bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic modeling of hydrophobic interaction chromatography for monoclonal antibody purification: process optimization in the quality by design paradigm
Authors: Shekhawat Lalita Kanwar , Chandak Monu , Rathore Anurag S
Published: May 2017

BACKGROUND

A mechanistic model has been developed for hydrophobic interaction chromatography (HIC) based purification of monoclonal antibodies (mAbs). The model has been used to gain thorough process understanding as desired by the quality by design paradigm. The model is based on the general rate model coupled with an exponentially modified Langmuir adsorption model. The latter has been modeled by using the solvophobic theory for correlating protein adsorption equilibrium on the hydrophobic media with the mobile phase salt concentration.

RESULTS

The proposed model satisfactorily predicts the elution profile of the monoclonal antibody product under consideration and its aggregates on a HIC column (Phenyl Sepharose 6 Fast FlowTM low sub) operated in linear gradient mode. The model has been used to elucidate the underlying mechanism behind separation of monomer and aggregate species. A comparison of the relative time scales for the various mass transfer events for mAb and aggregate species indicates that the intra‐particle (pore) diffusion transport of these molecules to their respective binding sites within the porous HIC resin is the rate limiting step whereas convection, film diffusion, and binding kinetics are relatively faster (time scales are 10−1 to 10−3 order of magnitude times the time scale of intra‐particle pore diffusion).

CONCLUSIONS

The proposed methodology for modeling can be successfully implemented to achieve efficient aggregate removal by HIC using minimal experimentation compared with the traditional experimentally extensive approaches. © 2017 Society of Chemical Industry
Improving catalytic activity of laccase immobilized on the branched polymer chains of magnetic nanoparticles under alternating magnetic field
Authors: Xia Ting‐Ting , Lin Wan , Liu Chun‐Zhao , Guo Chen
Published: May 2017

BACKGROUND

Immobilization of laccase may cause more or less mass transfer limitation in practical applications. In order to enhance the reaction rate, there is great interest in developing an effective way to increase the rate of diffusion in reactions catalyzed by immobilized laccase.

RESULTS

The laccase from Trametes versicolor (p‐diphenol: dioxygen oxidoreductases, EC 1.10.3.2) immobilized on different molecular weight polyethylenimine (PEI) modified amine‐functionalized Fe3O4 nanoparticles [Fe3O4–NH2–PEI (1200/10 000/60 000)–laccase] was separately fabricated. The oxidation reaction rate of catechol catalyzed by Fe3O4–NH2–PEI (1200)–laccase under an alternating magnetic field (600 Hz, 10 Gs) was separately 2.10 times and 1.16 times higher than the control without any external force and with mechanical stirring at 150 rpm. This was a larger increase than for Fe3O4–NH2–PEI (10 000/60 000)–laccase. In addition, the reaction rate catalyzed by Fe3O4–NH2–PEI (1200)–laccase was enhanced as the magnetic field frequency, strength and Fe3O4–NH2–PEI (1200)–laccase or catechol concentration was increased. The immobilized laccase retained 85% of its initial activity after six consecutive operations.

CONCLUSION

Using an alternating magnetic field was a powerful way to intensify the reaction rate catalyzed by laccase immobilized on branched polymer chains of magnetic nanoparticles and showed potential for large‐scale catalytic reaction. © 2017 Society of Chemical Industry
Morphological variations on microscopy in oocysts of coccidian parasites: A prospective study from a tertiary care hospital in north India
Authors: Choudhary Aashish , Gupta Nitin , Ahmad Hafiz , Mirdha Bijay Ranjan
Published: May 2017

The modified acid fast staining technique is a commonly used procedure for the detection of coccidian parasites in developing countries. The morphological variations observed in these parasites play a significant role to some extent in both identification and diagnosis of these parasitic infections. A prospective cross sectional study was performed over three years. The fecal smears were stained by modified Kinyoun acid‐fast staining technique and were extensively studied for morphological variations in the coccidian parasites. Out of a total of two thousand one hundred fifty one (n = 2,151) fecal samples received during the study period, 259 samples (12%) were positive for any one of the coccidian parasites. Morphological variations, especially in the staining character was noted in all the three coccidian parasites. This study was an attempt to characterize different variations in size, shape and staining characteristics of the three coccidian parasites.
Load‐induced changes in the diffusion tensor of ovine anulus fibrosus: A pilot MRI study
Authors: Tourell Monique C. , Kirkwood Margaret , Pearcy Mark J. , Momot Konstantin I. , Little J. Paige
Published: May 2017

Purpose

To assess the feasibility of diffusion tensor imaging (DTI) for evaluating changes in anulus fibrosus (AF) microstructure following uniaxial compression.

Materials and Methods

Six axially aligned samples of AF were obtained from a merino sheep disc; two each from the anterior, lateral, and posterior regions. The samples were mechanically loaded in axial compression during five cycles at a rate and maximum compressive strain that reflected physiological conditions. DTI was conducted at 7T for each sample before and after mechanical testing.

Results

The mechanical response of all samples in unconfined compression was nonlinear. A stiffer response during the first loading cycle, compared to the remaining cycles, was observed. Change in diffusion parameters appeared to be region‐dependent. The mean fractional anisotropy increased following mechanical testing. This was smallest in the lateral (2% and 9%) and largest in the anterior and posterior samples (17–25%). The mean average diffusivity remained relatively constant (<2%) after mechanical testing in the lateral and posterior samples, but increased (by 5%) in the anterior samples. The mean angle made by the principal eigenvector with the spine axis in the lateral samples was 73° and remained relatively constant (<2%) following mechanical testing. This angle was smaller in the anterior (55°) and posterior (47°) regions and increased by 6–16° following mechanical testing.

