bluuebunny/crossref_metadata_2025 huggingface dataset:
Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by Sulforaphane
Authors: Chen Ming-Jenn , Tang Wei-Yu , Hsu Che-Wei , Tsai Ya-Ting , Wu June-Fu , Lin Chen-Wei , Cheng Ya-Min , Hsu Yi-Chiang
Published: July 2011

We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential(ΔΨm). Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer.
Analysis of Soil-Vegetation Interrelationships in a South-Southern Secondary Forest of Nigeria
Authors: Eni D. D. , Iwara A. I. , Offiong R. A.
Published: July 2011

Soil-vegetation interrelationships in a secondary forest of South-Southern Nigeria were studied using principal component analysis (PCA) and canonical correlation analysis (CCA). The grid system of vegetation sampling was employed to randomly collect vegetation and soil data from fifteen quadrats of 10 m × 10 m. PCA result showed that exchangeable sodium, organic matter, cation exchange capacity, exchangeable calcium, and sand content were the major soil properties sustaining the regenerative capacity and luxuriant characteristics of the secondary forest, while tree size and tree density constituted the main vegetation parameters protecting and enriching the soil for its continuous support to the vegetation after decades of anthropogenic disturbance (food crop cultivation and illegal logging activities) before its acquisition and subsequent preservation by the Cross River State government in 2003. In addition, canonical correlation analysis showed result similar to PCA, as it indicated a pattern of relationship between soil and vegetation. The only retained canonical variate revealed a positive interrelationship between organic matter and tree size as well as an inverse relationship between organic matter and tree density. These extracted soil and vegetation variables are indeed significantly important in explaining soil-vegetation interrelationships in the highly regenerative secondary forest.
Complementary and Alternative Drugs Use among Preoperative Patients: A Cross-Sectional Study in Italy
Authors: Lucenteforte Ersilia , Gallo Eugenia , Pugi Alessandra , Giommoni Federica , Paoletti Angelica , Vietri Michele , Lupi Patrizia , La Torre Maristella , Diddi Gianluca , Firenzuoli Fabio , Mugelli Alessandro , Vannacci Alfredo , Lapi Francesco
Published: July 2011

Complementary and alternative drugs (CADs) are widely used in preoperative patients and may lead to potential interactions and adverse reactions. The aim of our study is to evaluate the prevalence and the predictors of CADs use among preoperative patients using data from an Italian survey. This cross-sectional study, which enrolled 478 patients (response rate: 83.5%), was carried out in three Tuscany hospitals (Italy). The prevalence of CADs use was 49.8%: 233 out of 238 participants used herbal products and/or dietary supplements.Valeriana officinaliswas the most reported product (19.4%). According to univariate analysis, users were commonly identified among middle-aged or older patients; unadjusted ORs were 2.1 (95% CI: 1.3–3.3) for patients aged 48–69 years, and 3.0 (95% CI: 1.9–4.7) for those of 70–95 years, when compared with individuals aged 18–47 years. Except for education and gender, adjusted estimates showed consistent results with univariate analyses: direct association was observed with higher education, and—although not significantly—with female gender. The high prevalence of CAD use in preoperative period could be suggestive of a certain risk of adverse effects due to CADs interactions. A careful medical history of CADs consumption should be ascertained before surgery.
Effectiveness of Core Stability Exercises and Recovery Myofascial Release Massage on Fatigue in Breast Cancer Survivors: A Randomized Controlled Clinical Trial
Authors: Cantarero-Villanueva Irene , Fernández-Lao Carolina , del Moral-Avila Rosario , Fernández-de-las-Peñas César , Feriche-Fernández-Castanys María Belén , Arroyo-Morales Manuel
Published: July 2011

The purpose of the present paper was to evaluate the effects of an 8-week multimodal program focused on core stability exercises and recovery massage with DVD support for a 6-month period in physical and psychological outcomes in breast cancer survivors. A randomized controlled clinical trial was performed. Seventy-eight (n=78) breast cancer survivors were assigned to experimental (core stability exercises plus massage-myofascial release) and control (usual health care) groups. The intervention period was 8 weeks. Mood state, fatigue, trunk curl endurance, and leg strength were determined at baseline, after the last treatment session, and at 6 months of followup. Immediately after treatment and at 6 months, fatigue, mood state, trunk curl endurance, and leg strength exhibited greater improvement within the experimental group compared to placebo group. This paper showed that a multimodal program focused on core stability exercises and massage reduced fatigue, tension, depression, and improved vigor and muscle strength after intervention and 6 months after discharge.
Differential Regulation of the Immune Response in the Spleen and Liver of Mice Infected withLeishmania donovani
Authors: Bankoti Rashmi , Stäger Simona
Published: July 2011

