bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model Informed Dose Optimization of Dichloroacetate for the Treatment of Congenital Lactic Acidosis in Children
Authors: Mangal Naveen , James Margaret O. , Stacpoole Peter W. , Schmidt Stephan 
Published: September 2017

AbstractDichloroacetate (DCA) is an investigational drug used to treat congenital lactic acidosis and other mitochondrial disorders. Response to DCA therapy in young children may be suboptimal following body weight–based dosing. This is because of autoinhibition of its metabolism, age‐dependent changes in pharmacokinetics, and polymorphisms in glutathione transferase zeta 1 (GSTZ1), its primary metabolizing enzyme. Our objective was to predict optimal DCA doses for the treatment of congenital lactic acidosis in children. Accordingly, a semimechanistic pharmacokinetic‐enzyme turnover model was developed in a step‐wise approach: (1) a population pharmacokinetic model for adults was developed; (2) the adult model was scaled to children using allometry and physiology‐based scaling; and (3) the scaled model was externally qualified, updated with clinical data, and optimal doses were projected. A 2‐compartment model accounting for saturable clearance and GSTZ1 enzyme turnover successfully characterized the DCA PK in adults and children. DCA‐induced inactivation of GSTZ1 resulted in phenoconversion of all subjects into slow metabolizers after repeated dosing. However, rate and extent of inactivation was 2‐fold higher in subjects without the wild‐type EGT allelic variant of GSTZ1, resulting in further phenoconversion into ultraslow metabolizers after repeated DCA administration. Furthermore, DCA‐induced GSTZ1 inactivation rate and extent was found to be 25‐ to 30‐fold lower in children than in adults, potentially accounting for the observed age‐dependent changes in PK. Finally, a 12.5 and 10.6 mg/kg twice‐daily DCA dose was optimal in achieving the target steady‐state trough concentrations (5–25 mg/L) for EGT carrier and EGT noncarrier children, respectively.
Changes in intermediate water conditions in the northern South China Sea using Globorotalia inflata over the last 20 ka
Authors: Yang Yiping , Xiang Rong , Liu Jianguo , Fu Shaoying , Zhou Liping , Du Shuhuan , Lü Honghong 
Published: September 2017

ABSTRACTIntermediate circulation is one of the crucial controls of thermohaline changes in seawater. Due to the lack of data for some of the more significant indicators, there has been little research into past intermediate waters in the South China Sea (SCS). In particular, little is known of the thermohaline properties of intermediate water. Here, we present paired Mg/Ca and δ18O data for the planktonic foraminifera Globorotalia inflata from core GHE27L in the northern SCS; these data provide records of temperature and residual δ18Oseawater (δ18Oresidual, being used as a proxy for salinity) to tentatively investigate changes in the intermediate water of the SCS over the last 20 ka. Our results show that G. inflata in the SCS grew principally within the 200–450 m water depth interval. Thermohaline changes recorded by G. inflata indicate warm and relatively freshening water during the Last Glacial Maximum (LGM, 20–17.7 ka BP), changing to warm and saline waters between 17.7 and 13.6 ka BP. In general, waters during the 13.6–8.3 ka BP period were characterized by high temperatures and salinity, with obvious millennial‐scale fluctuations, after which, during the Holocene, they became cold and fresh. We suggest that the temperature and salinity of the intermediate water of the SCS recorded by G. inflata in core GHE27L were possibly associated with a switch in intermediate water masses. During the LGM, the intermediate water in the northern SCS was mainly impacted by North Pacific Intermediate Water (NPIW), but that subsequently the influence of Antarctic Intermediate Water strengthened during the last deglaciation and Pre‐Boreal period (17.7–8.3 ka BP). After this period, NPIW was the principal control of the intermediate water of the SCS again.
Insights on the stilbenes in Raboso Piave grape (Vitis vinifera L.) as a consequence of postharvest vs on‐vine dehydration
Authors: Brillante Luca , De Rosso Mirko , Dalla Vedova Antonio , Maoz Itay , Flamini Riccardo , Tomasi Diego 
Published: September 2017

