bluuebunny/crossref_metadata_2025 huggingface dataset:
Northern Italy in the American South: Assessing interobserver reliability within the Milan System for Reporting Salivary Gland Cytopathology
Authors: Hollyfield Johnathan M. , O'Connor Siobhan M. , Maygarden Susan J. , Greene Kevin G. , Scanga Lori R. , Tang Sherry , Dodd Leslie G. , Wobker Sara E.
Published: March 2018

BACKGROUND

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has been proposed to standardize salivary gland fine‐needle aspiration (FNA) diagnoses. This study assessed salivary gland FNA results and risk of malignancy (ROM) rates at the University of North Carolina as well as the interobserver reliability (IOR) of the atypia of undetermined significance (AUS) and salivary gland neoplasm of uncertain malignant potential (SUMP) categories.

METHODS

The electronic medical record was searched for FNA cases from 2010 to 2017 with subsequent surgical resections. Histologic diagnosis was used for gold‐standard comparison. The original cytologic results were then converted into MSRSGC categories (nondiagnostic, nonneoplastic, AUS, benign neoplasm, SUMP, suspicious, and malignant). For the assessment of IOR, 23 cases were selected with enrichment for cases diagnosed as AUS (n = 11) or SUMP (n = 9). Six boarded cytopathologists and 1 cytopathology fellow assessed representative slides and provided an MSRSGC diagnosis for each case. Fleiss' κ coefficients were calculated to determine IOR.

RESULTS

The ROM was 33% for both AUS and SUMP cases; however, the risk of neoplasia was 56% for AUS cases and 100% for SUMP cases. Fleiss' κ for the AUS category was 0.217 (P < .05), and Fleiss' κ for the SUMP category was 0.024 (P = .74).

CONCLUSIONS

In this study assessing the IOR of MSRSGC categories, fair agreement and slight agreement were found for the AUS and SUMP categories, respectively. Observers preferentially used the AUS or benign neoplasm category for SUMP cases, perhaps because of unfamiliarity with SUMP as a diagnostic option. The initial adoption of a new reporting system will require a quality assessment to ensure that the system is reliable and useful for clinicians. Cancer Cytopathol 2018;126:390‐6. © 2018 American Cancer Society.
Barriers to the recognition of medullary thyroid carcinoma on FNA: Implications relevant to the new American Thyroid Association guidelines
Authors: Dyhdalo Kathryn S. , Chute Deborah J.
Published: March 2018

BACKGROUND

The 2016 American Thyroid Association guidelines recommend multiple endocrine neoplasia testing and evaluation for pheochromocytoma before thyroidectomy after a thyroid fine‐needle aspiration biopsy (FNA) is positive for medullary thyroid carcinoma (MTC). In the current study, the authors examined the reasons why FNA was unable to definitively diagnose MTC preoperatively, with attention to morphologic patterns that can be misleading.

METHODS

Cases of MTC diagnosed on thyroid surgical resection for which there was a prior FNA and slides available for review were included (28 cases). Clinicopathologic data were collected. Slides were reviewed for numerous features blinded to the original FNA interpretation. Morphologic features were compared between concordant cases (20 cases) (“positive for MTC” or “suspicious for MTC”) and discordant cases (4 cases) (any other interpretation). Three cases of microscopic MTC (measuring <1 cm) were excluded from statistical analysis, as was 1 case of sampling error (benign thyroid tissue).

RESULTS

Nine men and 19 women were diagnosed with MTC. Four patients ultimately were diagnosed with multiple endocrine neoplasia, and 1 had bilateral pheochromocytomas. At the time of surgical excision, the mean tumor size was 2.3 cm (range, 0.1‐7.5 cm). Review of morphologic features demonstrated that the discrepant cases were significantly more likely to have limiting factors (air‐drying artifact/excess blood), a cohesive pattern, or to lack plasmacytoid morphology. None of the discordant cases had pseudoinclusions or amyloid (finding was not statistically significant).

CONCLUSIONS

The majority (86%) of thyroid FNAs from patients with MTC are concordant (positive/suspicious for MTC). Patterns of failure include sampling error and limited typical morphologic features, particularly a lack of plasmacytoid morphology and cellular dyshesion. A high level of suspicion for MTC is critical to ensure patients receive appropriate preoperative testing. Cancer Cytopathol 2018;126:397‐405. © 2018 American Cancer Society.
Utility of the BRAF p.V600E immunoperoxidase stain in FNA direct smears and cell block preparations from patients with thyroid carcinoma
Authors: Smith Amber L. , Williams Michelle D. , Stewart John , Wang Wei‐Lien , Krishnamurthy Savitri , Cabanillas Maria E. , Roy‐Chowdhuri Sinchita
Published: March 2018

BACKGROUND

The identification of BRAF mutations in thyroid cancer has prognostic and therapeutic implications. Although the gold standard for identifying BRAF mutations is molecular testing, the ability to perform BRAF p.V600E immunostaining on fine‐needle aspiration (FNA) samples can facilitate the rapid triaging of patients to treatment options.

METHODS

A total of 50 thyroid carcinoma FNA samples, including papillary (29 samples), poorly differentiated (10 samples), anaplastic (9 samples), and Hurthle cell (2 samples) carcinomas, with a known BRAF p.V600E mutation status were selected for the current study. Immunostaining was performed on smears and cell block sections using an anti‐BRAF p.V600E antibody (clone VE1). The results were compared with the known mutation status obtained by molecular testing and/or immunostaining of surgical pathology material from the same patient.

