bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Novel In Silico Model to Predict Corneal Permeability for Congeneric Drugs: A QSPR Approach
Authors: Sharma Charu , Velpandian Thirumurthy , Biswas Nihar Ranjan , Nayak Niranjan , Vajpayee Rasik Bihari , Ghose Supriyo
Published: February 2011

This study was undertaken to determine in vivo permeability coefficients for fluoroquinolones and to assess its correlation with the permeability derived using reported models in the literature. Further, the aim was to develop novel QSPR model to predict corneal permeability for fluoroquinolones and test its suitability on other training sets. The in vivo permeability coefficient was determined using cassette dosing (N-in-One) approach for nine fluoroquinolones (norfloxacin, ciprofloxacin, lomefloxacin, ofloxacin, levofloxacin, sparfloxacin, pefloxacin, gatifloxacin, and moxifloxacin) in rabbits. The correlation between corneal permeability derived using in vivo studies with that derived from reported models was determined. Novel QSPR‐based model was developed using in vivo corneal permeability along with other molecular descriptors. The suitability of developed model was tested on β‐blockers (n = 15). The model showed better prediction of corneal permeability for fluoroquinolones (r2 > 0.9)
as well as β‐blockers (r2 > 0.6). The newly developed QSPR model based upon in vivo generated data was found suitable to predict corneal permeability for fluoroquinolones as well as other sets of compounds.
Laboratory Animal Models for Brucellosis Research
Authors: Silva Teane M. A. , Costa Erica A. , Paixão Tatiane A. , Tsolis Renée M. , Santos Renato L.
Published: February 2011

Brucellosis is a chronic infectious disease caused by Brucella spp., a Gram‐negative facultative intracellular pathogen that affects humans and animals, leading to significant impact on public health and animal industry. Human brucellosis is considered the most prevalent bacterial zoonosis in the world and is characterized by fever, weight loss, depression, hepato/splenomegaly, osteoarticular, and genital infections. Relevant aspects of Brucella pathogenesis have been intensively investigated in culture cells and animal models. The mouse is the animal model more commonly used to study chronic infection caused by Brucella. This model is most frequently used to investigate specific pathogenic factors of Brucella spp., to characterize the host immune response, and to evaluate therapeutics and vaccines. Other animal species have been used as models for brucellosis including rats, guinea pigs, and monkeys. This paper discusses the murine and other laboratory animal models for human and animal brucellosis.
Synergistic Antitumor Effect of Dichloroacetate in Combination with 5‐Fluorouracil in Colorectal Cancer
Authors: Tong Jingtao , Xie Ganfeng , He Jinxia , Li Jianjun , Pan Feng , Liang Houjie
Published: February 2011

Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been recently demonstrated as a promising nontoxic antineoplastic agent that promotes apoptosis of cancer cells. In the present study, we aimed to investigate the antitumor effect of DCA combined with 5‐Fluorouracil (5‐FU) on colorectal cancer (CRC) cells. Four human CRC cell lines were treated with DCA or 5‐FU, or a combination of DCA and 5‐FU. The cell viability was determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. The interaction between DCA and 5‐FU was evaluated by the median effect principle. Immunocytochemistry with bromodeoxyuridine (BrdU) was carried out to determine the proliferation of CRC cells. Cell cycle and apoptosis were measured by flow cytometry, and the expression of apoptosis‐related molecules was assessed by western blot. Our results demonstrated that DCA inhibited the viability of CRC cells and had synergistic antiproliferation in combination with 5‐FU. Moreover, compared with 5‐FU alone, the apoptosis of CRC cells treated with DCA and 5‐FU was enhanced and demonstrated with the changes of Bcl‐2, Bax, and caspase‐3 proteins. Our results suggest that DCA has a synergistic antitumor effect with 5‐FU on CRC cell lines in vitro.
A Novel Domperidone Hydrogel: Preparation, Characterization, Pharmacokinetic, and Pharmacodynamic Properties
Authors: Zhang Chun-Hui , Zhao Bing-Xiang , Huang Yue , Wang Ying , Ke Xi-Yu , Zhao Bo-Jun , Zhang Xuan , Zhang Qiang
Published: February 2011

The purpose of the present study was to prepare a novel domperidone hydrogel. The domperidone dispersion was prepared by the solvent evaporation method. The characteristics of domperidone dispersion were measured by dynamic light scattering (DLS), scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry, and solubility test, respectively. Domperidone hydrogel was prepared by directly incorporating the domperidone dispersion in Carbopol hydrogel to increase its mucoadhesive properties to gastrointestinal tract (GIT). The in vivo pharmacokinetic and pharmacodynamic studies were investigated to evaluate the relative oral bioavailability and the propulsion efficacy of domperidone hydrogel as compared with market domperidone tablet (Motilium tablet). The particle size of domperidone dispersion in distilled water was 454.0 nm. The results of DSC and X-ray indicated that domperidone in dispersion was in amorphous state. The solubility of domperidone in the dispersion in distilled water, pH of 1, 5, and 7 buffer solution was 45.7-, 63.9-, 13.1-, and 3.7-fold higher than that of raw domperidone, respectively. The area under the plasma concentration curve (AUC0–24) in domperidone hydrogel was 2.2-fold higher than that of tablet. The prolonged propulsion efficacy in the domperidone hydrogel group compared to that in tablet group was observed in the pharmacodynamic test.
Ragu: A Free Tool for the Analysis of EEG and MEG Event-Related Scalp Field Data Using Global Randomization Statistics
Authors: Koenig Thomas , Kottlow Mara , Stein Maria , Melie-García Lester
Published: February 2011

