bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of stability and size distribution of sunflower oil-coated micro bubbles for localized drug delivery
Authors: Filho Walter Duartede Araujo , Schneider Fábio Kurt , Morales Rigoberto EM
Published: September 2012

Background

Micro bubbles were initially introduced as contrast agents for ultrasound examinations as they are able to modify the signal-to-noise ratio in imaging, thus improving the assessment of clinical information on human tissue. Recent developments have demonstrated the feasibility of using these bubbles as drug carriers in localized delivery. In micro fluidics devices for generation of micro bubbles, the bubbles are formed at interface of liquid gas through a strangulation process. A device that uses these features can produce micro bubbles with small size dispersion in a single step.

Methods

A T-junction micro fluidic device constructed using 3D prototyping was made for the production of mono dispersed micro bubbles. These micro bubbles use sunflower oil as a lipid layer. Stability studies for micro bubbles with diameters different generated from a liquid phase of the same viscosity were conducted to evaluate whether micro bubbles can be used as drug carriers. The biocompatibility of coating layer, the ability to withstand environmental pressure variations combined with echogenicity, are key factors that they can safely play the role of drug transporters.

Results

The normal distribution curve with small dispersion of the diameter of bubbles validates the process of generating micro bubbles with low value of variation coefficient, i.e., 0.381 at 1.90%. The results also showed the feasibility of using sunflower oil as the lipid matrix with stable population of bubbles over 217 minutes for micro bubbles with an average diameter of 313.04 μm and 121 minutes for micro bubbles with an average diameter of 73.74 μm, considering bubbles with air as gaseous phase.

Conclusion

The results indicate that the micro fluidic device designed can be used for producing micro bubbles with low variation coefficient using sunflower oil as a coating of micro bubbles. These carriers were stable for periods of time that are long enough for clinical applications even when regular air is used as the gas phase. Improved stability can be achieved when biocompatible gas with lower permeability is used.
Acute ischemic stroke following Hump-nosed viper envenoming; first authenticated case
Authors: jeevagan Vijayabala , Chang Thashi , Gnanathasan Christeine Ariaranee
Published: September 2012

Hump-nosed pit viper (Genus Hypnale) is a medically important venomous snake in Sri Lanka and Southwestern India which causes significant morbidity and mortality. Envenoming of this snake results in hemostastic dysfunction, thrombotic microangiopathy, acute kidney injury and death. This case describes an authenticated first case of ischemic stroke in a 65 year old male following envenoming by H.hypnale in Sri Lanka.
Medullary thyroid cancer in a 9-week-old infant with familial MEN 2B: Implications for timing of prophylactic thyroidectomy
Authors: Shankar Roopa Kanakatti , Rutter Michael J , Chernausek Steven D , Samuels Paul J , Mo Jun Qin , Rutter Meilan M
Published: September 2012

Background

Patients with Multiple Endocrine Neoplasia type 2 (MEN 2) are at high risk of developing aggressive medullary thyroid carcinoma (MTC) in childhood, with the highest risk in those with MEN type 2B (of whom >95% have an M918T RET proto-oncogene mutation). Metastatic MTC has been reported as young as 3 months of age. Current guidelines recommend prophylactic thyroidectomy within the first year of life for MEN 2B.

Patient findings

We report a 9-week-old infant with MTC due to familial MEN 2B. A full-term male infant, born to a mother with known MEN 2B and metastatic MTC, had an M918T RET proto-oncogene mutation confirmed at 4 weeks of age. He underwent prophylactic total thyroidectomy at 9 weeks of age. Pathology showed a focal calcitonin-positive nodule (2.5 mm), consistent with microscopic MTC.

This case highlights the importance of early prophylactic thyroidectomy in MEN 2B. Although current guidelines recommend surgery up to a year of life, MTC may occur in the first few weeks of life, raising the question of how early we should intervene. In this report, we discuss the risks, benefits and barriers to performing earlier thyroidectomy, soon after the first month of life, and make suggestions to facilitate timely intervention. Prenatal anticipatory surgical scheduling could be considered in familial MEN 2B. Multidisciplinary collaboration between adult and pediatric specialists is key to the optimal management of the infant at risk.
Intracerebral delivery of Carboplatin in combination with either 6 MV Photons or monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98 rat glioma
Authors: Bobyk Laure , Edouard Magali , Deman Pierre , Rousseau Julia , Adam Jean-François , Ravanat Jean-Luc , Estève François , Balosso Jacques , Barth Rolf F , Elleaume Hélène
Published: September 2012

Background

The purpose of the present study was to compare side-by-side the therapeutic efficacy of a 6-day infusion of carboplatin, followed by X-irradiation with either 6 MV photons or synchrotron X-rays, tuned above the K-edge of Pt, for treatment of F98 glioma bearing rats.

Methods

Carboplatin was administered intracerebrally (i.c.) to F98 glioma bearing rats over 6 days using AlzetTM osmotic pumps starting 7 days after tumor implantation. Radiotherapy was delivered in a single 15 Gy fraction on day 14 using a conventional 6 MV linear accelerator (LINAC) or 78.8 keV synchrotron X-rays.

Results

Untreated control animals had a median survival time (MeST) of 33 days. Animals that received either carboplatin alone or irradiation alone with either 78.8 keV or 6 MV had a MeSTs 38 and 33 days, respectively. Animals that received carboplatin in combination with X-irradiation had a MeST of > 180 days with a 55% cure rate, irrespective of whether they were irradiated with either 78.8 KeV synchrotron X-rays or 6MV photons.

