bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of waiting time on patient outcomes: Evidence from early intervention in psychosis services in England
Authors: Reichert Anika , Jacobs Rowena
Published: July 2018

Recently, new emphasis was put on reducing waiting times in mental health services as there is an ongoing concern that longer waiting time for treatment leads to poorer health outcomes. However, little is known about delays within the mental health service system and its impact on patients. We explore the impact of waiting times on patient outcomes in the context of early intervention in psychosis (EIP) services in England from April 2012 to March 2015. We use the Mental Health Services Data Set and the routine outcome measure the Health of the Nation Outcome Scale. In a generalised linear regression model, we control for baseline outcomes, previous service use, and treatment intensity to account for possible endogeneity in waiting time. We find that longer waiting time is significantly associated with a deterioration in patient outcomes 12 months after acceptance for treatment for patients that are still in EIP care. Effects are strongest for waiting times longer than 3 months, and effect sizes are small to moderate. Patients with shorter treatment periods are not affected. The results suggest that policies should aim to reduce excessively long waits in order to improve outcomes for patients waiting for treatment for psychosis.
Oscillatory natural convection of water‐glycerin mixture in a tall rectangular cavity: Transition to the chaos
Authors: Al‐Rashed Abdullah A.A.A. , Hassen Walid , Aich Walid , Kolsi Lioua , Ayadi Badreddine , Borjini Mohamed Naceur
Published: July 2018

This paper presents results of a numerical investigation involving bifurcation sequence leading to chaos in natural convection inside a vertically tall rectangular cavity having an aspect ratio equal to 15 and a Prandtl number equal to 125, corresponding to water‐glycerin mixture. The flow is characterized by a vertical stratification of the temperature field for Grashof numbers greater than or equal to 200 that is outside the conduction regime and it is stationary monocellular up to a critical value Grc = 2800 where a periodic oscillatory regime appears. As Grashof number is increased, a transition from a steady periodic bicellular flow to an oscillatory multicellular flow, with 2 main central cells and 2 secondary cells, occurs. The regime remains periodic until Gr = 3100 where there is a first appearance of the chaotic regime which extends over a narrow interval of the Grashof number delimited by Gr = 3200.
Inhibition effects of pesticides on glutathione‐S‐transferase enzyme activity of Van Lake fish liver
Authors: Özaslan Muhammet Serhat , Demir Yeliz , Aksoy Mine , Küfrevioğlu Ömer Irfan , Beydemir Şükrü
Published: July 2018

Glutathione‐S‐transferases (GSTs) have a function in xenobiotic metabolism. They are a significant multifunctional family with a wide variety of catalytic activities. In the current study, we determined in vitro inhibition effects of 2,4‐dichlorophenoxyacetic acid dimethylamine salt (2,4‐D DMA), haloxyfop‐P‐methyl, glyphosate isopropylamine, dichlorvos, and λ‐cyhalothrin on purified GST. For this purpose, GST were purified from Van Lake fish (Chalcalburnus tarichii Pallas) liver with 29.25 EU mg−1 specific activity and 10.76% yield using GSH–agarose affinity chromatographic method. The pesticides were tested at various concentrations on in vitro GST activity. Ki constants were calculated as 0.17 ± 0.01, 0.25 ± 0.05, 3.72 ± 0.32, 0.42 ± 0.06, and 0.025 ± 0.004 mM, for 2,4‐D DMA, haloxyfop‐P‐methyl, glyphosate isopropylamine, dichlorvos, and λ‐cyhalothrin, respectively. λ‐Cyhalothrin showed a better inhibitory effect compared to the other pesticides. The inhibition mechanisms of λ‐cyhalothrin were competitive, while the other pesticides were noncompetitive.
Protein kinase CK2 modulation of pyruvate kinase M isoforms augments the Warburg effect in cancer cells
Authors: Yang Kyung Mi , Kim Kunhong
Published: July 2018

Protein kinase CK2 is active in cancer cells. Previously, we reported that increased CK2 activity could induce epithelial mesenchymal transition of cancer cells. CK2 also induced epithelial mesenchymal transition in colon cancer cell lines such as HT29 and SW620, and the transitioned cells (CK2α cells) became more proliferative than the controls. We assumed that CK2 could affect cancer cell growth by modulating their energy metabolism. Here, we examined the molecular effects of CK2 on the glucose metabolism of cancer cells. We found that CK2α cells consumed more glucose and produced more lactate than control cells did. An XF glycolysis stress test showed that aerobic glycolysis was augmented up to the cancer cell’s maximal glycolytic capacity in CK2α cells. Molecular analysis revealed that pyruvate kinase M1 was downregulated and pyruvate kinase M2 was nuclear localized in CK2α cells. Consequently, the expression and activity of lactate dehydrogenase A (LDHA) were upregulated. Treatment with FX11—a specific LDHA inhibitor—or clustered regularly interspaced short palindromic repeats (CRISPR)‐mediated knockout of LDHA inhibited the CK2‐driven proliferation of cancer cells. We conclude that CK2 augments the Warburg effect, resulting in increased proliferation of cancer cells.
The vividness of imagining emotional feelings in positive situations is attenuated in non‐clinical dysphoria and predicts the experience of positive emotional feelings
Authors: Tiba Alexandru I. , Manea Laura
Published: July 2018

Objective

The vividness of imagining emotional feelings in positive situations (EFP) in non‐clinically dysphoric and non‐dysphoric individuals and its relation to dysphoric and positive feelings was examined.

