bluuebunny/crossref_metadata_2025 huggingface dataset:
Protocol for the CONNECT project: a mixed methods study investigating patient preferences for communication technology use in orthopaedic rehabilitation consultations
Authors: Gilbert Anthony William , Jones Jeremy , Stokes Maria , Mentzakis Emmanouil , May Carl R
Published: December 2019

Introduction

Technology has been placed at the centre of global health policy and has been cited as having the potential to increase efficiency and remove geographical boundaries for patients to access care. Communication technology may support patients with orthopaedic problems, which is one of the leading causes of disability worldwide. There are several examples of technology being used in clinical research, although uptake in practice remains low. An understanding of patient preferences will support the design of a communication technology supported treatment pathway for patients undergoing orthopaedic rehabilitation.

Methods and analysis

This mixed methods project will be conducted in four phases. In phase I, a systematic review of qualitative studies reporting communication technology use for orthopaedic rehabilitation will be conducted to devise a taxonomy of tasks patients’ face when using these technologies to access their care. In phase II, qualitative interviews will investigate how the work of being a patient changes during face-to-face and communication technology consultations and how these changes influence preference. In phase III, a discrete choice experiment will investigate the factors that influence preferences for the use of communication technology for orthopaedic rehabilitation consultations. Phase IV will be a practical application of these results. We will design a ‘minimally disruptive’ communication technology supported pathway for patients undergoing orthopaedic rehabilitation.

Ethics and dissemination

The design of a pathway and underpinning patient preference will assist in understanding factors that might influence technology implementation for clinical care. This study requires ethical approval for phases II, III and IV. Approvals have been received for phase II (approval received on 4 December 2016 from the South Central-Oxford C Research Ethics Committee (IRAS ID: 255172, REC Reference 18/SC/0663)) and phase III (approval received on 18 October 2019 from the London-Hampstead Research Ethics Committee (IRAS ID: 248064, REC Reference 19/LO/1586)) and will be sought for phase IV. All participants will provide informed written consent prior to being enrolled onto the study.

PROSPERO registration number

CRD42018100896.
Massive transfusion in The Netherlands
Authors: Rijnhout Tim W H , Noorman Femke , Bek Annemarije , Zoodsma Margreet , Hoencamp Rigo
Published: December 2019

Objectives

Massive transfusion protocols (MTPs) may improve survival in patients with uncontrolled haemorrhage. An MTP was introduced into the Dutch transfusion guidelines in 2011, the ninth edition of the advanced trauma life support course in 2012 and the third version of the European guideline in 2013. This is the first survey of MTPs in Dutch trauma centres.

Methods

The aim of the study was to compare MTP strategies in level 1 trauma centres in The Netherlands, and with (inter)national guidelines. A contact in each government assigned level 1 trauma centre in The Netherlands and the Dutch Ministry of Defence was approached to share their MTPs and elucidate their protocol in a survey and oral follow-up interview.

Results

All 11 level 1 trauma centres responded. The content of the packages and transfusion ratios (red blood cells/plasma/platelets) were 3:3:1, 5:5:1, 5:3:1, 2:3:1, 4:4:1, 5:2:1, 2:2:1 and 4:3:1. Tranexamic acid was used in all centres and an additional dose was administered in eight centres. Fibrinogen was given directly (n=4), with persistent bleeding (n=3), based on Clauss fibrinogen (n=3) or rotational thromboelastometry (n=1). All centres used additional medication in patients in the form of anticoagulants, but their use was ambiguous.

Conclusion

MTPs differed between institutes and guidelines. The discrepancies in transfusion ratios can be explained by (inter)national differences in preparation and volume of blood components and/or interpretation of the '1:1:1' guideline. We recommend updating MTPs every year using the latest guidelines and evaluating the level of evidence for treatment during massive transfusion.
Emergency department visits during the 4/20 cannabis celebration
Authors: Staples John A , Merchant Ketki , Erdelyi Shannon , Lund Adam , Brubacher Jeffrey R
Published: December 2019

Background

Annual ‘4/20’ cannabis festivals occur around the world on April 20 and often feature synchronised consumption of cannabis at 4:20 pm. The relationship between these events and demand for emergency medical services has not been systematically studied.

Methods

We conducted a population-based retrospective cohort study in Vancouver, Canada, using 10 consecutive years of data (2009–2018) from six regional hospitals. The number of emergency department (ED) visits between 4:20 pm and 11:59 pm on April 20 were compared with the number of visits during identical time intervals on control days 1 week earlier and 1 week later (ie, April 13 and April 27) using negative binomial regression.

Results

A total of 3468 ED visits occurred on April 20 and 6524 ED visits occurred on control days. A non-significant increase in all-cause ED visits was observed on April 20 (adjusted relative risk: 1.06; 95% CI 1.00 to 1.12). April 20 was associated with a significant increase in ED visits among prespecified subgroups including a 5-fold increase in visits for substance misuse and a 10-fold increase in visits for intoxication. The hospital closest to the festival site experienced a clinically and statistically significant 17% (95% CI 5.1% to 29.6%) relative increase in ED visits on April 20 compared with control days.