Conclusions

These studies have conclusively demonstrated the equivalency of i.c. delivery of carboplatin in combination with X-irradiation with either 6 MV photons or synchrotron X-rays.
Activated STAT regulates growth and induces competitive interactions independently of Myc, Yorkie, Wingless and ribosome biogenesis
Authors: Rodrigues Aloma B. , Zoranovic Tamara , Ayala-Camargo Aidee , Grewal Savraj , Reyes-Robles Tamara , Krasny Michelle , Wu D. Christine , Johnston Laura A. , Bach Erika A.
Published: September 2012

Cell competition is a conserved mechanism that regulates organ size and shares properties with the early stages of cancer. In Drosophila, wing cells with increased Myc or with optimum ribosome function become supercompetitors that kill their wild-type neighbors (called losers) up to several cell diameters away. Here, we report that modulating STAT activity levels regulates competitor status. Cells lacking STAT become losers that are killed by neighboring wild-type cells. By contrast, cells with hyper-activated STAT become supercompetitors that kill losers located at a distance in a manner that is dependent on hid but independent of Myc, Yorkie, Wingless signaling, and of ribosome biogenesis. These results indicate that STAT, Wingless and Myc are major parallel regulators of cell competition, which may converge on signals that non-autonomously kill losers. As hyper-activated STATs are causal to tumorigenesis and stem cell niche occupancy, our results have therapeutic implications for cancer and regenerative medicine.
Zasp regulates integrin activation
Authors: Bouaouina Mohamed , Jani Klodiana , Long Jenny Y. , Czerniecki Stefan , Morse Elizabeth M. , Ellis Stephanie J. , Tanentzapf Guy , Schöck Frieder , Calderwood David A.
Published: September 2012

Integrins are heterodimeric adhesion receptors that link the extracellular matrix (ECM) to the cytoskeleton. Binding of the scaffold protein, talin, to the cytoplasmic tail of β-integrin causes a conformational change of the extracellular domains of the integrin heterodimer, thus allowing high-affinity binding of ECM ligands. This essential process is called integrin activation. Here we report that the Z-band alternatively spliced PDZ-motif-containing protein (Zasp) cooperates with talin to activate α5β1 integrins in mammalian tissue culture and αPS2βPS integrins in Drosophila. Zasp is a PDZ–LIM-domain-containing protein mutated in human cardiomyopathies previously thought to function primarily in assembly and maintenance of the muscle contractile machinery. Notably, Zasp is the first protein shown to co-activate α5β1 integrins with talin and appears to do so in a manner distinct from known αIIbβ3 integrin co-activators.
The role of microtubules in neutrophil polarity and migration in live zebrafish
Authors: Yoo Sa Kan , Lam Pui-ying , Eichelberg Mark R. , Zasadil Lauren , Bement William M. , Huttenlocher Anna
Published: September 2012

Microtubules control cell motility by positively regulating polarization in many cell types. However, how microtubules regulate leukocyte migration is not well understood, particularly in living organisms. Here we exploited the zebrafish system to study the role of microtubules in neutrophil migration in vivo. The localization of microtubules was visualized in motile neutrophils using various bioprobes, revealing that, in contrast to what has been seen in studies in vitro, the microtubule organizing center is positioned in front of the nucleus (relative to the direction of migration) in motile neutrophils. Microtubule disassembly impaired attraction of neutrophils to wounds but enhanced the polarity of F-actin dynamics as measured by the distribution of stable and dynamic F-actin. Microtubule depolymerization inhibited polarized phosphoinositol 3-kinase (PI(3)K) activation at the leading edge and induced rapid PI(3)K independent motility. Finally, we show that microtubules exert their effects on neutrophil polarity and motility at least in part by the negative regulation of both Rho and Rac activity. These results provide new insight into the role of microtubules in neutrophil migration in a living vertebrate and show that the motility of these professional migratory cells are subject to distinctly different rules from those established for other cell types.
Rab6 is required for the exocytosis of cortical granules and the recruitment of separase to the granules during the oocyte-to-embryo transition in Caenorhabditis elegans
Authors: Kimura Kenji , Kimura Akatsuki
Published: September 2012

Remodeling of the embryo surface after fertilization is mediated by the exocytosis of cortical granules derived from the Golgi complex. This process is essential for oocyte-to-embryo transition in many species. However, how the fertilization signal reaches the cortical granules for their timely exocytosis is largely unknown. In Caenorhabditis elegans, the recruitment of separase, a downstream effector of the fertilization signal, to the cortical granules is essential for exocytosis because separase is required for membrane fusion. However, the molecule that recruits separase to the cortical granules remains unidentified. In this study, we found that Rab6, a Golgi-associated GTPase, is essential to recruit separase to the cortical granules in C. elegans embryos. Knockdown of the rab-6.1 gene, a Rab6 homolog in C. elegans, resulted in failure of the membrane fusion step of cortical granule exocytosis. Using a transgenic strain that expresses GFP-fused RAB-6.1, we found that RAB-6.1 temporarily co-localized with separase on the cortical granules for a few minutes and then was dispersed in the cytoplasm concomitantly with membrane fusion. We found that RAB-6.1, as well as cyclin-dependent kinase (CDK)-1 and anaphase promoting complex/cyclosome (APC/C), was required to recruit separase to the cortical granules. RAB-6.1 was not required for the chromosome segregation process, unlike CDK-1, APC/C and SEP-1. The results indicate that RAB-6.1 is required specifically for the membrane fusion step of exocytosis and for the recruitment of separase to the granules. Thus, RAB-6.1 is an important molecule for the timely exocytosis of the cortical granules during oocyte-to-embryo transition.
Chronic destructive pulmonary tuberculosis: assessment of disease activity by computed tomography
Authors: Nam Kyung Jin , Jeong Yeon Joo , Kim Yeong Dae , Kim Kun-Il , Lee Jun Woo , Park Hye Kyung , Hoseok I
Published: September 2012

