bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired Endothelial Function and Microvascular Asymmetrical Dimethylarginine in Angiotensin II–Infused Rats
Authors: Wang Dan , Luo Zaiming , Wang Xiaoyan , Jose Pedro A. , Falck John R. , Welch William J. , Aslam Shakil , Teerlink Tom , Wilcox Christopher S.
Published: September 2010

Angiotensin (Ang) II causes endothelial dysfunction, which is associated with cardiovascular risk. We investigated the hypothesis that Ang II increases microvascular reactive oxygen species and asymmetrical dimethylarginine and switches endothelial function from vasodilator to vasoconstrictor pathways. Acetylcholine-induced endothelium-dependent responses of mesenteric resistance arterioles were assessed in a myograph and vascular NO and reactive oxygen species by fluorescent probes in groups (n=6) of male rats infused for 14 days with Ang II (200 ng/kg per minute) or given a sham infusion. Additional groups of Ang or sham-infused rats were given oral Tempol (2 mmol · L
−1
). Ang II infusion increased mean blood pressure (119±5 versus 89±7 mm Hg;
P
<0.005) and plasma malondialdehyde (0.57±0.02 versus 0.37±0.05 μmol · L
−1
;
P
<0.035) and decreased maximal endothelium-dependent relaxation (18±5% versus 54±6%;
P
<0.005) and hyperpolarizing (19±3% versus 29±3%;
P
<0.05) responses and NO activity (0.9±0.1 versus 1.6±0.2 U;
P
<0.01) yet enhanced endothelium-dependent contraction responses (23±5% versus 5±5%;
P
<0.05) and reactive oxygen species production (0.82±0.05 versus 0.15±0.03 U;
P
<0.01). Ang II decreased the expression of dimethylarginine dimethylaminohydrolase 2 and increased asymmetrical dimethylarginine in vessels (450±50 versus 260±35 pmol/mg of protein;
P
<0.01) but not plasma. Tempol prevented any significant changes with Ang II. In conclusion, Ang redirected endothelial responses from relaxation to contraction, reduced vascular NO, and increased asymmetrical dimethylarginine. These effects were dependent on reactive oxygen species and could, therefore, be targeted with effective antioxidant therapy.
The Hybrid Kelvin–Edge Wave and Its Role in Tidal Dynamics
Authors: Ke Ziming , Yankovsky Alexander E.
Published: September 2010

A full set of long waves trapped in the coastal ocean over a variable topography includes a zero (fundamental) mode propagating with the coast on its right (left) in the Northern (Southern) Hemisphere. This zero mode resembles a Kelvin wave at lower frequencies and an edge wave (Stokes mode) at higher frequencies. At the intermediate frequencies this mode becomes a hybrid Kelvin–edge wave (HKEW), as both rotational effects and the variable depth become important. Furthermore, the group velocity of this hybrid mode becomes very small or even zero depending on shelf width. It is found that in midlatitudes a zero group velocity occurs at semidiurnal (tidal) frequencies over wide (∼300 km), gently sloping shelves. This notion motivated numerical experiments using the Regional Ocean Modeling System in which the incident HKEW with a semidiurnal period propagates over a wide shelf and encounters a narrowing shelf so that the group velocity becomes zero at some alongshore location. The numerical experiments have demonstrated that the wave energy increases upstream of this location as a result of the energy flux convergence while farther downstream the wave amplitude is substantially reduced. Instead of propagating alongshore, the wave energy radiates offshore in the form of Poincaré modes. Thus, it is concluded that the shelf areas where the group velocity of the HKEW becomes zero are characterized by an increased tidal amplitude and (consequently) high tidal energy dissipation, and by offshore wave energy radiation. This behavior is qualitatively consistent with the dynamics of semidiurnal tides on wide shelves narrowing in the direction of tidal wave propagation, including the Patagonia shelf and the South China Sea.
Internal Tides in Monterey Submarine Canyon
Authors: Hall Rob A. , Carter Glenn S.
Published: September 2010

The M2 internal tide in Monterey Submarine Canyon is simulated using a modified version of the Princeton Ocean Model. Most of the internal tide energy entering the canyon is generated to the south, on Sur Slope and at the head of Carmel Canyon. The internal tide is topographically steered around the large canyon meanders. Depth-integrated baroclinic energy fluxes are up canyon and largest near the canyon axis, up to 1.5 kW m−1 at the mouth of the upper canyon and increasing to over 4 kW m−1 around Monterey and San Gregorio Meanders. The up-canyon energy flux is bottom intensified, suggesting that topographic focusing occurs. Net along-canyon energy flux decreases almost monotonically from 9 MW at the canyon mouth to 1 MW at Gooseneck Meander, implying that high levels of internal tide dissipation occur. The depth-integrated energy flux across the 200-m isobath is order 10 W m−1 along the majority of the canyon rim but increases by over an order of magnitude near the canyon head, where internal tide energy escapes onto the shelf. Reducing the size of the model domain to exclude remote areas of high barotropic-to-baroclinic energy conversion decreases the depth-integrated energy flux in the upper canyon by 20%. However, quantifying the role of remote internal tide generation sites is complicated by a pressure perturbation feedback between baroclinic energy flux and barotropic-to-baroclinic energy conversion.
How I treat adenovirus in hematopoietic stem cell transplant recipients
Authors: Lindemans Caroline A. , Leen Ann M. , Boelens Jaap Jan
Published: September 2010