Conclusion

These preliminary results suggest that axial compression reorients the collagen fibers, such that they become more consistently aligned parallel to the plane of the endplates.

Level of Evidence: 1

Technical Efficacy: Stage 1

J. MAGN. RESON. IMAGING 2017;45:1723–1735
Future projections of streamflow magnitude and timing differ across coastal watersheds of the western United States
Authors: Burke William D. , Ficklin Darren L.
Published: May 2017

Climate change has and will continue to impact the magnitude and timing of streamflow throughout the world. While streamflow timing of western United States watersheds has shifted earlier in mountainous snow‐dominated watersheds due to earlier snowmelt, timing for rain‐dominated coastal watersheds has shifted to later in the year. Despite these dissimilarities, coastal watersheds have received little attention in the literature. This research assesses changes in projected climate and hydrology for five small coastal basins (42–718 km2) in Washington, Oregon, and California. Projections of temperature and precipitation from General Circulation Models (GCMs) for Representative Concentration Pathways 4.5 and 8.5 are coupled with the Soil and Water Assessment Tool hydrologic model to simulate future hydrology for each watershed. The response of climate, streamflow discharge, and timing was analysed for each watershed by comparing the projected mid‐21st century (2035–2064) and late‐21st century (2070–2099) to the historical period (1970–1999). While temperature is projected to increase at each watershed from 1 to 6 °C by the end of the 21st century, precipitation varies widely with the median and mean change across all watersheds and GCMs being close to zero (just 2.0 and 3.6%, respectively). Changes in the magnitude of peak winter streamflow discharge differ across the region compared to the historical period. Streamflow timing also features latitudinal divergence, with the southern California watershed projecting later timing by 13 days and all other watersheds indicating smaller shifts (0–7 days) for the end of the 21st century compared to the historical time period, largely from corresponding shifts in precipitation timing. The projected decreases in peak winter streamflow magnitude, particularly in central and southern California, have critical implications for water supply, which is already strained from extensive drought and high demand. This research makes strides to assess new trends across coastal watersheds.
Fennel (Foeniculum vulgare Mill. subsp. piperitum) florets, a traditional culinary spice in Italy: evaluation of phenolics and volatiles in local populations, and comparison with the composition of other plant parts
Authors: Ferioli Federico , Giambanelli Elisa , D'Antuono L Filippo
Published: May 2017

BACKGROUND

Wild fennel (Foeniculum vulgare Mill. subsp. piperitum) florets are used as a typical spice in central and southern Italy. Although fennel (Foeniculum vulgare Mill.), belonging to the Apiaceae (syn. Umbelliferae) family, is a well‐known vegetable and aromatic plant, whose main phytochemical compounds have been extensively analysed and investigated as flavouring agents and for their putative health promoting functions, its florets have not been specifically considered up to now. Therefore, the volatile and phenolic composition of florets from an Italian wild fennel crop was determined at different developmental stages, and compared to that of leaves and fruits. Moreover, florets of nine Italian wild fennel populations of different geographical origin from northern–central Italy were also analysed.

RESULTS

The total phenolic amount increased from leaves to florets, reaching its highest value in early florets, at 58 012 mg kg−1 of dry matter (DM), then constantly decreased in fruits. In florets of wild populations, phenolics ranged from 6666 to 43 368 mg kg−1 DM. The total amount of volatile compounds was more than twice higher in florets (21 449 mg kg−1 DM) than in leaves (10 470 mg kg−1 DM), reaching its highest value in fruits (50 533 mg kg−1 DM). Estragole and trans‐anethole were the main compounds of the volatile fraction. Total volatiles ranged from 24 367 to 60 468 mg kg−1 DM in florets of local populations.

CONCLUSION

Significant changes in the total amount and profile of both phenolic and volatile compounds occurred during plant development. The consistent increase of estragole at later developmental stages supported the claim of different sensory properties of florets and fruits. Geographical origin significantly affected phenolic and volatile composition of wild fennel florets. © 2017 Society of Chemical Industry
The reconstruction of a parabolic system
Authors: Boumenir Amin
Published: May 2017

We are concerned with the identification and reconstruction of the coefficients of a linear parabolic system from finite time observations of the solution on the boundary. We present two procedures depending on whether the spectrum of the system is simple or multiple. Copyright © 2017 John Wiley & Sons, Ltd.
Exacerbation of liver steatosis following exposure to famine and overnutrition
Authors: Ning Zhiyuan , Zhang Kun , Zhao Li , Lu You , Sun Honglin , Chen Chi , Nie Xiaomin , Lu Meng , Wang Ningjian , Lu Yingli
Published: May 2017

Scope

People suffering from famine in early life and overnutrition in adulthood may have an increased risk for liver steatosis. We aimed to investigate the effects and mechanisms of early nutrition restriction and overnutrition on de novo lipogenesis in the liver.

