bluuebunny/crossref_metadata_2025 huggingface dataset:
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Authors: Thonus Terese , Hewett Beth L.
Published: May 2016

This paper examines conceptual metaphor use by graduate-student writing consultants in a university writing center. Our goal was to develop a taxonomy for consultant metaphor in asynchronous online consultations; to find evidence that consultants could produce deliberate metaphors as an instructional strategy when responding asynchronously by e-mail to students and their texts; and to compare these data with Thonus’s (2010) investigation of consultant metaphor use in face-to-face consultations, Results showed that writing consultants trained in the use of strategic metaphors employed them in subsequent consultations. In addition, trained consultants used deliberate, coherent, and systematic metaphors in all six categories of our analysis, and they exploited metaphors students had developed in their writing. In comparison with their pre-training metaphor use, the consultants demonstrated increased metaphor use after training and used metaphors significantly differently from consultants who had received no training. We discuss these results in terms of deliberate vs. non-deliberate metaphor use in writing instruction, and we consider the feasibility and advisability of training writing center consultants to employ metaphors — specifically coherent, systematic metaphors — as vehicles for writing instruction in an online setting.
Reaction to New Objects and Spatial Changes in Young and Aged Grey Mouse Lemurs (Microcebus murinus)
Authors: Picq Jean-Luc , Dhenain Marc
Published: May 2016

The exploratory behaviour of young and grey mouse lemurs (Microceb11s murinus) in an experimental enclosure containing various objects was recorded. A new object was added for each test session and could displace an object that had previously been introduced to a new position. For young grey mouse lemurs, there was an obvious preference for new objects and for displaced familiar objects. This indicates that they are able, like other primates, to “map out” and memorize their environment. For the aged grey mouse lemurs, preference for the new objects was very slight. No react ion to changes in the location of familiar objects was noted. Age- related deficits in memory, in particular spatial memory, could account for this lack of response to changes in the environment.
The Path more Travelled: Time Pressure Increases Reliance on Familiar Route-Based Strategies during Navigation
Authors: Brunyé Tad T. , Wood Matthew D. , Houck Lindsay A. , Taylor Holly A.
Published: May 2016

Navigating large-scale environments involves dynamic interactions between the physical world and individuals’ knowledge, goals, and strategies. Time pressure can result from self-imposed goals or relatively dynamic situational factors that induce varied constraints. While time pressure is ubiquitous in daily life and has been shown to influence affective states, cost-benefit analyses, and strategy selection, its influence on navigation behaviour is unknown. The present study examined how introducing varied time constraints during virtual urban navigation would influence spatial strategies and impact the efficiency and effectiveness of goal-directed wayfinding. Participants learned a large-scale urban virtual environment by wayfinding between a series of 20 successive landmark goals (e.g., You have reached the Theater. Now find the Bank.). A day later, they again performed the same task, but landmark-to-landmark trials were characterized by conditions of low-, moderate-, or high-pressure time limits as quantified by a pilot experiment. As time pressure increased, participants more likely navigated along previously experienced paths and less likely travelled in the global direction of the destination. Results suggest strategy shifts under time constraints that increase reliance on egocentric, route-based strategies and decrease reliance on global configural knowledge, probably in an attempt to reduce cognitive demands and support performance under pressure.
Collateral, Taxes, and Leverage
Authors: Li Shaojin , Whited Toni M. , Wu Yufeng
Published: May 2016

We quantify the importance of collateral versus taxes for firms' capital structures. We estimate a dynamic model in which a taxable firm seeks financing for investment, and a dynamic contracting environment motivates endogenous collateral constraints. Optimal leverage stays a safe distance from the constraint, balancing the tax benefit of debt with the cost of lost financial flexibility. We estimate this flexibility cost to be 7.2% of firm assets, a percentage that is comparable to the tax benefit. Models with different tax rates fit the data equally well, and leverage responds to the tax rate only when taxes are low.

Received January 20, 2015; accepted January 8, 2016 by Editor Itay Goldstein.
Evolutionary dynamics of chloroplast genomes in low light: a case study of the endolithic green algaOstreobium quekettii
Authors: Marcelino Vanessa R. , Cremen Ma Chiela M. , Jackson Christopher J. , Larkum Anthony W.D. , Verbruggen Heroen
Published: May 2016

Some photosynthetic organisms live in extremely low light environments. Light limitation is associated with selective forces as well as reduced exposure to mutagens, and over evolutionary timescales it can leave a footprint on species genome. Here we present the chloroplast genomes of four green algae (Bryopsidales, Ulvophyceae), including the endolithic (limestone-boring) alga Ostreobium quekettii, which is a low light specialist. We use phylogenetic models and comparative genomic tools to investigate whether the chloroplast genome of Ostreobium corresponds to our expectations of how low light would affect genome evolution. Ostreobium has the smallest and most gene-dense chloroplast genome among Ulvophyceae reported to date, matching our expectation that light limitation would impose resource constraints. Rates of molecular evolution are significantly slower along the phylogenetic branch leading to Ostreobium, in agreement with the expected effects of low light and energy levels on molecular evolution. Given the exceptional ability of our model organism to photosynthesize under extreme low light conditions, we expected to observe positive selection in genes related to the photosynthetic machinery. However, we observed stronger purifying selection in these genes, which might either reflect a lack of power to detect episodic positive selection followed by purifying selection and/or a strengthening of purifying selection due to the loss of a gene related to light sensitivity. Besides shedding light on the genome dynamics associated with a low light lifestyle, this study helps to resolve the role of environmental factors in shaping the diversity of genome architectures observed in nature.
Gene- and pathway-based association tests for multiple traits with GWAS summary statistics
Authors: Kwak Il-Youp , Pan Wei
Published: May 2016

