bluuebunny/crossref_metadata_2025 huggingface dataset:
THE CLINICAL UTILITY AND SAFETY OF A MODEL-BASED PATIENT-TAILORED DOSE REGIMEN OF VANCOMYCIN IN NEONATES
Authors: Leroux Stéphanie , Biran Valérie , Lopez Emmanuel , Madeleneau Doriane , Jacqz-Aigrain Evelyne , Zhao Wei
Published: December 2015

Background and objective

Pharmacokinetic modeling approach is often applied to evaluate antimicrobials in neonates. However, the clinical application of the model-based personalized antimicrobial therapy is still limited. Our objective is to evaluate the clinical utility and safety of the model-based patient-tailored dosing of vancomycin in neonates.

Methods

A model-based vancomycin dosing calculator, which was developed using the pharmacokinetic information from our previously published population pharmacokinetic model, has been integrated into the routine clinical care in 3 NICUs (Cochin, Robert Debré and Clocheville Hospitals) between June 2012 and November 2014. The target attainment rate was selected as the endpoint for evaluating the clinical utility. The percentage of patients achieving the target concentration of vancomycin was calculated using the first TDM samples taken 6–24 hours after starting vancomycin treatment. The safety evaluation was focused on nephrotoxicity, which was evaluated based on changes in serum creatinine concentration from a baseline value obtained within the 48 hours of starting vancomycin treatment.

Results

A total of 190 neonates were included. The mean of the 190 first TDM vancomycin concentrations was 20.0 mg/L (10th-90th percentiles: 13.1–27.6). After receiving patient-tailored doses, the target attainment rate was 71.6% (n=136) within the range of 15–25 mg/L (90.5%, n=172, within the range of 10–30 mg/L). None of the included patients has developed vancomycin-related nephrotoxicity.

Conclusion

The present work provides an evidence-based study to demonstrate the clinical utility and safety of a model-based patient-tailored dose regimen of vancomycin in neonates. The results from population pharmacokinetic study were successfully integrated in neonatal clinical practice to individualise vancomycin therapy.
SPONTANEOUS ADVERSE DRUG REACTION REPORTS FOR NEONATES AND INFANTS IN THE UK 2001–2010
Authors: Hawcutt Dan , Maqsood Hannah , Gomberg Simon , Riordan Andrew , Turner Mark
Published: December 2015

Aims

The UK Medicines and Healthcare products Regulatory Agency (MHRA) runs a national spontaneous reporting system (Yellow Card Scheme [YCS]) to collect ‘suspected' adverse drug reaction (ADR) data. We aim to describe the Yellow card reports received for patients aged ≤1 year for a 10 year period and assess their utility.

Methods

Data on all ADRs reported via the YCS in Infants aged ≤1 years from the years 2001–10 were supplied by the MHRA.

Results

In total, 3217 suspected ADRs were reported to the YCS between 2001–10 for infants age ≤1 year (Neonates n=97, vaccinations n=2673, infant [neither neonate nor vaccine] n=477). Overall only 0.88 YC per day were received by the MHRA with a male preponderance (Male 50.3%, Female 45.7%); only 25 (0.8%) YC reports stated a gestational age for the affected infant. The medications most frequently reported as suspected of causing an ADR were Swine Flu Vaccine (neonates n=8), Neisseria meningitides (vaccinations n=693) and oseltamivir (infants n=37). Reports associated with vaccinations followed the expected trends. ADRs highlighted by regulators for neonatal and infant populations are not represented in the YCs received by the regulator.

Conclusions

The frequency of YCS reports for those ≤1 year is low, with less than 1 per day overall. Neonates are poorly represented, and recording of gestational age is very limited. The YCS appears to be more effective for spontaneous reporting of vaccination-related ADRs in infants than for other medications. Action is required to improve reporting of suspected ADRs that affect neonates and infants.
PARACETAMOL DISPOSITION IN YOUNG WOMEN: BOTH PREGNANCY AND TOOLS TO AVOID PREGNANCY MATTER
Authors: Allegaert Karel , Peeters Mariska Y , Beleyn Bjorn , Smits Anne , Kulo Aida , van Calsteren Kristel , Deprest Jan , AJ Knibbe Catherijne
Published: December 2015

Introduction

In this pooled study, we focused on the population pharmacokinetic profile of intravenous paracetamol metabolism and its covariates in young women, including during pregnancy and postpartum.

Methods

Population PK parameters using non-linear mixed effect modelling were estimated in a pooled dataset of plasma and urine PK studies in 69 young women [47 at delivery, 8/47 again 10–15 weeks after delivery (early postpartum), and 7/8 again one year after delivery (late postpartum), 22 healthy female volunteers with or without oral contraceptives].

Results

Population PK parameters were estimated based on 815 plasma samples and 101 urine collections. Compared to healthy female volunteers (reference group) not on oral contraceptives, being at delivery was the most significant covariate for clearance to paracetamol glucuronide (F=2.03), while women in early postpartum had decreased paracetamol glucuronidation clearance (F=0.55). Women on contraceptives showed increased paracetamol glucuronidation clearance (F=1.46). The oestradiol level did not further affected this model. Being at delivery did not prove significant for clearance to paracetamol sulphate, but was higher in pregnant women who delivered preterm (<37 weeks, F=1.34) compared to term delivery and non-pregnant women. Finally, clearance of unchanged paracetamol was dependent on urine flow rate.