Immunity to pathogens requires generation of effective innate and adaptive immune responses.Leishmania donovanievades these host defense mechanisms to survive and persist in the host. A better understanding and identification of mechanisms thatL. donovaniemploys for its survival is critical for developing novel therapeutic interventions that specifically target the parasite. This paper will highlight some of the mechanisms that the parasite utilizes for its persistence and also discuss how the immune response is regulated.
Prostate-Specific Membrane Antigen-Based Therapeutics
Authors: Akhtar Naveed H. , Pail Orrin , Saran Ankeeta , Tyrell Lauren , Tagawa Scott T.
Published: July 2011

Prostate cancer (PC) is the most common noncutaneous malignancy affecting men in the US, leading to significant morbidity and mortality. While significant therapeutic advances have been made, available systemic therapeutic options are lacking. Prostate-specific membrane antigen (PSMA) is a highly-restricted prostate cell-surface antigen that may be targeted. While initial anti-PSMA monoclonal antibodies were suboptimal, the development of monoclonal antibodies such as J591 which are highly specific for the external domain of PSMA has allowed targeting of viable, intact prostate cancer cells. Radiolabeled J591 has demonstrated accurate and selective tumor targeting, safety, and efficacy. Ongoing studies using anti-PSMA radioimmunotherapy with177Lu-J591 seek to improve the therapeutic profile, select optimal candidates with biomarkers, combine with chemotherapy, and prevent or delay the onset of metastatic disease for men with biochemical relapse. Anti-PSMA monoclonal antibody-drug conjugates have also been developed with completed and ongoing early-phase clinical trials. As PSMA is a selective antigen that is highly overexpressed in prostate cancer, anti-PSMA-based immunotherapy has also been studied and utilized in clinical trials.
HERC2 Interacts with Claspin and Regulates DNA Origin Firing and Replication Fork Progression
Authors: Izawa Naoki , Wu Wenwen , Sato Ko , Nishikawa Hiroyuki , Kato Akihiro , Boku Narikazu , Itoh Fumio , Ohta Tomohiko
Published: July 2011

DNA replication, recombination, and repair are highly interconnected processes the disruption of which must be coordinated in cancer. HERC2, a large HECT protein required for homologous recombination repair, is an E3 ubiquitin ligase that targets breast cancer suppressor BRCA1 for degradation. Here, we show that HERC2 is a component of the DNA replication fork complex that plays a critical role in DNA elongation and origin firing. In the presence of BRCA1, endogenous HERC2 interacts with Claspin, a protein essential for G2–M checkpoint activation and replication fork stability. Claspin depletion slowed S-phase progression and additional HERC2 depletion reduced the effect of Claspin depletion. In addition, HERC2 interacts with replication fork complex proteins. Depletion of HERC2 alleviated the slow replication fork progression in Claspin-deficient cells, suppressed enhanced origin firing, and led to a decrease in MCM2 phosphorylation. In a HERC2-dependent manner, treatment of cells with replication inhibitor aphidicolin enhanced MCM2 phosphorylation. Taken together, our results suggest that HERC2 regulates DNA replication progression and origin firing by facilitating MCM2 phosphorylation. These findings establish HERC2 as a critical function in DNA repair, checkpoint activation, and DNA replication. Cancer Res; 71(17); 5621–5. ©2011 AACR.
Using Tandem Mass Spectrometry in Targeted Mode to Identify Activators of Class IA PI3K in Cancer
Authors: Yang Xuemei , Turke Alexa B. , Qi Jie , Song Youngchul , Rexer Brent N. , Miller Todd W. , Jänne Pasi A. , Arteaga Carlos L. , Cantley Lewis C. , Engelman Jeffrey A. , Asara John M.
Published: July 2011

Phosphatiditylinositide-3-kinase (PI3K) is activated in some cancers by direct mutation, but it is activated more commonly in cancer by mutation of upstream acting receptor tyrosine kinases (TK). At present, there is no systematic method to determine which TK signaling cascades activate PI3K in certain cancers, despite the likely utility of such information to help guide selection of tyrosine kinase inhibitor (TKI) drug strategies for personalized therapy. Here, we present a quantitative liquid chromatography tandem mass spectrometry approach that identifies upstream activators of PI3K both in vitro and in vivo. Using non–small cell lung carcinoma to illustrate this approach, we show a correct identification of the mechanism of PI3K activation in several models, thereby identifying the most appropriate TKI to downregulate PI3K signaling. This approach also determined the molecular mechanisms and adaptors required for PI3K activation following inhibition of the mTOR kinase TORC1. We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where tandem mass spectrometry detected and quantitatively measured the abundance of a helical domain mutant (E545K) of PIK3CA connected to PI3K activation. Overall, our findings establish a mass spectrometric approach to identify functional interactions that govern PI3K regulation in cancer cells. Using this technique to define the pathways that activate PI3K signaling in a given tumor could help inform clinical decision making by helping guide personalized therapeutic strategies for different patients. Cancer Res; 71(18); 5965–75. ©2011 AACR.
Cytotoxic Activity of Immunotoxin SS1P Is Modulated by TACE-Dependent Mesothelin Shedding
Authors: Zhang Yujian , Chertov Oleg , Zhang Jingli , Hassan Raffit , Pastan Ira
Published: July 2011

