bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Biomarkers and New Understanding of Traditional Markers in Personalized Therapy for Breast Cancer
Authors: Dowsett Mitch , Dunbier Anita K.
Published: December 2008

The era of personalized medicine is likely to see an escalation in the use of biomarkers to ensure breast cancer patients receive optimal treatment. A combination of prognostic and predictive biomarkers should enable better quantification of the residual risk faced by patients and indicate the potential value of additional treatment. Established biomarkers such as estrogen receptor and progesterone receptor already play a significant role in the selection of patients for endocrine therapy. Human epidermal growth factor receptor 2 (HER2) is recognized as a strong predictor of response to trastuzumab whereas, more recently, the role of estrogen receptor and HER2 as negative and positive indicators for chemotherapy has also been explored. Ki67 has traditionally been recognized as a modest prognostic factor, but recent neoadjuvant studies suggest that on-treatment measurement may be a more effective predictor of treatment efficacy for both endocrine treatment and chemotherapy. The last decade has seen the emergence of numerous multigene expression profiles that aim to outdo traditional predictive and prognostic factors. The Oncotype DX assay and the MammaPrint profile are currently undergoing prospective clinical trials to clearly define their role. Other gene expression–based assays also show potential but are yet to be tested clinically. Rigorous comparison of these emerging markers with current treatment selection criteria will be required to determine whether they offer significant benefit to justify their use.
Pharmacogenetics in Breast Cancer Therapy
Authors: Tan Sing-Huang , Lee Soo-Chin , Goh Boon-Cher , Wong John
Published: December 2008

Interindividual and interethnic variability of drug pharmacokinetics and pharmacodynamics may be contributed by commonly occurring genetic polymorphisms of drug-metabolizing enzymes and transporters. Polymorphisms of CYP2D6 in particular have been associated with effects on tamoxifen disposition and clinical efficacy, with interethnic differences in distribution of functional alleles that affect metabolizer phenotype. Other tamoxifen-related genetic variants of CYP3A4, CYP3A5, and sulfotransferase1A1 (SULT1A1) are also briefly reviewed here. Polymorphisms of CYP19A1 (aromatase gene) have been reported to correlate with clinical outcomes from aromatase inhibitors in small studies but require further confirmation. Many studies on chemotherapy are based on hypothesis-generating association studies and need to be validated through larger-scale cooperative group studies. For anthracyclines, polymorphisms in genes such as carbonyl reductase 3 (CBR3), ATP-binding cassette subfamily B, member 1 (ABCB1), glutathione-related transporter genes, and oxidative stress–related genes have been reported to correlate with clinical outcomes. The pharmacogenetics of taxanes has been extensively investigated, but associations of genetic polymorphisms in drug-metabolizing enzymes and transporters reported in earlier small studies have not been validated in a recent large clinical trial. Allelic variants associated with gemcitabine, capecitabine/5-fluorouracil, vinorelbine, and platinum disposition are reviewed. No pharmacogenetic studies have been published for targeted agents thus far, although several potential candidate genes warrant investigation. Future pharmacogenetic studies will need to focus on integration of multiple drug pathways to allow a more comprehensive analysis of genetic factors influencing drug efficacy and toxicity.
Phase II Trial of 17-Allylamino-17-Demethoxygeldanamycin in Patients with Metastatic Melanoma
Authors: Solit David B. , Osman Iman , Polsky David , Panageas Katherine S. , Daud Adil , Goydos James S. , Teitcher Jerrold , Wolchok Jedd D. , Germino F. Joseph , Krown Susan E. , Coit Daniel , Rosen Neal , Chapman Paul B.
Published: December 2008

Purpose: Activation of the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase/AKT pathway seems to be critical for melanoma proliferation. Components of these pathways are client proteins of heat-shock protein 90 (hsp90), suggesting that inhibition of hsp90 could have significant antimelanoma effects. We conducted a phase II trial using the hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in melanoma patients. The primary end points were clinical responses and whether treatment inhibited MAPK pathway activity.

Experimental Design: Melanoma patients with measurable disease were stratified on the basis of whether or not their tumor harbored a V600E BRAF mutation. The hsp90 inhibitor 17-AAG was administered i.v. once weekly ×6 weeks at 450 mg/m2. Tumor biopsies were obtained pretreatment and 18 to 50 hours after the first dose of 17-AAG, and were snap-frozen.

Results: Fifteen evaluable patients were treated; nine had BRAF mutations and six were wild-type. No objective responses were observed. Western blot analysis of tumor biopsies showed an increase in hsp70 and a decrease in cyclin D1 expression in the posttreatment biopsies but no significant effect on RAF kinases or phospho–extracellular signal-regulated kinase expression. Plasma analyzed by mutant-specific PCR for V600E BRAF showed 86% sensitivity and 67% specificity in predicting tumor DNA sequencing results.

