bluuebunny/crossref_metadata_2025 huggingface dataset:
Video-Kopfimpulstest: geringer Nutzen zur Unterscheidung peripherer und zentraler Schwindel
Authors: Patscheke Jochen Henrik , Plenz Pauline , Ernst Stephan , Klußmann Jens-Peter
Published: December 2017

Hintergrund Der Video-Kopfimpulstest (V-KIT) etabliert sich zunehmend in der Abklärung von Schwindel und Gleichgewichtsstörungen und
ergänzt die Funktionsprüfung des Vestibulo-okulären Reflexes (VOR). Die Videoaufzeichnung soll eine objektive Auswertung ermöglichen und
helfen, die Diagnose einer peripher-vestibulären Störung (PVS) zu sichern. Dies muss in der klinischen Routine noch bestätigt werden.

Material und Methode In einer Beobachtungsstudie wurden 171 konsekutive, unselektierte Patienten mit Schwindel einer
HNO-Universitätsklinik nach konventioneller klinischer und apparativer Abklärung unter Einschluss einer kalorischen Prüfung in
Diagnosegruppen aufgeteilt. Zusätzlich wurde bei allen Patienten ein V-KIT in horizontaler Ausrichtung durchgeführt. Dieser wurde dann
bezüglich der Größe des Gain, der Gain-Asymmetrie (GA) sowie des Auftretens von Catch-up Sakkaden (CS) in den Diagnosegruppen ausgewertet.
Zusätzlich wurde die GA mit der aus der kalorischen Prüfung berechneten Seitendifferenz (Canal Paresis, CP) verglichen.

Ergebnisse Bei den Patienten mit einseitiger PVS trat in 31 % ein pathologischer Gain (definiert als < 0,8) auf, die
durchschnittliche GA betrug 4,53 % (± 16,7 %) und es traten bei 60 % CS auf. Bei den Patienten mit zentraler Schwindelgenese trat bei 28 %
ein pathologischer Gain auf, die durchschnittliche GA betrug -1,56 % (± 17,9 %) und es traten bei 45 % CS auf. Isolierte Covert-Sakkaden
traten nur vereinzelt auf. Die GA korrelierte nicht mit der Seitendifferenz aus der kalorischen Prüfung (p = 0,114).

Schlussfolgerung Die klinisch wichtige Zuordnung einer zentralen oder peripher-vestibulären Schwindelursache ist an Hand des V-KIT in
der untersuchten Kohorte nicht möglich.
Verkörperte Gefühle – gefühlte Verkörperung
Authors: Sollmann Ulrich
Published: December 2017

Die Bioenergetische Analyse will helfen, das Zusammenspiel zwischen Emotionen, psychischem Gleichgewicht und körperlichem Wohlbefinden besser zu verstehen. Sie geht davon aus, dass alle körperlichen und sinnlichen Vorgänge nur verschiedene Formen eines einheitlichen Lebensprozesses sind. Durch Arbeit mit dem Körper wird die Seele therapiert. Verspannungen und Verhärtungen werden gelöst und die Energie im Körper wieder zum Fließen gebracht.
Körper und Seele in Harmonie
Authors: Arnold Johanna
Published: December 2017

Heilmagnetische Behandlungen haben in der Naturheilkunde eine lange Tradition. Schon Goethe schrieb davon in seinen Schriften. Der Behandlungsmethode liegt die Annahme zugrunde, dass der Behandelnde mit seinem eigenen magnetischen Feld das eines anderen ausrichten kann. Insbesondere bei psychischen Beschwerden wie Erschöpfungszuständen, Burnout, Niedergeschlagenheit sowie psychosomatischen Erkrankungen zeigt es gute Wirkung.
Computertomografie – Kosten-Nutzen-Analyse von Computertomografie-Scannern
Authors: Bretzke Pascal
Published: December 2017

Burgers LT et al. Cost-effectiveness analysis of new generation coronary CT scanners for difficult-to-image patients. The European Journal of
Health Economics 2017; 18: 731–742

Die koronare Herzkrankheit (KHK) zählt zu den häufigsten Todesursachen im Erwachsenenalter. Insbesondere die patientenassoziierten Folgen
sind gravierend, da jeder fünfte Sterbefall im Jahr 2003 durch eine KHK verursacht wurde. Zur Diagnostik einer KHK stehen sowohl die
invasive Koronarangiografie (ICA), als auch Geräte der neuen Generation (New generation dual-source coronoray CT/NGCCT) zur Verfügung.
Ziel der Studie war die Evaluation des Einsparpotenzials sowie des Nutzens beider Alternativen.
Discrete Choice Experiment – Bewertung von krankheitsspezifischen Nutzwerten
Authors: Thiem Helena
Published: December 2017

Sossong B et al. Evaluating the consequences of rheumatoid arthritis. Eur J Health Econ 2017; 18: 685–696

Es hat sich gezeigt, dass Patienten und Nicht-Erkrankte einem Leidenszustand häufig unterschiedliche Nutzwerte zuschreiben. Dies führt zu
der Frage, ob die Einschätzungen gut informierter Patienten oder der für die aufkommenden Kosten zuständigen Gesellschaft als Grundlage
für eine Kosten-Effektivitätsanalyse herangezogen werden sollten. Vor diesem Hintergrund wurden Daten aus einem Discrete Choice
Experiment (DCE) ausgewertet, an dem sowohl Patienten mit rheumatoider Arthritis als auch Nicht-Erkrankte teilgenommen haben.
Shakespeare and Gesture in Practice
Authors: Tunstall Darren
Published: December 2017

