bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered gentamicin pharmacokinetics in term neonates undergoing controlled hypothermia
Authors: Bijleveld Yuma A. , de Haan Timo R. , van der Lee Hanneke J. H. , Groenendaal Floris , Dijk Peter H. , van Heijst Arno , de Jonge Rogier C. J. , Dijkman Koen P. , van Straaten Henrica L. M. , Rijken Monique , Zonnenberg Inge A. , Cools Filip , Zecic Alexandra , Nuytemans Debbie H. G. M. , van Kaam Anton H. , Mathot Ron A. A. ,   for the PharmaCool study group
Published: January 2016

Aim(s)

Little is known about the pharmacokinetic (PK) properties of gentamicin in newborns undergoing controlled hypothermia after suffering from hypoxic−ischaemic encephalopathy due to perinatal asphyxia. This study prospectively evaluates and describes the population PK of gentamicin in these patients.

Methods

Demographic, clinical and laboratory data of patients included in a multicentre prospective observational cohort study (the ‘PharmaCool Study’) were collected. A non‐linear mixed‐effects regression analysis (nonmem®) was performed to describe the population PK of gentamicin. The most optimal dosing regimen was evaluated based on simulations of the final model.

Results

A total of 47 patients receiving gentamicin were included in the analysis. The PK were best described by an allometric two compartment model with gestational age (GA) as a covariate on clearance (CL). During hypothermia the CL of a typical patient (3 kg, GA 40 weeks, 2 days post‐natal age (PNA)) was 0.06 l kg−1 h−1 (inter‐individual variability (IIV) 26.6%) and volume of distribution of the central compartment (Vc) was 0.46 l kg−1 (IIV 40.8%). CL was constant during hypothermia and rewarming, but increased by 29% after reaching normothermia (>96 h PNA).

Conclusions

This study describes the PK of gentamicin in neonates undergoing controlled hypothermia. The 29% higher CL in the normothermic phase compared with the preceding phases suggests a delay in normalization of CL after rewarming has occurred. Based on simulations we recommend an empiric dose of 5 mg kg−1 every 36 h or every 24 h for patients with GA 36–40 weeks and GA 42 weeks, respectively.
Robust Nonparametric Estimation of Monotone Regression Functions With Interval-Censored Observations
Authors: Zhang Ying , Cheng Gang , Tu Wanzhu
Published: January 2016

Nonparametric estimation of monotone regression functions is a classical problem of practical importance. Robust estimation of monotone regression functions in situations involving interval-censored data is a challenging yet unresolved problem. Herein, we propose a nonparametric estimation method based on the principle of isotonic regression. Using empirical process theory, we show that the proposed estimator is asymptotically consistent under a specific metric. We further conduct a simulation study to evaluate the performance of the estimator in finite sample situations. As an illustration, we use the proposed method to estimate the mean body weight functions in a group of adolescents after they reach pubertal growth spurt.
Cañado, María Luisa Pérez & Padilla, Juan Ráez ed (2014) Digital competence development in higher educationPeter Lang (Frankfurt) isbn 978‐3‐631‐63803‐3 157 pp £32 http://www.peterlang.com/index.cfm?event=cmp.ccc.seitenstruktur.detailseiten&seitentyp=produkt&pk=68213
Authors: Dettori Giuliana
Published: January 2016

Addressed to language teachers and language teacher trainers, Digital competence development in higher education aims to reflect on the use of it in language education. The tools we have influence what we teach, how we teach and how our students learn; teachers help students develop competences by integrating knowledge, skills, abilities, strategies, attitudes, and values. The tools we can use supplement these, but do not substitute their role. If the content of this book is likely to be relevant to you, I advise that you will probably find only parts of it of interest or use.

Giuliana Dettori
Markey, Karen et al (2014) Designing online information games students want to playRowman & Littlefield (Lanham MD & Plymouth UK) isbn 978‐0‐8108‐9142‐5 279 pp £39.95 https://rowman.com/ISBN/9780810891432#
Authors: Dettori Giuliana
Published: January 2016

This book—aimed at game designers, librarians, and teachers with an interest in learning technology—defines information literacy and argues why it should be part of all students' preparation. It then examines the design, development and application of a game for undergraduates learning how to conduct library research. It also guides the design of information literacy games by discussing a number of best practices. Do you believe the content of this book is likely to be relevant to you? In that case, my advice is that you borrow a copy to see for yourself.

Giuliana Dettori
An adaptive perspective on revealed and concealed cues to empathy
Authors: Ward Robert , Shingler Polly
Published: January 2016

Wu, Sheppard, and Mitchell (Br. J. Psychol., 2016; 107, 1‐22) found that observers could accurately identify people with extreme but not more average empathy scores. Here, we further consider this U‐shaped discrimination function. We first examine a statistical issue regarding the construction of the average groups, which are less homogenous by definition than the extreme groups. We then consider the kinds of questions arising when these results are considered within the adaptive framework of signal theory. Some interesting questions arise relating to the signal sender, including the costs and benefits to the sender in revealing and concealing true empathy levels, and the effects of adopting behavioural norms to conceal true levels of empathy.
The relationship between parental attitudes and behaviours in the context of paediatric chronic pain
Authors: Jaaniste T. , Jia N. , Lang T. , Goodison‐Farnsworth E. M. , McCormick M. , Anderson D.
Published: January 2016

Background

Within the context of paediatric chronic pain, parental attitudes are of particular importance given that they have the potential to impact on how parents respond to their child. The current study was designed to assess whether parental attitudes, such as parental confidence and beliefs in their child's ability to function in spite of pain, and parental catastrophising about their child's pain, are associated with parental pain‐related behaviours known to be associated with poor child outcomes, such as protectiveness and high levels of monitoring.

