bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular Safety of Plant Sterol and Stanol Consumption
Authors: Silbernagel Guenther , Baumgartner Iris , März Winfried
Published: May 2015

Plant sterols and stanols as components of functional foods are widely used for cholesterol lowering. The regular intake of these functional foods is associated with a decrease in low density lipoprotein cholesterol of about 10 % and an increase in plasma plant sterol or stanol concentrations by about a factor of 2. There is no doubt that a decrease in low density lipoprotein cholesterol is beneficial to cardiovascular health. However, due to the concomitant increase in circulating plant sterols safety issues associated with the intake of plant sterol containing functional foods have been raised. Herein, we will review and evaluate those arguments raised against the use of plant sterols and stanols.
The Atherogenicity of Plant Sterols: The Evidence from Genetics to Clinical Trials
Authors: Weingärtner Oliver , Teupser Daniel , Patel Shailendra B
Published: May 2015

The human diet is naturally varied and contains not only essential nutrients, but also contains molecules that the body actively excludes or minimizes exposure. Among these molecules are xenosterols, of which plant sterols comprise the greatest exposure risk. These sterols comprise approximately 50% of the total sterols we eat, yet we retain <0.5% of these in our bodies. The bulk of this exclusion takes place in the intestine and the heterodimeric transporters ABCG5 and ABCG8 are key to keeping these xenosterols out of our bodies. In normal humans, pharmacological supplementation with plant sterols (and stanols) has been used to lower cholesterol as these impair intestinal absorption/ re-absorption of this molecule; lowering plasma cholesterol has cardiovascular risk benefits. This review challenges whether this intervention is beneficial and may even be harmful. We summarize the evidence involving humans who have genetic disruption of ABCG5/ABCG8 function, from clinical trial data examining plant sterols and cardiovascular risk, from genetic data affecting normal humans and ABCG5/ABCG8 variations to data obtained using animal models. Accumulation of xenosterols in any significant amount is clearly associated with increased toxicity, and data suggest that at even low levels there may be effects. Importantly, there is also a paucity of data showing cardiovascular end-point benefits with plant sterol/stanol supplementation. The summary of evidence highlights not only caution in recommending such strategies to lower plasma cholesterol, but also in investigating how these xenosterols can affect processes ranging from cardiovascular, endocrine, and neurological function.
Regulatory Aspects Related to Plant Sterol and Stanol Supplemented Foods
Authors: Zawistowski Jerzy , Jones Peter
Published: May 2015

This chapter reviews regulatory frameworks for plant sterol containing functional foods in various jurisdictions including Europe, North America, South America, Asia and, Australia/New Zealand. Included is a discussion on approval of plant sterols as novel food ingredients in some countries, as well as details on the type of health claims permitted in the marketing and sale of foods enriched with plant sterols within each jurisdiction. Based on the abundance of clinical trial data, many countries around the world have now approved the use of claims relating the cholesterol-lowering effect of plant sterols, further attesting to their value as functional food ingredients.
May 2015 Problems
Authors: Amidon Joel , Roscoe Matt
Published: May 2015

A monthly set of problems is aimed at a variety of ability levels.
Enhancing Students' Understanding of Square Roots
Authors: Wiesman Jeff L.
Published: May 2015

Students enrolled in a middle school prealgebra or algebra course often struggle to conceptualize and understand the meaning of radical notation when it is introduced. For example, although it is important for students to approximate the decimal value of a number such as √30 and estimate the value of a square root in the form ofa√b, many would struggle with such assignments. Similarly, students frequently have difficulties understanding, remembering, and applying the properties of radicals.
How Many Legs?
Authors: Kastberg Signe E.
Published: May 2015

Problem solving in the early grades draws from children's fantasy and imagination informed by early adventures in reading and life (Paley 1986). The richness of their insights coupled with newly created structures for reasoning quantitatively create opportunities for teachers and children to communicate what they “see” in images often not considered as mathematical problems. Such is the case with the illustration from Charlotte's Web (White 1952, p. 21) that captures the chaos of Lurvy, a farm hand, trying to catch the lovable pig Wilbur after he escapes into the barnyard. Legs are everywhere and, as other animals look on, Wilber continues to evade Lurvy. But how many legs are there?
Top Hat Organizer
Authors: Pace Michelle
Published: May 2015

Graphic organizers are as common in classrooms as books and desks; however, they are a valuable resource that is often underused in mathematics. A rich resource for engaging students in the Common Core's Standards for Mathematical Practice (SMPs), the Top Hat Organizer allows students to visually organize and structure information to see connections, patterns, and relationships between concepts. To use this organizer, set up two concepts against each other on the top of the hat. Each concept serves as a frame of reference for examining the other, which allows students to engage deeply with the topic of focus. With the descriptions complete, students can write powerful comparisons in the hat brim.
Gender Differences in Mathematics and Reading Trajectories among Children from Kindergarten to Eighth Grade
Authors: Wei Tianlan , Liu Xun , Barnard-Brak Lucy
Published: May 2015