AbstractBACKGROUNDGrape withering is a process used to produce reinforced wines and raisins. Dehydration is usually carried out postharvest by keeping ripe grapes in special warehouses in controlled conditions of temperature, relative humidity (RH) and air flow. Alternatively, grape clusters can be left on the vines after the canes have been pruned. In general, dehydration increases stilbenes in grape, but there are few studies on the effects of on‐vine withering. The stilbene profiles of Raboso Piave grape during postharvest and on‐vine dehydration were studied here.RESULTSHigh‐resolution mass spectrometry (MS) was used to identify 19 stilbenes, including resveratrol monomers, dimers (viniferins), oligomers and glucoside derivatives. The two dehydration methods generally had different effects on the above nutraceuticals in grape. The samples kept in warehouses revealed significant increases in Z‐ω‐viniferin, E‐ϵ‐viniferin, δ‐viniferin and another resveratrol dimer which were not observed in the plants. Trans‐Resveratrol increased significantly only in samples dehydrated in the warehouse at 21 °C and 60–70% RH.CONCLUSIONThe findings increase knowledge of stilbene composition in grapes subjected to withering on‐vine. The choice of dehydration method affects the contents of these nutraceuticals in the grape and consequently in wines. Reasonably, it could also affect other secondary metabolites important for wine quality. © 2017 Society of Chemical Industry
Bicovariograms and Euler characteristic of regular sets
Authors: Lachièze‐Rey R. 
Published: September 2017

AbstractWe establish an expression of the Euler characteristic of ar‐regular planar set in function of some variographic quantities. The usualframework is relaxed to aregularity assumption, generalising existing local formulas for the Euler characteristic. We give also general bounds on the number of connected components of a measurable set ofin terms of local quantities. These results are then combined to yield a new expression of the mean Euler characteristic of a random regular set, depending solely on the third order marginals for arbitrarily close arguments. We derive results for level sets of some moving average processes and for the boolean model with non‐connected polyrectangular grains in. Applications to excursions of smooth bivariate random fields are derived in the companion paper, and applied for instance toGaussian fields, generalising standard results.
Uniform convergence of sine transforms of general monotone functions
Authors: Debernardi Alberto 
Published: September 2017

AbstractWe obtain necessary and sufficient conditions for the uniform convergence of sine integrals
urn:x-wiley:0025584X:media:mana201600492:mana201600492-math-0001where g satisfies general monotonicity conditions. In contrast with the previous results on this topic, here we do not assume .
On slice hyperholomorphic fractional Hardy spaces
Authors: Alpay Daniel , Colombo Fabrizio , Sabadini Irene 
Published: September 2017

AbstractIn this paper we introduce and study the fractional Hardy spaces of the half space and of the unit ball in the quaternionic setting. In particular, we discuss their properties of invariance and of factorization in terms of functions in the Hardy space of the half space in the first case, and in terms of a suitable reproducing kernel Hilbert space in the case of the unit ball.
Vineyard diseases detection: a case study on the influence of weather instruments' calibration and positioning
Authors: Sanna Francesca , Calvo Angela , Deboli Roberto , Merlone Andrea 
Published: September 2017

ABSTRACTWeather‐monitoring instruments installed on hill and mountain agricultural sites are often forced into non‐ideal positioning due to slopes, tree proximity and other obstacles such as rivers and rocks that primarily affect relative humidity, temperature and solar radiation. Moreover, data from these weather stations do not take into account the measurement uncertainties related to these influences. The aim of this study is to investigate weather instruments' calibration and positioning in a vineyard located in the Monferrato region in northwestern Italy. Meteorological data from two weather stations were analysed metrologically in terms of the evaluation of calibration uncertainty and traceability to the International System of Units (SI), and using a statistical test, with the purpose of evaluating primarily the effect of the sensors' calibration and positioning on sloping hills. To understand these influences better, and in order to improve vineyard disease predictions reducing the use of chemicals in agriculture, the data recorded from the weather stations were included with the calibration uncertainties and used as inputs in an epidemiological forecasting model. The inclusion of the calibration uncertainties and positioning contribution affected disease prediction by up to five days; this can be explained by the effect of the tree canopy's spatial arrangement, which tends to alter the vineyard's microclimate.
A Metabolomic Approach Applied to a Liquid Chromatography Coupled to High‐Resolution Tandem Mass Spectrometry Method (HPLC‐ESI‐HRMS/MS): Towards the Comprehensive Evaluation of the Chemical Composition of Cannabis Medicinal Extracts
Authors: Citti Cinzia , Battisti Umberto Maria , Braghiroli Daniela , Ciccarella Giuseppe , Schmid Martin , Vandelli Maria Angela , Cannazza Giuseppe 
Published: September 2017