Adenovirus (AdV) infections are very common in the general pediatric population. The delayed clearance in young persons imposes a threat to immunocompromised patients after hematopoietic stem cell transplantation (HSCT), who can reactivate the virus, resulting in life-threatening disseminated disease. Although a definitive cure requires adequate immune reconstitution, 2 approaches appear to be feasible and effective to improve the outcomes of AdV infections. Strict monitoring with AdV quantitative polymerase chain reaction followed by preemptive treatment with low-dose (1 mg/kg) cidofovir 3 times a week, is effective in most cases to bridge the severely immunocompromised period shortly after HSCT, with acceptable toxicity rates. For centers who have the access, AdV-specific cytotoxic T cells can be the other important cornerstone of anti-AdV therapy with promising results so far. Methods to positively influence the reconstitution of the immune system after HSCT and optimizing new and currently available cellular immunotherapies will make HSCT safer against the threat of AdV infection/reactivation and associated disease.
Membrane proteomic analysis of pancreatic cancer cells
Authors: Liu Xiaojun , Zhang Min , Go Vay Liang W , Hu Shen
Published: September 2010

Background

Pancreatic cancer is one of the most aggressive human tumors due to its high potential of local invasion and metastasis. The aim of this study was to characterize the membrane proteomes of pancreatic ductal adenocarcinoma (PDAC) cells of primary and metastatic origins, and to identify potential target proteins related to metastasis of pancreatic cancer.

Methods

Membrane/membrane-associated proteins were isolated from AsPC-1 and BxPC-3 cells and identified with a proteomic approach based on SDS-PAGE, in-gel tryptic digestion and liquid chromatography with tandem mass spectrometry (LC-MS/MS). X! Tandem was used for database searching against the SwissProt human protein database.

Results

We identified 221 & 208 proteins from AsPC-1 and BxPC-3 cells, respectively, most of which are membrane or membrane-associated proteins. A hundred and nine proteins were found in both cell lines while the others were present in either AsPC-1 or BxPC-3 cells. Differentially expressed proteins between two cell lines include modulators of cell adhesion, cell motility or tumor invasion as well as metabolic enzymes involved in glycolysis, tricarboxylic acid cycle, or nucleotide/lipid metabolism.

Conclusion

Membrane proteomes of AsPC-1 (metastatic) and BxPC-3 (primary) cells are remarkably different. The differentially expressed membrane proteins may serve as potential targets for diagnostic and therapeutic interventions.
The Neural/Immune Gene Ontology: clipping the Gene Ontology for neurological and immunological systems
Authors: Geifman Nophar , Monsonego Alon , Rubin Eitan
Published: September 2010

Background

The Gene Ontology (GO) is used to describe genes and gene products from many organisms. When used for functional annotation of microarray data, GO is often slimmed by editing so that only higher level terms remain. This practice is designed to improve the summarizing of experimental results by grouping high level terms and the statistical power of GO term enrichment analysis.

Here, we propose a new approach to editing the gene ontology, clipping, which is the editing of GO according to biological relevance. Creation of a GO subset by clipping is achieved by removing terms (from all hierarchal levels) if they are not functionally relevant to a given domain of interest. Terms that are located in levels higher to relevant terms are kept, thus, biologically irrelevant terms are only removed if they are not parental to terms that are relevant.

Results

Using this approach, we have created the Neural-Immune Gene Ontology (NIGO) subset of GO directed for neurological and immunological systems. We tested the performance of NIGO in extracting knowledge from microarray experiments by conducting functional analysis and comparing the results to those obtained using the full GO and a generic GO slim. NIGO not only improved the statistical scores given to relevant terms, but was also able to retrieve functionally relevant terms that did not pass statistical cutoffs when using the full GO or the slim subset.

