bluuebunny/crossref_metadata_2025 huggingface dataset:
AVAILABILITY OF PEDIATRIC FORMULATIONS FOR THE 100 MOST PRESCRIBED DRUGS IN PEDIATRIC AMBULATORY CARE – 2002 VS. 2010
Authors: Ziesenitz Victoria C. , Anker Johannes N. van den , Amirshahi Maryann
Published: December 2015

Introduction

US legislative efforts over the past two decades have attempted to promote therapeutic equity for the pediatric population. The objective of this study was to explore trends in the availability of pediatric formulations for the most commonly prescribed drugs in US pediatric ambulatory care.

Methods

A retrospective review of the CDC's National Ambulatory Care Survey (NAMCS) from 2002–10 was performed focusing on visits involving children<6 years. The top 100 medications prescribed for which an oral dosage form was available were identified. The availability of a pediatric specific formulation was determined from FDA labeling data. Trends were compared between 2002 and 2010.

Results

In total, 94,152,217 prescriptions in 2002 and 2010 were analyzed. The most often prescribed drugs were anti-infectives (52.8 vs. 41.6%), respiratory agents (19.2 vs. 21.7%) and antipyretics/ analgesics (14.6 vs. 21.1%). In 2002, a pediatric formulation was available for 94.4% of prescriptions in comparison 95.5% in 2010 (p<0.05). Pediatric formulations were more commonly available for anti-infectives (95.3 vs. 95.9%), antipyretics/ analgesics (99.8 vs. 99.4%) as well as for respiratory (99.5 vs. 98.7%), endocrinologic (80.2 vs. 95.7%), and gastrointestinal (92.6 vs. 97.9%) agents, whereas pediatric formulations were lacking for cardiovascular (68.0 vs. 52.1%), neurologic (46.6 vs. 55.2%) and psychotherapeutic drugs (76.3 vs. 66.1%, all p<0.05).

Conclusion

Since the US Best Pharmaceuticals for Children Act 2002, more pediatric specific formulations have become available. Anti-infective agents, respiratory agents and antipyretics/analgesics have been the most commonly prescribed drugs in children <6 years.
A SYSTEMS PHARMACOLOGY MODEL TO EXPLAIN DEVELOPMENTAL DIFFERENCES IN SENSITIVITY TO DRUG-INDUCED QT PROLONGATION
Authors: Gotta Verena , Pfister Marc , Anker John van den , Graaf Piet van der
Published: December 2015

Background

Neonates have been reported to be more sensitive to drugs prolonging the QT-interval than adults. As explanation a developmental change in myocardial ion-channel density has been proposed. Here we explore changes in ion-channel density using a mechanistic pharmacodynamic model and clinical sotalol literature data.

Materials and Methods

The applied model relates in vitro and in vivo drug potency (regarding IKr-receptor occupancy and QTc-prolongation, respectively) by a system-specific transducer function. We characterized this function first for preclinical dog and in vitro data (moxifloxacin, sotalol, dofetilide). From a corresponding dofetilide model in adults we derived scaling factors for the system-specific parameters (maximal in vivo QTc-effect Em,dog/Em,adults, transducer ratio τ,dog/τ,adults; τ is proportional to the receptor density in vivo). The derived relationship was used to predict clinical sotalol pharmacodynamics in adults. Literature data was used to evaluate this scaling approach. Simulations of different τ values were performed to explore pharmacodynamic differences in neonates.

Results

In adults, the agonistic activity of dofetilide was higher than in dogs (τ,adults≈2x τ,dogs), while the estimated maximal in vivo QTc-prolongation was similar (Em≈27% from baseline). This relationship could also predict clinical sotalol pharmacodynamics in adults and children. The steeper PD profile in neonates could be explained by a higher IKr-receptor density (τ, neonates≈2x τ, adults).

Conclusion

This model-based approach allowed to integrate and scale in vitro and in vivo (preclinical, clinical adult and neonate) drug effects on the QTc-interval. The preliminary results confirm the hypothesis that IKr-receptor density is higher (≈2 times) in neonates than in adults and children.
INNOVATIVE REGULATORY-CONFORMING BIOANALYTICAL APPROACHES ENABLING SYSTEMATIC INVESTIGATIONS OF PHARMACOKINETICS AND PHARMACODYNAMICS BY PAEDIATRIC CLINICAL STUDIES IN ALL AGE GROUPS
Authors: Burckhardt Björn B , Tins Jutta , Läer Stephanie
Published: December 2015

Background

Clinical investigations on pharmacokinetics and pharmacodynamics are highly required to improve paediatric pharmacotherapy. Especially in neonates and infants the conduct is challenging due to e.g. high ethical and analytical burdens. The trial-related blood lost should not exceed 3% of the total blood volume within 4 weeks (1). Appropriate assays are lacking which leads to the fact that many drugs are not sufficiently investigated in small children.

Objective

Development of a tailored comprehensive bioanalytical setting for pharmacokinetic and pharmacodynamic investigations of drugs acting on the RAA system in neonates up to adolescents.

Methods

Bioanalytical HPLC-MS/MS methods for invasive and non-invasive determination of pharmacokinetics of aliskiren and enalapril in 50–100 µL serum, urine, and saliva were developed. Changes of humoral parameters of the RAA system were measured by five immunological assays in a total volume of 2.1 mL. All assays were scaled up to a high throughput approaches to meeting clinical demands. The applicability of the low-volume assays was assessed by a proof-of-concept study in 22 healthy volunteers and a regulatory-compliant Phase I study.