AbstractIntroductionCannabis sativa L. is a powerful medicinal plant and its use has recently increased for the treatment of several pathologies. Nonetheless, side effects, like dizziness and hallucinations, and long‐term effects concerning memory and cognition, can occur. Most alarming is the lack of a standardised procedure to extract medicinal cannabis. Indeed, each galenical preparation has an unknown chemical composition in terms of cannabinoids and other active principles that depends on the extraction procedure.ObjectiveThis study aims to highlight the main differences in the chemical composition of Bediol® extracts when the extraction is carried out with either ethyl alcohol or olive oil for various times (0, 60, 120 and 180 min for ethyl alcohol, and 0, 60, 90 and 120 min for olive oil).Methodology.Cannabis medicinal extracts (CMEs) were analysed by liquid chromatography coupled to high‐resolution tandem mass spectrometry (LC–MS/MS) using an untargeted metabolomics approach. The data sets were processed by unsupervised multivariate analysis.ResultsOur results suggested that the main difference lies in the ratio of acid to decarboxylated cannabinoids, which dramatically influences the pharmacological activity of CMEs. Minor cannabinoids, alkaloids, and amino acids contributing to this difference are also discussed. The main cannabinoids were quantified in each extract applying a recently validated LC–MS and LC‐UV method.ConclusionsNotwithstanding the use of a standardised starting plant material, great changes are caused by different extraction procedures. The metabolomics approach is a useful tool for the evaluation of the chemical composition of cannabis extracts. Copyright © 2017 John Wiley & Sons, Ltd.
Entanglement Entropy Evolution under Double‐trace Deformation
Authors: Song Yushu 
Published: September 2017

AbstractIn this paper, we study the bulk entanglement entropy evolution in conical BTZ black bole background using the heat kernel method. This is motivated by exploring the new examples where the quantum correction of the entanglement entropy gives the leading contribution. We find that in the large black hole limit the bulk entanglement entropy decreases under the double‐trace deformation which is consistent with the holographic c theorem and in the small black hole limit the bulk entanglement entropy increases under the deformation. We also discuss the minimal area correction.
Automatic structure prediction of oligomeric assemblies using Robetta in CASP12
Authors: Park Hahnbeom , Kim David E. , Ovchinnikov Sergey , Baker David , DiMaio Frank 
Published: September 2017

AbstractMany naturally occurring protein systems function primarily as symmetric assemblies. Prediction of the quaternary structure of these assemblies is an important biological problem. This article describes automated tools we have developed for predicting the structures of symmetric protein assemblies in the Robetta structure prediction server. We assess the performance of this pipeline on a set of targets from the recent CASP12/CAPRI blind quaternary structure prediction experiment. Our approach successfully predicted 5 of 7 symmetric assemblies in this challenge, and was assessed as the best participating server group, and 1 of only 2 groups (human or server) with 2 predictions judged as high quality by the assessors. We also assess the method on a broader set of 22 natively symmetric CASP12 targets, where we show that oligomeric modeling can improve the accuracy of monomeric structure determination, particularly in highly intertwined oligomers.
The application of low energy ion scattering spectroscopy (LEIS) in sub 28‐nm CMOS technology
Authors: Dittmar Kornelia , Triyoso Dina H. , Erben Elke , Metzger Joachim , Binder Robert , Brongersma Hidde H. , Weisheit Martin , Engelmann Hans‐Jürgen 
Published: September 2017