Methods

Participants were 138 child–parent dyads recruited from a tertiary chronic pain clinic. Patients were aged 8‐ to 17‐years. Prior to the initial clinic appointment, parents completed validated measures of parental pain catastrophising and parental responses to their child's pain. Patients completed measures of functional disability and pain intensity.

Results

Parents who reported lower confidence in their child's ability to cope with the pain engaged in significantly more protective, monitoring and distracting behaviours, even when controlling for the child's recent level of functioning. They also took more days off work due to their child's pain. Parents who catastrophised more about their child's pain engaged in significantly more protective and monitoring behaviours, even when controlling for the child's recent level of functioning.

Conclusions

Parental behaviours in response to their child's pain are significantly related to parental confidence in their child's coping and parental pain‐related catastrophising. Clinical interventions may benefit from addressing parental attitudes, especially their confidence in their child's ability to function.
Aspergillus fumigatus promotes T helper type 2 responses through thymic stromal lymphopoietin production by human corneal epithelial cells
Authors: Wang Luping , Wang Leyi , Wu Xinyi
Published: January 2016

Background

Fungal keratitis is a major cause of blindness. To understand the mechanism of both innate and adaptive immunity in corneal infection is of great significance in the treatment and prevention of fungal keratitis. Our previous study concerned innate immunity. Here, we explored the potential role of thymic stromal lymphopoietin (TSLP) in adaptive immunity of fungal keratitis.

Methods

Human corneal epithelial cells (HCECs) were stimulated with Aspergillus fumigatus hyphae (106 pieces per millilitre) with or without TSLP siRNA, and peripheral blood mononuclear cells (PBMCs) were cultured with or without TSLP. HCECs and PBMCs were co‐cultured in a transwell system for various periods. Then we collected PBMCs and detected the proliferation and activation as well as T helper type 2 (Th2) differentiation by flow cytometry and quantitative real‐time reverse transcription polymerase chain reaction. IgG and IgA levels in supernatants of PBMCs were measured by means of ELISA.

Results

Thymic stromal lymphopoietin could induce a Th2 response in vitro, and the expression of TSLP was highly increased in HCECs stimulated with A. fumigatus hyphae. A. fumigatus‐infected HCECs were capable of promoting human lymphocyte proliferation and activating human CD4+ T cells, CD8+ T cells and B cells by up‐regulating the expression of activation marker CD69. Importantly, Th2 differentiation of CD4+ T cells was induced during co‐culture with A. fumigatus‐infected HCECs in a transwell system. Interestingly, blockade of TSLP using siRNA prevented the proliferation and activation of lymphocytes as well as Th2 differentiation. We also detected an increased IgG level that was associated with TSLP.

Conclusion

These findings suggested that HCEC‐derived TSLP has a key role in adaptive immune responses of fungal keratitis via skewing Th2 differentiation and promoting humoral immunity.
Improving the Local Search Ability of Spider Monkey Optimization Algorithm Using Quadratic Approximation for Unconstrained Optimization
Authors: Gupta Kavita , Deep Kusum , Bansal Jagdish Chand
Published: January 2016

Spider monkey optimization (SMO) algorithm, which simulates the food searching behavior of a swarm of spider monkeys, is a new addition to the class of swarm intelligent techniques for solving unconstrained optimization problems. The purpose of this article is to study the performance of SMO after incorporating quadratic approximation (QA) operator in it. The proposed version is named as QA‐based spider monkey optimization (QASMO). An experimental study has been carried out to check the validity and applicability of QASMO. For validation purpose, the performance of QASMO is tested over a benchmark set of 46 scalable and nonscalable problems, and results are compared with the original SMO algorithm. In order to test the applicability of the proposed algorithm in solving real‐life optimization problems, one of the most challenging optimization problems, namely, Lennard–Jones (LJ) problem is considered. LJ clusters containing atoms from three to ten have been taken into consideration, and results are presented. To the best of our knowledge, this is the first attempt to apply SMO and its proposed variant on a real‐life problem. The results demonstrate that incorporation of QA in SMO has positive effects on its performance in terms of reliability, efficiency, and accuracy.
Gamma‐variate plasma clearance versus urinary plasma clearance of51Cr‐EDTAin patients with cirrhosis with and without fluid retention
Authors: Fuglsang Stefan , Henriksen Ulrik L. , Hansen Hanne B. , Bendtsen Flemming , Henriksen Jens H.
Published: January 2016