Methods and results

Three‐wk‐old male rats were food restricted for 4 wk and refed a high‐fat or normal fat diet individually in metabolic cages for 9 wk. Weight‐matched groups were also set up. Fatty acid synthetase expression was measured to estimate de novo lipogenesis in the liver. Parameters of glucose and lipid metabolism were measured with isotope assays. All four groups had comparable body weights. However, the famine high‐fat diet group had the highest degree of liver steatosis, the greatest body fat ratio, and insulin resistance. Lipid accumulation, fatty acid synthetase expression, and gluconeogenesis in the liver were significantly higher in the famine and high‐fat diet groups (p < 0.05). Moreover, these groups also had markedly lower muscle glucose uptake.

Conclusion

Under famine and high‐fat refeeding stress, rats were extremely susceptible to developing hepatic steatosis. This is presumably a consequence of upregulation of de novo lipogenesis and enhanced glucose flux from muscle to de novo lipogenesis in the liver.
Developing Bayesian networks from a dependency‐layered ontology: A proof‐of‐concept in radiation oncology
Authors: Kalet Alan M. , Doctor Jason N. , Gennari John H. , Phillips Mark H.
Published: May 2017

Purpose

Bayesian networks (BNs) are graphical representations of probabilistic knowledge that offer normative reasoning under uncertainty and are well suited for use in medical domains. Traditional knowledge‐based network development of BN topology requires that modeling experts establish relevant dependency links between domain concepts by searching and translating published literature, querying domain experts, or applying machine learning algorithms on data. For initial development these methods are time‐intensive and this cost hinders the growth of BN applications in medical decision making. Further, this approach fails to utilize knowledge representation in medical fields to automate network development. Our research alleviates the challenges surrounding BN modeling in radiation oncology by leveraging an ontology based hub and spoke system for BN construction.

Methods

We implement a hub and spoke system by developing (a) an ontology of knowledge in radiation oncology (the hub) which includes dependency semantics similar to BN relations and (b) a software tool that operates on ontological semantics using deductive reasoning to create BN topologies (the spokes). We demonstrate that network topologies built using the software are terminologically consistent and form networks that are topologically compatible with existing ones. We do this first by merging two different BN models for prostate cancer radiotherapy prediction which contain domain cross terms. We then use the logic to perform discovery of new causal chains between radiation oncology concepts.

Results

From the radiation oncology (RO) ontology we successfully reconstructed a previously published prostate cancer radiotherapy Bayes net using up‐to‐date domain knowledge. Merging this model with another similar prostate cancer model in the RO domain produced a larger, highly interconnected model representing the expanded scope of knowledge available regarding prostate cancer therapy parameters, complications, and outcomes. The causal discovery resulted in an automatically‐built causal network model of all ontologized radiotherapy concepts between a ‘Mucositis’ complication and anatomic tumor location.

Conclusions

The proposed model building approach lowers barriers to developing probabilistic models relevant to real‐world clinical decision making, and offers a solution to the consistency and compatibility problems. Further, the knowledge representation in this work demonstrates potential for broader radiation oncology applications outside of Bayes nets.
Accuracy evaluation of a six‐degree‐of‐freedom couch using cone beam CT and IsoCal phantom with an in‐house algorithm
Authors: Zhang Qinghui , Driewer Joseph , Wang Shuo , Li Sicong , Zhu Xiaofeng , Zheng Dandan , Cao Yijian , Zhang Jiaju , Jamshidi Abolghassem , Cox Brett W. , Knisely Jonathan P.S. , Potters Louis , Klein Eric E.
Published: May 2017

Purpose

The accuracy of a six degree of freedom (6DoF) couch was evaluated using a novel method.

Methods

Cone beam CT (CBCT) images of a 3D phantom (IsoCal) were acquired with different, known combinations of couch pitch and roll angles. Pitch and roll angles between the maximum allowable values of 357 and 3 degrees were tested in one degree increments. A total of 49 combinations were tested at 0 degrees of yaw (couch rotation angle). The 3D positions of 16 tungsten carbide ball bearings (BBs), each 4 mm in diameter and arranged in a known geometry within the IsoCal phantom, were determined in the 49 image sets with in‐house software. The BB positions at different rotation angles were determined using a rotation matrix from the original BB positions at zero pitch and roll angles. A linear least squares fit method estimated the rotation angles and differences between detected and nominal rotation angles were calculated. This study was conducted for the case with and without extra weight on the couch. Couch walk shifts for the system were investigated using eight combinations of rotation, roll and pitch.

Results

A total of 49 CBCT images with voxel sizes 0.5 × 0.5 × 1.0 mm3 were taken for the case without extra weight on the couch. The 16 BBs were determined to evaluate the isocenter translation and rotation differences between the calculated and nominal couch values. Among all 49 calculations, the maximum rotation angle differences were 0.10 degrees for pitch, 0.15 degrees for roll and 0.09 degrees for yaw. The corresponding mean and standard deviation values were 0.028 ± 0.032, −0.043 ± 0.058, and −0.009 ± 0.033 degrees. The maximum translation differences were 0.3 mm in the left–right direction, 0.5 mm in the anterior–posterior direction and 0.4 mm in the superior–inferior direction. The mean values and corresponding standard deviations were 0.07 ± 0.12, −0.05 ± 0.25, and −0.12±0.14 mm for the planes described above. With an 80 kg phantom on the couch, the maximum translation shift was 0.69 mm. The couch walk translation shifts were less than 0.1 mm and rotation shifts were less than 0.1 degree.