Interpretation

Substance use at annual ‘4/20’ festivals may be associated with an increase in ED visits among key subgroups and at nearby hospitals. These findings may inform harm reduction initiatives and festival medical care service planning.
A matter of time: grappling with everyday ethical tensions at the confluence between policy and practice in a psychiatric unit
Authors: Motta-Ochoa Rossio , Lencucha Raphael , Xu Jiameng , Park Melissa
Published: December 2019

Objective

To provide insights on emergent ethical tensions experienced by mental health practitioners during system re-organisation, which is sufficiently grounded in empirical data at the local level to inform policy on recovery at institutional and provincial levels.

Method

Ethnographic methods using narrative and critical phenomenological resources over 24 months.

Findings

Everyday ethical tensions emerged at the confluence of different experiences of time, for example, how a context of increasing pressure to decrease patients’ length of stay at the hospital (service-defined time) challenged efforts to listen to and advocate for what mattered to patients (personal time) and maintain the integrity of interventions (clinical time). In this context, practitioners drew on clinical language and that of personal recovery to strategically ‘push back’, ‘play with’ or ‘take back’ time.

Discussion

Examining everyday practices through ethnographic methods can illuminate the everyday ethical tensions that arise when mental health professionals and psychiatrists grapple with, often competing, goods. Critical phenomenological resources can help expand the structural considerations in empirical ethics, excavate underground practices and raise questions about the conceptual categories undergirding normative ethics. Experiencing-with practitioners in clinical contexts as they encounter and creatively resolve ethical tensions also propose a normative ethics of possibility, to help bridge the gap between empirical and normative ethics.

Conclusion

Focus on the relationship between policy, temporal practices and ethics suggests a reconfiguration of time and re-imagination of ethics in institutional settings in ways that can ultimately benefit patients and professionals alike.
The gift of less Christmas stress
Authors: Barker Penny
Published: December 2019

Christmas is around the corner, and both work and life pressures may be mounting as a result. Penny Barker offers some advice on how to cope with the additional stresses the festive period can bring.
Exploring a $$\Sigma _{c}\bar{D}$$ state: with focus on $$P_{c}(4312)^{+}$$
Authors: Zhang Jian-Rong
Published: December 2019

Stimulated by the new discovery of $$P_{c}(4312)^{+}$$Pc(4312)+ by LHCb Collaboration, we endeavor to perform the study of $$P_{c}(4312)^{+}$$Pc(4312)+ as a $$\Sigma _{c}\bar{D}$$ΣcD¯ state in the framework of QCD sum rules. Taking into account the results from two sum rules, a conservative mass range $$4.07{\sim }4.97~\text{ GeV }$$4.07∼4.97GeV is presented for the $$\Sigma _{c}\bar{D}$$ΣcD¯ hadronic system, which agrees with the experimental data of $$P_{c}(4312)^{+}$$Pc(4312)+ and could support its interpretation as a $$\Sigma _{c}\bar{D}$$ΣcD¯ state.
Gravity law in the Chinese highway freight transportation networks
Authors: Wang Li , Ma Jun-Chao , Jiang Zhi-Qiang , Yan Wanfeng , Zhou Wei-Xing
Published: December 2019

The gravity law has been documented in many socioeconomic networks, which states that the flow between two nodes positively correlates with the strengths of the nodes and negatively correlates with the distance between the two nodes. However, such research on highway freight transportation networks (HFTNs) is rare. We construct the directed and undirected highway freight transportation networks between 338 Chinese cities using about 15.06 million truck transportation records in five months and test the traditional and modified gravity laws using GDP, population, and per capita GDP as the node strength. It is found that the gravity law holds over about two orders of magnitude for the whole sample, as well as the daily samples, except for the days around the Spring Festival during which the daily sample sizes are significantly small. Accordingly, the daily exponents of the gravity law are stable except during the Spring Festival period. The results also show that the gravity law has higher explanatory power for the undirected HFTNs than for the directed HFTNs. However, the traditional and modified gravity laws have comparable explanatory power.
Performance analysis of an optically pumped magnetometer in Earth’s magnetic field
Authors: Oelsner Gregor , Schultze Volkmar , IJsselsteijn Rob , Stolz Ronny
Published: December 2019

We experimentally investigate the influence of the orientation of optically pumped magnetometers in Earth’s magnetic field. We focus our analysis to an operational mode that promises femtotesla field resolutions at such field strengths. For this so-called light-shift dispersed$M_{z}$Mz(LSD-Mz) regime, we focus on the key parameters defining its performance. That are the reconstructed Larmor frequency, the transfer function between output signal and magnetic field amplitude as well as the shot noise limited field resolution. We demonstrate that due to the use of two well balanced laser beams for optical pumping with different helicities the heading error as well as the field sensitivity of a detector both are only weakly influenced by the heading in a large orientation angle range.
A multiple objective evolutionary algorithm approach to find optimal design parameters for beam position monitoring systems
Authors: Aydin Ayhan , Bostanci Erkan , Tanriover Omer Ozgur
Published: December 2019

Diagnostic systems are key components for all accelerators, and Beam Position Monitor (BPM) systems are one of the primary functional units. Such systems allow us to observe the beam characteristics and hence interpret and adjust the beam parameters to achieve the required parameter range. This study aims to specify BPM parameters like antenna radius, capacitance, signal-to-noise ratio (SNR), etc. for Turkish Accelerator and Radiation Laboratory in Ankara (TARLA). Searching optimal values for such parameters is conventionally performed using methods including Finite Element Methods (FEM) or analytical approximation. Here, Multiple Objective Evolutionary Algorithms (MOEA) were employed as an alternative. We aimed to obtain a wide range of available results for possible production constraints. Considering TARLA beam parameters, button-type BPMs can be employed as diagnostic tools due to their low cost and simple mechanical structure. SNR levels of 20–40[Formula: see text]dB were achieved using antennas with radius parameters of 3–10[Formula: see text]mm. It is known that these SNR levels are in the acceptable range for the read-out electronic system.
Statistical Coulomb interactions in multi-beam SEM
Authors: Stopka Jan , Kruit Pieter
Published: December 2019