This study examined children's trajectories of mathematics and reading achievements from kindergarten to eighth grade along with the gender differences in these trajectories. A total of 8503 participants drawn from the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K) formed the sample of the study. The results of the latent growth curve modeling indicate that (a) children's growth is curvilinear, specially, quadratic for both mathematics and reading achievement, and their growth in reading demonstrate a more complex pattern than that of mathematics; (b) there appear to be positive correlations between the intercept parameter (i.e. initial status) and the slope parameter (i.e. growth rate) in both reading and mathematics trajectories, indicating the ‘Matthew effects’ in education; (c) despite the statistically equivalent initial status in mathematics, boys outperform girls as early as first grade in both achievement score and positive growth rate; (d) for reading trajectories, girls outperform boys in both initial status and positive growth rate starting the baseline measurement. Finally, limitations and recommendations for future studies are discussed.
Ultrasound-Guided Pulsed Radio Frequency Treatment in Morton's Neuroma
Authors: Deniz Suleyman , Purtuloglu Tarik , Tekindur Sukru , Cansız Kadir Hakan , Yetim Memduh , Kılıckaya Oguz , Senkal Serkan , Bilgic Serkan , Atim Abdulkadir , Kurt Ercan
Published: May 2015

Background

Morton's neuroma is a perineural fibrosis of an intermetatarsal plantar nerve. Burning, numbness, paresthesia, and tingling down the interspaces of involved toes may also be experienced. Taking into account all of this information, we designed a prospective open-label study to evaluate the efficacy of pulsed radio frequency on Morton's neuroma.

Methods

Twenty patients with Morton's neuroma were experiencing symptomatic neuroma pain in the foot not relieved by routine conservative treatment. All of the patients had been evaluated by a specialized orthopedist and were offered pulsed radio frequency as a last option before having surgery. Initially, pain level (numerical rating scale), successful pain control (a ≥50% pain decrease was accepted as successful pain control), comfort when walking (yes or no), and satisfaction level (satisfied or not satisfied) were evaluated.

Results

We found a decrease in the pain level in 18 of 20 patients, successful pain control in 12, and wearing shoes and walking without pain in 16. Overall, satisfaction was rated as excellent or good by 12 patients with Morton's neuroma in this series.

Conclusions

This evidence indicates that ultrasound-guided pulsed radio frequency is a promising treatment modality in the management of Morton's neuroma pain.
MorphoGraphX: A platform for quantifying morphogenesis in 4D
Authors: Barbier de Reuille Pierre , Routier-Kierzkowska Anne-Lise , Kierzkowski Daniel , Bassel George W , Schüpbach Thierry , Tauriello Gerardo , Bajpai Namrata , Strauss Sören , Weber Alain , Kiss Annamaria , Burian Agata , Hofhuis Hugo , Sapala Aleksandra , Lipowczan Marcin , Heimlicher Maria B , Robinson Sarah , Bayer Emmanuelle M , Basler Konrad , Koumoutsakos Petros , Roeder Adrienne HK , Aegerter-Wilmsen Tinri , Nakayama Naomi , Tsiantis Miltos , Hay Angela , Kwiatkowska Dorota , Xenarios Ioannis , Kuhlemeier Cris , Smith Richard S
Published: May 2015

Morphogenesis emerges from complex multiscale interactions between genetic and mechanical processes. To understand these processes, the evolution of cell shape, proliferation and gene expression must be quantified. This quantification is usually performed either in full 3D, which is computationally expensive and technically challenging, or on 2D planar projections, which introduces geometrical artifacts on highly curved organs. Here we present MorphoGraphX (www.MorphoGraphX.org), a software that bridges this gap by working directly with curved surface images extracted from 3D data. In addition to traditional 3D image analysis, we have developed algorithms to operate on curved surfaces, such as cell segmentation, lineage tracking and fluorescence signal quantification. The software's modular design makes it easy to include existing libraries, or to implement new algorithms. Cell geometries extracted with MorphoGraphX can be exported and used as templates for simulation models, providing a powerful platform to investigate the interactions between shape, genes and growth.
Computations underlying Drosophila photo-taxis, odor-taxis, and multi-sensory integration
Authors: Gepner Ruben , Mihovilovic Skanata Mirna , Bernat Natalie M , Kaplow Margarita , Gershow Marc
Published: May 2015

To better understand how organisms make decisions on the basis of temporally varying multi-sensory input, we identified computations made by Drosophila larvae responding to visual and optogenetically induced fictive olfactory stimuli. We modeled the larva's navigational decision to initiate turns as the output of a Linear-Nonlinear-Poisson cascade. We used reverse-correlation to fit parameters to this model; the parameterized model predicted larvae's responses to novel stimulus patterns. For multi-modal inputs, we found that larvae linearly combine olfactory and visual signals upstream of the decision to turn. We verified this prediction by measuring larvae's responses to coordinated changes in odor and light. We studied other navigational decisions and found that larvae integrated odor and light according to the same rule in all cases. These results suggest that photo-taxis and odor-taxis are mediated by a shared computational pathway.
Active flexural‐slip faulting: A study from the Pamir‐Tian Shan convergent zone, NW China
Authors: Li Tao , Chen Jie , Thompson Jessica A. , Burbank Douglas W. , Yang Xiaodong
Published: May 2015