Results

The conducted studies using the low-volume assays revealed comparable pharmacokinetic results of aliskiren and enalapril in serum and urine when compared to literature. Changes in the humoral parameters are also similar and prove the applicability of the bioanalytical platform. Very dense and reliable individual concentration-time profiles of the drugs and the humoral parameters over 192 h were obtained in 45 mL blood only. Saliva appeared inappropriate to replace invasive pharmacokinetic sampling.

Conclusion

The child-appropriate bioanalytical platform can be applied in upcoming paediatric Phase II and Phase III studies of the LENA (Labeling of Enalapril from Neonates up to Adolescents) project. Meaningful concentration-time profiles with 6–7 sampling points can be obtained even in neonates without infringing ethical recommendations on trial-related blood lost.

The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement n°602295 (LENA).
SAFE-PEDRUG: A NEW STRATEGY FOR PAEDIATRIC DRUG RESEARCH
Authors: Bruyne Pauline De , Meesters Kevin , Walle Johan Vande
Published: December 2015

Background

Drug evaluation in children is stimulated by initiatives of the Regulatory Authorities; in Europe by the ‘Paediatric Regulation'. As stated in this Regulation, Paediatric Investigational Plans must be submitted to the Paediatric Committee around the end of Phase I adult trials. However, the proposed paediatric trials tend to be amended frequently and postponed to the end of the drug evaluation process, as they are largely based on extrapolations of results of adult trials.

Materials and methods

Experts in paediatrics, pharmaceutical sciences, veterinary medicine and ethics (of three Belgian universities) collaborated to develop a research consortium that will focus mainly on generating paediatric pharmacokinetic and pharmacodynamic (PK/PD) knowledge before the actual human trials are performed. National and international stakeholders (including Industry, Regulatory Authorities, and Patient Organisations) support this consortium in the valorisation of results.

Results

The above-mentioned networking resulted in the SAFE-PEDRUG project, funded by the Agency for Innovation by Science and Technology (Flanders). This program will explore the value of the porcine juvenile animal model and PK modelling (physiologically-based pharmacokinetic modelling) in providing prior paediatric PK/PD-knowledge. For the evaluation of this approach, three case compounds were selected: desmopressin, lisinopril, and fluoroquinolones. The results of the models are plotted against human paediatric data. Furthermore, PK/PD in neonates and critically ill children will also be explored.

Conclusion

A close collaboration of experts and stakeholders is mandatory for the future of paediatric pharmacology. Exchange of ideas and knowledge can help to tailor paediatric clinical trials to the PK/PD-characteristics and needs of children.
GLATIRAMER ACETATE AND PREGNANCY IN WOMEN WITH MULTIPLE SCLEROSIS – RESULTS FROM THE GERMAN MULTIPLE SCLEROSIS AND PREGNANCY REGISTRY
Authors: Herbstritt Sandra , Gold Ralf , Hellwig Kerstin
Published: December 2015

Objective

To determine the effect of glatiramer acetate (GLAT) exposure during pregnancy on perinatal outcome in women with multiple sclerosis (MS).

Background

MS is one of the most common neurological diseases of the central nervous system, which mainly affects young women of reproductive age.

Only limited data are available on whether GLAT exposure during pregnancy has an effect on perinatal outcome.

Methods

We compared the outcome of pregnancies of patients with MS exposed to GLAT with pregnancies of unexposed controls. Women with MS were enrolled into the German Multiple Sklerosis and pregnancy registry. Data were assessed with a standardized questionnaire during pregnancy and the postpartum year. Detailed information on course of MS, concomitant medication, pregnancy course and outcome was obtained.

Results

We collected data on 230 pregnancies: 135 with exposure to GLAT and 95 MS controls unexposed to disease-modifying therapies (DMTs) during pregnancy.

While 25 of the exposed pregnancies are still ongoing we did not document any malformation in the first 110 GLAT exposed pregnancies with at least 6 months postpartum follow up. The rate of spontaneous abortions did not differ compared to unexposed controls. 3 (3.15%) infants of the DMT unexposed women were born with malformations of non-genetic origin and 1 (0.95%) newborn was diagnosed with Wolf Hirschhorn syndrome.

Conclusions

GLAT exposure does not constitute a major human teratogen or influence outcome of pregnancy negatively compared to untreated women with MS. Final data including the outcome of ongoing pregnancies will be presented at the time of the meeting.
ANTIEPILEPTIC DRUG PRESCRIBING FOR CHILDREN IN ITALY
Authors: Putignano Daria , Clavenna Antonio , Campi Rita , Bonati Maurizio
Published: December 2015

The aim of the study was to evaluate prescription profile of antiepileptic drugs (AEDs) in pediatric population.

Prescriptions reimbursed by the National Health System, involving 1,669,370 children and adolescents, dispensed between 2003–2012 by the retail pharmacies in the Lombardy Region, were analysed.

AEDs classified according to International Anatomic-Therapeutical-Chemical Classification system (ATC subgroup: N03A).

Prevalence was defined as the number of patients received at least one AED prescription per 1000 inhabitants and incidence was defined as the number of patients received an AED prescription for the first time (no AED prescriptions in the previous 12 months) per 1000 inhabitants. The first prescription dispensed to incident cases was analyzed.

During 2012, 6,088 children and adolescents (3.6‰ of the population) received at least one AED prescription. The incident cases were 1,465 (incidence 0.86‰). Prevalence and incidence showed significant differences across time.

