bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydraulic‐Mechanical Coupling Model with Dual‐Porosity Dual‐Permeability for Anisotropy Coal Seams and Its Application in Mine Gas Extraction
Authors: Huo Bingjie , Jing Xuedong , He Aiping , Fan Chaojun
Published: August 2019

The parameters of pore‐fracture structure and permeability have a controlling effect on the behaviors of gas adsorption/desorption and transportation in coal reservoir. A mathematic model for coal seams is of great significance to evaluate the mass migration within the coal fracture‐matrix system. In this paper, the hydraulic‐mechanical coupling model considering both dual‐porosity dual‐permeability and anisotropy characteristics is first established by using the methods of theoretical analysis, nuclear magnetic resonance (NMR) test, and numerical simulation. Then, this model is applied to simulate the gas migration characteristics of No. 3 coal seam in Changping Mine, China. Results show that the pore structure of No. 3 coal seam is characterized by small radius of pores and pore throats, which is determined by the NMR test, verifying the dual‐permeability dual‐porosity of coal seams. Both matrix permeability and fracture permeability increase approximately linearly with the process of mine gas extraction. The increased magnitude of the matrix permeability is greater than that of the fracture permeability. The permeability is inversely proportional to the anisotropy coefficient. The pressure gradient within the coal matrix and fracture increases first and then decreases with the extraction time. This pressure gradient is proportional to the anisotropy coefficient at the early stage of extraction and is inversely proportional to the anisotropy coefficient at the later stage. The seepage and diffusion flux are proportional to the anisotropy coefficient. The proportion of matrix‐to‐fracture seepage flux to the total flux increases first and then decreases to a certain value. The proposed model provides a guide for accurate designation of gas extraction from coal seams.
Behavior of the Correction Equations in the Jacobi–Davidson Method
Authors: Kong Yuan , Fang Yong
Published: August 2019

The Jacobi–Davidson iteration method is efficient for computing several eigenpairs of Hermitian matrices. Although the involved correction equation in the Jacobi–Davidson method has many developed variants, the behaviors of them are not clear for us. In this paper, we aim to explore, theoretically, the convergence property of the Jacobi–Davidson method influenced by different types of correction equations. As a by‐product, we derive the optimal expansion vector, which imposed a shift‐and‐invert transform on a vector located in the prescribed subspace, to expand the current subspace.
Controlled Gold Nanoparticle Placement into Patterned Polydimethylsiloxane Thin Films via Directed Self-Assembly
Authors: Berry Keith R. , Romo Ricardo L. , Mitchell Megan , Bejugam Vinith , Roper D. Keith
Published: August 2019

An economically scalable and reproducible method to assemble nanoparticles (NPs) into ordered arrays with high fidelity remains a fundamental roadblock. Methods like directed self-assembly have shown the highest promise resulting in >85% density of NP-filled prepatterned polymer cavities. This work refines directed self-assembly by controlling the evaporation rate, substrate velocity (deposition rate), and NP diameter resulting in reproducible fabrication of ordered arrays with areas >2 mm×2 mm and ~100% density of filled cavities. Measured optical spectra showed a blueshift in the localized surface plasmon resonance (LSPR) and surface lattice resonance (SLR) peaks with increasing NP density for both 100 and 150 nm gold (Au) NPs. Discrete dipole approximation (DDA), coupled dipole approximation (CDA), rapid semi-analytical CDA (rsa-CDA), and Mie theory simulations closely matched extinction per nanoparticle (extinction/NP) calculations for measured extinction spectra. An ordered array containing 150 nm AuNPs was used for comparison with rsa-CDA estimates using both polydimethylsiloxane (PDMS) and glass refractive indices (RI) resulting in peak location estimates within 1.7% and comparable relative increases in peak heights. Both the measured and simulated SLR peak heights were shown to significantly increase when the array was on glass as opposed to within PDMS.
Practical Aspects for the Integration of 5G Networks and IoT Applications in Smart Cities Environments
Authors: Minoli Daniel , Occhiogrosso Benedict
Published: August 2019

Both 5G cellular and IoT technologies are expected to see widespread deployment in the next few years. At the practical level, 5G will see initial deployments in urban areas. This is perhaps fortuitous from an IoT perspective, since many “mainstream” applications of IoT will support Smart Cities, Smart Campuses and Smart Buildings. Bandwidth demand for a number of Smart City applications is the main driver for enhanced mobile broadband (eMBB)-based 5G services in general, and new-generation 5G IoT applications, in particular. In turn, the use of the millimeter wave spectrum is required to enable 5G cellular technologies to support high data rates. Millimeter wave solutions, however, impose a requirement for small cells. Generally, an implementer tries to use one or a small handful of IoT technologies; preferably, and for managerial simplicity, the implementer would want to use a cellular/5G IoT technology for all nodes, whether indoors or outdoors, instead of a heterogenous mix of various IoT technologies that have evolved over the years. This overview paper discusses a number of practical issues related to 5G-based IoT applications, particularly in Smart City environments, including the need for small cells, the transmission issues at millimeter wave frequencies, building penetration issues, the need for Distributed Antenna Systems, and the near term introduction of pre-5G IoT technologies such as NB-IoT and LTE-M, these being possible proxies for the commercial deployment and acceptance of 5G IoT.
Evaluation of Contrast-Enhanced Intraoperative Ultrasound in the Detection and Management of Liver Lesions in Patients with Hepatocellular Carcinoma
Authors: Pace Cristina , Nardone Vittorio , Roma Silvia , Chegai Fabrizio , Toti Luca , Manzia Tommaso Maria , Tisone Giuseppe , Orlacchio Antonio
Published: August 2019