Method

Participants were university students in Study 1 (N = 106, 84 women; 18–45 years), in Study 2 (N = 43, 39 women; 20–47 years), in Study 3 (N = 109, 92 women; 18–50 years) who filled out a set of questionnaires assessing depressive symptoms, cognition measures, and then completed an affective imagery task, using a cross‐sectional design.

Results

Non‐clinically dysphoric participants imagined less vividly EFP than non‐dysphoric participants. The vividness of imagining EFP accounted for group differences in positive feelings beyond positive and negative cognition and negative mood.

Conclusions

In addition to deficits in the general imagery of positive events, the attenuation of vividness of EFP in non‐clinical dysphoric individuals warrants attention as a separate pathway by which non‐clinically dysphoric individuals develop deficiencies of conscious positive feelings.
Conceptual Growth in Engineering Practice
Authors: Bornasal Floraliza , Brown Shane , Perova‐Mello Natasha , Beddoes Kacey
Published: July 2018

Background

Concepts are defined generally as fundamental principles or global understandings specific to a field of expertise. Theories of situated cognition suggest that concepts may not have uniform meaning or representation in a particular social setting.

Purpose/Hypothesis

The goal of this study was to investigate the process by which practicing engineers come to understand and use concepts in the context of their work.

Design/Method

A researcher conducted ethnographic fieldwork at a private consulting engineering firm. Data sources included (a) field notes obtained via participant observation, (b) transcripts from interviews, and (c) artifacts collected on site.

Results

Five emergent themes from the data are presented: (1) engineers identify constraints before they apply concepts, (2) engineers address project constraints by contextualizing abstract features of concepts, (3) engineers expand individual understanding of the concept by engaging in social negotiation of meaning, (4) concepts have multiple representations in engineering practice, and (5) engineers use material resources to efficiently address complex processes and problems associated with engineering concepts. These themes were analyzed using situative perspective to develop a model of conceptual growth in engineering practice.

Conclusions

Findings suggest that student learning experiences should deliberately highlight the role of engineering concepts in the often ill‐structured engineering problems present in authentic engineering work. Specific suggestions for incorporating the model into engineering education are offered as are directions for future research.
Proficiency testing for the detection of Middle East respiratory syndrome coronavirus demonstrates global capacity to detect Middle East respiratory syndrome coronavirus
Authors: Theis Torsten , Lau Katherine A. , Gray Joanna L. , Oxenford Christopher J. , Walker Gregory J. , Rawlinson William D.
Published: July 2018

The first reported case of Middle East respiratory syndrome coronavirus (MERS‐CoV) infection was identified in Saudi Arabia in September 2012, since which time there have been over 2000 laboratory‐confirmed cases, including 750 deaths in 27 countries. Nucleic acid testing (NAT) is the preferred method for the detection of MERS‐CoV. A single round of a Proficiency Testing Program (PTP) was used to assess the capability of laboratories globally to accurately detect the presence of MERS‐CoV using NAT. A panel of eleven lyophilized specimens containing different viral loads of MERS‐CoV, common coronaviruses, and in vitro RNA transcripts was distributed to laboratories in all six World Health Organization regions. A total of 96 laboratories from 79 countries participating in the PTP, with 76 of 96 (79.2%) reporting correct MERS‐CoV results for all nine scored specimens. A further 10 laboratories (10.4%) scored correctly in eight of nine specimens of the PTP. The majority of laboratories demonstrated satisfactory performance in detecting the presence of MERS‐CoV using NAT. However, some laboratories require improved assay sensitivity, reduced cross contamination of samples, and improved speciation of coronavirus subtypes for potentially complex clinical specimens. Further PTP and enhanced links with expert laboratories globally may improve the laboratory performance.
Influence of freezing on the bioaccessibility of beetroot (Beta vulgaris) bioactive compounds during in vitro gastric digestion
Authors: Dalmau Maria Esperanza , Llabrés Pedro Juan , Eim Valeria S , Rosselló Carmen , Simal Susana
Published: July 2018

Background

The effect of freezing (in liquid nitrogen at −196 °C , at −80 °C and at −20 °C) on the food matrix structure and the consequent effect on the bioaccessibility of total polyphenol content (TPC) and antioxidant activity (AA) of beetroot was investigated by an in vitro digestion method. The in vitro digestion involved incubation in simulated saliva followed by incubation in simulated gastric juice. Bioaccessibility of bioactive compounds was evaluated by measuring the TPC and the AA during in vitro digestion in both the beetroot matrix and the gastric juice.

Results

Release of TPC and AA of beetroot was higher in frozen samples (55 ± 5% for TPC and 68 ± 5% for AA) than in the fresh beetroot sample (∼46% for TPC and ∼53% for AA). The mass transfer kinetics were described by using a Weibull model with mean relative errors lower than 8.5% contributing to a better understanding of the influence of freezing on the bioaccessibility of bioactive compounds.