Conclusions: At this dose and schedule of 17-AAG, the effects of 17-AAG on RAF kinase expression were short-lived, and no objective antimelanoma responses were seen. Future trials in melanoma should focus on a more potent hsp90 inhibitor or a formulation that can be administered chronically for a more prolonged suppression of the MAPK pathway.
Effect of Cigarette Smoking on Imatinib in Patients in the Soft Tissue and Bone Sarcoma Group of the EORTC
Authors: van Erp Nielka , Gelderblom Hans , van Glabbeke Martine , Van Oosterom Allan , Verweij Jaap , Guchelaar Henk-Jan , Debiec-Rychter Maria , Peng Bin , Blay Jean-Yves , Judson Ian
Published: December 2008

Purpose: Smoking is a potent inducer of cytochrome P450 (CYP) 1A2 and may affect the pharmacokinetics of CYP1A2 metabolized drugs. The effect of smoking on the pharmacokinetics of imatinib, which is metabolized by CYP3A4 and partly by CYP1A2, is unknown. We studied the effect of smoking on imatinib pharmacokinetics, safety, and efficacy.

Experimental Design: Imatinib pharmacokinetics, safety, and efficacy was analyzed in 45 patients with gastrointestinal stromal tumors (GIST) or soft-tissue sarcoma included in two European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group trials, including 15 smokers and 30 nonsmokers. Apparent oral clearance, distribution volume, elimination half-life, and dose-standardized area under the concentration curve (AUC) were assessed in 34 patients using nonlinear mixed-effect modeling.

Results: Mean ± SD pharmacokinetic variables in smokers (n = 9) versus nonsmokers (n = 25) groups were 9.6 ± 5.5 versus 9.2 ± 4.6 L/h (apparent oral clearance), 216.5 ± 114.3 versus 207.0 ± 116.9 L (distribution volume), 16.1 ± 6.0 versus 16.5 ± 6.0 h (elimination half-life), and 133.6 ± 71.0 versus 142.3 ± 84.0 ng h/mL mg area under the concentration curve; P > 0.05. Smokers experienced more grade 2/3 anemia (P = 0.010) and fatigue (P = 0.011) and those with GIST had a significantly shorter overall survival (P = 0.037) and time to progression (P = 0.052).

Conclusions: This retrospective study suggests that the pharmacokinetics of imatinib is not affected by smoking. However, smokers have an increased risk of anemia and fatigue. Smokers with GIST have a shorter overall survival and time to progression.
A peptide inhibitor derived from p55PIK phosphatidylinositol 3-kinase regulatory subunit: a novel cancer therapy
Authors: Hu Junbo , Xia Xianmin , Cheng Aiwu , Wang Guihua , Luo Xuelai , Reed Michael F. , Fojo Tito , Oetting Alexis , Gong Jianping , Yen Paul M.
Published: December 2008

p55PIK, a regulatory subunit of phosphatidylinositol 3-kinase (PI3K), specifically interacts with retinoblastoma protein (Rb) through the unique NH2 terminus of p55PIK, N24. This interaction is critical for cell proliferation and cell cycle progression. To examine p55PIK as a potential target for cancer therapy, we generated an adenovirus expressing N24 (Ad-N24-GFP) and studied its effects on the proliferation of cultured cancer cells, including human colon (HT29) and thyroid (FTC236) cancer cells. Ad-N24-GFP blocked cell proliferation and induced cell cycle arrest in all cancer cell lines tested. N24 induced cell cycle arrest at G0-G1 phase in cell lines that expressed Rb. Interestingly, N24 inhibited cell proliferation by blocking cell cycle transition at both S and G2-M phases in FTC236 cells, which did not express Rb. When Rb was knocked down by short hairpin RNA in HT29 cells, N24 also inhibited cell cycle progression at S and G2-M phases, suggesting that p55PIK regulates cell cycle progression by Rb-dependent and Rb-independent mechanisms. Finally, Ad-N24-GFP markedly decreased the growth of xenograft tumors derived from HT29 and FTC236 cancer cells in athymic nude mice. Our data strongly suggest that N24 peptide is an effective anticancer therapy, which specifically inhibits PI3K signaling pathways mediated by p55PIK. Moreover, they show that the regulatory subunit of an enzyme, in addition to its catalytic subunit, can be an important target for drug development. [Mol Cancer Ther 2008;07(12):3719–28]
1,1-Bis(3′-indolyl)-1-(p-chlorophenyl)methane activates the orphan nuclear receptor Nurr1 and inhibits bladder cancer growth
Authors: Inamoto Teruo , Papineni Sabitha , Chintharlapalli Sudhakar , Cho Sung-Dae , Safe Stephen , Kamat Ashish M.
Published: December 2008

Nurr1 is an orphan nuclear receptor and a member of the nerve growth factor I-B subfamily of transcription factors with no known endogenous ligand or stimulator. We show, for the first time, evidence that Nurr1 is expressed in a panel of 11 human bladder cancer cell lines. A new class of methylene-substituted diindolylmethanes (C-DIM) were screened and 1,1-bis(3′-indolyl)-1-(p-chlorophenyl)methane (DIM-C-pPhCl) activated the ligand-binding domain of Nurr1. Treatment of bladder cancer cells with Nurr1-active C-DIM resulted in decreased cell survival (MTT assay) and induction of cell death pathways, resulting in poly(ADP-ribose) polymerase cleavage and DNA fragmentation. The specificity of the Nurr1-active compound was shown using RNA interference in 253J B-V cells, whereby small interfering RNA against Nurr1 attenuated ligand-dependent activation of Nurr1 and poly(ADP-ribose) polymerase cleavage. Furthermore, activation of Nurr1 resulted in stimulation of tumor necrosis factor-related apoptosis-inducing ligand and small interfering RNA experiments attenuated tumor necrosis factor-related apoptosis-inducing ligand production. In an orthotopic model of human bladder tumors established in nude mice, administration of a Nurr1-active C-DIM suppressed bladder cancer growth. These results identify Nurr1 as a potential target for bladder cancer therapy and also identify a novel agent for activating Nurr1. [Mol Cancer Ther 2008;7(12):3825–33]
c-Src-p38 Mitogen-Activated Protein Kinase Signaling Is Required for Akt Activation in Response to Ionizing Radiation
Authors: Kim Min-Jung , Byun Joo-Yun , Yun Chang-Hwan , Park In-Chul , Lee Kee-Ho , Lee Su-Jae
Published: December 2008