RESULTS

Of the total of 50 cases, 26 cases had smears available for the evaluation of BRAF p.V600E immunostaining; positive immunostaining was noted in 16 samples and negative immunostaining was noted in 4 samples, whereas 6 cases were equivocal. Of the 34 cases for which cell blocks were available for evaluation, BRAF p.V600E immunostaining was positive in 17 cases, negative in 16 cases, and equivocal in 1 case. The overall sensitivity and specificity of BRAF p.V600E immunostaining on the cell block preparation was 94.4% and 100%, respectively, whereas for the smears it was 80% and 63.6%, respectively.

CONCLUSIONS

BRAF p.V600E immunostaining can be performed reliably on thyroid FNA cell block preparations. However, false‐positive results on direct smears limit their utility and therefore need to be interpreted with caution. Cancer Cytopathol 2018;126:406‐13. © 2018 American Cancer Society.
Morphological characterization of HVC projection neurons in the zebra finch (Taeniopygia guttata)
Authors: Benezra Sam E. , Narayanan Rajeevan T. , Egger Robert , Oberlaender Marcel , Long Michael A.
Published: March 2018

Singing behavior in the adult male zebra finch is dependent upon the activity of a cortical region known as HVC (proper name). The vast majority of HVC projection neurons send primary axons to either the downstream premotor nucleus RA (robust nucleus of the arcopallium, or primary motor cortex) or Area X (basal ganglia), which play important roles in song production or song learning, respectively. In addition to these long‐range outputs, HVC neurons also send local axon collaterals throughout that nucleus. Despite their implications for a range of circuit models, these local processes have never been completely reconstructed. Here, we use in vivo single‐neuron Neurobiotin fills to examine 40 projection neurons across 31 birds with somatic positions distributed across HVC. We show that HVC(RA) and HVC(X) neurons have categorically distinct dendritic fields. Additionally, these cell classes send axon collaterals that are either restricted to a small portion of HVC (“local neurons”) or broadly distributed throughout the entire nucleus (“broadcast neurons”). Overall, these processes within HVC offer a structural basis for significant local processing underlying behaviorally relevant population activity.
Fast uncertainty quantification of activation sequences in patient‐specific cardiac electrophysiology meeting clinical time constraints
Authors: Quaglino A. , Pezzuto S. , Koutsourelakis P. S. , Auricchio A. , Krause R.
Published: March 2018

We present a fast, patient‐specific methodology for uncertainty quantification in electrophysiology, aimed at meeting the time constraints of clinical practitioners. We focus on computing the statistics of the activation map, given the uncertainties associated with the conductivity tensor modeling the fiber orientation in the heart. We use a fast parallel solution method implemented on a graphics processing unit for the eikonal approximation, in order to compute the activation map and to sample the random fiber field with correlation on the basis of geodesic distances. While this enables to perform uncertainty quantification studies with a manageable computational effort, the required time frame still exceeds clinically suitable time expectations. In order to reduce it further by 2 orders of magnitude, we rely on Bayesian multifidelity methods. In particular, we propose a low‐fidelity model that is patient‐specific and free from the additional training cost associated with reduced models. This is achieved by a sound physics–based simplification of the full eikonal model. The low‐fidelity output is then corrected by the standard multifidelity framework. In practice, the complete procedure only requires approximately 100 new runs of our eikonal graphics processing unit solver for producing the sought estimates and their associated credible intervals, enabling a full online analysis in less than 5 minutes.
Intelligent Optimization of Na−Mn−W/SiO2 Catalysts for the Oxidative Coupling of Methane
Authors: Li Zhinian , Wang Shenliang , Hong Wei , Zou Shihui , Xiao Liping , Fan Jie
Published: March 2018

Optimizing the performance and understanding the mechanism of metal oxide catalysts in the oxidative coupling of methane (OCM) is one of the most important projects in industrial catalysis. Here, we report an intelligent approach to screen Na−Mn−W/SiO2 catalysts for the OCM reaction via ink‐jet printing and multidimensional group testing. The ink‐jet‐printing‐assisted (IJP‐A) synthetic methodology ensured a fast synthesis of 1536 catalysts that were evaluated in 24 tests via a multidimensional group testing strategy (m‐GT). After two‐round synthesis‐and‐screening processes, several excellent groups with different composition space were screened out. Among the excellent catalysts, the OCM performance of Na−Mn−W/SiO2 catalyst with higher Na, Mn and W content (G3 and G7) was less sensitive to its constituent than that of Na−Mn−W/SiO2 catalyst with lower Na, Mn and W content (G1). These results indicated the sensitivity of performance to its Na, Mn and W content decreased in larger Na, Mn and W spaces, consistent with the complex homogeneous/heterogeneous reaction mechanism and multi‐active sites. A series of Na−Mn−W/SiO2 formulas with good performance also provide a reasonable explanation to its excellent stability for the OCM reaction. In addition, this intelligent optimization in total space offers a pathway to study the multicomponent metal oxide catalyst in the OCM reaction.
Bioequivalence of Two Formulations of Gliclazide in a Randomized Crossover Study in Healthy Caucasian Subjects Under Fasting Conditions
Authors: Pop Diana Ioana , Oroian Monica , Bhardwaj Sandeep , Marcovici Adriana , Khuroo Arshad , Kochhar Ravi , Vlase Laurian
Published: March 2018