Conclusions

Errors of a new 6DoF couch were tested using CBCT images of a 3D phantom. The rotation errors were less than 0.3 degree and the translation errors were less than or equal to 0.8 mm in each direction. This level of accuracy is warranted for clinical radiotherapy utilization including stereotactic radiosurgery.
Determination of inter‐ionic and intra‐ionic interactions in a monofluorinated imidazolium ionic liquid by a combination of X‐ray crystallography and NOE NMR spectroscopy
Authors: Lingscheid Yves , Paul Mathias , Bröhl Andreas , Neudörfl Jörg‐Martin , Giernoth Ralf
Published: May 2017

We report the very first application of a Transient 1D 1H{19F} NOE NMR experiment in neat ionic liquids. In comparison with classical 2D HOESY NMR spectroscopy, a substantial reduction in measurement time is gained with comparable quality and information content of the spectra. In combination with classical X‐ray crystallography, we have applied this technique for the determination of inter‐ionic distances (i.e. probabilities of presence) utilizing an ionic liquid containing a monofluorinated imidazolium cation. Copyright © 2017 John Wiley & Sons, Ltd.
Using Eulerian video magnification to enhance detection of fasciculations in people with amyotrophic lateral sclerosis
Authors: Van Hillegondsberg Ludo , Carr Jonathan , Brey Naeem , Henning Franclo
Published: May 2017

Introduction

This study seeks to determine whether the use of Eulerian video magnification (EVM) increases the detection of muscle fasciculations in people with amyotrophic lateral sclerosis (PALS) compared with direct clinical observation (DCO).

Methods

Thirty‐second‐long video recordings were taken of 9 body regions of 7 PALS and 7 controls, and fasciculations were counted by DCO during the same 30‐s period. The video recordings were then motion magnified and reviewed by 2 independent assessors.

Results

In PALS, median fasciculation count per body region was 1 by DCO (range 0–10) and 3 in the EVM recordings (range 0–15; P < 0.0001). EVM revealed more fasciculations than DCO in 61% of recordings. In controls, median fasciculation count was 0 for both DCO and EVM.

Discussion

Compared with DCO, EVM significantly increased the detection of fasciculations in body regions of PALS. When it is used to supplement clinical examination, EVM has the potential to facilitate the diagnosis of ALS. Muscle Nerve 56: 1063–1067, 2017
Strength anisotropy of granular material consisting of perfectly round particles
Authors: Wang Rui , Fu Pengcheng , Tong Zhaoxia , Zhang Jian‐Min , Dafalias Yannis F.
Published: May 2017

The strength anisotropy of granular materials deposited under gravity has mostly been attributed to elongated particles' tendency to align long axes along the bedding plane direction. However, recent experiments on near‐spherical glass beads, for which preferred particle alignment is inapplicable, have exhibited surprisingly strong strength anisotropy. This study tests the hypothesis that certain amount of fabric anisotropy caused by the anisotropic stress during deposition under gravity can be locked in a circular‐particle deposit. Such locked‐in fabric anisotropy can withstand isotropic consolidation and leads to significant strength anisotropy. 2D discrete element method simulations of direct shear tests on circular‐particle deposits are conducted in this study, allowing for the monitoring of both stress and fabric. Simulations on both monodispersed and polydispersed circular‐particle samples generated under downward gravitational acceleration exhibit clear anisotropy in shear strength, thereby proving the hypothesis. When using contact normal‐based and void‐based fabric tensors to quantify fabric anisotropy in the material, we find that the intensity of anisotropy is discernible but low prior to shearing and is dependent on the consolidation process and the dispersity of the sample. The fact that samples with very low anisotropy intensity measurements still exhibit fairly strong strength anisotropy suggests that current typical contact normal‐based and void‐based second‐order fabric tensor formulations may not be very effective in reflecting the anisotropic peak shear strength of granular materials. Copyright © 2017 John Wiley & Sons, Ltd.
Children with low‐risk acute lymphoblastic leukemia are at highest risk of second cancers
Authors: Nielsen Stine N. , Eriksson Frank , Rosthoej Susanne , Andersen Mette K. , Forestier Erik , Hasle Henrik , Hjalgrim Lisa L. , Aasberg Ann , Abrahamsson Jonas , Heyman Mats , Jónsson Ólafur G. , Pruunsild Kaie , Vaitkeviciené Goda E. , Vettenranta Kim , Schmiegelow Kjeld
Published: May 2017

Background

The improved survival rates for childhood acute lymphoblastic leukemia (ALL) may be jeopardized by the development of a second cancer, which has been associated with thiopurine therapy.

Procedure

We retrospectively analyzed three sequential Nordic Society of Paediatric Haematology and Oncology's protocols characterized by increasing intensity of thiopurine‐based maintenance therapy. We explored the risk of second cancer in relation to protocols, risk group, thiopurine methyltransferase (TPMT) activity, ALL high hyperdiploidy (HeH), and t(12;21)[ETV6/RUNX1].

Results

After median 9.5 years (interquartile range, 5.4–15.3 yrs) of follow‐up, 40 of 3,591 patients had developed a second cancer, of whom 38 had non‐high‐risk B‐cell precursor ALL. Patients with standard‐risk ALL, who received the longest maintenance therapy, had the highest adjusted hazard of second cancer (hazard ratio [HR], intermediate vs. standard risk: 0.16, 95% CI: 0.06−0.43, P < 0.001; HR, high vs. standard risk: 0.09, 95% CI: 0.02−0.49, P = 0.006); no significant effects of protocol, age, or white blood cell count at diagnosis, ALL HeH, or t(12;21)[ETV6/RUNX1] were observed. A subset analysis on the patients with standard‐risk ALL did not show an increased hazard of second cancer from either HeH or t(12;21) (adjusted HR 2.02, 95% CI: 0.69−5.96, P = 0.20). The effect of low TPMT low activity was explored in patients reaching maintenance therapy in clinical remission (n = 3,368); no association with second cancer was observed (adjusted HR 1.43, 95% CI: 0.54−3.76, P = 0.47).