Conclusions

From the treatments tested in this study, freezing with liquid nitrogen resulted in the greatest increase in bioaccessibility of the antioxidant and phenolic compounds of beetroots. © 2018 Society of Chemical Industry
Determination of the softening point of rosin by a simple and automated headspace gas chromatographic technique
Authors: Dai Yi , Yu Zhen‐Hua , Zhan Jian‐Bo , Yue Bao‐Shan , Xie Jiao , Wang Hao , Chai Xin‐Sheng
Published: July 2018

We report a simple and automated headspace gas chromatographic technique for the determination of the softening point of rosin. A lumpy solid of rosin is added into a headspace vial, then an automated stepwise temperature ramping and headspace sampling was performed at each temperature stage and gas chromatography measurement. By plotting the gas chromatography signal for an impurity in rosin versus the temperature, a transition point (corresponding to the rosin softening point) was determined. The results show that the present method has a good precision (<0.76%), and good accuracy (the relative differences compared to the ring and ball method was <4.0%). The present method is simple, accurate, and automated. It is practical and suitable for testing the softening of rosin and derivatives in mills.
Simultaneous determination of total homocysteine, cysteine, glutathione, and N‐acetylcysteine in brain homogenates by HPLC
Authors: Kamińska Adrianna , Olejarz Patrycja , Borowczyk Kamila , Głowacki Rafał , Chwatko Grażyna
Published: July 2018

We have developed a simple, fast, accurate, and cheap method for the simultaneous determination of total cysteine, homocysteine, glutathione, and N‐acetylcysteine in brain homogenates based on the reduction of disulfide bonds by tris(2‐carboxyethyl) phosphine, pre‐column derivatization of free thiol groups with 2‐chloro‐1‐methylquinolinium tetrafluoroborate followed by ion‐pair reversed‐phase high‐performance liquid chromatography separation with ultraviolet detection. The separation of thiol derivatives was achieved in 10 min. Linearity was observed in the range of 10–300, 0.7–10, 2–30, and 3–20 μmol/L homogenate with a limit of detection of 3.7, 0.2, 0.8, and 1.2 μmol/L homogenate for cysteine, homocysteine, glutathione, and N‐acetylcysteine, respectively. The precision, calculated as relative standard deviation, was in the range of 1.21–4.77, 1.53–14.35, 0.47–1.92, and 1.61–8.95% for cysteine, homocysteine, glutathione, and N‐acetylcysteine, respectively. The presented method was successfully applied to the selective determination of total amino thiols in pig brain tissue samples.
Large‐scale comparison of flow‐variability dampening by lakes and wetlands in the landscape
Authors: Quin Andrew , Destouni Georgia
Published: July 2018

Considering the potential of wetlands to dampen temporal variability of water flow through the landscape, they are increasingly considered as possible nature‐based solutions to mitigate risks of flooding and drought. In this study, we investigate flow variability by means of a flow dampening factor and use observation data from 1984 to 2013 for 82 Swedish catchments to statistically and comparatively analyze the large‐scale effects on this factor of multiple wetlands and lakes in the landscape. The results show good correlation between large‐scale flow dampening and relative area of lakes and floodplain wetlands within a catchment. An increase in relative area up to around 15% for lakes and 0.5% for floodplain wetlands lowers the temporal standard deviation of runoff (R) to around 10%–15% of that for precipitation (P), compared with a common flow‐variability dampening of around 35% for catchments with lake‐wetland area close to zero. Further increase in these relative areas, or in those of wetland types other than floodplain wetlands, has little or no flow dampening effect. The results indicate that the large‐scale flow dampening effect of lakes and floodplain wetlands is mainly due to their water‐storage capacity and less due to their possible effects on the partitioning of P between R and evapotranspiration. Overall, the results emphasize the importance of accounting for the problem scale and relative water‐storage capacity of wetlands when considering their large‐scale efficiency as possible nature‐based solutions for large‐scale flow‐variability regulation in whole catchments.
Green roofs: Effects of plant species used on runoff
Authors: Li XiaoXiao , Cao JunJun , Xu PeiXian , Fei Ling , Dong Qin , Wang ZhaoLong
Published: July 2018

Green roofs are becoming a major nature‐based solution worldwide to reduce urban stormwater runoff. Runoff reduction and retention mainly depend on the hydrological characteristics of substrates and the water use strategies of plants. However, little is known about how plant species affect the hydrological performance of green roofs. Two commonly used succulent plants and four turfgrass species were investigated for their impacts on the hydrological performance and runoff reduction of green roof lysimeters under controlled conditions using a rainfall simulator. The results showed that two succulent plants (Sedum lineare and Callisia repens) did not make significant contributions to canopy interception in any of the four seasons and made only minor contributions to evapotranspiration (ET) water loss in autumn and winter, resulting in minor effects on runoff reduction by the green roofs. Festuca arundinacea contributed 47.4–116.7% of water loss via transpiration and 36.5% of runoff reduction under a 25 mm day−1 rainfall intensity in spring and 48.0% of runoff reduction under a 10 mm day−1 rainfall intensity in winter. Poa pratensis, Lolium perenne, and Agrostis stolonifera also significantly reduced runoff. Runoff reductions by extensive green roofs were mainly caused by ET rather than by their canopy interceptions. Plant shoot biomass and ET were the primary factors controlling the runoff reduction by extensive green roofs. Our results strongly suggest that the runoff reduction capacity of extensive green roofs can be greatly improved by selecting plant species with a higher shoot biomass and ET rate.
Deep Brain Stimulation at Variable Frequency to Improve Motor Outcomes in Parkinson's Disease
Authors: Jia Fumin , Wagle Shukla Aparna , Hu Wei , Almeida Leonardo , Holanda Vanessa , Zhang Jianguo , Meng Fangang , Okun Michael S. , Li Luming
Published: July 2018