The flexural‐slip fault (FSF), a type of secondary fault generated by bed‐parallel slip, occurs commonly and plays an important role in accommodating fold growth. Although the kinematics and mechanics of FSFs are well studied, relatively few field observations or geometric models explore its geomorphic expression. In the Pamir‐Tian Shan convergent zone, NW China, suites of well‐preserved FSF scarps displace fluvial terraces in the Mingyaole and Wulagen folds. Integrating interpretations of Google Earth images, detailed geologic and geomorphic mapping, and differential GPS measurements of terrace surfaces, we summarize geomorphic features that typify these faults and create kinematic models of active flexural‐slip faulting. Our study indicates the following: (i) FSF scarps commonly occur near synclinal hinges, irrespective of whether (a) the dip direction of beds on either side of the hinge is unidirectional or in opposite directions, (b) the hinge is migrating or fixed, or (c) the hinge shape is narrow and angular or wide and curved. (ii) Active FSFs are likely to produce higher scarps on steeper beds, whereas lower or no topographic scarps typify gentler beds. (iii) Tilt angles of the terrace surface displaced above FSFs progressively decrease farther away from the hinge, with abrupt changes in slope coinciding with FSF scarps; the changes in tilt angle and scarp height have a predictable geometric relationship. (iv) Active FSFs can accommodate a significant fraction of total slip and play a significant role in folding deformation. (v) Active FSFs may be used to assess seismic hazards associated with active folds and associated blind thrusts.
Spatial patterns of radiative forcing and surface temperature response
Authors: Shindell Drew T. , Faluvegi Greg , Rotstayn Leon , Milly George
Published: May 2015

Examination of effective radiative forcing (ERF), a measure of changes in Earth's energy balance, facilitates understanding the role of various drivers of climate change. For short‐lived compounds, ERF can be highly inhomogeneous geographically. The relationship between the spatial patterns of ERF and surface temperature response is poorly characterized, however. We examine that relationship in the latest generation of global climate models. We find that the uneven distribution of historical aerosol, ozone, and land use forcing leads to substantial differences compared to the well‐mixed greenhouse gases (WMGHG). There is a stronger response per unit global mean forcing to historical inhomogeneous forcing than to WMGHG both globally and in much of the Northern Hemisphere (NH) extratropics, in fairly good agreement with results inferred from observations. Our results indicate that the enhanced global mean response is attributable to the concentration of inhomogeneous forcing in the NH extratropics, where there is strongest sensitivity to forcing, rather than to processes specific to the inhomogeneous forcers. In many regions, inclusion of inhomogeneous forcing greatly increases the spread in historical temperature changes simulated by the models, suggesting that better forcing characterization could play an important role in improving modeling of decadal‐scale regional climate change. Finally, incorporating observed temperatures, the results provide estimates of global historical aerosol forcing (−1.0 ± 0.4 W m−2) consistent with other studies (though with narrower uncertainties) and also provide constraints on NH and NH extratropical historical aerosol forcing (−1.4 ± 0.6 and −1.2 ± 0.6 W m−2, respectively) and aerosol + ozone forcing.
The lithosphere‐asthenosphere transition and radial anisotropy beneath the Australian continent
Authors: Yoshizawa K. , Kennett B. L. N.
Published: May 2015

A new 3‐D S wave speed model for the Australian region derived from multimode surface waves allows us to examine the nature of the lithosphere‐asthenosphere transition (LAT) and its relation to radial anisotropy. In eastern Phanerozoic Australia the estimated depths of the LAT tie well with those from receiver functions. However, in the Archean and Proterozoic lithosphere in western and central Australia, the LAT derived from the surface wave model is generally much deeper than the discontinuities recognized from receiver functions and shows a smooth transition. There is significant radial anisotropy (SH > SV) in the upper lithosphere as well as in the LAT and the underlying asthenosphere. Strong anisotropy in the asthenosphere reflects the effects of present shear flow in the mantle beneath the continent. The lateral variation of lithospheric anisotropy correlates well with the suture zones between cratonic blocks, representing frozen anisotropy associated with the ancient tectonics of Australia.
Cloud‐radiative driving of the Madden‐Julian oscillation as seen by the A‐Train
Authors: Del Genio Anthony D. , Chen Yonghua
Published: May 2015

Cloud and water vapor radiative heating anomalies associated with convection may be an effective source of moist static energy driving the Madden‐Julian Oscillation (MJO). In this paper 5 years of radiative heating profiles derived from CloudSat radar and Cloud‐Aerosol Lidar and Infrared Pathfinder Satellite Observation data are analyzed to document radiative heating anomalies during the MJO. Atmospheric shortwave absorption and surface longwave radiation anomalies are of opposite sign and 10–20% as large as top‐of‐atmosphere outgoing longwave radiation (OLR) anomalies, confirming that OLR provides a useful estimate of the total column radiative heating anomaly. Positive anomalies generally peak about 1 week before the MJO peak and are smallest over the Indian Ocean. Anomalies over the Maritime Continent are strongest and coincident with the MJO peak. Shortwave heating profile anomalies are weaker than longwave anomalies in the active region of the MJO but generally of opposite sign; thus, shortwave heating damps the longwave destabilization of the lower troposphere. The exception is the onset phase of the MJO, where shortwave and longwave heating anomalies due to thin cirrus are both positive in the upper troposphere and exert a stabilizing influence. Specific humidity anomalies in the middle troposphere reach 0.5 g kg−1, but the associated clear‐sky heating anomaly is small. Radiative enhancement of column moist static energy becomes significant as precipitation increases before the MJO peak and remains high after the MJO peak as precipitation begins to decline. Elevated radiative heating after the peak may contribute to destabilizing the MJO.
Chemical Alkaline Etching of Silicon Mie Particles
Authors: Proust Julien , Bedu Frédéric , Chenot Stéphane , Soumahoro Ibrahima , Ozerov Igor , Gallas Bruno , Abdeddaim Redha , Bonod Nicolas
Published: May 2015