In 2012 about 96% of incident cases was treated with only one AED and of these approximately 78% was treated with an older, while 22% with a newer AED. Valproic acid was the most used at the first prescription (56.2%), followed by carbamazepine (11.5%) and levetiracetam (9.2%). The use of newer AEDs increased across time (χ2t=23.75 P<0.005): in particular the prescriptions of carbamazepine decreased accross time (CAGR: −5.3%), while those of levetiracetam increased (CAGR: +35.4%).

Despite conventional AEDs were still the main treatment for epileptic children, there was a decrease of carbamazepine and an increase of levetiracetam. These findings are consistent with results from drug utilization studies performed in other countries.
DO WE HAVE A CONSENSUS TO APPLY MODEL-BASED AMINOGLYCOSIDE THERAPY: A REVIEW OF POPULATION PHARMACOKINETIC MODELS
Authors: Hao Guo-Xiang , Teng Sophie , Jacqz-Aigrain Evelyne , Zhao Wei
Published: December 2015

Background and Objective

Aminoglycosides remain the standard antibiotic therapy for Gram-negative infections in both adults and children. The pharmacokinetic modeling approach has been widely used to evaluate aminoglycosides therapy. The aim of the present study is to review the published population pharmacokinetic models of commonly used aminoglycosides (gentamycin, amikacin and tobramycin), in order to determine if there was a consensus to apply model-based personalized aminoglycoside therapy in routine clinical practice.

Methods

The bibliographic search was performed electronically using PubMed on 30th January 2015, following the search strategy: “((population Pharmacokinetics) OR (Pharmacokinetic modeling)) AND (gentamycin OR gentamicin OR amikacin OR tobramycin)”.

Results

A total of 49 articles were identified. Persistent variabilities exist in terms of structure model; typical pharmacokinetic parameters and identified covariates.

Conclusion

A pharmacokinetic meta-analysis is required to evaluate the study-related factors influencing the pharmacokinetics of aminoglycosides. A clinical evaluation of pharmacokinetic model of aminoglycosides is required to demonstrate its clinical utility.
USE OF FLUOROQUINOLONES IN HOSPITALIZED CHILDEN, PRELIMINARY REPORT OF A CHART REVIEW IN A BELGIAN UNIVERSITY CHILDREN'S HOSPITAL
Authors: Meesters Kevin , Bruyne Pauline De , Mauel Reiner , Walle Johan Vande
Published: December 2015

According to international guidelines, fluoroquinolones (FQ) should only be prescribed to children when there is no alternative antibiotic. FQ resistance is a rapidly growing problem worldwide. We hypothesize that FQ are frequently prescribed off-label in children. To confirm this hypothesis, we analyzed FQ prescriptions for hospitalized children in a Belgian university hospital.

Method

We reviewed all prescriptions of FQ for children up to 17 years of age who were hospitalized at Universitair Ziekenhuis Brussel, a Belgian university children's hospital, in the period 2010–2013. Patient characteristics, indication for the FQ prescription and microbial cultures were obtained from the medical file. The study was approved by the institutional review board.

Results

As we foresee to finish our data analysis by the end of April 2015, we present results of our interim analysis here. Until now, a total of 178 FQ prescriptions in 79 children were analyzed. The majority of children had major comorbidities such as childhood cancer, cystic fibrosis or inflammatory bowel disease. FQ prescription was based on a microbial culture in 15.4% of cases. Frequent indications for FQ prescription were Pseudomonas eradication in cystic fibrosis patients, long term antibiotic prophylaxis in neutropenic patients and wound infections. Prescribed daily doses and consumed daily doses varied widely, even for the same indication. Concomitant medications were common and included mainly other antibiotics, steroids and chemotherapeutics.

Conclusion

FQ were used as ‘reserve antibiotic,' and so on-label, in a minority of all FQ prescriptions for hospitalized children.
DESIGN OF A EUROPEAN SURVEY ON THE PHARMACOLOGICAL MANAGEMENT OF PAEDIATRIC HEART FAILURE
Authors: Díez Cristina Castro , Khalil Feras , Dalinghaus Michiel , Meulen Marijke van der , de Wildt Saskia , Jovanović Ida , Bajčetić Milica , Burch Michel , Male Christoph , Läer Stephanie
Published: December 2015

Background

Little evidence is presently available to help clinicians guide decisions when tackling the pharmacological management of paediatric heart failure (HF). As a consequence, therapeutic strategies are largely supported by adults' data extrapolation and own expertise. The variability in drug treatment routines across Europe is expected to be high. Nevertheless, there are no epidemiological data that describe the current situation.

Aim

To develop a survey in the context of the LENA project to characterise the different therapeutic strategies for the management of paediatric HF that are currently practiced across Europe with special focus in the use of Angiotensin Converting Enzyme Inhibitors (ACE-I).

Methods

Items to be included in the survey were selected through a thorough literature review and expert group discussions. European hospitals providing paediatric cardiology care were identified using websites of European and national paediatric cardiology associations as well as the ones of congresses and conferences related to the field. Standard recommendations for survey design were followed. The study protocol was approved by a data protection officer and an ethics committee. Web-survey tool EvaSys® was used. The survey was pre- and pilot-tested by a group of experts. A statistical analysis plan for the later processing and analysis of the data to be obtained was elaborated.

Results

A Europe-wide web-based survey was started in January 2015. 203 clinicians were invited via e-mail to participate. The questionnaire consisted of 23 questions addressing different aspects of drug therapy for HF in children. Use patterns of ACE-I (dosage by age group, effectiveness and toxicity assessment, use according to HF aetiology) and drug therapy for dilated cardiomyopathy where explored. Participants' demographic characteristics were also asked.