Conclusions

Our results validate the pipeline used to generate NIGO, suggesting it is indeed enriched with terms that are specific to the neural/immune domains. The results suggest that NIGO can enhance the analysis of microarray experiments involving neural and/or immune related systems. They also directly demonstrate the potential such a domain-specific GO has in generating meaningful hypotheses.
Comparative study of three commonly used continuous deterministic methods for modeling gene regulation networks
Authors: Swain Martin T , Mandel Johannes J , Dubitzky Werner
Published: September 2010

Background

A gene-regulatory network (GRN) refers to DNA segments that interact through their RNA and protein products and thereby govern the rates at which genes are transcribed. Creating accurate dynamic models of GRNs is gaining importance in biomedical research and development. To improve our understanding of continuous deterministic modeling methods employed to construct dynamic GRN models, we have carried out a comprehensive comparative study of three commonly used systems of ordinary differential equations: TheS-system (SS), artificial neural networks (ANNs), and the general rate law of transcription (GRLOT)method. These were thoroughly evaluated in terms of their ability to replicate the reference models' regulatory structure and dynamic gene expression behavior under varying conditions.

Results

While the ANN and GRLOT methods appeared to produce robust models even when the model parameters deviated considerably from those of the reference models, SS-based models exhibited a notable loss of performance even when the parameters of the reverse-engineered models corresponded closely to those of the reference models: this is due to the high number of power terms in the SS-method, and the manner in which they are combined. In cross-method reverse-engineering experiments the different characteristics, biases and idiosynchracies of the methods were revealed. Based on limited training data, with only one experimental condition, all methods produced dynamic models that were able to reproduce the training data accurately. However, an accurate reproduction of regulatory network features was only possible with training data originating from multiple experiments under varying conditions.

Conclusions

The studied GRN modeling methods produced dynamic GRN models exhibiting marked differences in their ability to replicate the reference models' structure and behavior. Our results suggest that care should be taking when a method is chosen for a particular application. In particular, reliance on only a single method might unduly bias the results.
Relative validation of a food frequency questionnaire for national health and nutrition monitoring
Authors: Haftenberger Marjolein , Heuer Thorsten , Heidemann Christin , Kube Friederike , Krems Carolin , Mensink Gert BM
Published: September 2010

Background

Validation of a food frequency questionnaire (FFQ) is important as incorrect information may lead to biased associations. Therefore the relative validity of an FFQ developed for use in the German Health Examination Survey for Adults 2008-2011 (DEGS) was examined.

Methods

Cross-sectional comparisons of food consumption data from the FFQ and from two 24-hour recalls were made in a sample of 161 participants (aged 18 to 80 years) of an ongoing nationwide survey, the German National Nutrition Monitoring (NEMONIT). The data collection took place from November 2008 to April 2009.

Results

Spearman rank correlations between the FFQ and the 24-hour dietary recalls ranged from 0.15 for pizza to 0.80 for tea, with two third of the correlation coefficients exceeding 0.30. All correlation coefficients were statistically significant except those for pizza and cooked vegetables. The proportion of participants classified into the same or adjacent quartile of intake assessed by both methods varied between 68% for cooked vegetables and 94% for coffee. There were no statistically significant differences in food consumption estimates between both methods for 38% of the food groups. For the other food groups, the estimates of food consumption by the FFQ were not generally higher or lower than estimates from the 24-hour dietary recalls.

Conclusions

The FFQ appears to be reasonably valid in the assessment of food consumption of German adults. For some food groups, such as raw and cooked vegetables, relative risks estimates should be interpreted with caution because of the poor ranking agreement.
Failure to detect Xenotropic murine leukaemia virus-related virus in Chinese patients with chronic fatigue syndrome
Authors: Hong Ping , Li Jinming , Li Yongzhe
Published: September 2010

Background

Recent controversy has surrounded the question of whether xenotropic murine leukaemia virus-related virus (XMRV) contributes to the pathogenesis of chronic fatigue syndrome (CFS). To investigate the question in a Chinese population, 65 CFS patients and 85 blood donor controls were enrolled and multiplex real-time PCR or reverse transcriptase PCR (RT-PCR) was developed to analyze the XMRV infection status of the study participants. The assay was standardized by constructing plasmid DNAs and armored RNAs as XMRV standards and competitive internal controls (CICs), respectively.

Results

The sensitivities of the multiplex real-time PCR and RT-PCR assays were 20 copies/reaction and 10 IU/ml, respectively, with 100% specificity. The within-run precision coefficient of variation (CV) ranged from 1.76% to 2.80% and 1.70% to 2.59%, while the between-run CV ranged from 1.07% to 2.56% and 1.06% to 2.74%. XMRV was not detected in the 65 CFS patients and 65 normal individuals out of 85 controls.