The Akt and mitogen-activated protein kinase (MAPK) pathways have been implicated in tumor cell survival and contribute to radiation resistance. However, the molecular basis for link between MAPK and Akt in cell survival response to radiation is unclear. Here, we show that c-Src-Rac1-p38 MAPK pathway signals Akt activation and cell survival in response to radiation. Ionizing radiation triggered Thr308 and Ser473 phosphorylation of Akt. Exposure of cells to radiation also induced p38 MAPK and c-Jun NH2-terminal kinase activations. Inhibition of c-Jun NH2-terminal kinase suppressed radiation-induced cell death, whereas inhibition of p38 MAPK effectively increased sensitivity to radiation. Interestingly, inhibition of p38 MAPK completely attenuated radiation-induced Ser473 phosphorylation of Akt but did not affect Thr308 phosphorylation. Conversely, overexpression of p38 MAPK enhanced Ser473 phosphorylation of Akt in response to radiation. In addition, inhibition of p38 MAPK failed to alter phosphoinositide 3-kinase and phosphoinositide-dependent protein kinase activities. Ectopic expression of RacN17, dominant-negative form of Rac1, inhibited p38 MAPK activation and Ser473 phosphorylation of Akt. Following exposure to radiation, c-Src was selectively activated among Src family tyrosine kinases. Inhibition of c-Src attenuated Rac1 and p38 MAPK activations and Ser473 phosphorylation of Akt. Our results support the notion that the c-Src-Rac1-p38 MAPK pathway is required for activation of Akt in response to radiation and plays a cytoprotective role against radiation in human cancer cells. (Mol Cancer Res 2008;6(12):1872–80)
Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth
Authors: Agirre Xabier , Jiménez-Velasco Antonio , San José-Enériz Edurne , Garate Leire , Bandrés Eva , Cordeu Lucia , Aparicio Oscar , Saez Borja , Navarro Germán , Vilas-Zornoza Amaia , Pérez-Roger Ignacio , García-Foncillas Jesús , Torres Antonio , Heiniger Anabel , Calasanz María José , Fortes Puri , Román-Gómez José , Prósper Felipe
Published: December 2008

MicroRNAs (miRNA) are small noncoding, single-stranded RNAs that inhibit gene expression at a posttranscriptional level, whose abnormal expression has been described in different tumors. The aim of our study was to identify miRNAs potentially implicated in chronic myeloid leukemia (CML). We detected an abnormal miRNA expression profile in mononuclear and CD34+ cells from patients with CML compared with healthy controls. Of 157 miRNAs tested, hsa-miR-10a, hsa-miR-150, and hsa-miR-151 were down-regulated, whereas hsa-miR-96 was up-regulated in CML cells. Down-regulation of hsa-miR-10a was not dependent on BCR-ABL1 activity and contributed to the increased cell growth of CML cells. We identified the upstream stimulatory factor 2 (USF2) as a potential target of hsa-miR-10a and showed that overexpression of USF2 also increases cell growth. The clinical relevance of these findings was shown in a group of 85 newly diagnosed patients with CML in which expression of hsa-miR-10a was down-regulated in 71% of the patients, whereas expression of USF2 was up-regulated in 60% of the CML patients, with overexpression of USF2 being significantly associated with decreased expression of hsa-miR-10a (P = 0.004). Our results indicate that down-regulation of hsa-miR-10a may increase USF2 and contribute to the increase in cell proliferation of CML implicating a miRNA in the abnormal behavior of CML. (Mol Cancer Res 2008;6(12):1830–40)
DNA Methylation Represses IFN-γ–Induced and Signal Transducer and Activator of Transcription 1–Mediated IFN Regulatory Factor 8 Activation in Colon Carcinoma Cells
Authors: McGough Jon M. , Yang Dafeng , Huang Shuang , Georgi David , Hewitt Stephen M. , Röcken Christoph , Tänzer Marc , Ebert Matthias P.A. , Liu Kebin
Published: December 2008