We present a program (Ragu; Randomization Graphical User interface) for statistical analyses of multichannel event-related EEG and MEG experiments. Based on measures of scalp field differences including all sensors, and using powerful, assumption-free randomization statistics, the program yields robust, physiologically meaningful conclusions based on the entire, untransformed, and unbiased set of measurements. Ragu accommodates up to two within-subject factors and one between-subject factor with multiple levels each. Significance is computed as function of time and can be controlled for type II errors with overall analyses. Results are displayed in an intuitive visual interface that allows further exploration of the findings. A sample analysis of an ERP experiment illustrates the different possibilities offered by Ragu. The aim of Ragu is to maximize statistical power while minimizing the need for a-priori choices of models and parameters (like inverse models or sensors of interest) that interact with and bias statistics.
Long-term Use of Cholesterol-Lowering Drugs and Cancer Incidence in a Large United States Cohort
Authors: Jacobs Eric J. , Newton Christina C. , Thun Michael J. , Gapstur Susan M.
Published: February 2011

HMG-coA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use. However, little is known about the association between long-term statin use and incidence of most types of cancers. We examined the association between long-term use of cholesterol-lowering drugs, predominantly statins, and the incidence of ten common cancers, as well as overall cancer incidence, among 133,255 participants (60,059 men and 73,196 women) in the Cancer Prevention Study II Nutrition Cohort during the period from 1997 to 2007. Multivariate Cox proportional hazards regression was used to estimate relative risks (RR). Current use status and duration of use were updated during follow-up using information from biennial follow-up questionnaires. Current use of cholesterol-lowering drugs for five or more years was not associated with overall cancer incidence (RR = 0.97, 95% CI = 0.92–1.03), or incidence of prostate, breast, colorectal, lung, bladder, renal cell, or pancreatic cancer but was associated with lower risk of melanoma (RR = 0.79, 95% CI = 0.66–0.96), endometrial cancer (RR = 0.65, 95% CI = 0.45–0.94), and non-Hodgkin lymphoma (NHL; RR = 0.74, 95% CI = 0.62–0.89). These results suggest that long-term use of statins is unlikely to substantially increase or decrease overall cancer risk. However, associations between long-term statin use and risk of endometrial cancer, melanoma, and NHL deserve further investigation. Cancer Res; 71(5); 1763–71. ©2011 AACR.
p95HER2 and Breast Cancer
Authors: Arribas Joaquín , Baselga José , Pedersen Kim , Parra-Palau Josep Lluís
Published: February 2011

A subtype of HER2-positive tumors with distinct biological and clinical features expresses a series of carboxy-terminal fragments collectively known as p95HER2. One of these fragments, named 100- to 115-kDa p95HER2 or 611-CTF, is hyperactive because of its ability to form homodimers maintained by intermolecular disulfide bonds. Despite lacking the majority of the extracellular domain, this HER2 fragment drives breast cancer progression in vivo. The recent availability of specific anti-p95 antibodies has confirmed previous results indicating that the expression of p95HER2 is predictive of poor prognosis and correlates with resistance to the treatment with trastuzumab, a therapeutic antibody directed against the extracellular domain of HER2. Cancer Res; 71(5); 1515–9. ©2011 AACR.
Placental Growth Factor Upregulation Is a Host Response to Antiangiogenic Therapy
Authors: Bagley Rebecca G. , Ren Yi , Weber William , Yao Min , Kurtzberg Leslie , Pinckney Jason , Bangari Dinesh , Nguyen Cokey , Brondyk William , Kaplan Johanne , Teicher Beverly A.
Published: February 2011

Purpose: Placental growth factor (PlGF) is an angiogenic protein. Upregulation of PlGF has been observed in the clinic following antiangiogenic regimens targeting the VEGF pathway. PlGF has been proposed as a therapeutic target for oncology. sFLT01 is a novel fusion protein that neutralizes mouse and human PlGF (mPlGF, hPlGF) and mouse and human VEGF-A (mVEGF-A, hVEGF-A). It was tested in syngeneic and xenograft tumor models to evaluate the effects of simultaneously neutralizing PlGF and VEGF-A and to investigate changes observed in the clinic in preclinical models.

Experimental Design: Production of PlGF and VEGF-A by B16F10 and A673 cancer cells in vitro was assessed. Mice with subcutaneous B16F10 melanoma or A673 sarcoma tumors were treated with sFLT01. Tumor volumes and microvessel density (MVD) were measured to assess efficacy. Serum levels of hVEGF-A, hPlGF, and mPlGF at early and late time points were determined by ELISA.

Results: Exposure of cancer cell lines to sFLT01 caused a decrease in VEGF secretion. sFLT01 inhibited tumor growth, prolonged survival, and decreased MVD. Analysis of serum collected from treated mice showed that sFLT01 administration caused a marked increase in circulating mPlGF but not hPlGF or hVEGF. sFLT01 treatment also increased circulating mPlGF levels in non–tumor-bearing mice.