Background

Determination of disease activity of chronic destructive pulmonary tuberculosis (TB) on imaging studies can be difficult because several imaging findings due to disease chronicity such as a residual cavity can be misinterpreted as an active disease.

Purpose

To evaluate computed tomography (CT) findings to predict active disease in patients with chronic destructive pulmonary TB.

Material and Methods

CT findings of 36 patients with chronic active destructive pulmonary TB and 78 patients with chronic inactive destructive pulmonary TB were reviewed and their patterns of lung lesions were compared. Statistical comparisons were performed using chi-square and Student's T tests for univariate analyses, and a stepwise logistic regression method was used for multivariate analysis.

Results

Based on univariate analyses, cavitary destruction ( P = 0.015), non-branching centrilobular nodules ( P < 0.001), tree-in-bud pattern ( P < 0.001), airspace nodules ( P < 0.001), and cavities in other lobes ( P = 0.001) were more frequently seen in chronic active destructive pulmonary TB. A stepwise logistic regression analysis demonstrated that tree-in-bud pattern (odds ratio, 52.3; 95% confidence interval, 6.2-437.2; P < 0.001) were significant CT findings associated with active disease.

Conclusion

Tree-in-bud pattern were the most characteristic CT findings to predict active disease in patients with chronic destructive pulmonary TB.
Inter- and intraradiologist variability in the BI-RADS assessment and breast density categories for screening mammograms
Authors: Redondo A , Comas M , Macià F , Ferrer F , Murta-Nascimento C , Maristany M T , Molins E , Sala M , Castells X
Published: September 2012

Objective

The aim of this study was to evaluate reader variability in screening mammograms according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) assessment and breast density categories.

Methods

A stratified random sample of 100 mammograms was selected from a population-based breast cancer screening programme in Barcelona, Spain: 13 histopathologically confirmed breast cancers and 51 with true-negative and 36 with false-positive results. 21 expert radiologists from radiological units of breast cancer screening programmes in Catalonia, Spain, reviewed the mammography images twice within a 6-month interval. The readers described each mammography using BI-RADS assessment and breast density categories. Inter- and intraradiologist agreement was assessed using percentage of concordance and the kappa (κ) statistic.

Results

Fair interobserver agreement was observed for the BI-RADS assessment [κ=0.37, 95% confidence interval (CI) 0.36–0.38]. When the categories were collapsed in terms of whether additional evaluation was required (Categories III, 0, IV, V) or not (I and II), moderate agreement was found (κ=0.53, 95% CI 0.52–0.54). Intra-observer agreement for BI-RADS assessment was moderate using all categories (κ=0.53, 95% CI 0.50–0.55) and substantial on recall (κ=0.66, 95% CI 0.63–0.70). Regarding breast density, inter- and intraradiologist agreement was substantial (κ=0.73, 95% CI 0.72–0.74 and κ=0.69, 95% CI 0.68–0.70, respectively).

Conclusion

We observed a substantial intra-observer agreement in the BI-RADS assessment but only moderate interobserver agreement. Both inter- and intra-observer agreement in mammographic interpretation of breast density was substantial.

Advances in knowledge

Educational efforts should be made to decrease radiologists' variability in BI-RADS assessment interpretation in population-based breast screening programmes.
High-resolution CT findings of pulmonary infections after orthotopic liver transplantation in 453 patients
Authors: Qin J , Xu J , Dong Y , Tang W , Wu B , An Y , Shan H
Published: September 2012

Objectives

The objective of this study was to review the high-resolution CT (HRCT) findings in patients with pulmonary infection after orthotopic liver transplantation (OLT) and to determine distinguishing findings among the various types of infection.

Methods

This study included 453 consecutive liver transplant recipients with pulmonary infection, on whom HRCT of the chest was performed within 24 h of the beginning of symptoms and for whom proven diagnosis had taken place within 1 week of the onset of symptoms. Two radiologists analysed the CT images; final decisions regarding the findings were reached by consensus.

Results

Bacterial and viral pneumonia made up the bulk of infections (63.4% and 29.4%, respectively), followed by fungal infiltrates (24.5%). Large nodules were most common in patients with fungal pneumonia, having been seen in 38 (54%) of the 70 patients with fungal pneumonia, 22 (10%) of 220 with bacterial pneumonia (p=0.0059) and 6 (8%) of 78 with viral pneumonia (p=0.0011). The halo sign was also more frequent in patients with fungal pneumonia, having been seen in 38 (54%) of the 70 patients with fungal pneumonia, 17 (8%) of 220 with bacterial pneumonia (p=0.0026) and 7 (9%) of 78 with viral pneumonia (p=0.0015). There was no statistically significant difference in the prevalence of the other HRCT patterns including air-space consolidation, ground-glass attenuation and small nodules among bacterial, viral and fungal infections (all p>0.05).