Mesothelin is a cell-surface tumor-associated antigen expressed in several human cancers. The limited expression of mesothelin on normal tissues and its high expression in many cancers make it an attractive candidate for targeted therapies using monoclonal antibodies, immunoconjugates, and immunotoxins. Mesothelin is actively shed from the cell surface and is present in the serum of patients with malignant mesothelioma, which could negatively affect the response to these therapies. We have found that mesothelin sheddase activity is mediated by a TNF-α converting enzyme (TACE), a member of the matrix metalloproteinase/a disintegrin and metalloprotease family. We showed that EGF and TIMP-3 act through TACE as endogenous regulators of mesothelin shedding. We also found that reducing shedding significantly improved the in vitro cytotoxicity of immunotoxin SS1P, which targets mesothelin and is currently in clinical trials for the treatment of patients with mesothelioma and lung cancer. Our findings provide a mechanistic understanding of mesothelin shedding and could help improve mesothelin-based targeted therapies. Cancer Res; 71(17); 5915–22. ©2011 AACR.
Breast Field Cancerization: Isolation and Comparison of Telomerase-Expressing Cells in Tumor and Tumor Adjacent, Histologically Normal Breast Tissue
Authors: Trujillo Kristina A. , Hines William C. , Vargas Keith M. , Jones Anna C. , Joste Nancy E. , Bisoffi Marco , Griffith Jeffrey K.
Published: July 2011

Telomerase stabilizes chromosomes by maintaining telomere length, immortalizes mammalian cells, and is expressed in more than 90% of human tumors. However, the expression of human telomerase reverse transcriptase (hTERT) is not restricted to tumor cells. We have previously shown that a subpopulation of human mammary epithelial cells (HMEC) in tumor-adjacent, histologically normal (TAHN) breast tissues expresses hTERT mRNA at levels comparable with levels in breast tumors. In the current study, we first validated a reporter for measuring levels of hTERT promoter activity in early-passage HMECs and then used this reporter to compare hTERT promoter activity in HMECs derived from tumor and paired TAHN tissues 1, 3, and 5 cm from the tumor (TAHN-1, TAHN-3, and TAHN-5, respectively). Cell sorting, quantitative real-time PCR, and microarray analyses showed that the 10% of HMECs with the highest hTERT promoter activity in both tumor and TAHN-1 tissues contain more than 95% of hTERT mRNA and overexpress many genes involved in cell cycle and mitosis. The percentage of HMECs within this subpopulation showing high hTERT promoter activity was significantly reduced or absent in TAHN-3 and TAHN-5 tissues. We conclude that the field of “normal tissue” proximal to the breast tumors contains a population of HMECs similar in hTERT expression levels and in gene expression to the HMECs within the tumor mass and that this population is significantly reduced in tissues more distal to the tumor. Mol Cancer Res; 9(9); 1209–21. ©2011 AACR.
Contribution of Xanthine Oxidoreductase to Mammary Epithelial and Breast Cancer Cell Differentiation In Part Modulates Inhibitor of Differentiation-1
Authors: Fini Mehdi A. , Monks Jenifer , Farabaugh Susan M. , Wright Richard M.
Published: July 2011

Loss of xanthine oxidoreductase (XOR) has been linked to aggressive breast cancer in vivo and to breast cancer cell aggressiveness in vitro. In the present study, we hypothesized that the contribution of XOR to the development of the normal mammary gland may underlie its capacity to modulate breast cancer. We contrasted in vitro and in vivo developmental systems by differentiation marker and microarray analyses. Human breast cancer microarray was used for clinical outcome studies. The role of XOR in differentiation and proliferation was examined in human breast cancer cells and in a mouse xenograft model. Our data show that XOR was required for functional differentiation of mammary epithelial cells both in vitro and in vivo. Poor XOR expression was observed in a mouse ErbB2 breast cancer model, and pharmacologic inhibition of XOR increased breast cancer tumor burden in mouse xenograft. mRNA microarray analysis of human breast cancer revealed that low XOR expression was significantly associated with time to tumor relapse. The opposing expression of XOR and inhibitor of differentiation-1 (Id1) during HC11 differentiation and mammary gland development suggested a potential functional relationship. While overexpression of Id1 inhibited HC11 differentiation and XOR expression, XOR itself modulated expression of Id1 in differentiating HC11 cells. Overexpression of XOR both inhibited Id1-induced proliferation and -stimulated differentiation of Heregulin-β1–treated human breast cancer cells. These results show that XOR is an important functional component of differentiation whose diminished expression contributes to breast cancer aggressiveness, and they support XOR as both a breast cancer biomarker and a target for pharmacologic activation in therapeutic management of aggressive breast cancer. Mol Cancer Res; 9(9); 1242–54. ©2011 AACR.
Frameless Stereotactic Cerebral Biopsy: Our Experience in 296 Cases
Authors: Frati Alessandro , Pichierri Angelo , Bastianello Stefano , Raco Antonino , Santoro Antonio , Esposito Vincenzo , Giangaspero Felice , Salvati Maurizio
Published: July 2011