Conclusions

The rate of second cancer was generally highest in patients with low‐risk ALL, but we could not identify a subset at higher risk than others.
Nausea and vomiting in children and adolescents receiving intrathecal methotrexate: A prospective, observational study
Authors: Flank Jacqueline , Nadeem Komail , Moledina Sheliza , Khanna Mila , Schindera Christina , Punnett Angela , Dupuis L. Lee
Published: May 2017

Background

The prevalence of nausea and vomiting after receipt of intrathecal methotrexate (IT‐MTX) in pediatric oncology patients is unknown.

Methods

Patients (4–18 years) about to receive IT‐MTX were eligible to participate in this prospective, observational study. Patients received antiemetics as prescribed by their clinical team. Nausea severity (patient‐assessed), timing of emetic episodes, and administration of antiemetics were recorded beginning immediately prior to IT‐MTX administration, for the next 24 hr (acute phase), and for a maximum of 7 additional days (delayed phase). Complete chemotherapy‐induced nausea and vomiting (CINV) control was defined as no emetic episodes and no nausea.

Results

One hundred patients consented to participate in this study; 70 provided evaluable data (mean age: 8.3 years; range: 4.1–17.6). Most (94%) received propofol‐containing anesthesia for IT‐MTX administration. Most (89%) received a 5‐HT3 antagonist prior to IT‐MTX. During the acute phase, 36 children (51%) experienced complete CINV control, 67 (96%) complete vomiting control, and 36 (51%) complete nausea control. Severe acute phase nausea was reported by 12 children (17%). During the delayed phase, 35 patients (50%) experienced complete CINV control, 60 (86%) complete vomiting control, and 36 (51%) complete nausea control. Severe nausea was reported in the delayed phase by 27 (39%) patients.

Conclusions

Most pediatric patients who received IT‐MTX and prophylaxis with ondansetron or granisetron experienced complete acute and delayed vomiting control. However, nausea control was poor and severe nausea was reported by many children. Effective interventions to control nausea are needed.
Fungi resistance of organo‐montmorillonite modified lignocellulosic flour/polypropylene composites
Authors: Liu Ru , Liu Min , Cao Jinzhen , Ma Erni , Huang Anmin
Published: May 2017

Three types of organo‐montmorillonite (OMMT) modified lignocellulosic fibers/flours reinforced polypropylene (PP) composites were prepared with wood flour (WF), cellulose flour (CF), and lignin flour (LF). The fungi resistance of the composites was tested in laboratory against brown rot (Gloeophyllum trabeum) and white rot (Coriolus versicolor). The results showed that: (1) except for brown rot of LF/PP composites (with/without OMMT), all composites were showed weight loss after fungi decay. The values were ranging from 0% to 6%, suggesting very good fungi resistance for these composites; (2) the color changes and decreases in flexural property were found after fungi decay, indicating all the composites underwent biodegradation at different extents; (3) compared with brown rot, the composites were easier to be attacked by white rot; (4) for different types of lignocellulosic flours, the effects of OMMT modification were different. POLYM. COMPOS., 39:3831–3840, 2018. © 2017 Society of Plastics Engineers
The impact of regulatory action on the co‐prescribing of renin–angiotensin system blockers in UK primary care
Authors: Allen Craig , Donegan Katherine
Published: May 2017

Purpose

The aim of this study was to assess the impact of regulatory action taken in June 2014 on the co‐prescribing of renin–angiotensin system (RAS) blockers in UK primary care.

Methods

RAS blocker prescriptions, issued between 01/01/2009–30/06/2015, were extracted from the Clinical Practice Research Datalink to estimate the quarterly prevalence (number of patients with at least one co‐prescription) and incidence (number of patients first receiving a RAS blocker co‐prescription) of co‐prescribing. Two different RAS blockers prescribed on the same day constituted a co‐prescription.

Results

A total of 880 364 patients were prescribed a single RAS blocker during the study period. Prevalence of co‐prescribing increased from 4812 patients per million person‐years in Q1 2009 to 4865 in Q1 2010. A reduction then occurred decreasing to 2901 patients per million person‐years in Q2 2014 when the EU review concluded and continued to decrease thereafter despite a continued increase in the prevalence of prescribing of a single RAS blocker. Incidence of new co‐prescribing decreased from 454 patients per million person‐years in Q1 2009 to 159 in Q2 2014, but remained relatively constant at ~119 patients per million person‐years on average after the EU review concluded. A total of 96% of co‐prescriptions were for an ACE inhibitor + ARB, and 4% accounted for an ACE inhibitor or ARB + renin inhibitor.