Introduction

Deep brain stimulation (DBS) with high frequency (HFS) is a well‐established therapy for Parkinson's disease (PD); however, low frequency DBS (LFS) may control axial symptoms including freezing of gait (FOG). We conducted a pilot safety and feasibility study to examine if a novel DBS paradigm of variable frequency stimulation (VFS) that combined HFS and LFS would capture a broader set of motor symptoms.

Methods

Four PD patients with bilateral STN DBS and FOG were enrolled. A UPDRS III and 10 m timed up and go (TUG) task were performed off medications‐off DBS and then one hour after HFS and one hour after VFS programming.

Results

The UPDRS III motor score improved by additional 14% during VFS setting when compared to HFS. VFS also increased gait speed (mean change 45%) and reduced the number of freezing episodes (mean change 58%).

Conclusions

VFS improves UPDRS and FOG in PD when compared to HFS.Copyright © 2018 International Parkinson and Movement Disorder Society
4D robust optimization including uncertainties in time structures can reduce the interplay effect in proton pencil beam scanning radiation therapy
Authors: Engwall Erik , Fredriksson Albin , Glimelius Lars
Published: July 2018

Purpose

Interplay effects in proton radiotherapy can create large distortions in the dose distribution and severely degrade the plan quality. Standard methods to mitigate these effects include abdominal compression, gating, and rescanning. We propose a new method to include the time structures of the delivery and organ motion in the framework of four‐dimensional (4D) robust optimization to generate plans that are robust against interplay effects.

Methods

The method considers multiple scenarios reflecting the uncertainties in the delivery and in the organ motion. In each scenario, the pencil beam scanning spots are distributed to different phases of the breathing cycle according to each individual spot time stamp, and a partial beam dose is calculated for each phase. The partial beam doses are accumulated on a reference phase through deformable image registrations. Minimax optimization is performed to take all scenarios into account simultaneously. For simplicity, the uncertainties in this proof of concept study are limited to variations in the breathing pattern. The method is evaluated for three different nonsmall cell lung cancer patients and compared to plans using conventional 4D robust optimization both with and without rescanning. We assess the ability of the method to mitigate distortions from the interplay effect over multiple evaluation scenarios using 4D dose calculations. This interplay evaluation is performed in an experimentally validated framework, which is independent of the optimization in the plan generation step.

Results

For the three studied patients, 4D optimization including time structures is efficient, especially for large tumor motions, where rescanning of conventional 4D robustly optimized plans is not sufficient to mitigate the interplay effect. The most efficient approach of the new method is achieved when it is combined with rescanning. For the patient with the largest motion, the mean V95% is 99.2% and mean V107% is 3.65% for the best rescanned 4D plan optimized with time structure. This can be compared to conventional 4D optimized plans with mean V95% of 92.7% and mean V107% of 13.1%.

Conclusions

The current study shows the potential of reducing interplay effects in proton pencil beam scanning radiotherapy by incorporating organ motion and delivery characteristics in a 4D robust optimization.
A hierarchical thermo‐hydro‐plastic constitutive model for unsaturated soils and its numerical implementation
Authors: Song Xiaoyu , Wang Kaiqi , Bate Bate
Published: July 2018

Unsaturated soils are highly heterogeneous 3‐phase porous media. Variations of temperature, the degree of saturation, and density have dramatic impacts on the hydro‐mechanical behavior of unsaturated soils. To model all these features, we present a thermo‐hydro‐plastic model in which the hydro‐mechanical hardening and thermal softening are incorporated in a hierarchical fashion for unsaturated soils. This novel constitutive model can capture heterogeneities in density, suction, the degree of saturation, and temperature. Specifically, this constitutive model has 2 ingredients: (1) it has a “mesoscale” mechanical state variable—porosity and 3 environmental state variables—suction, the degree of saturation, and temperature; (2) both temperature and mechanical effects on water retention properties are taken into account. The return mapping algorithm is applied to implement this model at Gauss point assuming an infinitesimal strain. At each time step, the return mapping is conducted only in principal elastic strain space, assuming no return mapping in suction and temperature. The numerical results obtained by this constitutive model are compared with the experimental results. It shows that the proposed model can simulate the thermo‐hydro‐mechanical behavior of unsaturated soils with satisfaction. We also conduct shear band analysis of an unsaturated soil specimen under plane strain condition to demonstrate the impact of temperature variation on shear banding triggered by initial material heterogeneities.
Iterative solvers for generalized finite element solution of boundary‐value problems
Authors: Mohamed M Shadi , Seaid Mohammed , Bouhamidi Abderrahman
Published: July 2018