Conclusions

The procedure followed for the survey development should assure the quality of the tool. The results of this survey will provide an overview of the clinical treatment routine of paediatric heart failure across Europe.

The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement n°602295 (LENA).

The following authors will also be included in the later poster: Ingrid Klingmann (PHARMAPLEX BVBA, Germany), András Szatmári (GOTTSEGEN GYORGY ORSZAGOS KARDIOLOGIAI INTEZET, Hungary), László Ablonczy (GOTTSEGEN GYORGY ORSZAGOS KARDIOLOGIAI INTEZET, Hungary), Holger Schwender (HEINRICH-HEINE-UNIVERSITÄT DÜSSELDORF, GERMANY)
PHARMACEUTICAL CARE OF ADOLESCENTS WITH DIABETES MELLITUS TYPE 1: THE DIADEMA STUDY, A RANDOMIZED CONTROLLED TRIAL
Authors: Obarčanin Emina , Krueger Manfred , Mueller Petra , Nemitz Verena , Schwender Holger , Hasanbegović Sniježana , Kalajdzisalihovic Sena , Läer Stephanie
Published: December 2015

Background

Adolescents with type 1 diabetes mellitus (T1DM) often show low adherence to complex insulin regimens, leading to poor glycemic control. The benefit of pharmaceutical care in adults with diabetes mellitus type 2 (T2DM) has been widely explored; however, evidence in adolescents with T1DM remains scarce.

Objective

To evaluate the impact of pharmaceutical care in adolescents with T1DM provided by a multidisciplinary team on multiple important clinical outcomes.

Setting

At the outpatient Helios Paediatric Clinic and at the 12 regular community pharmacies of the study patients with 14 pharmacists in the Krefeld area, Germany, and at the University Pediatric Clinic with one pharmacist on-site in Sarajevo, Bosnia-Herzegovina.

Methods

A randomized, controlled, prospective, multicenter study in 68 adolescents with T1DM. The intervention group received monthly structured pharmaceutical care delivered by pharmacists plus supplementary phone calls for 6 months. The control group received usual diabetic care. Data were collected at baseline and after 3 and 6 months. In addition, HbA1c was measured after 12 months.

Main outcome measures The between-group difference in the change from baseline in glycosylated hemoglobin (HbA1c), the number of severe hypoglycemic events in both groups, and patient well-being in the intervention group.

Results

The improvement from baseline in HbA1c was significantly greater in the intervention group than in the control group after 6 months (change from baseline −0.54 vs. +0.32%, p=0.0075), even after adjustment for country-specific variables (p=0.0078). However, the effect was more pronounced after only 3 months (−1.09 vs. +0.23%, p=0.00002). There was no significant between-group difference in the number of severe hypoglycemia events. After 6 months, the well-being according to the WHO-5 index in the intervention group increased significantly from 52.8% to 63.3%. After 12 months the mean total HbA1c remained significantly reduced in the intervention compared to the control group (8.6% vs. 9.5%, p=0.0184).

Conclusion

The improved outcomes seen in this study provide new evidence that pharmaceutical care adds value to the management of T1DM in adolescents. However, the optimal methods of achieving sustained long-term improvements in this specific patient population require further study.
Ganciclovir concentrations in the cerebral extracellular space after valganciclovir treatment; a case study
Authors: Peredo Inti , Helldén Anders , Wolmer-Solberg Nina , Pohanka Anton , Stragliotto Giuseppe , Rahbar Afsar , Ståhle Lars , Bellander Bo-Michael , Söderberg-Nauclér Cecilia
Published: December 2015

Nearly all glioblastomas (GBMs), brain tumours with very poor prognosis, are infected with human cytomegalovirus (CMV). The anti-CMV drug valganciclovir (VGCV) has shown promise as a treatment option for patients with GBM, but its penetration into the central nervous system (CNS) is unknown. Here we describe a patient with GMB receiving VGCV in whom an intracerebral microdialysis catheter was implanted and ganciclovir (GCV) concentrations in brain extracellular fluid (BECF) and serum were monitored. GCV was rapidly absorbed. Cmaxvalues (at 3 h) in serum and BECF were 19.6 and 10.2 µmol/L, T½ values were 3.2 and 4.5 h, and plasma and BECF AUC0−∞values were 90.7 and 75.9 µmol h/L, respectively. Thus, VGCV treatment results in significant intracerebral levels of GCV that may be sufficient for therapeutic effects. Further studies of this drug in patients with GBM are warranted.
Early bilateral nephrectomy in infantile autosomal recessive polycystic kidney disease
Authors: Mallett Tamara Mary , O'Hagan Emma , McKeever Karl Gerard
Published: December 2015

The management of neonatal autosomal recessive polycystic kidney disease (ARPKD) complicated by severe pulmonary insufficiency presents complex clinical challenges. Where massive nephromegaly exists, early bilateral nephrectomy, supportive peritoneal dialysis and early aggressive nutrition can minimise infant mortality. Consensus, however, is lacking on the role and optimal timing of nephrectomy, with decision-making driven by the patient's clinical condition and the expertise of the centre. We report on our experience of an infant with ARPKD requiring neonatal renal replacement therapy and survival at 14 months following early bilateral nephrectomy.
Splenic abscess due toSalmonella schwarzengrundin a previously healthy individual returning from Bali
Authors: Hoff Erik , Nayeri Fariba
Published: December 2015