Aim. To evaluate the role of contrast-enhanced intraoperative ultrasound (CE-IOUS) during liver surgery in the detection and management of liver lesions in patients with hepatocellular carcinoma (HCC). Materials and Methods. From December 2016 to December 2017, 50 patients with HCC, who were candidates for liver resection, were evaluated with intraoperative ultrasound (IOUS). For all patients, MRI and/or CT were performed before surgery. During surgery, IOUS was performed after liver mobilization, and when nodules that had not been detected in the preoperative MRI and/or CT were observed, CE-IOUS scans were carried out with the dual purpose of better characterizing the unknown lesion and discovering new lesions. Results. In 12 patients, IOUS showed 14 nodules not detected by preoperative MRI and/or CT, before surgery. Out of the 12 lesions, five presented vascular features compatible with those of malignant HCC to the evaluation with CE-IOUS and four of these were simultaneously treated with intraoperative radiofrequency ablation (RFA). The fifth lesion was resected by the surgeon. The remaining nine lesions recognized by IOUS were evaluated as benign at CE-IOUS and considered regenerative nodules. The last diagnosis was confirmed during follow-up obtained by means of CT and/or MRI after 1, 3, 6, or 12 months. Conclusion. In our experience, CE-IOUS is a useful diagnostic tool in both benign pathologies, such as regenerative nodules, and malignant liver lesions. The advantage of this approach is the possibility of intraoperatively characterizing, based on vascularization patterns, lesions that could not be diagnosed by preoperative imaging, resulting in modification of the surgical therapy decision and expansion of the resection or intraoperative ablation.
The Dynamics of Sea Tide-Induced Fluctuations of Groundwater Level and Freshwater-Saltwater Interface in Coastal Aquifers: Laboratory Experiments and Numerical Modeling
Authors: Levanon Elad , Gvirtzman Haim , Yechieli Yoseph , Oz Imri , Ben-Zur Elad , Shalev Eyal
Published: August 2019

Laboratory experiments were conducted in a vertical, two-dimensional, rectangular flow tank, simulating the response of a phreatic coastal aquifer to a sea tide. Imposed sinusoidal fluctuations of the saltwater level at one side of the flow tank caused three types of fluctuations: (a) hydraulic head throughout the aquifer, (b) saturation degree within the capillary fringe, and (c) salt concentration surrounding the freshwater-saltwater interface (FSI), all recorded by head, saturation, and salinity sensors, respectively. Significant time lags were observed both in the saturation degree within the unsaturated zone and in the salinity within the FSI. All measured values, recorded by the three types of sensors, were simulated and reproduced using a numerical model. The calibrated model was used for mapping the time lags throughout the aquifer. It was found that the time lag of saturation fluctuations within the unsaturated zone increased upward from the groundwater level as the unsaturated hydraulic conductivity decreased. Similarly, the time lag of salinity fluctuations within the FSI increased downward, with distance from the groundwater level. We interpret the low hydraulic conductivity at the capillary zone as the source of attenuation of both saturation and salinity, because both are controlled by the vertical advection of the whole freshwater body. This advection is significantly slower compared to the dynamics of pressure diffusion. The uniqueness of this study is that it provides quantitative data on the attenuation at the capillary zone and its effect on the salinity time lag in coastal aquifer systems.
Combined Exercise Training Performed by Elderly Women Reduces Redox Indexes and Proinflammatory Cytokines Related to Atherogenesis
Authors: Bachi André L. L. , Barros Marcelo P. , Vieira Rodolfo P. , Rocha Gislene A. , de Andrade Paula B. M. , Victorino Angélica B. , Ramos Luiz R. , Gravina Claudia F. , Lopes José D. , Vaisberg Mauro , Maranhão Raul C.
Published: August 2019

Cardiovascular benefits for the general population of combined aerobic-resistance exercise training are well-known, but the impact of this exercise training modality on the plasma lipid, inflammatory, and antioxidant status in elderly women that are exposed to a great risk of developing ischemic cardio- and cerebrovascular diseases has not been well investigated. So, we aimed to evaluate the plasma lipids, oxidative stress, and inflammatory cytokines in 27 elderly women (TRAINED group,69.1±8.1 yrs) that were performing moderate intensity combined aerobic-resistance exercise training (3 times/week for at least 18 months) and in 27 sedentary elderly women (SED group,72.0±6.4 yrs), not submitted to exercise training for at least 5 yrs. Our results showed that BMI was lower in the TRAINED group than in the SED group (25.1±3.2vs.28.7±5.1,p<0.05). The TRAINED group had lower glycemia (92±3vs.118±12,p<0.05), glycated hemoglobin (5.9±0.1vs.6.4±0.2,p<0.05), and triglycerides (98 (75-122) vs. 139 (109-214),p<0.01); equal total cholesterol (199 (175-230) vs. 194 (165-220)), LDL-cholesterol (108 (83-133) vs. 109 (98-136)), and non-HDL-cholesterol (54 (30-74) vs. 62 (26-80)); and also higher HDL-cholesterol (64 (52-77) vs. 52 (44-63),p<0.01) and LDL-C/oxLDL ratio (13378±2570vs.11639±3113,p<0.05) compared to the SED group. Proinflammatory cytokines as IL-1β(11.31±2.4vs.28.01±4.7,p<0.05), IL-6 (26.25±7.4vs.49.41±17.8,p<0.05), and TNF-α(25.72±2.8vs.51.73±4.2,p<0.05) were lower in the TRAINED group than in the SED group. The TRAINED group had lower total peroxides (26.3±7.4vs.49.0±17.8,p<0.05) and oxidized LDL (1551±50.33vs.1773±74,p<0.02) and higher total antioxidant capacity (26.25±7.4vs.49.41±17.8,p<0.001) compared to the SED group. In conclusion, in TRAINED women, BMI was lower, plasma lipid profile was better, plasma oxidative stress was diminished, and there was less expression of proinflammatory interleukins than in SED, suggesting that combined aerobic-resistance exercise training may promote the protection against the complications of ischemic cardio- and cerebrovascular disease in elderly women.
Detecting Shilling Attacks with Automatic Features from Multiple Views
Authors: Hao Yaojun , Zhang Fuzhi , Wang Jian , Zhao Qingshan , Cao Jianfang
Published: August 2019