Most of generalized finite element methods use dense direct solvers for the resulting linear systems. This is mainly the case due to the ill‐conditioned linear systems that are associated with these methods. In this study, we investigate the performance of a class of iterative solvers for the generalized finite element solution of time‐dependent boundary‐value problems. A fully implicit time‐stepping scheme is used for the time integration in the finite element framework. As enrichment, we consider a combination of exponential functions based on an approximation of the internal boundary layer in the problem under study. As iterative solvers, we consider the changing minimal residual method based on the Hessenberg reduction and the generalized minimal residual method. Compared with dense direct solvers, the iterative solvers achieve high accuracy and efficiency at low computational cost and less storage as only matrix–vector products are involved in their implementation. Two test examples for boundary‐value problems in two space dimensions are used to assess the performance of the iterative solvers. Comparison to dense direct solvers widely used in the framework of generalized finite element methods is also presented. The obtained results demonstrate the ability of the considered iterative solvers to capture the main solution features. It is also illustrated for the first time that this class of iterative solvers can be efficient in solving the ill‐conditioned linear systems resulting from the generalized finite element methods for time domain problems.
The subtleties of stress: A comparative analysis of skeletal lesions between the Medieval and post‐Medieval Black Friars cemetery population (13th to 17th centuries)
Authors: Scott Amy B. , Hoppa Robert D.
Published: July 2018

The study of stress from an osteological perspective is challenging as we use skeletal remains to explore the lived experience and patterns of health. As an intricate overlap of multiple biological processes, the stress response system guides our understanding of how and why stress manifests as it does. Using traditional osteological methods of stress analysis, specifically cribra orbitalia, porotic hyperostosis, and enamel hypoplastic lesions, this study focuses on the relationship between these indicators to explore differences in stress manifestation in the Medieval and post‐Medieval periods in Denmark. Using the Black Friars cemetery population (13th–17th centuries), results show an increase in stress from the Medieval into the post‐Medieval period likely dictated by the strains of urbanism on a predominantly poor population. Additionally, a younger mean age at death was noted when multiple mild–moderate indicators were present as compared with one severe indicator being present. A recognition of the intricacies of the stress response effectively aids in the exploration of stress manifestation and the relationship, if any, between these well‐used skeletal indicators.
Improvements in the oxygen barrier property of polypropylene nanocomposites
Authors: Kim Dong Hyun , Ryu Yeon Sung , Kim Seong Hun
Published: July 2018

A nanocomposite consisting of polypropylene (PP)/nanoclay (montmorillonite) was prepared by means of a melt‐compounding process with the use of a twin‐screw extruder. Because of the complex dispersion of polar and hydrophilic clays that have many cations in the nonpolar and hydrophobic PP, amino‐silane was introduced to modify the surface of the clays. Also, to improve the compatibility of the modified nanoclay with PP, a PP‐graft‐maleic anhydride was used as a compatibilizer. From Fourier transform infrared spectroscopy analysis and the mechanical property test results, it was confirmed that the surface of the nanoclay was properly modified, and it was successfully dispersed in the PP matrix. The composite was investigated by electron microscopy to analyze its morphology and the degree of dispersion of the nanoclay. An analysis of oxygen permeability according to nanoclay content was performed, and it was found that the higher nanoclay content makes the decrease in oxygen permeability. In addition, a shelf‐life test was carried out to determine the relationship between decreased oxygen permeability and food preservation performance. The preservation performance of the food package prepared with the resin made in this study was improved because of the improvement in mechanical properties and oxygen barrier property.
Reduced expression of the RNA‐binding protein HuD in pancreatic neuroendocrine tumors correlates with low p27Kip1 levels and poor prognosis
Authors: Kim Chongtae , Jeong Da Eun , Heo Sungeun , Ji Eunbyul , Rho Jun Gi , Jung Myeongwoo , Ahn Sojin , Kim Ye‐Jin , Kim Yong‐Sung , Nam Suk Woo , Kulkarni Rohit N , Lee Kyoung Bun , Lee Eun Kyung , Kim Wook
Published: July 2018