This study aimed to investigate the bioequivalence of 2 formulations of gliclazide modified‐release tablets 60 mg in 48 healthy Caucasian volunteers under fasting conditions. A test product, Gliclazide MR (Ranbaxy Laboratories Limited, now Sun Pharmaceutical Industries, India), was compared with a reference product, Diamicron MR (Servier, France). The study was performed under a single‐dose, 2‐treatment, 2‐period, 2‐sequence crossover design in a fasted condition with a washout period of 21 days. Blood samples were collected for 96 hours after drug administration. Drug plasma concentrations were determined by a liquid chromatography–tandem mass spectrometry method. Analysis of pharmacokinetic characteristics was based on a noncompartmental model. The logarithmically transformed data of Cmax and AUC were analyzed for 90% confidence intervals using analysis of variance. There was no significant difference in pharmacokinetic characteristics between the products, and the 90% confidence intervals were within the acceptance range of 80.00%–125.00%. The investigated products were bioequivalent under fasted conditions.
A regression data mining approach in Lean Production
Authors: Bragança Ricardo , Portela Filipe , Santos Manuel
Published: March 2018

Nowadays, companies want technologies that are able to help them to make the best decision. Data Mining is an excellent tool to estimate the sales. It allows the company to optimize its production and reduce costs, eg, in storage. When these models are combined with Lean Production, it becomes easier to remove waste and optimize industrial production. This case study followed the CRISP‐DM methodology in order to create a model able to reduce and, if possible, eliminate wastage. Several statistics measures were applied to the dataset. Regression algorithms were induced with the goal to find which one of the models are less likely to make mistakes, in other words, what model correctly predict the target result. After executing the tests, the model M1 from the scenario C1 with RandomTree algorithm, average data grouping and average method class creation is the less likely one to give errors regarding regression, having produced an RAE of 6.75%.
Cobalt Complex with Redox‐Active Imino Bipyridyl Ligand for Electrocatalytic Reduction of Carbon Dioxide to Formate
Authors: Liu Fang‐Wei , Bi Jiaojiao , Sun Yuanyuan , Luo Shuping , Kang Peng
Published: March 2018

An imino bipyridine cobalt(II) complex was developed for the electrocatalytic reduction of CO2 to formate in acetonitrile with a faradaic efficiency of approximately 80 %. For comparison, a symmetric bis‐imino pyridine complex showed lower catalytic activity because of less conjugation in the system. Cyclic voltammetry, electron paramagnetic resonance and IR spectroscopy studies provided mechanistic details and the structures of the key intermediates. DFT calculations confirmed the role of large π‐conjugated groups for stabilizing key intermediates through electronic conjugation.
Myeloperoxidase, superoxide dismutase‐3, cardiometabolic risk factors, and distal sensorimotor polyneuropathy: The KORA F4/FF4 study
Authors: Herder Christian , Kannenberg Julia M. , Huth Cornelia , Carstensen‐Kirberg Maren , Rathmann Wolfgang , Koenig Wolfgang , Strom Alexander , Bönhof Gidon J. , Heier Margit , Thorand Barbara , Peters Annette , Roden Michael , Meisinger Christa , Ziegler Dan
Published: March 2018

Background

Oxidative stress has been proposed as important pathomechanism of cardiometabolic diseases and distal sensorimotor polyneuropathy (DSPN). However, the relevance of biomarkers of oxidative stress has not been investigated in this context. Therefore, this study aimed to assess the association of the prooxidant myeloperoxidase (MPO) and the antioxidant extracellular superoxide dismutase (SOD3) with cardiometabolic risk factors and with prevalence and incidence of DSPN.

Methods

Cross‐sectional analyses comprised 1069 participants (40.3% with prediabetes and 20.5% with type 2 diabetes) of the population‐based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006‐2008), 181 of whom had DSPN at baseline. Prospective analyses included 524 individuals without DSPN at baseline who also participated in the KORA FF4 study (2013‐2014), 132 of whom developed DSPN during the 6.5‐year follow‐up. Serum MPO and SOD3 were measured by ELISA, and their association with cardiometabolic risk factors and DSPN were estimated by using linear and logistic regression analyses.

Results

Higher MPO and SOD levels showed multiple positive associations with cardiometabolic risk factors including age, indices of obesity, insulin resistance, serum lipids, renal dysfunction, and biomarkers of inflammation. Higher MPO levels were associated with prevalent DSPN (fully adjusted OR 1.38 [95% CI 1.10; 1.72] per doubling of MPO). Higher baseline SOD3 levels were related to incident DSPN (age and sex‐adjusted OR 2.14 [1.02; 4.48] per doubling of SOD3), which was partially explained by cardiometabolic risk factors.