IFN regulatory factor 8 (IRF8) is both constitutively expressed and IFN-γ inducible in hematopoietic and nonhematopoietic cells. We have shown that IRF8 expression is silenced by DNA methylation in human colon carcinoma cells, but the molecular mechanism underlying methylation-dependent IRF8 silencing remains elusive. In this study, we observed that IRF8 protein level is inversely correlated with the methylation status of the IRF8 promoter and the metastatic phenotype in human colorectal carcinoma specimens in vivo. Demethylation treatment or knocking down DNMT1 and DNMT3b expression rendered the tumor cells responsive to IFN-γ to activate IRF8 transcription in vitro. Bisulfite genomic DNA sequencing revealed that the entire CpG island of the IRF8 promoter is methylated. Electrophoresis mobility shift assay revealed that DNA methylation does not directly inhibit IFN-γ–activated phosphorylated signal transducer and activator of transcription 1 (pSTAT1) binding to the IFN-γ activation site element in the IRF8 promoter in vitro. Chromatin immunoprecipitation assay revealed that pSTAT1 is associated with the IFN-γ activation site element of the IRF8 promoter in vivo regardless of the methylation status of the IRF8 promoter. However, DNA methylation results in preferential association of PIAS1, a potent inhibitor of pSTAT1, with pSTAT1 in the methylated IRF8 promoter region. Silencing methyl-CpG binding domain protein 1 (MBD1) expression resulted in IRF8 activation by IFN-γ in human colon carcinoma cells with methylated IRF8 promoter. Our data thus suggest that human colon carcinoma cells silence IFN-γ–activated IRF8 expression through MBD1-dependent and PIAS1-mediated inhibition of pSTAT1 function at the methylated IRF8 promoter. (Mol Cancer Res 2008;6(12):1841–51)
Specific Activity of Class II Histone Deacetylases in Human Breast Cancer Cells
Authors: Duong Vanessa , Bret Caroline , Altucci Lucia , Mai Antonello , Duraffourd Céline , Loubersac Julie , Harmand Pierre-Olivier , Bonnet Sandrine , Valente Sergio , Maudelonde Thierry , Cavailles Vincent , Boulle Nathalie
Published: December 2008

Although numerous studies have underlined the role of histone deacetylases (HDAC) in breast physiology and tumorigenesis, little is known on the particular contribution of the various classes of HDACs in these processes. Using estrogen receptor-α (ERα)–positive MCF-7 breast cancer cells, the effects of MC1575 and MC1568, two novel class II–specific HDAC inhibitors, were analyzed on cell proliferation, apoptosis, and estrogen signaling. The specificity of these HDAC inhibitors was validated by measuring histone and α-tubulin acetylation and by the specific in vitro inhibition of recombinant HDAC4 using histone and nonhistone substrates, contrasting with the lack of inhibition of class I HDACs. In addition, MC1575 did not inhibit class I HDAC gene expression, thus confirming the specific targeting of class II enzymes. Similar to trichostatin A (TSA), MC1575 displayed a dose-dependent antiproliferative effect and induced cell cycle arrest although this blockade occurred at a different level than TSA. Moreover, and in contrast to TSA, MC1575 had no effect on MCF-7 cells apoptosis. Interestingly, MC1575 was able to increase p21waf1/CIP1 mRNA levels but did not regulate the expression of other genes such as cyclin D1, p27, p14ARF, Bcl2, Baxα, Trail-R1, and Trail-R2. Finally, MC1575 strongly induced ERβ gene expression but did not decrease ERα expression, nor did it switch hydroxytamoxifen to an agonist activity. Altogether, these data suggest that the class II HDAC subfamily may exert specific roles in breast cancer progression and estrogen dependence. (Mol Cancer Res 2008;6(12):1908–19)
Common Anatomical and External Coding for Hands and Feet in Tactile Attention: Evidence from Event-related Potentials
Authors: Heed Tobias , Röder Brigitte
Published: December 2008

Recent studies have suggested that the location of tactile stimuli is automatically recoded from anatomical into external coordinates, independent of the task requirements. However, research has mainly involved the two hands, which may not be representative for the whole body because they are excessively used for the visually guided manipulation of objects and tools. We recorded event-related potentials (ERPs) while participants received tactile stimuli to the hands and feet, but attended only one limb. The hands were placed near the feet either in an uncrossed or a crossed posture, thus varying the spatial distance of each hand from each foot. Centro-parietal ERPs 100–140 msec poststimulus were more positive when stimulating the anatomically same-side hand while attending a foot. They were also more positive when the Euclidean distance between the stimulated hand and the attended foot was small rather than large. When a foot was stimulated and a hand attended, a similar modulation of foot ERPs was observed for the right foot. To assess the spatial distance between two limbs in space, the external location of both must be known. The present ERP results therefore suggest that not only the hands but also other body parts are remapped into external coordinates. The use of both anatomical and external coordinates may facilitate the control of actions toward tactile events and the choice of the most suitable effector.
Monitoring in Language Perception: Mild and Strong Conflicts Elicit Different ERP Patterns
Authors: van de Meerendonk Nan , Kolk Herman H. J. , Vissers Constance Th. W. M. , Chwilla Dorothee J.
Published: December 2008