Conclusions

Compared to healthy female volunteers, the urine paracetamol glucuronidation elimination in young women is affected by pregnancy (higher), early postpartum (lower) or exposure to oral contraceptives (higher). This may be of relevance to predict variability in glucuronidation activity in young women and to predict fetal exposure to paracetamol and its metabolites.
EXTREMELY PREMATURE NEONATES EXHIBIT INSULIN RESISTANCE
Authors: Salis Emma R , Reith David M , Broadbent Roland S , Wheeler Benjamin J , Medlicott Natalie J
Published: December 2015

Introduction

Preterm birth disrupts normal timing of physiological adaptation of insulin secretion putting premature neonates at risk of abnormal glucose homeostasis. The insulin/C-peptide (I/CP) ratio gives an indication of insulin clearance but has not been reported in neonates. Premature neonates have significantly higher fasting levels of GLP-1 than adults that increase even further with feeding.

Aims

To determine I/CP and insulin/blood glucose level (I/BGL) ratios in neonates and the effect of postmenstrual age (PMA) on these measures. To determine GLP-1 concentrations in never-fed versus fed neonates.

Methods

Plasma samples were obtained from 102 neonates admitted to Dunedin Hospital NICU. Plasma was analysed for insulin and C-peptide using chemiluminescent kits (Invitron, UK), GLP-1 and glucagon using ELISA (BioCore Pty Ltd, Australia). Statistical analyses were performed using Stata/IC (v11.2).

Results

The PMA range was 24–51.3 weeks. The median I/CP ratio was 0.44, 95% CI (0.44, 0.61). The median I/BGL ratio was 9.3, 95% CI (8.2, 10.6). Linear regressions of ln-transformed data were performed. I/CP and I/BGL ratios were significantly affected by PMA (p<0.01). Negative correlations were found (r=−0.21 and −0.35 for I/CP and I/BGL respectively, p<0.01) and I/CP changed around 34 weeks. Insulin concentrations were negatively correlated (r=−0.38, p<0.01) with increasing PMA. ANOVA showed higher GLP-1 concentrations (p=0.011) in fed versus never-fed neonates.

Conclusions

These findings indicate insulin resistance in premature neonates prior to 34 weeks gestation. The significantly higher GLP-1 concentrations in fed neonates confirm that GLP-1 increases with the establishment of feeding.
HOW SAFE IS ON-LABEL DRUG USE IN PAEDIATRICS? THE CASE OF FIRST GENERATION H1-ANTIHISTAMINES
Authors: Bruyne Pauline De , Boussery Koen , Christiaens Thierry , Mehuys Els , Winckel Myriam Van
Published: December 2015

Background

For obvious reasons, much attention has recently been paid to off-label prescriptions in paediatrics. However, on-label prescribing can cause health issues too: we discuss the case of first generation H1-antihistamines (FGAs). These have been in use for over 70 years, for a variety of indications such as relief of allergic conditions, cough and insomnia.

Materials and methods

The FGAs were listed using their International Nonproprietary Names (INN). For each formulation, the information of the Summary of Product Characteristics issued in five selected European countries (Belgium, France, Germany, the Netherlands and United Kingdom) was collected. This was plotted against the published evidence on efficacy and safety of each FGA.

Results

16 different FGAs are currently marketed in single-drug oral preparations in the evaluated countries. When investigating each drug separately, a huge variability in labelled indications, licensing age for paediatric use, and availability characteristics in the different countries is observed. Most of the indications are not supported by evidence from published clinical trials.

Conclusion

Both health care professionals and consumers generally assume that all approved H1-antihistamines have been shown to be efficacious and safe, but many in this class – in particular those introduced before 1985 – have not been optimally studied. This might explain the inconsistencies in indications and licensing ages of the evaluated drugs in different countries. Moreover, many of the antihistamines are sold over the counter, which may contribute to overuse. Such overuse can be a serious problem, as sedation is a known side effect of all FGAs.
EVALUATION OF A PEDIATRIC LIQUID FORMULATION TO IMPROVE 6-MERCAPTOPURINE THERAPY IN CHILDREN
Authors: de Beaumanis Tiphanie Adam , Hjalgrim Lisa Lynqsie , Nersting Jacob , Breitkreutz Jörg , Bertrand Yves , Stanulla Martin , Leverger Guy , Baruchel André , Schmiegelow Kjeld , Jacqz-Aigrain Evelyne
Published: December 2015

Background

6-mercaptopurine (6-MP), a key drug for treatment of acute lymphoblastic leukemia (ALL), has until recently had no adequate formulation for pediatric patients. Several approaches have been taken but the only oral paraben-free 6-MP liquid formulation named Loulla was developed and evaluated in the target population. Preclinical and clinical evaluation was performed according to a Pediatric Investigation Plan, in order to apply for a Pediatric Use Marketing Authorization.

Methods

The pre-clinical study assessed the maximum tolerated dosage-volume and evaluated local mucosal toxicity of 28 daily administrations in treated compared to controls gold hamsters. The multi-centre clinical study was single-dose, open-label, crossover trial, conducted in 15 ALL children during maintenance therapy. The bioavailability and palatability of a single 50 mg fixed dose of Loulla compared to 50 mg registered tablets were evaluated in a random order on two consecutive days. Seven blood samples over 9 hours were obtained each day at to determine 6-MP pharmacokinetic parameters, including Tmax, Cmax, AUC0–9 and AUC0–∞. A questionnaire adapted to children testing Loulla palatability and preference for either Loulla or the usual 6-MP tablet was completed. Occurrence of adverse events was determined at study visits by vital sign measurements, patient's spontaneous reporting, investigator's questioning and clinical examination.

Results

The preclinical study in gold hamsters showed that dosage-volume of 75 mg/kg/day was well tolerated. The relative bioavailability of liquid Loulla formulation compared to the reference presentation is 76% for AUC0-9 and AUC0-∞ and 80% for Cmax. The taste of Loulla and the mouth feeling after ingestion compare favorably to the tablet. No adverse event occurred.