Conclusions

Systemic levels of both pro‐ and antioxidant enzymes appear involved in cardiometabolic risk and development of DSPN.
What's in a name? Perspectives of dyslexia assessors working with students in the UK higher education sector
Authors: Ryder Denise , Norwich Brahm
Published: March 2018

Research findings and positions concerning the nature of the dyslexia construct are currently diverse and increasingly complex. The ability of assessor practitioners to operationalize such knowledge and categorically diagnose dyslexia in any reliable and consistent way is being questioned. This study aimed to explore the way in which diverse and complex research findings are operationalized in the dyslexia diagnostic assessment of UK higher education students. The perspectives of 118 professional assessors of dyslexia working within the sector were collected using a questionnaire and some interviews. Data were analysed both quantitatively and qualitatively, as appropriate, and then integrated. The results confirmed critics' concerns about the consistency and reliability of the construct as currently diagnosed within the higher education context. Key controversial aspects of practice that emerged included the contextualized interpretation of literacy difficulties, a general commitment to discrepancy concepts, scepticism about the face validity of prescribed psychometric tests, and a related reliance on professional observation and experience above test results. The findings pointed to the need for a more informed nuanced understanding of the dyslexia label and a more cautious and responsible attitude towards its use.
Carbohydrate‐Appended TQNPEN [N,N,N′,N′‐Tetrakis(2‐quinolylmethyl)‐3‐aza‐1,5‐pentanediamine] Derivatives for Fluorescence Detection of Intracellular Cd2+
Authors: Mikata Yuji , Nozaki Kana , Kaneda Minori , Yasuda Keiko , Aoyama Masato , Tamotsu Satoshi , Matsumoto Arimasa
Published: March 2018

Carbohydrate‐appended TQNPEN [N,N,N′,N′‐tetrakis(2‐quinolylmethyl)‐3‐aza‐1,5‐pentanediamine] derivatives were developed as intracellular fluorescent Cd2+ sensors. Glucose (L1), galactose (L2), and maltose (L3) were utilized as sugar moieties. All glycosylated derivatives exhibit a fluorescence increase (ICd/I0 = 11–25) at 415 nm upon addition of 1 equiv. of Cd2+; however, 1 equiv. of Zn2+ induces negligible fluorescence change due to weak metal–ligand interaction (IZn/I0 = 3, IZn/ICd = 11–31 %). The properties of the Cd2+ complex with parent TQNPEN, including maximum fluorescence wavelength and lifetime, Cd2+ specificity of the fluorescence, and strong metal binding affinity, were well preserved in L1–L3. The intracellular Cd2+ detection was successfully achieved by glucose‐ and galactose‐appended derivatives L1 and L2, likely due to enhanced cell membrane permeability and intracellular distribution in HeLa cells.
Functionalized Inorganic Nanoparticles for Magnetic Separation and SERS Detection of Water Pollutants
Authors: Pinheiro Paula C. , Daniel‐da‐Silva Ana L. , Nogueira Helena I. S. , Trindade Tito
Published: March 2018

Inorganic nanoparticles (NPs) have emerged in the last decades as key materials for a number of technologies. In particular, noble metal (Ag, Au) and iron oxide NPs have revealed important applications due to their plasmonic and magnetic properties, respectively. Among these applications, this review provides, on one hand, an overview on the use of colloidal metal NPs in surface enhanced Raman scattering (SERS) chemical analysis and, on the other hand, the application of iron oxides as a new class of nanosorbents for water pollutants. These distinct types of NPs are the main building blocks to produce magneto‐plasmonic nanostructures, that comprise both functionalities, and whose morphologies and surface functionalities are controlled using chemical methodologies. Thus, this review presents an overall picture of these hybrid nanostructures that, albeit less explored than the corresponding single phased materials, show an enormous potential for fundamental and applied studies. In particular, there will be a focus on important aspects for the application of magneto‐plasmonic nanostructures in water analysis.
Highly Efficient Synthesis and Structure–Activity Relationships of a Small Library of Substituted 1,4‐Naphthoquinones
Authors: Bao Na , Ou Jinfeng , Shi Wei , Li Na , Chen Li , Sun Jianbo
Published: March 2018

A platform of highly efficient synthetic methodologies has been established to access a focused library of substituted 1,4‐naphthoquinones derivatives functionalized with a diversity of amino/hydroxy/alkyl groups. Furthermore, the structure–activity relationship deduced from antiproliferative activities and toxicities of this 1,4‐naphthoquinone library and intracellular reactive oxygen species (ROS) level detections might warrant future potential of plumbagin (2) and compound 13 as promising basic structures to develop novel anti‐cancer agents.
Fear of pain and cortisol reactivity predict the strength of stress‐induced hypoalgesia
Authors: Timmers I. , Kaas A.L. , Quaedflieg C.W.E.M. , Biggs E.E. , Smeets T. , de Jong J.R.
Published: March 2018

Background

Acute stress can have an effect on pain sensitivity, yet the direction of the effect – whether it is hypoalgesic or hyperalgesic – is mixed across studies. Moreover, which part of the stress response influences pain sensitivity is still unclear. In the current experimental study, we aim to examine the effect of acute stress on heat pain thresholds and pain tolerance levels in healthy participants, while taking into account individual differences in stress responses.

Methods

Forty‐two healthy participants were randomly assigned to either a well‐validated stress paradigm: the Maastricht Acute Stress Task (MAST; combining physical and psychological stressors) or to a nonstressful version of the task. Heat pain thresholds and tolerance levels were assessed at three times: prior to the MAST, immediately after the MAST during the presumed sympatho‐adrenal medullary (SAM) response, and 15 min after MAST to cover the presumed hypothalamus–pituitary–adrenal (HPA) axis response. Stress responses were assessed both subjectively and physiologically.

Results

We observed that the acute stress induction led to increased heat pain thresholds, an effect that was present only in participants showing a cortisol response following stress induction and only in the presumed HPA axis time window. The strength of this hypoalgesic effect was further predicted by the change in cortisol and by fear of pain levels.