After an episode of diarrhoea, a previously healthy young man developed a splenic abscess due to invasive non-typhoidalSalmonella. The patient was presented with >1 month of fever, diffuse abdominal pain, raised C reactive protein and increased white cell count. Ultrasonography revealed a 5×5 cm abscess in the spleen. After an unsuccessful treatment attempt with percutaneous drainage and antibiotics, the patient was successfully treated with splenectomy and antibiotics. This case highlights the difficulties inherent in making a correct diagnosis of splenic abscess in patients without risk factors. Splenic abscess is rare in previously healthy individuals. Antibiotics are inadequate as a sole treatment, and percutaneous drainage is usually only a temporary solution. Splenectomy is still the standard treatment in most cases.
Resolution of incontinence using an artificial urethral sphincter in feline genitourinary dysplasia
Authors: Roundell Candice D G , Friend Edward James
Published: December 2015

Limited information exists about surgical techniques to treat incontinence in cats. In this case, a four‐month‐old female entire domestic shorthair cat was presented with a history of severe urinary incontinence. Contrast studies supported a diagnosis of genitourinary and urethral dysplasia with urethral sphincter mechanism incompetence (USMI). The incontinence was unresponsive to medical treatment. At 10 months old, an artificial urethral sphincter (AUS) was surgically placed, restoring urinary continence completely. This case report demonstrates that an AUS—a technique previously described only for treatment in dogs with refractory incontinence—may be suitable for the management of refractory USMI in cats with congenital urinary incontinence. Also, in cases of persistent or recurrent incontinence, and at any time subsequent to the surgery, an increase in pressure around the urethra can be achieved, non‐invasively, by inflating the AUS's percutaneous occluder.
Stabilized MLPG-VF-based method with CBS scheme for laminar flow at high Reynolds and Rayleigh numbers
Authors: Enjilela Vali , Salimi Davood , Tavasoli Ali , Lotfi Mohsen
Published: December 2015

In the present work, the meshless local Petrov–Galerkin vorticity-stream function (MLPG-VF) method is extended to solve two-dimensional laminar fluid flow and heat transfer equations for high Reynolds and Rayleigh numbers. The characteristic-based split (CBS) scheme which uses unity test function is employed for discretization, and the moving least square (MLS) method is used for interpolation of the field variables. Four test cases are considered to evaluate the present algorithm, namely lid-driven cavity flow with Reynolds numbers up to and including [Formula: see text], flow over a backward-facing step at Reynolds number of [Formula: see text], natural convection in a square cavity for Rayleigh numbers up to and including [Formula: see text], and natural convection in a concentric square outer cylinder and circular inner cylinder annulus for Rayleigh numbers up to and including [Formula: see text]. In each case, the result obtained using the proposed algorithm is either compared with the results from the literatures or with those obtained using conventional numerical techniques. The present algorithm shows stable results at lower or equal computational cost compared to the other upwinding schemes usually employed in the MLPG method. Close agreements between the compared results as well as higher accuracy of the proposed method show the ability of this stabilized algorithm.
Strain-induced asymmetric modulation of band gap in narrow armchair-edge graphene nanoribbon
Authors: Fang Hui , Zhang Fei-Peng , Jiang Zhi-Nian , Peng Jin-Yun , Wang Ru-Zhi
Published: December 2015

We investigate the band structure of narrow armchair-edge graphene nanoribbons (AGNRs) under tensile strain by means of an extension of the Extended Hückel method. The strain-induced band gap modulation presents asymmetric behavior. The asymmetric modulation of band gap is derived from the different changes of conduction and valence bands near Fermi level under tensile strain. Further analysis suggests that the asymmetric variation of band structure near Fermi level only appear in narrow armchair-edge graphene nanoribbons.
Hopf–Galois objects of Calabi–Yau Hopf algebras
Authors: Yu Xiaolan
Published: December 2015

By using the language of cogroupoids, we show that Hopf–Galois objects of a twisted Calabi–Yau (CY) Hopf algebra with bijective antipode are still twisted CY, and give their Nakayama automorphism explicitly. As applications, cleft Galois objects of twisted CY Hopf algebras and Hopf–Galois objects of the quantum automorphism groups of non-degenerate bilinear forms are proved to be twisted CY.
On the maximum number of the pairwise noncommuting elements in a finite group
Authors: Jafarian Amiri Seyyed Majid , Madadi Halimeh
Published: December 2015

For a finite group [Formula: see text], let [Formula: see text] be the maximum size of a set of pairwise noncommuting elements in [Formula: see text]. In this paper, we give an upper bound of [Formula: see text] for an arbitrary nilpotent group [Formula: see text]. As an application of this result, we give a partial answer to Question 2.8 of [A. R. Ashrafi, On finite groups with a given number of centralizers, Algebra Colloq. 7(2) (2000) 139–146]. Also we compute [Formula: see text] when [Formula: see text] is a Frobenius group. Finally we describe structural properties of all groups [Formula: see text] with [Formula: see text].
Late Cretaceous–Cenozoic tectonic transition from collision to transtension, Honduran Borderlands and Nicaraguan Rise, NW Caribbean Plate boundary
Authors: Sanchez Javier , Mann Paul , Emmet Peter A.
Published: December 2015