For the majority of patients diagnosed with pancreatic neuroendocrine tumors (NETs), there is significant malignant potential with a poor prognosis; however, the molecular abnormalities and pathogenesis of pancreatic NETs have not been firmly established. Here, we report that loss of expression of the RNA‐binding protein HuD correlates with low p27Kip1 (p27) levels and poor prognosis in pancreatic NETs. HuD expression was frequently lost in many human pancreatic NETs, and these pancreatic NETs showed aggressive clinicopathological phenotypes with low p27 levels, increased tumor size, higher World Health Organization grade and pT stage of the tumor, and the presence of angioinvasion. Furthermore, loss of HuD was an independent, progression‐free prognostic factor in multivariate survival analysis. However, the level of HuR, a member of the same Hu protein family as HuD, was not significantly correlated with pancreatic NET size and progression. Mechanistically, HuD enhanced p27 mRNA translation by interacting with both the 5′‐untranslated region (UTR) and the 3′‐UTR of p27 mRNA, and consequently suppressed cell cycle progression and tumor growth. In addition, HuD competed with miR‐30a‐3p for binding to the 3′‐UTR of p27 mRNA, suggesting an interplay between HuD and miR‐30a‐3p in controlling p27 translation. Our results identify HuD as a pivotal suppressor of pancreatic NET growth, and suggest that HuD has potential value as a prognostic factor of pancreatic NETs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Biallelic tumour suppressor loss and DNA repair defects in de novo small‐cell prostate carcinoma
Authors: Chedgy Edmund CP , Vandekerkhove Gillian , Herberts Cameron , Annala Matti , Donoghue Adam J , Sigouros Michael , Ritch Elie , Struss Werner , Konomura Saki , Liew Janet , Parimi Sunil , Vergidis Joanna , Hurtado‐Coll Antonio , Sboner Andrea , Fazli Ladan , Beltran Himisha , Chi Kim N , Wyatt Alexander W
Published: July 2018

Small‐cell prostate carcinoma (SCPC) is an aggressive malignancy that is managed similarly to small‐cell lung cancer. SCPC can evolve from prostate adenocarcinoma in response to androgen deprivation therapy, but, in rare cases, is present at initial cancer diagnosis. The molecular aetiology of de novo SCPC is incompletely understood, owing to the scarcity of tumour tissue and the short life‐expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology, and the remainder had some admixed adenocarcinoma foci, but all were treated with first‐line platinum‐based chemotherapy. The median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin‐fixed paraffin‐embedded archival tumour tissue. We observed frequent biallelic deletion and/or mutation of the tumour suppressor genes TP53, RB1, and PTEN, similarly to what was found in treatment‐related SCPC. Indeed, at the RNA level, pure de novo SCPC closely resembled treatment‐related SCPC. However, five patients had biallelic loss of DNA repair genes, including BRCA1, BRCA2, ATM, and MSH2/6, potentially underlying the high genomic instability of this rare disease variant. Two patients with pure de novo SCPC harboured ETS gene rearrangements involving androgen‐driven promoters, consistent with the evolution of de novo SCPC from an androgen‐driven ancestor. Overall, our results reveal a highly aggressive molecular landscape that underlies this unusual pathological variant, and suggest opportunities for targeted therapy strategies in a disease with few treatment options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Panobinostat inhibits the proliferation of CD34+CD38−cells under stimulation of hematopoietic growth factors on AGM‐S3 cells in juvenile myelomonocytic leukemia
Authors: Kurata Takashi , Matsuda Kazuyuki , Hirabayashi Koichi , Shigemura Tomonari , Sakashita Kazuo , Nakahata Tatsutoshi , Koike Kenichi
Published: July 2018

Background

Encouraging responses to histone deacetylase inhibitors have been reported for hematologic malignancies. Here, we report effects of panobinostat and 5‐azacytidine on the proliferation of juvenile myelomonocytic leukemia (JMML) CD34+ cells.

Procedure

We previously reported that stimulation of JMML CD34+ cells with stem cell factor and thrombopoietin on irradiated murine AGM‐S3 cells led to substantial expansion of JMML CD34+ cells that contained leukemic stem cells capable of transplantation into immunodeficient mice. Using this culture system, we evaluated effects of panobinostat and 5‐azacytidine on the proliferation of JMML CD34+ cells.

Results

Panobinostat dose dependently reduced the numbers of day 7 CD34+ cells generated under stimulation of hematopoietic growth factors on AGM‐S3 cells in all eight patients with JMML. These patients possessed various genetic and/or karyotypic abnormalities. CD34+CD38− cells were substantially more sensitive to panobinostat at 10 and 20 nM than CD34+CD38+ cells. Panobinostat, however, failed to influence the ability of AGM‐S3 cells to stimulate JMML CD34+ cell production. In contrast to HL60 cells, apoptosis and cell cycle arrest in panobinostat‐mediated inhibition were at low levels in JMML. The inhibitor also suppressed the factor‐dependent proliferation of normal CD34+ cells on AGM‐S3 cells. Meanwhile, no substantial inhibitory effects of 5‐azacytidine on the growth of JMML CD34+ cells were observed.

Conclusions

These results demonstrate that panobinostat directly suppresses the growth of JMML CD34+ cells, in particular CD34+CD38− cells, regardless of the genetic abnormality type, suggesting that it is a useful antileukemic drug to target JMML stem cells at a pretransplant stage.
Examining correlates of teacher receptivity to social influence strategies within a school consultation relationship
Authors: Owens Julie Sarno , Allan Darcey M. , Hustus Chelsea , Erchul William P.
Published: July 2018