Statistical Coulomb interactions in conventional scanning electron microscopy mostly affect the probe size via energy spread and virtual source broadening in the emitter vicinity. However, in a multi-beam probe forming system such as a multi-beam scanning electron microscopes (MBSEM), the trajectory displacement due to interactions in the whole column can give a contribution to the final probe size. For single-beam systems, this can be expressed using approximate formulae for the total trajectory displacement in a beam segment (Jansen’s theory) or by integrating contributions of infinitesimally thin beam slices (the slice method). We build on Jansen’s theory of statistical Coulomb interactions and develop formulae for the trajectory displacement in a multi-beam system. We also develop a more precise semi-analytical result using the slice method. We compare both approaches with a Monte Carlo simulation and show a good agreement with the results of the slice method. Finally, we discuss the implications of our results for the optical design of multi-beam SEM. In a multi-beam with probe size dominated by Coulomb interactions, an increase in the number of beamlets does not necessarily provide an increase of throughput, because the probe size is limited by the total current. Furthermore, we disprove the notion of “the fewer the crossovers — the less the Coulomb interactions” by showing the quadratic dependence of trajectory displacement on segment length.
An achromatic gantry for proton therapy with fixed-field superconducting magnets
Authors: Brouwer Lucas , Huggins Anthony , Wan Weishi
Published: December 2019

A novel concept for a superconducting, fixed-field bending section is presented for use in a proton therapy gantry. The large momentum acceptance of this design allows for treatment over the full proton energy range of 70–220 MeV with fixed field in the superconducting magnets, eliminating the technical risks associated with fast-field ramping to match beam energy changes during treatment. A combined study of beam dynamics and magnet design is shown for such a system in which a simple magnet geometry with straight Nb–Ti racetrack coils is used to produce the desired fields. Particle tracking through this design is compared with clinical requirements for beam spot shape and size at isocenter over the full range of proton energy.
Dynamical simulations of the Muon Campus at Fermilab
Authors: Tarazona D. A. , Berz M. , Makino K. , Stratakis D. , Syphers M. J.
Published: December 2019

The Muon Campus at Fermilab is a system through which muons are delivered to the storage ring of the Muon [Formula: see text] Experiment (E989). It consists of a set of 1 km beamlines that transport and prepare a highly polarized muon beam out of secondaries produced downstream a target station. Realistic simulations of this beam delivery system (BDS) using COSY INFINITY, and presented here, contribute to the understanding and characterization of the muon beam production in relation to the statistical and systematic uncertainties of the E989 measurement, intended to be smaller than 0.14 parts per million to achieve the goals of the experiment. The impact of nonlinearities from fringe fields and high-order contributions on the BDS performance are presented, as well as detailed studies of the interactions between secondaries and the beamline elements apertures, particle decay channels, spin dynamics and beamline misalignments.
Computation of lossy higher order modes in complex SRF cavities using Beyn’s and Newton’s methods on reduced order models
Authors: Pommerenke Hermann W. , Heller Johann D. , Zadeh Shahnam Gorgi , van Rienen Ursula
Published: December 2019

Superconducting radio frequency cavities meet the demanding performance requirements of modern accelerators and high-brilliance light sources. Their design requires a precise knowledge of their electromagnetic resonances. A numerical solution of Maxwell’s equations is required to compute the resonant eigenmodes, their frequencies and losses due to the complex cavity shape. The consideration of resonances damped by external losses leads to a nonlinear eigenvalue problem. Previous work showed that, using State-Space Concatenation to construct a reduced order model and Newton iteration to solve the arising eigenvalue problem, solutions can be obtained on workstation computers even for large-scale problems without extensive simplification of the structure itself. In this paper, we augment the solution workflow by Beyn’s contour integral algorithm to increase the number of found eigenmodes. Numerical experiments are presented for one academic and two real-life superconducting cavities and partially compared to measurements.
Convergence theorems for barycentric maps
Authors: Hiai Fumio , Lim Yongdo
Published: December 2019

We first develop a theory of conditional expectations for random variables with values in a complete metric space [Formula: see text] equipped with a contractive barycentric map [Formula: see text], and then give convergence theorems for martingales of [Formula: see text]-conditional expectations. We give the Birkhoff ergodic theorem for [Formula: see text]-values of ergodic empirical measures and provide a description of the ergodic limit function in terms of the [Formula: see text]-conditional expectation. Moreover, we prove the continuity property of the ergodic limit function by finding a complete metric between contractive barycentric maps on the Wasserstein space of Borel probability measures on [Formula: see text]. Finally, the large deviation property of [Formula: see text]-values of i.i.d. empirical measures is obtained by applying the Sanov large deviation principle.
Olshanski spherical pairs of semigroups type
Authors: Bouali Mohamed
Published: December 2019