Chemical etching via alkaline solutions is associated with electronic litho­graphy to structure at a nanometer scale silicon Mie resonators. Two different alkaline solutions are employed and their influences on the shape of the resonators are discussed. The method is applied on both amorphous and crystalline silicon coatings and silicon resonators are characterized by electron microscopy and optical spectroscopy, and then the different modes are identified thanks to numerical simulations. This method avoids the use of reactive ion etching and appears to be very well adapted to design silicon particles at a nanometer scale for applications in nanophotonics.
Breastfeeding over two years is associated with longer birth intervals, but not measures of growth or health, among children in Kilimanjaro, TZ
Authors: Mattison Siobhán M. , Wander Katherine , Hinde Katie
Published: May 2015

Objectives

Breastfeeding has been associated with numerous health and well‐being benefits for both children and their mothers, including prolonging the birth interval to the subsequent sibling. The clearest associations between breastfeeding and health outcomes, per se, reflect exclusive breastfeeding in the first months of postnatal life and are most evident during infancy. Fewer studies explore the consequences of breastfeeding for multiple years. In this article, we ask whether breastfeeding for more than 2 years is associated with discernible health and well‐being benefits to children.

Methods

Data were collected from 315 children, aged 2 to 7, and their caretakers residing in Kilimanjaro, Tanzania. Basic demographic and health information was solicited, and anthropometric and blood markers of health were evaluated.

Results

Our results indicate a strong positive relationship between breastfeeding for 2 or more years and interbirth interval, but little evidence for a relationship between prolonged breastfeeding and several indicators of child growth and health.

Conclusions

We suggest that these relationships may support the recently rekindled birth spacing hypothesis, positing selection for longer interbirth intervals, rather than, or in addition to, more direct health benefits associated with breastfeeding for 2 or more years. Our results may indicate attenuating health benefits associated with longer breastfeeding. Am. J. Hum. Biol. 27:807–815, 2015. © 2015 Wiley Periodicals, Inc.
Risk of cancer among firefighters in California, 1988–2007
Authors: Tsai Rebecca J. , Luckhaupt Sara E. , Schumacher Pam , Cress Rosemary D. , Deapen Dennis M. , Calvert Geoffrey M.
Published: May 2015

Background

Most studies of firefighter cancer risks were conducted prior to 1990 and do not reflect risk from advances in building materials.

Methods

A case–control study using California Cancer Registry data (1988–2007) was conducted to evaluate the risk of cancer among firefighters, stratified by race.

Results

This study identified 3,996 male firefighters with cancer. Firefighters were found to have a significantly elevated risk for melanoma (odds ratio [OR] = 1.8; 95% confidence interval [CI] 1.4–2.1), multiple myeloma (OR 1.4; 95%CI 1.0–1.8), acute myeloid leukemia (OR 1.4; 95%CI 1.0–2.0), and cancers of the esophagus (OR 1.6; 95%CI 1.2–2.1), prostate (OR 1.5; 95%CI 1.3–1.7), brain (OR 1.5; 95%CI 1.2–2.0), and kidney (OR 1.3; 95%CI 1.0–1.6).

Conclusions

In addition to observing cancer findings consistent with previous research, this study generated novel findings for firefighters with race/ethnicity other than white. It provides additional evidence to support the association between firefighting and several specific cancers. Am. J. Ind. Med. 58:715–729, 2015. © 2015 This article has been contributed to by US Government employees and their work is in the public domain in the USA.
The predictive power of family history measures of alcohol and drug problems and internalizing disorders in a college population
Authors: Kendler Kenneth S , Edwards Alexis , Myers John , Cho Seung Bin , Adkins Amy , Dick Danielle
Published: May 2015

A family history (FH) of psychiatric and substance use problems is a potent risk factor for common internalizing and externalizing disorders. In a large web‐based assessment of mental health in college students, we developed a brief set of screening questions for a FH of alcohol problems (AP), drug problems (DP) and depression‐anxiety in four classes of relatives (father, mother, aunts/uncles/grandparents, and siblings) as reported by the student. Positive reports of a history of AP, DP, and depression‐anxiety were substantially correlated within relatives. These FH measures predicted in the student, in an expected pattern, dimensions of personality and impulsivity, alcohol consumption and problems, smoking and nicotine dependence, use of illicit drugs, and symptoms of depression and anxiety. Using the mean score from the four classes of relatives was more predictive than using a familial/sporadic dichotomy. Interactions were seen between the FH of AP, DP, and depression‐anxiety and peer deviance in predicting symptoms of alcohol and tobacco dependence. As the students aged, the FH of AP became a stronger predictor of alcohol problems. While we cannot directly assess the validity of these FH reports, the pattern of findings suggest that our brief screening items were able to assess, with some accuracy, the FH of substance misuse and internalizing psychiatric disorders in relatives. If correct, these measures can play an important role in the creation of developmental etiologic models for substance and internalizing psychiatric disorders which constitute one of the central goals of the overall project. © 2015 Wiley Periodicals, Inc.
Preparation of conductive polyphenylene sulfide/polyamide 6/multiwalled carbon nanotube composites using the slow migration rate of multiwalled carbon nanotubes from polyphenylene sulfide to polyamide 6
Authors: Xu Ling , Zhang Bo‐Yuan , Xiong Zhuo‐Yue , Guo Zhao‐Xia , Yu Jian
Published: May 2015

