bluuebunny/crossref_metadata_2025 huggingface dataset:
Thin Film Photovoltaics: Markets and Industry
Authors: Jäger-Waldau Arnulf
Published: March 2012

Since 2000, total PV production increased almost by two orders of magnitude, with a compound annual growth rate of over 52%. The most rapid growth in annual cell and module production over the last five years could be observed in Asia, where China and Taiwan together now account for about 60% of worldwide production. Between 2005 and 2009, thin film production capacity and volume increased more than the overall industry but did not keep up in 2010 and 2011 due to the rapid price decline for solar modules. Prices for photovoltaic electricity generation systems have more than halved over the last five years making the technology affordable to an ever-increasing number of customers worldwide. With worldwide over 60 GW cumulative installed photovoltaic electricity generation capacity installed in November 2011, photovoltaics still is a small contributor to the electricity supply, and another 10 to 15 years of sustained and aggressive growth will be required for photovoltaic solar electricity to become one of the main providers of electricity. To achieve this, a continuous improvement of the current solar cell technologies will be necessary.
Looking Back on Contributions in the Field of Atmospheric Corrosion Offered by the MICAT Ibero-American Testing Network
Authors: Morcillo M. , Chico B. , de la Fuente D. , Simancas J.
Published: March 2012

The Ibero-American Map of Atmospheric Corrosiveness (MICAT) project was set up in 1988 sponsored by the International Ibero-American programme “Science and Technology for Development (CYTED)” and ended in 1994 after six years of activities. Fourteen countries were involved in this project: Argentina, Brazil, Chile, Colombia, Costa Rica, Cuba, Ecuador, Mexico, Panama, Peru, Portugal, Spain, Uruguay, and Venezuela. Research was conducted both at laboratories and in a network of 75 atmospheric exposure test sites throughout the Ibero-American region, thus considering a broad spectrum of climatological and pollution conditions. Although with its own peculiarities, the project basically followed the outline of the ISOCORRAG and ICP/UNECE projects, with the aim of a desirable link between the three projects. This paper summarizes the results obtained in the MICAT project for mild steel, zinc, copper, and aluminum specimens exposed for one year in different rural, urban, and marine atmospheres in the Ibero-American region. Complementary morphological and chemical studies were carried out using scanning electron microscopy (SEM) coupled with energy dispersive spectrometry (EDS), X-ray diffraction (XRD), and fourier transform infrared Spectroscopy (FTIR) techniques, in order to correlate climatic and atmospheric conditions and properties of the corrosion products.
Current Status of New Anticoagulants in the Management of Venous Thromboembolism
Authors: Montoya Roberto C. , Gajra Ajeet
Published: March 2012

Venous Thromboembolism, manifested as deep venous thrombosis and pulmonary embolism, is a common problem associated with significant morbidity, mortality, and resource expenditure. Unfractionated heparin, low-molecular-weight heparin, and vitamin K antagonists are the most common treatment and prophylaxis, and have demonstrated their efficacy in a vast number of previous studies. Despite their broad use, these agents have important limitations that have led to the development of new drugs in a bid to overcome the disadvantages of the old ones without decreasing their therapeutic effect. These novel medications, some approved and others in different stages of development, include direct thrombin inhibitors like dabigatran etexilate, and direct activated factor X inhibitors like rivaroxaban. The current paper will review the characteristics, clinical trial results, and current and potential therapeutic uses of these new agents with a focus on the categories of direct thrombin inhibitors and activated factor X inhibitors.
Xenogenic Esophagus Scaffolds Fixed with Several Agents: ComparativeIn VivoStudy of Rejection and Inflammation
Authors: Koch Holger , Graneist Cora , Emmrich Frank , Till Holger , Metzger Roman , Aupperle Heike , Schierle Katrin , Sack Ulrich , Boldt Andreas
Published: March 2012

Most infants with long-gap esophageal atresia receive an esophageal replacement with tissue from stomach or colon, because the native esophagus is too short for true primary repair. Tissue-engineered esophageal conducts could present an attractive alternative. In this paper, circular decellularized porcine esophageal scaffold tissues were implanted subcutaneously into Sprague-Dawley rats. Depending on scaffold cross-linking with genipin, glutaraldehyde, and carbodiimide (untreated scaffolds : positive control; bovine pericardium : gold standard), the number of infiltrating fibroblasts, lymphocytes, macrophages, giant cells, and capillaries was determined to quantify the host response after 1, 9, and 30 days. Decellularized esophagus scaffolds were shown to maintain native matrix morphology and extracellular matrix composition. Typical inflammatory reactions were observed in all implants; however, the cellular infiltration was reduced in the genipin group. We conclude that genipin is the most efficient and best tolerated cross-linking agent to attenuate inflammation and to improve the integration of esophageal scaffolds into its surrounding tissue after implantation.
Vanilloid Receptor-1 Regulates Neurogenic Inflammation in Colon and Protects Mice from Colon Cancer
Authors: Vinuesa Amaya G. , Sancho Rocío , García-Limones Carmen , Behrens Axel , ten Dijke Peter , Calzado Marco A. , Muñoz Eduardo
Published: March 2012