Conclusion: With the tumor cell lines and mouse models we used, antiangiogenic therapies that target both PlGF and VEGF may elicit a host response rather than, or in addition to, a malignant cell response that contribute to therapeutic resistance and tumor escape as suggested by others. Clin Cancer Res; 17(5); 976–88. ©2011 AACR.
Prevention of Motor Neuron Degeneration by Novel Iron Chelators in SOD1G93A Transgenic Mice of Amyotrophic Lateral Sclerosis
Authors: Wang Qian , Zhang Xiaojie , Chen Sheng , Zhang Xin , Zhang Sufang , Youdium Moussa , Le Weidong
Published: February 2011

Background: The causes of amyotrophic lateral sclerosis (ALS) are largely unknown. Oxidative stress is considered to play a major role in motor neuron degeneration associated with iron homeostasis disturbance. Objective: Iron chelation treatment might be a potential therapeutic approach on the basis of its ability to reduce the oxygen free radical generation caused by iron accumulation. Methods and Results: In the present study, we applied the brain-permeable iron chelators VK-28 and M30 in a G93A mutant superoxide dismutase 1 transgenic (SOD1G93A) mouse model of ALS and found that VK-28 and M30 significantly delayed disease onset, extended the life span and reduced spinal cord motor neuron loss. Furthermore, we documented that both iron chelators significantly attenuated the elevated iron level and transferrin receptor expression, decreased oxygen free radicals and suppressed microglial and astrocytic activation in the spinal cords of the SOD1G93A mice. Moreover, we demonstrated that both iron chelators were able to decrease TDP-43 protein aggregation and the proapoptotic molecule Bax, and to enhance antiapoptotic protein Bcl-2 expression, in the ALS mice. Conclusions: These results provide evidence that iron is involved in the pathogenesis of ALS and iron chelation therapy may have the potential for the prevention and treatment of ALS.
Developmental Expression Mapping of a Gene Implicated in Multiple Neurodevelopmental Disorders, A2bp1 (Fox1)
Authors: Hammock Elizabeth A.D. , Levitt Pat
Published: February 2011

The neuronal transcription splicing factor, A2BP1, has been implicated in a variety of neurodevelopmental disorders; however, the role of A2BP1 in brain development and gene regulatory function remains to be explicated. Here, we map A2bp1 gene expression, focusing on the developing forebrain of the C57BL6J mouse. Early in forebrain development, A2bp1 expression is highly reminiscent of the expression of genes marking postmitotic GABAergic cells emanating from the ventral telencephalon during migration to the dorsal pallium. Ventral pallial expression remains low after the migratory period. Broader dorsal pallial expression becomes more evident late prenatally and early postnatally. This is paralleled by dense, restricted expression in the ventrobasal dorsal thalamic complex and mid-hypothalamic region. Outside of the forebrain, there is significant expression in motor pathways. These data indicate that A2BP1 mutations may clinically affect very selective forebrain neuron types from early periods of development.
MicroRNAs in Oligodendrocyte and Schwann Cell Differentiation
Authors: Dugas Jason C. , Notterpek Lucia
Published: February 2011

MicroRNAs (miRNAs) are a class of small (approx. 22 nt) noncoding RNAs that are capable of post-transcriptionally silencing mRNAs that contain sequences complementary to the miRNAs’ 7- to 8-bp ‘seed’ sequence. As single miRNAs are often predicted to target up to hundreds of individual transcripts, miRNAs are able to broadly affect the overall protein expression state of the cell. This can translate into global effects on cellular health and differentiation state. Recently, several reports have identified crucial roles for miRNAs in controlling the production, differentiation, and health of myelinating cells of the mammalian nervous system. In this review, we will discuss how individual miRNAs regulate these various processes, and also how miRNA production in general is required for several stages of myelin generation and maintenance.
How to Deal with Continuous and Dichotomic Outcomes in Epidemiological Research: Linear and Logistic Regression Analyses
Authors: Tripepi Giovanni , Jager Kitty J. , Stel Vianda S. , Dekker Friedo W. , Zoccali Carmine
Published: February 2011

Because of some limitations of stratification methods, epidemiologists frequently use multiple linear and logistic regression analyses to address specific epidemiological questions. If the dependent variable is a continuous one (for example, systolic pressure and serum creatinine), the researcher will use linear regression analysis. Otherwise, if the dependent variable is dichotomic (for example, presence/absence of microalbuminuria), one could use logistic regression analysis. In both linear and logistic regression analyses the independent variables may be either continuous or categorical. In this paper we will describe linear and logistic regression analyses by discussing methodological features of these techniques and by providing clinical examples and guidance (syntax) for performing these analyses by commercially available statistical packages. Furthermore, we will also focus on the use of multiple linear and logistic regression analyses to control for confounding in etiological research.
Apolipoprotein E Polymorphism and the Progression of Diabetic Nephropathy in Type 2 Diabetes
Authors: Tien Kai-Jen , Tu Shih-Te , Chou Chien-Wen , Yang Chwen-Yi , Hsiao Jeng-Yueh , Shin Shyi-Jang , Chen Hung-Chun , Hsieh Ming-Chia
Published: February 2011