Conclusion

The presence of large nodules with the halo sign is most suggestive of fungal infection after OLT. Other HRCT patterns are not helpful in distinguishing among the various types of infection seen in liver transplant recipients.
Register as a predictor of linguistic variation
Authors: Biber, Douglas
Published: September 2012

Over the last two decades, corpus analysis has been used as the basis for several important reference grammars and dictionaries of English. While these reference works have made major contributions to our understanding of English lexis and grammar, most of them share a major limitation: the failure to consider register differences. Instead, most reference works describe lexico-grammatical patterns as if they applied generally to English.

The main goal of the present paper is to challenge this practice and the underlying assumption that the patterns of lexical-grammatical use in English can be described in general/global terms. Specifically, I argue that descriptions of the average patterns of use in a general corpus do not accurately describe any register. Rather, the patterns of use in speech are dramatically different from the patterns in writing (especially academic writing), and so minimally an adequate description must recognize the two major poles in this continuum (i.e., conversation versus informational written prose).

The paper begins by comparing two general corpus approaches to the study of language use: variationist and text-linguistic. Although both approaches can be used to investigate the use of words, grammatical features, and registers, the two approaches differ in their bases: the first gives primacy to each linguistic token, while the second gives primacy to each text. This difference has important consequences for the overall research design, the kinds of variables that can be measured, the statistical techniques that can be applied, and the particular research questions that can be asked. As a result, the importance of register has been more apparent in text-linguistic studies than in studies of linguistic variation.

The bulk of the paper, then, argues for the importance of register at all linguistic levels: lexical, grammatical, and lexico-grammatical. Analyses comparing conversation and academic writing are discussed for each level, showing how a general ‘average’ description includes some characteristics that are not applicable to one or the other register, while also omitting other important patterns of use found in particular registers.
Preparation and characterizations of ternary biodegradable blends composed of polylactide, poly(ε-caprolactone), and wood flour
Authors: Liao Hsin-Tzu , Wu Chin-San
Published: September 2012

Melt blending of polylactide (PLA), poly(ε-caprolactone) (PCL), and wood flour (WF) was performed in an effort to overcome the major drawbacks (brittleness and high price) of PLA. In addition, the acrylic acid (AA)-grafted PLA70PCL30 (PLA70PCL30-g-AA) was used as the alternative for the preparation of ternary blends to improve the compatibility and the dispersability of WF within the PLA70PCL30 matrix. As expected, PCL improved the elongation at break and the toughness of PLA but decreased the tensile strength and modulus. Because the hydrophilic WF is dispersed physically in the hydrophobic PLA70PCL30 matrix, as the result of Fourier transform infrared analysis, the mechanical properties of PLA70PCL30 became noticeably worse when it was blended with WF. This problem was successfully conquered by using PLA70PCL30-g-AA to replace PLA70PCL30 due to the formation of an ester carbonyl group between PLA70PCL30-g-AA and WF. Furthermore, the PLA70PCL30-g-AA/WF blend provided a plateau tensile strength at break when the WF content was up to 50 wt%. PLA70PCL30/WF exhibited a tensile strength at break of approximately 3–25 MPa more than PLA70PCL30-g-AA/WF. By using p-cresol and tyrosinase, the enzymatic biodegradable test showed that PLA70PCL30-g-AA is somewhat more biodegradable than PLA70PCL30 because the former has better water absorption. After 16 weeks, the weight loss of the PLA70PCL30/WF (50 wt%) composite was >80%. PLA70PCL30-g-AA/WF exhibited a weight loss of approximately 1–12 wt% more than PLA70PCL30-g-AA/WF. It was also found that the addition of WF to PLA70PCL30 or PLA70PCL30-g-AA decreased the crystallinity of PLA and PCL in PLA70PCL30 or PLA70PCL30-g-AA and then increased their biodegradable property.
Statistical Inference and Decision Making in Conservation Biology
Authors: SALTZ DAVID
Published: September 2012

Since the formulation of hypothesis testing by Neyman and Pearson in 1933, the approach has been subject to continuous criticism. Yet, until recently this criticism, for the most part, has gone unheeded. The negative appraisal focuses mainly on the fact thatP-valuesprovide no evidential support for either the null hypothesis (H0) or the alternative hypothesis (Ha). Although hypothesis testing done under tightly controlled conditions can provide some insight regarding the alternative hypothesis based on the uncertainty ofH0, strictly speaking, this does not constitute evidence. More importantly, well controlled research environments rarely exist in field-centered sciences such as ecology. These problems are manifestly more acute in applied field sciences, such as conservation biology, that are expected to support decision making, often under crisis conditions. In conservation biology, the consequences of a Type II error are often far worse than a Type I error. The "advantage" afforded toH0by setting the probability of committing a Type I error (α) to a low value (0.05), in effect, increases the probability of committing a Type II error, which can lead to disastrous practical consequences. In the past decade, multi-model inference using information-theoretic or Bayesian approaches have been offered as better alternatives. These techniques allow comparing a series of models on equal grounds. Using these approaches, it is unnecessary to select a single "best" model. Rather, the parameters needed for decision making can be averaged across all models, weighted according to the support accorded each model. Here, I present a hypothetical example of animal counts that suggest a possible population decline, and analyze the data using hypothesis testing and an information-theoretic approach. A comparison between the two approaches highlights the shortcomings of hypothesis testing and advantages of multi-model inference.
A atenção à saúde do trabalhador nas unidades básicas de saúde do SUS: estudo de caso em Campinas, São Paulo
Authors: Balista Salma Regina Rodrigues , Santiago Sílvia Maria , Corrêa Filho Heleno Rodrigues
Published: September 2012