Due to the openness of the recommender systems, the attackers are likely to inject a large number of fake profiles to bias the prediction of such systems. The traditional detection methods mainly rely on the artificial features, which are often extracted from one kind of user-generated information. In these methods, fine-grained interactions between users and items cannot be captured comprehensively, leading to the degradation of detection accuracy under various types of attacks. In this paper, we propose an ensemble detection method based on the automatic features extracted from multiple views. Firstly, to collaboratively discover the shilling profiles, the users’ behaviors are analyzed from multiple views including ratings, item popularity, and user-user graph. Secondly, based on the data preprocessed from multiple views, the stacked denoising autoencoders are used to automatically extract user features with different corruption rates. Moreover, the features extracted from multiple views are effectively combined based on principal component analysis. Finally, according to the features extracted with different corruption rates, the weak classifiers are generated and then integrated to detect attacks. The experimental results on the MovieLens, Netflix, and Amazon datasets indicate that the proposed method can effectively detect various attacks.
Finite-Time Control of One Dimensional Crowd Evacuation System
Authors: Qin Wei , Cui Baotong , Jiang Zhengxian
Published: August 2019

This paper pertains to the study of finite-time control of one dimensional crowd evacuation system. Benefiting from the research of fluid dynamics and vehicle traffic, a one dimensional crowd evacuation system is constructed, whose density-velocity relationship is represented by a diffusion model. In order to deal with the nondirectionality of crowd movement, the free flow speed is chosen as a control variable. Since the control variable is included in a partial derivative, it increases the difficulty of designing the controller. In this paper, finite-time controller is designed, which not only guarantees the effective evacuation, but also obtains the estimation of evacuation time. Then, finite-time tracking problem is solved, which makes the density converge to a given density. Finally, numerical examples illustrate the effectiveness of the controllers.
Retinal Vasculature and Microstructure in Early Dry-Type Myopic Maculopathy
Authors: Sun Jiao , Wang Jialin , Wang Yanling
Published: August 2019

Purpose. The aim of this cross-sectional study was to characterize and compare the retinal vasculature and microstructure in patients with early dry-type myopic maculopathy. Methods. Patients with a refractive error of less than −6 diopters were enrolled and classified into two groups. Group 1 comprised 82 eyes with a tessellated fundus, and group 2 comprised 56 eyes with diffuse chorioretinal atrophy (DCA). The clinical characteristics, refractive error, axial length, retinal vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), macular choroidal thickness, and best-corrected visual acuity (BCVA), were compared between the groups. Logistic regression was used to determine the protective and risk factors for DCA. Results. Group 1 patients were significantly younger and had better BCVA, less myopia, and shorter axial length than group 2 patients. The vessel densities of the SCP and DCP, choroidal thickness, retinal nerve fiber layer thickness, ganglion cell complex thickness, and retinal thickness were reduced in group 2. Multiple logistic regression analysis revealed that the vessel densities of the SCP and DCP were protective factors for DCA. Conclusions. The vessel density of the SCP had the highest diagnostic value (sensitivity = 78.0% and specificity = 96.6%). When the SCP vessel density was reduced to ≤49.98%, DCA was indicated. The retinal vessel densities of the SCP and DCP and parameters of the microstructure were reduced significantly in patients with DCA. Vessel density may be a better diagnostic indicator of the development of DCA.
Mathematical Modeling and Discrete Firefly Algorithm to Optimize Scheduling Problem with Release Date, Sequence‐Dependent Setup Time, and Periodic Maintenance
Authors: Qamhan Mustafa A. , Qamhan Ammar A. , Al-Harkan Ibrahim M. , Alotaibi Yousef A.
Published: August 2019

An evolutionary discrete firefly algorithm (EDFA) is presented herein to solve a real‐world manufacturing system problem of scheduling a set of jobs on a single machine subject to nonzero release date, sequence‐dependent setup time, and periodic maintenance with the objective of minimizing the maximum completion time “makespan.” To evaluate the performance of the proposed EDFA, a new mixed‐integer linear programming model is also proposed for small‐sized instances. Furthermore, the parameters of the EDFA are regulated using full factorial analysis. Finally, numerical experiments are performed to demonstrate the efficiency and capability of the EDFA in solving the abovementioned problem.
Intraneural Synovial Cyst of the Common Peroneal Nerve: An Unusual Cause of Foot Drop with Four-Year Follow-Up
Authors: Adil Abrar , Basener Clint , Checketts Jake
Published: August 2019

In our case report, we describe a 55-year-old male patient with isolated foot drop due to an intraneural synovial ganglion. We successfully treated the lesion with decompression via epineurotomy combined with primary division of the recurrent articular branch of the common peroneal nerve (CPN). Compression neuropathies of the common peroneal nerve arise from a variety of causes. Intrinsic compression due to intraneural ganglion cysts of the CPN is rare. Previous reports of simple decompression of the cystic fluid have resulted in recurrence. The unified articular theory describes a pathway for fluid to fill from the proximal tibiofibular joint into the CPN via a recurrent articular branch. In our case, we divide this articular branch which we feel prevents recurrence.
Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during Ischemia
Authors: Pacienza Natalia , Santa-Cruz Diego , Malvicini Ricardo , Robledo Oscar , Lemus-Larralde Gastón , Bertolotti Alejandro , Marcos Martín , Yannarelli Gustavo
Published: August 2019