Background/Aims: Three different apo E alleles (E2, E3 and E4) produce apo E isoproteins, which regulate the metabolism of lipoproteins. This study investigated the apo E polymorphisms as a prognostic factor for the development of diabetic nephropathy (DN). Methods: A total of 525 type 2 diabetic patients were enrolled to participate in this prospective observational study. Apo E gene polymorphisms were analyzed by polymerase chain reaction. The progression of DN was defined as a shift to a higher stage of DN or a doubling of the baseline serum creatinine level by the end of the study. Results: The mean follow-up period was 42.4 months. The patients whose DN progressed had significantly higher urine albumin/creatinine ratios and fewer used diuretics than those in whom DN did not progress. In the Cox regression analysis, the apo E4 carriers were found to be at greater risk of progression of DN than non-apo E4 carriers (p = 0.007, hazard ratio 2.252). After adjusting for confounding factors, apo E4 carriers remained at increased risk of progression to more severe DN (p = 0.002, hazard ratio 2.820). Conclusion: Our study suggests the apo E4 carrier might serve as a predictor of DN progression in Taiwan.
The Trial of the Refuseniks
Authors: Ezraty Igal , Rokem Freddie
Published: February 2011

The Trial of the Refuseniks drew attention to the moral issues of the conflict over the Israeli occupation of Gaza and the West Bank, a conflict that is still tearing Israeli society in two irreconcilable directions. The “theatrical documentary reading” is a reenactment of the military trial of five conscientious objectors, based on court transcripts.
Staging the Other Israel: The Documentary Theatre of Nola Chilton
Authors: Ben-Zvi Linda
Published: February 2011

Since 1970, the American-born Israeli director and acting teacher Nola Chilton has used documentary theatre to critique Israeli myths and to provide a space where groups generally excluded from the Israeli stage—Arabs, women, the poor, the elderly—can be seen and heard. Chilton's pioneering “theatre of testimony” bears a striking resemblance to recent documentary theatre practices proliferating in the U.S. and Europe.
Bodies of Evidence
Authors: Martin Carol
Published: February 2011

Documentary theatre is created from archived materials that foreground the nonfictional, even as it uses the literary and theatrical devises of fiction. The extratextual language of the body of the actor separates evidence from testimony, creating a space where the archive is interpolated by the repertory.
Antigone's Bones
Authors: Worthen W.B.
Published: February 2011

Returning to a formative moment in the discourse of performance studies with a glancing dialogue between Richard Schechner and Michael Goldman, this article traces a series of efforts by Benjamin Bennett, Herbert Blau, Elin Diamond, and Stanton Garner, among others, to seize the work of dramatic performance as performance and to develop a critical vocabulary that understands dramatic theatre as an encounter with writing rather than as a reinscription of the archive.
Baring and Bearing Life Behind Bars: Pat Graney's “Keeping the Faith” Prison Project
Authors: Berson Jessica
Published: February 2011

For the past 10 years Seattle-based choreographer Pat Graney has directed “Keeping the Faith” at the Washington State Women's Correctional Facility. The project provides participants with rare opportunities for self-expression and group cooperation, apparently serving the prison's stated goal of rehabilitation; but it also offers possibilities for transgression as it extends freedom of movement to highly regulated bodies.
Seeing Deb Margolin: Ontological Vandalism and Radical Amazement
Authors: Dolan Jill
Published: February 2011

Playwright and performer Deb Margolin's contributions to contemporary American theatre over the course of her now 25-plus year career have been eclectic. In the 1980s and early '90s she performed with Peggy Shaw and Lois Weaver as the feminist performance troupe Split Britches, for which Margolin did much of the writing, based on the trio's improvisations and experiments. In the interstices of her work with Split Britches, Margolin built her own career as a solo performer and playwright. In her autobiographical Index to Idioms, premiered in 2005, and in conversation with Jill Dolan, Margolin addresses her process, politics, and pleasures in performance and playwrighting.
There Began to Be a Learnability Puzzle
Authors: Becker Misha
Published: February 2011

One of the fundamental puzzles language learners must solve is the mapping of a string of words onto a particular (correct) syntactic structure. In this article, I examine the problem of how learners should resolve the ambiguity presented by a string that could have either a raising or a control structure. I provide both logical and empirical arguments against the view that children should be biased to assume that such a string has a control structure. Instead, I propose two families of cues, based on a psycholinguistic experiment with adults, which can be used in a probabilistic manner to parse an ambiguous string and to categorize raising and control verbs.
Tropopause Characteristics and Variability from 11 yr of SHADOZ Observations in the Southern Tropics and Subtropics
Authors: Sivakumar V. , Bencherif H. , Bègue N. , Thompson A. M.
Published: February 2011

In this paper, tropopause characteristics observed from tropical to subtropical Southern Hemisphere stations using Southern Hemisphere Additional Ozonesonde (SHADOZ) data are presented for the 11-yr period of 1998–2008. Three different definitions of tropopause—cold-point tropopause (CPT), lapse-rate tropopause (LRT), and ozone tropopause (OT)—are determined, and their variability for nine different SHADOZ sites is studied for the purpose of evaluating their usefulness as indicators of possible tropopause trends. For each station, the OT is uniquely defined by the ozone gradient and is found to be more variable than either LRT or CPT. The OT roughly coincides with the upper boundary of the region of most active convective mixing over the western Pacific Ocean and with the lower boundary of the transition region from the troposphere to the lower stratosphere that is generally referred to as the tropical tropopause layer. The monthly and year-to-year variations in the tropopause are examined, and the annual cycle in OT, the dominant signal, is described. The distance of separation of the OT from the CPT or LRT is smaller for the tropics (stations at 0°–15°S) than for the subtropics (15°–25°S). The decadal trend in tropopause heights is measured using a statistical model that accounts for natural variations expressed in El Niño–Southern Oscillation, the quasi-biennial oscillation, and the Indian Ocean dipole. The decadal trend estimation shows no statistically significant trend for the CPT and LRT in the tropics, in contrast to other studies. A decrease in altitude for the OT is significant. In the subtropics, the CPT and LRT decline significantly, by −240 and −190 m (10 yr)−1, respectively, but the OT increases.
Modulations of the Phase Speed of Convectively Coupled Kelvin Waves by the ITCZ
Authors: Dias Juliana , Pauluis Olivier
Published: February 2011