To identify novel genetic variants associated with complex traits and to shed new insights on underlying biology, in addition to the most popular single SNP-single trait association analysis, it would be useful to explore multiple correlated (intermediate) traits at the gene-or pathway-level by mining existing single GWAS or meta-analyzed GWAS data. For this purpose, we present an adaptive gene-based test and a pathway-based test for association analysis of multiple traits with GWAS summary statistics. The proposed tests are adaptive at both the SNP-and trait-levels; that is, they account for possibly varying association patterns (e.g. signal sparsity levels) across SNPs and traits, thus maintaining high power across a wide range of situations. Furthermore, the proposed methods are general: they can be applied to mixed types of traits, and to Z-statistics or p-values as summary statistics obtained from either a single GWAS or a meta-analysis of multiple GWAS. Our numerical studies with simulated and real data demonstrated the promising performance of the proposed methods.

The methods are implemented in R package aSPU, freely and publicly available on CRAN at:https://cran.r-project.org/web/packages/aSPU/.
Detection of human adaptation during the past 2,000 years
Authors: Field Yair , Boyle Evan A , Telis Natalie , Gao Ziyue , Gaulton Kyle J. , Golan David , Yengo Loic , Rocheleau Ghislain , Froguel Philippe , McCarthy Mark I. , Pritchard Jonathan K.
Published: May 2016

Detection of recent natural selection is a challenging problem in population genetics, as standard methods generally integrate over long timescales. Here we introduce the Singleton Density Score (SDS), a powerful measure to infer very recent changes in allele frequencies from contemporary genome sequences. When applied to data from the UK10K Project, SDS reflects allele frequency changes in the ancestors of modern Britons during the past 2,000 years. We see strong signals of selection at lactase and HLA, and in favor of blond hair and blue eyes. Turning to signals of polygenic adaptation we find, remarkably, that recent selection for increased height has driven allele frequency shifts across most of the genome. Moreover, we report suggestive new evidence for polygenic shifts affecting many other complex traits. Our results suggest that polygenic adaptation has played a pervasive role in shaping genotypic and phenotypic variation in modern humans.
Cell-cycle coupled expression minimizes random fluctuations in gene product levels
Authors: Soltani Mohammad , Singh Abhyudai
Published: May 2016

Expression of many genes varies as a cell transitions through different cell-cycle stages. How coupling between stochastic expression and cell cycle impacts cell-to-cell variability (noise) in the level of protein is not well understood. We analyze a model, where a stable protein is synthesized in random bursts, and the frequency with which bursts occur varies within the cell cycle. Formulas quantifying the extent of fluctuations in the protein copy number are derived and decomposed into components arising from the cell cycle and stochastic processes. The latter stochastic component represents contributions from bursty expression and errors incurred during partitioning of molecules between daughter cells. These formulas reveal an interesting trade-off: cell-cycle dependencies that amplify the noise contribution from bursty expression also attenuate the contribution from partitioning errors. We investigate existence of optimum strategies for coupling expression to the cell cycle that minimize the stochastic component. Intriguingly, results show that a zero production rate throughout the cell cycle, with expression only occurring just before cell division minimizes noise from bursty expression for a fixed mean protein level. In contrast, the optimal strategy in the case of partitioning errors is to make the protein just after cell division. We provide examples of regulatory proteins that are expressed only towards the end of cell cycle, and argue that such strategies enhance robustness of cell-cycle decisions to the intrinsic stochasticity of gene expression.
Using fractional GM(1,1) model to predict the life of complex equipment
Authors: Wu Lifeng
Published: May 2016

Purpose

– The purpose of this paper is to improve performance for predicting the life spans of complex equipment systems.

Design/methodology/approach

– The gray system model with fractional order accumulation (FGM(1,1)) is used to predict the life spans of complex equipment systems using small samples.

Findings

– FGM(1,1) yielded a lower mean absolute percentage error (MAPE) for an in-sample and a much lower MAPE for an out-of-sample forecast, which means that FGM(1,1) can predict memory processes.

Practical implications

– FGM(1,1) can predict the life spans of other complex equipment.

Originality/value

– FGM(1,1) yielded a lower MAPE for an in-sample and a much lower MAPE for out-of-sample forecasts, which means that FGM(1,1) can predict memory processes.
Antibiotic use during pregnancy and asthma in preschool children: the influence of confounding
Authors: Mulder B. , Pouwels K. B. , Schuiling‐Veninga C. C. M. , Bos H. J. , de Vries T. W. , Jick S. S. , Hak E.
Published: May 2016

Background

A recent study suggested that early‐life intestinal microbiota may play an important role in the development of childhood asthma, indicating that antibiotics taken during early life or in late pregnancy may be associated with childhood asthma.