In the language domain, most studies of error monitoring have been devoted to language production. However, in language perception, errors are made as well and we are able to detect them. According to the monitoring theory of language perception, a strong conflict between what is expected and what is observed triggers reanalysis to check for possible perceptual errors, a process reflected by the P600. This is at variance with the dominant view that the P600 reflects syntactic reanalysis or repair, after syntactic violations or ambiguity. In the present study, the prediction of the monitoring theory of language perception was tested, that only a strong conflict between expectancies triggers reanalysis to check for possible perceptual errors, reflected by the P600. Therefore, we manipulated plausibility, and hypothesized that when a critical noun is mildly implausible in the given sentence (e.g., “The eye consisting of among other things a pupil, iris, and eyebrow …”), a mild conflict arises between the expected and unexpected event; integration difficulties arise due to the unexpectedness but they are resolved successfully, thereby eliciting an N400 effect. When the noun is deeply implausible however (e.g., “The eye consisting of among other things a pupil, iris, and sticker …”), a strong conflict arises; integration fails and reanalysis is triggered, eliciting a P600 effect. Our hypothesis was confirmed; only when the conflict between the expected and unexpected event is strong enough, reanalysis is triggered.
El Niño–Southern Oscillation Impacts on Rice Production in Luzon, the Philippines
Authors: Roberts Martha G. , Dawe David , Falcon Walter P. , Naylor Rosamond L.
Published: December 2008

This study uses regression analysis to evaluate the relationships among sea surface temperature anomalies (SSTA) averaged over the Niño-3.4 region (5°N–5°S, 120°–170°W), rainfall, and rice production, area harvested, and yield in Luzon, the large island on which most Philippine rice is grown. Previous research on Philippine rice production and El Niño–Southern Oscillation (ENSO) has found negative associations between El Niño events and rice yields in rainfed systems. This analysis goes further and shows that both irrigated and rainfed ecosystems are impacted. It also compares impacts on area harvested and yield. Variations in average July–September Niño-3.4 SSTAs explain approximately 29% of the interannual variations in the deviations of total January–June (dry season) rice production from a polynomial trend for 1970–2005. In contrast, no impact was found on July–December production in either year t or t + 1. The impact of ENSO on dry-season rice production in Luzon appears to be primarily due to changes in area harvested rather than yield. Production declines for rainfed ecosystems are relatively larger than for irrigated ecosystems: a 1°C increase in average July–September Niño-3.4 SSTA is associated with a 3.7% decrease in irrigated dry-season production but with a 13.7% decline in rainfed dry-season production.
The Environment of Precipitating Shallow Cumulus Convection
Authors: Nuijens Louise , Stevens Bjorn , Siebesma A. Pier
Published: December 2008

Quantitative estimates of precipitation in a typical undisturbed trade wind region are derived from 2 months of radar reflectivity data and compared to the meteorological environment determined from soundings, surface flux, and airborne-lidar data. Shallow precipitation was ubiquitous, covering on average about 2% of the region and contributing to at least half of the total precipitation. Echo fractions on the scale of the radar domain range between 0% and 10% and vary greatly within a period from a few hours to a day. Variability in precipitation relates most strongly to variability in humidity and the zonal wind speed, although greater inversion heights and deeper clouds are also evident at times of more rain. The analysis herein suggests that subtle fluctuations in both the strength of the easterlies and in subsidence play a major role in regulating humidity and hence precipitation, even within a given meteorological regime (here, the undisturbed trades).
The Maximum Intensity of Tropical Cyclones in Axisymmetric Numerical Model Simulations
Authors: Bryan George H. , Rotunno Richard
Published: December 2008

An axisymmetric numerical model is used to evaluate the maximum possible intensity of tropical cyclones. As compared with traditionally formulated nonhydrostatic models, this new model has improved mass and energy conservation in saturated conditions. In comparison with the axisymmetric model developed by Rotunno and Emanuel, the new model produces weaker cyclones (by ∼10%, in terms of maximum azimuthal velocity); the difference is attributable to several approximations in the Rotunno–Emanuel model. Then, using a single specification for initial conditions (with a sea surface temperature of 26°C), the authors conduct model sensitivity tests to determine the sensitivity of maximum azimuthal velocity (υmax) to uncertain aspects of the modeling system. For fixed mixing lengths in the turbulence parameterization, a converged value of υmax is achieved for radial grid spacing of order 1 km and vertical grid spacing of order 250 m. The fall velocity of condensate (Vt) changes υmax by up to 60%, and the largest υmax occurs for pseudoadiabatic thermodynamics (i.e., for Vt > 10 m s−1). The sensitivity of υmax to the ratio of surface exchange coefficients for entropy and momentum (CE/CD) matches the theoretical result, υmax ∼ (CE/CD)1/2, for nearly inviscid flow, but simulations with increasing turbulence intensity show less dependence on CE/CD; this result suggests that the effect of CE/CD is less important than has been argued previously. The authors find that υmax is most sensitive to the intensity of turbulence in the radial direction. However, some settings, such as inviscid flow, yield clearly unnatural structures; for example, υmax exceeds 110 m s−1, despite a maximum observed intensity of ∼70 m s−1 for this environment. The authors show that turbulence in the radial direction limits maximum axisymmetric intensity by weakening the radial gradients of angular momentum (which prevents environmental air from being drawn to small radius) and of entropy (which is consistent with weaker intensity by consideration of thermal wind balance). It is also argued that future studies should consider parameterized turbulence as an important factor in simulated tropical cyclone intensity.
A Historical Analysis of Desegregation and Racism in a Racially Polarized Region
Authors: Dara Hill K.
Published: December 2008

This study chronicles the historical divisions of race and class between Detroit and its suburban neighbor as an explanation for current tensions in the communities and schools. This analysis poses implications for educational apartheid and stark disparities between urban and suburban boundaries and consequent discomfort among practitioners when urban children enroll in suburban schools. Ultimately, changing demography in historically affluent suburbs presents an argument for culturally responsive teacher preparation.
Insulin Devices
Authors: Spollett Geralyn
Published: December 2008

Purpose

The purpose of this article was to identify and address barriers to initiating insulin therapy in patients with type 2 diabetes.