Northern Honduras and its offshore area include an active transtensional margin separating the Caribbean and North American plates. We use deep-penetration seismic-reflection lines combined with gravity and magnetic data to describe two distinct structural domains in the Honduran offshore area: (1) an approximately 120 km-wide Honduran Borderlands (HB) adjacent to the Cayman Trough characterized by narrow rift basins controlled by basement-involving normal faults subparallel to the margin; and (2) the Nicaraguan Rise (NR), characterized by small-displacement normal faulting and sag-type basins influenced by Paleocene–Eocene shelf sedimentation beneath an Oligocene–Recent, approximately 1–2 km-thick carbonate platform. Thinning of continental crust from 25–30 km beneath the NR to 6–8 km beneath the oceanic Cayman Trough is attributed to an Oligocene–Recent phase of transtension. Five tectonostratigraphic phases established in the HB and NR include: (1) a Late Cretaceous uplift in the north and south-dipping thrusting related to the collision in the south, between the Chortis continental block and arc and oceanic plateau rocks of the Caribbean; (2) Eocene sag basins in the NR and minor extension in the HB; two phases (3) and (4) of accelerated extension (transtension) across the subsidence mainly of the HB; and (5) Pliocene–Recent minor fault activity in the HB and a stable carbonate platform in the NR.
The Slottsmøya marine reptile
Lagerstätte
: depositional environments, taphonomy and diagenesis
Authors: Delsett Lene L. , Novis Linn K. , Roberts Aubrey J. , Koevoets Maayke J. , Hammer Øyvind , Druckenmiller Patrick S. , Hurum Jørn H.
Published: December 2015

The Late Jurassic Slottsmøya Member
Lagerstätte
on Spitsbergen offers a unique opportunity to study the relationships between vertebrate fossil preservation, invertebrate occurrences and depositional environment. In this study, 21 plesiosaurian and 17 ichthyosaur specimens are described with respect to articulation, landing mode, preservation, and possible predation and scavenging. The stratigraphic distribution of marine reptiles in the Slottsmøya Member is analysed, and a correlation between high total organic content, low oxygen levels, few benthic invertebrates and optimal reptile preservation is observed. A new model for 3D preservation of vertebrates in highly compacted organic shales is explained.

Supplementary material:

A taphonomic description of each marine reptile specimen is available at
https://doi.org/10.6084/m9.figshare.c.2133549
ZNF423 and ZNF521: EBF1 Antagonists of Potential Relevance in B-Lymphoid Malignancies
Authors: Mesuraca Maria , Chiarella Emanuela , Scicchitano Stefania , Codispoti Bruna , Giordano Marco , Nappo Giovanna , Bond Heather M. , Morrone Giovanni
Published: December 2015

The development of the B-lymphoid cell lineage is tightly controlled by the concerted action of a network of transcriptional and epigenetic regulators. EBF1, a central component of this network, is essential for B-lymphoid specification and commitment as well as for the maintenance of the B-cell identity. Genetic alterations causing loss of function of these B-lymphopoiesis regulators have been implicated in the pathogenesis of B-lymphoid malignancies, with particular regard to B-cell acute lymphoblastic leukaemias (B-ALLs), where their presence is frequently detected. The activity of the B-cell regulatory network may also be disrupted by the aberrant expression of inhibitory molecules. In particular, two multi-zinc finger transcription cofactors named ZNF423 and ZNF521 have been characterised as potent inhibitors of EBF1 and are emerging as potentially relevant contributors to the development of B-cell leukaemias. Here we will briefly review the current knowledge of these factors and discuss the importance of their functional cross talk with EBF1 in the development of B-cell malignancies.
Medicinal Plants Qua Glucagon-Like Peptide-1 Secretagogue via Intestinal Nutrient Sensors
Authors: Kim Ki-Suk , Jang Hyeung-Jin
Published: December 2015

Glucagon-like peptide-1 (GLP-1) participates in glucose homeostasis and feeding behavior. Because GLP-1 is rapidly inactivated by the enzymatic cleavage of dipeptidyl peptidase-4 (DPP4) long-acting GLP-1 analogues, for example, exenatide and DPP4 inhibitors, for example, liraglutide, have been developed as therapeutics for type 2 diabetes mellitus (T2DM). However, the inefficient clinical performance and the incidence of side effects reported on the existing therapeutics for T2DM have led to the development of a novel therapeutic strategy to stimulate endogenous GLP-1 secretion from enteroendocrine L cells. Since the GLP-1 secretion of enteroendocrine L cells depends on the luminal nutrient constituents, the intestinal nutrient sensors involved in GLP-1 secretion have been investigated. In particular, nutrient sensors for tastants, cannabinoids, and bile acids are able to recognize the nonnutritional chemical compounds, which are abundant in medicinal plants. These GLP-1 secretagogues derived from medicinal plants are easy to find in our surroundings, and their effectiveness has been demonstrated through traditional remedies. The finding of GLP-1 secretagogues is directly linked to understanding of the role of intestinal nutrient sensors and their recognizable nutrients. Concurrently, this study demonstrates the possibility of developing novel therapeutics for metabolic disorders such as T2DM and obesity using nutrients that are readily accessible in our surroundings.
Adoption of Sinter Addition in Steelmaking Converter to Control Spitting
Authors: Gupta Sanjay Kumar , Prasad Abdhesh , Chatterjee Abhinandan , Kumar Manoranjan , Ghosh Somnath , Datta Ramen
Published: December 2015