Let [Formula: see text] be the infinite semigroup, inductive limit of the increasing sequence of the semigroups [Formula: see text], where [Formula: see text] is the unitary group of matrices and [Formula: see text] is the semigroup of positive hermitian matrices. The main purpose of this work is twofold. First, we give a complete classification of spherical functions defined on [Formula: see text], by following a general approach introduced by Olshanski and Vershik.10 Second, we prove an integral representation for functions of positive-type analog to the Bochner–Godement theorem, and a Lévy–Khinchin formula for functions of negative type defined on [Formula: see text].
UPPER BODY AXIAL ROTATIONS IN DIFFERENT AGE-GROUPS DURING LEVEL WALKING
Authors: JEON HYEONG MIN , HEO JAE HOON , CHOI EUI BUM , EOM GWANG MOON
Published: December 2019

High amplitude of movements in the lower body during walking is attenuated in the upper body to stabilize the head, which serves as the platform of critical sensory systems (vestibular and visual). The upper body attenuation has been investigated on the linear acceleration, however, not on the angular motion. This study aimed to compare the attenuation of axial rotation in different age-groups. Methods: Thirty healthy men (15 young and 15 elderly) participated in this study. Subjects walked on a level surface with gyro sensors attached at four locations of the back (pelvis, thorax, shoulder, and head), from which the angular motion was derived. Outcome measures included the average peak-to-peak amplitude of axial rotation at all sensor locations and the phase delay at each location with reference to the pelvis. Results: Age-position interaction was significant for both the amplitude and phase delay. Post hoc test revealed that rotation amplitude was similar at pelvis, thorax and shoulder in the elderly, whereas it was significantly reduced at the thorax-shoulder section in the young. The elderly also showed smaller phase delay at shoulder and head than those of the young. Discussion: The results suggest that the attenuation by upper trunk was reduced and the shoulder and head motions were more tightly coupled to the pelvis in the elderly, i.e., the upper body moved more like a rigid body in the axial motion.
Cross-Dataset Activity Recognition via Adaptive Spatial-Temporal Transfer Learning
Authors: Qin Xin , Chen Yiqiang , Wang Jindong , Yu Chaohui
Published: December 2019

Human activity recognition (HAR) aims at recognizing activities by training models on the large quantity of sensor data. Since it is time-consuming and expensive to acquire abundant labeled data, transfer learning becomes necessary for HAR by transferring knowledge from existing domains. However, there are two challenges existing in cross-dataset activity recognition. The first challenge is source domain selection. Given a target task and several available source domains, it is difficult to determine how to select the most similar source domain to the target domain such that negative transfer can be avoided. The second one is accurately activity transfer. After source domain selection, how to achieve accurate knowledge transfer between the selected source and the target domain remains another challenge. In this paper, we propose an Adaptive Spatial-Temporal Transfer Learning (ASTTL) approach to tackle both of the above two challenges in cross-dataset HAR. ASTTL learns the spatial features in transfer learning by adaptively evaluating the relative importance between the marginal and conditional probability distributions. Besides, it captures the temporal features via incremental manifold learning. Therefore, ASTTL can learn the adaptive spatial-temporal features for cross-dataset HAR and can be used for both source domain selection and accurate activity transfer. We evaluate the performance of ASTTL through extensive experiments on 4 public HAR datasets, which demonstrates its effectiveness. Furthermore, based on ASTTL, we design and implement an adaptive cross-dataset HAR system called Client-Cloud Collaborative Adaptive Activity Recognition System (3C2ARS) to perform HAR in the real environment. By collecting activities in the smartphone and transferring knowledge in the cloud server, ASTTL can significantly improve the performance of source domain selection and accurate activity transfer.
DrawingPresence
Authors: Mai Christian , Thiem Niklas , Hussmann Heinrich
Published: December 2019

One of the main measures to evaluate a head-mounted display (HMD) based experience is the state of feeling present in virtual reality (VR). The detection of disturbances of such an experience that occur over time, namely breaks in presence (BIP), enables the evaluation and improvement of these. Existing methods do not detect BIPs, e.g., questionnaires, or are complex in their application and evaluation, e.g., physiological and behavioral measures. We propose a handy post-experience method in which users reflect on their experienced state of presence by drawing a line in a paper-based drawing template. The amplitude of the drawn line represents the state of presence of the temporal progress of the experience. We propose a descriptive model that describes temporal variations in the drawings by the definition of relevant points over time, e.g., putting on the HMD, phases of the experience, transition into VR, and parameters, e.g., the transition time. The descriptive model enables us to objectively evaluate user drawings and represent the course of the drawings by a defined set of parameters. Our exploratory user study (N = 30) showed that the drawings are very consistent between participants and the method is able to securely detect a variety of BIPs. Moreover, the results indicate that the method might be used in the future to evaluate the strength of BIPs and to reflect the temporal course of a presence experience in detail. Additional application examples and a detailed discussion pave the way for others to use our method. Further, they serve as a motivation to continue working on the method and the general understanding of temporal fluctuations of the presence experience.
Design and Evaluation of DIO Construction Toolkit for Co-making Shared Constructions
Authors: Arora Jatin , Mathur Kartik , Goel Manvi , Kumar Piyush , Mishra Abhijeet , Parnami Aman
Published: December 2019