Successful school consultation depends largely on the consultant's ability to influence teacher behavior and the teacher's receptivity to that influence. The goal of this study was to examine correlates of teacher receptivity to social influence strategies within school consultation. Participants were 365 general education teachers (K‐5) recruited through Amazon's Mechanical Turk. Teachers completed questionnaires that included (1) three subscales of the modified Consultee/Teacher Version of the Interpersonal Power Inventory assessing soft social influence strategies; and measures assessing (2) personality constructs; (3) knowledge of behavior modification and mental health literacy; (4) need for cognition and beliefs about student behavior and interventions; and (5) work‐related stress. As expected, the subscales of the modified Interpersonal Power Inventory had acceptable internal consistency (alphas > .70). Hierarchical regression analyses revealed that teacher beliefs, need for cognition, and the interaction between need for cognition and stress, were significantly positively associated with receptivity to positive expert and direct information influences, after accounting for personality characteristics. These relationships were not found for receptivity to positive referent influences. Instead, knowledge of behavioral principles was negatively associated with this social influence. Results are discussed in relation to consultation research and practice.
Silybum marianum (milk thistle) and its main constituent, silymarin, as a potential therapeutic plant in metabolic syndrome: A review
Authors: Tajmohammadi Atefeh , Razavi Bibi Marjan , Hosseinzadeh Hossein
Published: July 2018

Metabolic syndrome describes a complex metabolic risk factors including obesity, hypertension, dyslipidemia, and diabetes. This syndrome is diagnosed by medical conditions such as weight gain, high blood pressure, high blood glucose, and disturbance in lipid profile. Metabolic syndrome has become as an important and increasing global health problem, so finding potentially novel solutions with less adverse effects is favorable for health problems. Herbal therapy plays an important role for treatment of different diseases. Silybum marianum is a plant that is used for centuries as a herbal treatment in liver and biliary tract diseases. Silymarin is the main component of S. marianum and derived from fruits and seeds of S. marianum (milk thistle). S. marianum has been found to exhibit antioxidant, lipid‐lowering, antihypertensive, antidiabetic, antiatherosclerotic, anti‐obesity, and hepatoprotective effects. Therefore, the aim of this review is to summarize different animal and human studies regarding the effect of S. marianum in metabolic syndrome and to identify the underlying mechanisms of action.
Measurement and analysis of vibration levels for express logistics transportation in South China
Authors: Zhou Hao , Wang Zhi‐Wei
Published: July 2018

Trunk transportation and terminal distribution are two important parts of express delivery in China. Heavy truck and medium truck are two main vehicles of trunk transportation. Mini van and two‐wheel electric bicycle are widely used for terminal distribution. Four vehicles mentioned previously and a sedan car were chosen for vibration level measurement and analysis in this paper. The results revealed that vibration levels were significantly higher in the vertical axis, and decreased with the increase of payload, and increased with the increase of speed again. Similar power spectral density peak frequencies were found in a comparison study with previous results in the low‐frequency region (1‐10 Hz), occurred at approximately 2 Hz in the van and sedan car and at 3 to 4 Hz in the truck and at 4 to 5 Hz in the two‐wheel electric bicycle. Except the two‐wheel electric bicycle, the second peak frequency occurred at approximately 20 to 30 Hz in the sedan car and at 10 to 20 Hz in the mini van and at 20 to 40 Hz in the heavy truck, which were also similar to the previous studies. Vibration levels of the sedan car were the lowest, and the trunk transportation vehicles (heavy truck, medium truck) were the highest. The terminal distribution vehicles (mini van, two‐wheel electric bicycle) were somewhere in the middle.
Investigating the predictability of a Mediterranean tropical‐like cyclone using a storm‐resolving model
Authors: Cioni Guido , Cerrai Diego , Klocke Daniel
Published: July 2018

Predicting the trajectory and structure of Mediterranean tropical‐like cyclones (MTLCs) has always been a challenge even within a few hours of verification time, given the inadequacy of numerical weather prediction (NWP) models to resolve the relatively small spatial scale of these systems. In particular, the event of 7–8 November 2014 was poorly predicted by operational NWP models which failed to reproduce the trajectory of the cyclone. Using a state‐of‐the‐art storm‐resolving model, we show that simulations with a grid spacing of approximately 1 km are able to reproduce the fine‐scale structure of this MTLC. Simulations performed with grid spacing larger than 2.5 km fail to represent the features of the cyclone, while additional nested simulations with very high resolution (300 m) reveal the ability of the model to fully capture the internal structure of the cyclone. Thus, there is a noticeable convergence towards the observed trajectory of the cyclone with increasing resolution. Finally, a potential vorticity (PV) analysis highlights the mutual interaction between a PV streamer and a low‐level PV maximum induced by convection. Only convection‐resolving simulations, with a grid spacing smaller than 5 km, show a low‐level maximum of PV which impacts the redistribution of PV at the higher atmospheric levels.
Multiple imputation in Cox regression when there are time‐varying effects of covariates
Authors: Keogh Ruth H. , Morris Tim P.
Published: July 2018