In patients with fluid retention, the plasma clearance of51Cr‐EDTA(Clexpobtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma‐variate plasma clearance (Clgv)with the urinary plasma clearance of51Cr‐EDTA(Clu) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of51Cr‐EDTAfollowed by plasma and quantitative urinary samples for 5 h. Clgvwas determined from the injected dose relative to the plasma concentration‐time area, obtained by a gamma‐variate iterative fit. Clexpand Cluwere determined by standard technique. In patients without fluid retention, Clgv, Clexpand Cluwere closely similar. The difference between Clgvand Clu(Clgv– Clu = ΔCl) was mean −0·6 ml min−1 1·73 m−2. In patients with ascites, ΔCl was significantly higher (11·8 ml min−1 1·73 m−2,P<0·0001), but this value was lower than Clexp– Clu(17·5 mL min−1 1·73 m−2,P<0·01). ΔCl increased with lower values ofGFR(P<0·001). In conclusion, in patients with fluid retention and ascites Clgvand ClexpoverestimatesGFRsubstantially, but the overestimation is smaller with Clgv. Although Clumay underestimateGFRslightly, patients with ascites should collect urine quantitatively to obtain a reliable measurement ofGFR.
Threatened or Data Deficient: assessing the conservation status of poorly known species
Authors: Roberts David L. , Taylor Lin , Joppa Lucas N.
Published: January 2016

Aim

To determine whether extinction risk assessments based on biological collections and using Criterion B of the IUCN Red List Criteria reflect in part an accurate measure of species rarity and thus extinction risk.

Location

Madagascar.

Methods

We calculate the extent of occurrence (EOO) and area of occupancy (AOO) for orchids using herbarium specimen data. Correlations were made against range, occupancy, extinction risk, number of specimens and the date of description. We calculated the average increase in range per species specimen, correlated this against the date of description and determined significance of the observed EOO accumulation using randomization tests.

Results

Significant negative correlations were found between date of description and all measures of range, occupancy and associated Red List Categories and number of specimens, as well as between the average range accumulation per specimen and date of description. Seventy‐five percentage of species’ observed EOO accumulations significantly differed from random. Maximum deviations between observed EOO accumulations and those derived from random sampling were always significantly positive. For most species, this occurred more frequently during the first half of the accumulation sequence.

Main conclusions

Species described more recently have smaller ranges and occupancies, fewer specimens and greater perceived extinction risk status. Levels of geographic uniqueness of collections are higher in species described more recently. Awareness of a species range increased faster than random, particularly in the first half of the sampling process, suggesting that newly discovered or yet to be discovered species are rare and likely have a higher risk of extinction. For many species, biological collections represent the sum of our knowledge. While data may be limited, such species should be listed in an appropriate Red List Category in accordance with the IUCN Red List Guidelines rather than as Data Deficient.
Sellars and Nonconceptual Content
Authors: Levine Steven
Published: January 2016

In this paper I take up the question of whether Wilfrid Sellars has a notion of non‐conceptual perceptual content. The question is controversial, being one of the fault lines along which so‐called left and right Sellarsians diverge. In the paper I try to make clear what it is in Sellars' thought that leads interpreters to such disparate conclusions. My account depends on highlighting the importance of Sellars' little discussed thesis that perception involves a systematic form of mis‐categorization, one where perceivers mistake their sensory states to be properties of physical objects. I argue that the counterpart color and shape attributes of these states, which become ‘point of viewish’ when organized by the productive imagination, provides perceptual experience with its non‐conceptual representational content. I then argue that this content is not a form of the mythical Given because one can only have a non‐conceptual point of view on an object when an object is introduced into one's perceptual experience through the conceptual mis‐taking of one's sensory states. So, while Sellars has a notion of non‐conceptual representational content, it can only be salient in the context of a perceptual act that is conceptual overall.
From unwitnessed fatality to witnessed rescue: Nonpharmacologic interventions in sudden unexpected death in epilepsy
Authors: Rugg‐Gunn Fergus , Duncan John , Hjalgrim Helle , Seyal Masud , Bateman Lisa
Published: January 2016

Sudden unexpected death in epilepsy (SUDEP) risk reduction remains a critical aim in epilepsy care. To date, only aggressive medical and surgical efforts to control seizures have been demonstrated to be of benefit. Incomplete understanding of SUDEP mechanisms limits the development of more specific interventions. Periictal cardiorespiratory dysfunction is implicated in SUDEP; postictal electroencephalography (EEG) suppression, coma, and immobility may also play a role. Nocturnal supervision is protective against SUDEP, presumably by permitting intervention in the case of a life‐threatening event. Resuscitative efforts were implemented promptly in near‐SUDEP cases but delayed in SUDEP deaths in the Mortality in Epilepsy Monitoring Unit Study (MORTEMUS) study. Nursing interventions—including repositioning, oral suctioning, and oxygen administration—reduce seizure duration, respiratory dysfunction, and EEG suppression in the epilepsy monitoring unit (EMU), but have not been studied in outpatients. Cardiac pacemakers or cardioverter‐defibrillator devices may be of benefit in a few select individuals. A role for implantable neurostimulators has not yet been established. Seizure detection devices, including those that monitor generalized tonic–clonic seizure‐associated movements or cardiorespiratory parameters, may provide a means to permit timely periictal intervention. However, these and other devices, such as antisuffocation pillows, have not been adequately investigated with respect to SUDEP prevention.
Who to target in sudden unexpected death in epilepsy prevention and how? Risk factors, biomarkers, and intervention study designs
Authors: Tomson Torbjörn , Surges Rainer , Delamont Robert , Haywood Serena , Hesdorffer Dale C.
Published: January 2016