A number of studies suggest a two-way feedback between convectively coupled Kelvin waves (CCKWs) and the intertropical convergence zone (ITCZ). Viewed here as a proxy for deep convection, analysis of brightness temperature data reveals several aspects of these interdependencies. A wavenumber–frequency spectral analysis is applied to the satellite data in order to filter CCKWs. The ITCZ is characterized by a region of low brightness temperature and a proxy for both the ITCZ location and width are defined. The phase speed of CCKW data is determined using the Radon transform method. Linear regression techniques and probability density analysis are consistent with previous theoretical predictions and observational results. In particular, the fastest waves are found when the ITCZ is the farthest from the equator and the narrowest. Conversely, the slowest waves coincide with broad ITCZs that are located near the equator.
Genetic determinants of plasma von Willebrand factor antigen levels: a target gene SNP and haplotype analysis of ARIC cohort
Authors: Campos Marco , Sun Wei , Yu Fuli , Barbalic Maja , Tang Weihong , Chambless Lloyd E. , Wu Kenneth K. , Ballantyne Christie , Folsom Aaron R. , Boerwinkle Eric , Dong Jing-fei
Published: February 2011

von Willebrand factor (VWF) is an essential component of hemostasis and has been implicated in thrombosis. Multimer size and the amount of circulating VWF are known to impact hemostatic function. We associated 78 VWF single nucleotide polymorphisms (SNPs) and haplotypes constructed from those SNPs with VWF antigen level in 7856 subjects of European descent. Among the nongenomic factors, age and body mass index contributed 4.8% and 1.6% of VWF variation, respectively. The SNP rs514659 (tags O blood type) contributed 15.4% of the variance. Among the VWF SNPs, we identified 18 SNPs that are associated with levels of VWF. The correlative SNPs are either intronic (89%) or silent exonic (11%). Although SNPs examined are distributed throughout the entire VWF gene without apparent cluster, all the positive SNPs are located in a 50-kb region. Exons in this region encode for VWF D2, D′, and D3 domains that are known to regulate VWF multimerization and storage. Mutations in the D3 domain are also associated with von Willebrand disease. Fifteen of these 18 correlative SNPs are in 2 distinct haplotype blocks. In summary, we identified a cluster of intronic VWF SNPs that associate with plasma levels of VWF, individually or additively, in a large cohort of healthy subjects.
Importance of Expert Central Review in the Diagnosis of Lymphoid Malignancies in a Regional Cancer Network
Authors: Proctor Ian E. , McNamara Christopher , Rodriguez-Justo Manuel , Isaacson Peter G. , Ramsay Alan
Published: February 2011

Purpose

The accurate diagnosis of hematologic malignancies remains a challenging area for histopathologists. In 2003, the North Central London Lymphoma network was established to provide a centralized expert review service for general histopathologists based in peripheral nonspecialist hospitals. By studying samples sent for review, we sought to assess the diagnostic and clinical impact of centralized expert review in lymphoma diagnosis.

Methods

A total of 1,949 patient samples were subject to expert review between 2003 and 2008. Diagnostic discordance rates were identified after expert review, and the impact on patient management was assessed by a hematologic oncology specialist.

Results

An overall discordance rate of 27.3% was identified. Among the 10 most commonly referred lymphoid malignancies, the discordance rate varied between 3.6% and 34.1%. A small but significant number of reactive (n = 17) and malignant (n = 5) discordant diagnoses were also identified. Expert central review resulted in a major change to patient management in 2.1% of patients and prevented delays in treatment in 9.3% of patients. During the 6-year study, the discordance rate improved significantly, decreasing from 32% to 13%. Although centralized review incurred additional costs, these were relatively small compared with the costs associated with treatment.

Conclusion

This retrospective study demonstrates the importance of expert central review in the accurate diagnosis and timely management of lymphoid malignancies. Furthermore, it shows that where full centralization of services is not viable, a network comprising nonspecialist hospitals linked to a center providing expert review is a practical alternative to full unification of services at a single location and can help prevent local deskilling.
Mineralocorticoid Receptors: Evolutionary and Pathophysiological Considerations
Authors: Kassahn Karin S. , Ragan Mark A. , Funder John W.
Published: February 2011