Conclusion

Pharmacokinetic, palatability and safety data support the use of Loulla in children.
SAFETY OF LAMOTRIGINE IN PAEDIATRICS: A SYSTEMIC REVIEW
Authors: Egunsola Oluwaseun , Choonara Imti , Sammons Helen
Published: December 2015

Background

Lamotrigine has been increasingly used for the treatment of paediatric epilepsy. It is the most commonly prescribed new generation antiepileptic drug in the UK.

Objectives

To identify adverse drug reactions associated with lamotrigine in children, compare the safety profile with other antiepileptic drugs and identify all clinical studies and case reports involving lamotrigine safety in children.

Methods

Databases EMBASE (1974-November 2013), Medline (1946-November 2013), PubMed and the Cochrane library for randomised controlled trials were searched for original research or reports in which paediatric patients received at least a single dose of lamotrigine for the treatment of epilepsy, with safety as an outcome measure.

Results

A total of 76 articles involving 2,184 paediatric patients were identified. There were 1,952 adverse events (AEs) reported. Fifty two of these AEs were from 49 case reports. Rash was most commonly reported, with a risk of 8.96 per 100 patients. Other common AEs included headache, fever, somnolence, vomiting, seizure aggravation, dizziness, cough, aggression, ataxia and insomnia. There were significantly higher risks of dizziness [RR 4.57, 95% CI: 1.88–11.12, p<0.001], abdominal pain [RR: 2.53, 95% CI: 1.12–5.70, p=0.03] and nausea [RR: 5.94, 95% CI: 1.59–22.13, p=0.008] with lamotrigine than placebo. When compared with valproic acid, the risk of somnolence and vomiting was significantly lower for lamotrigine [RR: 0.35, 95% CI: 0.13–0.89, p=0.04] and [RR: 0.20, 95% CI: 0.04–0.89, p=0.03]. Discontinuation due to an adverse drug reaction was recorded in 72 children (3.2% of all treated patients). Rash was the most common reason, with 58% of treatment discontinuation attributed to different forms of rash.

Conclusion

Rash is the most common adverse reaction of lamotrigine, seen in around 9% of patients, and it is the most common reason for treatment discontinuation.
QUALITY ASSESSMENT OF ANTIBIOTIC PRESCRIPTIONS IN PAEDIATRIC PRIMARY CARE SETTINGS IN SERBIA, USING EUROPEAN QUALITY INDICATORS
Authors: Božić Bojana , Bajčetić Milica
Published: December 2015

Objective

The aim of the study was to compare the quality of antibiotic use among children in primary care settings for acute upper respiratory tract infections, acute tonsillitis and acute otitis media (AOM) with the internationally developed disease-specific antibiotic prescribing quality indicators (APQI) and with National Guidelines.

Methods

Prescriptions of systemic antibiotics to the paediatric population (<18 years) with three conditions for the period between 2011 and 2013, at the primary level of health care were analysed by using the National Health Insurance Fund's outpatient reimbursement database.

Results

During the followed up period acute upper respiratory infections, 42%, acute tonsillitis, 25%, and AOM/myringitis, 2%, represented more than 69% of the all indications for prescribing antibiotics. The percentage of patients prescribed an antibiotic for acute upper respiratory tract infections, acute tonsillitis and acute otitis media (AOM) was above the proposed range (≤20), 87%–96%. The percentage of patients prescribed a recommended antibiotic was below the proposed range (≥80%), 1%–17%, while the adherence rate to National Guidelines was low, 19%–28%. The percentage of patients prescribed quinolones was above the proposed range for AOM (≤5%), 7%. There were no significant differences in indicators value at the regional level in Serbia.

Conclusion

Based on results for disease-specific quality indicators for the most common children diseases and low adherence rates with our National guidelines we can conclude that antibiotic use is inappropriate in Serbia.
Human acetyl-CoA:glucosamine-6-phosphate N-acetyltransferase 1 has a relaxed donor specificity and transfers acyl groups up to four carbons in length
Authors: Brockhausen Inka , Nair Dileep G. , Chen Min , Yang Xiaojing , Allingham John S. , Szarek Walter A. , Anastassiades Tassos
Published: December 2015

Glucosamine-6-phosphate N-acetyltransferase1 (GNA1) catalyses the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to glucosamine-6-phosphate (GlcN6P) to form N-acetylglucosamine-6-phosphate (GlcNAc6P), which is an essential intermediate in UDP-GlcNAc biosynthesis. An analog of GlcNAc, N-butyrylglucosamine (GlcNBu) has shown healing properties for bone and articular cartilage in animal models of arthritis. The goal of this work was to examine whether GNA1 has the ability to transfer a butyryl group from butyryl-CoA to GlcN6P to form GlcNBu6P, which can then be converted to GlcNBu. We developed fluorescent and radioactive assays and examined the donor specificity of human GNA1. Acetyl, propionyl, n-butyryl, and isobutyryl groups were all transferred to GlcN6P, but isovaleryl-CoA and decanoyl-CoA did not serve as donor substrates. Site-specific mutants were produced to examine the role of amino acids potentially affecting the size and properties of the AcCoA binding pocket. All of the wild type and mutant enzymes showed activities of both acetyl and butyryl transfer and can therefore be used for the enzymatic synthesis of GlcNBu for biomedical applications.
Arrest of blow up for the 3D semi-relativistic Schrödinger–Poisson system with pseudo-relativistic diffusion
Authors: Abou Salem W. , Chen T. , Vougalter V.
Published: December 2015