Conclusions

Our findings indicate that the HPA axis – and not the autonomic – stress response specifically underlies this stress‐induced hypoalgesic effect, having important implications for clinical states with HPA axis dysfunctions.

Significance

This experimental study shows that an acute stress induction – that combines physical and psychological stressors – increases heat pain thresholds, but not tolerance in healthy participants. Furthermore, the magnitude of this stress‐induced hypoalgesic effect is predicted by cortisol reactivity and fear of pain, revealing specific involvement of the HPA axis stress system and interactions with pain‐related psychosocial aspects.
Determination of topiramate by capillary electrophoresis with capacitively‐coupled contactless conductivity detection: A powerful tool for therapeutic monitoring in epileptic patients
Authors: Ishikawa Aline Akemi , da Silva Rodrigo Moreira , Santos Mauro Sérgio Ferreira , da Costa Eric Tavares , Sakamoto Americo Ceiki , Carrilho Emanuel , de Gaitani Cristiane Masetto , Garcia Carlos D.
Published: March 2018

Topiramate (TPM) is the main antiepileptic drug used for the control of partial and generalized seizures in both adults and children. In association with clinical observations, the analysis of plasmatic concentration of TPM is of utmost importance for the individual adjustment of the administered dose to the patient. In the present work, a bioanalytical method was developed and validated for TPM analysis in plasma samples by capillary electrophoresis with capacitively‐coupled contactless conductivity detection (CE‐C4D). A simple background electrolyte composed of 15 mmol/L triethylamine, hydrodynamic injections (0.8 psi for 5 s) and a moderate separation voltage (20 kV) were used, rendering relatively short analysis times (<3 min). The sample pre‐treatment was carried out by liquid‐liquid extraction using methyl terc‐butyl ether as solvent and 200 μL of plasma. The method was validated according to the official guidelines from the European Medicine Agency and showed linearity in plasmatic concentration range from 1 to 30 μg/mL, which covers the clinically‐relevant interval. The lower limit of quantification of 1 μg/mL obtained also allows following patients with low dosage of the drug. The method was successfully applied to analysis of plasma samples and allowed the identification of 80% under‐medicated patients in the analyzed patient pool.
Profiling of small molecule metabolites and neurotransmitters in crustacean hemolymph and neuronal tissues using reversed‐phase LC‐MS/MS
Authors: Cao Qinjingwen , Ouyang Chuanzi , Zhong Xuefei , Li Lingjun
Published: March 2018

Crustaceans have been long used as model animals for neuromodulation studies because of their well‐defined neural circuitry. The identification of small molecule metabolites and signaling molecules in circulating fluids and neuronal tissues presents unique challenges due to their diverse structures, biological functions, and wide range of concentrations. LC combined with high resolution MS/MS is one of the most powerful tools to uncover endogenous small molecules. Here we explored several sample preparation techniques (solid‐phase extraction and denaturing) and MS data acquisition strategies (data‐dependent acquisition and targeted MS2‐based acquisition) that provided complementary coverage and improved overall identification rate in C18 LC‐MS/MS experiment. By MS/MS spectral matching with mzCloud database and those generated from standard compounds, a total of 129 small molecule metabolites and neurotransmitters were identified from crustacean hemolymph and neuronal tissues. These confidently identified small molecules covered predominant biosynthetic pathways for major neurotransmitters, validating the effectiveness of the high‐throughput RPLC‐MS/MS approach in studying the metabolism of neurotransmitters.
Cognitive remediation therapy (CRT) in a specialist inpatient eating disorder service for children and adolescents: CAN‐CRT study protocol for a pilot randomised controlled trial
Authors: Giombini Lucia , Nesbitt Sophie , Cox Hannah , Foxall Anna , Sharia Teo , Easter Abigail , Tchanturia Kate
Published: March 2018

Introduction

Research on treatments for young people (YP) with anorexia nervosa (AN) is scarce. Evidence supports the use of cognitive remediation therapy (CRT) to improve central coherence and set‐shifting, inefficiencies that can negatively impact on prognosis.

Objective

The study aims to evaluate the feasibility of individual CRT in an inpatient setting for YP aged 10–18 years with AN and to qualitatively examine YP's and their parents experiences.

Method

In a single‐centre, pilot, randomised controlled trial, 80 patients aged 10–18 years with AN will be randomly allocated to the immediate or delayed CRT group, in addition to standard treatment. A repeated measures design will be conducted across 3 time points.

Discussion

The data will provide evidence regarding the feasibility of individual CRT in YP with AN, informing directions of further development of CRT. The study is in preparation for a definitive randomised controlled trial. The aim of this manuscript is to describe the study protocol.
Enhancing momentum investment strategy using leverage
Authors: Forner Carlos , Muradoglu Yaz Gülnur , Sivaprasad Sheeja
Published: March 2018