Objective

This study aims to assess the association between prenatal antibiotic use and asthma in preschool children using data from the prescription database IADB.nl. To assess the influence of potential confounding, we conducted both a case–sibling and a case–control study and compared the results.

Methods

We conducted a case–sibling study in which 1228 children with asthma were compared to 1228 siblings without asthma, using data from the prescription database IADB.nl. In addition, a case–control study was conducted. Asthma in preschool children was defined as ≥ 3 prescriptions for anti‐asthma medication within a year before the fifth birthday. Conditional logistic regression was used to estimate crude and adjusted odds ratios (aORs).

Results

In both the case–sibling and case–control analysis, the use of antibiotics in the third trimester of pregnancy was associated with an increased risk of asthma in preschool children (aOR 1.37; 95% CI 1.02–1.83 and aOR 1.40; 95% CI 1.15–1.47). Time‐trend analyses showed that results were not influenced by a time trend in antibiotic exposure. A significant association between exposure to antibiotics in any trimester of pregnancy and the development of asthma in preschool children was observed in the case–control analysis only (aOR 1.46; 95% CI 1.34–1.59).

Conclusion

Antibiotic use in the third trimester of pregnancy was associated with a small increased risk of asthma in preschool children. This association was robust to time‐invariant confounding or exposure time trends, further supporting the important role for early‐life intestinal microbiota in the development of childhood asthma.
Comparison of centring ability and transportation between four nickel titanium instrumentation techniques by micro‐computed tomography
Authors: Saberi N. , Patel S. , Mannocci F.
Published: May 2016

Aim

To compare the centring ability and transportation of ProTaper Next (PTN), ProTaper Universal (PTU), Race 123 and RevoS using micro‐computed tomography (μCT).

Methodology

Sixty mesial root canals of thirty mandibular molars were divided virtually into coronal, middle and apical thirds, and two reproducible reference points were marked on the external surface of the roots creating 360 measurement points. Samples were randomly allocated to four NiTi instrumentation techniques. Group 1: PTU up to F2 (n = 16), group 2: PTN up to X2 (n = 18), group 3: Race 123 up to T2 (n = 12) and group 4: RevoS up to SU (n = 14). To reproduce a clinical situation, samples were prepared on a phantom head using a surgical operating microscope. Samples were scanned pre‐ and postoperatively using μCT to compare and calculate the transportation and centring ratio. The data were analysed using parametric statistics.

Results

In the coronal and middle third of the root canals, there were significant differences in centring between PTN and PTU (coronal P < 0.001), PTN and RevoS (coronal P < 0.001), Race and PTU (coronal P < 0.01), Race and RevoS (coronal P < 0.01), PTN and RevoS (middle P < 0.01) and Race and RevoS (P < 0.05). Furthermore, there were significant differences in centring between PTN root canal preparations and other instruments in the apical third (PTN and PTU P < 0.01, PTN and Race P < 0.001, PTN and RevoS P < 0.001). In terms of transportation, in the coronal third, there was a significant difference between PTN and PTU (P < 0.05). However, there were no significant differences between the other instruments. In the middle third, significant differences were observed between PTN and PTU (P < 0.05), PTN and RevoS (P < 0.05), Race and PTU (P < 0.05) and Race and RevoS (P < 0.05). However, there were no significant differences between other systems. There was no significant difference in terms of transportation between the four systems in the apical third.

Conclusions

ProTaper Next prepared more centred root canal shapes when compared with Race, PTU and RevoS. In the coronal and middle third of the root canals, the differences in centring between PTN and PTU/RevoS were significant. PTN root canal preparations were more centred than those achieved with all other instruments in the apical third.
Entry and Technological Performance in New Technology Domains: Technological Opportunities, Technology Competition and Technological Relatedness
Authors: Leten Bart , Belderbos Rene , Looy Bart Van
Published: May 2016

Entry and success in new technology domains (NTDs) is essential for firms' long‐term performance. We argue that firms' choices to enter NTDs and their subsequent performance in these domains are not only governed by firm‐level factors but also by environmental characteristics. Entry is encouraged by the richness of opportunities for technology development, while technology competition by incumbent firms discourages entry and render entries that do take place less successful. Firms are expected to be positioned heterogeneously to recognize and capitalize on technological opportunities, depending on the presence of a related technology base. We find qualified support for these conjectures in a longitudinal analysis of entry and technological performance in NTDs by 176 R&D intensive firms. While opportunity rich technology environments attract entries by firms even if these NTDs are distal from firms' existing technologies, firms require related technological expertise in order to exploit technological opportunities post‐entry.
Prehospital Imaging‐Based Triage of Head Trauma with a Mobile Stroke Unit: First Evidence and Literature Review
Authors: Schwindling L. , Ragoschke‐Schumm A. , Kettner M. , Helwig S. , Manitz M. , Roumia S. , Lesmeister M. , Grunwald I. Q. , Fassbender K.
Published: May 2016

BACKGROUND

An ambulance equipped with a computed tomography (CT) scanner, point‐of‐care laboratory, and telemedicine capabilities (Mobile Stroke Unit [MSU]) has been shown to enable delivery of thrombolysis to stroke patients at the emergency site, thereby significantly decreasing time to treatment. However, the MSU frequently assesses patients with cerebral disorders other than stroke. For some of these disorders, prehospital CT scanning may also be beneficial.