Lung transplantation is a lifesaving therapy for people living with severe, life-threatening lung disease. The high mortality rate among patients awaiting transplantation is mainly due to the low percentage of lungs that are deemed acceptable for implantation. Thus, the current shortage of lung donors may be significantly reduced by implementing different therapeutic strategies which facilitate both organ preservation and recovery. Here, we studied whether the anti-inflammatory effect of human umbilical cord-derived mesenchymal stem cells (HUCPVCs) increases lung availability by improving organ preservation. We developed a lung preservation rat model that mimics the different stages by which donor organs must undergo before implantation. The therapeutic schema was as follows: cardiac arrest, warm ischemia (2 h at room temperature), cold ischemia (1.5 h at 4°C, with Perfadex), and normothermic lung perfusion with ventilation (Steen solution, 1 h). After 1 h of warm ischemia, HUCPVCs (1×106 cells) or vehicle was infused via the pulmonary artery. Physiologic data (pressure-volume curves) were acquired right after the cardiac arrest and at the end of the perfusion. Interestingly, although lung edema did not change among groups, lung compliance dropped to 34% in the HUCPVC-treated group, while the vehicle group showed a stronger reduction (69%, p<0.0001). Histologic assessment demonstrated less overall inflammation in the HUCPVC-treated lungs. In addition, MPO activity, a neutrophil marker, was reduced by 41% compared with vehicle (p<0.01). MSC therapy significantly decreased tissue oxidative damage by controlling reactive oxygen species production. Accordingly, catalase and superoxide dismutase enzyme activities remained at baseline levels. In conclusion, these results demonstrate that the anti-inflammatory effect of MSCs protects donor lungs against ischemic injury and postulates MSC therapy as a novel tool for organ preservation.
A Hybrid Approach Using Oversampling Technique and Cost‐Sensitive Learning for Bankruptcy Prediction
Authors: Le Tuong , Vo Minh Thanh , Vo Bay , Lee Mi Young , Baik Sung Wook
Published: August 2019

The diagnosis of bankruptcy companies becomes extremely important for business owners, banks, governments, securities investors, and economic stakeholders to optimize the profitability as well as to minimize risks of investments. Many studies have been developed for bankruptcy prediction utilizing different machine learning approaches on various datasets around the world. Due to the class imbalance problem occurring in the bankruptcy datasets, several special techniques would be used to improve the prediction performance. Oversampling technique and cost‐sensitive learning framework are two common methods for dealing with class imbalance problem. Using oversampling techniques and cost‐sensitive learning framework independently also improves predictability. However, for datasets with very small balancing ratios, combining two above techniques will produce the better results. Therefore, this study develops a hybrid approach using oversampling technique and cost‐sensitive learning, namely, HAOC for bankruptcy prediction on the Korean Bankruptcy dataset. The first module of HAOC is oversampling module with an optimal balancing ratio found in the first experiment that will give the best overall performance for the validation set. Then, the second module uses the cost‐sensitive learning model, namely, CBoost algorithm to bankruptcy prediction. The experimental results show that HAOC will give the best performance value for bankruptcy prediction compared with the existing approaches.
Innovative Means of Surface Blowing towards Heat Alleviation for Hypersonic Flows
Authors: Khalid Mahmood , Juhany Khalid A.
Published: August 2019

A computational-based investigation has been carried out to examine the heat transfer effects of normal and tangential blowing on blunt surfaces exposed to high Mach number flows. Experimental results from such studies where a controlled outflow is imposed upon a surface under hypersonic conditions are few and far between. Simple 3D axisymmetric configurations supporting flat front surfaces suited to accommodate uniform frontal flow or round-nosed conical bodies with a stepped shoulder to provide uniform parallel flow to the conical surface were selected from a NASA experiment for validation purposes. Uniform outflow of 0.55 to 1.0 kg/s was applied in the presence of the prevailing free stream of M=6.8 to assess the extent of heat transfer rate alleviation. The numerical simulation confirmed the experiment that the application of outflow in both cases leads to the surface heat transfer relief.
Performance Analysis of Reheat Steam Temperature Control System of Thermal Power Unit Based on Constrained Predictive Control
Authors: Li Xiaoli , Liu Jian , Wang Kang , Wang Fuqiang , Li Yang
Published: August 2019

The reheat steam temperature control system of thermal power unit is a complex control object with time‐varying parameters and large delay. In order to achieve precise control of reheat steam temperature, the performance of the reheat temperature control system is analyzed according to the data that are obtained based on the constrained predictive control algorithm. Firstly, the process and mathematical model of reheat steam temperature control system are introduced. Then the principle of constrained predictive control algorithm is analyzed. Finally, the steady‐state values of control quantities of reheat steam temperature control system under different conditions are given by MATLAB simulation, and, by analyzing the steady‐state values and steady‐state time of the input and output of the system, the reference values and the regulating law of the control quantities and the specific constraint range of the control quantities of the system are given, which can provide reference data and theoretical basis for the field adjustment of the reheat steam temperature control system in power plant and improve the safety and effectiveness of the system.
Ocoxin Modulates Cancer Stem Cells and M2 Macrophage Polarization in Glioblastoma
Authors: Hernández-SanMiguel Esther , Gargini Ricardo , Cejalvo Teresa , Segura-Collar Berta , Núñez-Hervada Paula , Hortigüela Rafael , Sepúlveda-Sánchez Juan M. , Hernández-Laín Aurelio , Pérez-Núñez Angel , Sanz Eduardo , Sánchez-Gómez Pilar
Published: August 2019