Previous studies examine investment strategies based on leverage and momentum; none investigates both variables jointly as an investment strategy. This paper is the first incorporating leverage and momentum together. We show that low past returns (losers) forecast future negative abnormal returns only among stocks with high leverage levels, but not among stocks with low leverage levels. However, high past returns (winners) forecast future positive abnormal returns independently of leverage level. As a result, the negative relation between leverage and future abnormal returns is only observed among loser stocks, and the positive relation between past returns and future abnormal returns is only shown among non‐low leverage stocks. Our results are important in achieving better investment strategies: buying winners' stocks (independently of their level of leverage) and short‐selling losers' stocks with high leverage yield higher abnormal returns than strategies based on only one of these variables. Our two‐dimensional strategy yields risk‐adjusted abnormal returns of 15.66% per annum, whereas the single leverage or momentum strategies yield 7.70% and 7.96% per annum, respectively. The difference is nearly 8% and economically significant. If leverage is considered as proxy for default risk, our results, contrary to previous evidence, show that momentum profits are not exclusive of default stocks, and that momentum returns are not only driven by negative returns yielded by distress stocks.
Effect of ethanol on flavor perception of Rum
Authors: Ickes Chelsea M. , Cadwallader Keith R.
Published: March 2018

This is the first sensory study to evaluate the effects of ethanol concentration on flavor perception of distilled spirits. Dilution series of two rums (R1 and R2) were evaluated to gain insight into the effects of ethanol concentration on the flavor perception of distilled spirits. Rums were diluted 1:2 (v/v) either with pure water to a final alcohol by volume (ABV) of 20% (R1‐W and R2‐W) or with an aqueous 40% ABV solution (R1‐E and R2‐E). The later dilution accounted for the flavor dilution effect while keeping the ethanol concentration the same as the original liquors. Descriptive sensory analysis was conducted on both dilution series and the original rums. Twenty‐three attributes were evaluated consisting of eight aroma, four aroma‐by‐mouth, four mouthfeel, two taste, and five aftertaste terms. Results revealed 18 significant attributes for the R1 series. With the exception of silky mouthfeel, all attributes were rated highest in R1 and lowest in R1‐E. The R2 series contained sixteen significant attributes, all of which were rated higher in R2 compared with R2‐E. The flavor profiles of the original rums and those diluted with water were very similar, with the diluted rums generally having slightly lower attribute intensities. In contrast, the rums diluted with 40% ABV had significantly different flavor profiles than the original rums. Results indicate that diluting spirits with water may reduce the odor suppression effects of ethanol or enhance flavor release which appears to counteract the flavor dilution effect.
Device‐scale CFD modeling of gas‐liquid multiphase flow and amine absorption for CO2capture
Authors: Pan Wenxiao , Galvin Janine , Huang Wei Ling , Xu Zhijie , Sun Xin , Fan Zhen , Liu Kunlei
Published: March 2018

In this paper we aim to develop a validated device‐scale CFD model that can predict quantitatively both hydrodynamics and CO2capture efficiency for an amine‐based solvent absorber column with random Pall ring packing. A Eulerian porous‐media approach and a two‐fluid model were employed, in which the momentum and mass transfer equations were closed by literature‐based empirical closure models. We proposed a hierarchical approach for calibrating the parameters in the closure models to make them accurate for the packed column. Specifically, a parameter for momentum transfer in the closure was first calibrated based on data from a single experiment. With this calibrated parameter, a parameter in the closure for mass transfer was next calibrated under a single operating condition. Last, the closure of the wetting area was calibrated for each gas velocity at three different liquid flow rates. For each calibration, cross validations were pursued using the experimental data under operating conditions different from those used for calibrations. This hierarchical approach can be generally applied to develop validated device‐scale CFD models for different absorption columns. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd.
The boundaries of the firm in global strategy
Authors: Cuervo‐Cazurra Alvaro , Mudambi Ram , Pedersen Torben
Published: March 2018

Research summary

We briefly review the evolution in the analysis of the boundaries of the firm in global strategy. We explain how initial studies that argued that firm boundaries were driven by the minimization of transaction costs were later complemented by analyses that proposed that firm boundaries were driven by the development and use of resources to maximize value creation and capture. Studies of global strategy combine these two approaches and introduce the influence of location—both the home and host countries—as a third influence on boundary decisions. We encourage future studies to focus more deeply on the complexity, dynamics, and mechanisms of three themes: the consideration of all boundary options, the study of the entirety of the multinational, and the simultaneous consideration analysis of the characteristics of all the locations in which the multinational is active. These suggestions help better connect the three drivers of firm boundaries: transactions, resources, and locations.

Managerial summary

We briefly review the evolution in academic thinking regarding the scope of activities of a firm, that is, a firm's boundaries, in global strategy. We explain how initial studies that argued that firm boundaries are driven by a desire to reduce costs were complemented by analyses that proposed that firm boundaries are driven by a desire to increase value creation and capture. Studies of global strategy combine these two drivers and introduce the influence of the location of operation—the home and host countries—as a third influence on boundary decisions. We provide suggestions for future studies on how to incorporate the complexity, dynamics, and mechanisms of the complete array of methods to manage boundaries, the complete set of subsidiaries of the multinational, and the complete set of characteristics of the relevant locations.
2SLS versus 2SRI: Appropriate methods for rare outcomes and/or rare exposures
Authors: Basu Anirban , Coe Norma B. , Chapman Cole G.
Published: March 2018

This study used Monte Carlo simulations to examine the ability of the two‐stage least squares (2SLS) estimator and two‐stage residual inclusion (2SRI) estimators with varying forms of residuals to estimate the local average and population average treatment effect parameters in models with binary outcome, endogenous binary treatment, and single binary instrument. The rarity of the outcome and the treatment was varied across simulation scenarios. Results showed that 2SLS generated consistent estimates of the local average treatment effects (LATE) and biased estimates of the average treatment effects (ATE) across all scenarios. 2SRI approaches, in general, produced biased estimates of both LATE and ATE under all scenarios. 2SRI using generalized residuals minimized the bias in ATE estimates. Use of 2SLS and 2SRI is illustrated in an empirical application estimating the effects of long‐term care insurance on a variety of binary health care utilization outcomes among the near‐elderly using the Health and Retirement Study.
Alternative evaluation metrics for risk adjustment methods
Authors: Park Sungchul , Basu Anirban
Published: March 2018