When actors perform Shakespeare, what do they do with their bodies? How do they display to the spectator what is hidden in the imagination? This is a history of Shakespearean performance as seen through the actors body. Tunstall draws upon social, cognitive and moral psychology to reveal how performers from Sarah Siddons to Ian McKellen have used the language of gesture to reflect the minds of their characters and shape the reactions of their audiences. This book is rich in examples, including detailed analysis of recent performances and interviews with key figures from the worlds of both acting and gesture studies. Truly interdisciplinary, this provocative and original contribution will appeal to anyone interested in Shakespeare, theatre history, psychology or body language.
High-resistivity unintentionally carbon-doped GaN layers with nitrogen as nucleation layer carrier gas grown by metal-organic chemical vapor deposition
Authors: Chen Fu , Sun Shichuang , Deng Xuguang , Fu Kai , Yu Guohao , Song Liang , Hao Ronghui , Fan Yaming , Cai Yong , Zhang Baoshun
Published: December 2017

In this letter, high-resistivity unintentionally carbon-doped GaN layers with sheet resistivity greater than 106 Ω/□ have been grown on c-plane sapphire substrates by metal-organic chemical vapor deposition (MOCVD). We have observed that the growth of GaN nucleation layers (NLs) under N2 ambient leads to a large full width at half maximum (FWHM) of (102) X-ray diffraction (XRD) line in the rocking curve about 1576 arc sec. Unintentional carbon incorporation can be observed in the secondary ion mass spectroscopy (SIMS) measurements. The results demonstrate the self-compensation mechanism is attributed to the increased density of edge-type threading dislocations and carbon impurities. The AlGaN/GaN HEMT grown on the high-resistivity GaN template has also been fabricated, exhibiting a maximum drain current of 478 mA/mm, a peak transconductance of 60.0 mS/mm, an ON/OFF ratio of 0.96×108 and a breakdown voltage of 621 V.
Enhanced recoverable energy storage density and high efficiency of SrTiO3-based lead-free ceramics
Authors: Yang Haibo , Yan Fei , Lin Ying , Wang Tong
Published: December 2017

In this study, (1−x)SrTiO3-x(Bi0.48La0.02Na0.48Li0.02Ti0.98Zr0.02O3) [(1−x)ST-xBLNLTZ] lead-free ceramics with x = 0–0.4 were designed and fabricated using the tape casting process and the subsequent conventional solid-state sintering method. The (1−x)ST-xBLNLTZ ceramics are characterized by the excellent frequency stability of the dielectric constant, large maximum polarization (Pmax), low remnant polarization (Pr), and slim polarization-electric field (P-E) loops. For the composition of x = 0.4, Pmax is increased to 30.35 μC/cm2, 3.82 times higher than that of pure SrTiO3 (7.95 μC/cm2). The breakdown strength is larger than 200 kV/cm for all the samples. The sample with x = 0.1 exhibits a high recoverable energy storage density (Wrec) of 2.59 J/cm3 and a high energy storage efficiency (η) of 85% simultaneously. The results demonstrate that the (1−x)ST-xBLNLTZ ceramics are promising lead-free materials for high energy storage applications.
Generation of high-power broadband terahertz radiation during stimulated backscattering of the pump wave by an intense relativistic electron beam
Authors: Ginzburg N. S. , Vilkov M. N. , Kocharovskaya E. R. , Sergeev A. S.
Published: December 2017

The possibility of generation of high-power (multi-megawatt) broadband terahertz radiation during stimulated backscattering of an intense millimeter-wavelength pump wave by a high-current relativistic electron beam (REB) is shown. With allowance for a significant parameter spread that is typical for intense REBs, the kinetic interaction regime is expedient. This regime leads to the broadening of the scattered-radiation spectrum, but simultaneously increases the efficiency of the beam energy conversion into short-wavelength radiation.
Enhanced performance of 17.7 GHz SAW devices based on AlN/diamond/Si layered structure with embedded nanotransducer
Authors: Wang Lei , Chen Shuming , Zhang Jinying , Xiao Dingbang , Han Kaifeng , Ning Xi , Liu Jingtian , Chen Zhe , Zhou Jian
Published: December 2017

Surface acoustic wave (SAW) devices using embedded interdigital transducers (IDTs) on an AlN/diamond/Si layered substrate are fabricated, and their performances are investigated. The Sezawa mode is the dominant resonance with the highest resonant frequency up to 17.7 GHz, a signal amplitude of 20 dB, and an electromechanical coupling coefficient of 0.92%. Comparing these SAW devices with those having the conventional IDTs on the same layered structure, the output SAW power and resonant frequency of devices are improved by 10.7% and 1.1%, respectively, for the embedded IDT devices. This is because the different field distribution leads to the different Bragg reflection and phase velocity for the two types of IDTs. The radiation frequency characteristics indicate that the advantages of the embedded IDTs would be useful for high frequency, high power applications such as monolithic integrated millimeter-wave integrated circuit and high speed communications.
Speeding up nanomagnetic logic by DMI enhanced Pt/Co/Ir films
Authors: Ziemys Grazvydas , Ahrens Valentin , Mendisch Simon , Csaba Gyorgy , Becherer Markus
Published: December 2017