We show global well-posedness in energy norm of the semi-relativistic Schrödinger–Poisson system of equations with attractive Coulomb interaction in [Formula: see text] in the presence of pseudo-relativistic diffusion. We also discuss sufficient conditions to have well-posedness in [Formula: see text]. In the absence of dissipation, we show that the solution corresponding to an initial condition with negative energy blows up in finite time, which is as expected, since the nonlinearity is critical.
Constraints of nonresponding flows based on cross layers in the networks
Authors: Zhou Zhi-Chao , Xiao Yang , Wang Dong
Published: December 2015

In the active queue management (AQM) scheme, core routers cannot manage and constrain user datagram protocol (UDP) data flows by the sliding window control mechanism in the transport layer due to the nonresponsive nature of such traffic flows. However, the UDP traffics occupy a large part of the network service nowadays which brings a great challenge to the stability of the more and more complex networks. To solve the uncontrollable problem, this paper proposes a cross layers random early detection (CLRED) scheme, which can control the nonresponding UDP-like flows rate effectively when congestion occurs in the access point (AP). The CLRED makes use of the MAC frame acknowledgement (ACK) transmitting congestion information to the sources nodes and utilizes the back-off windows of the MAC layer throttling data rate. Consequently, the UDP-like flows data rate can be restrained timely by the sources nodes in order to alleviate congestion in the complex networks. The proposed CLRED can constrain the nonresponsive flows availably and make the communication expedite, so that the network can sustain stable. The simulation results of network simulator-2 (NS2) verify the proposed CLRED scheme.
On stable solutions of the fractional Hénon–Lane–Emden equation
Authors: Fazly Mostafa , Wei Juncheng
Published: December 2015

We derive monotonicity formulae for solutions of the fractional Hénon–Lane–Emden equation [Formula: see text] when [Formula: see text], [Formula: see text] and [Formula: see text]. Then, we apply these formulae to classify stable solutions of the above equation.
Strong nonuniform spectrum for arbitrary growth rates
Authors: Barreira Luis , Dragičević Davor , Valls Claudia
Published: December 2015

We consider the notion of strong nonuniform spectrum for a nonautonomous dynamics with discrete time obtained from a sequence of matrices, which is defined in terms of the existence of strong nonuniform exponential dichotomies with an arbitrarily small nonuniform part. The latter exponential dichotomies are ubiquitous in the context of ergodic theory and correspond to have both lower and upper bounds along the stable and unstable directions, besides possibly a nonuniform conditional stability although with an arbitrarily small exponential dependence on the initial time. Moreover, we consider arbitrary growth rates instead of only the usual exponential rates. We give a complete characterization of the possible strong nonuniform spectra and for a Lyapunov regular trajectory, we show that the spectrum is the set of Lyapunov exponents. In addition, we provide explicit examples of nonautonomous dynamics for all possible strong nonuniform spectra. A remarkable consequence of our results is that for a sequence of matrices [Formula: see text], either [Formula: see text] does not admit a strong exponential dichotomy for any [Formula: see text], or if [Formula: see text] admits an exponential dichotomy for some [Formula: see text], then it also admits a strong exponential dichotomy for that [Formula: see text]. We emphasize that this result is not in the literature even in the special case of uniform exponential dichotomies.
Generalized edge-colorings of weighted graphs
Authors: Obata Yuji , Nishizeki Takao
Published: December 2015

Let [Formula: see text] be a graph with a positive integer weight [Formula: see text] for each vertex [Formula: see text]. One wishes to assign each edge [Formula: see text] of [Formula: see text] a positive integer [Formula: see text] as a color so that [Formula: see text] for any vertex [Formula: see text] and any two edges [Formula: see text] and [Formula: see text] incident to [Formula: see text]. Such an assignment [Formula: see text] is called an [Formula: see text]-edge-coloring of [Formula: see text], and the maximum integer assigned to edges is called the span of [Formula: see text]. The [Formula: see text]-chromatic index of [Formula: see text] is the minimum span over all [Formula: see text]-edge-colorings of [Formula: see text]. In the paper, we present various upper and lower bounds on the [Formula: see text]-chromatic index, and obtain three efficient algorithms to find an [Formula: see text]-edge-coloring of a given graph. One of them finds an [Formula: see text]-edge-coloring with span smaller than twice the [Formula: see text]-chromatic index.
Cenozoic structural evolution of the Andaman Sea: evolution from an extensional to a sheared margin
Authors: Morley C. K.
Published: December 2015

The Andaman Sea is proposed to have developed from a margin where Palaeogene back-arc collapse closed a mid-Cretaceous back-arc oceanic basin, and resulted in the collision between island arc crust to the west and the western margin of Sundaland. Subsequent east–west to WNW–ESE extension during the Late Eocene–Oligocene resulted in highly extended continental crust underlying the Alcock and Sewell rises, and the East Andaman Basin, and moderately extended crust in the Megui–North Sumatra Basin. As India coupled with western Myanmar, the margin became dominated by dextral strike-slip and NNW–SSE transtensional deformation during the Miocene. The narrow belt of NNW–SSE-directed extension is proposed to have focused on the region where ductile middle crust remained following Late Eocene–Oligocene extension, whereas strike-slip faults are located in the regions of necking where ductile middle crust was considerably thinned by Late Eocene–Oligocene extension. The last phase of NNW–SSE-extension switched between probable Late Miocene–Early Pliocene seafloor spreading, and extension (by dyke intrusion and faulting) in the Alcock and Sewell rises, and then recently back to the spreading centre.
Development history of the southern terminus of the Central Atlantic; Guyana–Suriname case study
Authors: Nemčok M. , Rybár S. , Odegard M. , Dickson W. , Pelech O. , Ledvényiová L. , Matejová M. , Molčan M. , Hermeston S. , Jones D. , Cuervo E. , Cheng R. , Forero G.
Published: December 2015

