bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral Human Abuse Potential of Oxycodone DETERx® (Xtampza® ER)
Authors: Kopecky Ernest A. , Fleming Alison B. , Levy‐Cooperman Naama , O'Connor Melinda , M. Sellers Edward 
Published: September 2016

AbstractOxycodone DETERx® (Collegium Pharmaceutical Inc, Canton, Massachusetts) is an extended‐release, microsphere‐in‐capsule, abuse‐deterrent formulation designed to retain its extended‐release properties after tampering (eg, chewing/crushing). This randomized, double‐blind, placebo‐controlled, triple‐dummy study evaluated the oral abuse potential of intact and chewed oxycodone DETERx capsules compared with crushed immediate‐release oxycodone. Subjects with a history of recreational opioid use who were nondependent/nontolerant to opioids were enrolled. Treatments included intact oxycodone DETERx (high‐fat, high‐calorie meal and fasted), chewed oxycodone DETERx (high‐fat, high‐calorie meal and fasted), crushed immediate‐release oxycodone (fasted), and placebo (high‐fat, high‐calorie meal). Plasma samples were collected to determine pharmacokinetic parameters. The primary endpoint was drug liking at the moment; other endpoints included drug effects questionnaire scores, Addiction Research Center Inventory/Morphine Benzedrine Group score, pupillometry measurements, and safety. Thirty‐eight subjects completed the study. Chewed and intact oxycodone DETERx were bioequivalent, unlike crushed immediate‐release oxycodone, which yielded higher peak oxycodone plasma concentrations compared with all methods of oxycodone DETERx administration. The mean maximum (peak) effect (Emax) for drug liking was significantly lower for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .01). The time to Emax was significantly longer for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .0001). Scores for feeling high and Addiction Research Center Inventory/Morphine Benzedrine Group scores demonstrated lower abuse potential for chewed and intact oxycodone DETERx compared with crushed immediate‐release oxycodone. Study treatments were well tolerated; no subjects experienced serious adverse events. These results demonstrate the lower oral abuse potential of chewed and intact oxycodone DETERx than crushed immediate‐release oxycodone.
Selexipag in Pulmonary Arterial Hypertension: Most Updated Evidence From Recent Preclinical and Clinical Studies
Authors: Ghosh Raktim K. , Ball Somedeb , Das Avash , Bandyopadhyay Dhrubajyoti , Mondal Samhati , Saha Debjit , Gupta Anjan 
Published: September 2016

AbstractPulmonary arterial hypertension (PAH) is a relatively rare disease that, due to its chronic nature, has always been difficult to treat effectively. Selexipag is an oral prostacyclin (PGI2) agonist that was approved by US Food and Drug Administration (US FDA) in December 2015 for the treatment of PAH. After its success in phase 1 and phase 2 clinical trials regarding the convenient oral twice‐daily dosing and low side‐effect profile, selexipag raised the hope of controlling the disease progression in PAH patients. In the recently completed multicentered phase 3 study (GRIPHON), selexipag has been shown to reduce death and hospitalization due to PAH significantly, an effect that was consistent across different ranges of maintenance dose. In the same study selexipag use was also associated with an increase in 6‐minute walk distance (a measure of symptom severity) from baseline, but no significant improvement in all‐cause mortality could be observed. The results of the ongoing phase 3 studies (TRITON and TRANSIT‐1) are expected to throw some more light on the safety and efficacy of this novel molecule across various treatment scenarios. Hence, our article aims to summarize all the available information from preclinical and clinical studies published to date on the pharmacodynamics, pharmacokinetics, efficacy, safety (in general and in scenarios such as hepatic and renal function impairment), significant drug interactions (with warfarin and antiretroviral drugs), and clinical significance of oral selexipag in patients with PAH.
Diatom blooms and associated vegetation shifts in a subarctic peatland: responses to distant volcanic eruptions?
Authors: Kokfelt U. , Muscheler R. , Mellström A. , Struyf E. , Rundgren M. , Wastegård S. , Hammarlund D. 
Published: September 2016