We investigated a new type of multilayer film for Nanomagnetic Logic with perpendicular anisotropy (pNML) enhanced by the Dzyaloshinskii-Moriya interaction (DMI). The DMI effect provides an additional energy term and widens the design space for pNML film optimization. In this work we added an Ir layer between Co and Pt to our standard pNML multilayer (ML) film stack - [Co/Pt]x4. Multilayer stacks of films with and w/o Ir were sputtered and patterned to nanowires of 400 nm width by means of focused ion beam lithography (FIB). For comparability of the films they were tuned to show identical anisotropy for multilayer stacks with and w/o Ir. The field-driven domain wall (DW) velocity in the nanowires was measured by using wide-field MOKE microscopy. We found a strong impact of Ir on the DW velocity being up to 2 times higher compared to the standard [Co/Pt]x4 ML films. Moreover, the maximum velocity is reached at much lower magnetic field, which is beneficial for pNML operation. These results pave the way for pNML with higher clocking rates and at the same time allow a further reduce power consumption.
The change of domain structure of the amorphous microwire of Fe73.5Cu1Nb3Si13.5B9 composition under thermal treatment
Authors: Aksenov O. I. , Abrosimova G. E. , Aronin A. S. , Orlova N. N. , Churyukanova M. N. , Zhukova V. A. , Zhukov A. P.
Published: December 2017

The investigation on domain structure evolution under variation of magnetostriction, phase composition and internal stresses was provided. Glass-coated amorphous microwires of Fe73.5Cu1Nb3Si13.5B9 composition with positive magnetostriction were studied. The decrease of internal stresses and controlled crystallization leading to changes in the phase composition and reduction of magnetostriction were observed under different thermal treatment. The domain structure of the as-prepared and annealed microwires was studied by the method of magneto-optical indicator films. The estimation of the domain size was realized by Fourier transform from the domain contrast of magneto-optical images. The regularities of the influence of thermal treatment on the magnetic domain structure of microwires have been estimated.
Charge transport and dipolar relaxations in phosphonium-based ionic liquids
Authors: Cosby Tyler , Vicars Zachariah , Mapesa Emmanuel Urandu , Tsunashima Katsuhiko , Sangoro Joshua
Published: December 2017

The role of anions in charge transport and localized dipolar relaxations in tributyloctylphosphonium ionic liquids is investigated by broadband dielectric spectroscopy and rheology. The dielectric spectra are quantitatively described by a combination of the random barrier model which accounts for ion transport and empirical Havriliak-Negami functions to characterize dipolar relaxations. Two secondary relaxations are observed at temperatures below the calorimetric glass transition temperature, where the primary structural relaxation is essentially frozen at the relevant experimental time scales. The faster process has an anion independent activation energy of 30 kJ/mol and is attributed to libration motion of the phosphonium cation. The slower relaxation is similar to a process previously assigned to a Johari-Goldstein relaxation in imidazolium-based ionic liquids; however, the activation energy is significantly higher in the phosphonium systems. For the charge transport dominated regime, it is observed that variation of the anion results in differences in the dc ionic conductivity and characteristic charge transport rates by ∼2.5 decades. Upon scaling by the calorimetric glass transition temperature, both transport quantities are observed to coincide. From these results, a picture of glass transition assisted hopping emerges as the underlying microscopic mechanism of ion conduction, in agreement with recent results obtained for other classes of aprotic ionic liquids.
Characterization of long-range plasmonic waveguides at visible to near-infrared regime
Authors: Huang Sheng-Ting , Lai Chien-Chih , Sheu Fang-Wen , Tsai Wan-Shao
Published: December 2017

Long-range surface plasmon polariton waveguides composed with thin gold stripes embedded in SU-8 polymer cladding with various stripe widths were fabricated. Material properties of the polymer cladding layer, gold thin film, and the device structures were discussed. Optical properties based on modal propagation were characterized at visible to near-infrared wavelengths. The measured propagation losses of waveguide widths from 3 to 9 μm at 633, 785, and 1550 nm are 7.5-18.8, 6.8-12.5, and 1.9-3.9 dB/mm, respectively. Guiding mode properties such as overlap integrals between the simulated and the measured fields and the polarization extinction ratios of the waveguides with different stripe widths were investigated at the telecommunication wavelength. Good accordance between the measurement and simulation results was presented.
Experimental study of the accumulative deformation effect on wide-shallow composite bucket foundation for offshore wind turbines
Authors: Wang Xuyue , Zhang Puyang , Ding Hongyan , Liu Run
Published: December 2017

In this study, a new type of foundation for offshore wind turbines (OWTs), called wide-shallow composite bucket foundation (WSCBF), in which the bucket is divided into seven rooms by steel bulkheads, was developed and further studied. The influence of the bulkheads on the long-term performance of the WSCBF for OWTs is investigated in cyclic loading model tests. A new type of cyclic loading device is used in model tests. Neutral axis vertical displacement is introduced as a unified standard to measure accumulative deformation results. Test results show that the bulkheads are utilized not only to delay the appearance of plastic deformation for potential engineering applications but also to effectively reduce the final value of accumulative deformation and long-term settlement of WSBCF. Moreover, the natural frequency of the whole structural system is shown to increase under long-term cycle loading. Nevertheless, the accumulative deformation based on WSCBF has a limited effect on the safety of an OWT throughout its operational life. These conclusions are useful for engineering applications and provide guidance for OWT foundation design.
Size-driven quantum phase transitions
Authors: Bausch Johannes , Cubitt Toby S. , Lucia Angelo , Perez-Garcia David , Wolf Michael M.
Published: December 2017

Significance

In this work we construct simple examples of 2D quantum spin-lattice models with small (

≤

10) local state spaces which exhibit very unusual finite-size effects that we term “size-driven phase transitions”: For all system sizes smaller than some threshold
N
, the low-energy physics are classical; for all sizes larger than
N
, the system exhibits topological quantum order. Most quantum many-body models are too complex to be solved analytically; our theoretical understanding comes from extrapolating numerical simulations of finite systems to the thermodynamic limit. However, this approach cannot work for the size-driven effects revealed here. We give explicit examples where the threshold size is beyond the capability of any foreseeable numerics (
N