Risk adjustment is instituted to counter risk selection by accurately equating payments with expected expenditures. Traditional risk‐adjustment methods are designed to estimate accurate payments at the group level. However, this generates residual risks at the individual level, especially for high‐expenditure individuals, thereby inducing health plans to avoid those with high residual risks. To identify an optimal risk‐adjustment method, we perform a comprehensive comparison of prediction accuracies at the group level, at the tail distributions, and at the individual level across 19 estimators: 9 parametric regression, 7 machine learning, and 3 distributional estimators. Using the 2013–2014 MarketScan database, we find that no one estimator performs best in all prediction accuracies. Generally, machine learning and distribution‐based estimators achieve higher group‐level prediction accuracy than parametric regression estimators. However, parametric regression estimators show higher tail distribution prediction accuracy and individual‐level prediction accuracy, especially at the tails of the distribution. This suggests that there is a trade‐off in selecting an appropriate risk‐adjustment method between estimating accurate payments at the group level and lower residual risks at the individual level. Our results indicate that an optimal method cannot be determined solely on the basis of statistical metrics but rather needs to account for simulating plans' risk selective behaviors.
Occupational injuries and risk assessment of apartment guards work
Authors: Park Myoung Hwan , Jeong Byung Yong
Published: March 2018

The purpose of this study is to analyze the characteristics of occupational injuries in apartment guards and to suggest the risk matrix based on risk assessment. The 432 incident reports approved as work‐related injuries were used to investigate the characteristics of occupational injuries. Results showed that 88.7% of the total incidents occurred in workers older than 60 years of age, and 52.9% occurred in less than 1 year of work experience. The most incidents took place in the process of cleaning (48.2%), followed by patrol (28.3%), facility management (13.6%), and guard office work (10.0%). Possible incidents predicted as high level of risk management were in the forms of “parking control: slips and trips,” “repair facility: fall from a height,” “patrol: slips and trips,” “street cleaning: slips and trips,” “waste sorting: slips and trips,” and “snow removal: slips and trips.” The results could be used to develop an effective injury prevention policy and contribute to providing a workplace where older workers can work safely.
Trickle‐down effect: The impact of female board members on executive gender diversity
Authors: Gould Jill A. , Kulik Carol T. , Sardeshmukh Shruti R.
Published: March 2018

Female representation at senior organizational levels lags well behind male representation. We investigate whether there is a positive nonlinear relationship between female board representation and female executive representation: the trickle‐down effect. We investigated 1,387 organizations listed on the Australian Securities Exchange between 2003 and 2012 and found the hypothesized nonlinear trickle‐down effect operating between board and executive levels. The trickle‐down effect was strongest after 1 year but still significant after 5 years. We investigated two potential moderators of the effect: organization size and gender diversity recommendations. There was no moderating effect of organization size, but contrary to expectations, gender diversity recommendations slowed the trickle‐down effect. Our findings suggest that organizations can address the paucity of women at senior organizational levels by starting at the top. Specifically, organizations making multiple appointments of female board members should expect improvements in female executive representation. However, the signaling and advocacy opportunities afforded by female board appointments may be less potent in the context of external interventions. Our findings contribute to the ongoing policy debate about the value of regulatory interventions to increase female representation at senior organizational levels and highlight the need for research on the unintended consequences of these interventions across national contexts.
Effect of a tissue selective estrogen complex on breast cancer: Role of unique properties of conjugated equine estrogen
Authors: Yue Wei , Wang Jiping , Atkins Kristen A. , Bottalico Lisa , Mesaros Clementina , Blair Ian A. , Santen Richard J.
Published: March 2018

The Women's Health Initiative studies reported that the menopausal hormone therapy (MHT) regimen containing conjugated equine estrogen (CEE) and medroxyprogesterone acetate increased, whereas CEE alone reduced breast cancer incidence. These observations suggest the possibility that CEE might exert unique actions on breast and also suggest the need to eliminate the progestogen from MHT regimens. A MHT regimen called a tissue selective estrogen complex (TSEC), containing CEE plus bazedoxifene (BZA), to avoid the need for a progestogen, was developed and FDA approved. Our study addressed two questions regarding this TSEC: (i) whether CEE exert effects on breast cancer which differ from those of estradiol (E2) and (ii) whether BZA antagonize the effects of E2 and CEE on breast cancer? Two rodent models (NMU and ACI) were used to compare the effect of CEE with E2 on mammary tumor formation, proliferation and apoptosis. In both the NMU and ACI models, E2 significantly increased tumor incidence and multiplicity whereas in striking contrast CEE did not, even though the estrogenic effects of CEE and E2 on uterine weight were identical. Mechanistically E2 blocked whereas CEE stimulated apoptosis (cleaved caspase‐3) in ACI animals and only E2 stimulated proliferation (Ki67). BZA exerted highly potent anti‐estrogenic effects on tumors by completely blocking palpable tumor formation. These data suggest that the CEE/BZA TSEC may be a safer, breast‐antagonistic, MHT agent for women and might have potential to prevent breast cancer while relieving menopausal symptoms.
Soluble γc receptor attenuates anti‐tumor responses of CD8+ T cells in T cell immunotherapy
Authors: Kim Geona , Hwang Hyunju , Jo Yuna , Lee Byunghyuk , Lee Young‐Ho , Kim Chan Hyuk , Hong Changwan
Published: March 2018