Aims: To evaluate the reliability, safety and accuracy of a the frameless stereotactic system in our clinical series and the differences between head fixation by means of a standard Mayfield head holder and the pinless FESS frame, and to evaluate the usefulness of biopsy targeting on the basis of magnetic resonance spectroscopy (MRS) data. Methods: The spectroscopic analysis was used to facilitate the targeting of the lesion. The fusion image function embedded in the Neuronavigation Unit was used postoperatively to assess the level of accuracy of the biopsy. The grading of the glioma specimens was correlated to the spectroscopic data. Results: 296 patients underwent cerebral biopsy in 8 years. The diagnostic yield was 99.7%. The spectroscopic choline/N-acetyl aspartate ratio in different areas of the same tumor correlated well with the histological grading of the lesion. Conclusion: The frameless stereotactic systems guarantee excellent biopsy results. Advanced imaging, in particular MRS, facilitates the correct targeting of nonenhancing lesions.
A Non-Parametric Method for Building Predictive Genetic Tests on High-Dimensional Data
Authors: Ye Chengyin , Cui Yuehua , Wei Changshuai , Elston Robert C. , Zhu Jun , Lu Qing
Published: July 2011

Objective: Predictive tests that capitalize on emerging genetic findings hold great promise for enhanced personalized healthcare. With the emergence of a large amount of data from genome-wide association studies (GWAS), interest has shifted towards high-dimensional risk prediction.Methods: To form predictive genetic tests on high-dimensional data, we propose a non-parametric method, called the ‘forward ROC method’. The method adopts a computationally efficient algorithm to search for environment risk factors, genetic predictors on the entire genome, and their possible interactions for an optimal risk prediction model, without relying on prior knowledge of known risk factors. An efficient yet powerful procedure is also incorporated into the method to handle missing data. Results:Through simulations and real data applications, we found our proposed method outperformed the existing approaches. We applied the new method to the Wellcome Trust rheumatoid arthritis GWAS dataset with a total of 460,547 markers. The results from the risk prediction analysis suggested important roles of HLA-DRB1 and PTPN22 in predicting rheumatoid arthritis. Conclusion: We proposed a powerful and robust approach for high-dimensional risk prediction. The new method will facilitate future risk prediction that considers a large number of predictors and their interaction for improved performance.
A Systematic Review on the Use of Bortezomib in Multiple Myeloma Patients with Renal Impairment: What Is the Published Evidence?
Authors: Piro Eugenio , Molica Stefano
Published: July 2011

This report presents the totality of evidence through a systematic review that assessed either the efficacy or safety of bortezomib-based regimens in multiple myeloma with renal impairment. A systematic and comprehensive search of the literature was performed using MEDLINE databases from 1978 to December 1, 2010, and a hand search of references. We used the following medical subject headings (MESH) to identify potential studies: ‘myeloma renal failure’ (1,225 hits) and ‘bortezomib’ (2,554 hits). An additional search performed by combining the MESH terms ‘myeloma renal failure’ and ‘bortezomib’ yielded 50 citations. Five additional case-control studies judged relevant for the purpose of study were also included. In total, 6 case reports, 9 case series and 9 case-control studies were identified that reported on myeloma, renal failure and bortezomib. In this review, only the case series and case-control studies were considered. The results of our search led to the following conclusions: (1) bortezomib is feasible and well tolerated and its efficacy and safety are not substantially modified by renal failure patients, (2) renal failure should not induce physicians to reduce doses, since the efficacy of bortezomib is attained also in dialyzed patients who may achieve dialysis independence, and (3) standard doses of bortezomib (i.e. 1.3 mg/m2 on days 1, 4, 8, 11) associated with dexamethasone yield satisfactory tumor response, generally obtained shortly after starting therapy. Although many questions remain unanswered, our effort should be considered a relevant scientific and practical address for generating a diagnostic and therapeutic algorithm to be used in patients with renal impairment related to multiple myeloma.
Randomized Study of Minocycline and Edetic Acid as a Locking Solution for Central Line (Port-A-Cath) in Children with Cancer
Authors: Ferreira Chacon Julieta Maria , Hato de Almeida Emília , de Lourdes Simões Regina , Lazzarin C. Ozório Viviane , Alves Benaia Cândida , Mello de Andréa Maria Lydia , Santiago Biernat Marcela , Biernat João Carlos
Published: July 2011

Background: Contamination of central catheters is frequent, and biofilm perpetuates infections. Heparin does not protect against infections because it has no antibiotic action. Minocycline and edetic acid (M-EDTA), a potent calcium chelating agent that destroys bacterial and fungal cell membrane and disrupts biofilm, may be an alternative to allow the associated antibiotic to act locally at a high and safe concentration. Methods: Fifty children with cancer and a port-a-cath were followed up: 26 received heparin (group 1) and 24 M-EDTA (group 2). A total of 762 serial prospective blood cultures were obtained, 387 from group 1 and 375 from group 2. Results: In group 1 (heparin), 19 blood cultures were positive, and infection incidence was 73.1% (19/26 ports). In group 2 (M-EDTA), 5 blood cultures were positive, and the incidence rate was 20.8% (5/24 ports). Conclusion: M-EDTA, compared with heparin, prevents and treats catheter infections, and is a promising alternative to decrease sepsis during chemotherapy.
Growth Hormone Receptor: Structure Function Relationships
Authors: Waters Michael J. , Brooks Andrew J.
Published: July 2011