Neuroinflammation driven by the vanilloid-type ion channel receptor transient receptor potential vanilloid type 1 (TRPV-1) is suspected to play a role in the pathophysiology of inflammatory bowel disease. Because inflammatory bowel disease is known to elevate the risk of colon cancer, we examined postulated roles for TRPV-1–driven neuroinflammation in promoting colitis-associated and spontaneous colon cancer development. Using a well-established model of colitis-associated cancer (CAC), we found that mice genetically deficient in TRPV-1 showed a higher incidence and number of tumors in the distal colon. In like manner, genetic deficiency of TRPV-1 in the APCMin/+ model of spontaneous colon cancer accentuated the number of colonic adenomas formed. Mechanistic analyses in the CAC model revealed an increased infiltration of inflammatory cells into the tumors along with elevated expression of interleukin (IL)-6 and IL-11 and activation of the STAT3 and NF-κB signaling pathways. Notably, TPRV-1–deficient mice exhibited a defect in expression of the anti-inflammatory neuropeptides, vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase–activating peptide (PACAP) which contributed to the generation of a local proinflammatory environment. Together, our findings argue that by limiting neuroinflammatory processes, TRPV-1 exerts a protective role that restricts the initiation and progression of colon cancer. Cancer Res; 72(7); 1705–16. ©2012 AACR.
Predictors of Cancer Survivors' Receptivity to Lifestyle Behavior Change Interventions
Authors: K Basen-Engquist , C Carmack , J Blalock , G Baum , W Rahming , W Demark-Wahnefried
Published: March 2012

Purpose: To assess cancer survivors' interest in lifestyle behavior change interventions, and to identify predictors of interest.

Methods: Mailed surveys were sent to a stratified random sample of breast, colorectal, and prostate cancer survivors ascertained from the MD Anderson tumor registry and departmental databases. Surveys queried survivors about their diet, exercise, and smoking behaviors; symptoms; and their interest in interventions.

Results: Surveys were received from 1053 cancer survivors. Roughly half of the sample were very/extremely interested in programs to help them get in shape (45%), eat a healthy diet (54%), and control weight (49%), and 20% had no interest at all. Because they were highly intercorrelated we combined interest in diet/exercise/weight control into a single interest index. Interest was related to race/ethnicity (AA and Hispanics more interested than whites), age (p = .000, younger more interested), marital status (p = .000, divorced most interested, widowed least interested), education (p = .008, college-educated less interested than those with HS degree or some college/vocational training), and gender (p = .000; women more interested). Interest was not related to time from diagnosis, and there were no differences by cancer site after controlling for gender. BMI had a small but significant correlation with interest in programs (r = .19, p = .000; the correlation was higher in women [r = .24] than men [r = .18]). Symptom severity and interference, and feelings of distress and sadness, were positively correlated to interest (r = .07–.12, p = .000–.034); relationships were stronger among men than women. Among the 78 smokers, 51% were very/extremely interested in smoking cessation, while 20% were not at all interested. Demographic and disease-related predictors were not significantly related to interest in smoking cessation, but symptom severity and interference, and feelings of sadness were positively related to interest.

Conclusion: Survivors' interest in lifestyle behavior change interventions varies with demographic variables, but also with symptom distress. Experiencing symptoms after cancer diagnosis is related to higher receptivity to intervention opportunities.
Deficits in Health-Promoting Behaviors Among Veteran and Non-Veteran Male Cancer Survivors in Texas
Authors: M Kowalkowski , H Goltz , D Latini
Published: March 2012

Objectives: Cancer survivors may have increased risk for additional malignancies and illnesses. Veterans comprise a significant proportion of Texas male cancer survivors and may differ in their health status and needs from non-veterans. It is unknown whether they differ in general health-promotion strategies. This study sought to identify deficits in health-promoting behaviors among Texas male cancer survivors and to determine whether veteran-status predicts differences along these behaviors.

Methods: Using the Behavioral Risk Factor Surveillance System 2009 survey, we conducted secondary analysis of 280 veteran and 250 non-veteran Texas male cancer survivors. Data were analyzed using Fisher's exact test and logistic-regression models.

Results: Survivors averaged 68 years (SD = 11.4) and were primarily white (93%), married (71.5%), college graduates (51%), and non-smokers (91%). Respondents reported several different cancer diagnoses; most commonly prostate (28%). More non-veterans than veterans were obese (31.6% vs. 22.5%; p = 0.03). Veteran-status was not associated with other co-morbidities, current smoking, binge drinking, or fruit/vegetable consumption. However, only 22% met recommendations for daily fruits/vegetables. In multivariate regression, veterans were less likely to meet moderate (OR = 0.54, 95% CI = 0.30–0.95) and vigorous (OR = 0.67, 95% CI = 0.45–0.99) physical-activity recommendations, but were more likely to have had health examinations within the previous year (OR = 1.77, 95% CI = 1.11–2.83).

Conclusion: Texas male cancer survivors reported deficits across important health behaviors, including dietary and physical-activity recommendations. Veterans reported low compliance with physical-activity guidelines, in spite of evidence-based veterans health-promotion programs, e.g., MOVE! ®. Our results suggest veterans' adherence to routine care may offer a point of intervention to implement health-promotion guidelines among cancer survivors. Further research is needed to understand how to use the growing focus on cancer survivorship within the VA healthcare system to encourage greater adoption of health promotion practices among veteran cancer survivors.
Relationship Between Use of Different Oral Contraceptive Formulations and Breast Cancer Risk Among Young Women
Authors: E Beaber , D Buist , W Barlow , K Malone , S Reed , C Li
Published: March 2012

Purpose: Prior studies suggest that recent oral contraceptive (OC) use is associated with a modest increased risk of breast cancer among young women. However, the majority of these reports have relied on self-reported use and have not characterized risks associated with newer OC formulations.