With the transition to ≤28‐nm CMOS technology nodes, the surface analytical challenges with regard to steadily decreasing dimensions and still growing materials options raise the demand of high performing surface analysis techniques. Characterization of ultrathin films and multilayer stacks, especially in high‐k metal gate stacks, by means of low energy ion scattering spectroscopy (LEIS) with its monolayer sensitivity has been established as a very useful analysis technique next to Auger electron spectroscopy, X‐ray photoelectron spectroscopy, and time‐of‐flight secondary ion mass spectrometry. Questions regarding film nucleation, growth, coverage, and diffusion can be answered, thereby enabling those processes to be controlled appropriately.In this work, growth studies of ALD HfO2 and TiN are shown, as well as film thickness determination based on surface spectra. PVD aluminum and lanthanum, acting as work function metals on the gate oxide, were deposited, and their film formation and closure were investigated. Further application fields of LEIS have emerged from the characterization of in‐die features on patterned wafers. As presented on test arrays, it is possible to detect material deep in trenches. This is an advantage if residues need to be identified after etch or clean processes.
Whitewash and After: ‘Most Good Is Done by Stealth’
Authors: Hilton Claire 
Published: September 2017

Abstract
Kenneth Robinson, Minister of Health, announced that the inquiries disproved the allegations in Sans Everything and vindicated the hospitals. However, careful reading of the reports indicated much unsatisfactory practice. Newspapers criticised the Ministry for its deceitful and ‘deplorably hostile’ view of Sans Everything, and public support for AEGIS increased. More hospital staff voiced concerns and attempted to make improvements. In 1969, investigations at Ely Hospital revealed appalling standards, gave credence to Sans Everything and reiterated AEGIS’s proposed remedies. AEGIS continued to chip away at the shield defending officialdom and worked to improve hospital provision. The government established a NHS inspectorate (1969), reviewed the complaints system (1971–1973), appointed an ombudsman (1973) and created blueprints for improved services for people of all ages with mental handicap and mental illness (1971–1972).
A Clinical Scoring System to Predict the Clinical Sequelae of Computed Tomography Diagnosed Intussusception
Authors: Tan Hwee Leong , Koh Ye Xin , Taufik Mohammad , Lye Weng Kit , Goh Brian Kim Poh , Ong Hock Soo 
Published: September 2017

AbstractIntroductionIntussusception in adults is increasingly diagnosed on cross‐sectional imaging with a lack of clear recommendations on management. The presence of an underlying lead point is a key to guiding management as its absence can predict spontaneous resolution. We studied adult patients with computed tomography (CT) diagnosed intussusception formulate a clinical scoring system to predict the risk of an underlying lead point.MethodologyWe performed a retrospective review of all adult patients who underwent CT scans of the abdomen and pelvis in our institution between 2001 and 2014. Independent associations of an underlying lead point were derived following multivariable analysis, from which a clinical scoring system was developed.ResultsWe studied 140 patients. In multivariable analysis, six factors were found to be independently associated with the presence of an underlying lead point, namely gender, abdominal pain, CT evidence of colonic involvement, CT evidence of a lead point, distal diameter ≥27 mm and minimum wall thickness ≥3 mm. A nine‐point clinical scoring system was developed, with a cutoff score of four or higher yielding a sensitivity and specificity of 0.75 and 0.81, respectively.ConclusionOur clinical scoring system provides a quantitative tool to predict the likelihood of an underlying lead point in CT‐diagnosed intussusception in adults to help guide management.
Bilateral Sequential Total Knee Replacement versus Unilateral Total Knee Replacement in a High Volume Hospital
Authors: Pui-kan Chan Calvin , Quun-jid Lee , Yiu-chung Wong , Yuk-leung Wai 
Published: September 2017