The study focuses on the offshore Guyana–Suriname–French Guiana region. It draws from seismic, well, gravimetric and magnetic data. They indicate that the continental break-up along the western margin of the Demerara Plateau took place during the Callovian–Oxfordian, associated with the Central Atlantic opening, and accommodated by normal faults. The continental break-up in the SE offshore Guyana accommodated by strike-slip faults was coeval. The continental break-up along the NE and eastern margins of the Demerara Plateau took place during the late Aptian–Albian, associated with the opening of the Equatorial Atlantic, and accommodated by dextral strike-slip and normal faults, respectively.

Different spreading vectors of the Central and Equatorial Atlantic required development of the Accommodation Block during the late Aptian/Albian–Paleocene in their contact region, and in the region between the Central Atlantic and its southernmost portion represented by the Offshore Guyana Block, which were separated from each other by the opening Equatorial Atlantic. Its role was to accommodate for about 20° mismatch between the Central and Equatorial Atlantic spreading vectors, which has decreased from the late Aptian/Albian to Paleocene down to 0°.

Differential movements between the Central and Equatorial Atlantic oceans were also accommodated by strike-slip faults of the Guyana continental margin, some active until the Paleocene.

Supplementary material:

Extended methods and discussion chapters are available at
http://www.geolsoc.org.uk/SUP18875
Transpressional structures and hydrocarbon potential along the Romanche Fracture Zone: a review
Authors: Davison Ian , Faull Theodore , Greenhalgh Jenny , O Beirne Eoin , Steel Ian
Published: December 2015

The Romanche Fracture Zone was originally a corridor of Aptian-age dextral transtensional rifting along the Equatorial Atlantic margins. Late Albian plate tectonic compression occurred due to a change in plate vectors, when the African and South American continents were still in contact across a 500 km-long section of the Romanche Fracture Zone. This dextral compression produced reactivation of the rift faults to produce asymmetric landward-vergent anticlines and thrusts that trend ENE to NE. Fold-axial planes dip seaward, parallel to the rift faults. Minor asymmetric anticlines were developed on the long seaward-dipping fold limbs and these have subvertical axial planes. The asymmetry of the minor folds is due to the southward stratal dip having been oblique to the horizontal maximum principal stress during the Albian inversion. The folds on the African margin were subsequently tightened by compression in Santonian and Oligo-Miocene times. Aptian-age ENE strike-slip faults were reactivated during the compression phases to produce broad positive flower structures up to 30 km wide that formed topographical ridges along the original strike-slip faults. The intervening and broader flat-bottomed synclines do not appear to be associated with rift faults.

The folding and thrust faulting created seabed relief of 1–2 km at the end of the Albian; evidenced by the amount of subsequent erosion that removed the better-quality reservoirs in the upper Albian sequence from the major fold crests. Consequently, there has been a significant number of failed oil exploration wells drilled along the fold crests. The fold ridges would have diverted turbidite channels in the onlapping Cenomanian–Campanian sequence and these will be preferentially located on the landward side of the anticlinal crests. Late Cretaceous stratigraphic and structural traps located between the major anticlines have not yet been explored for hydrocarbons along the Romanche Fracture Zone margins.
The role of break-up localization in microcontinent separation along a strike-slip margin: the East India–Elan Bank case study
Authors: Sinha Sudipta Tapan , Nemčok Michal , Choudhuri Mainak , Sinha Neeraj , Rao D. Pundarika
Published: December 2015

The Elan Bank microcontinent was separated from East India during the Early Cretaceous break-up. The crustal architecture and rifting geometry of East India and the Elan Bank margins document that the early break-up between India and Antarctica was initiated in the eastern portions of the Cauvery and Krishna–Godavari rift zones, and in the southern portion of Elan Bank. However, the westwards break-up propagation along the Krishna–Godavari Rift Zone continued even after the break-up in the overstepping portion of the Cauvery Rift Zone. Eventually, the western propagating end of the Krishna–Godavari Rift Zone became hard-linked with the failed western portion of the Cauvery Rift Zone by the dextral Coromandel transfer fault zone. Consequently, the break-up location between India and Antarctica shifted from its initial to its final location along the northern portion of the Elan Bank formed by the western Krishna–Godavari Rift Zone. The competition between the two rift zones to capture continental break-up and asymmetric ridge propagation resulted in a ridge jump and the Elan Bank microcontinent release.

Supplementary material:

Supplementary figures are available at
http://www.geolsoc.org.uk/SUP18864
Lower-crust ductility patterns associated with transform margins
Authors: Henk A. , Nemčok M.
Published: December 2015

A three-dimensional (3D) thermal–kinematic modelling approach based on finite-element techniques is used to study lower-crustal viscosity at transform margins during the continent–ocean transform development stage and after the ridge has passed by. Nine modelling scenarios combining different equilibrium surface heat flows and lower-crustal rheologies are studied. Modelling results indicate that substantial parts of the lower crust at transform margins have the potential to flow at geologically appreciable strain rates, which can lead to uplift/subsidence, as well as lateral variations, in upper- and lower-crustal thicknesses and Moho depth. These low-viscosity zones (i.e. parts of the lower crust with effective viscosities of less than 10
18
Pa s) make up distinct ductility distributions that vary in space and time during margin evolution. Three basic ductility patterns and related thermal processes can be identified: reduced lower-crustal viscosities originating at the continental rift and the continent–ocean boundary (COB), respectively; reduced lower-crustal viscosities along the transform caused by the migrating ridge; and the background distribution of lower-crustal ductility resulting from the equilibrium temperature field. Superposition of all three ductility patterns and the complex interaction of the underlying perturbations of the temperature field result in distinct differences in the potential of lower-crustal flow both in space (parallel and perpendicular to the transform) and with time. Thus, modelling results provide templates for understanding lower-crustal flow at transform margins in general and await further studies comparing model predictions with actual field observations.
Self-Care Technologies in HCI
Authors: Nunes Francisco , Verdezoto Nervo , Fitzpatrick Geraldine , Kyng Morten , Grönvall Erik , Storni Cristiano
Published: December 2015