Methods: We conducted a nested case-control study among health plan enrollees at a large health maintenance organization, Group Health Cooperative, which serves the greater Seattle-Puget Sound region. Cases consisted of 1,102 women 20–49 years of age diagnosed with invasive breast cancer from 1990–2009. We randomly selected 21,952 controls matched on age, year, and enrollment length. Detailed information on recent OC use, including formulation, dose, and duration was ascertained from electronic pharmacy records. Multivariate-adjusted conditional logistic regression was used to calculate odds ratios (ORs) as estimates of relative risks and 95% confidence intervals (CIs).

Results: Recent OC use (within 1 year of diagnosis) was associated with a 60% (95% CI = 1.3–1.9) increased breast cancer risk. The association was slightly stronger for estrogen receptor (ER) positive compared to ER-negative disease (ER-positive OR = 1.7, 95% CI = 1.3–2.1 and ER-negative OR = 1.2, 95% CI = 0.8–1.8), though this difference was not statistically significant. The ORs varied somewhat by OC formulation, with recent use of OCs containing the progestin ethynodiol diacetate (OR = 2.6, 95% CI = 1.4–4.7) or high dose estrogen (OR = 2.7, 95% CI = 1.2–6.4) associated with particularly elevated risk estimates compared to non-use of OCs in the prior year. In contrast, risk estimates for recent use of OCs with the progestin norgestimate or low dose estrogen suggested either a modest association or no association (OR = 1.2, 95% CI = 0.6–2.2 and OR = 1.0, 95% CI = 0.6–1.7, respectively).

Conclusions: These results suggest that recent use of contemporary OC formulations is associated with an elevated risk of breast cancer among women ages 20–49, with associations varying somewhat by OC formulation. Although breast cancer is rare among young women, the potential risk of breast cancer associated with certain formulations could impact OC recommendations by providers if these findings are confirmed.
Research Addressing Follow-Up for Abnormal Cancer Screening Tests: NCI Portfolio Analyses
Authors: J Zapka , H Edwards , V Chollette , S Taplin
Published: March 2012

Purpose: The study's purposes were to identify the portfolio of grants awarded by the National Cancer Institute that addressed follow-up to abnormal screening tests for colon, breast and cervical cancer, document key research design characteristics, and discuss questions and issues for future practice and research.

Methods: A standardized form was used to audit grants funded from 2002 through 2011. Grant text was independently reviewed by two auditors; differences in reports were discussed until consensus was reached. The investigators then summarized findings in order to distill trends and issues.

Results: Twelve grants met inclusion criteria; 5, 4, 2 and 1 addressed follow-up of Pap tests, mammography, and colorectal tests and multiple screens respectively. Fifty percent were R01 awards, the majority of which applied group or individual RCT designs. One was a prospective cohort study. R21s typically emphasized qualitative methods and stressed behavioral epidemiology, measurement tool development and intervention planning; several listed aims related to determining prevalence. Definition of outcome measures was variable: e.g. completion of a follow-up test; time to follow-up; and steps until diagnosis. Four studies explicitly focused on ethnic/racial disparities; 5 on low income and underserved populations. Several emphasized measurement development. Three included cost analyses research questions. Most focused on individual level change, although changes in the broader multi-level context were proposed, but at times implicit, often viewed as process measures. A majority included aims related to understanding important mediator and moderator variables. Few explicated multilevel theories, although models reflected an ecological orientation.

Conclusions: Future practice and research priorities include development of clear operational definitions of follow-up; conceptual and descriptive evaluations of how providers, patients, and organizations interact across the steps and interfaces of follow-up care; determination of priorities for multilevel intervention testing and improvement of measures, and application of appropriate and innovative study designs using multi-methods.

This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E.
Fas Expression in Renal Cell Carcinoma Accurately Predicts Patient Survival after Radical Nephrectomy
Authors: Sejima Takehiro , Morizane Shuichi , Hinata Nobuyuki , Yao Akihisa , Isoyama Tadahiro , Saito Motoaki , Takenaka Atsushi
Published: March 2012

Objectives: To investigate Fas, Fas ligand (FasL) and Bcl-2 expression, which are considered to be important apoptotic regulatory factors in renal cell carcinomas (RCCs). Patients and Methods: mRNA quantification and immunohistochemistry allowed for the determination of the expression of these three factors in surgically resected tumors from 82 patients with RCC. The correlation of protein and gene expression with more than 10 years of survival data following nephrectomy (along with clinical and pathologic parameters) was analyzed using uni- and multivariate statistical models. Results: A significantly poorer outcome was observed in patients with tumors expressing high levels of Fas mRNA in the multivariate analysis (p = 0.0002). In addition, patient survival was significantly worse in FasL mRNA-positive tumor cases when compared with FasL mRNA-negative cases (p = 0.0345). Ten cases relapsed more than 5 years after nephrectomy. Among them, the tumors of 8 cases (80%) did not express FasL mRNA. Analysis of Bcl-2 did not show statistical significance of Bcl-2 expression as a prognostic indicator. Conclusions: The data suggest that pronounced Fas expression is a surrogate biomarker of active cancer cell proliferation. Given the FasL tumor counterattack theory, FasL overexpression in RCC may be one of the host immune deficiencies, consequently leading to poor prognosis.
Association between the Self-Perception Period of Lower Urinary Tract Symptoms and the International Prostate Symptom Score
Authors: Shim Sung Ryul , Kim Jae Heon , Kim Khae Hawn , Yoon Sang Jin , Lee Won Jin , Kim Hae Joon , Bae Jae Hyun
Published: March 2012