Conductive polyphenylene sulfide (PPS)/polyamide 6 (PA6)/multiwalled carbon nanotube (MWCNT) composites having 10–30 wt % PA6 and 1 wt % MWCNTs are prepared by melt mixing at 300°C for 8 min using a high concentration PPS/MWCNT masterbatch approach, and the migration kinetics of MWCNTs from thermodynamically unfavored PPS to favored PA6 was investigated. The morphology of the composites was investigated by field emission scanning electron microscopy and transmission electron microscopy, showing the localization of most MWCNTs in the PPS phase and at the interface, being different from the case of direct melt mixing where non‐conductive materials were obtained with most MWCNTs found in the PA6 phase and at the interface. The electrical resistivity and morphology of the materials as a function of time were investigated, showing that the conductive materials can be prepared within a mixing time of 4–16 min because of the slow migration rate of MWCNTs from PPS toward PA6, and MWCNTs can eventually migrate into the PA6 phase after a long mixing time of 30 min. The slow migration rate of MWCNTs was attributed to the high viscosity ratio of the two phases. This article shows a good example where the migration of MWCNTs was slow enough to control and can be used to prepare conductive polymer blends. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42353.
Geometric Approaches to State Feedback Control for Continuous and Switched Linear Systems
Authors: Bajcinca N. , Flockerzi D.
Published: May 2015

The usability of underdetermined state feedback in the context of pole placement, eigenstructure assignment, stabilization and robustness analysis of continuous and switched linear systems is explored. Analytical tools for system design and analysis are discussed from the geometric perspective. Thereby, several new results are obtained and some well‐known ones are recovered and generalized by utilization of the computational methods based on the concept of invariance subspaces.
Exploring the Underdiagnosis and Prevalence of Autism Spectrum Conditions in Beijing
Authors: Sun Xiang , Allison Carrie , Matthews Fiona E. , Zhang Zhixiang , Auyeung Bonnie , Baron‐Cohen Simon , Brayne Carol
Published: May 2015

Previous studies reported that the prevalence of Autism Spectrum Conditions (ASC) in mainland China is much lower than estimates from developed countries (around 1%). The aim of the study is to apply current screening and standardized diagnostic instruments to a Chinese population to establish a prevalence estimate of ASC in an undiagnosed population in mainland China. We followed the design development used previously in the UK published in 2009 by Baron‐Cohen and colleagues. The Mandarin Childhood Autism Spectrum Test (CAST) was validated by screening primary school pupils (n = 737 children age 6–10 years old) in Beijing and by conducting diagnostic assessments using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview‐Revised. The prevalence estimate was generated after adjusting and imputing for missing values using the inverse probability weighting. Response was high (97%). Using the UK cutoff (≥15), CAST performance has 84% sensitivity and 96% specificity (95% confidence interval [CI]: 46, 98, and 96, 97, respectively). Six out of 103 children, not previously diagnosed, were found to the meet diagnostic criteria (8.5 after adjustment, 95% CI: 1.6, 15.4). The preliminary prevalence in an undiagnosed primary school population in mainland China was 119 per 10,000 (95% CI: 53, 265). The utility of CAST is acceptable as a screening instrument for ASC in large epidemiological studies in China. Using a comparable method, the preliminary prevalence estimate of ASC in mainland China is similar to that of those from developed countries. Autism Res 2015, 8: 250–260. © 2015 The Authors. Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research
Human amniocyte‐derived cells are a promising cell host for adenoviral vector production under serum‐free conditions
Authors: Silva Ana Carina , Simão Daniel , Küppers Claudia , Lucas Tanja , Sousa Marcos F. Q. , Cruz Pedro , Carrondo Manuel J. T. , Kochanek Stefan , Alves Paula M.
Published: May 2015

Recombinant adenovirus vectors (AdVs) have been used for the development of vaccines, as gene therapy vectors and for protein production. Currently, the production of clinical grade batches of recombinant E1‐deleted adenovirus type 5 vectors is performed using human‐derived HEK293 or PER.C6® cell lines. In this work we describe the generation of a new human amniocyte‐derived cell line named 1G3 and show that it can be used as a very promising cell host for AdV production in serum‐free conditions, allowing for production in high cell density cultures and avoiding the typical cell density effect observed for HEK293. By design, this cell line makes the generation of replication‐competent adenovirus during production of E1‐deleted AdVs very unlikely. The impact of the culture system (static versus agitated) and AdV infection parameters such as multiplicity of infection, time of harvesting and cell concentration at infection were evaluated and compared with HEK293. Using stirred tanks bioreactors, it was possible to grow 1G3 cells to cell densities of up to 9 × 106cells/mL using serum‐free media. Moreover, without a medium exchange step at infection, a three‐fold increase in AdV volumetric titers was obtained, as no cell density effect was observed at CCI 3. Overall, our results clearly demonstrate the potential of the human amniocyte‐derived newly established cell line 1G3 for AdV production in a serum‐free scalable process, paving the way for further process improvements based on fed‐batch or perfusion strategies.
Development of robust antibody purification by optimizing protein‐A chromatography in combination with precipitation methodologies
Authors: Chollangi Srinivas , Parker Ray , Singh Nripen , Li Yi , Borys Michael , Li Zhengjian
Published: May 2015