The risk of dying suddenly and unexpectedly is increased 24‐ to 28‐fold among young people with epilepsy compared to the general population, but the incidence of sudden unexpected death in epilepsy (SUDEP) varies markedly depending on the epilepsy population. This article first reviews risk factors and biomarkers for SUDEP with the overall aim of enabling identification of epilepsy populations with different risk levels as a background for a discussion of possible intervention strategies. The by far most important clinical risk factor is frequency of generalized tonic–clonic seizures (GTCS), but nocturnal seizures, early age at onset, and long duration of epilepsy have been identified as additional risk factors. Lack of antiepileptic drug (AED) treatment or, in the context of clinical trials, adjunctive placebo versus active treatment is associated with increased risks. Despite considerable research, reliable electrophysiologic (electrocardiography [ECG] or electroencephalography [EEG]) biomarkers of SUDEP risk remain to be established. This is an important limitation for prevention strategies and intervention studies. There is a lack of biomarkers for SUDEP, and until validated biomarkers are found, the endpoint of interventions to prevent SUDEP must be SUDEP itself. These interventions, be they pharmacologic, seizure‐detection devices, or nocturnal supervision, require large numbers. Possible methods for assessing prevention measures include public health community interventions, self‐management, and more traditional (and much more expensive) randomized clinical trials.
Introduction—Epilepsy Research UK expert workshop 2014
Authors: Nashef Lina , Richardson Mark P.
Published: January 2016

We offer Epilepsia readers this supplement based on the proceedings of an international workshop on sudden death in epilepsy (SUDEP) held in 2014 at St Anne's College at Oxford and hosted by Epilepsy Research UK (ERUK). This is the second Epilepsia supplement dedicated to SUDEP and its focus is on prevention. As workshop co‐chairs, in this introduction we outline why we believe we are on the threshold of a new era of prevention in SUDEP.
Managerial Social Capital and Financial Development: A Cross‐Country Analysis
Authors: Javakhadze David , Ferris Stephen P. , French Dan W.
Published: January 2016

This study examines the issue of whether managerial social capital, defined as aggregate benefits of social obligations and informal contacts formed through social networks, has an impact on financial development. Utilizing a large cross‐country sample for the period 1999–2012, we provide evidence that higher levels of social capital have a positive effect on financial development. We are able to examine different types of social connections for our sample firms and find that informal and nonprofessional relationships matter the most for financial market development. These findings are robust to alternative model specifications, variable measurement, and estimation techniques.
Serum osteopontin level and common carotid artery intima‐media wall thickness in psoriasis
Authors: Robati Reza M. , Partovi‐Kia Masoud , Sadat‐Amini Hadi , Haghighatkhah Hamid Reza , Younespour Shima , Toossi Parviz
Published: January 2016

Background

The association between psoriasis and cardiovascular disease is well documented, but the underlying mechanisms remain unknown. The relationship between osteopontin and psoriasis has been studied. High serum levels of osteopontin are reported in psoriasis, with increased cardiovascular risk factors in these patients.

Objectives

We evaluate the extent of subclinical atherosclerosis by measuring the mean intima–media wall thickness (MIMT) of the common carotid artery (CCA) in patients with psoriasis and assessing its correlation with osteopontin to identify vascular risk factors associated with psoriasis.

Methods

Intima–media wall thickness of the CCA and plasma osteopontin were determined in 40 patients and 40 age‐ and sex‐matched healthy control subjects.

Results

Median serum osteopontin was significantly higher in patients with psoriasis than in healthy control subjects. Mean intima–media wall thickness of the CCA was positively associated with plasma osteopontin level (r = 0.47, P < 0.0001), body mass index (r = 0.62, P < 0.0001), age (r = 0.54, P < 0.0001), total cholesterol (r = 0.54, P < 0.0001), and triglycerides (r = 0.65, P < 0.0001).

Conclusions

This study shows higher levels of plasma osteopontin and MIMT‐CCA in psoriasis patients than in healthy controls. This is the first study to show a positive correlation between plasma osteopontin and MIMT‐CCA.
Wald's mighty maximin: a tutorial
Authors: Sniedovich Moshe
Published: January 2016

Ever since its appearance on the scene in the 1940s, in the then nascent field of statistical decision theory, Wald's maximin paradigm has played a vital role in many disciplines in the treatment of nonprobabilistic uncertainty, both as a tool of thought and as a practical instrument. In fact, in some fields, such as modern robust optimization, Wald's paradigm dominates the scene. It is important to note that this paradigm's preeminence in many fields continues unabated, despite its obvious limitations and the criticism that had been and continues to be leveled at it. So, in this tutorial we examine the methodological aspects of this stalwart of decision theory from the viewpoint of robust decision‐making, paying special attention to its obvious and not so obvious limitations and to its relation to other maximin paradigms.
A novel approach to solve the split delivery vehicle routing problem
Authors: Chen Ping , Golden Bruce , Wang Xingyin , Wasil Edward
Published: January 2016

The split delivery vehicle routing problem (SDVRP) is a relaxed version of the classic capacitated vehicle routing problem (CVRP). Customer demands are allowed to split among vehicles. This problem is computationally challenging and the state‐of‐the‐art heuristics are often complicated to describe and difficult to implement, and usually have long computing times. All these hinder their application by practitioners to solve real‐world problems. We propose a novel, efficient, and easily implemented approach to solve the SDVRP using an a priori split strategy, that is, each customer demand is split into small pieces in advance. Our computational experiments on 82 benchmark instances show that our algorithm is overall much more efficient and produces results that are comparable to those from the state‐of‐the‐art approaches.
Epidermal growth factor attenuates blood‐spinal cord barrier disruption via PI3K/Akt/Rac1 pathway after acute spinal cord injury
Authors: Zheng Binbin , Ye Libing , Zhou Yulong , Zhu Sipin , Wang Qingqing , Shi Hongxue , Chen Daqing , Wei Xiaojie , Wang Zhouguang , Li Xiaokun , Xiao Jian , Xu Huazi , Zhang Hongyu
Published: January 2016