>

10

36,000

).
Computation of extreme heat waves in climate models using a large deviation algorithm
Authors: Ragone Francesco , Wouters Jeroen , Bouchet Freddy
Published: December 2017

Significance

We propose an algorithm to sample rare events in climate models with a computational cost from 100 to 1,000 times less than direct sampling of the model. Applied to the study of extreme heat waves, we estimate the probability of events that cannot be studied otherwise because they are too rare, and we get a huge ensemble of realizations of an extreme event. Using these results, we describe the teleconnection pattern for the extreme European heat waves. This method should change the paradigm for the study of extreme events in climate models: It will allow us to study extremes with higher-complexity models, to make intermodel comparison easier, and to study the dynamics of extreme events with unprecedented statistics.
GRAM-CNN: a deep learning approach with local context for named entity recognition in biomedical text
Authors: Zhu Qile , Li Xiaolin , Conesa Ana , Pereira Cécile
Published: December 2017

Motivation

Best performing named entity recognition (NER) methods for biomedical literature are based on hand-crafted features or task-specific rules, which are costly to produce and difficult to generalize to other corpora. End-to-end neural networks achieve state-of-the-art performance without hand-crafted features and task-specific knowledge in non-biomedical NER tasks. However, in the biomedical domain, using the same architecture does not yield competitive performance compared with conventional machine learning models.

Results

We propose a novel end-to-end deep learning approach for biomedical NER tasks that leverages the local contexts based on n-gram character and word embeddings via Convolutional Neural Network (CNN). We call this approach GRAM-CNN. To automatically label a word, this method uses the local information around a word. Therefore, the GRAM-CNN method does not require any specific knowledge or feature engineering and can be theoretically applied to a wide range of existing NER problems. The GRAM-CNN approach was evaluated on three well-known biomedical datasets containing different BioNER entities. It obtained an F1-score of 87.26% on the Biocreative II dataset, 87.26% on the NCBI dataset and 72.57% on the JNLPBA dataset. Those results put GRAM-CNN in the lead of the biological NER methods. To the best of our knowledge, we are the first to apply CNN based structures to BioNER problems.

Availability and implementation

The GRAM-CNN source code, datasets and pre-trained model are available online at: https://github.com/valdersoul/GRAM-CNN.

Supplementary information

Supplementary data are available at Bioinformatics online.
The Neural Specificity of Movement Preparation During Actual and Imagined Movements
Authors: Lebon Florent , Ruffino Célia , Greenhouse Ian , Labruna Ludovica , Ivry Richard B , Papaxanthis Charalambos
Published: December 2017

Current theories consider motor imagery, the mental representation of action, to have considerable functional overlap with the processes involved in actual movement preparation and execution. To test the neural specificity of motor imagery, we conducted a series of 3 experiments using transcranial magnetic stimulation (TMS). We compared changes in corticospinal excitability as people prepared and implemented actual or imagined movements, using a delayed response task in which a cue indicated the forthcoming response. TMS pulses, used to elicit motor-evoked responses in the first dorsal interosseous muscle of the right hand, were applied before and after an imperative signal, allowing us to probe the state of excitability during movement preparation and implementation. Similar to previous work, excitability increased in the agonist muscle during the implementation of an actual or imagined movement. Interestingly, preparing an imagined movement engaged similar inhibitory processes as that observed during actual movement, although the degree of inhibition was less selective in the imagery conditions. These changes in corticospinal excitability were specific to actual/imagined movement preparation, as no modulation was observed when preparing and generating images of cued visual objects. Taken together, inhibition is a signature of how actions are prepared, whether they are imagined or actually executed.
Surrogate Fecal Biomarkers in Inflammatory Bowel Disease: Rivals or Complementary Tools of Fecal Calprotectin?
Authors: Di Ruscio Mirko , Vernia Filippo , Ciccone Antonio , Frieri Giuseppe , Latella Giovanni
Published: December 2017

Background

Current noninvasive methods for assessing intestinal inflammation in inflammatory bowel disease (IBD) remain unsatisfactory. Along with C-reactive protein and erythrocyte sedimentation rate, fecal calprotectin (FC) is the standard test for assessing IBD activity, even though its specificity and accuracy are not optimal and it lacks a validated cutoff. Over the past few decades, several fecal markers released from intestinal inflammatory cells have been investigated in IBD; they are the subject of this systematic review.

Methods

A systematic electronic search of the English literature up to April 2017 was performed using Medline and the Cochrane Library. Only papers written in English that analyzed fecal biomarkers in IBD were included. In vitro studies, animal studies, studies on blood/serum samples, and studies analyzing FC or fecal lactoferrin alone were excluded.

Results

Out of 1023 citations, 125 eligible studies were identified. Data were grouped according to each fecal marker including S100A12, high-mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, human neutrophil peptides, neutrophil gelatinase-associated lipocalin, chitinase 3-like-1, matrix metalloproteinase 9, lysozyme, M2-pyruvate kinase, myeloperoxidase, fecal eosinophil proteins, human beta-defensin-2, and beta-glucuronidase. Some of these markers showed a high sensitivity and specificity and correlated with disease activity, response to therapy, and mucosal healing. Furthermore, they showed a potential utility in the prediction of clinical relapse.

Conclusions

Several fecal biomarkers have the potential to become useful tools complementing FC in IBD diagnosis and monitoring. However, wide variability in their accuracy in assessment of intestinal inflammation suggests the need for further studies.
Factors Associated With Length of Stay in Veterans With Inflammatory Bowel Disease Hospitalized for an Acute Flare
Authors: Kelso Michael , Weideman Rick A , Cipher Daisha J , Feagins Linda A
Published: December 2017

Background

Reducing hospital costs and risk of complications by shortening length of stay has become paramount. The aim of our study was to identify predictors and potentially modifiable factors that influence length of stay among veterans with inflammatory bowel disease admitted for an acute flare.