To be administered to patients, therapeutic monoclonal antibodies must have very high purity, with process related impurities like host‐cell proteins (HCPs) and DNA reduced to <100 ppm and <10 ppb, respectively, relative to desired product. Traditionally, Protein‐A chromatography as a capture step has been the work horse for clearing a large proportion of these impurities. However, remaining levels of process and product related impurities still present significant challenges on the development of polishing steps further downstream. In this study, we have incorporated high throughput screening to evaluate three areas of separation: (i) Harvest treatment; (ii) Protein‐A Chromatography; and (iii) Low pH Viral Inactivation. Precipitation with low pH treatment of cell culture harvest resulted in selective removal of impurities while manipulating the pH of wash buffers used in Protein‐A chromatography and incorporating wash additives that disrupt various modes of protein–protein interaction resulted in further and more pronounced reduction in impurity levels. In addition, our study also demonstrate that optimizing the neutralization pH post Protein‐A elution can result in selective removal of impurities. When applied over multiple mAbs, this optimization method proved to be very robust and the strategy provides a new and improved purification process that reduces process related impurities like HCPs and DNA to drug substance specifications with just one chromatography column and open avenues for significant decrease in operating costs in monoclonal antibody purification. Biotechnol. Bioeng. 2015;112: 2292–2304. © 2015 Wiley Periodicals, Inc.
Ion‐exchange vs reversed‐phase chromatography for separation and determination of basic psychotropic drugs
Authors: Petruczynik Anna , Wróblewski Karol , Deja Michał , Waksmundzka‐Hajnos Monika
Published: May 2015

Ion exchange chromatography, an alternative to reversed‐phase (RP) chromatography, is described in this paper. We aimed to obtain optimal conditions for the separation of basic drugs because silica‐based RP stationary phases show silanol effect and make the analysis of basic analytes hardly possible. The retention, separation selectivity, symmetry of peaks and system efficiency were examined in different eluent systems containing different types of buffers at acidic pH and with the addition of organic modifiers: methanol and acetonitrile. The obtained results reveal a large influence of the salt cation used for buffer preparation and the type of organic modifier on the retention behavior of the analytes. These results were also compared with those obtained on an XBridge C18 column. The obtained results demonstrated that SCX stationary phases can be successfully used as alternatives to C18 stationary phases in the separation of basic compounds. The most selective and efficient chromatographic systems were applied for the quantification of some psychotropic drugs in fortified human serum samples. Copyright © 2015 John Wiley & Sons, Ltd.
Acute anoxic changes in peripheral nerve: anatomic and physiologic correlations
Authors: Punsoni Michael , Drexler Steven , Palaia Thomas , Stevenson Matthew , Stecker Mark M.
Published: May 2015

Introduction

The response of the peripheral nerve to anoxia is modulated by many factors including glucose and temperature. The purposes of this article are to demonstrate the effects of these factors on the pathological changes induced by anoxia and to compare the electrophysiologic changes and pathological changes in the same nerves.

Methods

Sciatic nerves were harvested from rats and placed in a perfusion apparatus where neurophysiologic responses could be recorded continuously during a 16 h experiment. After the experiment, light microscopy and electron microscopy were performed.

Results

Light microscopic images showed mild changes from anoxia at normoglycemia. Hypoglycemic anoxia produced massive axonal swelling while hyperglycemic anoxia produced apparent changes in the myelin. Anoxic changes were not uniform in all axons. Electron microscopy showed only minor disruptions of the cytoskeleton with anoxia during normoglycemia. At the extremes of glucose concentration especially with hyperglycemia, there was a more severe disruption of intermediate filaments and loss of axonal structure with anoxia. Hypothermia protected axons from the effect of anoxia and produced peak axonal swelling in the 17–30°C range.

Conclusions

The combination of hyperglycemia or hypoglycemia and anoxia produces extremely severe axonal disruption. Changes in axonal diameter are complex and are influenced by many factors.
GPU‐assisted real‐time coupling of blood flow and vessel wall
Authors: Guo Jiaxiang , Yuan Zhiyong , Liao Xiangyun , Bai Yaoyi , Lai Qianfeng
Published: May 2015