Mineralocorticoid receptors (MR), glucocorticoid receptors (GR), progesterone receptors (PR), and androgen receptors (AR) comprise a closely related subfamily within the human 49-member nuclear receptor family. These receptors and their cognate ligands play major roles in homeostasis, reproduction, growth, and development, despite which their evolution and diversification remains incompletely understood. Several conflicting models have been advanced for the evolution of this subfamily. We have thus undertaken Bayesian and maximum likelihood phylogenetic analyses of this subfamily. The Bayesian consensus and maximum likelihood trees support a basal position for MR, with the PR and AR forming a sister clade. We next performed analyses using topological constraints to directly contrast the likelihood of seven phylogenetic models. In these analyses, three models have similar support: one proposes two sister clades (MR and GR, PR and AR); the other two propose a different subfamily member (MR or GR) to be the first to have diverged. Ancestral state reconstructions at sites critical for physiological function show that the S810L mutation in the MR, which results in the MR being similar to estrogen receptors and the more distantly related retinoic acid receptor-α is likely to reflect the ancestral receptor sequence before the divergence of this subfamily and provides further support for MR having been the first of the subfamily to diverge. Finally, we drew on pathophysiological comparisons to help to distinguish the different models. On the basis of our phylogenetic analyses and pathophysiological considerations, we propose that the MR was the first to diverge from the ancestral gene lineage from which this subfamily derived.
Two pairs of tentacles and a pair of procerebra: optimized functions and redundant structures in the sensory and central organs involved in olfactory learning of terrestrial pulmonates
Authors: Matsuo Ryota , Kobayashi Suguru , Yamagishi Miki , Ito Etsuro
Published: February 2011

Terrestrial pulmonates can learn olfactory-aversion tasks and retain them in their long-term memory. To elucidate the cellular mechanisms underlying learning and memory, researchers have focused on both the peripheral and central components of olfaction: two pairs of tentacles (the superior and inferior tentacles) and a pair of procerebra, respectively. Data from tentacle-amputation experiments showed that either pair of tentacles is sufficient for olfactory learning. Results of procerebrum lesion experiments showed that the procerebra are necessary for olfactory learning but that either one of the two procerebra, rather than both, is used for each olfactory learning event. Together, these data suggest that there is a redundancy in the structures of terrestrial pulmonates necessary for olfactory learning. In our commentary we exemplify and discuss functional optimization and structural redundancy in the sensory and central organs involved in olfactory learning and memory in terrestrial pulmonates.
Changes in plasma melatonin levels and pineal organ melatonin synthesis following acclimation of rainbow trout (Oncorhynchus mykiss) to different water salinities
Authors: López-Patiño Marcos A. , Rodríguez-Illamola Arnau , Gesto Manuel , Soengas José L. , Míguez Jesús M.
Published: February 2011

Melatonin has been suggested to play a role in fish osmoregulation, and in salmonids has been related to the timing of adaptive mechanisms during smolting. It has been described that acclimation to different environmental salinities alters levels of circulating melatonin in a number of fish species, including rainbow trout. However, nothing is known regarding salinity effects on melatonin synthesis in the pineal organ, which is the main source of rhythmically produced and secreted melatonin in blood. In the present study we have evaluated, in rainbow trout, the effects of acclimation to different salinities on day and night plasma melatonin values and pineal organ melatonin synthesis. Groups of freshwater (FW)-adapted rainbow trout were placed in tanks with four different levels of water salinity (FW, 6, 12, 18 p.p.t.; parts per thousand) and maintained for 6 h or 5 days. Melatonin content in plasma and pineal organs, as well as the pineal content of serotonin (5-HT) and its main oxidative metabolite (5-hydroxyindole-3-acetic acid; 5-HIAA) were measured by high performance liquid chromatography. In addition, day–night changes in pineal organ arylalkylamine N-acetyltransferase (AANAT2) activity and aanat2 gene expression were studied. Plasma osmolalities were found to be higher in rainbow trout exposed to all salinity levels compared with the control FW groups. A salinity-dependent increase in melatonin content was found in both plasma and pineal organs. This effect was observed during the night, and was related to an increase in aanat2 mRNA abundance and AANAT2 enzyme activity, both of which also occurred during the day. Also, the levels of indoles (5-HT, 5-HIAA) in the pineal organ were negatively affected by increasing water salinity, which seems to be related to the higher recruitment of 5-HT as a substrate for the increased melatonin synthesis. A stimulatory effect of salinity on pineal aanat2 mRNA expression was also identified. These results indicate that increased external salinity promotes melatonin synthesis in the pineal organ of rainbow trout by enhancing synthesis of AANAT protein independently of its regulation by light. The possibility that pineal melatonin is a target for hormones involved in the response of fish to osmotic challenge is discussed, as well as the potential role of melatonin in the timing of osmoregulatory processes.
Iron depletion in the intestines ofMalvoliomutant flies does not occur in the absence of a multicopper oxidase
Authors: Bettedi Lucia , Aslam Mohamad F. , Szular Joanna , Mandilaras Konstantinos , Missirlis Fanis
Published: February 2011

Malvolio (Mvl) encodes the sole Drosophila melanogaster homologue of divalent metal transporter-1 (DMT1). The Drosophila transporter has been implicated in iron, manganese and copper cellular import. Indeed, the extent of metal specificity for this family of transporters is still under investigation in many eukaryotic species. Here, we revisit metal accumulation in Mvl mutants raised under normal and metal-supplemented diets. We found iron deficiency in Mvl mutant flies, whereas whole body copper and manganese concentrations remained unaltered. Iron supplementation restored total body iron concentrations in Mvl mutants, but without replenishing iron stores in the middle midgut, suggesting a role for Mvl in systemic iron trafficking, in addition to a role in intestinal iron absorption. Interestingly, dietary copper sulphate supplementation further exacerbated the iron deficiency. We investigated whether dietary copper affected iron storage through the function of an insect multicopper oxidase (MCO), because the mammalian MCO ceruloplasmin is known to regulate iron storage in the liver. We identified a Drosophila MCO mutant that suppressed aspects of the Mvl mutant phenotype and most notably Mvl, MCO3 double mutants showed normal intestinal iron storage. Therefore, MCO3 may encode an insect ferroxidase. Intriguingly, MCO3 mutants had a mild accumulation of copper, which was suppressed in Mvl mutants, revealing a reciprocal genetic interaction between the two genes.
Efficient Synthesis of a Bisglycosyl Kaempferol from Fagonia taeckholmiana
Authors: Liu Qingchao , Li Wenhong , Guo Tiantian , Li Dong , Fan Zhen , Yan Suihong
Published: February 2011