Background: The growth hormone receptor (GHR) was the first class 1 cytokine receptor to be cloned, and it has been studied intensively. The crystal structures of the bound and unbound forms have been solved and the energetic contributions of residues involved in the binding interaction have been quantified. Two receptor subunits bind to opposite sides of the hormone through site 1 and site 2, and a third interaction occurs between receptors in the lower β-sandwich module at site 3. All three interactions are required for receptor activation, which was thought to be a consequence of hormone-induced receptor dimerization. However, substantial data support the existence of a constitutive receptor dimer that interacts via the transmembrane domain (TMD), with receptor activation triggered by a hormone-induced conformational change. Mutagenesis studies and crystal structure data indicate that receptor activation involves a relative rotation and scissor movement of subunits to activate the associated tyrosine kinase, Janus kinase 2 (JAK2). We have recently reported that a second tyrosine kinase, an Src-family kinase, also associates constitutively with the receptor and activates the Ras–extracellular-signal-regulated kinase pathway. Activation of this kinase requires a conformational change in a loop of the lower sandwich module, and a different orientation of the TMDs than needed for JAK2 activation. Conclusions: This structural difference could allow differential activation of these two kinases by GH analogues such as I179M human GH.
Lessons Learned from 15 Years of KIMS and 5 Years of ACROSTUDY
Authors: Luger Anton , Feldt-Rasmussen Ulla , Abs Roger , Gaillard Rolf C. , Buchfelder Michael , Trainer Peter , Brue Thierry
Published: July 2011

Background: Pharmacoepidemiological surveys provide a valuable contribution to the continued monitoring of drug-related effects in patients with rare disorders. One of the earliest examples of this type of survey is KIGS (Pfizer International Growth Study Database), which has monitored the safety and effectiveness of growth hormone (GH) therapy in GH-deficient children since its inception in 1987. Following closely in the footsteps of KIGS is KIMS (Pfizer International Metabolic Database). As of 2009, KIMS has been collecting data on the long-term safety and clinical outcomes of GH replacement in GH-deficient adults for 15 years. Approximately 5 years ago, the ACROSTUDY database was established to monitor the long-term safety and effectiveness of pegvisomant in patients with acromegaly. Conclusions: By collecting data on the treatment of relatively rare conditions in routine clinical practice, pharmacoepidemiological surveys such as KIMS and ACROSTUDY provide valuable information on the safety and effectiveness of treatment with GH replacement and pegvisomant in the real world.
Epidemiology of Childhood Type 1 Diabetes Mellitus: Lessons from Central and Eastern European Data
Authors: Cinek Ondrej
Published: July 2011

Background: Over the past 15 years, the incidence of type 1 diabetes mellitus (T1DM) in Central and Eastern Europe has grown rapidly from an initially low rate. This growth cannot be attributed to genetic factors: it appears that changing environmental exposures are responsible, though no single environmental factor can be pinpointed. Since the end of the 1980s, the populations in this part of Europe have experienced rapid changes that are being investigated as possible etiologic environmental factors. These changes may not differ in nature from similar changes observed in Western Europe, yet they undoubtedly differ in the speed of the change. This is exemplified by recent changes in reproductive behavior that resulted in the extremely swift increase in average maternal age and varying patterns of crude natality observed in some populations. However, studies performed in Central and Eastern Europe have not revealed any unique patterns of associations with putative risk factors. Conclusion: No data indicate that Eastern or Central European countries form any special entity with respect to T1DM epidemiology. The T1DM incidence trends should continue to be actively observed, as such observations are a potential source of information on disease etiology.
Growth Hormone in Sports: Detecting the Doped or Duped
Authors: Ho Ken K.Y. , Nelson Anne E.
Published: July 2011

Background: Doping with growth hormone (GH) is banned; however, there is anecdotal evidence that it is widely abused. GH is reportedly often used in combination with anabolic steroids at high doses for several months. Development of a robust test for detecting GH has been challenging since recombinant human 22-kDa GH used in doping is indistinguishable analytically from endogenous GH and there are wide physiological fluctuations in circulating GH concentrations. Discussion: One approach to GH testing is based on measurement of different circulating GH isoforms using immunoassays that differentiate between 22-kDa and other GH isoforms. Administration of 22-kDa GH results in a change in its abundance relative to other endogenous pituitary GH isoforms. The differential isoform method is, however, limited by its short time window of detection. A second approach that extends the time window of detection is based on detection of increased levels of circulating GH-responsive proteins, such as the insulin-like growth factor (IGF) axis and collagen peptides. As age and gender are the major determinants of variability for IGF-I and the collagen markers, a test based on these markers must take these factors into account. Extensive data now validate the GH-responsive marker approach, and implementation is largely dependent on establishing an assured supply of standardized assays. Conclusions: Robust tests are available to detect GH and enforce the ban on its abuse in sports. Novel approaches that include gene expression and proteomic profiling must continue to be pursued to expand the repertoire of testing approaches available and to maintain deterrence of GH doping.
Protection of Inner Ear Function after Cochlear Implantation: Compound Action Potential Measurements after Local Application of Glucocorticoids in the Guinea Pig Cochlea
Authors: Braun Susanne , Ye Qing , Radeloff Andreas , Kiefer Jan , Gstoettner Wolfgang , Tillein Jochen
Published: July 2011