Conclusions

This study failed to show XMRV in peripheral blood mononuclear cells (PBMCs) and plasma of Chinese patients with CFS. The absence of XMRV nucleic acids does not support an association between XMRV infection and the development of CFS in Chinese.
Semi-supervised drug-protein interaction prediction from heterogeneous biological spaces
Authors: Xia Zheng , Wu Ling-Yun , Zhou Xiaobo , Wong Stephen TC
Published: September 2010

Background

Predicting drug-protein interactions from heterogeneous biological data sources is a key step for in silico drug discovery. The difficulty of this prediction task lies in the rarity of known drug-protein interactions and myriad unknown interactions to be predicted. To meet this challenge, a manifold regularization semi-supervised learning method is presented to tackle this issue by using labeled and unlabeled information which often generates better results than using the labeled data alone. Furthermore, our semi-supervised learning method integrates known drug-protein interaction network information as well as chemical structure and genomic sequence data.

Results

Using the proposed method, we predicted certain drug-protein interactions on the enzyme, ion channel, GPCRs, and nuclear receptor data sets. Some of them are confirmed by the latest publicly available drug targets databases such as KEGG.

Conclusions

We report encouraging results of using our method for drug-protein interaction network reconstruction which may shed light on the molecular interaction inference and new uses of marketed drugs.
Impairment of circulating endothelial progenitors in Down syndrome
Authors: Costa Valerio , Sommese Linda , Casamassimi Amelia , Colicchio Roberta , Angelini Claudia , Marchesano Valentina , Milone Lara , Farzati Bartolomeo , Giovane Alfonso , Fiorito Carmela , Rienzo Monica , Picardi Marco , Avallone Bice , Marco Corsi Massimiliano , Sarubbi Berardo , Calabrò Raffaele , Salvatore Paola , Ciccodicola Alfredo , Napoli Claudio
Published: September 2010

Background

Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome.

Methods

Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis.

Results

We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells.

Conclusions

Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.
Concurrent sexual partnerships do not explain the HIV epidemics in Africa: a systematic review of the evidence
Authors: Sawers Larry , Stillwaggon Eileen
Published: September 2010

The notion that concurrent sexual partnerships are especially common in sub‐Saharan Africa and explain the region's high HIV prevalence is accepted by many as conventional wisdom. In this paper, we evaluate the quantitative and qualitative evidence offered by the principal proponents of the concurrency hypothesis and analyze the mathematical model they use to establish the plausibility of the hypothesis.

We find that research seeking to establish a statistical correlation between concurrency and HIV prevalence either finds no correlation or has important limitations. Furthermore, in order to simulate rapid spread of HIV, mathematical models require unrealistic assumptions about frequency of sexual contact, gender symmetry, levels of concurrency, and per‐act transmission rates. Moreover, quantitative evidence cited by proponents of the concurrency hypothesis is unconvincing since they exclude Demographic and Health Surveys and other data showing that concurrency in Africa is low, make broad statements about non‐African concurrency based on very few surveys, report data incorrectly, report data from studies that have no information about concurrency as though they supported the hypothesis, report incomparable data and cite unpublished or unavailable studies. Qualitative evidence offered by proponents of the hypothesis is irrelevant since, among other reasons, there is no comparison of Africa with other regions.

Promoters of the concurrency hypothesis have failed to establish that concurrency is unusually prevalent in Africa or that the kinds of concurrent partnerships found in Africa produce more rapid spread of HIV than other forms of sexual behaviour. Policy makers should turn attention to drivers of African HIV epidemics that are policy sensitive and for which there is substantial epidemiological evidence.
Development of a macromolecular prodrug for the treatment of inflammatory arthritis: mechanisms involved in arthrotropism and sustained therapeutic efficacy
Authors: Quan Ling-dong , Purdue P Edward , Liu Xin-ming , Boska Michael D , Lele Subodh M , Thiele Geoffrey M , Mikuls Ted R , Dou Huanyu , Goldring Steven R , Wang Dong
Published: September 2010

Introduction

The purpose of the present manuscript is to test the hypothesis that arthrotropic localization and synovial cell internalization account for the unique capacity of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex, a macromolecular prodrug of dexamethasone) to induce sustained amelioration of joint inflammation and inhibition of tissue damage in an animal model of inflammatory arthritis.

Methods

Rats with adjuvant-induced arthritis (AA) were treated with P-Dex, free dexamethasone, saline or HPMA homopolymer. To define the biodistribution of P-Dex, conjugates with different imaging labels were given to AA rats and analyzed. Isolated joint tissues were evaluated by fluorescence-activated cell sorting (FACS) and immunohistochemical staining. Cellular uptake of P-Dex and its effects on apoptosis and production of proinflammatory cytokines were examined using human monocyte-macrophages and fibroblasts.