Results

Insulin pen devices address many of the mechanical barriers associated with a syringe and vial. In addition, pen devices are increasingly being improved, offering long-term pen users benefits over earlier pen users. These devices can be tailored to address the specific needs of different patient populations, such as elderly patients or those with visual or manual dexterity disabilities. Although insulin devices offer benefits over the syringe and vial, features desirable in the ideal pen have not been established.

Conclusions

Data suggest that currently available insulin pens possess various features that make them suitable for particular patients. Individual needs of each patient should be considered before an insulin pen device is prescribed.
Vitamin D and Diabetes
Authors: Penckofer Sue , Kouba JoAnne , Wallis Diane E. , Emanuele Mary Ann
Published: December 2008

Diabetes is a leading cause of cardiovascular disease. Persons with diabetes are at greater risk for early cardiac mortality, and for repeat events if they survive their first cardiac event. Recently, low serum concentrations of vitamin D have been associated with increased risk for cardiac events. Evidence indicates that persons with diabetes have lower serum concentrations of vitamin D. In addition, persons at risk for diabetes or metabolic syndrome have inadequate serum concentrations of vitamin D. This review will assess the evidence relative to the impact of vitamin D in the development of diabetes, metabolic syndrome, and diabetes complications. Studies that address vitamin D and its impact on metabolic outcomes as well as possible mechanisms of action are provided. Finally, the assessment and suggested treatment for vitamin D deficiency is addressed. Effective detection and treatment of inadequate vitamin D concentrations in persons with diabetes or those at risk for diabetes may be an easy and cost-effective therapy which could improve their long-term health outcomes as well as their quality of life.
Insights and Trends in Diabetes Education
Authors: Lenzi Martin Annette , Lumber Terry , Compton Terry , Ernst Kristina , Haas Linda , Regan-Klich Janet , Letassy Nancy , McKnight Karen A. , Nelson Joseph B. , Seley Jane Jeffrie , Toth Judith A. , Mensing Carole
Published: December 2008

Purpose

The purpose of this study is to describe current diabetes education practice and specific interventions and responsibilities of diabetes educators in the United States.

Methods

The 2008 National Practice Survey (NPS) instrument consisted of 53 items addressing diabetes education program structure, processes and interventions, outcomes and quality improvement activities, and the chronic care model. The survey was hosted online for American Association of Diabetes Educators (AADE) members. Participants totaled 2447 members, constituting a 25% return rate. Data from the 2008 NPS were analyzed and compared with results from previous surveys.

Results

Nearly two-thirds of respondents in 2008 provided diabetes education in a single location, most commonly in a clinical outpatient/managed care setting (39%). Most programs provided comprehensive services. Managers noted that 42% of their programs were either cost/revenue neutral or profitable. Programs varied in types of services, number of patient visits, team member functions, time spent on services, and instructional methods used. At least 50% of managers said their programs report outcome data, and 88% participate in quality/performance improvement activities. Nearly two-thirds of respondents were unfamiliar with the AADE-adopted chronic care model.

Conclusions Many 2008 NPS results concur with those obtained in 2005 through 2007. Areas of variability among programs suggest a need for standardized interventions and prac- tice guidelines. Educators are encouraged to report out- comes to elucidate the contributions of their programs to patient care. AADE can use the results and comparative data obtained from the 2008 survey when developing practice, research, and advocacy activities
The Effects of an Emotional Intelligence Program on the Quality of Life and Well-Being of Patients With Type 2 Diabetes Mellitus
Authors: Yalcin Bektas Murat , Karahan Tevfik Fikret , Ozcelik Muhittin , Igde Fusun Artiran
Published: December 2008

Purpose The purpose of the study is to investigate the effect of an emotional intelligence program on the health-related quality of life and well-being of individuals with type 2 diabetes.

Methods The BarOn Emotional Intelligence Scale (EQ-I), WHO Well-Being Questionnaire (WHO-WBQ-22), WHO Quality of Life Measure (WHOQOL-Bref), and the Medical Outcomes Study 36-Item Health Survey (SF-36) were administered to 184 patients with type 2 diabetes who volunteered to participate. Thirty-six patients with the lowest test scores on the WHO-WBQ-22, WHOQOL-Bref, and SF-36 were randomized into study and control groups (18 patients each). A 12-week emotional intelligence program was administered to the study group. At the end of the program, scales were readministered to both groups and again at 3 and 6 months.

Results There were no differences between the quality of life, well-being, and emotional intelligence levels of the study and control groups before the commencement of the program ( P > .05). At the conclusion of the program, quality of life, well-being, and emotional intelligence levels of study group patients increased in comparison with those in the control group (P < .001). The positive effect of the program on study groups' quality of life, wellbeing, and emotional intelligence persisted at the 3- and 6-month follow-up.