In Cox regression, it is important to test the proportional hazards assumption and sometimes of interest in itself to study time‐varying effects (TVEs) of covariates. TVEs can be investigated with log hazard ratios modelled as a function of time. Missing data on covariates are common and multiple imputation is a popular approach to handling this to avoid the potential bias and efficiency loss resulting from a “complete‐case” analysis. Two multiple imputation methods have been proposed for when the substantive model is a Cox proportional hazards regression: an approximate method (Imputing missing covariate values for the Cox model in Statistics in Medicine (2009) by White and Royston) and a substantive‐model‐compatible method (Multiple imputation of covariates by fully conditional specification: accommodating the substantive model in Statistical Methods in Medical Research (2015) by Bartlett et al). At present, neither accommodates TVEs of covariates. We extend them to do so for a general form for the TVEs and give specific details for TVEs modelled using restricted cubic splines. Simulation studies assess the performance of the methods under several underlying shapes for TVEs. Our proposed methods give approximately unbiased TVE estimates for binary covariates with missing data, but for continuous covariates, the substantive‐model‐compatible method performs better. The methods also give approximately correct type I errors in the test for proportional hazards when there is no TVE and gain power to detect TVEs relative to complete‐case analysis. Ignoring TVEs at the imputation stage results in biased TVE estimates, incorrect type I errors, and substantial loss of power in detecting TVEs. We also propose a multivariable TVE model selection algorithm. The methods are illustrated using data from the Rotterdam Breast Cancer Study. R code is provided.
Estimating individualized optimal combination therapies through outcome weighted deep learning algorithms
Authors: Liang Muxuan , Ye Ting , Fu Haoda
Published: July 2018

With the advancement in drug development, multiple treatments are available for a single disease. Patients can often benefit from taking multiple treatments simultaneously. For example, patients in Clinical Practice Research Datalink with chronic diseases such as type 2 diabetes can receive multiple treatments simultaneously. Therefore, it is important to estimate what combination therapy from which patients can benefit the most. However, to recommend the best treatment combination is not a single label but a multilabel classification problem. In this paper, we propose a novel outcome weighted deep learning algorithm to estimate individualized optimal combination therapy. The Fisher consistency of the proposed loss function under certain conditions is also provided. In addition, we extend our method to a family of loss functions, which allows adaptive changes based on treatment interactions. We demonstrate the performance of our methods through simulations and real data analysis.
Modeling Doctoral Population Growth in Premier Technology Institutions in India
Authors: Menon Balagopal G. , Kumar Ghatak Supriya , Mahanty Biswajit , Sahadev Sunil
Published: July 2018

The present study utilizes the basic reproductive number ‘R0’ to make sense of the Indian Institute of Technologies' (IITs) doctoral population growth. The analysis shows that the R0 for seven IITs under study, and for the engineering disciplines in these IITs, has increased over time. The estimation shows that for the seven IITs, every faculty member, on average, graduates 12.81 PhD students during their entire career. For the engineering disciplines, this rate is 11.3 PhD graduates per faculty. This implies that in a steady state, only 7.8% of PhD graduates can secure faculty positions in IITs. This, further, shows that the remaining IIT PhD graduates need to find employment outside IIT academia. Moreover, engineering disciplines with a high R0 show higher research productivity compared with those with a low R0 that gives scope for the latter to make improvements in their future research activities. © 2018 John Wiley & Sons, Ltd.
Transparency and Reproducibility in Participatory Systems Modelling: the Case of Fuzzy Cognitive Mapping
Authors: Olazabal Marta , Neumann Marc B. , Foudi Sébastien , Chiabai Aline
Published: July 2018

By aggregating semi‐quantitative mind maps from multiple agents, fuzzy cognitive mapping (FCM) allows developing an integrated, cross‐sectoral understanding of complex systems. However, and especially for FCM based on individual interviews, the map‐building process presents potential pitfalls. These are mainly related to the different understandings of the interviewees about the FCM semantics as well as the biases of the analyst during the elicitation and treatment of data. This paper introduces a set of good practice measures to increase transparency and reproducibility of map‐building processes in order to improve credibility of results from FCM applications. The case study used to illustrate the proposed good practices assesses heatwave impacts and adaptation options in an urban environment. Agents from different urban sectors were interviewed to obtain individual cognitive maps. Using this set of data, we suggest good practices to collect, digitalize, interpret, pre‐process and aggregate the individual maps in a traceable and coherent way. © 2018 The Authors Systems Research and Behavioral Science published by International Federation for Systems Research and John Wiley & Sons Ltd
Virtual reality objects improve learning efficiency and retention of diagnostic ability in fetal ultrasound
Authors: Ebert J. , Tutschek B.
Published: July 2018

Objective

Virtual reality (VR) objects of fetal ultrasound volumes have been proposed for teaching and learning diagnostic ultrasound. The aim of this study was to determine if VR objects improve learning efficiency and retention of diagnostic ability in fetal ultrasound.

Methods

Medical students and junior doctors were taught normal and abnormal sonographic fetal brain anatomy using conventional means (video lectures and review articles; control group) or additionally with selected VR objects from a novel fetal brain atlas (Pocket Brain,
http://pb.fetal.ch; study group). Knowledge, speed of recognition and retention of diagnostic ability were tested in multiple‐choice questionnaires 1 and 4 months after teaching, and the results were compared between those taught using conventional means only and those taught using VR objects.

Results

Participants taught using VR objects answered significantly more questions correctly and solved the tests quicker than those taught using conventional methods only, both 1 and 4 months after teaching.

Conclusion

The use of VR objects in teaching fetal ultrasound significantly improves learning efficiency and knowledge retention. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.