Results

A single systemic administration of P-Dex completely suppressed AA for >20 days. Magnetic resonance imaging demonstrated higher HPMA copolymer influx into the inflamed joints than the normal joints. Immunohistochemistry and FACS analyses of arthritic joints revealed extensive uptake of the polymer conjugate by synovial fibroblasts and myeloid lineage cells. The capacity of P-Dex to suppress inflammation was confirmed in monocyte-macrophage cultures in which P-Dex treatment resulted in suppression of lipopolysaccharide-induced IL-6 and TNFα release. Similarly, TNFα-induced expression of matrix metalloproteinases (MMP1 and MMP3) in synovial fibroblasts from a rheumatoid arthritis patient was suppressed by P-Dex. P-Dex showed no detectable effect on monocyte apoptosis.

Conclusions

P-Dex provides superior and sustained amelioration of AA compared with an equivalent dose of free dexamethasone. The arthrotropism and local retention of P-Dex is attributed to the enhanced vascular permeability in arthritic joints and the internalization of P-Dex by synovial cells. The uptake and processing of P-Dex by macrophages and fibroblasts, and downregulation of proinflammatory mediators, provides an explanation for the sustained anti-inflammatory efficacy of P-Dex in this model of inflammatory arthritis.
Host adaptive immunity deficiency in severe pandemic influenza
Authors: Bermejo-Martin Jesus F , Martin-Loeches Ignacio , Rello Jordi , Antón Andres , Almansa Raquel , Xu Luoling , Lopez-Campos Guillermo , Pumarola Tomás , Ran Longsi , Ramirez Paula , Banner David , Cheuk Ng Derek , Socias Lorenzo , Loza Ana , Andaluz David , Maravi Enrique , Gómez-Sánchez Maria J , Gordón Mónica , Gallegos Maria C , Fernandez Victoria , Aldunate Sara , León Cristobal , Merino Pedro , Blanco Jesús , Martin-Sanchez Fernando , Rico Lucia , Varillas David , Iglesias Veronica , Marcos Maria Ángeles , Gandía Francisco , Bobillo Felipe , Nogueira Begoña , Rojo Silvia , Resino Salvador , Castro Carmen , Ortiz de Lejarazu Raul , Kelvin David
Published: September 2010

Introduction

Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown.

Methods

We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1.

Results

The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum.

Conclusions

Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.
A Phase I Study of Sunitinib Plus Capecitabine in Patients With Advanced Solid Tumors
Authors: Sweeney Christopher J. , Chiorean E. Gabriela , Verschraegen Claire F. , Lee Fa Chyi , Jones Suzanne , Royce Melanie , Tye Lesley , Liau Katherine F. , Bello Akintunde , Chao Richard , Burris Howard A.
Published: September 2010

Purpose

This open-label, phase I, dose-escalation study assessed the maximum-tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of sunitinib in combination with capecitabine in patients with advanced solid tumors.

Patients and Methods

Sunitinib (25, 37.5, or 50 mg) was administered orally once daily on three dosing schedules: 4 weeks on treatment, 2 weeks off treatment (Schedule 4/2); 2 weeks on treatment, 1 week off treatment (Schedule 2/1); and continuous daily dosing (CDD schedule). Capecitabine (825, 1,000, or 1,250 mg/m2) was administered orally twice daily on days 1 to 14 every 3 weeks for all patients. Sunitinib and capecitabine doses were escalated in serial patient cohorts.

Results

Seventy-three patients were treated. Grade 3 adverse events included abdominal pain, mucosal inflammation, fatigue, neutropenia, and hand-foot syndrome. The MTD for Schedule 4/2 and the CDD schedule was sunitinib 37.5 mg/d plus capecitabine 1,000 mg/m2 twice per day; the MTD for Schedule 2/1 was sunitinib 50 mg/d plus capecitabine 1,000 mg/m2 twice per day. There were no clinically significant pharmacokinetic drug-drug interactions. Nine partial responses were confirmed in patients with pancreatic cancer (n = 3) and breast, thyroid, neuroendocrine, bladder, and colorectal cancer, and cholangiocarcinoma (each n = 1).

Conclusion

The combination of sunitinib and capecitabine resulted in an acceptable safety profile in patients with advanced solid tumors. Further evaluation of sunitinib in combination with capecitabine may be undertaken using the MTD for any of the three treatment schedules.
Longitudinal Assessment of Cognitive Changes Associated With Adjuvant Treatment for Breast Cancer: Impact of Age and Cognitive Reserve
Authors: Ahles Tim A. , Saykin Andrew J. , McDonald Brenna C. , Li Yuelin , Furstenberg Charlotte T. , Hanscom Brett S. , Mulrooney Tamsin J. , Schwartz Gary N. , Kaufman Peter A.
Published: September 2010

Purpose

To examine the impact of age and cognitive reserve on cognitive functioning in patients with breast cancer who are receiving adjuvant treatments.