Many studies show that self-care technologies can support patients with chronic conditions and their carers in understanding the ill body and increasing control of their condition. However, many of these studies have largely privileged a medical perspective and thus overlooked how patients and carers integrate self-care into their daily lives and mediate their conditions through technology. In this review, we focus on how patients and carers use and experience self-care technology through a Human-Computer Interaction (HCI) lens. We analyse studies of self-care published in key HCI journals and conferences using the Grounded Theory Literature Review (GTLR) method and identify research trends and design tensions. We then draw out opportunities for advancing HCI research in self-care, namely, focusing further on patients' everyday life experience, considering existing collaborations in self-care, and increasing the influence on medical research and practice around self-care technology.
Eradication of Invading Insect Populations: From Concepts to Applications
Authors: Liebhold Andrew M. , Berec Ludek , Brockerhoff Eckehard G. , Epanchin-Niell Rebecca S. , Hastings Alan , Herms Daniel A. , Kean John M. , McCullough Deborah G. , Suckling David M. , Tobin Patrick C. , Yamanaka Takehiko
Published: December 2015

Eradication is the deliberate elimination of a species from an area. Given that international quarantine measures can never be 100% effective, surveillance for newly arrived populations of nonnative species coupled with their eradication represents an important strategy for excluding potentially damaging insect species. Historically, eradication efforts have not always been successful and have sometimes been met with public opposition. But new developments in our understanding of the dynamics of low-density populations, the availability of highly effective treatment tactics, and bioeconomic analyses of eradication strategies offer new opportunities for developing more effective surveillance and eradication programs. A key component that connects these new developments is the harnessing of Allee effects, which naturally promote localized species extinction. Here we review these developments and suggest how research might enhance eradication strategies.
IL-1β inhibits β-Klotho expression and FGF19 signaling in hepatocytes
Authors: Zhao Yueshui , Meng Chenling , Wang Yang , Huang Huihui , Liu Wenjing , Zhang Jin-Fang , Zhao Hui , Feng Bo , Leung Po Sing , Xia Yin
Published: December 2015

Fibroblast growth factor (FGF) 19 is a member of the FGF15/19 subfamily of FGFs that includes FGF15/19, FGF21, and FGF23. FGF19 has been shown to have profound effects on liver metabolism and regeneration. FGF19 binds to FGFR4 and its coreceptor β-Klotho to activate intracellular kinases, including Erk1/2. Studies have shown that proinflammatory cytokines such as TNFα impair FGF21 signaling in adipose cells by repressing β-Klotho expression. However, little is known about the effects of inflammation on the FGF19 pathway in the liver. In the present study, we found that lipopolysaccharide (LPS) inhibited β-Klotho and Fgfr4 expression in livers in mice, whereas LPS had no effects on the two FGF19 receptors in Huh-7 and HepG2 cells. Of the three inflammatory cytokines TNFα, IL-1β, and IL-6, IL-1β drastically inhibited β-Klotho expression, whereas TNFα and IL-6 had no or minor effects. None of the three cytokines had any effects on FGFR4 expression. IL-1β directly inhibited β-Klotho transcription, and this inhibition required both the JNK and NF-κB pathways. In addition, IL-1β inhibited FGF19-induced Erk1/2 activation and cell proliferation. These results suggest that inflammation and IL-1β play an important role in regulating FGF19 signaling and function in the liver.
Decreased Circulating T Regulatory Cells in Egyptian Patients with Nonsegmental Vitiligo: Correlation with Disease Activity
Authors: Hegab Doaa Salah , Attia Mohamed Attia Saad
Published: December 2015

Background. Vitiligo is an acquired depigmentary skin disorder resulting from autoimmune destruction of melanocytes. Regulatory T cells (Tregs), specifically CD4+CD25+and Forkhead box P3+(FoxP3+) Tregs, acquired notable attention because of their role in a variety of autoimmune pathologies. Dysregulation of Tregs may be one of the factors that can break tolerance to melanocyte self-antigens and contribute to vitiligo pathogenesis.Methods. In order to sustain the role of Tregs in pathogenesis and disease activity of vitiligo, surface markers for CD4+CD25+and FoxP3+peripheral Tregs were evaluated by flow cytometry in 80 Egyptian patients with nonsegmental vitiligo in addition to 60 healthy control subjects and correlated with clinical findings.Results. Vitiligo patients had significantly decreased numbers of both peripheral CD4+CD25+and FoxP3+T cells compared to control subjects (11.49%  ± 8.58% of CD4+T cells versus 21.20%  ± 3.08%, and 1.09%  ± 0.96% versus 1.44%  ± 0.24%, resp.,P<0.05for both). Peripheral numbers of CD4+CD25+and FoxP3+Tregs correlated negatively with VIDA score.Conclusion. Treg depletion with impaired immune downregulatory function might play a key role in the autoimmune conditions beyond nonsegmental vitiligo particularly in active cases. Effective Treg cell-based immunotherapies might be a future hope for patients with progressive vitiligo.
Synthesis of Cinnamanilide Derivatives and Their Antioxidant and Antimicrobial Activity
Authors: Nimse Satish Balasaheb , Pal Dilipkumar , Mazumder Avijit , Mazumder Rupa
Published: December 2015