Conclusions

Recently, there has been a decrease in the prevalence and incidence of RAS blocker co‐prescribing. Reassuringly, overall co‐prescribing reduced in line with recommendations, although there was a decreasing trend prior to this likely due in part to prior publication of the data used in the EU review. © 2017 Crown copyright. Pharmacoepidemiology and Drug Safety © 2017 John Wiley & Sons, Ltd.
Early Prediction Tool to Identify the Need for Pharmacotherapy in Infants at Risk of Neonatal Abstinence Syndrome
Authors: Isemann Barbara T. , Stoeckle Elaina C. , Taleghani Afshin A. , Mueller Eric W.
Published: May 2017

Objective

To develop a tool to predict the need for pharmacologic treatment of neonatal abstinence syndrome (NAS) within 36 hours from birth in infants at risk for opioid withdrawal.

Study Design

Retrospective study of infants born at gestation of ≥34 weeks with in utero exposure to opioids during two time periods from January 2013 through October 2016. Period 1 was used to develop a predictive tool for validation during period 2. Birth weight, gestational age, four categories of opioid exposure, and individual scores for 21 withdrawal symptoms from the Modified Finnegan Score at 36 hours of life were recorded. During period 1, a best subsets multiple regression analysis was performed on factors that were associated with pharmacotherapy on univariate analysis. Two tools were designed: one based on three highly predictive symptoms associated with need for pharmacotherapy for NAS and the other incorporating opioid exposure. Sensitivity, specificity, and positive and negative predictive values for the tools were calculated during period 2.

Results

The study included 264 infants (period 1, n=143; period 2, n=121). Polysubstance exposure and three withdrawal symptoms present at 36 hours of life that were significantly associated with pharmacotherapy for NAS comprised the tools. The “symptoms only tool” was able to predict that infants with a score <1 would not receive pharmacotherapy, and infants with scores of ≥4 would receive pharmacotherapy with positive predictive values of 90% and 100%, respectively. When opioid exposure was included, the “symptoms + exposure tool” was able to predict that infants with a score of ≤1 would not receive pharmacotherapy and infants with scores of ≥5 would receive pharmacotherapy with positive predictive values of 94% and 86%, respectively.

Conclusion

An NAS prediction tool combining three clinical signs with and without category of opioid exposure had high positive predictive values for requiring and for not requiring pharmacotherapy. This tool may expedite pharmacotherapy decisions and optimize management for infants at risk for NAS.
The common parasite Toxoplasma gondii induces prostatic inflammation and microglandular hyperplasia in a mouse model
Authors: Colinot Darrelle L. , Garbuz Tamila , Bosland Maarten C. , Wang Liang , Rice Susan E. , Sullivan William J. , Arrizabalaga Gustavo , Jerde Travis J.
Published: May 2017

Background

Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia and prostate cancer. Several factors have been hypothesized to cause inflammation, yet the role each may play in the etiology of prostatic inflammation remains unclear. This study examined the possibility that the common protozoan parasite Toxoplasma gondii induces prostatic inflammation and reactive hyperplasia in a mouse model.

Methods

Male mice were infected systemically with T. gondii parasites and prostatic inflammation was scored based on severity and focality of infiltrating leukocytes and epithelial hyperplasia. We characterized inflammatory cells with flow cytometry and the resulting epithelial proliferation with bromodeoxyuridine (BrdU) incorporation.

Results

We found that T. gondii infects the mouse prostate within the first 14 days of infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii‐induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of proliferative inflammatory microglandular hyperplasia in inflamed mouse prostates.

Conclusions

This study identifies the common parasite T. gondii as a new trigger of prostatic inflammation, which we used to develop a novel mouse model of prostatic inflammation. This is the first report that T. gondii chronically encysts and induces chronic inflammation within the prostate of any species. Furthermore, T. gondii‐induced prostatic inflammation persists and progresses without genetic manipulation in mice, offering a powerful new mouse model for the study of chronic prostatic inflammation and microglandular hyperplasia.
Finite‐time stabilization of stochastic nonlinear systems with SiISS inverse dynamics
Authors: Min Huifang , Xu Shengyuan , Ma Qian , Qi Zhidong , Zhang Zhengqiang
Published: May 2017

This paper investigates the finite‐time control problem for a class of stochastic nonlinear systems with stochastic integral input‐to‐state stablility (SiISS) inverse dynamics. Motivated by finite‐time stochastic input‐to‐state stability and the concept of SiISS using Lyapunov functions, a novel finite‐time SiISS using Lyapunov functions is introduced firstly. Then, by adopting this novel finite‐time SiISS small‐gain arguments, using the backstepping technique and stochastic finite‐time stability theory, a systematic design and analysis algorithm is proposed. Given the control laws that guarantee global stability in probability or asymptotic stability in probability, our design algorithm presents a state‐feedback controller that can ensure the solution of the closed‐loop system to be finite‐time stable in probability. Finally, a simulation example is given to demonstrate the effectiveness of the proposed control scheme. Copyright © 2017 John Wiley & Sons, Ltd.
A practical sensorless commutation method based on virtual neutral voltage for brushless DC motor
Authors: Yu Chih‐Hsien
Published: May 2017

This paper presents a low‐cost and highly practical sensorless control method for brushless DC (BLDC) motor drives. The developed methodology can generate an accurate commutation signal for the BLDC motor by sensing the back electromotive force zero‐crossing point through the virtual neutral voltage of the motor. Since commutation control is critical for the BLDC motor control, a voltage‐controlled phase shifter comprising a hysteresis comparator and voltage‐controlled resistor is proposed in order to perform phase compensation at different speeds and prevent rapid output oscillations due to noise or high‐frequency ripples in the virtual neutral voltage. Finally, several experiments have been performed on a prototype motor to verify the theoretical analysis and demonstrate the practicality and reliability of the proposed sensorless drive method. © 2017 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Fast switch fault diagnosis for PWM DC–DC low power converters
Authors: Qian Qinsong , Sun Weifeng , Yu Juzheng
Published: May 2017