Patients and Methods

Patients with breast cancer exposed to chemotherapy (n = 60; mean age, 51.7 years) were evaluated with a battery of neuropsychological and psychological tests before treatment and at 1, 6, and 18 months after treatment. Patients not exposed to chemotherapy (n = 72; mean age, 56.6 years) and healthy controls (n = 45; mean age, 52.9 years) were assessed at matched intervals.

Results

Mixed-effects modeling revealed significant effects for the Processing Speed and Verbal Ability domains. For Processing Speed, a three-way interaction among treatment group, age, and baseline cognitive reserve (P < .001) revealed that older patients with lower baseline cognitive reserve who were exposed to chemotherapy had lower performance on Processing Speed compared with patients not exposed to chemotherapy (P = .003) and controls (P < .001). A significant group by time interaction for Verbal Ability (P = .01) suggested that the healthy controls and no chemotherapy groups improved over time. The chemotherapy group failed to improve at 1 month after treatment but improved during the last two follow-up assessments. Exploratory analyses suggested a negative effect of tamoxifen on Processing Speed (P = .036) and Verbal Memory (P = .05) in the no-chemotherapy group.

Conclusion

These data demonstrated that age and pretreatment cognitive reserve were related to post-treatment decline in Processing Speed in women exposed to chemotherapy and that chemotherapy had a short-term impact on Verbal Ability. Exploratory analysis of the impact of tamoxifen suggests that this pattern of results may be due to a combination of chemotherapy and tamoxifen.
Randomized Phase II Window Trial of Two Schedules of Irinotecan With Vincristine in Patients With First Relapse or Progression of Rhabdomyosarcoma: A Report From the Children's Oncology Group
Authors: Mascarenhas Leo , Lyden Elizabeth R. , Breitfeld Philip P. , Walterhouse David O. , Donaldson Sarah S. , Paidas Charles N. , Parham David M. , Anderson James R. , Meyer William H. , Hawkins Douglas S.
Published: September 2010

Purpose

To compare response rates for two schedules of irinotecan with vincristine in patients with rhabdomyosarcoma at first relapse or disease progression.

Patients and Methods

Patients with first relapse or progression of rhabdomyosarcoma and an unfavorable prognosis were randomly assigned to one of two treatment schedules of irinotecan with vincristine: regimen 1A included irinotecan 20 mg/m2/d intravenously for 5 days at weeks 1, 2, 4, and 5 with vincristine 1.5 mg/m2 administered intravenously on day 1 of weeks 1, 2, 4, and 5; regimen 1B included irinotecan 50 mg/m2/d intravenously for 5 days at weeks 1 and 4 with vincristine as in regimen 1A. Disease response was assessed at week 6. Those with responsive disease continued to receive 44 weeks of multiagent chemotherapy that incorporated the assigned irinotecan-vincristine regimen.

Results

Ninety-two eligible patients were randomly assigned (1A, 45; 1B, 47). Response could be assessed in 89 patients (1A, 42; 1B, 47). There were five complete responses and six partial responses on regimen 1A (response rate, 26%; 95% CI, 16% to 42%) and 17 partial responses on regimen 1B (response rate, 37%; 95% CI, 25% to 51%; P = .36). Neutropenia was less common on regimen 1A (P = .04). One-year failure-free and overall survival rates for regimen 1A were 37% (95% CI, 23% to 51%) and 55% (95% CI, 39% to 69%), respectively, and for 1B, they were 38% (95% CI, 25% to 53%) and 60% (95% CI, 44% to 72%).

Conclusion

There was no difference in the response rates between the two irinotecan-vincristine schedules. We recommend the shorter, more convenient regimen (1B) for further investigation.
Adjuvant Gemcitabine Alone Versus Gemcitabine-Based Chemoradiotherapy After Curative Resection for Pancreatic Cancer: A Randomized EORTC-40013-22012/FFCD-9203/GERCOR Phase II Study
Authors: Van Laethem Jean-Luc , Hammel Pascal , Mornex Françoise , Azria David , Van Tienhoven Geertjan , Vergauwe Philippe , Peeters Marc , Polus Marc , Praet Michel , Mauer Murielle , Collette Laurence , Budach Volker , Lutz Manfred , Van Cutsem Eric , Haustermans Karin
Published: September 2010

Purpose

The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer.

Patients and Methods

Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a < 60% treatment completion and a > 40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS).

Results

Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58.1% to 85.4%) in the control and CRT arms, respectively, and grade 4 toxicity was 0% and 4.7% (two of 43; 80% CI, 1.2% to 11.9%), respectively. In the CRT arm, three patients experienced grade 3–related late toxicity. Median DFS was 12 months in the CRT arm and 11 months in the control arm. Median OS was 24 months in both arms. First local recurrence was less frequent in the CRT arm (11% v 24%).