Methods

Retrospective review of patients admitted to the Dallas VA with an acute flare of their inflammatory bowel disease between 2000 and 2015. Patients with a length of stay of ≤4 days were compared with those whose length of stay >4 days.

Results

A total of 180 admissions involving 113 patients (59 with ulcerative colitis and 54 with Crohn’s disease) were identified meeting inclusion criteria. The mean length of stay was 5.3 ± 6.8 days, and the median length of stay was 3.0 days. On multiple logistic regression analysis, initiation of a biologic, having undergone 2 or more imaging modalities, and treatment with intravenous steroids were significant predictors of longer lengths of stay, even after controlling for age and comorbid diseases.

Conclusions

We identified several predictors for longer hospital length of stay, most related to disease severity but several of which may be modifiable to reduce hospital stays, including most importantly consideration of earlier prebiologic testing. Future studies are needed to evaluate the impact of interventions targeting modifiable predictors of length of stay on health care utilization and patient outcomes.

10.1093/ibd/izx020_video1 izx020.video1 5732756865001
A Survey Study of Gastroenterologists’ Attitudes and Barriers Toward Therapeutic Drug Monitoring of Anti-TNF Therapy in Inflammatory Bowel Disease
Authors: Grossberg Laurie B , Papamichael Konstantinos , Feuerstein Joseph D , Siegel Corey A , Ullman Thomas A , Cheifetz Adam S
Published: December 2017

Background

Therapeutic drug monitoring (TDM) may improve the efficacy and cost-effectiveness of anti-TNF therapy. A standardized approach of utilizing TDM has not been established. The objective of this study was to determine gastroenterologists’ attitudes and barriers toward TDM of anti-TNF therapy in clinical practice.

Methods

An 18-question survey was distributed to members of the American College of Gastroenterology and Crohn’s and Colitis Foundation via email. We collected physician characteristics, practice demographics, and data regarding TDM use and perceived barriers to TDM. Factors associated with the use of TDM were determined by logistic regression analysis.

Results

A total of 403 gastroenterologists from 42 US states (76.4% male) met inclusion criteria: 90.1% use TDM, mostly reactively for secondary loss of response (87.1%) and primary nonresponse (66%); 36.6% use TDM proactively. The greatest barriers to TDM implementation were uncertainty about insurance coverage (77.9%), high out-of-pocket patient costs (76.4%), and time lag from serum sample to result (38.5%). Factors independently associated with the use of TDM and proactive TDM were practice in an academic setting (P = 0.019), and more IBD patients seen per month (P = 0.015), and Crohn’s and Colitis Foundation membership (P < 0.001), and more IBD patients on anti-TNF therapy per month (P = 0.006), respectively. If all barriers were removed, an additional one-third of physicians would apply proactive TDM.

Conclusions

Lack of insurance coverage, high out-of-pocket costs, and the time lag from test to result limit use of TDM in the United States. Validation of low-cost assays, point of care testing, and studies that standardize the use of TDM are needed to make TDM more commonplace.

10.1093/ibd/izx023_video1 izx023.video1 5732761268001
Dimension Bound for Badly Approximable Grids
Authors: Lim Seonhee , de Saxcé Nicolas , Shapira Uri
Published: December 2017

We show that there exists a subset of full Lebesgue measure $V\subset \mathbb{R}^{n}$ such that for every ϵ > 0 there exists δ > 0 such that for any v ∈ V the dimension of the set of vectors w satisfying $$ \liminf_{k\to\infty} k^{1/n}\langle kv-w\rangle\geqslant \epsilon$$

(where 〈⋅〉 denotes the distance from the nearest integer) is bounded above by n − δ. This result is obtained as a corollary of a discussion in homogeneous dynamics and the main tool in the proof is a relative version of the principle of uniqueness of measures with maximal entropy.
Large-scale correlations in gas traced by Mg ii absorbers around low-mass galaxies
Authors: Kauffmann Guinevere
Published: December 2017

The physical origin of the large-scale conformity in the colours and specific star formation rates of isolated low-mass central galaxies and their neighbours on scales in excess of 1 Mpc is still under debate. One possible scenario is that gas is heated over large scales by feedback from active galactic nuclei (AGNs), leading to coherent modulation of cooling and star formation between well-separated galaxies. In this Letter, the metal line absorption catalogue of Zhu & Ménard is used to probe gas out to large projected radii around a sample of a million galaxies with stellar masses ∼1010M⊙ and photometric redshifts in the range 0.4 < z < 0.8 selected from Sloan Digital Sky Survey imaging data. This galaxy sample covers an effective volume of 2.2 Gpc3. A statistically significant excess of Mg ii absorbers is present around the red-low-mass galaxies compared to their blue counterparts out to projected radii of 10 Mpc. In addition, the equivalent width distribution function of Mg ii absorbers around low-mass galaxies is shown to be strongly affected by the presence of a nearby (Rp < 2 Mpc) radio-loud AGNs out to projected radii of 5 Mpc.
Cropping History Effects on Pathogen Suppressive and Signaling Dynamics in Streptomyces Communities
Authors: Jauri Patricia Vaz , Altier Nora , Pérez Carlos A. , Kinkel Linda
Published: December 2017