ABSTRACTWe test the hypothesis that rich occurrences of diatoms observed at transitions between major peat units representing different vegetation communities in a peat sequence from subarctic northern Sweden reflect responses to acid deposition from the Samalas AD 1257 and Laki AD 1783/1784 eruptions. We observe sudden changes in the mire ecosystem and thereby in the trophic status and biogeochemical cycling of the peatland. Both the eruptions are known to have been associated with significant acid deposition events and climatic anomalies, as recorded in polar ice cores. To test the hypothesis, new chronological analyses and age modelling were applied to existing biogeochemical and biological records from the peat sequence. This approach yielded modelled age ranges of AD 1239–1284 (1σ)/AD 1210–1303 (2σ) (median: AD 1260) and AD 1674–1795 (1σ)/AD 1665–1875 (2σ) (median AD 1743), respectively, for the stratigraphic transitions. Hence, the modelled age ranges bracket the ages of the eruptions in question and the hypothesis could therefore not be rejected. Impacts of acid deposition from the eruptions are assumed to have caused instant acidification, vegetation damage, increased nutrient cycling and blooms of opportunistic epiphytic diatoms. In addition, cooling may have contributed to vegetation changes through permafrost inception, frost heave and thereby altered hydrological conditions.
A multi‐proxy analysis of late Quaternary palaeoenvironments, Sekhokong Range, eastern Lesotho
Authors: Fitchett Jennifer M. , Grab Stefan W. , Bamford Marion K. , Mackay Anson W. 
Published: September 2016

ABSTRACTThe eastern Lesotho Highlands host an array of periglacial and glacial geomorphic features. Their analysis has provided past climate interpretations predominantly for cold periods, yet no multi‐proxy temporally continuous palaeoenvironmental records exist. This study presents a palaeoenvironmental reconstruction based on sedimentary characteristics, fossil pollen and diatoms from an alpine wetland located in the Sekhokong Mountain Range. The record commences in the late Pleistocene with a wet period from ∼16 450 to 14 440 cal a BP, interrupted by dry conditions from ∼16 350 to 15 870 cal a BP. From ∼14 150 to 8560 cal a BP, drier conditions are inferred, slowly transitioning to warmer, wetter conditions. Warmer, dry conditions are inferred for ∼8560–7430 cal a BP, followed by cold, wet conditions from ∼7280 to 6560 cal a BP. A dry, warmer period occurs from ∼6560 to 3640 cal a BP indicated by pollen, diatom and sedimentary records, followed by cool, wet conditions from ∼3400 to 1200 cal a BP. The period from ∼1110 cal a BP to the present is characterized by progressive drying. Pronounced cold events are detected from the diatom record. Moisture records appear relatively specific to the topographic setting of Sekhokong near the Great Escarpment edge, probably driven by orographically constrained synoptic controls.
Highly Conductive Graphene and Polyelectrolyte Multilayer Thin Films Produced From Aqueous Suspension
Authors: Stevens Bart , Guin Tyler , Sarwar Owais , John Alyssa , Paton Keith R. , Coleman Jonathan N. , Grunlan Jaime C. 
Published: September 2016

Rapid, large‐scale exfoliation of graphene in water has expanded its potential for use outside niche applications. This work focuses on utilizing aqueous graphene dispersions to form thin films using layer‐by‐layer processing, which is an effective method to produce large‐area coatings from water‐based solutions of polyelectrolytes. When layered with polyethyleneimine, graphene flakes stabilized with cholate are shown to be capable of producing films thinner than 100 nm. High surface coverage of graphene flakes results in electrical conductivity up to 5500 S m−1. With the relative ease of processing, the safe, cost effective nature of the ingredients, and the scalability of the deposition method, this system should be industrially attractive for producing thin conductive films for a variety of electronic and antistatic applications.
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Neurophysiological correlates of abnormal somatosensory temporal discrimination in dystonia
Authors: Antelmi Elena , Erro Roberto , Rocchi Lorenzo , Liguori Rocco , Tinazzi Michele , Di Stasio Flavio , Berardelli Alfredo , Rothwell John C. , Bhatia Kailash P. 
Published: September 2016