Glioblastoma (GBM) is the most common and devastating primary brain tumor. The presence of cancer stem cells (CSCs) has been linked to their therapy resistance. Molecular and cellular components of the tumor microenvironment also play a fundamental role in the aggressiveness of these tumors. In particular, high levels of hypoxia and reactive oxygen species participate in several aspects of GBM biology. Moreover, GBM contains a large number of macrophages, which normally behave as immunosuppressive tumor-supportive cells. In fact, the presence of both, hypoxia and M2-like macrophages, correlates with malignancy and poor prognosis in gliomas. Antioxidant agents, as nutritional supplements, might have antitumor activity. Ocoxin® oral solution (OOS), in particular, has anti-inflammatory and antioxidant properties, as well as antitumor properties in several neoplasia, without known side effects. Here, we describe how OOS affects stem cell properties in certain GBMs, slowing down their tumor growth. In parallel, OOS has a direct effect on macrophage polarization in vitro and in vivo, inhibiting the protumoral features of M2 macrophages. Therefore, OOS could be a feasible candidate to be used in combination therapies during GBM treatment because it can target the highly resilient CSCs as well as their supportive immune microenvironment, without adding toxicity to conventional treatments.
Long-term Effects of Moderate versus High Durations of Aerobic Exercise on Biomarkers of Breast Cancer Risk: Follow-up to a Randomized Controlled Trial
Authors: Friedenreich Christine M. , Wang Qinggang , Yasui Yutaka , Stanczyk Frank Z. , Duha Aalo , Brenner Darren R. , Courneya Kerry S.
Published: August 2019

Background:

The optimal lifestyle for breast cancer prevention over the long term is unclear. We aimed to determine whether or not the amount of exercise prescribed in a year-long exercise intervention influences breast cancer biomarker levels 1 year later.

Methods:

We conducted a 24-month follow-up study (2012–2014) to the Breast Cancer and Exercise Trial in Alberta (BETA), a 12-month, two-armed (1:1), two-center randomized controlled trial of exercise in 400 cancer-free, postmenopausal women. The exercise prescription was moderate–vigorous aerobic exercise, 5 days/week (3 days/week supervised) for 30 minutes/session (MODERATE) or 60 minutes/session (HIGH). Participants were asked not to change their usual diet. We used linear mixed models to compare biomarker concentrations (C-reactive protein, insulin, glucose, HOMA-IR, estrone, sex hormone binding globulin, total estradiol, and free estradiol) over time (0, 12, and 24 months) by group (MODERATE, HIGH), using group–time interactions.

Results:

After 12 months of no intervention, 24-month fasting blood samples were available for 84.0% and 82.5% of MODERATE and HIGH groups, respectively (n = 333/400). We found no evidence that 0 to 24– or 12 to 24–month biomarker changes differed significantly between randomized groups (HIGH:MODERATE ratio of mean biomarker change ranged from 0.97 to 1.06, P values >0.05 for all). We found more favorable biomarker profiles among participants who experienced greater than the median fat loss during the trial.

Conclusions:

Prescribing aerobic exercise for 300 versus 150 minutes/week for 12 months to inactive, postmenopausal women had no effects on longer-term biomarkers.

Impact:

Exercise may lead to larger improvements in breast cancer biomarkers after intervention among women who also experience fat loss with exercise.
Abemaciclib Is Effective Against Pancreatic Cancer Cells and Synergizes with HuR and YAP1 Inhibition
Authors: Dhir Teena , Schultz Christopher W. , Jain Aditi , Brown Samantha Z. , Haber Alex , Goetz Austin , Xi Chunhua , Su Gloria H. , Xu Liang , Posey James , Jiang Wei , Yeo Charles J. , Golan Talia , Pishvaian Michael J. , Brody Jonathan R.
Published: August 2019

Mutation or promoter hypermethylation of CDKN2A is found in over 90% of pancreatic ductal adenocarcinomas (PDAC) and leads to loss of function of cell-cycle inhibitors p16 (INK4A) and p14 (ARF) resulting in unchecked proliferation. The CDK4/6 inhibitor, abemaciclib, has nanomolar IC50s in PDAC cell lines and decreases growth through inhibition of phospho-Rb (pRb), G1 cell-cycle arrest, apoptosis, and the senescent phenotype detected with β-galactosidase staining and relevant mRNA elevations. Daily abemaciclib treatments in mouse PDAC xenograft studies were safe and demonstrated a 3.2-fold decrease in tumor volume compared with no treatment (P < 0.0001) accompanying a decrease in both pRb and Ki67. We determined that inhibitors of HuR (ELAVL1), a prosurvival mRNA stability factor that regulates cyclin D1, and an inhibitor of Yes-Associated Protein 1 (YAP1), a pro-oncogenic, transcriptional coactivator important for CDK6 and cyclin D1, were both synergistic with abemaciclib. Accordingly, siRNA oligonucleotides targeted against HuR, YAP1, and their common target cyclin D1, validated the synergy studies. In addition, we have seen increased sensitivity to abemaciclib in a PDAC cell line that harbors a loss of the ELAVL1 gene via CRISP-Cas9 technology. As an in vitro model for resistance, we investigated the effects of long-term abemaciclib exposure. PDAC cells chronically cultured with abemaciclib displayed a reduction in cellular growth rates (GR) and coresistance to gemcitabine and 5-fluorouracil (5-FU), but not to HuR or YAP1 inhibitors as compared with no treatment controls. We believe that our data provide compelling preclinical evidence for an abemaciclib combination–based clinical trial in patients with PDAC.