Objectives: The timing of visiting a hospital after self-perception of lower urinary tract symptoms (LUTS) is different between individuals. The association between the self-perception period (S-PP) of LUTS and the progression of LUTS has seldom been documented. The aim of this study was to investigate the association between the S-PP of LUTS and the International Prostate Symptom Score (IPSS). Subjects and Methods: This was a cross-sectional study comprising 267 men aged 40 years and older who participated in a prostate examination survey between February and May 2009. Survey questionnaires included items on the IPSS, the S-PPs of seven individual LUTSs assessed in the IPSS. Results: The S-PP of LUTS became significantly longer as the severity of LUTS increased. Of the seven symptoms, a weak urinary stream and nocturia showed longer S-PPs than others. Partial correlation between the S-PP and IPSS showed a statistically significant positive correlation. Linear regression analysis showed a statistically significant relationship that unstandardized coefficients included 0.051 and 0.005 for IPSS and quality of life. Conclusions: These findings suggest that the S-PP is an independent risk factor for LUTS progression. S-PPs have to be considered for treatment or prevention of LUTS.
Public Health Genomics in Spain: The Status of a Non-Existing Reality
Authors: Gutiérrez-Ibarluzea I. , Ibarreta D. , Malats N. ,   on behalf of the Spanish National Task Force on Public Health Genomics
Published: March 2012

Aims: The Public Health Genomics European Network (PHGEN) aimed, among other objectives, to identify the geographical variability and legal barriers of genomic medicine and public health genomics (PHG) at an international market, where the lack of policy coherence may limit its development in Europe. PHGEN supported the creation of National Task Forces (NTF) to overview the national settings and identify proposals in different European countries. Here we summarize the key issues which emerged during the discussions conducted within the Spanish NTF. Methods: The Spanish NTF is composed of 25 experts and key leaders in PHG-related areas of knowledge and met 3 times between January 2007 and 2008 to identify, discuss and propose recommendations for the development and use of PHG in Spain. Discussions were recorded and shared with participants for amendments. Results: We observed lack of applied knowledge on PHG, training skills and capacities on genomics of the involved specialists (gynecology, pediatrics, oncology, etc.), lack of applied research on diagnostics and knowledge on the topic in the population and mass media. Some promoting factors were observed, such as plans on genetics in the different regional autonomous communities, guidance on the introduction of genomic technologies and the new regional health technology regulatory frameworks. Conclusion: Although there is a current Spanish regulatory framework for the introduction of health technologies and a published biomedical law that could be useful for the development of PHG in Spain, specific and tailored initiatives should be promoted by regional and national authorities to improve the accreditation professionals and to inform the citizens on genomic technologies in order to empower them.
Correlation between the Resistive Index Values of Renal and Orbital Arteries
Authors: Basturk T. , Akcay M. , Albayrak R. , Unsal A. , Ulas T. , Koc Y.
Published: March 2012

Background: Resistive index (RI) is an indirect measurement of blood flow resistance that can be used to evaluate vascular damage. Aims: The purpose of this study is to evaluate the association between RI values of orbital and intrarenal arteries by means of Doppler ultrasonography (US). Methods: We evaluated 103 diabetic patients. As a control group, 30 subjects were examined. The patients were divided into two groups. Group 1 consisted of patients with urinary albumin excretion (UAE) <300 mg/day and estimated glomerular filtration rate (eGFR) levels >90 ml/min (n = 50); Group 2 had a UAE >300 mg/day and/or eGFR levels between 89 and 60 ml/min (n = 53). The association between RI values obtained with Doppler US of the ophthalmic artery, central retinal artery, posterior ciliary artery and intrarenal arteries were calculated. Results: Both orbital and intrarenal arterial RI values in Group 1 and Group 2 were higher than the control group (p = 0.001); furthermore, values were higher in Group 2 than in Group 1 (p = 0.0004/0.029/0.036, p = 0.016, respectively). A positive correlation was found between orbital and intrarenal arterial RI values in Group 2 (r = 0.475, 0.285, 0.363, p < 0.01, respectively). Conclusion: Both orbital and renal arterial RI values were shown to be higher than the control group. Further, a trend towards higher RI values was observed with renal disease. RI may be useful as one of the markers for early diagnosis and follow-up of diabetic nephropathy and retinopathy.
Integrated Genome-Wide Pathway Association Analysis with INTERSNP
Authors: Herold Christine , Mattheisen Manuel , Lacour André , Vaitsiakhovich Tatsiana , Angisch Marina , Drichel Dmitriy , Becker Tim
Published: March 2012