Diseases remain a yield-limiting factor for crops despite the availability of control measures for many pathogens. Indigenous soil microorganisms can suppress some plant pathogens, yet there is little systematic information on the effects of cropping systems on disease-suppressive populations in soil. Streptomyces have been associated with suppression of plant diseases in several naturally occurring disease-suppressive soils. Pathogen-suppressive activity of Streptomyces communities is correlated with higher bacterial densities and with inhibitory phenotypes, driven by competition among indigenous soil bacteria. We sought to characterize relationships between cropping practices and pathogen suppression among soil Streptomyces. We evaluated bacterial and Streptomyces densities and inhibitory activities in soils from a long-term crop rotation experiment. Signaling interactions that altered inhibitory phenotypes among sympatric populations were also evaluated for a subset of samples. Soils from longer rotations, which had a higher number of plant species over time, had larger bacterial and Streptomyces densities, and more inhibitors than soils from shorter rotations. In addition, signaling occurred more frequently among isolates from higher-density communities. Our work shows that bacterial density, pathogen suppression and signaling are interrelated and are affected by crop rotation, suggesting the potential for management to optimize suppressive populations.
Condoliase for the Treatment of Lumbar Disc Herniation
Authors: Chiba Kazuhiro , Matsuyama Yukihiro , Seo Takayuki , Toyama Yoshiaki
Published: December 2017

Study Design.

A randomized, double-blind, placebo-controlled, multicenter phase III clinical trial.

Objective.

To evaluate the efficacy and safety of chemonucleolysis with condoliase in patients with lumbar disc herniation (LDH).

Summary of Background Data.

Condoliase is a pure mucopolysaccharidase derived from a bacterium, Proteus vulgaris that has high substrate specificity for chondroitin sulfate and hyaluronic acid in the nucleus pulposus of the intervertebral disc.

Methods.

In this study, patients aged 20 to 70 years with unilateral leg pain, positive straight leg raise test, and a contained LDH were recruited in Japan. Patients were treated with a single injection of condoliase (1.25 U) or placebo and were followed for 1 year after administration. The primary endpoint was change in worst leg pain from baseline to week 13. The secondary endpoints included responder rate, and the changes from baseline up to week 52 in the worst leg pain, worst back pain, Oswestry Disability Index, 36-Item Short-Form Health Survey, neurologic examinations, and imaging parameters.

Results.

A total of 82 and 81 patients received an injection of condoliase and placebo, respectively. The average changes in worst leg pain from baseline to week 13 (primary endpoint) were −49.5 mm in the condoliase group and −34.3 mm in the placebo group, and the difference of −15.2 mm was significant (95% confidence interval, −24.2 to −6.2; P = 0.001). Significant improvements were observed in the condoliase groups, compared with the placebo group, in most secondary endpoints at 1 year after administration. In the condoliase group, back pain, Modic type 1 change, and decrease in disc height were frequently reported, without any clinically relevant consequences.

Conclusion.

Condoliase significantly improved symptoms in patients with LDH and was well tolerated. Condoliase is a novel and potent chemonucleolytic drug for the treatment of LDH.

Level of Evidence: 1
Outpatient Spine Clinic Utilization is Associated With Reduced Emergency Department Visits Following Spine Surgery
Authors: Pak Linda M. , Fogel Harold A. , Chaudhary Muhammad Ali , Kwon Nicollette K. , Barton Lauren B. , Koehlmoos Tracey , Haider Adil H. , Schoenfeld Andrew J.
Published: December 2017

Study Design.

Review of TRICARE claims (2006–2014) data to assess Emergency Department (ED) utilization following spine surgery.

Objective.

The aim of this study was to determine utilization rates and predictors of ED utilization following spine surgical interventions.

Summary of Background Data.

Visits to the ED following surgical intervention represent an additional stress to the healthcare system. While factors associated with readmission following spine surgery have been studied, drivers of postsurgical ED visits, including appropriate and inappropriate use, remain underinvestigated.

Methods.

TRICARE claims were queried to identify patients who had undergone one of three common spine procedures (lumbar arthrodesis, discectomy, decompression). ED utilization at 30- and 90 days was assessed as the primary outcome. Outpatient spine surgical clinic utilization was considered the primary predictor variable. Multivariable logistic regression was used to adjust for confounders.

Results.

Between 2006 and 2014, 48,868 patients met inclusion criteria. Fifteen percent (n = 7183) presented to the ED within 30 days postdischarge. By 90 days, 29% of patients (n = 14,388) presented to an ED. The 30- and 90-day complication rates were 6% (n = 2802) and 8% (n = 4034), respectively, and readmission rates were 5% (n = 2344) and 8% (n = 3842), respectively. Use of outpatient spine clinic services significantly reduced the likelihood of ED utilization at 30 [odds ratio (OR) 0.48; 95% confidence interval (95% CI) 0.46–0.53] and 90 days (OR 0.55; 95% CI 0.52–0.57).

Conclusion.

Within 90 days following spine surgery, 29% of patients sought care in the ED. However, only one-third of these patients had a complication recorded, and even fewer were readmitted. This suggests a high rate of unnecessary ED utilization. Outpatient utilization of spine clinics was the only factor independently associated with a reduced likelihood of ED utilization.

Level of Evidence: 3
Update on adjuvant melanoma therapy
Authors: Dimitriou Florentia , Braun Ralph Peter , Mangana Joanna
Published: December 2017

Purpose of review

We review the results from relevant clinical trials and discuss current strategies in the melanoma adjuvant setting.

Recent findings

The favorable therapeutic efficacy and the significant less toxicity of nivolumab compared with ipilimumab, fully substitutes today‘s approval of ipilimumab, regardless mutation status, whereas in BRAF-mutated patients, dabrafenib and trametinib seem to confirm their high efficacy also in adjuvant setting. The use of interferon is restricted to patients with ulcerated melanoma and countries with no access to the new drugs.