We present the design and implementation of DIO, a novel digital-physical construction toolkit to enable constructionist learning for children from age group 8-12 years. The toolkit comprises of dome-shaped (D) tangible modules with various attachments that allow suspension on the body of multiple children and/or in the environment to support a variety of sensing/input (I), actuation/output (O) functionalities. The modules are enabled for wireless communication and can be linked together using an Augmented Reality based programming interface running on a smartphone. The smartphone recognizes our hemispherical modules omnidirectionally through novel computer vision based 3D patterns; custom made to provide logical as well as semantic encoding. In this paper, we show how, owing to its unique form-factor, the toolkit enables multi-user constructions for the children and offers a shared learning experience. We further reflect on our learning from a one-year long iterative design process and contribute a social scaffolding based procedure to engage children with such constructionist toolkits effectively.
Acute mountain sickness: Do different time courses point to different pathophysiological mechanisms?
Authors: Berger Marc M. , Sareban Mahdi , Bärtsch Peter
Published: December 2019

Acute mountain sickness (AMS) is a syndrome of nonspecific symptoms (i.e., headache, anorexia, nausea, vomiting, dizziness, and fatigue) that may develop in nonacclimatized individuals after rapid exposure to altitudes ≥2,500 m. In field studies, mean AMS scores usually peak after the first night at a new altitude. Analyses of the individual time courses of AMS in four studies performed at 3,450 m and 4,559 m revealed that three different patterns are hidden in the above-described overall picture. In 41% of those who developed AMS (i.e., AMS-C score >0.70), symptoms peaked on day 1, in 39%, symptoms were most prominent on day 2, and in 20%, symptoms were most prominent on day 3. We suggest to name the different time courses of AMS type I, type II, and type III, respectively. Here, we hypothesize that the variation of time courses of AMS are caused by different pathophysiological mechanisms. This assumption could explain why no consistent correlations between an overall assessment of AMS and single pathophysiological factors have been found in a large number of studies over the past 50 yr. In this paper, we will briefly review the fundamental mechanisms implicated in the pathophysiology of AMS and discuss how they might contribute to the three different AMS time courses.
Useful Irregularity Indices in QSPR Study for Bismuth Tri-Iodide
Authors: Virk Abaid ur Rehman , Rehman M. A. , Shi Ce , Nazeer Waqas
Published: December 2019

Topological indices give us a mathematical language to study molecular structures. They convert a chemical compound into a single number which foresees properties, for example, boiling points, viscosity, and the radius of gyrations. Drugs and other chemical compounds are often modeled as various polygonal shapes, trees, and graphs. In this paper, we will compute some irregularity indices for bismuth tri-iodide chain and sheet that are useful in the quantitative structure-activity relationship.
Wenxin Granules Influence the TGFβ-P38/JNK MAPK Signaling Pathway and Attenuate the Collagen Deposition in the Left Ventricle of Myocardial Infarction Rats
Authors: Huang Ya , Wu Aiming , Lou Lixia , Zhang Dongmei , Nie Bo , Zhao Yizhou , Liu Keke , Zhao Mingjing , Shang Hongcai
Published: December 2019

Background. A large number of proinflammatory/anti-inflammatory cytokines are produced in the extracellular matrix (ECM) after myocardial infarction (MI), and the inflammatory pathways activated by these inflammatory stimuli are involved in the regulation of lesions with excessive accumulation of ECM. Wenxin granules can play a protective role against MI, but the mechanism of its effect on the inflammatory pathway and ECM collagen expression is still unclear. Objective. To verify the effect of Wenxin granules on the inflammatory pathway and collagen expression after MI. Method. The proximal left anterior descending coronary artery in rats was ligated to induce acute MI. Then, animals were randomly assigned to the model group, the Carvedilol group, and the Wenxin Granules group. In addition, sham operation rats were used as the control group. 10 rats were allocated in each group. Gavage was given once a day for 4 weeks. The changes of cardiac hemodynamics were detected by the catheter method, morphological changes were observed by HE staining, and myocardial tissue collagen volume was counted by Immunohistochemistry combined with Masson staining, and the expression of inflammatory TGFβ-p38/JNK MAPK signal pathway markers was detected by Western blot. Results. Wenxin granules could significantly improve the hemodynamics, so that the fibrosis scar was relatively dense and uniform, and the residual myocardium was relatively neat, while Collagen type I and III volume and TGFβ expression levels were lessened. Although there were no differences in the expression of CTGF, p38, and JNK proteins, their phosphorylation levels showed significant differences. Conclusion. Wenxin granules can affect the inflammation-related TGFβ-p38/JNK MAPK signaling pathway and change the structural properties of myocardium and scar after MI by attenuated collagen deposition in the left ventricular myocardial tissue to improve cardiac function.
Influence of Pore Structure on Chloride Penetration in Cement Pastes Subject to Wetting-Drying Cycles
Authors: Chang Honglei , Zuo Zhiwu , Qu Mingyue , Wang Fei , Ge Zhi , Liu Jian
Published: December 2019