The vessel wall and the blood flow interact and influence each other, and real‐time coupling between them is of great importance to the virtual surgery as well as the research and diagnosis of vascular disease. On the basis of smoothed particle hydrodynamics (SPH), we present a new approach to solve non‐Newtonian viscous force of blood and a parallel mixed particles‐based coupling method for blood flow and vessel wall. Meanwhile, we also design a proxy particle‐based vessel wall force visualization method. Our method is as follows. Firstly, we solve the non‐Newtonian viscous forces of blood through the SPH method to discretize the Casson equation. Secondly, in each time step, we combine blood particles and sampling proxy particles on the blood vessel wall to form mixed particles and calculate the interaction forces through the SPH method between every pair of the neighboring mixed particles inside the graphics processing unit. Thirdly, the forces of the proxy particles will be mapped to the color display of the proxy particle. Experimental results demonstrate that our method is able to implement real‐time sizeable coupling of blood flow and vessel wall while mainly ensuring physical authenticity and it can also provide real‐time and obvious information about vessel wall force distribution. Copyright © 2015 John Wiley & Sons, Ltd.
Risk stratification in 3‐vessel coronary artery disease: Applying the SYNTAX Score II in the Heart Team Discussion of the SYNTAXII trial
Authors: Campos Carlos M. , Stanetic Bojan M. , Farooq Vasim , Walsh Simon , Ishibashi Yuki , Onuma Yoshinobu , Garcia‐Garcia Hector M. , Escaned Javier , Banning Adrian , Serruys Patrick W. ,   on behalf of the SYNTAX II Study Group
Published: May 2015

Background

Heart Team (HT) and the SYNTAX Score II (SSII) have been integrated to the contemporary guidelines with the aim to provide a multidisciplinary decision‐making process between coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI).

Aims

To prospectively assess the agreement between the HT decision and the SSII recommendation regarding the revascularization strategy in patients with 3‐vessel coronary artery disease (CAD) of the SYNTAX II trial.

Methods

The SSII predicts the 4‐year mortality of an individual patient both after PCI and after CABG. Patients were treated by PCI when the SSII predicted a mortality risk favoring PCI or when risk predictions were equipoise between PCI and CABG. However, the HT could overrule the SSII and recommend either CABG or PCI.

Results

A total of 202 patients have been screened and 24 did not fulfill inclusion criteria. The median age was 67.0 (IQR 59.0–73.3), and 167 (82.7%) were male. The HT endorsed SSII treatment recommendation, for CABG or PCI, in 152 patients (85.4%). Three patients had preference for PCI, irrespective of the HT decision. The main reason for the HT to overrule the SSII and recommend CABG was the prospect of a more complete revascularization (21 of 25 patients). Patients recommended for CABG by the HT had significantly higher anatomical SYNTAX score (P = 0.03) and higher predicted mortality risk for PCI (P = 0.04) when compared with patients that were enrolled in the trial.

Conclusion

The SYNTAX score II showed to be a suitable tool for guiding treatment decisions of patients with 3‐vessel coronary artery disease being endorsed by the HT in the vast majority of the patients that have been enrolled in the SYNTAX II trial. © 2015 Wiley Periodicals, Inc.
Production of High‐Tensile‐Strength Paracetamol Tablets Using the Freeze‐Casting Process
Authors: Nguyen Phuong Thi Nhat , Ulrich Joachim
Published: May 2015

A fast‐dissolving solid dosage form (tablet), containing in this case paracetamol as an active pharmaceutical ingredient and modified starch as an additive, was successfully produced by means of the freeze‐casting process. The structure and two key properties, namely, disintegration time and tensile strength, of freeze‐casted tablets were investigated. The produced tablets exhibit a threefold faster disintegration time with equal tensile strength in comparison to the commercial compressed tablets. Sugar as a binder, however, can just improve the disintegration rate but not enhance the tensile strength due to different mechanisms working.
Clinical utility of plasma Epstein‐Barr virus DNA and ERCC1 single nucleotide polymorphism in nasopharyngeal carcinoma
Authors: Hui Edwin P. , Ma Brigette B. Y. , Chan K. C. Allen , Chan Charles M. L. , Wong Cesar S. C. , To Ka Fai , Chan Anthony W. H. , Tung Stewart Y. , Ng Wai‐Tong , Cheng Ashley C. , Lee Victor H. F. , Chan Stephen L. , Loong Herbert H. F. , Kam Michael K. M. , Leung Sing‐Fai , Ho Rosalie , Mo Frankie , Ngan Roger K. C. , Chan Anthony T. C.
Published: May 2015

BACKGROUND

Single nucleotide polymorphism (SNP) of the excision repair cross‐complementing group 1 (ERCC1) gene has been linked with sensitivity to platinum and radiation. The authors hypothesized that the ERCC1 genotype for the SNPs cytosine‐to‐thymine substitution at codon 118 (C118T) and cytosine‐to‐adenine substitution at codon 8092 (C8092A) is prognostic in patients with nasopharyngeal carcinoma (NPC) who receive either radiotherapy (RT) or cisplatin plus RT.

METHODS

The authors tested their hypothesis using biomarker screening samples from the Hong Kong NPC Study Group 0502 trial, which was a prospective, multicenter clinical trial that used post‐RT plasma Epstein‐Bar virus (EBV) DNA (pEBV) levels to screen patients with high‐risk NPC for adjuvant chemotherapy.

RESULTS

ERCC1 SNPs were analyzed in 576 consecutive patients who were screened by pEBV. In the total biomarker population, there was no significant association of ERCC1 C118T or C8092A genotype with relapse‐free survival (RFS) or overall survival (OS). There also was no correlation between ERCC1 genotype and ERCC1 protein or messenger RNA expression in a subset of patients who had available paired biopsies. Post‐RT pEBV status was the only independent prognosticator for RFS and OS in multivariate analyses. However, there was a significant interaction between ERCC1 C118T genotype and post‐RT pEBV status (RFS, P = .0106; OS, P = .0067). The ERCC1 C118T genotype was significantly associated with both RFS (hazard ratio, 1.67; 95% confidence interval, 1.07‐2.61; P = .024) and OS (hazard ratio, 2.31; 95% confidence interval, 1.22‐4.40; P = .0106) in the post‐RT pEBV‐negative population, but not in the pEBV‐positive population.