Objectives: Pathway association analysis (PAA) tests for an excess of moderately significant SNPs in genes from a common pathway. Methods: We present a Monte-Carlo simulation framework that allows to formulate the main ideas of existing PAA approaches using a self-contained rather than a competitive null hypothesis. A stand-alone implementation in INTERSNP makes time-consuming communication with standard GWAS software redundant. By additional parallelization with the OpenMP API, we achieve a reduction in running time for PAA by orders of magnitude, making a power simulation study for PAA feasible. Our approach properly accounts for linkage disequilibrium and is robust with respect to residual λ inflation. Results: We demonstrate that under simple, realistic disease models, PAA can actually strongly outperform the GWAS single-marker approach. PAA methods that make use of the strength of the SNP association (GenGen, Fisher’s combination test), in general, perform better than ratio-based methods (ALIGATOR, SNP ratio), whereas the relative performance of gene-based scoring (ALIGATOR, GenGen) and pathway-based scoring (SNP ratio, Fisher’s combination test) depends on the architecture of the assumed disease model. Finally, we present a new PAA score that models independent signals from the same gene in a regression framework and show that it is a reasonable compromise that combines the advantages of existing ideas.
Elevated Temperature Applied during Gonadal Transformation Leads to Male Bias in Zebrafish (Danio rerio)
Authors: Abozaid H. , Wessels S. , Hörstgen-Schwark G.
Published: March 2012

Temperature effects on sex determination or differentiation exist in many fish species, with high temperatures predominantly producing more males. The present study aimed at elucidating the genetic background of temperature effects on sex differentiation in zebrafish. Experimental fish were generated by matings between 4 or 6 golden females and a normal or a mitotic gynogenetic male, respectively. All the larvae were reared at 28.5°C until they were divided into 3 groups per full-sib family, a control group raised at 28.5°C and 2 treatment groups reared at 35°C from 20 to 30 dpf or 25 to 35 dpf, respectively. Backcross progenies, reared at 28.5°C, were derived from F1 temperature-treated sons (35°C, 25–35 dpf) that were sired by a mitotic gynogenetic male and their corresponding mothers. No significant differences were observed regarding the survival rate between the control and treatment groups. Significant differences in the phenotypic male proportions from the controls were observed in groups treated at 35°C. The sex ratio in zebrafish was influenced by the male spawner, the female spawner, and a significant interaction of genotype by temperature. Backcross experiments point to a continuum of major genetic, minor genetic, and environmental factors in the expression of the phenotypic sex in zebrafish.
Prognostic Value of 48-Hour Ambulatory Blood Pressure Measurement and Cardiovascular Mortality in Hemodialysis Patients
Authors: Ekart Robert , Kanič Vojko , Pečovnik Balon Breda , Bevc Sebastjan , Hojs Radovan
Published: March 2012

Background: Hypertension is common and contributes to high cardiovascular morbidity and mortality in hemodialysis (HD) patients. It is unknown which blood pressure (BP) better defines the influence on cardiovascular mortality. The purpose of our study was to analyze the relationship between various BP measurements, traditional risk factors, markers of asymptomatic atherosclerosis [left ventricular mass (LVM), carotid intima media thickness (IMT)], and cardiovascular mortality in HD patients. Methods: Seventy-three patients (44 males and 29 females; mean age: 54.2 years) were included. BP was measured before and after HD and 48-hour ambulatory blood pressure monitoring (ABPM) was performed. Using sonography, the LVM index and carotid IMT were measured. Results: During a follow-up period up to 3,664 days, 28 patients died – 16 of them from cardiovascular causes. In a Cox regression model, which included age, gender, smoking, diabetes, sensitive C-reactive protein, albumin, hemoglobin, troponin T, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, calcium, phosphorus, carotid IMT, and LVM index, only 48-hour systolic ABPM (p = 0.037) and 48-hour diastolic ABPM (p = 0.006) turned out to be independent predictors of cardiovascular death. Conclusion: Only 48-hour ABPM and not single BP measurements before or after HD were associated with cardiovascular mortality in HD patients.
Corneocyte Quantification by NIR Densitometry and UV/Vis Spectroscopy for Human and Porcine Skin and the Role of Skin Cleaning Procedures
Authors: Schwarz J.C. , Klang V. , Hoppel M. , Wolzt M. , Valenta C.
Published: March 2012

Optical methods of corneocyte quantification during tape stripping experiments on the skin are useful tools for the rapid evaluation of the skin penetration potential of dermally applied substances. However, a comparative investigation of the different methods proposed for this task, namely NIR densitometry and UV/Vis spectroscopy, is still missing. Thus, the aim of the present work was to employ these two techniques in comparative tape stripping experiments both in vivo on human forearm skin and in vitro on porcine ear skin. Standard tape stripping experiments were performed in the absence and presence of a marketed formulation containing flufenamic acid as a model drug. In the context of these methodological investigations, different methods of skin cleaning prior to the tape stripping procedure were evaluated to identify the most appropriate working protocol among the approaches proposed in the respective literature. The results showed that the investigated methods of NIR densitometry and UV/Vis spectroscopy deliver highly comparable results. Both optical methods are suitable to determine the skin penetration profiles of active substances during in vivo and in vitro tape stripping, especially if a simple working protocol without any cleaning procedures is maintained.
Unique Genomic Structure and Distinct Mitotic Behavior of Ring Chromosome 21 in Two Unrelated Cases
Authors: Zhang H.Z. , Xu F. , Seashore M. , Li P.
Published: March 2012