Systemic adjuvant treatment after complete disease resection in high-risk melanoma patients aims to increase relapse-free survival (RFS) and overall survival (OS). According to the eighth edition of melanoma classification of American Joint Committee on Cancer (AJCC), the prognosis in stage III patients is heterogeneous and depends not only on N (nodal) but also on T (tumor thickness) category criteria. Recent data from randomized, phase-3 clinical trials analyzing the use of adjuvant anti-programmed death-1 and targeted therapies ultimately affect the standard of care and change the landscape of the adjuvant treatment.
Enhanced antinociception with repeated microinjections of apomorphine into the periaqueductal gray of male and female rats
Authors: Schoo Shauna M. , Bobeck Erin N. , Morgan Michael M.
Published: December 2017

Dopamine neurons in the ventrolateral periaqueductal gray (PAG) have been reported to contribute to antinociception. The objective of this study was to determine how this dopamine-mediated antinociception differs from what is known about morphine-induced antinociception. Microinjection of the dopamine receptor agonist apomorphine into the PAG produced a dose-dependent increase in hot plate latency and a decrease in open field activity that was greater in male than in female rats. The peak antinociceptive effect occurred 5 min after apomorphine administration. Surprisingly, the antinociceptive potency of apomorphine was enhanced following systemic administration of the opioid receptor antagonist naloxone in male, but not in female rats. The antinociceptive potency of microinjecting apomorphine into the ventrolateral PAG in male and female rats was also enhanced following twice-daily injections for 2 days. The characteristics of apomorphine-induced antinociception differ from previous reports of morphine antinociception following PAG microinjections in that morphine antinociception peaks at 15 min, is blocked by naloxone, and is susceptible to tolerance with repeated administration. These results indicate that apomorphine-induced antinociception is distinct from opioid-induced antinociception, and that dopamine receptor agonists may provide a novel approach to pain modulation.
Fast and Straightforward Method for the Quantification of Pazopanib in Human Plasma Using LC-MS/MS
Authors: Verheijen Remy B. , Thijssen Bas , Rosing Hilde , Schellens Jan H. M. , Nan Lianda , Venekamp Nikkie , Beijnen Jos H. , Steeghs Neeltje , Huitema Alwin D. R.
Published: December 2017

Background:

Pazopanib is an angiogenesis inhibitor approved for renal cell carcinoma and soft-tissue sarcoma. Studies indicate that treatment with pazopanib could be optimized by adapting the dose based on measured pazopanib plasma concentrations.

Methods:

We describe the validation and clinical application of a fast and straightforward method for the quantification of pazopanib in human plasma for the purpose of therapeutic drug monitoring and bioanalytical support of clinical trials. Stable isotopically labeled 13C,2H3-pazopanib was used as internal standard. Plasma samples were prepared for analysis by protein precipitation using methanol and diluted with 10 mmol/L ammonium hydroxide buffer. Chromatographic separation was performed on a C18 column using isocratic elution with ammonium hydroxide in water and methanol. For detection, a tandem mass spectrometer, equipped with a turbo ion spray interface was used in positive ion mode at m/z 438 → m/z 357 for pazopanib and m/z 442 → m/z 361 for the internal standard.

Results:

Final runtime was 2.5 minutes. All validated parameters were within pre-established limits and fulfilled the FDA and EMA requirements for bioanalytical method validation. After completion of the validation, the routine application of the method was tested by analyzing clinical study samples that were collected for the purpose of therapeutic drug monitoring.

Conclusions:

In conclusion, the described method was successfully validated and was found to be robust for routine application to analyze samples from cancer patients treated with pazopanib.
Association between the age-related decline in renal function and lumbar spine bone mineral density in healthy Chinese postmenopausal women
Authors: Han Wen , Bai Xiao-Juan , Han Lu-Lu , Akhtari Sebastian , Sun Xue-Feng , Chen Xiang-Mei
Published: December 2017

Objectives:

The relationship between the decline of renal function and bone mineral density (BMD) in healthy populations is not well-researched. The aim of this study was to investigate the association between the age-related decline in renal function and lumbar spine BMD (LBMD) in a community-based cross-sectional study of 390 healthy postmenopausal women (mean age 62.97 ± 8.79 years) from Shenyang, China.

Methods:

Dual-energy x-ray absorptiometry was used to measure LBMD. Estimated glomerular filtration rate (eGFR) was calculated using a modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for Asians and the CKD-EPI serum creatinine-cystatin c equation. Pearson's correlation analysis and binary logistic regression were used to evaluate associations.

Results:

The eGFR-ASIA and eGFR-Scys were positively correlated with LBMD (r = 0.120 and r = 0.108, respectively). After adjustments for numerous potential confounders, the odds ratio for participants with LBMD decline in eGFR-ASIA quartile 3 group and 4 group were 2.45 (95% confidence interval [CI] 1.12-5.38, P < 0.05) and 3.89 (95% CI 1.55-9.76, P < 0.01), respectively, with P = 0.003 for the trend in eGFR-ASIA compared with the lowest quartile 1 group of eGFR-ASIA, where the odds ratio of eGFR-Scys for the quartile of 3 and 4 groups were 2.47 (95% CI 1.09-5.62, P < 0.05) and 2.63 (95% CI 1.10-6.29, P < 0.05), respectively, with P = 0.016 for the trend in eGFR-Scys compared with the lowest quartile 1 group of eGFR-Scys.