METHODS

Our institution manages a program investigating prehospital stroke treatment of patients with neurological emergencies. We assessed a patient with head trauma for whom prehospital CT scanning and laboratory tests allowed cause‐based triage to the most appropriate hospital. We examined implications of this case for clinical practice in light of a literature review.

RESULTS

The MSU was dispatched to assess a 74‐year‐old woman with suspected head trauma or stroke, found lying on the floor with a left frontal laceration. Her Glasgow Coma Scale score was 13, apart from drowsiness she exhibited no neurologic deficit. A CT scan ruled out intracranial hemorrhage and skull fracture. On the basis of these prehospital diagnostic findings, the patient was taken to the nearest primary care hospital rather than to a trauma center with neurosurgery facilities.

CONCLUSION

Patients with neurologic disorders other than stroke, such as traumatic brain injury, may also benefit from prehospital CT studies. This case report and the results of our analysis of the literature support the potential benefit of prehospital imaging in correctly triaging patients with suspected traumatic brain injury to the appropriate target hospital.
Translationally controlled tumour protein (TCTP) from tomato and Nicotiana benthamiana is necessary for successful infection by a potyvirus
Authors: Bruckner Fernanda Prieto , Xavier André Da Silva , Cascardo Renan De Souza , Otoni Wagner Campos , Zerbini Francisco Murilo , Alfenas‐Zerbini Poliane
Published: May 2016

Translationally controlled tumour protein (TCTP) is a ubiquitously distributed protein in eukaryotes, involved in the regulation of several processes, including cell cycle progression, cell growth, stress protection, apoptosis and maintenance of genomic integrity. Its expression is induced during the early stages of tomato (Solanum lycopersicum) infection by the potyvirus Pepper yellow mosaic virus (PepYMV, a close relative of Potato virus Y). Tomato TCTP is a protein of 168 amino acids, which contains all the conserved domains of the TCTP family. To study the effects of TCTP silencing in PepYMV infection, Nicotiana benthamiana plants were silenced by virus‐induced gene silencing (VIGS) and transgenic tomato plants silenced for TCTP were obtained. In the early stages of infection, both tomato and N. benthamiana silenced plants accumulated less virus than control plants. Transgenic tomato plants showed a drastic reduction in symptoms and no viral accumulation at 14 days post‐inoculation. Subcellular localization of TCTP was determined in healthy and systemically infected N. benthamiana leaves. TCTP was observed in both the nuclei and cytoplasm of non‐infected cells, but only in the cytoplasm of infected cells. Our results indicate that TCTP is a growth regulator necessary for successful PepYMV infection and that its localization is altered by the virus, probably to favour the establishment of virus infection. A network with putative interactions that may occur between TCTP and Arabidopsis thaliana proteins was built. This network brings together experimental data of interactions that occur in other eukaryotes and helps us to discuss the possibilities of TCTP involvement in viral infection.
Molecular speciation and tissue compartmentation of zinc in durum wheat grains with contrasting nutritional status
Authors: Persson Daniel Pergament , de Bang Thomas C. , Pedas Pai R. , Kutman Umit Baris , Cakmak Ismail , Andersen Birgit , Finnie Christine , Schjoerring Jan K. , Husted Søren
Published: May 2016

Low concentration of zinc (Zn) in the endosperm of cereals is a major factor contributing to Zn deficiency in human populations. We have investigated how combined Zn and nitrogen (N) fertilization affects the speciation and localization of Zn in durum wheat (Triticum durum).

Zn‐binding proteins were analysed with liquid chromatography ICP‐MS and Orbitrap MS2, respectively. Laser ablation ICP‐MS with simultaneous Zn, sulphur (S) and phosphorus (P) detection was used for bioimaging of Zn and its potential ligands.

Increasing the Zn and N supply had a major impact on the Zn concentration in the endosperm, reaching concentrations higher than current breeding targets. The S concentration also increased, but S was only partly co‐localized with Zn. The mutual Zn and S enrichment was reflected in substantially more Zn bound to small cysteine‐rich proteins (apparent size 10–30 kDa), whereas the response of larger proteins (apparent size > 50 kDa) was only modest. Most of the Zn‐responsive proteins were associated with redox‐ and stress‐related processes.

This study offers a methodological platform to deepen the understanding of processes behind endosperm Zn enrichment. Novel information is provided on how the localization and speciation of Zn is modified during Zn biofortification of grains.
Bone morphogenetic protein‐2 expression in an intraductal papillary mucinous neoplasm with marked ossification: A case report
Authors: Hadano Atsuko , Hirabayashi Kenichi , Yamamuro Hiroshi , Takanashi Yumi , Yamada Misuzu , Kawanishi Aya , Kawaguchi Yoshiaki , Furukawa Daisuke , Nakagohri Toshio , Imai Yutaka , Nakamura Naoya , Mine Tetsuya
Published: May 2016