ABSTRACTBackgroundSomatosensory temporal discrimination threshold is often prolonged in patients with dystonia. Previous evidence suggested that this might be caused by impaired somatosensory processing in the time domain. Here, we tested if other markers of reduced inhibition in the somatosensory system might also contribute to abnormal somatosensory temporal discrimination in dystonia.MethodsSomatosensory temporal discrimination threshold was measured in 19 patients with isolated cervical dystonia and 19 age‐matched healthy controls. We evaluated temporal somatosensory inhibition using paired‐pulse somatosensory evoked potentials, spatial somatosensory inhibition by measuring the somatosensory evoked potentials interaction between simultaneous stimulation of the digital nerves in thumb and index finger, and Gamma‐aminobutyric acid‐ergic (GABAergic) sensory inhibition using the early and late components of high‐frequency oscillations in digital nerves somatosensory evoked potentials.ResultsWhen compared with healthy controls, dystonic patients had longer somatosensory temporal discrimination thresholds, reduced suppression of cortical and subcortical paired‐pulse somatosensory evoked potentials, less spatial inhibition of simultaneous somatosensory evoked potentials, and a smaller area of the early component of the high‐frequency oscillations. A logistic regression analysis found that paired pulse suppression of the N20 component at an interstimulus interval of 5 milliseconds and the late component of the high‐frequency oscillations were independently related to somatosensory temporal discrimination thresholds. “Dystonia group” was also a predictor of enhanced somatosensory temporal discrimination threshold, indicating a dystonia‐specific effect that independently influences this threshold.ConclusionsIncreased somatosensory temporal discrimination threshold in dystonia is related to reduced activity of inhibitory circuits within the primary somatosensory cortex. © 2016 International Parkinson and Movement Disorder Society.
Evaluation of non‐Gaussian diffusion in cardiac MRI
Authors: McClymont Darryl , Teh Irvin , Carruth Eric , Omens Jeffrey , McCulloch Andrew , Whittington Hannah J. , Kohl Peter , Grau Vicente , Schneider Jürgen E. 
Published: September 2016

PurposeThe diffusion tensor model assumes Gaussian diffusion and is widely applied in cardiac diffusion MRI. However, diffusion in biological tissue deviates from a Gaussian profile as a result of hindrance and restriction from cell and tissue microstructure, and may be quantified better by non‐Gaussian modeling. The aim of this study was to investigate non‐Gaussian diffusion in healthy and hypertrophic hearts.MethodsThirteen rat hearts (five healthy, four sham, four hypertrophic) were imaged ex vivo. Diffusion‐weighted images were acquired at b‐values up to 10,000 s/mm2. Models of diffusion were fit to the data and ranked based on the Akaike information criterion.ResultsThe diffusion tensor was ranked best at b‐values up to 2000 s/mm2 but reflected the signal poorly in the high b‐value regime, in which the best model was a non‐Gaussian “beta distribution” model. Although there was considerable overlap in apparent diffusivities between the healthy, sham, and hypertrophic hearts, diffusion kurtosis and skewness in the hypertrophic hearts were more than 20% higher in the sheetlet and sheetlet‐normal directions.ConclusionNon‐Gaussian diffusion models have a higher sensitivity for the detection of hypertrophy compared with the Gaussian model. In particular, diffusion kurtosis may serve as a useful biomarker for characterization of disease and remodeling in the heart. Magn Reson Med 78:1174–1186, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Investigating intracranial tumour growth patterns with multiparametric MRI incorporating Gd‐DTPA and USPIO‐enhanced imaging
Authors: Boult Jessica K.R. , Borri Marco , Jury Alexa , Popov Sergey , Box Gary , Perryman Lara , Eccles Suzanne A. , Jones Chris , Robinson Simon P. 
Published: September 2016