The amide derivatives of cinnamic acid were synthesized and their antimicrobial and antioxidant activities were investigated. The investigation of antimicrobial potentials of the compounds demonstrated a strong activity against 21 bacterial strains comprising Gram-positive and Gram-negative bacteria. Compounds2a,2b, and3bshowed strong antimicrobial activity against all microorganisms with the pMIC value ranging from 2.45 to 3.68. Compounds2a,3a, and3bdemonstrated strong antioxidant activity with % inhibition of the DPPH radical of 51% (±1.14), 41% (±1.01), and 50% (±1.23), respectively. These findings indicate that the amide derivatives of the cinnamic acid possess strong antibacterial and antioxidant activities.
Computational Modeling and Theoretical Calculations on the Interactions between Spermidine and Functional Monomer (Methacrylic Acid) in a Molecularly Imprinted Polymer
Authors: Huang Yujie , Zhu Qiujin
Published: December 2015

This paper theoretically investigates interactions between a template and functional monomer required for synthesizing an efficient molecularly imprinted polymer (MIP). We employed density functional theory (DFT) to compute geometry, single-point energy, and binding energy (ΔE) of an MIP system, where spermidine (SPD) and methacrylic acid (MAA) were selected as template and functional monomer, respectively. The geometry was calculated by using B3LYP method with 6-31+(d) basis set. Furthermore, 6-311++(d, p) basis set was used to compute the single-point energy of the above geometry. The optimized geometries at different template to functional monomer molar ratios, mode of bonding between template and functional monomer, changes in charge on natural bond orbital (NBO), and binding energy were analyzed. The simulation results show that SPD and MAA form a stable complex via hydrogen bonding. At 1 : 5 SPD to MAA ratio, the binding energy is minimum, while the amount of transferred charge between the molecules is maximum; SPD and MAA form a stable complex at 1 : 5 molar ratio through six hydrogen bonds. Optimizing structure of template-functional monomer complex, through computational modeling prior synthesis, significantly contributes towards choosing a suitable pair of template-functional monomer that yields an efficient MIP with high specificity and selectivity.
Effect of Pore Thickness and the State of Polarization on the Optical Properties of Hexagonal Nanoarray of Au/Nanoporous Anodic Alumina Membrane
Authors: Shaban Mohamed
Published: December 2015

Hexagonal nanoarrays of Au particles were deposited on nanoporous anodic alumina membrane (NAAM) utilizing r.f. magnetron sputtering. The thickness of the NAAMs is adjusted by changing the second anodization time from 5 min to 20 min. The surface morphology, composition, and optical properties are characterized by using SEM, EDX, and spectrophotometer, respectively. The effects of the NAAM thickness and state of polarization on the morphological changes and on the optical properties of the fabricated nanoarrays were addressed. According to the measured optical spectra, the rate of decrease of NAAMs refractive index was found to be 3.825 × 10−4 nm−1. Using the modified Kubelka‐Munk radiative transfer model, the energy gap of NAAMs was calculated from diffused reflectance and was decreased from 1.682 to 1.376 as the anodization time increased from 5 to 20 min. Also, the saturation of interference fringes is substantially enhanced, and field enhancement can be achieved due to the excitation and constructive interference of surface plasmon waves by coating NAAMs with the hexagonal nanoarrays of Au. Based on the advantages of the fabrication approach and the enhanced and controlled properties, this new generation of samples can be used as promising building blocks for nanophotonic and nanoelectronics devices.
Splitting Travel Time Based on AFC Data: Estimating Walking, Waiting, Transfer, and In-Vehicle Travel Times in Metro System
Authors: Zhang Yong-Sheng , Yao En-Jian
Published: December 2015

The walking, waiting, transfer, and delayed in-vehicle travel times mainly contribute to route’s travel time reliability in the metro system. The automatic fare collection (AFC) system provides huge amounts of smart card records which can be used to estimate all these times distributions. A new estimation model based on Bayesian inference formulation is proposed in this paper by integrating the probability measurement of the OD pair with only one effective route, in which all kinds of times follow the truncated normal distributions. Then, Markov Chain Monte Carlo method is designed to estimate all parameters endogenously. Finally, based on AFC data in Guangzhou Metro, the estimations show that all parameters can be estimated endogenously and identifiably. Meanwhile, the truncated property of the travel time is significant and the threshold tested by the surveyed data is reliable. Furthermore, the superiority of the proposed model over the existing model in estimation and forecasting accuracy is also demonstrated.
Evaluation of Agreement between HRT III and iVue OCT in Glaucoma and Ocular Hypertension Patients
Authors: Perdicchi A. , Iester M. , Iacovello D. , Cutini A. , Balestrieri M. , Mutolo M. G. , Ferreras A. , Contestabile M. T. , Recupero S. M.
Published: December 2015