After spinal cord injury (SCI), disruption of blood–spinal cord barrier (BSCB) elicits blood cell infiltration such as neutrophils and macrophages, contributing to permanent neurological disability. Previous studies show that epidermal growth factor (EGF) produces potent neuroprotective effects in SCI models. However, little is known that whether EGF contributes to the integrity of BSCB. The present study is performed to explore the mechanism of BSCB permeability changes which are induced by EGF treatment after SCI in rats. In this study, we demonstrate that EGF administration inhibits the disruption of BSCB permeability and improves the locomotor activity in SCI model rats. Inhibition of the PI3K/Akt pathways by a specific inhibitor, LY294002, suppresses EGF‐induced Rac1 activation as well as tight junction (TJ) and adherens junction (AJ) expression. Furthermore, the protective effect of EGF on BSCB is related to the activation of Rac1 both in vivo and in vitro. Blockade of Rac1 activation with Rac1 siRNA downregulates EGF‐induced TJ and AJ proteins expression in endothelial cells. Taken together, our results indicate that EGF treatment preserves BSCB integrity and improves functional recovery after SCI via PI3K‐Akt‐Rac1 signalling pathway.
Effect of closed v. intermittent‐flow respirometry on hypoxia tolerance in the shiner perch Cymatogaster aggregata
Authors: Snyder S. , Nadler L. E. , Bayley J. S. , Svendsen M. B. S. , Johansen J. L. , Domenici P. , Steffensen J. F.
Published: January 2016

This study compares the critical oxygen saturation (O2crit) levels of the shiner perch Cymatogaster aggregata obtained using two different methods wherein hypoxia is induced either by the fish's respiration (closed respirometry) or by degassing oxygen with nitrogen (intermittent‐flow respirometry). Fish exhibited loss of equilibrium at a higher O2 saturation in the closed respirometry method when compared with the intermittent‐flow method. Utilization of closed respirometry yielded O2crit measurements that were almost twice as high as those obtained with intermittent‐flow respirometry. The lower hypoxia tolerance in closed respirometry is consistent with additional stress, caused by a build‐up of ammonia and carbon dioxide and a faster rate in dissolved oxygen decline. The results indicate that these two methods of determining hypoxia tolerance in aquatic organisms are not comparable, and that much care should be given to method choice.
Impact of aldo‐keto reductase family 1 member B10 on the risk of hepatitis C virus‐related hepatocellular carcinoma
Authors: Sato Shunsuke , Genda Takuya , Ichida Takafumi , Murata Ayato , Tsuzura Hironori , Narita Yutaka , Kanemitsu Yoshio , Ishikawa Sachiko , Kikuchi Tetsu , Mori Masashi , Hirano Katsuharu , Iijima Katsuyori , Wada Ryo , Nagahara Akihito , Watanabe Sumio
Published: January 2016

Background and Aim

Aldo‐keto reductase family 1 member B10 (AKR1B10), a cancer‐related oxidoreductase, was recently reported to be upregulated in some chronic liver diseases. However, its relevance in hepatocellular carcinoma (HCC) development is not fully assessed, especially in patients with chronic hepatitis C virus (HCV) infection.

Methods

Aldo‐keto reductase family 1 member B10 expression in the liver of 550 patients with chronic HCV infection was immunohistochemically assessed and quantified. A multivariate Cox model was used to estimate the hazard ratios (HRs) of AKR1B10 expression for HCC development, and the cumulative incidence of HCC was evaluated using the Kaplan–Meier method.

Results

Aldo‐keto reductase family 1 member B10 expression in the patients ranged from 0% to 80%. During the median follow‐up of 3.2 years, 43 of 550 patients developed HCC. Multivariate analysis demonstrated that high AKR1B10 expression (≥6%) was an independent risk factor for HCC (HR, 6.43; 95% confidence interval, 2.90–14.25; P < 0.001). The 5‐year cumulative incidences of HCC were 22.8% and 2.2% in patients with high and low AKR1B10 expression, respectively (P < 0.001). In subgroup analyses, the effects of high AKR1B10 expression on HCC development risk were significant over strata. In particular, HRs attributed to high AKR1B10 expression were significant in the subgroups that had been considered at a lower risk of HCC, such as in patients with younger age and mild hepatic fibrosis or those who achieved sustained virological response after interferon therapy.

Conclusion

Various degrees of AKR1B10 upregulation in the liver were observed in patients with chronic HCV infection, and high AKR1B10 expression could be a novel predictor of HCC.
A business of some heat: molecular imaging of phosphodiesterase 5
Authors: Cumming Paul
Published: January 2016

G‐protein coupled receptors activate intracellular signaling by well‐known pathways involving cyclic nucleotides or phosphatidylinositol. However, these signaling pathways (second messenger systems) have scarcely been investigated with molecular imaging techniques. This Editorial highlights a preclinical PET study by Gómez‐Vallejo and coworkers, in which the authors studied the cerebral uptake of the prototypic phosphodiesterase 5 (PDE5) inhibitor sildenafil and showed that its action manifested in elevated cGMP levels in cerebrospinal fluid of non‐human primates, but their rat PET studies with [11C]sildenafil failed to show specific binding in brain. This negative PET study underlines that abundance (Bmax) of the target molecule can be decisive for success of a new ligand, and emphasizes the need for further quantitative PET studies of PDE5 as calculations suggest that it might yet be detected with a PET tracer of higher affinity than [11C]sildenafil.