RESUMO OBJETIVO: avaliar o processo de implantação das ações de vigilância em saúde do trabalhador nas Unidades Básicas de Saúde (UBS) do SUS, em Campinas, SP. Métodos: foram usados métodos qualitativos e quantitativos para produzir uma aproximação sob diferentes aspectos do objeto em estudo. Os acidentes e as doenças relacionados ao trabalho registrados em 2006 foram eleitos para verificar se as UBS conduziram ações de vigilância e se ocorreram mudanças preventivas e protetoras no processo de trabalho e no ambiente. Realizamos entrevistas com os profissionais responsáveis pela vigilância em saúde do trabalhador das unidades. RESULTADOS: as ações de atenção à saúde e a notificação foram implantadas com êxito principalmente para acidentes de trabalho. Todavia, o vínculo das doenças relacionadas com o trabalho foi menos reconhecido. Os acidentes e as doenças receberam uma abordagem burocrática, negligenciando a relevância epidemiológica para a tomada de decisão. Trabalhadores do mercado informal não receberam ações específicas. A gestão dos sistemas locais de saúde ainda necessita de regras específicas para estabelecer seu papel na integração dos sistemas de informação com a vigilância da saúde do trabalhador na atenção primária. CONCLUSÃO: o presente estudo apontou que a descentralização da vigilância da saúde do trabalhador para a atenção primária foi parcialmente efetivada em Campinas.
Impacto de um programa piloto de promoção da saúde para trabalhadores marítimos de rebocadores
Authors: Baena Cristina Pellegrino , Muccillo-Baisch Ana Luísa , Almeida Tabajara Lucas , De La Rocha Clarice , Franco Ozéia Simões , Olmedo Daniel , Soares Maria Cristina Flores
Published: September 2012

RESUMO OBJETIVO: analisar um programa piloto de promoção de saúde com trabalhadores marítimos de rebocadores baseado no estímulo à prática de atividade física regular e no acompanhamento nutricional. METODOLOGIA: fizeram parte do estudo 10 trabalhadores do porto do Rio Grande, sul do Brasil, que foram submetidos a um programa de 22 semanas, composto de atividade física e acompanhamento nutricional regular. Antes e após a intervenção foram realizadas as seguintes avaliações: física, bioquímica sanguínea, VO2 máximo e qualidade de vida (WHOQOL Bref). Na análise foram utilizados os testes t de Student pareado, o de Wilcoxon e o de Correlação de Pearson. Resultados: foi verificado diminuição na média de peso (84,3 vs. 82,1 kg; p = 0,03), da circunferência abdominal (97,1 vs. 91,7 cm; p = 0,005) e do quadril (103,5 vs. 100,7 cm; p = 0,005). O tempo de atividade física se correlacionou com a redução da circunferência abdominal (r = 0,636; p = 0,048) e com o índice cintura-quadril (r = 0,683; p=0,03). Houve redução no número de trabalhadores com triglicerídeos alterados (7 vs. 3; p = 0,04). A análise da qualidade de vida não apresentou alteração. CONCLUSÃO: o modelo de intervenção de promoção de saúde proposto mostrou, para os trabalhadores participantes, resultados positivos em parâmetros importantes para o risco cardiovascular.
Genetically Engineered Cancer Models, But Not Xenografts, Faithfully Predict Anticancer Drug Exposure in Melanoma Tumors
Authors: Combest Austin J. , Roberts Patrick J. , Dillon Patrick M. , Sandison Katie , Hanna Suzan K. , Ross Charlene , Habibi Sohrab , Zamboni Beth , Müller Markus , Brunner Martin , Sharpless Norman E. , Zamboni William C.
Published: September 2012

Background.

Rodent studies are a vital step in the development of novel anticancer therapeutics and are used in pharmacokinetic (PK), toxicology, and efficacy studies. Traditionally, anticancer drug development has relied on xenograft implantation of human cancer cell lines in immunocompromised mice for efficacy screening of a candidate compound. The usefulness of xenograft models for efficacy testing, however, has been questioned, whereas genetically engineered mouse models (GEMMs) and orthotopic syngeneic transplants (OSTs) may offer some advantages for efficacy assessment. A critical factor influencing the predictability of rodent tumor models is drug PKs, but a comprehensive comparison of plasma and tumor PK parameters among xenograft models, OSTs, GEMMs, and human patients has not been performed.

Methods.

In this work, we evaluated the plasma and tumor dispositions of an antimelanoma agent, carboplatin, in patients with cutaneous melanoma compared with four different murine melanoma models (one GEMM, one human cell line xenograft, and two OSTs).

Results.

Using microdialysis to sample carboplatin tumor disposition, we found that OSTs and xenografts were poor predictors of drug exposure in human tumors, whereas the GEMM model exhibited PK parameters similar to those seen in human tumors.