The first total synthesis of kaempferol-3-O-β-l-arabinopyranosyl-(1→4)-α-l-rhamnopyranoside-7-O-α-l-rhamnopyranoside (1), a 3,7-triglycosylflavone, which was isolated from the aerial parts of Fagonia taeckholmiana, was accomplished in 13 steps and 9.2% overall yield from commercially available kaempferol. We efficiently employed phase-transfer-catalyzed (PTC) glycosylation for the construction of phenol glycosides. Applying this approach will allow the preparation of derivatives for further study of structure–activity relationships (SAR).
Unmentionable Others: Representing Participation Frameworks in School Science
Authors: Kuipers Joel
Published: February 2011

In the current US educational world—obsessed with accountability, measurement and testing—allocating responsibility for intellectual activity in school science can be problematic. While science education promotes "hands-on" learning and "lab work" that typically occur in a group context, many curriculum units also require students to represent their experiences as solitary, individual, and private. The data for this paper are drawn from a video ethnography of diverse middle school students experiencing a curriculum unit on Motion and Force. The analysis shows that since the curriculum unit "addresses" the students as individuals but requires them to act in groups, they must learn to systematically erase the role of the group at strategic moments required by the curriculum. The reasons for this situation are linked not only to federal policies, but widespread theories of learning in the field of education.
Once More with Feeling: A Forbidden Performance of the 'Great Speech' of the Mopan Maya
Authors: Danziger Eve
Published: February 2011

The Great Speech of the Mopan Maya cannot be simulated, for fear of supernatural consequences. Above all, sexual partners may not engage in it. On one occasion, however, a Mopan husband and wife did agree to demonstrate this genre to me. They were well aware that what they were doing was highly taboo, as their use of containment strategies makes clear. I propose from this example that utterances which are immune to hedging by explicit quotation may nevertheless be mitigable by indexical double-voicing, because indexical double-voicing inverts the process by which taboo is produced. Indexical signs, with their necessary relation of form to content, are mobilized in taboo and ritual speech as semiotic icons of the desired necessary relations between proximate form and primary, authoritative motivation. Such an iconic function is unavailable to arbitrary symbols, whose sign relations are instead icons of contingency.
Leaky Registers and Eight-Hundred-Pound Gorillas
Authors: Irvine Judith T.
Published: February 2011

Everywhere, there are topics and words that local conventions brand as "unmentionable" yet people manage to communicate about the unmentionable nevertheless. What are their strategies for doing so, and how well can those strategies work? This paper considers communicative means for mentioning or implicating the unmentionable, without actually breaching the norms that made the material noxious. Also considered are the larger cultural issues and social dramas that may be at stake. Register shifts and footing shifts are common strategies for containing noxious material in a linguistic cordon sanitaire . So is conspicuous avoidance (of the gorilla in the room). But the public game of containment is only the most overt manifestation of the issues potentially concerned. Much mischief and many unforeseen entailments lurk in the shadows of these communicative efforts. The moral life of language resides in much larger arenas than the existing literature on "verbal taboo" and politeness generally envisions. Words not spoken, discourse contexts and histories, interlocutors' responses, genre conventions, local regimes of language, truth, and knowledge—all these combine with the actual utterances, to multiple, often unforeseeable, effects.
Presidential Ethno-blooperology: Performance Misfires in the Business of "Message"-ing
Authors: Silverstein Michael
Published: February 2011

In the spectator sport of American presidential politics a generally savored moment is the perception of a candidate's misfire or gaffe. Recorded, disseminated and reframed by evaluative commentary the mere blooper or would-be "out-take" is transformed. Whether or not it was an obvious blooper at the time, the gaffe is potentially turned into an index of something more deeply revelatory of personality, character, or identity. In our regime of "message" politics, it comes either to count as a symptomatic bit of truth about its maker, emergent with negative value despite all precaution of deliberate staging, or to count as the positively valuated, deliberately delivered telling blow that injures an opponent in the theatricalized political agōn of "message."
"If I Actually Talked Like That, I'd Pull a Gun on Myself": Accent, Avoidance, and Moral Panic in Irish English
Authors: Moore Robert
Published: February 2011

The robust "accent culture" of English-language speech in the Irish Republic provides an opportunity to explore the concept of verbal taboo in terms of non-referential indexical function (in this case, phonological variants). The paper documents an ongoing moral panic of language in Irish society, centering on a new and fashionable accent of Irish English. This new accent, termed "D4" (after the postal code of a mostly well-to-do part of south Dublin), has been explained by observers and commentators in the Irish media as a way for younger, newly affluent speakers to "hive off" from the masses, by avoiding pronunciations seen as emblematic either of working-class Dublin identity or of rural Irish provincialism. And now, "D4" itself has become an accent to avoid. Determined at the intersection of this double avoidance, D4, and voicings of D4, reveal the anxieties surrounding the compulsive mentionability of "accent" in contemporary Irish media texts.
Avoiding "The Issues" as Addressivity in US Electoral Politics
Authors: Lempert Michael
Published: February 2011