Read the highlighted article ‘Pharmacokinetic investigation of sildenafil using positron emission tomography and determination of its effect on cerebrospinal fluid cGMP levels’ on page 403.
Evaluation of Palate Cleansers for Astringency Evaluation of Red Wines
Authors: Vidal Leticia , Antúnez Lucía , Giménez Ana , Ares Gastón
Published: January 2016

Astringency has been reported to be strongly time‐dependent and to exhibit buildup on repeated ingestions. A common approach to deal with this phenomenon during astringency evaluation is the use of palate cleansers. The aim of this work was to evaluate palate cleansers for red wine astringency evaluation, considering both reduction of astringency buildup and sample discrimination. Fourteen trained panelists evaluated two sets of four Tannat wine samples using time‐intensity methodology. In the first sample set the same wine was presented four times, while the second one comprised four samples with different added concentrations of added grape seed tannins. Each assessor evaluated both sample sets with five different palate cleansers (still mineral water, plain unsalted crackers, skimmed milk, drinkable plain sweetened yogurt and 2 g/L pectin solution) in triplicate. None of the evaluated palate cleansers could prevent the occurrence of astringency buildup, while sample discrimination ability differed among the five palate cleansers considered.

Practical Applications

Astringency is one of the most relevant sensory characteristics involved in wine quality and complexity, which makes its evaluation very important for wine industry and wine research. Results from this study provide information for the selection of best practices in astringency evaluation. The fact that none of the evaluated palate cleansers was efficient in preventing astringency buildup over repeated ingestions highlights the importance of limiting the number of wine samples evaluated in a single session and/or considering a predetermined waiting time between samples. Regarding sample discrimination, drinkable plain sweetened yogurt, followed by a water rinse, provided the best results compared to other usual alternatives, such as water, pectin solutions or plain crackers. In fact, plain crackers, which have been recommended in other studies, showed the lowest discrimination.
Chondrules in CK carbonaceous chondrites and thermal history of the CV–CK parent body
Authors: Chaumard Noël , Devouard Bertrand
Published: January 2016

CK chondrites are the only group of carbonaceous chondrites with petrologic types ranging from 3 to 6. It is commonly reported than ~15 vol% of CK4–6 samples are composed of chondrules. The modal abundance of chondrules estimated here for 18 CK3–6 (including five CK3s) ranges from zero (totally recrystallized) to 50.5%. Although almost all chemically re‐equilibrated with the host matrix, we recognized in CK3s and Tanezrouft (Tnz) 057 (CK4) up to 85% of chondrules as former type I chondrules. Mean diameters of chondrules range from 0.22 to 1.05 mm for Karoonda (CK4) and Tnz 057 (CK4), respectively. Up to ~60% of chondrules in CK3–4 are surrounded by igneous rims (from ~20 μm to 2 mm width). Zoned olivines were found in unequilibrated chondrules from DaG 431 (CK3‐an), NWA 4724 (CK3.8), NWA 4423 (CK3.9), and Tnz 057 (CK4). We modeled Fe/Mg interdiffusion profiles measured in zoned olivines to evaluate the peak metamorphic temperatures and time scales of the CK parent body metamorphism, and proposed a two‐stage diffusion process in order to account for the position of inflection points situated within chondrules. Time scales inferred from Fe/Mg interdiffusion in olivine from unequilibrated chondrules are on the order of tens to a hundred thousand years (from 50 to 70,000 years for peak metamorphic temperatures of 1140 and 920 K, respectively). These durations are longer than what is commonly accepted for shock metamorphism and shorter than what is required for nuclide decay. Using the concept of a continuous CV–CK metamorphic series, which is reinforced by this study, we estimated peak metamorphic temperatures <850 K for CV, 850–920 K for CK3, and 920–1140 K for CK4–6 chondrites considering a duration of 70,000 years.
Predictors of proton pump inhibitor failure in non‐erosive reflux disease: A study with impedance‐pH monitoring and high‐resolution manometry
Authors: Shi Y. , Tan N. , Zhang N. , Xiong L. , Peng S. , Lin J. , Chen M. , Xiao Y.
Published: January 2016

Background

Approximately one‐third of gastroesophageal reflux disease (GERD) patients have symptoms resistant to proton pump inhibitor (PPI). We used the high‐resolution manometry (HRM) and multichannel intraluminal impedance‐pH (MII‐pH) monitoring to investigate potential predictors of PPI failure in non‐erosive reflux disease (NERD) patients.

Methods

One hundred and seventeen NERD patients were included, within which there were 44 PPI failure patients. The symptomatic questionnaire GerdQ, HRM and 24‐hour MII‐pH monitoring were performed before PPI therapy. PPI failure was defined as persistent reflux symptoms for more than 1 day during the last week on esomeprazole (20 mg twice daily) for continuous 4 weeks. The predictors for PPI failure were investigated by multivariable logistic regression analysis.