Implications:

Our data suggest that abemaciclib may be therapeutically relevant for the treatment in PDAC, especially as part of a combination regimen inhibiting YAP1 or HuR.
Comprehensive Stroke Center Certification Series: Setting the Vision
Authors: Livesay Sarah
Published: August 2019

The road to Comprehensive Stroke Center (CSC) certification is challenging and requires full integration of neurological, neurosurgical, neurointerventional, and neurocritical care and rehabilitation services across the entire continuum of care. To successfully achieve this level of certification, centers must coordinate significant resources and services into an organized program. This paper is the first in a three-part series outlining common pitfalls facing many organizations during their journey to initial CSC certification and re-certification and offers a roadmap and pearls for success on this journey. Setting the vision for certification is a key first step in the certification process. This includes fully understanding the certification standards, requirements, and supporting documents. Program leadership must then conduct a thorough gap analysis and build a business plan to support the program as it transitions to a CSC. These key steps should inform the timeline for certification application.
Prognostic Value of Pre-Autologous Stem Cell Transplantation PET/CT in Diffuse Large B-Cell Lymphoma: The Deauville Score Is Prognostically Superior to ΔSUVmax
Authors: Zhang Xi-Yuan , Song Li , Wang Pei-Jun , Wang Ling , Li Ying , Wang Yuan-Yuan , Shi Chun-Lei
Published: August 2019

Objective: The predictive value of pre-autologous stem cell transplantation (pre-ASCT) positron emission tomography/computed tomography (PET/CT) scans according to different criteria remains elusive in patients with diffuse large B-cell lymphoma (DLBCL). Methods: A total of 46 DLBCL patients treated with pre-ASCT were enrolled in the present study, and two methods, Deauville score and maximal standardized uptake value reduction (ΔSUVmax), were used to evaluate the PET/CT scans before transplantation. Results:In patients with Deauville 1–3 and ≥4, the 2-year progression-free survival (PFS) rates were 82.8 and 11.8% (p < 0.001), respectively, while the 2-year overall survival (OS) rates were 89.7 and 41.2%, respectively (p < 0.001). When using the ΔSUVmax cut-off of 66% criterion, in patients with a ΔSUVmax of >66 and ≤66%, the 2-year PFS rates were 78.1 and 7.1%, respectively (p < 0.001), while the 2-year OS rates were 87.5 and 35.7%, respectively (p < 0.001). In the univariate analysis, the ΔSUVmax, Deauville score, NCCN-IPI and serum lactate dehydrogenase levels were significantly correlated with the 2-year PFS/OS. Furthermore, the multivariate analysis revealed that the Deauville score was an independent prognostic factor for 2-year PFS. Conclusion: The present results indicate that PET/CT scans at pre-ASCT can predict the survival of DLBCL patients, and the Deauville score is better than ΔSUVmax in prognostic prediction.
Erklärung von Vilnius zu chronischen Atemwegserkrankungen: multisektorale Versorgungswege, die angeleitetes Selbstmanagement, mHealth und Luftverschmutzung bei der Versorgung chronischer Atemwegserkrankungen einschließen
Authors: Valiulis Arunas , Bousquet Jean , Veryga Aurelijus , Suprun Ulana , Sergeenko Davit , Cebatori Svetlana , Borelli Danielle , Pietikäinen Sirpa , Banys Joanna , Agache Ioana , Billo Nils E. , Bush Andrew , Chkaidze Ivane , Dubey Lokesh , Fokkens Wytske Johanna , Grigg Jonathan , Haahtela Tari , Julge Kaja , Katilov Oleksander , Khaltaev Nikolai , Odemyr Mikaela , Palkonen Susana , Savli Roberta , Utkus Algirdas , Vilc Valentina , Alasevicius Tomas , Bedbrook Anna , Bewick Michael , Chorostowska-Wynimko Joanna , Danila Edvardas , Hadjipanayis Adamos , Karseladze Rusudan , Kvedariene Violeta , Lesinskas Eugenijus , Münter Lars , Samolinski Boleslaw Krzysztof , Sargsyan Sergey , Sitkauskiene Brigita , Somekh David , Vaideliene Laimute , Valiulis Algirdas , Hellings Peter W.
Published: August 2019

Hintergrund: Mehr als eine Milliarde Menschen leiden an chronischen Atemwegserkrankungen wie Asthma, COPD, Rhinitis und Rhinosinusitis. Diese verursachen enorme Belastungen und gelten als schwerwiegende nicht übertragbare Erkrankungen. Viele Patienten sind noch unbehandelt und die Kosten der Untätigkeit sind nicht akzeptabel. Am 23. März 2018 fand in Vilnius eine Konferenz unter der Schirmherrschaft des Gesundheitsministeriums und verschiedener wissenschaftlicher Fachgesellschaften statt, auf der multisektorale Versorgungswege vorgeschlagen wurden, die angeleitetes Selbstmanagement, mHealth und Luftverschmutzung bei der Versorgung bestimmter chronischer Atemwegserkrankungen (Rhinitis, chronische Rhinosinusitis, Asthma und COPD) einschließen. Das Treffen schloss mit der Erklärung von Vilnius, die von den Teilnehmern des EU-Gipfels zu chronischen Atemwegserkrankungen unter der Federführung von Euforea entwickelt wurde. Schlussfolgerung: Die Erklärung von Vilnius ist ein wichtiger Schritt im Kampf gegen die weltweite Luftverschmutzung und ihre Auswirkungen für Patienten mit chronischen Atemwegserkrankungen und sie spielt im Hinblick auf die EU-Gesundheitsstrategie eine wichtige Rolle, da sie einen Zusatznutzen zu dem bereits vorhandenen Wissen über die öffentliche Gesundheit liefert.
Inhalative Antibiotika-Behandlung von Patienten mit chronischer Pseudomonas-aeruginosa-Infektion
Authors: Haidl Peter
Published: August 2019