Conclusions.

The tumor PKs of carboplatin in a GEMM of melanoma more closely resembles the tumor disposition in patients with melanoma than transplanted tumor models. GEMMs show promise in becoming an improved prediction model for intratumoral PKs and response in patients with solid tumors.
Briefing: Predicting ‘post-failure' structural condition in pressure-retaining structures
Authors: Dameron Robert A.
Published: September 2012

Highly accurate prediction of post-failure structural condition is increasingly essential for high-risk, pressure-retaining structures such as nuclear reactor and containment vessels, dams, tunnels and tanks. After a severe loading event occurs, determining exactly where, how large and how many leaks will result has become the holy grail of applied computational mechanics for this class of structures. This article concludes that as computational tools continue to improve, and the demand for quantitative leakage information increases, the use of finite-element-based fracture mechanics is on the rise for predicting the post-failure structural condition of such pressure-retaining structures.
A cnoidal approximation wave theory
Authors: Sobey Rodney J.
Published: September 2012

Periodic progressive waves in shallow to transitional water are described by a cnoidal approximation wave theory. The formulation is analytical and largely classical. Periodic waves are assumed, so that the theory does not extend to solitary waves. The solution is completed numerically, as a problem in non-linear optimisation. The suitability of the theory in shallow to transitional water is demonstrated to 88% of the limit wave height.
Mapping Tobacco Quitlines in North America: Signaling Pathways to Improve Treatment
Authors: Leischow Scott J. , Provan Keith , Beagles Jonathan , Bonito Joseph , Ruppel Erin , Moor Gregg , Saul Jessie
Published: September 2012

Objectives. This study was designed to better understand how the network of quitlines in the North American Quitline Consortium (NAQC) interact and share new knowledge on quitline practices.

Methods. Network relationship data were collected from all 63 publicly funded quitlines in North America, including information sharing, partner trust, and reputation.

Results. There was a strong tendency for US and Canadian quitlines to seek information from other quitlines in the same country, with few seeking information from quitlines from the other country. Quitlines with the highest reputation tended to more centrally located in the network, but the NAQC coordinating organization is highly central to the quitline network—thus demonstrating their role as a broker of quitline information.

Conclusions. This first “snapshot” of US and Canadian quitlines demonstrated that smoking cessation quitlines in North America are not isolated, but are part of an interconnected network, with some organizations more central than others. As quitline use expands with the inclusion of national toll-free numbers on cigarette packs, how quitlines share information to improve practice will become increasingly important.
Effectiveness of a Risk Screener in Identifying Hepatitis C Virus in a Primary Care Setting
Authors: Drainoni Mari-Lynn , Litwin Alain H. , Smith Bryce D. , Koppelman Elisa A. , McKee M. Diane , Christiansen Cindy L. , Gifford Allen L. , Weinbaum Cindy M. , Southern William N.
Published: September 2012

Objectives. We evaluated an intervention designed to identify patients at risk for hepatitis C virus (HCV) through a risk screener used by primary care providers.

Methods. A clinical reminder sticker prompted physicians at 3 urban clinics to screen patients for 12 risk factors and order HCV testing if any risks were present. Risk factor data were collected from the sticker; demographic and testing data were extracted from electronic medical records. We used the t test, χ2 test, and rank-sum test to compare patients who had and had not been screened and developed an analytic model to identify the incremental value of each element of the screener.

Results. Among screened patients, 27.8% (n = 902) were identified as having at least 1 risk factor. Of screened patients with risk factors, 55.4% (n = 500) were tested for HCV. Our analysis showed that 7 elements (injection drug use, intranasal drug use, elevated alanine aminotransferase, transfusions before 1992, ≥ 20 lifetime sex partners, maternal HCV, existing liver disease) accounted for all HCV infections identified.

Conclusions. A brief risk screener with a paper-based clinical reminder was effective in increasing HCV testing in a primary care setting.
Incidence of Disability Among Children 12 Months After Traumatic Brain Injury
Authors: Rivara Frederick P. , Koepsell Thomas D. , Wang Jin , Temkin Nancy , Dorsch Andrea , Vavilala Monica S. , Durbin Dennis , Jaffe Kenneth M.
Published: September 2012

Objectives. We examined the burden of disability resulting from traumatic brain injuries (TBIs) among children younger than 18 years.

Methods. We derived our data from a cohort study of children residing in King County, Washington, who were treated in an emergency department for a TBI or for an arm injury during 2007–2008. Disabilities 12 months after injury were assessed according to need for specialized educational and community-based services and scores on standardized measures of adaptive functioning and social–community participation.

Results. The incidence of children receiving new services at 12 months was about 10-fold higher among those with a mild TBI than among those with a moderate or severe TBI. The population incidence of disability (defined according to scores below the norm means on the outcome measures included) was also consistently much larger (2.8-fold to 28-fold) for mild TBIs than for severe TBIs.

Conclusions. The burden of disability caused by TBIs among children is primarily accounted for by mild injuries. Efforts to prevent these injuries as well as to decrease levels of disability following TBIs are warranted.
The Role of Personal Attributes in the Genesis and Progression of Lung Disease and Cigarette Smoking
Authors: Brook Adam , Zhang Chenshu
Published: September 2012

Objectives. We examined early maladaptive personal attributes (e.g., depression), later lung disease, and later maladaptive personal attributes over a significant part of a woman’s life.