Background/Purpose Bilateral simultaneous or sequential total knee replacement (TKR) is performed on a portion of patients but the benefits and risks remain controversial. Methods A total of 89 sequential bilateral TKR (BTKR) patients were compared with 89 unilateral TKR (UTKR) patients in our total joint replacement centre from October 2011 to October 2014. The baseline parameters were matched and postoperative results were compared. Results The BTKR group had a shorter length of stay per knee (4.8 days vs. 6.5 days) but with a higher total drain output, higher haemoglobin drop, higher transfusion rate, and more postoperative acute retention of urine. Both groups had similar major complication rates and no 90 days mortality. Conclusion BTKR is a safe surgery in selected patients performed in a high volume hospital with fast-track programme.
Fixation of Pelvic-Acetabular Fractures Using a Midline-Modified Stoppa Approach: Clinical and Operative Outcomes
Authors: Chan Kenneth Kin-yan , Chui King-him , Ip Ka-chun , Lee Kin-bong , Li Wilson 
Published: September 2017

Background/Purpose This served as the first report from our locality to evaluate the modified Stoppa approach, via a low-midline wound, for treating pelvic–acetabular fractures. Methods A total of 17 polytrauma patients with pelvic and/or acetabular fractures were consecutively treated using the modified Stoppa approach. They were followed up for at least 1 year postoperatively for radiographic and clinical assessments, which included the Modified Merle d'Aubigne Score, Harris Hip Score, and pain visual analogue scale. Results Among the 17 patients, 11 had pelvic ring fractures, two had isolated acetabular fractures, and four had a combination of both. Excellent and anatomical reduction was achieved in 73.3% of pelvic fractures and 71.4% of acetabular fractures. Functional outcomes simulated a bimodal distribution. Age of patient and Injury Severity Score were significant predictors for functional results, whereas fracture characteristics and quality of reduction were not correlated with clinical outcomes in this series. We experienced a low complication rate. Conclusion Excellent exposure for fracture reduction and fixation with low complication rate was achieved with the modified Stoppa approach. We were encouraged by the results of this preliminary series for treating pelvic–acetabular fractures in polytrauma patients.
Increasing convex order on generalized aggregation of SAI random variables with applications
Authors: Pan Xiaoqing , Li Xiaohu 
Published: September 2017

Abstract
In this paper we study general aggregation of stochastic arrangement increasing random variables, including both the generalized linear combination and the standard aggregation as special cases. In terms of monotonicity, supermodularity, and convexity of the kernel function, we develop several sufficient conditions for the increasing convex order on the generalized aggregations. Some applications in reliability and risks are also presented.
Large deviation principle for epidemic models
Authors: Pardoux Etienne , Samegni-Kepgnou Brice 
Published: September 2017

Abstract
We consider a general class of epidemic models obtained by applying the random time changes of Ethier and Kurtz (2005) to a collection of Poisson processes and we show the large deviation principle for such models. We generalise the approach followed by Dolgoarshinnykh (2009) in the case of the SIR epidemic model. Thanks to an additional assumption which is satisfied in many examples, we simplify the recent work of Kratz and Pardoux (2017).
Re-thinking social exclusion in later life: a case for a new framework for measurement
Authors: MACLEOD CATHERINE A. , ROSS ANDY , SACKER AMANDA , NETUVELI GOPALAKRISHNAN , WINDLE GILL 
Published: September 2017

ABSTRACTSocial exclusion is a dynamic multi-dimensional process that is interactive in nature. The complex interplay between domains, whereby each domain can act as a determinant, indicator and/or outcome of social exclusion, hinders understanding of the process and the mechanisms through which social exclusion exists. This article highlights the need to disentangle these pathways and move beyond descriptive accounts of social exclusion, presenting a new working framework that allows direct hypothesis testing of these between-domain relationships. Whilst this working framework can be applied to any population, this article focuses on older adults. Life events that can drive social exclusion such as bereavement and changes in health are more likely to occur in later life, and occur more frequently, increasing the risk of social exclusion for this population. Rooted in the new working framework, this article presents the construction of later life social exclusion measures for use with Understanding Society – the United Kingdom Household Longitudinal Study. The validity of these measures are considered by examining the characteristics of those aged 65 years and over who score the highest, and therefore experience the greatest level of exclusion. This new working framework and developed social exclusion measures provide a platform from which to explore the complex relationships between domains of social exclusion and ultimately provide a clearer understanding of this intricate multi-dimensional process.