Background: Inhaled antibiotics allow the delivery of higher drug concentrations at the site of infection without the systemic adverse effects observed with the use of parenteral or oral antibiotics. These antibiotics have shown to decrease the number of exacerbations, reduce bacterial load or improve pulmonary function in several chronic respiratory conditions. Objectives: The aim of this study was to describe changes in the bacteriology of sputum in patients with chronic bronchial infection with Pseudomonas aeruginosa treated with nebulized colistin. Material and Methods: All patients with chronical infection with P. aeruginosa treated with nebulised colistin attending a day care unit during a 5-year (January 2010 to December 2014) period were included. Repeated-measures t tests were used to assess whether the introduction of colistin was associated with changes in the number of exacerbations or the length of the hospitalisations. Results: Treatment with colistin was associated with a decrease in the number of ambulatory exacerbations (1.87-1.1, p = 0.007), of hospital exacerbations (1.3-0.7, p = 0.010) and of length of stay (15.7-8.6 days, p = 0.005). There was no linear trend in the proportion of isolate Enterobacteriaceae, gram-positive cocci, Haemophilus influenzae or fungi. Isolation of Enterobacteriaceae within 1 year after the beginning of the treatment with nebulized colistin was associated with an increase in the number of ambulatory exacerbations (incidence rate ratio 1.99, 95% CI 1.05-3.79). Conclusions: Nebulised colistin was effective in the treatment of chronic infection with P. aeruginosa, and no significant changes in the microbiological evolution were observed. Isolation of Enterobacteriaceae within 1 year after the beginning of the treatment with nebulised colistin was associated with an increase in the number of exacerbations.
A Phenomenological Contribution to Substance Misuse Treatment: Principles for Person-Centered Care
Authors: Messas Guilherme P. , Fukuda Lívia  , Pienkos Elizabeth
Published: August 2019

Despite the significant need for coordinated approaches to the treatment of substance misuse worldwide, there are still major gaps in both the provision of services and in the development of a theoretically unified approach to care. We suggest that a phenomenological approach to care can provide comprehensive, theoretically grounded guidelines that coordinate and help choose between a range of interventions while respecting the values of the patient and other stakeholders. The aim of this paper is to present a framework for a person-centered approach to substance misuse care, based on general principles of phenomenology. In particular, we emphasize a dialectic conception of phenomenological care, one that considers the various tensions and conflicts of human life, and the ways these are managed by individuals. Two dialectics are presented here: the dialectic of anthropological proportions, involved in the existential situation of the substance misuser, and the dialect of decision, which is essential to all approaches to the treatment of substance misuse. The dialectic of proportions in the substance misuser’s experience involves hyperpresentification, the tendency to emphasize the present moment to the relative exclusion or reduction of the past and future considerations, and feelings of plenitude, an oversimplification of experience that ignores the complexity present in every situation. Interventions should reflect a dialectic of decision, which allows the clinician and patient to choose pathways that promote movement and expand the limitations of hyperpresentification and plenitude. This phenomenological framework, we suggest, permits a collaborative and values-based approach to comprehensive clinical decision-making.
Acute Kidney Injury in Critically Ill Children: A Retrospective Analysis of Risk Factors
Authors: De Zan Francesca , Amigoni Angela , Pozzato Roberta , Pettenazzo Andrea , Murer Luisa , Vidal Enrico
Published: August 2019

Introduction: Children admitted to paediatric intensive care unit (PICU) are at risk of acute kidney injury (AKI). However, few paediatric studies have focused on the identification of factors potentially associated with the development of this condition. The aim of our study was to assess the incidence rate of AKI, identify risk factors, and evaluate clinical outcome in a large sample of critically ill children. Methods: This retrospective observational study was conducted including patients admitted to our PICU from January 2014 to December 2016. AKI was defined according to Kidney Disease: Improving Global Outcome criteria. Results: A total of 222 PICU patients out of 811 (27%) had AKI (stage I 39%, stage II 24%, stage III 37%). The most common PICU admission diagnoses in AKI cases were heart disease (38.6%), respiratory failure (16.8%) and postsurgical non-cardiac patients (11%). Hypoxic-ischaemic was the most frequent cause of AKI. Significant risk factors for AKI following multivariate analysis were age >2 months (OR 2.43; 95% CI 1.03–7.87; p = 0.05), serum creatinine at admission >44 µmol/L (OR 2.23; 95% CI 1.26–3.94; p = 0.006), presence of comorbidities (OR 1.84; 95% CI 1.03–3.30; p = 0.04), use of inotropes (OR 2.56; 95% CI 1.23–5.35; p= 0.012) and diuretics (OR 2.78; 95% CI 1.49–5.19; p = 0.001), exposure to nephrotoxic drugs (OR 1.66; 95% CI 1.01–2.91; p= 0.04), multiple organ dysfunction syndrome (OR 2.68; 95% CI 1.43–5.01; p = 0.002), and coagulopathy (OR 1.89; 95% CI 1.05–3.38, p = 0.03). AKI was associated with a significant longer PICU stay (median LOS of 8 days, interquartile range [IQR] 3–16, versus 4 days, IQR 2–8, in non-AKI patients; p < 0.001). The mortality rate resulted tenfold higher in AKI than non-AKI patients (12.6 vs. 1.2%; p < 0.001). Conclusions: The incidence of AKI in critically ill children is high, with an associated increased length of stay and risk of mortality. In the PICU setting, risk factors of AKI are multiple and mainly associated with illness severity.
As crianças, a educação e os sonhos adultos em tempos de autismo
Authors: Lajonquière Leandro De
Published: August 2019