Previous studies have shown that soluble common γ‐chain (sγc) modulates CD4+ T cell immunity with antagonistic functions in γc cytokine signaling. However, the role of sγc in functional properties of effector CD8+ T cells has not been fully defined. In this study, we report a new mechanism by which the anti‐tumor activity of mouse CD8+ T cells is suppressed in sγc of their own producing. While sγc significantly inhibits cytotoxicity of CD8+ T cells, blocking sγc production by genetic modification leads to potentiated effector function of CD8+ T cells, establishing persistent CD8+ T cells. This is due to the modulation of IL‐2 and IL‐15 signaling, which is required for expansion and survival of CD8+ T cells as well as for optimal cytotoxic activity. More efficient management of tumor growth was achieved by an adoptive transfer of sγc‐deficient CD8+ T cells than that of wild‐type or sγc‐overexpressing CD8+ T cells. Blocking of IL‐2 and IL‐15 signaling by sγc attenuates the capacity of CD8+ T cells to mount an optimal response to the tumor, with both quantitative and qualitative effects on antigen‐specific CD8+ T cells. These results could have a critical implication for the generation and survival of optimal effector T cells for adoptive immunotherapy of cancer.
Impact of introducing specific measures to reduce the frequency of cesarean delivery for non‐obstetric indications
Authors: Psenkova Petra , Bucko Marek , Braticak Michal , Baneszova Ruth , Zahumensky Jozef
Published: March 2018

Objective

To identify the frequency of cesarean delivery for non‐obstetric indications before and after the introduction of specific measures to lower the rate of elective cesarean, and to evaluate the effectiveness of the introduced measures.

Methods

In the present single‐center retrospective cohort study at University Hospital Trnava, Trnava, Slovak Republic, the frequency of elective cesarean was evaluated before (January 1, 2010, to December 31, 2014) and after (January 1, 2015, to December 31, 2016) the implementation of specific measures applied in January 2015 to confirm the indications for primary cesarean delivery. The frequency of elective cesarean delivery for non‐obstetric indications was compared between the two periods.

Results

Before the intervention in 2015, 229 (2.9%) of 7768 women had elective cesarean deliveries for non‐obstetric indications. After implementation of the intervention, the frequency decreased to 27 (0.8%) of 3203 women (P<0.001).

Conclusion

The frequency of cesarean delivery for non‐obstetric indications was reduced significantly by introducing specific reasonable measures. These included all non‐obstetric indications for cesarean delivery being approved by a leading specialist of the related department, close cooperation with professionals from other specialties, and, additionally, staff attending professional educational lectures.
In vivo blind‐deconvolution photoacoustic ophthalmoscopy with total variation regularization
Authors: Xie Deyan , Li Qin , Gao Quanxue , Song Wei , Zhang Hao F. , Yuan Xiaocong
Published: March 2018

Photoacoustic ophthalmoscopy (PAOM) is capable of noninvasively imaging anatomic and functional information of the retina in living rodents. However, the strong ocular aberration in rodent eyes and limited ultrasonic detection sensitivity affect PAOM's spatial resolution and signal‐to‐noise ratio (SNR) in in vivo eyes. In this work, we report a computational approach to combine blind deconvolution (BD) algorithm with a regularizing constraint based on total variation (BDTV) for PAOM imaging restoration. We tested the algorithm in retinal and choroidal microvascular images in albino rat eyes. The algorithm improved PAOM's lateral resolution by around 2‐fold. Moreover, it enabled the improvement in imaging SNR for both major vessels and capillaries, and realized the well‐preserved blood vessels' edges simultaneously, which surpasses conventional Richardson‐Lucy BD algorithm. The reported results indicate that the BDTV algorithm potentially facilitate PAOM in extracting retinal pathophysiological information by enhancing in vivo imaging quality without physically modifying PAOM's optical configuration.
Self‐assembled, ellipsoidal polymeric nanoparticles for intracellular delivery of therapeutics
Authors: Desai Prachi , Venkataramanan Anjana , Schneider Rebecca , Jaiswal Manish K. , Carrow James K. , Purwada Alberto , Singh Ankur , Gaharwar Akhilesh K.
Published: March 2018

Nanoparticle shape has emerged as a key regulator of nanoparticle transport across physiological barriers, intracellular uptake, and biodistribution. We report a facile approach to synthesize ellipsoidal nanoparticles through self‐assembly of poly(glycerol sebacate)‐co‐poly(ethylene glycol) (PGS‐co‐PEG). The PGS‐PEG nanoparticle system is highly tunable, and the semiaxis length of the nanoparticles can be modulated by changing PGS‐PEG molar ratio and incorporating therapeutics. As both PGS and PEG are highly biocompatible, the PGS‐co‐PEG nanoparticles show high hemo‐, immuno‐, and cytocompatibility. Our data suggest that PGS‐co‐PEG nanoparticles have the potential for use in a wide range of biomedical applications including regenerative medicine, stem cell engineering, immune modulation, and cancer therapeutics. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2048–2058, 2018.