Conclusions:

The renal function decline was independently associated with decreased LBMD, and it was possible that the age-related decline in kidney function was an independent risk factor for decreased LBMD in healthy Chinese postmenopausal women.
Left ventricular remodeling and arterial afterload in older women with uncontrolled and controlled hypertension
Authors: Yoo Jeung-Ki , Okada Yoshiyuki , Best Stuart A. , Parker Rosemary S. , Hieda Michinari , Levine Benjamin D. , Fu Qi
Published: December 2017

Objective:

The prevalence of hypertension increases with advancing age in women. Blood pressure control is more difficult to achieve in older women, and despite well-controlled blood pressure, the cardiovascular mortality remains high. However, the underlying mechanisms are not understood.

Methods:

Nineteen women with uncontrolled hypertension on drug treatment (70 ± 2 [SE] years, ambulatory awake blood pressure; 152 ± 2/84 ± 2 mm Hg), 19 with controlled hypertension (68 ± 1 years, 128 ± 2/71 ± 2 mm Hg), and 31 healthy normotensive women (68 ± 1 years, 127 ± 1/73 ± 1 mm Hg) were recruited. Participants were weaned from antihypertensive drugs and underwent 3 weeks of run-in before cardiac-vascular assessments. Left ventricular morphology was evaluated with cardiac magnetic resonance imaging. Arterial load and vascular stiffness were measured via ultrasound and applanation tonometry.

Results:

Left ventricular mass normalized by body surface area was not different between hypertension groups (uncontrolled vs controlled: 50.0 ± 1.7 vs 51.8 ± 2.3 g/m2), but it was lower in the normotensive group (41.7 ± 0.9 g/m2; one-way analysis of variance [ANOVA] P = 0.004). Likewise, central pulse wave velocity was not different between hypertension groups (11.5 ± 0.6 vs 11.1 ± 0.5 m/s) and lower in the normotensive group (9.1 ± 0.3 m/s; 1-way ANOVA P = 0.0001). Total peripheral resistance was greater in uncontrolled hypertension (HTN) compared with normotensive group (2051 ± 323 vs 1719 ± 380 dyn∗s/cm5), whereas controlled HTN group (1925 ± 527 dyn∗s/cm5) was not different to either groups.

Conclusion:

Regardless of current blood pressure control, hypertensive older women exhibited increased cardiac mass and arterial stiffness compared with normotensives. Future large-scale longitudinal studies are warranted to directly investigate the mechanisms for the high cardiovascular mortality among older hypertensive women with well-controlled blood pressure.
Diagnostic Accuracy of Mediastinal Lymph Node Staging Techniques in the Preoperative Assessment of Nonsmall Cell Lung Cancer Patients
Authors: Fréchet Benoît , Kazakov Jordan , Thiffault Vicky , Ferraro Pasquale , Liberman Moishe
Published: December 2017

Background:

Nonsmall cell lung cancer (NSCLC) treatment is based on an accurate staging. Mediastinal lymph nodes staging has a critical impact on treatment management.

Methods:

The objective was to assess the current accuracy of preoperative tools for predicting mediastinal and hilar lymph nodes staging with NSCLC. Retrospective analysis of 997 biopsy-proven NSCLC patients treated at a single academic medical center between January 2006 and April 2012. Mediastinal lymph nodes were evaluated with preoperatively with: computed tomography (CT), positron emission tomography (PET), endobronchial ultrasound-guided fine needle aspiration, and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Results are compared with pathologic surgical biopsy.

Results:

A total of 217 cervical mediastinoscopies, 15 anterior mediastinotomies, and 952 surgical lymphadenectomies were performed. The sensitivity of CT scan for mediastinal lymph nodes detection was 18.9% and PET-CT scan was 33.8%. Specificities were 94.9% and 93.8%, respectively. For hilar lymph nodes detection, CT was less sensitive (17.0% vs. 39.7%); however, more specific (94.7% vs. 80.3%) than PET-CT. Endobronchial ultrasound-guided fine needle aspiration (72.7% sensitivity and 100% specificity) and endoscopic ultrasound-guided fine needle aspiration (51.9% sensitivity and 100% specificity) both demonstrated superior results.

Conclusions:

The majority of biopsy-proven mediastinal lymph nodes metastases are not associated with positive results on preoperative CT or PET. CT and PET have low positive predictive value for mediastinal lymph node. This study supports the routine utilization of invasive mediastinal lymph nodes staging in NSCLC, especially for patients with tumors of >4 cm diameter, regardless of CT or PET-CT results.
Driver mutations in primary myelofibrosis and their implications
Authors: Szuber Natasha , Tefferi Ayalew
Published: December 2017

Purpose of review

Primary myelofibrosis (PMF) is one of the classic BCR-ABL1 negative myeloproliferative neoplasms (MPN). Oncogenic driver mutations in PMF include Janus kinase 2, calreticulin (CALR), and myeloproliferative leukemia virus oncogene. These mutations are not only pathogenetically relevant but might also influence disease outcome. Our objective for the current communication is to comprehensively review the distinct phenotypic, therapeutic, and prognostic implications of driver mutations in PMF.

Recent findings

The discovery of driver mutations has revolutionized our understanding of pathogenic mechanisms and clinical heterogeneity in MPN, including PMF. Recently, there have been further advances in our knowledge of the molecular pathogenesis of MPN, particularly pertaining to CALR and its mutation. Moreover, the type and number of additional mutations, their order of acquisition, and their myriad combinatorial interactions with driver mutations may have dynamic pathogenic and clinical consequences. There are also additional data supporting the role of these genetic lesions and their associated allele burdens in modulating clinical features, including outcomes following treatment.

Literature exists to support both phenotypic and prognostic correlates of conventional driver mutations in PMF. As the genetic landscape becomes increasingly complex, establishing the functional impact of these mutations and defining their interactions with other molecular, cytogenetic, and extrinsic factors will further our insight and potentially alter our clinical approach.