Intratumoral ossification has been reported in a number of epithelial tumors, but its presence in intraductal papillary mucinous neoplasms (IPMNs) is very rare. Herein, we present a rare case of IPMN with marked ossification. A 56‐year‐old Japanese man was under follow‐up for a previously diagnosed IPMN. Seven years later, he was found to have dilatation of the main pancreatic duct and an enlarged solid mass, for which pancreaticoduodenectomy was performed. Macroscopically, multiple and cystically dilated pancreatic branch ducts, as well as a dilated main pancreatic duct, were identified. There was a solid, polypoid hard mass measuring 15 × 12 mm in the cystically dilated branch of the duct in the pancreatic head. Histological examination revealed papillary proliferation of atypical cuboidal or columnar epithelial cells in the dilated main and branch pancreatic ducts. The solid mass included an invasive adenocarcinoma component with a tubular or trabecular structure that showed pronounced ossification. We diagnosed the patient with invasive IPMN accompanied by marked ossification. Immunohistochemically, tumor cells in both the non‐invasive and invasive lesions expressed bone morphogenetic protein‐2 (BMP‐2). While the mechanism of intratumoral ossification is unclear, it may have involved BMP‐2 in the present case.
Refrigeration and cryopreservation of platelets differentially affect platelet metabolism and function: a comparison with conventional platelet storage conditions
Authors: Johnson Lacey , Tan Shereen , Wood Ben , Davis April , Marks Denese C.
Published: May 2016

BACKGROUND

Alternatives to room temperature storage of platelets (PLTs) may be beneficial to extend the limited shelf life and support transfusion logistics in rural and military areas. The aim of this study was to assess the morphologic, metabolic, and functional aspects of PLTs stored at room temperature or in refrigerated conditions or cryopreserved.

STUDY DESIGN AND METHODS

A three‐arm pool‐and‐split study was carried out using buffy coat–derived PLTs stored in 30% plasma/70% SSP+. The three matched treatment arms were room temperature stored (20‐24°C), cold‐stored (2‐6°C), and cryopreserved (−80°C with dimethyl sulfoxide). Liquid‐stored PLTs were tested over a 21‐day period, while cryopreserved PLTs were examined immediately after thawing and after 6 and 24 hours of storage at room temperature.

RESULTS

Cold‐stored and cryopreserved PLTs underwent a significant shape change, although the cryopreserved PLTs appeared to recover from this during subsequent storage. Glycolytic metabolism was reduced in cold‐stored PLTs, but accelerated in cryopreserved PLTs, while oxidative phosphorylation was negatively affected by both storage conditions. PLT aggregation was potentiated by cold storage and diminished by cryopreservation in comparison to room temperature–stored PLTs. Cold storage and cryopreservation resulted in faster clot formation (R‐time; thromboelastography), which was associated with an increase in microparticles.

CONCLUSION

Cold storage and cryopreservation of PLTs led to morphologic and metabolic changes. However, storage under these conditions appears to maintain or even enhance certain aspects of in vitro PLT function.
Modeling of higher order systems using artificial bee colony algorithm
Authors: Bağış Aytekin , Senberber Halit
Published: May 2016

In this work, modeling of the higher order systems based on the use of the artificial bee colony (ABC) algorithm were examined. Proposed model parameters for the sample systems in the literature were obtained by using the algorithm, and its performance was presented comparatively with the other methods. Simulation results show that the ABC algorithm based system modeling approach can be used as an efficient and powerful method for higher order systems.
Dynamical Models of a Wire Scanner
Authors: Barjau Ana , Herranz Juan , Dehning Bernd
Published: May 2016

The accuracy of the beam profile measurements achievable by the current wire scanners at CERN is limited by the vibrations of their mechanical parts. In particular, the vibrations of the carbon wire represent the major source of wire position uncertainty which limits the beam profile measurement accuracy. In the coming years, due to the Large Hadron Collider (LHC) luminosity upgrade, a wire traveling speed up to 20 m s−1 and a position measurement accuracy of the order of 1 μm will be required. A new wire scanner design based on the understanding of the wire vibration origin is therefore needed. We present the models developed to understand the main causes of the wire vibrations observed in an existing wire scanner. The development and tuning of those models are based on measurements and tests performed on that CERN proton synchrotron (PS) scanner. The final model for the (wire + fork) system has six degrees-of-freedom (DOF). The wire equations contain three different excitation terms: inertia forces associated with the fork rotation, parametric terms associated with the fork tips approaching/separating motion, and terms associated with the wire stiffness (Duffing terms). Though forced, parametric, and Duffing oscillators have been treated in the literature, it is the first time that a model containing all those terms is treated through a purely analytical model. The model has been run for different rotation patterns, and the results show the same trends as the measurements. From the simulations, we conclude that fork flexibility is the main cause of the wire vibration.
Interindividual registration and dose mapping for voxelwise population analysis of rectal toxicity in prostate cancer radiotherapy
Authors: Dréan Gaël , Acosta Oscar , Lafond Caroline , Simon Antoine , de Crevoisier Renaud , Haigron Pascal
Published: May 2016

Purpose:

Recent studies revealed a trend toward voxelwise population analysis in order to understand the local dose/toxicity relationships in prostate cancer radiotherapy. Such approaches require, however, an accurate interindividual mapping of the anatomies and 3D dose distributions toward a common coordinate system. This step is challenging due to the high interindividual variability. In this paper, the authors propose a method designed for interindividual nonrigid registration of the rectum and dose mapping for population analysis.