Background: Cochlear implant users with residual hearing often benefit greatly from simultaneous electric and acoustic stimulation. However, implantation can cause trauma to the inner ear, resulting in poorer hearing postoperatively. We investigated whether a single local injection of glucocorticoids can reduce hearing loss in long-term implanted guinea pigs. Methods: Three groups of animals underwent bilateral surgery. One ear was implanted with an electrode, and the contralateral ear received a cochleostomy only. A single dose of the glucocorticoids triamcinolone or dexamethasone, or of artificial perilymph was infused into cochleae via cochleostomy. Compound action potentials were measured before and after application and for 3 months postoperatively. Tissue growth was measured as the percentage of the total area of the scala tympani that was obliterated. Results: Ears subjected to cochleostomy only and treated with glucocorticoids demonstrated a mild hearing loss. In the implanted ears, both glucocorticoids preserved hearing at least temporarily. The volume of tissue growth within the scala tympani was not reduced, and there was no relation between the amount of tissue and hearing loss. Conclusions: Both glucocorticoids show a potential benefit for hearing preservation in implanted ears. Glucocorticoid therapy may be useful to protect residual hearing during cochlear implantation.
G Protein Coupled Receptor Kinases as Therapeutic Targets in Cardiovascular Disease
Authors: Belmonte Stephen L. , Blaxall Burns C.
Published: July 2011

G protein-coupled receptors (GPCRs) represent the largest family of membrane receptors and are responsible for regulating a wide variety of physiological processes. This is accomplished via ligand binding to GPCRs, activating associated heterotrimeric G proteins and intracellular signaling pathways. G protein-coupled receptor kinases (GRKs), in concert with β-arrestins, classically desensitize receptor signal transduction, thus preventing hyperactivation of GPCR second-messenger cascades. As changes in GRK expression have featured prominently in many cardiovascular pathologies, including heart failure, myocardial infarction, hypertension, and cardiac hypertrophy, GRKs have been intensively studied as potential diagnostic or therapeutic targets. Herein, we review our evolving understanding of the role of GRKs in cardiovascular pathophysiology.
Regulators of G-Protein Signaling in the Heart and Their Potential as Therapeutic Targets
Authors: Zhang Peng , Mende Ulrike
Published: July 2011

Signal transduction through G-protein–coupled receptors (GPCRs) is central for the regulation of virtually all cellular functions and has been widely implicated in human disease. Regulators of G-protein signaling (RGS proteins) belong to a diverse protein family that was originally discovered for their ability to accelerate signal termination in response to GPCR stimulation, thereby reducing the amplitude and duration of GPCR effects. All RGS proteins share a common RGS domain that interacts with G protein α subunits and mediates their biological regulation of GPCR signaling. However, RGS proteins differ widely in size and the organization of their sequences flanking the RGS domain, which contain several additional functional domains that facilitate protein-protein (or protein-lipid) interactions. RGS proteins are subject to posttranslational modifications, and, in addition, their expression, activity, and subcellular localization can be dynamically regulated. Thus, there exists a wide array of mechanisms that facilitate their proper function as modulators and integrators of G-protein signaling. Several RGS proteins have been implicated in the cardiac remodeling response and heart rate regulation, and changes in RGS protein expression and/or function are believed to participate in the pathophysiology of cardiac hypertrophy, failure and arrhythmias as well as hypertension. This review is based on recent advances in our understanding of the expression pattern, regulation, and functional role of canonical RGS proteins, with a special focus on the healthy heart and the diseased heart. In addition, we discuss their potential and promise as therapeutic targets as well as strategies to modulate their expression and function.
Social Justice Advocacy in Rural Communities
Authors: Bradley Joshua M. , Werth James L. , Hastings Sarah L.
Published: July 2011

The professional literature related to social justice has increased, but there has been little discussion of the practical issues and implications associated with social advocacy. However, adding new roles will result in new considerations for counseling psychologists. The need to be attuned to how the practical aspects of advocacy intersect with the context of psychological work may be especially present in rural areas where practitioners may be more involved in the community and thus their actions highly visible. Because the data indicate that rural communities may have few resources, a limited number of mental health professionals, and higher rates of mental illness, psychologists practicing in these areas may feel compelled to engage in advocacy. Yet there is little practical guidance for these psychologists. Therefore, the authors present considerations for social justice advocacy in rural areas, using the American Counseling Association advocacy competencies as an organizing framework.
Multigroup Generalizability Analysis of Verbal, Quantitative, and Nonverbal Ability Tests for Culturally and Linguistically Diverse Students
Authors: Lakin Joni M. , Lai Emily R.
Published: July 2011