A ring chromosome replacing a normal chromosome could involve variable structural rearrangements and mitotic instability. However, most previously reported cases lacked further genomic characterization. High-resolution oligonucleotide array comparative genomic hybridization with single-nucleotide polymorphism typing (aCGH+SNP) was used to study 2 unrelated cases with a ring chromosome 21. Case 1 had severe myopia, hypotonia, joint hypermobility, speech delay, and dysmorphic features. aCGH detected a 1.275-Mb duplication of 21q22.12–q22.13 and a 6.731-Mb distal deletion at 21q22.2. Case 2 showed severe growth and developmental retardations, intractable seizures, and dysmorphic features. aCGH revealed a contiguous pattern of a 3.612- Mb deletion of 21q22.12–q22.2, a 4.568-Mb duplication of 21q22.2–q22.3, and a 2.243-Mb distal deletion at 21q22.3. Mitotic instability was noted in 13, 30, and 76% of in vitro cultured metaphase cells, interphase cells, and leukocyte DNA, respectively. The different phenotypes of these 2 cases are likely associated with the unique genomic structure and distinct mitotic behavior of their ring chromosome 21. These 2 cases represent a subtype of ring chromosome 21 probably involving somatic dicentric ring breakage and reunion. A cytogenomic approach is proposed for characterizing the genomic structure and mitotic instability of ring chromosome abnormalities.
Modelling and simulation of edoxaban exposure and response relationships in patients with atrial fibrillation
Authors: Mendell Jeanne , Kastrissios Helen , Green Michelle , Carrothers Timothy J. , Song SaeHeum , Patel Indravadan , Antman Elliott M. , Giugliano Robert P. , Kunitada Satoshi , Dornseif Bruce , Shi Minggao , Tachibana Masaya , Zhou Simon , Rohatagi Shashank , Salazar Daniel E. , Bocanegra Tomas S.
Published: March 2012

Edoxaban is a novel, orally available, highly specific direct inhibitor of factor Xa and is currently being developed for the treatment and prevention of venous thromboembolism and prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). The objectives of the present analyses were to characterise edoxaban population pharmacokinetics (PPK) and identify potential intrinsic and extrinsic factors affecting variability in edoxaban exposure, determine if there are relationships between edoxaban pharmacokinetics or biomarkers and the risk of bleeding in patients with NVAF using an exposure-response model, and to use the PPK and exposure-response model to support dose selection for a phase III trial of edoxaban in patients with NVAF. PPK analysis of data from 1,281 edoxaban-dosed subjects with intrinsic factors such as renal impairment or NVAF and extrinsic factors such as concomitant medications revealed significant effects of renal impairment and concomitant strong P-glycoprotein (P-gp) inhibitors on the pharmacokinetics of edoxaban. Exposure-response analysis found that in patients with NVAF, the incidence of bleeding events increased significantly with increasing edoxaban exposure, with steady-state minimum concentration (Cmin,ss) showing the strongest association. Clinical trial simulations of bleeding incidence were used to select 30 mg and 60 mg once-daily edoxaban with 50% dose reductions for patients with moderate renal impairment or receiving concomitant strong P-gp inhibitors as the treatment regimens in the ENGAGE AF-TIMI 48 (NCT00781391) trial.

The results of this study were previously presented at the 2009 International Society on Thrombosis and Haemostasis, July 2009, Boston, Massachusetts, USA.
Immunosuppressive function of mesenchymal stem cells from human umbilical cord matrix in immune thrombocytopenia patients
Authors: Ma Li , Zhou Zeping , Zhang Donglei , Yang Shaoguang , Wang Jinhong , Xue Feng , Yang Yanhui , Yang Renchi
Published: March 2012

Human umbilical cord matrix/Wharton's Jelly (hUC)-derived mesenchymal stem cells (MSC) have been shown to have marked therapeutic effects in a number of inflammatory diseases and autoimmune diseases in humans based on their potential for immunosuppression and their low immunogenicity. Currently, no data are available on the effectiveness of UC-MSC transplantation in immune thrombocytopenia (ITP) patients. It was the objective of this study to assess the effect of allogeneic UC-MSCs on ITP patients in vitro and in vivo. Peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BM-MNCs) from ITP patients and healthy controls were co-cultured with UC-MSCs for three days and seven days, respectively. Flow cytometry and ELISA were applied to assess the various parameters. In PBMCs from ITP patients, the proliferation of autoreactive T, B lymphocytes and destruction of autologous platelets were dramatically suppressed by UC-MSCs. UC-MSCs not only suppressed co-stimulatory molecules CD80, CD40L and FasL expression but also in shifting Th1/Th2/Treg cytokines profile in ITP patients. UC-MSCs obviously reversed the dysfunctions of megakaryocytes by promoting platelet production and decreasing the number of living megakaryocytes as well as early apoptosis. In addition, the level of thrombopoietin was increased significantly. Our clinical study showed that UC-MSCs play a role in alleviating refractory ITP by increasing platelet numbers. These findings suggested that UC-MSCs transplantation might be a potential therapy for ITP.
Early Detection of an Underperforming Implantable Cardiovascular Device Using an Automated Safety Surveillance Tool
Authors: Hauser Robert G. , Mugglin Andrew S. , Friedman Paul A. , Kramer Daniel B. , Kallinen Linda , McGriff Deepa , Hayes David L.
Published: March 2012

Background—

Postmarket medical device surveillance in the United States depends largely on voluntary reporting of adverse events. Consequently, early safety signals may be missed, exposing patients to potentially hazardous products. The aim of this study was to assess the feasibility of using an automated safety surveillance tool to detect early signals that a marketed implantable cardiac device was underperforming.