AbstractHigh grade and metastatic brain tumours exhibit considerable spatial variations in proliferation, angiogenesis, invasion, necrosis and oedema. Vascular heterogeneity arising from vascular co‐option in regions of invasive growth (in which the blood–brain barrier remains intact) and neoangiogenesis is a major challenge faced in the assessment of brain tumours by conventional MRI.A multiparametric MRI approach, incorporating native measurements and both Gd‐DTPA (Magnevist) and ultrasmall superparamagnetic iron oxide (P904)‐enhanced imaging, was used in combination with histogram and unsupervised cluster analysis using a k‐means algorithm to examine the spatial distribution of vascular parameters, water diffusion characteristics and invasion in intracranially propagated rat RG2 gliomas and human MDA‐MB‐231 LM2–4 breast adenocarcinomas in mice.Both tumour models presented with higher ΔR1 (the change in transverse relaxation rate R1 induced by Gd‐DTPA), fractional blood volume (fBV) and apparent diffusion coefficient than uninvolved regions of the brain. MDA‐MB‐231 LM2–4 tumours were less densely cellular than RG2 tumours and exhibited substantial local invasion, associated with oedema, whereas invasion in RG2 tumours was minimal. These additional features were reflected in the more heterogeneous appearance of MDA‐MB‐231 LM2–4 tumours on T2‐weighted images and maps of functional MRI parameters.Unsupervised cluster analysis separated subregions with distinct functional properties; areas with a low fBV and relatively impermeable blood vessels (low ΔR1) were predominantly located at the tumour margins, regions of MDA‐MB‐231 LM2–4 tumours with relatively high levels of water diffusion and low vascular permeability and/or fBV corresponded to histologically identified regions of invasion and oedema, and areas of mismatch between vascular permeability and blood volume were identified.We demonstrate that dual contrast MRI and evaluation of tissue diffusion properties, coupled with cluster analysis, allows for the assessment of heterogeneity within invasive brain tumours and the designation of functionally diverse subregions that may provide more informative predictive biomarkers.
Incident cancers and late mortality in Australian children treated by allogeneic stem cell transplantation for non‐malignant diseases
Authors: Nelson Adam S. , Vajdic Claire M. , Ashton Lesley J. , Le Marsney Renate E. , Nivison‐Smith Ian , Wilcox Leonie , Dodds Anthony J. , O'Brien Tracey A. ,   the CAST investigators
Published: September 2016

AbstractBackgroundHematopoietic stem cell transplantation (HSCT) is a life‐saving procedure for children with a variety of non‐malignant conditions. However, these children face an increased risk of late death and incident cancers after HSCT, which may occur many years after their initial HSCT.ProcedureWe examined cancer occurrence and late mortality in a population‐based cohort of 318 Australian children who underwent allogeneic HSCT for non‐malignant disease. Standardized incident ratios (SIRs) and standardized mortality ratios (SMRs) were calculated and compared with population controls.ResultsWe identified six (1.9%) cancers at a median 9.2 years post‐HSCT. Cancer occurred 15 times more frequently than in the general population (SIR 15.4, 95% CI = 6.9–34.2). Of the 198 patients who survived for at least 2 years post‐HSCT, 11 (5.6%) died at a median 7.5 years post‐HSCT. The mortality rate was 17 times higher than in the general population (SMR 17.5, 95% CI = 9.7–31.2).DiscussionChildren transplanted for non‐malignant conditions require evidence‐based survivorship programs to reduce excess morbidity and mortality.
Determining prescription durations based on the parametric waiting time distribution
Authors: Støvring Henrik , Pottegård Anton , Hallas Jesper 
Published: September 2016

AbstractPurposeThe purpose of the study is to develop a method to estimate the duration of single prescriptions in pharmacoepidemiological studies when the single prescription duration is not available.MethodsWe developed an estimation algorithm based on maximum likelihood estimation of a parametric two‐component mixture model for the waiting time distribution (WTD). The distribution component for prevalent users estimates the forward recurrence density (FRD), which is related to the distribution of time between subsequent prescription redemptions, the inter‐arrival density (IAD), for users in continued treatment. We exploited this to estimate percentiles of the IAD by inversion of the estimated FRD and defined the duration of a prescription as the time within which 80% of current users will have presented themselves again. Statistical properties were examined in simulation studies, and the method was applied to empirical data for four model drugs: non‐steroidal anti‐inflammatory drugs (NSAIDs), warfarin, bendroflumethiazide, and levothyroxine.ResultsSimulation studies found negligible bias when the data‐generating model for the IAD coincided with the FRD used in the WTD estimation (Log‐Normal). When the IAD consisted of a mixture of two Log‐Normal distributions, but was analyzed with a single Log‐Normal distribution, relative bias did not exceed 9%. Using a Log‐Normal FRD, we estimated prescription durations of 117, 91, 137, and 118 days for NSAIDs, warfarin, bendroflumethiazide, and levothyroxine, respectively. Similar results were found with a Weibull FRD.ConclusionsThe algorithm allows valid estimation of single prescription durations, especially when the WTD reliably separates current users from incident users, and may replace ad‐hoc decision rules in automated implementations. Copyright © 2016 John Wiley & Sons, Ltd.
Synthesis and electrical properties of copolymers of o‐phenylenediamine with aniline, 3,4‐ethylenedioxythiophene and 2,3,5,6‐tetrafluoroaniline
Authors: Yamaguchi Isao , Morisaka Reika 
Published: September 2016