For educators seeking to differentiate instruction, cognitive ability tests sampling multiple content domains, including verbal, quantitative, and nonverbal reasoning, provide superior information about student strengths and weaknesses compared with unidimensional reasoning measures. However, these ability tests have not been fully evaluated with respect to fairness and validity for English-language learners (ELL). In particular, reliability is an important aspect of validity that has not been sufficiently evaluated. In this study, multivariate generalizability methodologies were used to explore the differential reliability of the Cognitive Abilities Test across ELL and non-ELL students in two schools with large Hispanic populations. Results suggest that verbal and quantitative reasoning skills are measured less precisely for ELL students than for non-ELL students. However, the composite score of the three batteries showed strong reliability in both groups. We conclude that multidimensional tests provide reliable information about the academic strengths of ELL and non-ELL students, though further research is needed.
The Poisoned Madeleine: The Autobiographical Turn in Historical Writing
Authors: Vinen Richard
Published: July 2011

This article examines the recent fashion for autobiographical writing among historians. It argues that this fashion goes with a rehabilitation of contemporary history, which was sometimes regarded with disdain during the time in the mid-1960s when approaches associated with the Annales school seemed most influential. Autobiographies by historians have attracted particular attention in France and all such works are sometimes labelled with the term first coined by Pierre Nora: ego-histoire. However, this article argues that the historians brought together by Nora (all French, mostly born between 1917 and 1930 and heavily influenced by the political upheavals of the period 1940 to 1962) were rather different from those historians (mostly from a younger generation) who have been drawn to autobiographical writing in the Anglo-American world. It is finally suggested that there is now something of a reaction against autobiographical writing by a younger generation of historians who argue that, even when writing about the very recent past, absence of direct personal experience can be an advantage.
Blogging Current Affairs History
Authors: Cole Juan
Published: July 2011

The internet poses acute challenges to historians. Blogging and other forms of internet communication have outstripped the reach of more conventional forms of academic publications. They also provide new types of sources that would otherwise be impossible for historians to access, not least in areas of conflict. These new forms of communication must be embraced by contemporary historians as they seek to speak truth to power. They allow contemporary historians to engage with public and political debate in critical new ways. Blogging will not replace the monograph or the peer-reviewed journal article, nor will it replace archival research. In affecting public debates and political outcomes, and in obtaining new sources, blogging is a form of communication contemporary historians ignore at their peril.
The Past Under Erasure? History, Memory, and the Contemporary
Authors: Eley Geoff
Published: July 2011

This article seeks to explore some particularities of history writing in the present. It considers in turn the meanings of the contemporary interest in memory, the different ways in which ideas about and images of the past circulate through the mass-mediated public sphere of the late twentieth and early twenty-first centuries, the complexities of publicness and the public sphere, and the shifting boundaries between popular ideas of the past and changes in the discipline of history. It then turns to the example of (West) Germany between the 1960s and now. The article concludes with some reflections on changing perceptions of the overall character of the twentieth century.
Contemporary History in Europe: From Mastering National Pasts to the Future of Writing the World
Authors: Spohr Readman Kristina
Published: July 2011

Debates surrounding the approach to and distinctiveness of contemporary history qua history that had been simmering ever since the professionalization of history in the late nineteenth century re-emerged with vigour after 1990. This article attempts to identify what characterizes and distinguishes (the history of) our present time, by comparing the evolution of what has been labelled ‘contemporary history’ in France, Germany and Britain over the last 90 years. In discussing some of the conceptual problems and methodological challenges of contemporary history, it will be revealed that many in Europe remain stuck in an older, ‘national’ (and transnational) fixation with the second world war and the nazis’ atrocities, although working in medias res today appears to point to the investigation of events and phenomena that are ‘global’. The article will seek to make a fresh suggestion of how to delimit ‘contemporariness’ from the older ‘past’ and end with some comments on the significance of the role of contemporary history within the broader historical discipline and society at large.
The arts and modern Christian architecture
Authors: Jasper David
Published: July 2011

Modern Christian architecture has stood largely in isolation from movements in contemporary art, driven primarily by the demands of the liturgy, especially after the Second Vatican Council. But Rudolf Schwarz regarded ecclesiastical architecture as a dynamic space for the human experience of the divine presence. In the work of Le Corbusier, the church building is theology enacted in stone. Rather than dictated by the form of the liturgy, church architecture should make the celebration of the liturgy possible, a sacred space consonant also with the spirit of contemporary art.
Pentecostal and charismatic theology comes of age
Authors: Cartledge Mark J.
Published: July 2011