Conclusion

Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gemcitabine after resection of pancreatic cancer should be evaluated in a phase III trial.
Electrochemical nanogravimetric studies of adsorption, deposition, and dissolution processes occurring at platinum electrodes in acid media
Authors: Inzelt György , Berkes Balázs B. , Kriston Ákos
Published: September 2010

Polycrystalline smooth and platinized platinum electrodes have been extensively employed in electrochemistry. It is of utmost importance to gain a deeper insight into the processes occurring during their electrochemical transformations. Piezoelectric nanogravimetry by using electrochemical quartz crystal nanobalance (EQCN) is one of the most powerful tools for obtaining information on the events occurring at the electrode surface. This method has been exploited to monitor the surface mass changes as a function of the electrode potential varying the experimental conditions (time scale, solution composition, temperature), which allows one to draw conclusions in respect of the formation and removal of adsorbed and deposited species as well as changes in the electrochemical double layer. Furthermore, platinum dissolution processes, which are of importance (e.g., regarding the long-term stability of proton exchange fuel cells), are also discussed.
From Chiefdom to State: Toward an Integrative Theory of the Evolution of Polity
Authors: Abrutyn Seth , Lawrence Kirk
Published: September 2010

The evolution of the polity, particularly the transition of chiefdoms to states, has been the subject of considerable debate. In this article, the authors engage the discussion surrounding the meta-theoretical positions on the tempo of change, specifically whether states emerged gradually from quantitative changes in chiefdom societies—gradualism—or if their appearance was the result of punctuated and qualitative change—punctuated equilibrium. After revisiting the classic debate, the authors update it with new contributions drawn from the natural and social sciences. They contend that chiefdoms do not simply become states as a result of increases in the size of component parts; instead, punctuated equilibrium, stemming from responses to selection pressures from social forces, has more empirical support than gradualism in explaining state formation. The authors then take steps toward an integrative model of polity evolution, in which the state emerges as a discrete change resulting from social forces reaching critical thresholds.
The Return of the American Voter? Party Polarization and Voting Behavior, 1988 to 2004
Authors: Dodson Kyle
Published: September 2010

A frequent concern voiced by social commentators has been the persistence of mass disengagement over the past two decades—despite evidence of improving democratic involvement. In particular, since 1988, voter turnout in presidential elections has dramatically rebounded, to the point that they now rival the turnout rates of the 1960s. Yet little is known about the cause of this trend. The primary theoretical focus of the following study is to examine what factors were behind this increase in turnout, paying particular attention to the electoral relevance of increasing party polarization. Results indicate that the rise in polarization was a central driver behind the turnout boom. Changes in the electoral environment account for almost 80 percent of the total increase in voter turnout. The analysis suggests that party polarization represents a key mechanism that links citizens to the larger political process. Implications for the current state of mass engagement generally and political behavior specifically are discussed.
Prenatal and Infant Exposure to Thimerosal From Vaccines and Immunoglobulins and Risk of Autism
Authors: Price Cristofer S. , Thompson William W. , Goodson Barbara , Weintraub Eric S. , Croen Lisa A. , Hinrichsen Virginia L. , Marcy Michael , Robertson Anne , Eriksen Eileen , Lewis Edwin , Bernal Pilar , Shay David , Davis Robert L. , DeStefano Frank
Published: September 2010

OBJECTIVE:

Exposure to thimerosal, a mercury-containing preservative that is used in vaccines and immunoglobulin preparations, has been hypothesized to be associated with increased risk of autism spectrum disorder (ASD). This study was designed to examine relationships between prenatal and infant ethylmercury exposure from thimerosal-containing vaccines and/or immunoglobulin preparations and ASD and 2 ASD subcategories: autistic disorder (AD) and ASD with regression.

METHODS:

A case-control study was conducted in 3 managed care organizations (MCOs) of 256 children with ASD and 752 controls matched by birth year, gender, and MCO. ASD diagnoses were validated through standardized in-person evaluations. Exposure to thimerosal in vaccines and immunoglobulin preparations was determined from electronic immunization registries, medical charts, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We used conditional logistic regression to assess associations between ASD, AD, and ASD with regression and exposure to ethylmercury during prenatal, birth-to-1 month, birth-to-7-month, and birth-to-20-month periods.

RESULTS:

There were no findings of increased risk for any of the 3 ASD outcomes. The adjusted odds ratios (95% confidence intervals) for ASD associated with a 2-SD increase in ethylmercury exposure were 1.12 (0.83–1.51) for prenatal exposure, 0.88 (0.62–1.26) for exposure from birth to 1 month, 0.60 (0.36–0.99) for exposure from birth to 7 months, and 0.60 (0.32–0.97) for exposure from birth to 20 months.