Copious studies have discovered a phenomenon that a chloride concentration peak appears on the surface of concrete under cyclic drying-wetting environments. In such cases, the chloride diffusion coefficient (D) obtained through directly fitting the standard error function of Fick’s second law is no longer accurate. The more reliable D obtained by the method proposed by Andrade is employed in this research to investigate the influence of pore structure on chloride penetration rate of pastes. The results show that both the effective coefficient (Deff) and the apparent coefficient (Dapp) increase with total porosity, the most probable pore size, and water absorption porosity, suggesting that the increase of the three pore structure parameters accelerates chloride penetration rate under cyclic wetting-drying condition. The increase of the three parameters makes more room available and eases the difficulty for salt solution to enter the matrix and thus leads to the augmentation of chloride transporting in matrix.
Endogenous Bufadienolides, Fibrosis and Preeclampsia
Authors: Reznik Vitaliy A. , Kashkin Vladimir A. , Agalakova Natalia I. , Adair C. David , Bagrov Alexei Y.
Published: December 2019

Frequency of preeclampsia has no tendency to decrease, and it still takes the leading position in the structure of maternal mortality and morbidity worldwide. In this review, we present the “fibrotic concept” of the etiology and pathogenesis of preeclampsia which involves system consisting of Na/K-ATPase and its endogenous ligands including marinobufagenin. New therapy of preeclampsia includes modulation of the Na/K-ATPase system by immunoneutralization of the marinobufagenin and use of mineralocorticoid antagonists which are capable to impair marinobufagenin-Na/K-ATPase interactions.
A Case of Diffuse Alveolar Hemorrhage Associated with High-Titer of MPO-ANCA Demonstrating Cytoplasmic Staining Pattern
Authors: Ben Gabr Jihad , Kato Hiroshi
Published: December 2019

Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of ANCA-associated vasculitis (AAV) that requires urgent recognition and treatment. A presumptive diagnosis is often rendered without histopathology if concordant positivity of ANCA by indirect immunofluorescence (IIF) and ELISA assays, i.e., P-ANCA+/myeloperoxidase (MPO) Ab+ or C-ANCA+/proteinase-3 (PR3) Ab+, is documented in the context of pulmonary-renal syndrome or rapidly progressive glomerulonephritis. In this respect, the discordance between IIF and ELISA assays poses a diagnostic challenge in the absence of convincing histopathology and involves the risks of delaying the implementation of timely immunosuppressive therapy. Here, we report a 74-year-old woman who developed DAH and was found to have a high titer of MPO-ANCA exhibiting cytoplasmic staining on IIF, i.e., MPO-C-ANCA. The literature suggests that the availability of distinct epitopes on the MPO molecule dictates the perinuclear versus cytoplasmic staining pattern, which potentially explains the discordance between ELISA and IIF assays. Her DAH was controlled in association with seven sessions of plasmapheresis, methylprednisolone 1 gram daily for 3 days followed by 1 mg/kg/day, and rituximab. This case exemplifies the importance of consideration of pretest probability of suspected diagnosis that would realize a plausible interpretation of seemingly inconsistent serological profile and its effective incorporation into the diagnostic reasoning.
Increased Tissue Penetration of Doxorubicin in Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) after High-Intensity Ultrasound (HIUS)
Authors: Khosrawipour Veria , Reinhard Sören , Martino Alice , Khosrawipour Tanja , Arafkas Mohamed , Mikolajczyk Agata
Published: December 2019

Background. High‐intensity ultrasound (HIUS) has been studied for the past two decades as a new therapeutic option for solid tumor direct treatment and a method for better chemotherapy delivery and perfusion. This treatment approach has not been tested to our knowledge in peritoneal metastatic therapy, where limited tissue penetration of intraperitoneal chemotherapy has been a main problem. Both liquid instillations and pressurized aerosols are affected by this limitation. This study was performed to evaluate whether HIUS improves chemotherapy penetration rates. Methods. High-intensity ultrasound (HIUS) was applied for 0, 5, 30, 60, 120, and 300 seconds on the peritoneal tissue samples from fresh postmortem swine. Samples were then treated with doxorubicin via pressurized intraperitoneal aerosol chemotherapy (PIPAC) under 12 mmHg and 37°C temperature. Tissue penetration of doxorubicin was measured using fluorescence microscopy on frozen thin sections. Results. Macroscopic structural changes, identified by swelling of the superficial layer of the peritoneal surface, were observed after 120 seconds of HIUS. Maximum doxorubicin penetration was significantly higher in peritoneum treated with HIUS for 300 seconds, with a depth of 962.88 ± 161.4 μm (p < 0.05). Samples without HIUS had a penetration depth of 252.25 ± 60.41. Tissue penetration was significantly increased with longer HIUS duration, with up to 3.8-fold increased penetration after 300 sec of HIUS treatment. Conclusion. Our data indicate that HIUS may be used as a method to prepare the peritoneal tissue for intraperitoneal chemotherapy. Higher tissue penetration rates can be achieved without increasing chemotherapy concentrations and preventing structural damage to tissue using short time intervals. More studies need to be performed to analyze the effect of HIUS in combination with intraperitoneal chemotherapy.
High-Frequency Repetitive Transcranial Magnetic Stimulation Could Improve Impaired Working Memory Induced by Sleep Deprivation
Authors: Guo Zhiwei , Jiang Zhijun , Jiang Binghu , McClure Morgan A. , Mu Qiwen
Published: December 2019