This article reviews five recent books from Pentecostal scholars: William K. Kay, Frank D. Macchia, James K. A. Smith, Wolfgang Vondey and Amos Yong. Each book is briefly reviewed in turn and placed within the broader context of Pentecostal and Charismatic theology. It could now be said that Pentecostal and Charismatic theology has come of age because these texts represent important contributions not only to Pentecostal and Charismatic scholarship but also to the wider Christian tradition. They are part of a much greater and exciting development in the field.
Evaluating corn starch and corn stover biochar as renewable filler in carboxylated styrene–butadiene rubber composites
Authors: Peterson Steven C.
Published: July 2011

Corn starch, corn flour, and corn stover biochar were evaluated as potential renewable substitutes for carbon black as filler in rubber composites using carboxylated styrene–butadiene as the rubber matrix. Previous work has shown that starch-based fillers have very good reinforcement properties at the expense of brittleness in the final rubber composite. In an attempt to alleviate this, starch was blended with corn stover biochar; the biochar does not have as good reinforcement properties but makes composites that are less brittle. It was found that carboxylated styrene–butadiene rubber composites filled with 10% (by weight) corn starch or a 3:1 blend of corn starch:biochar had better reinforcement, tensile strength, elongation, and toughness than the corresponding carbon black-filled control sample. These renewable fillers therefore show good potential in replacing carbon black filler for applications utilizing more ductile styrene–butadiene rubber composites.
Concordance Theory, Targeted Partnership, and Counterinsurgency Strategy
Authors: Schiff Rebecca L.
Published: July 2011

This study introduces the new concept of targeted partnership, which encourages robust dialogue between military officers and policy makers to create and implement effective military strategy such as counterinsurgency. Targeted partnership is a distillate form of concordance theory or agreement involving reciprocity between the military, political elites, and society for a limited period of time to accomplish a very specific objective. Targeted partnership may involve the temporary co-mingling of military, political, and societal boundaries even when the broader institutional and cultural relationship between military and society may be one of separation. In other words, separation and integration may exist at the same time for very specific reasons central to a nation’s foreign policy. Targeted partnership is a practical extension of concordance theory that enables the military to have effective interactive dialogue with policy makers to explore critical military strategies, such as counterinsurgency, while considering the cultural and institutional contexts of foreign nations.
Crisis Management
Authors: Christensen Tom , Fimreite Anne Lise , Lægreid Per
Published: July 2011

This article describes and explains perceptions of how able government bodies are to prevent and handle crises based on surveys of Norwegian citizens and civil servants. The citizens generally have a rather high level of trust in the government’s ability to handle and prevent crises, and there are no big differences between the general public and the civil servants regarding their perception of crisis management. Trust-related factors are the main explanatory variables among the citizens, whereas the variations in the views of the bureaucrats are related to policy area, perceived coordinative capability, and mutual trust between governmental bodies.
Stealth Economy? Economic Theory and the Politics of Administrative Reform
Authors: Pierre Jon
Published: July 2011

Market-based administrative reform has triggered a debate argument in the public administration field. Some argue that it enhances cost efficiency and customer responsiveness. Others maintain that the public sector is not just a service-producing system delivering “public value” but that it stands for legality, due process, and legal security in addition to being a service provider. The article first compares the impact of market-based reform in Rechtsstaat administrative systems and “public interest” systems. It then discusses the potential democratic downsides to market solutions in the public administration and assesses under what conditions “publicness” can be delegated to private sector organizations.
The Paradox of Rules
Authors: Portillo Shannon
Published: July 2011

There is limited scholarship considering how social status factors such as race, ethnicity, gender, and age frame rules in public organizations. Using data collected from semistructured interviews with 49 local government officials, the author argues that there is a paradox of rules. Women and people of color are increasingly entering the ranks of local bureaucracies, but they experience their authority differently than white men. Their claim to authority is challenged more often. Unable to rely on implicit rank and social status as a defense, they must rely instead on official rights and rules. The very meaning of their authority is therefore different: It is more rule and rights based, more formal than informal, more explicit than implicit. Yet, because it is more rule based, formal, and explicit, their authority is also more open to question and challenge, and more resented as an artifice. People of color and women in positions of authority thus face the paradox of rules: They must rely on formal rules as a key basis for their authority, but relying on rules makes their authority seem more artificial than real.
Knowledge Work, Working Time, and Use of Time Among Finnish Dual-Earner Families
Authors: Nätti Jouko , Anttila Timo , Tammelin Mia
Published: July 2011

The industrial working-time regime is dissolving—not dramatically, but rather as a trend. A new trend is that those in dynamic sectors and in a good labor market position work long hours: Demanding knowledge work appears to require the marginalization of private life. This study investigates the family situation of knowledge workers, the concentration of knowledge workers into family, working time, and use of time in different family types. The analysis is based on the Finnish Use of Time data (1999-2000) using family(spouse)-level data. Compared with other categories of employment, the results suggest only minor quantitative differences between knowledge worker families in working time and use of time. However, the results show that qualitative experience of time varied across families. Knowledge work families especially experienced feelings of hurriedness and time famine.