AbstractCopolymers (P(PDA/Ar)) of o‐phenylenediamine with aniline (Ar = ANi), 3,4‐ethylenedioxythiophene (Ar = EDOT) and 2,3,5,6‐tetrafluoroaniline (Ar = TFANi) were synthesized via polycondensation initiated by ammonium persulfate. The NH2 group content in the copolymers was determined by analyzing the 1H NMR spectra of the N‐acetylated copolymers. Copolymers crosslinked by viologen (1,1'‐disubstituted 4,4'‐bipyridinium dichloride) were obtained by reaction involving the reactive NH2 groups in the copolymers. The absorption wavelengths of solutions of the copolymers and the electrochemical oxidation and reduction potentials of cast films of the copolymers were affected by the electrical properties of the Ar unit. © 2016 Society of Chemical Industry
Impact of native defects and impurities in m−HfO2 and β−Si3N4 on charge trapping memory devices: A first principle hybrid functional study
Authors: Lu Wenjuan , Dai Yuehua , Wang Feifei , Jin Bo 
Published: September 2016

AbstractUsing hybrid density functional calculations, this paper systematically investigated the common defects in m‐HfO2 and ‐Si3N4 trapping layer, respectively, on the performance of charge trapping memory (CTM) devices. Defects may act as charge traps or fixed charges, however, only traps can be used to store charges. Thus, firstly, the paper distinguished traps or fixed charges of defects in trapping layer through the band alignment method. Then we can restrain the formation of defects that act as fixed charges in manufacturing CTM devices, which is very meaningful in improving the performance of CTM. Secondly, it studied the storage performance of traps in m‐HfO2 and ‐Si3N4 by analyzing the formation energy, the atomistic structural change during program/erase (P/E) cycles, and localization energy. The simulation results found that only some defects can be charge traps in m‐HfO2 and ‐Si3N4, and the charge transition of these traps only appeared between certain charged states. In addition, these traps show reversible structural change during P/E cycles and different localizing abilities for holes and electrons. Therefore, this study would provide some theoretical guidance for improving the performance of CTM.
Freeze'nSense: estimation of performance isolation in cloud environments
Authors: Kandalintsev Alexander , Kliazovich Dzmitry , Lo Cigno Renato 
Published: September 2016

SummaryModern computing hardware has a very good task parallelism, but resource contention between tasks remains high. This renders large fractions of CPU time wasted and leads to application interference. Even tasks running on dedicated CPU cores can still incur interference from other tasks, most notably because of the caches and other hardware components shared by more than one core. The level of interference depends on the nature of executed tasks and is difficult to predict. A customer who has been granted that his task will run as if it were alone (e.g., a CPU core dedicated to a virtual machine), indeed suffers from significant performance degradation due to the time spent waiting for resources occupied by other tasks. Measuring actual performance of a task or a virtual machine can be difficult. However, even more challenging is estimating what the performance of the task should be if it were running completely in isolation. In this paper, we present a measurement technique Freeze'nSense. It is based on the hardware performance counters and allows measuring actual performance of a task and estimating performance as if the task were in isolation, all during runtime. To estimate performance in isolation, the proposed technique performs a short‐time freezing of the potentially interfering tasks. Freeze'nSense introduces lower than 1% overhead and is confirmed to provide accurate and reliable measurements. In practice, Freeze'nSense becomes a valuable tool helping to automatically identify tasks that suffer the most in a shared environment and move them to a distant core. The observed performance improvement can be as large as 80–100% for individual tasks, and scale up to 15–20% for the computing node. Copyright © 2016 John Wiley & Sons, Ltd.