Steel Melting Shop-I, Rourkela Steel Plant, Rourkela, produces 0.5 MT of various special steels through BOF-VAR/VOR-LF-CC route. One of the most serious problems in BOF operations was lance skulling, hood jamming, and build-up of metal in the mouth and cone of the furnace due to spitting and slopping. As spitting occurring during blowing increases, these particles of metal are deposited inside the mouth and cone and affect badly BOF productivity. In the present work, control of spitting has been established by addition of sinter during the period of spitting. It also helped to improve the slag formation and fluidity of slag through increase of FeO content during peak decarburisation period.
Ruxolitinib Associated Tuberculosis Presenting as a Neck Lump
Authors: Shamil Eamon , Cunningham David , Wong Billy L. K. , Jani Piyush
Published: December 2015

Tuberculosis is an opportunistic infection with protean clinical manifestations. We describe a case of Ruxolitinib induced miliary tuberculosis presenting as a neck lump. A 78-year-old female presented with a two-month history of right-sided neck lump associated with fever, night sweats, and significant weight loss. She had a past medical history that included myelofibrosis, being treated with Ruxolitinib. Examination demonstrated 4 × 4 cm right-sided cervical lymphadenopathy. A chest radiograph showed extensive shadowing in both lungs. CT scan demonstrated perilymphatic nodes in addition to the cervical mass. An ultrasound-guided biopsy of a cervical lymph node demonstrated confirmedMycobacterium tuberculosisinfection. It was hypothesized that use of Ruxolitinib through its selective inhibition of Janus-activated kinases 1 and 2 resulted in immunosuppression and miliary tuberculosis in this patient. The medication was stopped and a 12-month regime of antituberculosis therapy commenced. She remained well at one-year follow-up with resolution of lung involvement. Clinicians should consider tuberculosis as a differential diagnosis for patients presenting with a neck lump, particularly in those taking immunosuppressant medication such as Ruxolitinib. A multidisciplinary approach is needed to promptly treat the tuberculosis and consider discontinuation of Ruxolitinib.
Increasing the Time Interval between PCV Chemotherapy Cycles as a Strategy to Improve Duration of Response in Low-Grade Gliomas: Results from a Model-Based Clinical Trial Simulation
Authors: Mazzocco Pauline , Honnorat Jérôme , Ducray François , Ribba Benjamin
Published: December 2015

Background. We previously developed a mathematical model capturing tumor size dynamics of adult low-grade gliomas (LGGs) before and after treatment either with PCV (Procarbazine, CCNU, and Vincristine) chemotherapy alone or with radiotherapy (RT) alone.Objective. The aim of the present study was to present how the model could be used as a simulation tool to suggest more effective therapeutic strategies in LGGs. Simulations were performed to identify schedule modifications that might improve PCV chemotherapy efficacy.Methods. Virtual populations of LGG patients were generated on the basis of previously evaluated parameter distributions. Monte Carlo simulations were performed to compare treatment efficacy acrossin silicoclinical trials.Results. Simulations predicted that RT plus PCV would be more effective in terms of duration of response than RT alone. Additional simulations suggested that, in patients treated with PCV chemotherapy, increasing the interval between treatment cycles up to 6 months from the standard 6 weeks can increase treatment efficacy. The predicted median duration of response was 4.3 years in LGGs treated with PCV cycles given every 6 months versus 3.1 years in patients treated with the classical regimen.Conclusion. The present study suggests that, in LGGs, mathematical modeling could facilitate clinical research by helping to identify,in silico, potentially more effective therapeutic strategies.
Uncertainty Analysis of Mixing Efficiency Variation in Passive Micromixers due to Geometric Tolerances
Authors: Stanciu Irina
Published: December 2015

The geometric layout is the key factor for enhancing the efficiency of the fluid mixing in passive micromixers. Therefore, by adjusting the geometric design and by controlling the geometric parameters, one can enhance the mixing process. However, through any fabrication process, the geometric parameters present slight, inherent variation from the designed values than might affect the performance of the micromixer. This paper proposes a numerical study on the influence of the unavoidable geometric tolerances on the mixing efficiency in passive micromixers. A probabilistic simulation model, based on the Monte Carlo method, is developed and implemented for this purpose. An uncertainty simulation model shows that significant deviations from the deterministic design can appear due to small variations in the geometric parameters values and demonstrates how a more realistic mixing performance can be estimated.
Experimental Study of Stabilized Soil Utilizing Circulating Fluidized Bed Combustion Desulfurization Ash with Carbide Slag and Desulfurization Gypsum
Authors: Shao Dezhi , Liu Jinlong , Huang Xin
Published: December 2015

This paper discusses the feasibility of preparing soil stabilizer which is circulating fluidized bed combustion ash-based, supplemented with carbide slag and desulfurization gypsum, composed entirely of complete industrial wastes. The results show that CFBC ash has better pozzolanic activity than fly ash. When stabilizer total content is 10% and the ratio of CFBC ash : carbide slag : desulfurization gypsum is 7.2 : 1.8 : 1, compressive strength of stabilized soil can reach the maximum of 2.12 MPa at the age of 28 d of curing. Stabilizer can meet the strength requirements of cement-soil mixing pile composite foundation and cement-soil mixing pile waterproof curtain.
Cholangiocarcinoma Arising from a Type VI Biliary Cyst: A Case Report and Review of the Literature
Authors: Çamlıdağ İlkay , Nural Mehmet Selim , Danacı Murat , Karabıçak İlhan , Karabulut Kağan
Published: December 2015

