulator of centriole biogenesis and is crucial for maintaining constant centriole number, but the mechanisms regulating its activity and expression are only beginning to emerge. Here, we show that human Plk4 is subject to βTrCP-dependent proteasomal degradation, indicating that this pathway is conserved from Drosophila to human. Unexpectedly, we found that stable overexpression of kinase-dead Plk4 leads to centriole overduplication. This phenotype depends on the presence of endogenous wild-type Plk4. Our data indicate that centriole overduplication results from disruption of Plk4 trans-autophosphorylation by kinase-dead Plk4, which then shields endogenous Plk4 from recognition by βTrCP. We conclude that active Plk4 promotes its own degradation by catalyzing βTrCP binding through trans-autophosphorylation (phosphorylation by the other kinase in the dimer) within homodimers.
Serum glycated albumin to haemoglobin A1C ratio can distinguish fulminant type 1 diabetes mellitus from type 2 diabetes mellitus
Authors: Koga Masafumi , Murai Jun , Saito Hiroshi , Kasayama Soji , Imagawa Akihisa , Hanafusa Toshiaki , Kobayashi Tetsuro ,   the Members of the Japan Diabetes Society's Committee on Research on Type 1 Diabetes
Published: June 2010

Background

Fulminant type 1 diabetes mellitus (FT1DM), a subtype of type 1 diabetes mellitus, was first reported as a disease entity in 2000. Ketoacidosis at initial onset due to acute pancreatic cell destruction makes early diagnosis and treatment for FT1DM mandatory. In the early period of FT1DM, haemoglobin (Hb)A1C levels are not markedly elevated. This study investigated serum glycated albumin (GA), which reflects acute short-term changes in plasma glucose, as a new clinical index for FT1DM at disease onset.

Methods

Subjects comprised 35 patients with FT1DM who had undergone measurement of HbA1C and serum GA at initial visit and 42 patients with type 2 diabetes mellitus (T2DM) with HbA1C <8.5% and no history of diabetes treatment as controls.

Results

HbA1C was significantly lower in FT1DM than in T2DM, whereas serum GA was significantly higher. GA/HbA1C ratio was thus significantly higher in FT1DM than in T2DM (3.9 ± 0.5 versus 2.8 ± 0.3; P < 0.0001). GA/HbA1C ratio was >3.2 in 41 of 42 FT1DM patients (98%), compared with only one of 32 T2DM patients (3%).

Conclusions

Serum GA is significantly higher in FT1DM than in T2DM, whereas HbA1C is significantly lower. FT1DM can thus be distinguished from untreated T2DM by GA/HbA1C ratio at initial visit before treatment for diabetes.
Dr Heribert Schmidt's (1914–95) visit to Hong Kong in 1954 and the exchange of Chinese medicine between Hong Kong and Germany
Authors: Fan Ka Wai
Published: June 2010

Heribert Schmidt, a German doctor, was an expert on Chinese medicine and acupuncture. He was renowned in both clinical practice and research on acupuncture in Germany and European countries. In March 1954 he visited Hong Kong and the visit attracted much attention and sparked discussions on the value of Chinese medicine. This paper aims to analyse the speech made by Heribert Schmidt during his visit to Hong Kong and also the follow-up discussions about scientification of Chinese medicine after his speech. The situation in which Chinese medical staff were pushed to the periphery in Hong Kong since the 1950s is also discussed. This should help us better to understand how practitioners of Chinese medicine in Hong Kong and Mainland China reacted to Heribert Schmidt's speech.
Walter Max Dale (formerly Deutsch) (1894–1969): pioneer and eminent radiobiochemist at the Christie Hospital and Holt Radium Institute, Manchester
Authors: Shreeve David R
Published: June 2010

The political upheaval in Germany in 1933 and subsequent movement of medical scholars with the support of the Rockefeller Foundation allowed Manchester to benefit from the arrival of Dr Walter Deutsch, later known as Dr Walter Dale. His research background enabled him to develop a radiobiochemistry laboratory at the Christie Hospital and Holt Radium Institute where he became a world authority on the effects of X-rays on enzymes and also the protective effect of additional solutes. In 1959 he initiated and then edited the International Journal of Radiation Biology. By the time of his retirement in 1962 the strength of his research resulted in his laboratory being recognized by the Medical Research Council.
Sir Herbert Isambard Owen (1850–1927)
Authors: McIntyre Neil , Morgan H Gethin , James D Geraint
Published: June 2010

Isambard Owen, born in Chepstow to a Welsh father, studied at Cambridge and St George's Hospital where he qualified in 1875 and was later physician and Dean. In 1904 he moved to Newcastle-upon-Tyne as Principal of Armstrong College. He left in 1909 to become Bristol University's Vice-Chancellor, retiring in 1921. Although not resident in Wales he was an ardent Welshman. After joining the Cymmrodorion Society in 1877 he became involved in the struggle to improve primary and secondary education in Wales, partly by promoting use of the Welsh language in schools. His main contribution to Welsh academic life was in the foundation of the University of Wales and, later, of the medical school in Cardiff. He wrote the University's Charter and from 1895 until 1910 was its Senior Deputy Chancellor – and stand-in for two Princes of Wales (later Edward VII and George V) who served as Chancellor.
Catherine Walpole (1703–22), an 18th-century teenaged patient: a case study from the letters of the physician George Cheyne (1671 or 73–1743)
Authors: Charlton Anne
Published: June 2010

In 1720 Catherine Walpole the 16-year-old eldest daughter of Robert Walpole, later to become Prime Minister, became very ill. She was unable to eat, fainted, took fits frequently, and had a persistent pain and swelling in her side. Sir Hans Sloane, the Walpole's doctor, referred her to Dr Cheyne in Bath because he specialized in dietary problems and nervous diseases. Cheyne kept in regular touch with Sir Hans by letter and this correspondence tells the story of Catherine's treatment from her first referral to Cheyne to her death in 1722. The contents and purposes of treatments he used are identifiable in dispensatories of the period. The letters reflect Cheyne's medical skills and knowledge as well as his sympathetic personality. Catherine's family loyalties, personal concerns and personality also emerge as the correspondence progresses. The limitations of 18th-century diagnosis and treatments available are clear but Cheyne is always concerned with Catherine's quality of life, even when he becomes aware that he cannot cure her.