In televised debates in US electoral politics, behavior before The Issues is scrupulously monitored, so much so that even a candidate's dysfluencies can be perilous, often registering to commentators as 'avoidance' and spurring them to speculate about addressivity, about which category of implied voter the candidate's avoidance was "to" and "for." Focusing on the 2007-2008 primary debates and post-debate coverage, I examine how infelicities around The Issues are read as addressivity and used to cast candidates as social types (e.g., "flip-flopper"). I situate these critical readings in relation to the political marketing industry and compare this kind of ascribed performativity with the rigid performativity of verbal taboo.
Brain Drain and Return Migration in CARICOM: A Review of the Challenges
Authors: Bristol Marlon A.
Published: February 2011

Cet article analyse des questions pertinentes en ce qui a trait à la réduction de capital humain, spécialemente dans le cadre des plus récents documents qui expliquent le phénomène du contexte des pays anglophones de la Communauté Caribéenne (identifiée par son sigle anglais CARICOM). Dans le but de déterminer son sens pratique et démontrer leur capacité, le chercheur essai d’évaluer les politiques migratoires de la région. Il est clair que les démarches politiques sont importantes, mais aucune analyse soutient son efficacité, malgré les efforts déployés pour expliquer son importance. Le motif principal d’un retour à une politique de facilitation est né a partir d’une reconnaissance du potentiel de la diaspora et de la contribution qu’elle peut apporter dans le développement des nations de la CARICOM. L’idée de cette politique de facilitation de retour permet à des individus en retraite de reintégrer leur pays d’origine. En regardant la nature et la structure de cette démarche, on voit qu’elle ne possède pas les conditions nécessaires pour faciliter le retour des professionnels dans leur étape de production. Le problème qui se pose, c’est que l’âge de retraite adopté par ces états membres, empêche à ces retraités de transmettre leurs connaissances et leurs expériences. Cette faiblesse générale de la politique de facilitation de retour empêche aux émigrants de se mettre au service du pays d’origine, par exemple de contribuer dans des réseaux de connections, entre autres.
Unfinished Synthesis: Georg Simmel’s Adventure, Two Chinese Jamaican Migration Narratives, and the Negotiation of Modern Identity
Authors: Lee-Loy Anne-Marie
Published: February 2011

Dans cet article, nous explorerons la façon dont le concept simmelien de «l’aventure» peut servir de catégorie symbolique offrant un cadre pour mieux comprendre les souvenirs d’enfance de l’experience de migration de la part de deux Sino-jamaïcains ainsi que leur tentative de négocier et de synthétiser les tensions causées par cette expérience dans une expression globale d’identité. L’aventure simmelienne tient compte du fait que le processus même de synthétiser les événements vécus attire l’attention sur les déconnexions et les perturbations —définies par Simmel comme des «dualités»—, qu’il considère caractéristiques des identités modernes. Les récits des Sino-jamaïcains étudies ici mettent en évidence les dualités de ces aventures, telles qu’elles ont été conçues par Simmel et, à ce titre, reconfirment la vision des Caraïbes comme un espace de la modernité. De même, elles nous permettent de reconnaitre les expériences et les contributions d’un groupe minoritaire de cette région comme étant importantes pour notre compréhension des identités diasporiques modernes en général et aux Caraïbes en particulier.
Race and Health in Guyana: An Empirical Assessment from Survey Data
Authors: Wilson Leon C. , Wilson Colwick M. , Johnson Bridgette M.
Published: February 2011

Cet article examine les différences raciales au point de vue de la santé, physique et du bien-être mental en Guyane, Amérique du Sud : un pays qui a des liens culturels avec la Caraïbe. Il explore la relation complexe entre la race, le statut économique social et les résultats de santé ce qui, dans les societés développées, continue d’être d’un intérêt significatif pour les chercheurs. Utilisant une probabilité d’échantillon aléatoire de plus de 900 adultes, les analyses pourvoient des informations sur le statut de l’état de santé générale physique et mental de cette population et examinent les différences par groupes raciales quand d’autres facteurs sont contrôles. Les résultats indiquent des différences significatives qui sont spécifiques à l’âge et la race au point de vue de la santé physique et mentale en Guyane. On nota des taux plus élevés de diabète, arthrite ou rhumatisme, des problèmes de dos et de respiration chez les Indo Guyanais comparé à d’autres groupes. Les différences raciales au point de vue santé physique furent atténuées quant au sexe et au niveau d’éducation.
The Right to Development: The Politics and Polemics of Power and Resistance
Authors: Ibhawoh Bonny
Published: February 2011

The polarized debate amongst states, scholars, and practitioners over the right to development is underlined by salient paradoxes and contradictions. The rhetoric of the right to development has been deployed both as a language of resistance to oppose a hegemonic global economic system and as a language of power to assert national sovereignty and legitimize statist political and economic agendas. Apart from bedeviling the elaboration and implementation of the right to development, the insular political and ideological jockeying that has characterized the discourse raises pertinent questions about the normative objectivity of the international human rights movement.