CONCLUSIONS

The current results prospectively validate pEBV as the most significant prognostic biomarker in NPC that can be used to select high‐risk patients for adjuvant therapy. The ERCC1 C118T genotype may help to identify a favorable subgroup (approximately 7%) of pEBV‐negative patients with NPC who have an excellent prognosis and can be spared the toxicities of further therapy. Cancer 2015;121:2720‐2729. © 2015 American Cancer Society
Psychometric properties of an Australian supportive care needs assessment tool for Indigenous patients with cancer
Authors: Garvey Gail , Beesley Vanessa L. , Janda Monika , O'Rourke Peter K. , He Vincent Y.F. , Hawkes Anna L. , Elston Jacinta K. , Green Adele C. , Cunningham Joan , Valery Patricia C.
Published: May 2015

BACKGROUND

There are significant disparities in cancer outcomes between Indigenous and non‐Indigenous Australians. Identifying the unmet supportive care needs of Indigenous Australians with cancer is imperative to improve their cancer care. The purpose of the current study was to test the psychometric properties of a supportive cancer care needs assessment tool for Indigenous people (SCNAT‐IP) with cancer.

METHODS

The SCNAT‐IP was administered to 248 Indigenous Australians diagnosed with a range of cancer types and stages, and who received treatment in 1 of 4 Queensland hospitals. All 39 items were assessed for ceiling and floor effects and were analyzed using exploratory factor analysis to determine construct validity. Identified factors were assessed for internal consistency and convergent validity to validated psychosocial tools.

RESULTS

Exploratory factor analysis revealed a 4‐factor structure (physical and psychological, hospital care, information and communication, and practical and cultural needs) explaining 51% of the variance. Internal consistency of the 4 subscales was good, with Cronbach alpha reliability coefficients ranging from .70 to .89. Convergent validity was supported by significant correlations between the SCNAT‐IP with the National Comprehensive Cancer Network Distress Thermometer (correlation coefficient [r] = 0.60; P<.001) and the Cancer Worry Chart (r = 0.58; P<.001) and a moderately strong negative correlation with the Assessment of Quality of Life questionnaire (r = ‐0.56; P<.001).

CONCLUSIONS

These data provide initial support for the SCNAT‐IP, a measure of multiple supportive care needs domains specific to Indigenous Australian patients with cancer undergoing treatment. Cancer 2015;121:3018–3026. © 2015 American Cancer Society.
In‐situ observation of InGaN quantum well decomposition during growth of laser diodes
Authors: Hoffmann V. , Mogilatenko A. , Zeimer U. , Einfeldt S. , Weyers M. , Kneissl M.
Published: May 2015

The deterioration of the InGaN active region of laser diode structures emitting around 440 nm is observed in‐situ during epitaxial growth and analyzed ex‐situ by cathodoluminescence spectroscopy and transmission electron microscopy. The growth conditions of the p‐layers on top of the InGaN active region are found to affect the homogeneity of the InGaN material properties which can be monitored by the in‐situ reflectance signal at 950 nm. The deposition of the p‐layers at 950 °C results in the formation of metallic indium platelets as well as voids changing the refractive index of the active region and thus the reflectance. A reduction of the p‐layer deposition temperature by 30 °C prevents this undesirable decomposition.
Focus on perfectionism in female adolescent anorexia nervosa
Authors: Hurst Kim , Zimmer‐Gembeck Melanie
Published: May 2015

Objective

Maudsley Family‐Based Treatment (FBT) for anorexia is successful for between 50 and 80% of adolescents. To improve this success rate, various approaches to augmenting the treatment have been proposed.

Method

In this study, we describe the treatment of three girls with FBTaugmented with a module focusing on perfectionism, defined as personally prescribed or socially derived irrational and rigid expectations and exceedingly high standards of self performance. Multiple times across the 1 year of treatment, girls completed the measures of perfectionism and other outcomes.

Results

The results were optimistic for remission, and showed reductions in girls? perfectionism and obsessional and rigid thinking. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:936–941).
Hypothyroidism due to Hashimoto's thyroiditis masked by anorexia nervosa
Authors: Smalls‐Mantey Adjoa , Steinglass Joanna , Primack Marshall , Clark‐Hamilton Jill , Bongiovi Mary
Published: May 2015

Anorexia nervosa (AN) is typically associated with altered thyroid function tests, notably a low total and free T3, and lower, but within normal range, free T4 and TSH. A 16‐year‐old girl with a four‐year history of AN presented with elevated TSH that fluctuated with changes in weight. TSH was within normal limits (1.7–3.64 mIU/L) following periods of weight loss and elevated with weight gain (5.9–21.66 mIU/L). Antithyroperoxidase antibodies were markedly elevated, suggesting chronic Hashimoto's thyroiditis. Of note, the elevated TSH that would be expected in Hashimoto's thyroiditis was blunted by weight loss associated with AN. Physicians should be aware that AN may contribute to masking thyroid abnormalities in Hashimoto's thyroiditis. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:932–935).