CONCLUSIONS:

In our study of MCO members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to increased risk of ASDs.
Recommendation for Mandatory Influenza Immunization of All Health Care Personnel
Authors: Bernstein Henry H. , Starke Jeffrey R. ,   Committee on Infectious Diseases
Published: September 2010

This Policy Statement was revised. See https://doi.org/10.1542/peds.2015-2922.

The purpose of this statement is to recommend implementation of a mandatory influenza immunization policy for all health care personnel. Immunization of health care personnel is a critically important step to substantially reduce health care–associated influenza infections. Despite the efforts of many organizations to improve influenza immunization rates with the use of voluntary campaigns, influenza coverage among health care personnel remains unacceptably low. Mandatory influenza immunization for all health care personnel is ethically justified, necessary, and long overdue to ensure patient safety.
Influence of strain rate and acceleration on the behaviour of reconstituted clays at small strains
Authors: SORENSEN K.K. , BAUDET B.A. , SIMPSON B.
Published: September 2010

This paper attempts to bridge the gap between the well-known characteristics of strain rate-independent elastic stiffness and of the time-dependent behaviour of clays at large strains. Effects of acceleration, strain rate and ageing are examined in the very small to small strain region, using results from tests on reconstituted London Clay and kaolin. Static measurements of the shear modulus at small strains, using local instrumentation, indicate that the shear modulus is rate-independent when the soil is subjected to elastic deformations only. Most often, in practice, soil specimens are left to rest between the compression and shearing stages, until deformations associated with creep become negligible. The testing strain rate imposed upon shearing induces a temporary acceleration of strains, which results in very high measured stiffnesses. Test data show, however, that when the shearing axial strain rate is of the same order of magnitude as that measured at the end of the compression/creep stage, the remaining plastic creep strains influence the measured stiffness, which is then measured to be comparatively low. Test data also seem to show that temporary strain acceleration may hide effects of recent stress path rotation. Additionally, bender element tests were performed during isotropic compression tests with changes in stress rate and creep stages. The data indicate that the strain rate affects the value of the dynamic shear modulus of the soil. It is suggested that the increase in dynamic shear modulus during short-term creep is caused by mechanisms linked to the gradual decrease in strain rate during creep, but further investigation would be needed to clarify which physical mechanisms. A new method to account for strain rate in evaluating the dynamic shear modulus of normally consolidated reconstituted clays is finally proposed.
Optimal conditions for producing reactive powder concrete
Authors: Tam C.M. , Tam V.W.Y. , Ng K.M.
Published: September 2010

There is growing interest in the development of innovative cementitious materials that possess superior properties. A relatively new cementitious material, reactive powder concrete, is recognised as a revolutionary material that provides a combination of ultra-high strength and excellent durability. However, production of reactive powder concrete is not yet available with the limited research in this area in Hong Kong. This paper investigates mechanical and fresh concrete properties of reactive powder concrete, aiming to achieve the optimal conditions for producing reactive powder concrete using local materials by investigating the material composition, curing and heating regimes and the microstructure of reactive powder concrete. Based on the experimental results, it is found that reactive powder concrete with a water-to-binder ratio of 0·2, superplasticiser dosage of 2·5%, 150–600 μm quartz sand cured at 27°C in water condition provides the best results in terms of mechanical and composite properties as well as for practical and economical reasons, although heat treatment of the reactive powder concrete can result in a significant increase in compressive strength.
Influence of surgical sutures on wound healing
Authors: Mirkovic Sinisa , Selakovic Srecko , Sarcev Ivan , Bajkin Branislav
Published: September 2010

Historical data on closing and suturing of surgical wounds describe a wide range of various suture materials. The choice of the surgical catgut, i.e. the type and diameter, depends on the locality, characteristics and condition of the tissue to be treated. From the standpoint of oral-surgical practice the following clinical parameters are of outstanding importance with respect to the selection of suture material: accumulation of soft deposits on the sutures, score of the adjacent soft tissues and dehiscence of the operative wound. Our prospective clinical study included 150 patients distributed into three groups of 50 subjects. The surgical procedure performed on each patient involved resection (apicotomy) of the tooth root end in the intercanine sector of the upper jaw. The following suture materials were applied: Black Silc 5-0, Nylon 5-0 and Vicryl 5-0. The effects of the selected sutures were evaluated according to the wound dehiscence. The effects of the applied sutures were recorded on Days 2, 5 and 7 after the surgery. The comparison of cited parameters of the investigated materials after suturing the oral mucosa revealed that none of the used material was ideal; however, a certain advantage might be given to the synthetic monofilament suture materials.