Methods:

The method is based on the computation of a normalized structural description of the rectum using a Laplacian‐based model. This description takes advantage of the tubular structure of the rectum and its centerline to be embedded in a nonrigid registration‐based scheme. The performances of the method were evaluated on 30 individuals treated for prostate cancer in a leave‐one‐out cross validation.

Results:

Performance was measured using classical metrics (Dice score and Hausdorff distance), along with new metrics devised to better assess dose mapping in relation with structural deformation (dose‐organ overlap). Considering these scores, the proposed method outperforms intensity‐based and distance maps‐based registration methods.

Conclusions:

The proposed method allows for accurately mapping interindividual 3D dose distributions toward a single anatomical template, opening the way for further voxelwise statistical analysis.
Characterization of scintillator‐based detectors for few‐ten‐keV high‐spatial‐resolution x‐ray imaging
Authors: Larsson Jakob C. , Lundström Ulf , Hertz Hans M.
Published: May 2016

Purpose:

High‐spatial‐resolution x‐ray imaging in the few‐ten‐keV range is becoming increasingly important in several applications, such as small‐animal imaging and phase‐contrast imaging. The detector properties critically influence the quality of such imaging. Here the authors present a quantitative comparison of scintillator‐based detectors for this energy range and at high spatial frequencies.

Methods:

The authors determine the modulation transfer function, noise power spectrum (NPS), and detective quantum efficiency for Gadox, needle CsI, and structured CsI scintillators of different thicknesses and at different photon energies. An extended analysis of the NPS allows for direct measurements of the scintillator effective absorption efficiency and effective light yield as well as providing an alternative method to assess the underlying factors behind the detector properties.

Results:

There is a substantial difference in performance between the scintillators depending on the imaging task but in general, the CsI based scintillators perform better than the Gadox scintillators. At low energies (16 keV), a thin needle CsI scintillator has the best performance at all frequencies. At higher energies (28–38 keV), the thicker needle CsI scintillators and the structured CsI scintillator all have very good performance. The needle CsI scintillators have higher absorption efficiencies but the structured CsI scintillator has higher resolution.

Conclusions:

The choice of scintillator is greatly dependent on the imaging task. The presented comparison and methodology will assist the imaging scientist in optimizing their high‐resolution few‐ten‐keV imaging system for best performance.
Control of Herpesvirus Infection in Organ Transplant Recipients
Authors: Tolkoff-Rubin Nina E , Rubin Robert H
Published: May 2016

The most important causes of infectious disease morbidity and
mortality in organ transplant recipients are the herpesviruses, particularly cytomegalovirus (CMV) and
Epstein‐Barrvirus (EBV). Because of their properties of latency, cell association, and potential oncogenicity,
they are particularly well suited to causing disease in the transplant patient. Antilymphocyte antibody
therapies are potent reactivators of these viruses, and cyclosporine, by inhibiting the critical host defense
(virus specific cytotoxic T cells) in a dose‐dependent fashion, amplifies the extent and effects of the viral
replication. This in turn is translated into clinical disease: fever; pneumonia; gastrointestinal ulcerations;
broad‐based suppression of host defences leading to opportunistic superinfection and, perhaps, allograft
injury in the case of CMV; and B cell lymphoproliferative disease in the case of EBV. New approaches to
controlling these viruses in which pre‐emptive therapy is linked to immunosuppressive therapy, and new
diagnostic techniques for viral monitoring, hold promise for limiting clinical disease due to these viruses.
Optimizing Wellness in Chronic Obstructive Pulmonary Disease
Authors: Goldstein Roger S , Brooks Dina , Ford Gordon T
Published: May 2016

Optimizing wellness in chronic obstructive pulmonary disease (COPD) is an emerging theme, in response to the substantial burden of COPD among Canadians. Population surveillance, from the Public Health Agency of Canada, as well as from international initiatives, such as the Burden of Obstructive Lung Disease (BOLD) study, has revealed the prevalence and regional disparities of a condition in which mortality, morbidity and health care resource use often reflect what was happening in the population more than 20 years previously. As COPD emerges to be an important women’s health issue, it raises questions as to how female mortality from COPD can rise at double the rate of breast cancer, why the COPD patient population is still predominantly male and whether women experience breathlessness differently than men.

There is increasing awareness of the frequency and importance of assessing secondary impairments, such as muscle atrophy, an important prognostic indicator. The availability of pulmonary rehabilitation, despite its beneficial effects on exercise and quality of life, remains far behind the demand for services, a care gap unlikely to be filled by institutionally based programs. New models of chronic disease management require the health care system to proactively meet the needs of individuals with chronic conditions, rather than reacting to them through the acute care system. Such approaches occur best in partnership between health authorities and local municipalities. The present supplement includes several examples of this partnership, especially in Alberta and Saskatchewan. An increasing body of evidence supports the importance of exercise training, combined with selfmanagement, as a cornerstone of chronic disease management.
Canadian Thoracic Society Recommendations for Management of Chronic Obstructive Pulmonary Disease - 2008 Update - Highlights for Primary Care
Authors: O’donnell Denis E , Hernandez Paul , Kaplan Alan , Aaron Shawn , Bourbeau Jean , Marciniuk Darcy , Balter Meyer , Ford Gordon , Gervais Andre , Lacasse Yves , Maltais Francois , Road Jeremy , Rocker Graeme , Sin Don , Sinuff Tasmin , Voduc Nha
Published: May 2016