Conclusion The emotional intelligence program may have positive effects on quality of life and well-being of individuals with type 2 diabetes.
MORAL COMPETITION AND THE THRILL OF THE SPECTACULAR
Authors: Green Nile
Published: December 2008

At 10:15 on the night of 31 May 1903, the D–block of the recently completed Sita Ram Building in Bombay suddenly came down with a crash. Most of the building was unoccupied, but on the ground floor was a saloon bar, which over the past months had done a brisk trade with British soldiers and sailors. The customers of this bar comprised most of the dead and injured when the building collapsed.

Since the bar stood across the road from the tomb of a Muslim saint, rumours spread that the disaster was the direct result of the insult to the holy man and implicitly of the transgression of Muslim space by the combined efforts of the Hindu bar–owner and his bibulous patrons. This short essay explores the moral tensions that found expression with the collapse of the Sita Ram Building through a comparison of its reportage in an English–language newspaper and an Urdu hagiography of the offended saint. At the same time, it draws attention to the neglected importance of colonial Bombay as a prime location of the early Muslim experience of globalising modernity.
Towards a European Minimum Wage Policy? Fair Wages and Social Europe
Authors: Schulten Thorsten
Published: December 2008

The notion of Social Europe is usually taken to entail the payment of fair wages, defined as at least a minimum sufficient for a decent standard of living. In all European countries there is some regulation of minimum wages, either by law or by collective agreements. However, the value of minimum wages in Europe differs significantly both in absolute level and relative to average or median national wages. Moreover, some national systems of wage regulation have proved ineffectual in preventing the growth of employment paying below the minimum. Against this background there is an ongoing debate on the possibility and desirability of a European minimum wage policy. This article gives an overview of national minimum wage regulation and discusses the opportunity for and resistance to the introduction of a coordinated minimum wage policy at European level.
Labour Mobility and Wage Dumping: The Case of Norway
Authors: Alsos Kristin , Eldring Line
Published: December 2008

This article examines wage regulation mechanisms, based on statutory provisions or on collective agreements, designed to protect migrant and posted workers from `wage dumping'. The Norwegian mixed model is compared to mechanisms in other European countries, and is also contrasted with the autonomous collective-agreement models of Denmark and Sweden. The experience gained from extension of collective agreements in Norway suggests that such mechanisms may be more generally effective as a means to protect foreign workers.
Opportunities and Challenges of EU Accession: Industrial Relations in Romania
Authors: Trif Aurora
Published: December 2008

This study examines the outcomes of EU accession for industrial relations institutions and workers' rights in Eastern Europe, using Romania as an example. It focuses on EU influence on labour law, the development of the social partners and collective bargaining as well as the impact of foreign direct investment and migration. EU enlargement resulted in both opportunities (improvement of statutory rights for workers) and challenges (labour shortages and difficulties in implementing labour law). Comparisons between the new member states suggest that the effects of the EU accession process vary across countries, depending on national macro-economic strategies and the strength of trade unions.
Financial Participation of Employees in the European Union: Much Ado about Nothing?
Authors: Welz Christian , Fernández-Macías Enrique
Published: December 2008

This article updates previous research on financial participation, using employee data from the latest (fourth) edition of the European Working Conditions Survey. This is the first to provide the employee perspective on this subject and to cover all sizes of private company in all sectors across the whole enlarged European Union. The contrast between these new findings and those from previous (company-based) surveys is considerable.
Anjuman Samaji Falahi Behbood
Authors: Khattak Naseer Khan , Khan Bashir Ahmad
Published: December 2008

The North West Frontier Province of Pakistan has historically been amongst the most backward regions of the country, and its rural communities, in particular, have suffered from the absence of social services and modern infrastructure including roads, sewage, drinking water and health facilities. This case looks at Anjuman Samaji Falahi Behbood's effort to set up infrastructure development projects in a village community. The focus of the case is on the issue of partnerships in providing services to such communities, and it highlights some of the major problems which arise when multiple stakeholders are involved. In the case, the critical issues raised include problems of participatory development, the natural outgrowth of partnerships and major impediments such as the unwillingness of the target communities to share the responsibilities associated with partnerships.
Chainaya Lozhka (Teaspoon) Company
Authors: Shirokova Galina V.
Published: December 2008

This case study gives an overview of the Russian fast food industry and how the Chainaya Lozhka (Teaspoon) Company entered this very competitive market. It pro-vides information about the company's development during the first five years of its existence and gives special attention to issues such as company management within the company life cycle theory. The case contains extensive information that can help in working out future strategies for the company's development and in choosing a suitable organizational structure that would meet business demands.
Revisiting old haunts through new technologies
Authors: Mowlabocus Sharif
Published: December 2008