Purpose. To determine the agreement between Moorfields Regression Analysis (MRA), Glaucoma Probability Score (GPS) of Heidelberg retinal tomograph (HRT III), and peripapillary nerve fibers thickness by iVue Optical Coherence Tomography (OCT).Methods. 72 eyes with ocular hypertension or primary open angle glaucoma (POAG) were included in the study: 54 eyes had normal visual fields (VF) and 18 had VF damage. All subjects performed achromatic 30° VF by Octopus Program G1X dynamic strategy and were imaged with HRT III and iVue OCT. Sectorial and global MRA, GPS, and OCT parameters were used for the analysis. Kappa statistic was used to assess the agreement between methods.Results. A significant agreement between iVue OCT and GPS for the inferotemporal quadrant (κ: 0.555) was found in patients with abnormal VF. A good overall agreement between GPS and MRA was found in all the eyes tested (κ: 0.511). A good agreement between iVue OCT and MRA was shown in the superonasal (κ: 0.656) and nasal (κ: 0.627) quadrants followed by the superotemporal (κ: 0.602) and inferotemporal (κ: 0.586) sectors in all the studied eyes.Conclusion. The highest percentages of agreement were found per quadrant of the MRA and the iVue OCT confirming that in glaucoma damage starts from the temporal hemiretina.
Existence and Continuous Dependence for Fractional Partial Hyperbolic Differential Equations
Authors: Dong Qixiang , Wu Guangxian , Zhu Lanping
Published: December 2015

This paper is concerned with a class of fractional hyperbolic partial differential equations with the Caputo derivative. Existence and continuous dependence results of solutions are obtained under the hypothesis of the Lipschitz condition without any restriction on the Lipschitz constant. Examples are discussed to illustrate the results.
Insulin Secretory Defect and Insulin Resistance in Isolated Impaired Fasting Glucose and Isolated Impaired Glucose Tolerance
Authors: Aoyama-Sasabe Sae , Fukushima Mitsuo , Xin Xin , Taniguchi Ataru , Nakai Yoshikatsu , Mitsui Rie , Takahashi Yoshitaka , Tsuji Hideaki , Yabe Daisuke , Yasuda Koichiro , Kurose Takeshi , Inagaki Nobuya , Seino Yutaka
Published: December 2015

Objective.To investigate the characteristics of isolated impaired glucose tolerance (IGT) and isolated impaired fasting glucose (IFG), we analyzed the factors responsible for elevation of 2-hour postchallenge plasma glucose (2 h PG) and fasting plasma glucose (FPG) levels.Methods.We investigated the relationship between 2 h PG and FPG levels who underwent 75 g OGTT in 5620 Japanese subjects at initial examination for medical check-up. We compared clinical characteristics between isolated IGT and isolated IFG and analyzed the relationships of 2 h PG and FPG with clinical characteristics, the indices of insulin secretory capacity, and insulin sensitivity.Results.In a comparison between isolated IGT and isolated IFG, insulinogenic index was lower in isolated IGT than that of isolated IFG (0.43 ± 0.34 versus 0.50 ± 0.47, resp.;p<0.01). ISI composite was lower in isolated IFG than that of isolated IGT (6.87 ± 3.38 versus 7.98 ± 4.03, resp.;p<0.0001). In isolated IGT group, insulinogenic index showed a significant correlation with 2 h PG (r=-0.245,p<0.0001) and had the strongest correlation with 2 h PG (β=-0.290). In isolated IFG group, ISI composite showed a significant correlation with FPG (r=-0.162,p<0.0001) and had the strongest correlation with FPG (β=-0.214).Conclusions.We have elucidated that decreased early-phase insulin secretion is the most important factor responsible for elevation of 2 h PG levels in isolated IGT subjects, and decreased insulin sensitivity is the most important factor responsible for elevation of FPG levels in isolated IFG subjects.
A Glyoxalase-1 Knockdown Does Not Have Major Short Term Effects on Energy Expenditure and Atherosclerosis in Mice
Authors: Wortmann Markus , Hakimi Maani , Fleming Thomas , Peters Andreas S. , Sijmonsma Tjeerd P. , Herzig Stephan , Nawroth Peter P. , Böckler Dittmar , Dihlmann Susanne
Published: December 2015

Objective. Glyoxalase-1 is an enzyme detoxifying methylglyoxal (MG). MG is a potent precursor of advanced glycation endproducts which are regarded to be a key player in micro- and macrovascular damage. Yet, the role of Glo1 in atherosclerosis remains unclear. In this study, the effect of Glo1 on mouse metabolism and atherosclerosis is evaluated.Methods. Glo1 knockdown mice were fed a high fat or a standard diet for 10 weeks. Body weight and composition were investigated by Echo MRI. The PhenoMaster system was used to measure the energy expenditure. To evaluate the impact of Glo1 on atherosclerosis, Glo1KDmice were crossed with ApoE-knockout mice and fed a high fat diet for 14 weeks.Results. Glo1 activity was significantly reduced in heart, liver, and kidney lysates derived from Glo1KDmice. Yet, there was no increase in methylglyoxal-derived AGEs in all organs analyzed. The Glo1 knockdown did not affect body weight or body composition. Metabolic studies via indirect calorimetry did not show significant effects on energy expenditure. Glo1KDmice crossed to ApoE−/−mice did not show enhanced formation of atherosclerosis.Conclusion. A Glo1 knockdown does not have major short term effects on the energy expenditure or the formation of atherosclerotic plaques.
A Comparative Study of Target Tracking Approaches in Wireless Sensor Networks
Authors: Ez-Zaidi Asmaa , Rakrak Said
Published: December 2015

Wireless sensor networks have been the subject of intense research in recent years. Sensor nodes are used in wide range of applications such as security, military, and environmental monitoring. One of the most interesting applications in wireless sensor networks is target tracking, which mainly consists in detecting and monitoring the motion of mobile targets. In this paper, we present a comprehensive survey of target tracking approaches. We then analyze them according to several metrics. We also discuss some of the challenges that influence the performance of tracking schemes. In the end, we conduct detailed analysis and comparison between these algorithms and we conclude with some future directions.