Key Results

Proton pump inhibitor failure patients had lower body mass index (BMI) and more concomitant functional dyspepsia (FD) symptoms. PPI failure patients had a higher percentage of type I esophagogastric junction (EGJ) morphology (p = 0.005), increased EGJ augmentation (p = 0.000), higher prevalence of esophageal motility disorders (p = 0.005) and a higher ratio of negative symptom index (SI, p = 0.000). Multivariable regression analysis showed that concomitance of FD symptoms, EGJ augmentation and negative SI were independent risk factors for PPI failure in NERD.

Conclusions & Inferences

Approximately half of PPI failure patients were found to have esophageal motility disorders in HRM. The independent risk factors for PPI failure in NERD were concomitant FD symptoms, increased EGJ augmentation and negative SI.
Spontaneous Goal Inference (SGI)
Authors: Moskowitz Gordon B. , Olcaysoy Okten Irmak
Published: January 2016

When people learn about or observe the behaviors of others, they tend to make implicit inferences from these behaviors (e.g., Uleman, Saribay, & Gonzalez, 2008). Such inferences are an essential part of a person's ability to understand his/her environment and to prepare appropriate behavior within that environment. In the present paper, we review the conditions under which people are more likely to make implicit goal inferences versus implicit trait inferences. The distinction between these two ways of understanding the behavior we observe has important consequences for how we make predictions about future behavior, set expectations for our interaction partners, and how we choose to behave. It can determine when we stereotype. However, until now, the literature has focused on trait inference as the dominant way perceivers make sense of their environment, with little discussion of inferences concerning a person's goals.
Validation of an enzyme‐linked immunosorbent assay (ELISA) for the measurement of canine S100A12
Authors: Heilmann Romy M. , Cranford Shannon M. , Ambrus Andy , Grützner Niels , Schellenberg Stefan , Ruaux Craig G. , Suchodolski Jan S. , Steiner Jörg M.
Published: January 2016

Background

Canine S100 calcium‐binding protein A12 (cS100A12) shows promise as biomarker of inflammation in dogs. A previously developedcS100A12‐radioimmunoassay (RIA) requires radioactive tracers and is not sensitive enough for fecalcS100A12 concentrations in 79% of tested healthy dogs. AnELISAassay may be more sensitive thanRIAand does not require radioactive tracers.

Objective

The purpose of the study was to establish a sandwichELISAfor serum and fecalcS100A12, and to establish reference intervals (RI) for normal healthy canine serum and feces.

Methods

Polyclonal rabbit anti‐cS100A12 antibodies were generated and tested by Western blotting and immunohistochemistry. A sandwichELISAwas developed and validated, including accuracy and precision, and agreement withcS100A12‐RIA. TheRI, stability, and biologic variation in fecalcS100A12, and the effect of corticosteroids on serumcS100A12 were evaluated.

Results

Lower detection limits were 5 μg/L (serum) and 1 ng/g (fecal), respectively. Intra‐ and inter‐assay coefficients of variation were ≤ 4.4% and ≤ 10.9%, respectively. Observed‐to‐expected ratios for linearity and spiking recovery were 98.2 ± 9.8% (mean ±SD) and 93.0 ± 6.1%, respectively. There was a significant bias between theELISAand theRIA. TheRIwas 49−320 μg/L for serum and 2−484 ng/g for fecalcS100A12. FecalcS100A12 was stable for 7 days at 23, 4, −20, and −80°C; biologic variation was negligible but variation within one fecal sample was significant. Corticosteroid treatment had no clinically significant effect on serumcS100A12 concentrations.

Conclusions

ThecS100A12‐ELISAis a precise and accurate assay for serum and fecalcS100A12 in dogs.
Molecular Dynamics Study on Explosive Boiling of Thin Liquid Argon Film on Nanostructured Surface Under Different Wetting Conditions
Authors: Shavik Sheikh Mohammad , Hasan Mohammad Nasim , Monjur Morshed A. K. M.
Published: January 2016

Molecular dynamics (MDs) simulations have been performed to investigate the boiling phenomena of thin liquid film adsorbed on a nanostructured solid surface with particular emphasis on the effect of wetting condition of the solid surface. The molecular system consists of liquid and vapor argon and solid platinum wall. The nanostructures which reside on top of the solid wall have shape of rectangular block. The solid–liquid interfacial wettability, in other words whether the solid surface is hydrophilic or hydrophobic, has been altered for different cases to examine its effect on boiling phenomena. The initial configuration of the simulation domain comprises a three-phase system (solid platinum, liquid argon, and vapor argon), which was equilibrated at 90 K. After equilibrium period, the wall temperature was suddenly increased from 90 K to 250 K which is far above the critical point of argon and this initiates rapid or explosive boiling. The spatial and temporal variation of temperature and density as well as the variation of system pressure with respect to time were closely monitored for each case. The heat flux normal to the solid surface was also calculated to illustrate the effectiveness of heat transfer for different cases of wetting conditions of solid surface. The results show that the wetting condition of surface has significant effect on explosive boiling of the thin liquid film. The surface with higher wettability (hydrophilic) provides more favorable conditions for boiling than the low-wetting surface (hydrophobic), and therefore, the liquid argon responds quickly and shifts from liquid to vapor phase faster in the case of hydrophilic surface. The heat transfer rate is also much higher in the case of hydrophilic surface.
Dynamics of Tire Blowout Events and Driver Assist System for Controlling Them
Authors: Horak Dan T. , Lack Shane K.
Published: January 2016