Objective. To investigate whether and how the working memory impairment induced by sleep deprivation (SD) could be recovered by using repetitive transcranial magnetic stimulation (rTMS), as well as to clarify the corresponding brain activity changes. Methods. Seventeen healthy adults received one session of 5.0 Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) following 24 hours of SD. Resting state functional magnetic resonance imaging (fMRI) and working memory test were performed during a rested waking period, after SD and rTMS. The amplitude of low-frequency fluctuations (ALFF) was used to detect the spontaneous neural activity changes after both SD and rTMS. The relationship between ALFF and the performance of working memory was also assessed by using correlation analysis. Results. After SD, the participants exhibited lower response accuracies and longer reaction times on the working memory tests of letters and numbers. The decreased response accuracy of numbers was significantly improved after rTMS similarly to the state of the rested waking period after a normal night of sleep. ALFF values decreased from the rested waking period state to the state of SD in the brain regions involving the frontal gyrus, precuneus, angular gyrus, and parietal lobe which showed significantly increased ALFF after rTMS. Furthermore, significantly positive correlations were observed between changes of response accuracy and the changes of ALFF value of the inferior frontal gyrus and supramarginal gyrus. Conclusion. These results indicate that high-frequency rTMS applied over left DLPFC may contribute to the recovery of the impaired working memory after SD by modulating the neural activity of related brain regions.
Plant Sterol Ester of α-Linolenic Acid Attenuates Nonalcoholic Fatty Liver Disease by Rescuing the Adaption to Endoplasmic Reticulum Stress and Enhancing Mitochondrial Biogenesis
Authors: Han Hao , Guo Yan , Li Xiaoyu , Shi Dongxing , Xue Tingli , Wang Linqi , Li Yanyan , Zheng Mingming
Published: December 2019

Nonalcoholic fatty liver disease (NAFLD) is becoming more common in the world and is presenting a great challenge concerning prevention and treatment. Plant sterol ester of α-linolenic acid (PS-ALA) has a potential benefit to NAFLD. To examine the effect of PS-ALA on NAFLD, C57BL/6J mice were given a control diet, high fat and high cholesterol diet (HFD), and HFD plus 2% PS, 1.3% ALA, or 3.3% PS-ALA for 16 weeks. Our results showed that PS-ALA treatment suppressed hepatic steatosis, ameliorated lipid disorder, attenuated inflammatory response, and inhibited oxidative stress. In the molecular level, PS-ALA downregulated high transcriptional and translational levels of endoplasmic reticulum (ER) stress markers (Grp78 and Chop) leading to decreased protein expression of transcription factor and key enzymes involved in de novo lipogenesis (Srebp-1c and Fas) and cholesterol synthesis (Srebp-2 and Hmgcr). In parallel, PS-ALA blocked Nlrp3 activation and reduced release of IL-1β and IL-18 via inhibiting ER stress-induced sensitization of unfolded protein response sensors (Ire1α and Xbp1s). Finally, PS-ALA improved HFD-induced mitochondrial damage and fatty acid accumulation as exhibited by higher protein and mRNA expression of key genes administering mitochondrial biogenesis (Pgc-1α, Nrf1, and Tfam) and fatty acid β-oxidation (Pparα and Cpt1a). In conclusion, our study originally demonstrated that PS-ALA rescued ER stress, enhanced mitochondrial biogenesis, and thus ameliorated NAFLD.
Electric Vehicles and Storage Systems Integrated within a Sustainable Urban District Fed by Solar Energy
Authors: Bracco Stefano , Delfino Federico , Longo Michela , Siri Silvia
Published: December 2019

In this paper, an optimization model is defined for the design of a smart energy infrastructure integrating different technologies to satisfy the electrical demand of a given site. The considered smart energy infrastructure includes a photovoltaic plant, electrical storage systems, electric vehicles (EVs), and charging stations. The objective function of the optimization model considers the costs related to the installation and maintenance of the considered technologies, as well as the costs associated with the energy exchanges with the external grid. A very extensive numerical analysis is reported in the paper, referred to a test case in a real site in Liguria Region, in the north of Italy. Many scenarios are analyzed and discussed, with specific attention to evaluate the role of electric mobility within a smart energy infrastructure and a focus on EVs acting as mobile storage systems.
Preclinical Assessment with Clinical Validation of Selinexor with Gemcitabine and Nab-Paclitaxel for the Treatment of Pancreatic Ductal Adenocarcinoma
Authors: Azmi Asfar S. , Khan Husain Yar , Muqbil Irfana , Aboukameel Amro , Neggers Jasper E. , Daelemans Dirk , Mahipal Amit , Dyson Gregory , Kamgar Mandana , Al-Hallak Mohammad Najeeb , Tesfaye Anteneh , Kim Steve , Shidham Vinod , M. Mohammad Ramzi , Philip Philip A.
Published: December 2019

Purpose:

Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease urgently requiring new treatments. Overexpression of the protein transporter exportin-1 (XPO1) leads to mislocalization of tumor-suppressor proteins (TSP) and their inactivation. Earlier, we showed that blocking XPO1 by CRISPR/Cas9 validated Selective Inhibitor of Nuclear Export (SINE) compounds (selinexor and analogs) restores the antitumor activity of multiple TSPs leading to suppression of PDAC in vitro and in orthotopic models.

Experimental Design:

We evaluate the synergy between SINE compounds and standard-of-care treatments in preclinical models and in a PDAC Phase Ib trial.