Methods and Results—

For this purpose, we performed simulated prospective monthly full-cohort and propensity-matched comparative survival analyses on our 3-center database of Sprint Fidelis and Quattro Secure implantable cardioverter-defibrillator leads, using a commercially available automated surveillance tool that was preset to trigger an alert if the log rank probability value was <0.05. During the study, 84 of 1035 Fidelis (8.1%) and 23 of 1675 Quattro (1.4%) leads failed. The simulated full-cohort analysis triggered a sustained alert for Fidelis leads beginning 13 months after the first implant and 2 years before Fidelis leads were removed from the market. Of the 1035 patients who had Fidelis leads, up to 969 (93.6%) were successfully matched to Quattro patients. In the propensity-matched analysis, the alert triggered 22 months after the first Fidelis implant and more than 1 year before the lead was recalled.

Conclusions—

An active automated safety surveillance system could have identified this implantable cardiovascular device problem substantially sooner than was achieved through existing postmarket surveillance methods. Such a tool, when applied to clinical registries and remote monitoring databases, may limit the exposure of large populations to underperforming and potentially hazardous cardiovascular devices.
Addition of Frailty and Disability to Cardiac Surgery Risk Scores Identifies Elderly Patients at High Risk of Mortality or Major Morbidity
Authors: Afilalo Jonathan , Mottillo Salvatore , Eisenberg Mark J. , Alexander Karen P. , Noiseux Nicolas , Perrault Louis P. , Morin Jean-Francois , Langlois Yves , Ohayon Samuel M. , Monette Johanne , Boivin Jean-Francois , Shahian David M. , Bergman Howard
Published: March 2012

Background—

Cardiac surgery risk scores perform poorly in elderly patients, in part because they do not take into account frailty and disability which are critical determinants of health status with advanced age. There is an unmet need to combine established cardiac surgery risk scores with measures of frailty and disability to provide a more complete model for risk prediction in elderly patients undergoing cardiac surgery.

Methods and Results—

This was a prospective, multicenter cohort study of elderly patients (≥70 years) undergoing coronary artery bypass and/or valve surgery in the United States and Canada. Four different frailty scales, 3 disability scales, and 5 cardiac surgery risk scores were measured in all patients. The primary outcome was the STS composite end point of in-hospital postoperative mortality or major morbidity. A total of 152 patients were enrolled, with a mean age of 75.9±4.4 years and 34% women. Depending on the scale used, 20–46% of patients were found to be frail, and 5–76% were found to have at least 1 disability. The most predictive scale in each domain was: 5-meter gait speed ≥6 seconds as a measure of frailty (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.17–5.90), ≥3 impairments in the Nagi scale as a measure of disability (OR, 2.98; 95% CI, 1.35–6.56) and either the Parsonnet score (OR, 1.08; 95% CI, 1.04–1.13) or Society of Thoracic Surgeons Predicted Risk of Mortality or Major Morbidity (STS-PROMM) (OR, 1.05; 95% CI, 1.01–1.09) as a cardiac surgery risk score. Compared with the Parsonnet score or STS-PROMM alone, (area under the curve, 0.68–0.72), addition of frailty and disability provided incremental value and improved model discrimination (area under the curve, 0.73–0.76).

Conclusions—

Clinicians should use an integrative approach combining frailty, disability, and risk scores to better characterize elderly patients referred for cardiac surgery and identify those that are at increased risk.
TMS of the FEF Interferes with Spatial Conflict
Authors: Bardi Lara , Kanai Ryota , Mapelli Daniela , Walsh Vincent
Published: March 2012

In the Simon task, a conflict arises because irrelevant spatial information competes for response selection either facilitating or interfering with performance. Responses are faster when stimulus and response position correspond than when they do not. The FEFs, which have long been characterized for their role in oculomotor control, are also involved in the control of visuospatial attention when eye movements are not required. This study was aimed at investigating whether the FEFs contribute to spatial conflict. Double-pulse TMS was applied to the FEF of either left or right hemisphere during the execution of a Simon task at different time windows after the onset of the visual stimulus. A suppression of the Simon effect was observed after stimulation of the FEF for stimuli appearing in the contralateral hemifield when TMS was applied to the left hemisphere after stimulus onset (0–40 and 40–80 msec). A reduction of the correspondence effect was observed after right FEF TMS for stimuli presented in the left visual hemifield when stimulation was delivered in the 80–120 msec range after stimulus onset. These outcomes indicate that the FEF play a critical role in encoding spatial attribute of a stimulus for response priming, which is the prerequisite for response conflict in the Simon task. Moreover, our finding that the left FEF have a dominant role during spatial conflict extends the idea of the left-hemisphere lateralization of the motor network in action selection by suggesting that the FEF may constitute part of this network.
Human Brain Activity Predicts Individual Differences in Prior Knowledge Use during Decisions
Authors: Hansen Kathleen A. , Hillenbrand Sarah F. , Ungerleider Leslie G.
Published: March 2012