Chronic obstructive pulmonary disease (COPD) is a major respiratory illness in Canada that is preventable and treatable but unfortunately remains underdiagnosed. The purpose of the present article from the Canadian Thoracic Society is to provide up-to-date information so that patients with this condition receive optimal care that is firmly based on scientific evidence. Important summary messages for clinicians are derived from the more detailed Update publication and are highlighted throughout the document. Three key messages contained in the update are: use targeted screening spirometry to establish a diagnosis and initiate prompt management (including smoking cessation) of mild COPD; improve dyspnea and activity limitation in stable COPD using new evidence-based treatment algorithms; and understand the importance of preventing and managing acute exacerbations, particularly in moderate to severe disease.
Asthma Worsenings: Approaches to Prevention and Management from the Asthma Worsenings Working Group
Authors: Balter Meyer , Ernst Pierre , Watson Wade , Kim Harold , Cicutto Lisa , Beauchesne Marie-France , Cave Andrew J , Kaplan Alan , Hogg Donna , McIvor Andrew , Smiley Tom , Rouleau Michel , FitzGerald J Mark
Published: May 2016

Most asthma patients prescribed maintenance asthma therapies still experience periods of asthma worsenings characterized by daytime or night-time symptoms, or an increased need for rescue medication. In fact, these episodes are highly prevalent even in patients with well-controlled disease. Published literature suggests that asthma worsenings likely represent a window of opportunity during which patients could intervene early to prevent exacerbations or further deterioration of asthma symptoms. However, current evidence suggests that most patients fail to respond or to self-manage appropriately during these periods.

To address the issue of asthma worsenings, an interdisciplinary committee of respirologists, allergists, family physicians, pharmacists and certified asthma educators from across Canada developed a practical definition of asthma worsenings and provided approaches to the prevention and management of these episodes based on current literature. To date, combination inhaled corticosteroid/long-acting beta-agonist therapy, particularly single inhaler maintenance and reliever therapy, appears to be an effective strategy for preventing asthma worsenings and exacerbations. Addressing the potential barriers to appropriate patient self-management of asthma worsenings, such as failure to adequately identify and respond to worsenings, low expectations for controlling asthma, low health literacy and poor patient-health care professional communication, are also critical to the successful prevention and management of these episodes. Finally, an interdisciplinary team approach involving patients and their families, certified asthma educators, primary care physicians, pharmacists and specialists is likely to have the greatest impact on the identification, prevention and management of asthma worsenings.
Montelukast as Add-On Therapy to Inhaled Corticosteroids in the Management of Asthma (the SAS trial)
Authors: Fitzgerald J Mark , Foucart Sylvain , Coyle Stephen , Sampalis John , Haine Denis , Psaradellis Eliofotisti , McIvor R Andrew
Published: May 2016

AIM: To evaluate the effectiveness of montelukast as add-on therapy for asthmatic patients who remain uncontrolled with low, moderate or high doses of inhaled corticosteroid monotherapy.

DESIGN: An eight-week, multicentre, open-label, observational study.

RESULTS: Of 320 patients enrolled, 288 (90.0%) completed the study. Of patients who had uncontrolled asthma symptoms (Canadian Asthma Consensus Guidelines Update, 2003) but were controlled according to the Asthma Control Questionnaire (ACQ score of less than 1.5), 93.9% maintained asthma control at week 8. Of patients with uncontrolled asthma at baseline for both definitions, 63.5% achieved asthma control by week 8. The mean ± SD ACQ score decreased from 1.13±0.28 to 0.57±0.50 (P<0.001) for controlled patients at baseline and from 2.38±0.73 to 1.03±0.80 (P<0.001) for patients who were uncontrolled at baseline, each representing a clinically significant improvement.

CONCLUSION: Montelukast add-on therapy is an effective alternative to inhaled corticosteroid monotherapy.
Propolis, a Constituent of Honey, Inhibits the Development of Sugar Cataracts and High-Glucose-Induced Reactive Oxygen Species in Rat Lenses
Authors: Shibata Teppei , Shibata Shinsuke , Shibata Naoko , Kiyokawa Etsuko , Sasaki Hiroshi , Singh Dhirendra P. , Kubo Eri
Published: May 2016

Purpose.This study investigated the effects of oral propolis on the progression of galactose-induced sugar cataracts in rats and thein vitroeffects of propolis on high-glucose-induced reactive oxygen species (ROS) and cell death in cultured rat lens cells (RLECs).Methods. Galactose-fed rats and RLECs cultured in high glucose (55 mM) medium were treated with propolis or vehicle control. Relative lens opacity was assessed by densitometry and changes in lens morphology by histochemical analysis. Intracellular ROS levels and cell viability were measured.Results. Oral administration of propolis significantly inhibited the onset and progression of cataract in 15% and 25% of galactose-fed rats, respectively. RLECs cultured with high glucose showed a significant increase in ROS expression with reduced cell viability. Treatment of these RLECs with 5 and 50 μg/mL propolis cultured significantly reduced ROS levels and increased cell viability, indicating that the antioxidant activity of propolis protected cells against ROS-induced damage.Conclusion. Propolis significantly inhibited the onset and progression of sugar cataract in rats and mitigated high-glucose-induced ROS production and cell death. These effects may be associated with the ability of propolis to inhibit hyperglycemia-evoked oxidative or osmotic stress-induced cellular insults.
Cerebral Malaria: An Unusual Cause of Central Diabetes Insipidus
Authors: Premji Resmi , Roopnarinesingh Nira , Cohen Joshua , Sen Sabyasachi
Published: May 2016