While gay male culture becomes increasingly visible and accepted by mainstream Britain, other forms of homosexual desire remain firmly outside the boundaries of what is deemed acceptable by British society. This article considers how small groups of men are using the decentralized nature of the internet to engage in one such form of homosexuality, namely cottaging (British gay slang for sexual acts in public lavatories). Via an analysis of these `subaltern' spaces the article demonstrates that, far from being the domain of closeted homosexuals (and in contrast to the cultural stereotype), `cybercottages' are being constructed and populated by men who otherwise hold confident gay or bisexual identities both on- and off-line. As such, the cybercottage becomes a site of `nostalgized' performance and play, where gay men explore `older' articulations of male—male desire, outside of the confines of a sanitized commercial gay scene.
Maradona Inc
Authors: Salazar-Sutil Nicolás
Published: December 2008

This article addresses the blurring boundaries between celebrity, media sports, cultural identity and politics. I explore the case of media sport star Diego Maradona, whose strategies of public representation highlight the way in which politics and popular culture can overlap. First, the article offers a general overview of the theorization of football in Latin America. Central to my discussion is the problematic use of concepts like `identity' and `belonging' to define football politics. I insist on a theoretical reformulation of political culture in global contexts, and point to an understanding of media personalities such as Maradona as currency within markets of cultural and political production. This analysis suggests that `Maradona Inc.' can be understood as a corporate and performative semiosphere that is continuously shifting, so that fans can project onto the fetish-like and vacant image of the celebrity whatever they wish.
`There is one in every home'
Authors: Ureta Sebastian
Published: December 2008

This article studies the symbolic and practical meaning of the placement of television sets in different home spaces. Based on fieldwork conducted among a low-income population in Santiago, Chile, it shows how their move to a social housing estate constitutes for these families an opportunity to start organizing their domestic space in a different way, particularly in accordance with modernist distinctions between public and private spaces. In this context television sets appear as a central element of the material culture of the home, symbolizing for family members their access to the normal stock of material culture in urban homes. But at the same time the practice of watching television both in public and private places is commonly resisted, showing that the device still occupies an ambiguous place within the ideas of domesticity of the members of the families under study.
Postcolonial Studies and the Hebrew Bible
Authors: Crowell Bradley L.
Published: December 2008

As the field of biblical studies continues to become more diverse, scholars incorporate theories and methods from other areas of research. One of these fields is postcolonial theory, which makes the role of empires and their effects on society and literature the primary focus of the interpretive effort. This essay explores how postcolonial theory is currently being integrated with the study of the Hebrew Bible. Biblical scholars incorporating postcolonial theory focus on three major areas: how colonial empires interpreted the Hebrew Bible and how indigenous populations reacted to the colonial interpretations, interpretations from previously colonized populations, and the role of empires and reactions to them in the composition of the texts of the Hebrew Bible.
Recent Trends in the Study of Midrash and Rabbinic Narrative
Authors: Bakhos Carol
Published: December 2008

The present article surveys some significant developments in scholarship on rabbinic midrash and narrative (aggadic) sources. The contemporary trends in the study of midrash can be traced back to the work of Jacob Neusner in the early 1970s. This article traces developments from that time, and does so by isolating trends in (1) literary analysis, (2) cultural studies, and (3) new historicism. A final section (4) looks at equally important developments concerning still unfinished business of producing critical editions of rabbinic texts.
Outcomes of In-school Leadership Development Work
Authors: Simkins Tim , Coldwell Mike , Close Paul , Morgan Anne
Published: December 2008

This article presents the results of a study of the impact of three programmes of the National College for School Leadership (NCSL), namely Leading from the Middle, the National Professional Qualification for Headship and the Leadership Programme for Serving Headteachers. All three programmes embody a blended learning approach that includes an in-school component. This article focuses on factors within the programmes that influence learning from the in-school components. It focuses particularly on factors relating to individual participants and to the school contexts within which they work. The article relates the findings to previous literature on work-based learning and suggests a broader model of the factors that influence the outcomes of leadership development programmes.
`It's OK for people to feel angry'
Authors: Duperouzel Helen
Published: December 2008

Ward managers working in a medium secure learning disability service were asked to identify members of staff who they believed to be superior in the management of violent and aggressive individuals. A grounded theory approach was used to interview staff about their management of imminent aggression. The participants explained their strategies in terms of the following eight themes, which were common to all interviews: safety and de-escalation, attribution and control, relationships, understanding and empowerment, anticipating reactions, creating a faÇade, communication, and humour. The participants described the importance of building up trusting relationships with clients when trying to understand the reasons for the client's behaviour. They also explained how they offer a `get-out clause' to the client, a way for the client to decide to calm down without losing face. The participants also reported that creating the appearance of being in control can help, as does the use of humour to aid communication.
Following up Fighting Fit
Authors: Chapman Melanie J. , Craven Michael J. , Chadwick Darren D.
Published: December 2008

This article presents findings on the long-term impact of health practitioner input to reduce obesity amongst adults with intellectual disabilities. Body mass index (BMI) was measured for an input group ( N = 33) and a comparison group ( N = 40) 6 years after the input group first received input. Data on BMI were collected at baseline, 6 months, 1 year and 6 years. Mean BMI for the input group reduced steadily over 6 years. Mean BMI in the non-input group rose initially, stabilized and then decreased (although remaining higher than at baseline). The input group demonstrated improvements in obesity levels and lost more weight than the non-input group. However, the differences between groups did not reach statistical significance. This and the improvements in BMI within the non-input group may be due to the relatively small sample size, effect size and the impact of other local initiatives.