Cystic dilatations of the cystic duct which are suggested as type VI biliary cysts are very rare and many of them go unrecognized or are confused with other cysts until the operation although they are obvious on imaging studies. They can present with fusiform or saccular dilatations and can be accompanied by common bile duct dilatations. It is important to identify these cysts as they share the same characteristics as the other biliary cyst types and can be complicated with malignancy. We herein present a very unusual case of a cholangiocarcinoma arising from a type VI biliary cyst in a 58-year-old female patient and review the literature. The patient presented with jaundice, weight loss, and abdominal pain. On imaging, the cystic duct and common bile duct were fusiformly dilated and had a wide communication. There was a mass filling the distal parts of both ducts. The patient was urgently operated on after perforation following ERCP. Histopathology was compatible with a type VI biliary cyst and an associated cholangiocarcinoma.
Performances Evaluation of a Novel Hadoop and Spark Based System of Image Retrieval for Huge Collections
Authors: Costantini Luca , Nicolussi Raffaele
Published: December 2015

A novel system of image retrieval, based on Hadoop and Spark, is presented. Managing and extracting information from Big Data is a challenging and fundamental task. For these reasons, the system is scalable and it is designed to be able to manage small collections of images as well as huge collections of images. Hadoop and Spark are based on the MapReduce framework, but they have different characteristics. The proposed system is designed to take advantage of these two technologies. The performances of the proposed system are evaluated and analysed in terms of computational cost in order to understand in which context it could be successfully used. The experimental results show that the proposed system is efficient for both small and huge collections.
Deep Vein Thrombosis Provoked by Inferior Vena Cava Agenesis
Authors: Haddad Raad A. , Saadaldin Mazin , Kumar Binay , Bachuwa Ghassan
Published: December 2015

Inferior vena cava agenesis (IVCA) is a rare congenital anomaly that can be asymptomatic or present with vague, nonspecific symptoms, such as abdominal or lower back pain, or deep vein thrombosis (DVT). Here, we present a 55-year-old male who came with painless swelling and redness of his left lower limb. On examination, swelling and redness were noted extending from the left foot to the upper thigh; it was also warm compared to his right lower limb. Venous Doppler ultrasound was done which showed DVT extending up to the common femoral vein. Subsequently, computed-tomography (CT) of the chest and abdomen was done to exclude malignancy or venous flow obstruction; it revealed congenital absence (agenesis) of the infrarenal inferior vena cava (IVC).
Tailored sPP/Silica Nanocomposite for Ecofriendly Insulation of Extruded HVDC Cable
Authors: Dang Bin , He Jinliang , Hu Jun , Zhou Yao
Published: December 2015

Cross‐linked polyethylene (XLPE) is a thermosetting material that cannot be recycled at the end of its lifetime. This study investigated the potential of syndiotactic polypropylene (sPP)/silica as an ecofriendly extruded insulation system for HVDC cables. We investigated the morphology, Fourier transform infrared, and thermal, thermomechanical, and electrical behaviors of sPP modified with 0.5–3% nanosilica. We found that the silica/sPP nanocomposite without cross‐linking offered a suitable mechanical modulus at room temperature and sufficient intensity at high temperatures, and adding nanosilica modified by a silane coupling agent to the sPP resulted in significant DC resistivity and space charge improvement. The optimal nanosilica content in the sPP was determined by balancing the mechanical and thermomechanical characteristics and the DC resistivity. The sPP/silica nanocomposite reported here shows great potential as a candidate insulation material for future ecofriendly extruded HVDC cables.
Designing of Collagen Based Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) Scaffolds for Tissue Engineering
Authors: Vigneswari S. , Abdul Khalil H. P. S. , Amirul A. A.
Published: December 2015

P(3HB-co-4HB) copolymer was modified using collagen by adapting dual solvent system. The surface properties of samples were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), organic elemental analysis (CHN analysis), and water contact angle measurements. The effects of collagen concentration, scaffold thickness, and 4HB molar fraction on the hydrophilicity were optimized by the Taguchi method. The orthogonal array experiment was conducted to obtain the response for a hydrophilic scaffold. Analysis of variance (ANOVA) was used to determine the significant parameters and determine the optimal level for each parameter. The results also showed that the hydrophilicity of P(3HB-co-4HB)/collagen blend scaffolds increased as the collagen concentration increased up to 15 wt% with a molar fraction of 50 mol% at 0.1 mm scaffold thickness. The biocompatibility of the P(3HB-co-4HB)/collagen blend surface was evaluated by fibroblast cell (L929) culture. The collagen blend scaffold surfaces showed significant cell adhesion and growth as compared to P(3HB-co-4HB) copolymer scaffolds.
Niemann-Pick Disease Type C Presenting as a Developmental Coordination Disorder with Bullying by Peers in a School-Age Child
Authors: Suzuki Ryo , Tanaka Atsushi , Matsui Toshiharu , Gunji Tetsuki , Tohyama Jun , Nairita Aya , Nanba Eiji , Ohno Kousaku
Published: December 2015

Niemann-Pick disease type C (NPC) is a rare progressive neurodegenerative disorder, often with onset after normal early childhood development. Juvenile onset NPC patients slowly develop cerebellar symptoms and cognitive impairment and often experience difficulties at school. However, these problems may be overlooked due to the unpublicized nature of NPC, given that it is a rare metabolic disorder. In this report, we present an 11-year-old male NPC patient, who suffered from clumsiness and difficulties in attention and academic and social skills. His symptoms were initially considered to be due to developmental coordination disorder (DCD) coexisting with bullying by peers. DCD is a type of neurodevelopmental disorder defined according to DSM-IV and is characterized by clumsiness that interferes with academic achievement and social integration not due to other general medical conditions. However, a detailed investigation of the patient suggested that the problems could be attributed to the onset of NPC. Clinicians should keep neurodegenerative disorders as differential diagnosis of children with multiple school problems.