Results:

SINE compounds synergize with gemcitabine (GEM) and nanoparticle albumin–bound (nab)-paclitaxel leading to suppression of PDAC cellular growth and cancer stem cell (CSC) spheroids disintegration. Label-free quantitative proteome profiling with nuclear and cytoplasmic enrichment showed superior enhancement in nuclear protein fraction in combination treatment. Selinexor inhibited the growth of PDAC CSC and two patient-derived (PDX) subcutaneous xenografts. Selinexor–GEM–nab-paclitaxel blocked PDX and orthotopic tumor growth. In a phase 1b study (NCT02178436), 9 patients were exposed to selinexor (60 mg oral) with GEM (1,000 mg/m2 i.v.) and nab-paclitaxel (125 mg/m2 i.v.) on days 1, 8, and 15 of 28-day cycle. Two patients showed partial response, and 2 had stable disease. An outstanding, durable objective response was observed in one of the responders with progression-free survival of 16 months and overall survival of 22 months.

Conclusions:

Our preclinical and ongoing clinical study lends support to the use of selinexor–GEM–nab-paclitaxel as an effective therapy for metastatic PDAC.
Pulmonary Vein Isolation With a Novel Multielectrode Radiofrequency Balloon Catheter That Allows Directionally Tailored Energy Delivery
Authors: Reddy Vivek Y. , Schilling Richard , Grimaldi Massimo , Horton Rodney , Natale Andrea , Riva Stefania , Tondo Claudio , Kuck Karl-Heinz , Neuzil Petr , McInnis Kendra , Bishara Moe , Zhang Baohui , Govari Assaf , Abdelaal Ahmed , Mansour Moussa
Published: December 2019

Background:

Balloon catheters facilitate pulmonary vein (PV) isolation, but current technology is limited by either a single ablative element, potentially leading to over-ablation of thin and under-ablation of thick tissue, or prolonged procedure times. Visualized by electroanatomical mapping, a novel compliant radiofrequency balloon catheter with 10 irrigated, flexible electrodes can simultaneously and independently deliver energy. Herein, we evaluated the feasibility, safety, and short-term efficacy of this radiofrequency balloon in a multicenter, single-arm, first-in-human study.

Methods:

Paroxysmal atrial fibrillation patients underwent PV isolation with the radiofrequency balloon delivered over-the-wire with a deflectable 13.5F sheath. Radiofrequency energy is delivered simultaneously from all electrodes—up to 30 s posteriorly and 60 s anteriorly. Esophageal temperature was monitored in all patients; the esophagus was also mechanically deviated in 10 patients.

Results:

At 4 sites, 39 patients were treated by 9 operators. The radiofrequency balloon isolated all targeted PVs (152/152), 79.6% with a single application. Electrical reconnection occurred in only 7/150 PVs (4.7%) on adenosine/isoproterenol challenge. Mean procedure, balloon dwell, and fluoroscopy times were 101.6, 40.5, and 17.4 min, respectively. Esophagogastroduodenoscopy revealed asymptomatic esophageal erythema in 5 patients. Phrenic nerve palsy occurred in a patient in whom phrenic pacing was inadvertently omitted. At 3 months, imaging revealed no PV stenosis, and early atrial arrhythmia recurrence occurred in only 10/39 (25.6%) patients.

Conclusions:

The compliant radiofrequency balloon can directionally tailor energy delivery for efficient, effective, and reasonably safe acute PV isolation.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: ISRCTN 11764506.
Echocardiographic Assessment of Cardiac Function in Pediatric Survivors of Anthracycline-Treated Childhood Cancer
Authors: Slieker Martijn G. , Fackoury Cheryl , Slorach Cameron , Hui Wei , Friedberg Mark K. , Fan Chun-Po Steve , Manlhiot Cedric , Dillenburg Rejane , Kantor Paul , Mital Seema , Liu Peter , Nathan Paul C. , Mertens Luc ,   on behalf of the PCS2 Working Group*, Greenberg Mark , Hodgson David , Barr Ronald , Marjerrison Stacey , Lougheed Jane , Bassal Mylene , Rosenberg Herschel , Zelcer Shayna , Sender Leonard
Published: December 2019

Background:

Anthracycline-induced cardiotoxicity is a major cause of morbidity and mortality in childhood cancer survivors (CCSs). Echocardiographic myocardial strain imaging is recommended in adult patients with cancer, but its role in pediatric CCSs has not been well established. Aims of this study were to determine the prevalence of abnormalities in left ventricular strain in pediatric CCSs, to compare strain with other echocardiographic measurements and blood biomarkers, and to explore risk factors for reduced strain.

Methods:

CCSs ≥3 years from their last anthracycline treatment were enrolled in this multicenter study and underwent a standardized functional echocardiogram and biomarker collection. Regression analysis was used to identify factors associated with longitudinal strain (LS).

Results:

Five hundred forty-six pediatric CCSs were compared with 134 healthy controls. Abnormal left ventricular ejection fraction (<50%) and mean LS (
Z
score, <−2) was found in 0.8% and 7.7% of the CCSs, respectively. LS was significantly lower in CCSs than in controls, but the absolute difference was small (0.7%). Lower LS in CCSs was associated with older current age and higher body surface area. Sex, cumulative anthracycline dose, radiotherapy, and biomarkers were not independently associated with LS. Circumferential strain, diastolic parameters, and biomarkers were not significantly different in pediatric CCSs.

Conclusions:

Global systolic function and LS are only mildly reduced in pediatric CCSs, and most LS values are within normal range. This makes single LS measurements of limited added value in identifying CCSs at risk for cardiac dysfunction. The utility of strain imaging in the long-term follow-up of CCS remains to be demonstrated.