Central diabetes insipidus is an uncommon feature of malaria. A previously healthy 72-year-old man presented with fever, rigors, and altered mental status after a recent trip to Liberia, a country known for endemic falciparum malaria. Investigations confirmed plasmodium falciparum parasitemia. Within one week after admission, the serum sodium rose to 166 mEq/L and the urine output increased to 7 liters/day. Other labs were notable for a high serum osmolality, low urine osmolality, and low urine specific gravity. The hypernatremia did not respond to hypotonic fluids. Diabetes insipidus was suspected and parenteral desmopressin was started with a prompt decrease in urinary output and improvement in mental status. Additional testing showed normal anterior pituitary hormones. The desmopressin was eventually tapered off with complete resolution of symptoms. Central diabetes insipidus occurred likely as a result of obstruction of the neurohypophyseal microvasculature. Other endocrinopathies that have been reported with malaria include hyponatremia, adrenal insufficiency, hypothyroidism, hypocalcemia, hypophosphatemia, hyper-, and hypoglycemia, but none manifested in our patient. Though diabetes insipidus is a rare complication of malaria, clinicians need to be aware of this manifestation, as failure to do so may lead to fatality particularly if the patient is dehydrated.
Emerging Utilization of Chrysin Using Nanoscale Modification
Authors: Jung Joohee
Published: May 2016

Chrysin is a flavone found in several plants, mushroom, and honeycomb. This constituent is broadly used in herbal medicine in Asia. Since its biological activities were identified in various studies, the focus has shifted to the development of chrysin as a complementary medicine for health promotion. Chrysin is known to have chemopreventive and therapeutic effects in skin aging, atherosclerosis, inflammation, diabetes, AIDS, and cancer. However, its poor bioavailability is a bottleneck for pharmaceutical applications. To overcome the limitations and enhance the bioactive effects, methods like nanoencapsulation or conjugation have been attempted. In this review, current trends of chrysin use in the biomedical field are summarized.
A Novel Method for Fabricating Double Layers Porous Anodic Alumina in Phosphoric/Oxalic Acid Solution and Oxalic Acid Solution
Authors: Xu Yanfang , Li Xiaojiu , Liu Hao , Xu Jie
Published: May 2016

A novel method for fabricating ordered double layers porous anodic alumina (DL-PAA) with controllable nanopore size was presented. Highly ordered large pore layer with interpore distance of 480 nm was fabricated in phosphoric acid solution with oxalic acid addition at the potential of 195 V and the small pore layer was fabricated in oxalic acid solution at the potential from 60 to 100 V. Experimental results show that the thickness of large pore layer is linearly correlative with anodizing time, and pore diameter is linearly correlative with pore widening time. When the anodizing potential in oxalic acid solution was adjusted from 60 to 100 V, the small pore layers with continuously tunable interpore distance from 142 to 241 nm and pore density from1.94×109to4.89×109 cm−2were obtained. And the interpore distance and the pore density of small pore layers are closely correlative with the anodizing potential. The fabricated DL-PAA templates can be widely utilized for fabrication of ordered nanomaterials, such as superhydrophobic or gecko-inspired adhesive materials and metal or semiconductor nanowires.
Effect of Chromatin‐Remodeling Agents in Hepatic Differentiation of Rat Bone Marrow‐Derived Mesenchymal Stem Cells In Vitro and In Vivo
Authors: Ye Danna , Li Tong , Heraud Philip , Parnpai Rangsun
Published: May 2016

Epigenetic events, including covalent histone modifications and DNA methylation, play fundamental roles in the determination of lineage‐specific gene expression and cell fates. The aim of this study was to determine whether the DNA methyltransferase inhibitor (DNMTi) 5‐aza‐2′‐deoxycytidine (5‐aza‐dC) and the histone deacetylase inhibitor (HDACi) trichostatin A (TSA) promote the hepatic differentiation of rat bone marrow‐derived mesenchymal stem cells (rBM‐MSCs) and their therapeutic effect on liver damage. 1 μM TSA and 20 μM 5‐aza‐dC were added to standard hepatogenic medium especially at differentiation and maturation steps and their potential function on hepatic differentiation in vitro and in vivo was determined. Exposure of rBM‐MSCs to 1 μM TSA at both the differentiation and maturation steps considerably improved hepatic differentiation. TSA enhanced the development of the hepatocyte shape, promoted the chronological expression of hepatocyte‐specific markers, and improved hepatic functions. In contrast, treatment of rBM‐MSCs with 20 μM 5‐aza‐dC alone or in combination with TSA was ineffective in improving hepatic differentiation in vitro. TSA and/or 5‐aza‐dC derived hepatocytes‐like cells failed to improve the therapeutic potential in liver damage. We conclude that HDACis enhance hepatic differentiation in a time‐dependent manner, while DNMTis do not induce the hepatic differentiation of rBM‐MSCs in vitro. Their in vivo function needs further investigation.