Studies by cognitive psychologists, psychophysicists, neuroscientists, and economists provide ample evidence that humans use prior knowledge to bias decisions adaptively. In this study, we sought to locate and investigate the brain areas mediating this behavior. Participants viewed ambiguous abstract shapes and decided whether a shape was of Category A (smoother) or B (bumpier). The decision was made in the context of one of two prior knowledge cues, 80/20 and 50/50. The 80/20 cue indicated that upcoming shapes had an 80% probability of being of one category, for example, B, and a 20% probability of being of the other. The 50/50 cue indicated that upcoming shapes had an equal probability of being of either category. The shift in bias produced by the 80/20 cue relative to the 50/50 cue was of the predicted sign for every subject but varied in magnitude. We searched for brain regions in which activity changes correlated with the extent of the bias shift; these were dorsolateral pFC (middle frontal gyrus), inferior frontal junction, anterior insula, inferior parietal lobule, intraparietal sulcus, head of the caudate, posterior cingulate cortex, and fusiform gyrus. The findings indicate that an individual's brain activity in these regions reflects the extent to which that individual makes use of prior knowledge to bias decisions. We also created within-ROI tuning curves by binning the shape curvature levels and plotting brain activity levels at each of the nine bins. In the fronto-parietal and anterior insula ROIs, the tuning curves peaked at targets contraindicated by the prior knowledge cue (e.g., Category B targets if the 80/20 cue meant 20% probability B). The increased activity in these regions likely indicates a no-go response when sufficient perceptual evidence favored the alternative contraindicated by the 80/20 cue.
Climate Divisions for Alaska Based on Objective Methods
Authors: Bieniek Peter A. , Bhatt Uma S. , Thoman Richard L. , Angeloff Heather , Partain James , Papineau John , Fritsch Frederick , Holloway Eric , Walsh John E. , Daly Christopher , Shulski Martha , Hufford Gary , Hill David F. , Calos Stavros , Gens Rudiger
Published: March 2012

Alaska encompasses several climate types because of its vast size, high-latitude location, proximity to oceans, and complex topography. There is a great need to understand how climate varies regionally for climatic research and forecasting applications. Although climate-type zones have been established for Alaska on the basis of seasonal climatological mean behavior, there has been little attempt to construct climate divisions that identify regions with consistently homogeneous climatic variability. In this study, cluster analysis was applied to monthly-average temperature data from 1977 to 2010 at a robust set of weather stations to develop climate divisions for the state. Mean-adjusted Advanced Very High Resolution Radiometer surface temperature estimates were employed to fill in missing temperature data when possible. Thirteen climate divisions were identified on the basis of the cluster analysis and were subsequently refined using local expert knowledge. Divisional boundary lines were drawn that encompass the grouped stations by following major surrounding topographic boundaries. Correlation analysis between station and gridded downscaled temperature and precipitation data supported the division placement and boundaries. The new divisions north of the Alaska Range were the North Slope, West Coast, Central Interior, Northeast Interior, and Northwest Interior. Divisions south of the Alaska Range were Cook Inlet, Bristol Bay, Aleutians, Northeast Gulf, Northwest Gulf, North Panhandle, Central Panhandle, and South Panhandle. Correlations with various Pacific Ocean and Arctic climatic teleconnection indices showed numerous significant relationships between seasonal division average temperature and the Arctic Oscillation, Pacific–North American pattern, North Pacific index, and Pacific decadal oscillation.
The Effect of Variable Sea Surface Temperature on Forecasting Sea Fog and Sea Breezes: A Case Study
Authors: Tang Yongming
Published: March 2012

A preliminary study of the effect of sea surface temperature (SST) temporal and spatial variability on regional coastal weather forecasts is described. A high-resolution numerical weather forecast model from the Met Office is run for the U.K. region with hourly updates of SST data obtained from a shelf sea model. When compared with a control run in which SST is maintained with Operational Sea Surface Temperature and Sea Ice Analysis (OSTIA) data, it is found that there are significant differences in the coastal-region forecasts for sea breezes and fog formation. The control run underestimates surface temperature and the strength of the sea breeze when compared with the run with hourly SST updates.
A Linear Theory of Three-Dimensional Land–Sea Breezes
Authors: Jiang Qingfang
Published: March 2012

Land–sea breezes (LSBs) induced by diurnal differential heating are examined using a three-dimensional linear model employing fast Fourier transform with emphasis on the complex coastline shape and geometry, the earth’s rotation, and background wind effects. It has been demonstrated that the low-level vertical motion associated with LSB can be significantly enhanced over a bay (peninsula) because of convergence of perturbations induced by differential heating along a seaward concave (convex) coastline. The dependence of surface winds and vertical motion patterns and their evolutions on the coastline geometries such as the width and the aspect ratio of the bay, the earth’s rotation, and the background winds are investigated.

The LSB induced by an isolated tropical island is characterized by onshore flow and ascent over the island in the afternoon to early evening, with a reversal of direction from midnight to early morning. The diurnal heating–induced vertical motion is greatly enhanced over the island and weakened offshore because of the convergence and divergence of perturbations. In the presence of background flow, stronger diurnal perturbations are found at the downwind side of the island, which can extend far downstream associated with inertia–gravity waves.