Methods. We gathered longitudinal data on a prospective cohort of community-dwelling women (n = 498) followed from young adulthood to late midlife.

Results. We used structural equation modeling to assess the interrelations of maladaptive personal attributes, cigarette smoking, lung disease, and financial strain. The results supported a mediational model through which early maladaptive personal attributes were associated with smoking (b = 0.17, P < .001), which in turn predicted later lung disease (b = 0.33, P < .001), and lung disease was related to later family financial difficulties (b = 0.09, P < .05), which in turn were associated with later maladaptive personal attributes (b = 0.35, P < .001).

Conclusions. Our results address a number of important public health and clinical issues. An understanding of the interrelations of smoking, underlying mental health conditions, financial stress, and later mental health conditions on the part of physicians and other health care providers can be critical in managing patients with lung disease.
Household Food Insecurity During Childhood and Subsequent Health Status: The Early Childhood Longitudinal Study—Kindergarten Cohort
Authors: Ryu Jeong-Hee , Bartfeld Judith S.
Published: September 2012

Objectives. We examined long-term patterns of household food insecurity in children from kindergarten through eighth grade and the association between those patterns and children’s proxy-reported health status in eighth grade.

Methods. We obtained data from the Early Childhood Longitudinal Study—Kindergarten Cohort, a study that followed a nationally representative sample of students from kindergarten entry in 1998–1999 through eighth grade. We classified food insecurity according to the number of years of reported household food insecurity over 4 observation years. We estimated logistic regression models to estimate the association between cumulative food insecurity exposure and health outcomes.

Results. Food insecurity was generally a transient rather than a persistent condition. Persistent food insecurity over the 9-year period was associated with lower health status in eighth grade, whereas more transient food insecurity was not significantly associated with health outcomes in most models.

Conclusions. Single-year estimates substantially underestimate the share of children whose households experienced food insecurity at some point during their childhood years. Persistent food insecurity is an important public health issue for children. Policy interventions to alleviate children’s persistent food insecurity may promote child health.
Common Fragile Sites: Genomic Hotspots of DNA Damage and Carcinogenesis
Authors: Ma Ke , Qiu Li , Mrasek Kristin , Zhang Jun , Liehr Thomas , Quintana Luciana Gonçalves , Li Zheng
Published: September 2012

Genomic instability, a hallmark of cancer, occurs preferentially at specific genomic regions known as common fragile sites (CFSs). CFSs are evolutionarily conserved and late replicating regions with AT-rich sequences, and CFS instability is correlated with cancer. In the last decade, much progress has been made toward understanding the mechanisms of chromosomal instability at CFSs. However, despite tremendous efforts, identifying a cancer-associated CFS gene (CACG) remains a challenge and little is known about the function of CACGs at most CFS loci. Recent studies of FATS (for Fragile-site Associated Tumor Suppressor), a new CACG at FRA10F, reveal an active role of this CACG in regulating DNA damage checkpoints and suppressing tumorigenesis. The identification of FATS may inspire more discoveries of other uncharacterized CACGs. Further elucidation of the biological functions and clinical significance of CACGs may be exploited for cancer biomarkers and therapeutic benefits.
Anti-Epidermal Growth Factor Receptor (EGFR) Antibodies Overcome Resistance of Ovarian Cancer Cells to Targeted Therapy and Natural Cytotoxicity
Authors: Gottschalk Nina , Kimmig Rainer , Lang Stephan , Singh Mahavir , Brandau Sven
Published: September 2012

The poor outcome of advanced ovarian cancer under conventional therapy stimulated the exploration of new strategies to improve therapeutic efficacy. In our preclinical in vitro study we investigated a combination of targeted therapy and immunotherapy. Combination treatment with the anti-EGFR-antibody Cetuximab, related tyrosine kinase inhibitors (TKI) and cytolytic NK cells was tested against different ovarian cancer cell lines and primary tumour cells cultured from patient ascites. We found that selected ovarian cancer cells were susceptible to cetuximab and anti-EGFR-TKI-treatment, while the majority of cell lines were resistant to single or combination treatment with both substances. In addition, most ovarian cancer cells displayed low susceptibility to natural cytotoxicity of unstimulated NK cells. Notably, NK cytotoxicity against resistant ovarian cancer cells could be effectively enhanced by addition of Cetuximab mediating antibody-dependent cellular cytotoxicity (ADCC). Neither natural cytotoxicity nor ADCC of NK cells were negatively affected by the presence of TKIs. ADCC could be further increased when NK cells were pre-stimulated with monocytes and the immunostimulatory mycobacterial protein PstS-1. Our data suggest that targeted antibody therapy could be beneficial even against resistant tumour cells by augmenting supplementary cytolytic NK functions. Future studies should evaluate the combination of targeted therapy and immunotherapeutic approaches in patients with advanced ovarian cancer being resistant to standard treatment.
Clinical Trial: Marine Lipid Suppositories as Laxatives
Authors: Ormarsson Orri Thor , Geirsson Thormodur , Bjornsson Einar Stefan , Jonsson Tomas , Moller Pall Hegli , Loftsson Thorsteinn , Stefansson Einar
Published: September 2012