In this paper, a fast switching fault diagnostic scheme is proposed for low‐power pulse width modulation (PWM) DC–DC converters operating in different conduction modes. The outstanding feature of the proposed scheme is that no additional sensing circuits are needed. This is achieved by using the differential of output ripple voltage and the switch gate driver signal for diagnosis. Since the output voltage has to be normally measured for control purposes and the PWM signals are known to the controller, no additional sensors are needed in the proposed scheme. Moreover, based on the real‐time output voltage measurement and switch gate driver signal, the characteristics of switch open‐ and short‐circuit faults can be rapidly extracted, specifically, in less than one switching cycle. Besides, the fault detection scheme can be implemented by a low‐cost logical hardware circuit, which can be integrated into the control unit. The fault diagnosis principle, design considerations, and implementation of the detection scheme are discussed in this paper. Experimental results show that the fault detection system can detect the switching fault in four‐tenths of the switching period. Besides, the proposed method can be used in the applications where the output voltage ripple rate is more than 4%, which covers most situations. © 2017 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Fictitious reference iterative tuning considering friction
Authors: Wakasa Yuji , Adachi Shojiro
Published: May 2017

This letter presents a controller parameter tuning technique for systems with negligible friction by using the so‐called fictitious reference iterative tuning (FRIT) method. In order to demonstrate the effectiveness of the presented FRIT method, experiments are carried out with a DC motor control system. © 2017 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Modelling the effect of coating on the stresses and microstructure evolution in chill casting of wind turbine main shafts
Authors: Sonne M.R. , Thorborg J. , Hattel J.H.
Published: May 2017

The purpose of the present work is to quantify the effect of the inside coating on chills for casting of large wind turbine main shafts with respect to the evolution of internal stresses. These are known to affect the lifetime of the chills, and this is a major cost for the foundries today. Simulations of the casting process are performed with four different heat transfer coefficients (HTCs) between the casting and the chill, and the resulting transient stress fields are reported in the chill. The microstructural evolution in the casting in terms of the nodule count is also modelled in the simulations. The outcome is validated by comparisons with samples taken out from a critical region of main shafts cast in sand and in chills. The results reveal minor reductions in the maximum principal stresses on the inner and outer surfaces of the chill of 3.1% and 18.5%, respectively, from changing the HTC from 2000 to 500 W m−2 K−1. These results indicate that the lifetime of the chill will not be significantly improved by adding a thicker layer of coating. The microstructure evolution is not very much affected by the HTC value with a maximum reduction in nodule count of 6.5%. Therefore, it is concluded that the material quality obtained from casting the main shafts in chills (and hence the performance of the part) is still much better than for sand casting, even though a very thick layer of coating is applied. Copyright © 2017 John Wiley & Sons, Ltd.
Mid-Term Outcomes of Metal-Backed Unicompartmental Knee Arthroplasty Show Superiority to All-Polyethylene Unicompartmental and Total Knee Arthroplasty
Authors: van der List Jelle P. , Kleeblad Laura J. , Zuiderbaan Hendrik A. , Pearle Andrew D.
Published: May 2017

Background

Two commonly used tibial designs for unicompartmental knee arthroplasty (UKA) are all-polyethylene “inlay” and metal-backed “onlay” components. Biomechanical studies showed that the metal baseplate in onlay designs better distributes forces over the tibia but studies failed to show differences in functional outcomes between both designs at mid-term follow-up. Furthermore, no studies have compared both designs with total knee arthroplasty (TKA).

Questions/Purposes

The goal of this study was to compare outcomes of inlay UKA and onlay UKA at mid-term follow-up and compare these with TKA outcomes.

Methods

In this retrospective study, 52 patients undergoing inlay medial UKA, 59 patients undergoing onlay medial UKA, and 59 patients undergoing TKA were included. Western Ontario and McMaster Universities Arthritis Index scores were collected preoperatively and at mean 5.1-year follow-up (range 4.0–7.0 years).

Results

Preoperatively, no differences were observed in patient characteristics or outcome scores. At mid-term follow-up, patients undergoing onlay medial UKA reported significant better functional outcomes than those of inlay medial UKA (92.0 ± 10.4 vs. 82.4 ± 18.7, p = 0.010) and when compared to TKA (92.0 ± 10.4 vs. 79.6 ± 18.5, p < 0.001) while no significant differences between inlay medial UKA and TKA were noted. No significant differences in revision rates were found.

Conclusion

Functional outcomes following onlay metal-backed medial UKA were significantly better compared to inlay all-polyethylene medial UKA and to TKA. Based on the results of this study and on biomechanical and survivorship studies in the literature, we recommended using metal-backed onlay tibial components for unicompartmental knee arthroplasty.
Linking eating and weight control attitudes to relationship experiences: A large‐scale survey of adolescent females
Authors: Thomas Rebekah L. , Kelly Adrian B. , Chan Gary C.K. , Williams Joanne W.
Published: May 2017

Objective

To examine the extent to which family conflict, peer bullying and psychological distress account for eating and weight loss attitudes in adolescent females. This study examined the degree to which psychological distress mediated the association between family conflict and eating and weight loss attitudes, and the association of bullying and eating and weight loss attitudes.