Dynamics of a pickup truck undergoing a rear tire blowout are analyzed as a system controlled by a human driver. Analysis is based on a large nonlinear vehicle dynamics model combined with a human driver model. The main reason why some tire blowouts result in accidents is identified. Insight is generated in experiments with human drivers in a driving simulator that runs the same vehicle model as the one used for analysis. A driver assist system for controlling tire blowouts is developed and validated in real time in the driving simulator.
An Optimization-Based Approach for Prosthesis Dynamic Modeling and Parameter Identification
Authors: Yang Ting , Wu Fen , Liu Ming , Huang He (Helen)
Published: January 2016

In this paper, we propose an effective approach to model the prosthetic leg dynamics for amputees wearing active-transfemoral prosthesis (ATP) which is self-powered. To accommodate unexpected effects of thigh on knee joints, the dynamic prosthesis model has been derived using both the thigh-knee-shank and the knee-shank configurations. Correlated with the amputee’s walking data, a nonlinear optimization problem is then formulated to identify the model parameters and the gains of the PD controller which is used to control the input torque for the ATP, while reducing measurement errors of the data. Moreover, the identified models are validated by comparing the predicted dynamics with experimental measurements. The advantages of proposed method in terms of simplicity, flexibility, and accuracy are demonstrated by the high correlation coefficients and the low root-mean-square errors.
Consensus of Conspecific Agents via Collaborative and Antagonistic Interactions
Authors: Roy Subhradeep , Abaid Nicole
Published: January 2016

The vast majority of the existing agent-based models of consensus consider the interactions among the agents to be collaborative. In the present work, we define superimposed stochastically-switching network topologies which capture collaborative and antagonistic interactions among the agents. We consider a general class of agents, so-called conspecifics, which encompasses a wide range of protocols explored in the literature, ranging from Erdos-Renyi random networks to numerosity-constrained networks. We find closed form expressions for necessary and sufficient conditions for consensus. We validate the main results using Monte Carlo simulations and study the consensus conditions for Erdos-Renyi networks. We find that, for certain selections of system parameters, the presence of antagonistic interactions permits consensus in systems that would not reach accordance otherwise.
Adaptation for Air-Intake System Throttle Control in a Gasoline Engine With Low-Pressure Exhaust-Gas Recirculation
Authors: Santillo Mario , Wait Suzanne , Buckland Julia
Published: January 2016

We investigate control strategies for traditional throttle-in-bore as well as low-cost cartridge-style throttle bodies for the air-intake system (AIS) throttle used in low-pressure exhaust-gas recirculation (LPEGR) on a turbocharged gasoline engine. Pressure sensors placed upstream and downstream of the AIS throttle are available as signals from the vehicle’s engine control unit, however, we do not use high-bandwidth feedback control of the AIS throttle in order to maintain frequency separation from the higher-rate EGR loop, which uses the downstream pressure sensor for feedback control. A design-of-experiments conducted using a feed-forward lookup table-based AIS throttle control strategy exposes controller sensitivity to part-to-part variations. For accurate tracking in the presence of these variations, we explore the use of adaptive feedback control. In particular, we use an algebraic model representing the throttle plate effective opening area to develop a recursive least-squares (RLS)-based estimation routine. A low-pass filtered version of the estimated model parameters is subsequently used in the forward-path AIS throttle controller. Results are presented comparing the RLS-based feedback algorithm with the feed-forward lookup table-based control strategy. RLS is able to adapt for part-to-part and change-over-time variabilities and exhibits an improved steady-state tracking response compared to the feed-forward control strategy.
Control of a Base Load and Load-Following Regulating Organic Rankine Cycle for Waste Heat Recovery in Heavy-Duty Diesel Powertrain
Authors: Luong David , Tsao Tsu-Chin
Published: January 2016

This paper builds upon previous work on modeling and controlling an organic Rankine Cycles (ORC) used for heavy-duty diesel powertrain. The novel contribution of this paper is operating the ORC as a base load regulating waste heat recovery (WHR) system in addition to the pressure regulation examined in previous work. Specifically, the expander power is expected to follow a power demand while maintaining pressure regulation. The ORC’s heat exchangers are modeled as control-oriented, nonlinear Moving Boundary models. The pump and expander, which are coupled to the engine crankshaft, have relatively faster dynamics than the heat exchangers and are modeled as static components. The driving cycle produces transient heat source and engine conditions for the ORC to recover waste heat energy. The ORC operating point is chosen at a steady-state that meets operating constraints, which may be violated from the heat source transients. During operation, low and high constant demand loads are given to the ORC’s expander to follow while regulating to pressure setpoints. A varying square-wave demand is also examined for partload operation. The ORC is to maintain pressure and power setpoints through independent proportional-integrator controllers (PI). A pair of PI controllers are designed for regulating the evaporating and condensing pressures and a third PI controller to follow the power demand. The results demonstrate pressure and base load power regulation to setpoints when the base load is feasible for constant and varying loads. When the base load power demand is infeasibly too high, both pressure and power regulations exhibit steady-state error. In the considered scenarios, initial pressure transients violate constraints and show the need for advanced controllers. The ORC improves the engine power efficiency by 0.5–2.5%.