Cod-liver oil and other marine products containing polyunsaturated fatty acids have anti-inflammatory, anti-bacterial and anti-viral effects and may be useful in the treatment of various inflammatory and infectious diseases. We developed suppositories and ointment with 30% free fatty acid (FFA) extract from omega-3 fish oil. Our purpose was to evaluate the safety of marine lipid suppositories and ointment in healthy volunteers and to explore the laxative effect of the suppositories. Thirty healthy volunteers were randomized either to a study group administrating 30% FFA suppositories and applying 30% FFA ointment to the perianal region twice per day for two weeks, or to a control group using placebo suppositories and ointment in a double blinded manner. Results: No serious toxic effects or irritation were observed. In the study group 93% felt the urge to defecate after administration of the suppositories as compared to 37% in the control group (P = 0.001). Subsequently 90% in the study group defecated, compared to 33% in the control group (P = 0.001). Conclusion: The marine lipid suppositories and ointment were well tolerated with no significant toxic side effects observed during the study period. The suppositories have a distinct laxative effect and we aim to explore this effect in further clinical trials.
Global connexity and circulation of knowledge
Authors: Arellano Hernández Antonio , Arvanitis Rigas , Vinck Dominique
Published: September 2012

The authors show how scientific and technological research in Latin America has become institutionalised and has given rise to science policy questions and debates. This development has become a subject of study. Thus, the text describes the emergence and development of social studies on science in Latin America since the 1950s with the development of an original Latin American thought on science and technology (PLACTS), the formation of the first social studies on science and technology (STS) research groups working on scientific disciplines and producing diagnoses on the scientific development, then the institutionalisation of these STS studies and the consolidation of research groups in this domain giving rise to new approaches concerning the conditions of scientific development in a peripheral context, the social and local utility of scientific and technological knowledge, the processes of re-signifying established knowledge, the creation of new relations between research and industry and the emergence of research policies. Finally, the text shows how Latin American researchers are today questioning the articulations between local and globalized knowledge, between local activities and policies and global networks, and the role of technological knowledge in Latin America in a globalized world, which raises a reflexive questioning of the role of STS-produced research in Latin American societies.
Internet et les nouvelles formes de liens publics/artistes
Authors: Garcin Pierre
Published: September 2012

Résumé Le nombre de groupes/artistes en activité n’a cessé d’augmenter depuis les trente glorieuses. Leurs partenaires traditionnels, les maisons de disques, connaissent depuis le début des années 2000 une baisse importante de leurs revenus et ont réduit leurs dépenses dans le développement des projets émergents. Internet s’est imposé comme moyen d’autopromotion à la portée de tous, mais la concurrence y est tout aussi importante. Certains artistes sont parvenus à se démarquer en développant des liens avec une audience de passionnés, souvent artistes eux-mêmes ou impliqués dans les médias numériques (webzines, webradios). Ces passionnés sont souvent le premier public des artistes émergents. Désireux de pouvoir développer une relation personnalisée avec l’artiste, leur investissement peut s’avérer suffisant pour permettre à des groupes/projets/artistes de développer leur carrière, pour peu que ceux-ci parviennent à utiliser au mieux les potentialités offertes par le réseau et à développer un lien avec leur public qui dépasse le simple cadre producteur/acheteur.
Technology and the Multipolar Global Economy
Authors: McGuire Steven
Published: September 2012

The European Union has engaged in several attempts to increase the level of innovation in member states – largely without success. This chapter argues that a combination of global and regional issues explain this failure. What was once a process dominated by Europe and America, innovation is “going global,” with many countries now developing national innovation systems. European firms are conducting more of their research in emerging markets, and in Europe, firms seem unable to raise their share of overall research and development spending. The Commission, for its part, lacks the necessary regulatory and legislative powers to forge a new regional innovation system and is instead reliant on a policy mix of overarching objectives, some directed funding, and comparative analysis of member state policies.
GIS Technique for Territorial Analysis
Authors: Riccioli Francesco , El Asmar Toufic
Published: September 2012

Territorial analysis is related to the complexity of an area where human activities and environmental characteristics are the main development factors. Human activities have a direct (e.g. farm activities) and indirect (e.g. urban development/sprawl) influence on a territory and its environment, which gives an important function to such activities when strategies for territorial planning have to be defined. Several actors are involved in the assessment of a territory, which is a complicated feature of decision making to be achieved with the use of complex data-analysis process. The evolution of personal computer and specific software for the analysis of spatial data is giving important contribution to “Territorial Planning Strategies.” Spatial Decision Support System is an example of how problems occurred during a decision making process can be solved using methodologies that combine “Multicriteria Approach” and “Geographic Information System.” One of these methodologies is represented by “Spatial Multicriteria Decision Analysis.”
Design and Implementation Approaches for Location-Based, Tourism-Related Services
Authors: Kakaletris George , Varoutas Dimitris , Katsianis Dimitris , Sphicopoulos Thomas
Published: September 2012

The globally observed recession of mobile services market has pushed mobile network operators into looking for opportunities to provide value added services on top of their high cost infrastructures. Recent advances in mobile positioning technologies enable services that make use of the mobile user location information, offering intuitive, attractive applications to the potential customer. Mobile tourism services are among the primary options to be considered by service providers for this new market. This chapter presents the key concepts, capabilities, and considerations of infrastructures and applications targeted to the mobile tourist, covering data and content delivery, positioning, systems’ interactions, platforms, protocols, security, and privacy as well as business modelling aspects.