Method

Females aged between 11 and 17 years (N = 5125) were recruited from schools in the State of Victoria (Australia). Key measures included psychological distress, family conflict, and bullying victimisation.

Results

A structural model showed good fit, and all predictors were significant. Psychological distress mediated the association between eating and weight loss attitudes, and family problems and bullying.

Conclusion

Family conflict and peer bullying were associated with eating and weight loss attitudes and this association may occur via psychological distress. Early intervention programs may benefit from a focus on family and peer relationships.
On Europeanisation, national sentiments and confused identities in Georgia
Authors: Tsuladze Lia
Published: May 2017

This paper analyses Georgians’ popular online discourses on Europeanisation in the period between Georgia’s initialling and signing of the Association Agreement with the EU (November 2013–June 2014). It investigates the ambivalence encountered by Georgians: Despite their long-lasting aspiration towards EU integration, hopes of gaining political security, economic stability, and cultural integration are accompanied by doubts and fears of asymmetric power relations, diminishing national sovereignty, and declining national identity. Despite these doubts, EU integration is considered to be the only right choice for the country, encouraging Georgians, who readily perform their pro-European aspirations on the international “front stage”, to push their uncertainties and respective national sentiments to the domestic “backstage”.
A Novel Cooling Method and Comparison of Active Rewarming of Mildly Hypothermic Subjects
Authors: Christensen Mark L. , Lipman Grant S. , Grahn Dennis A. , Shea Kate M. , Einhorn Joseph , Heller H. Craig
Published: May 2017

Objective

To compare the effectiveness of arteriovenous anastomosis (AVA) vs heated intravenous fluid (IVF) rewarming in hypothermic subjects. Additionally, we sought to develop a novel method of hypothermia induction.

Methods

Eight subjects underwent 3 cooling trials each to a core temperature of 34.8±0.6 (32.7 to 36.3°C [mean±SD with range]) by 14°C water immersion for 30 minutes, followed by walking on a treadmill for 5 minutes. Core temperatures (Δtes) and rates of cooling (°C/h) were measured. Participants were then rewarmed by 1) control: shivering only in a sleeping bag; 2) IVF: shivering in sleeping bag and infusion of 2 L normal saline warmed to 42°C at 77 mL/min; and 3) AVA: shivering in sleeping bag and circulation of 45°C warmed fluid through neoprene pads affixed to the palms and soles of the feet.

Results

Cold water immersion resulted in a decrease of 0.5±0.5°C Δtes and 1±0.3°C with exercise ( P < .01); with an immersion cooling rate of 0.9±0.8°C/h vs 12.6±3.2°C/h with exercise ( P < .001). Temperature nadir reached 35.0±0.5°C. There were no significant differences in rewarming rates between the 3 conditions (shivering: 1.3±0.7°C/h, R 2 = 0.683; IVF 1.3±0.7 °C/h, R 2 = 0.863; and AVA 1.4 ±0.6°C/h, R 2 = 0.853; P = .58). Shivering inhibition was greater with AVA but was not significantly different ( P = .07).

Conclusions

This study developed a novel and efficient model of hypothermia induction through exercise-induced convective afterdrop. Although there was not a clear benefit in either of the 2 active rewarming methods, AVA rewarming showed a nonsignificant trend toward greater shivering inhibition, which may be optimized by an improved interface.
Interfaces of uniform momentum zones in turbulent boundary layers
Authors: de Silva Charitha M. , Philip Jimmy , Hutchins Nicholas , Marusic Ivan
Published: May 2017

In this paper we examine the characteristics of the interfaces that demarcate regions of relatively uniform streamwise momentum in turbulent boundary layers. The analysis utilises particle image velocimetry databases that span more than an order of magnitude of friction Reynolds number ($Re_{\unicode[STIX]{x1D70F}}=10^{3}$–$10^{4}$), enabling us to provide a detailed description of the interfacial layers as a function of Reynolds number. As reported by Adrianet al.(J. Fluid Mech., vol. 422, 2000, pp. 1–54), these interfaces appear as persistent regions of strong shear with distinct patches of vorticity consistent with a packet-like structure. Here, however, we treat these interfaces as continuous lines, thus averaging the properties of the vortical patches, and find that their geometry is highly contorted and exhibits self-similarity across a wide range of scales. Specifically, the lengths of the edges of uniform momentum zones exhibit a power-law behaviour with a fractal scaling that has a constant exponent across the boundary layer, while the topmost edge or the turbulent/non-turbulent interface shows a sudden increase in the exponent. The accompanying sharp changes in velocity that occur at these edges are found to change in magnitude as a function of wall-normal height, being larger closer to the wall. Further, a Reynolds number invariance is exhibited when the magnitude of the step-like changes in velocity is scaled by the skin-friction velocity, meanwhile, the width across which it occurs is shown to be of the order of the Taylor microscale. Based on these quantitative measures, the Reynolds number scaling observed and the persistent presence of sharp changes in momentum in turbulent boundary layers, a simple model is used to reconstruct the mean velocity profile. Insight gained from the model enhances our understanding of how instantaneous phenomena (such as a zonal-like structural arrangement) manifests in the averaged flow statistics and confirms that the instantaneous momentum in a turbulent boundary layer appears to mainly consist of a step-like profile as a function of wall-normal distance.