O imaginário pedagógico contemporâneo estrutura-se em torno de um personagem chamado autista. Trata-se de um ser ficcional que não deve ser confundido com nenhuma criança autista em particular. Isso permite afirmar que vivemos em tempos de autismo que entranham um empobrecimento da vida cotidiana com as crianças de carne e osso. Embora não se possa afirmar o caráter patogênico desse empobrecimento educativo à maneira de um vírus ou conforme o raciocínio determinista clássico “causa-efeito”, propomos pensar o imaginário atual como uma espécie de caldo de cultivo no interior do qual cada criança confronta-se com o desafio de conquistar por si e para si um lugar de sujeito de palavra numa história mais ou menos aberta para o futuro. A criança bem pode virar vítima de um mal-entendido educativo e assim vir a ficar em certa medida à deriva no mundo. Talvez, pois isso não pode ser sabido, mais de uma criança autista esteja a testemunhar de semelhante infortúnio.
Secular Trends in Procedural Stroke or Death Risks of Stenting Versus Endarterectomy for Symptomatic Carotid Stenosis
Authors: Müller Mandy D. , von Felten Stefanie , Algra Ale , Becquemin Jean-Pierre , Bulbulia Richard , Calvet David , Eckstein Hans-Henning , Fraedrich Gustav , Halliday Alison , Hendrikse Jeroen , Howard George , Gregson John , Jansen Olav , Brown Martin M. , Mas Jean-Louis , Brott Thomas G. , Ringleb Peter A. , Bonati Leo H. ,   for the Carotid Stenosis Trialists’ Collaboration
Published: August 2019

Background:

Over the past decades, stroke risk associated with carotid disease has decreased, reflecting improvements in medical therapy and a more rigorous control of vascular risk factors. It is less clear whether the procedural risk of carotid revascularization has declined over time.

Methods:

We analyzed temporal changes in procedural risks among 4597 patients with symptomatic carotid stenosis treated with carotid artery stenting (n=2326) or carotid endarterectomy (n=2271) in 4 randomized trials between 2000 and 2008, using generalized linear mixed-effects models with a random intercept for each source trial. Models were additionally adjusted for age and other baseline characteristics predicting treatment risk. The primary outcome event was any procedural stroke or death, occurring during or within 30 days after revascularization.

Results:

The procedural stroke or death risk decreased significantly over time in all patients (unadjusted odds ratio per year, 0.91; 95% CI, 0.85–0.97;
P
=0.006). This effect was driven by a decrease in the carotid endarterectomy group (unadjusted odds ratio per year, 0.82; 95% CI, 0.73–0.92;
P
=0.003), whereas no significant decrease was found after carotid artery stenting (unadjusted odds ratio, 0.96; 95% CI, 0.88–1.04;
P
=0.33). Carotid endarterectomy patients had a lower procedural stroke or death risk compared with carotid artery stenting patients, and the difference significantly increased over time (interaction
P
=0.031). After adjustment for baseline characteristics, the results remained essentially the same.

Conclusions:

The risk of stroke or death associated with carotid endarterectomy for symptomatic carotid stenosis decreased over an 8-year period, independent of clinical predictors of procedural risk. No corresponding reduction in procedural risk was seen in patients treated with stenting.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
;
http://www.isrctn.com
. Unique identifier: NCT00190398 (EVA-3S), NCT00004732 (CREST), ISRCTN57874028 (SPACE), and ISRCTN25337470 (ICSS).
Sympathetic Nerve Traffic and Arterial Baroreflex Function in Apparent Drug-Resistant Hypertension
Authors: Dell’Oro Raffaella , Quarti-Trevano Fosca , Seravalle Gino , Zanchettin Francesca , Bertoli Silvio , Airoldi Flavio , Mancia Giuseppe , Grassi Guido
Published: August 2019

True drug-resistant hypertension (RHT) is characterized by a marked neuroadrenergic activation and reflex alterations compared with the nonresistant hypertensive state. It is unknown however, whether this behavior is specific for the RHT state or is also shared by apparent RHT (ARHT). In 38 middle-age patients with RHT, 44 treated essential controlled hypertensives (HT) and 32 ARHT; we evaluated sphygmomanometric, beat-to-beat (Finapres) and 24-hour (Spacelabs) blood pressure, heart rate and muscle sympathetic nerve traffic (microneurography). Measurements included plasma aldosterone, plasma norepinephrine, homeostasis model assessment index, and spontaneous baroreflex-muscle sympathetic nerve traffic sensitivity. All the various above-mentioned blood pressure values were significantly greater in both RHT and ARHT as compared with HT, while 24-hour blood pressure was significantly lower in ARHT as compared with RHT. In ARHT, muscle sympathetic nerve traffic was significantly lower than RHT (74.8±5.2 versus 89.2±4.8 bursts/100 hb,
P
<0.01) and similar to HT (69.7±4.8 bursts/100 hb,
P
=NS). RHT showed, at variance from the other 2 groups, greater plasma aldosterone and homeostasis model assessment index values and an impaired baroreflex function. In RHT, but not in ARHT and HT, muscle sympathetic nerve traffic was significantly and inversely related to baroreflex function (
r
=−0.40,
P
<0.02) and directly to plasma aldosterone and homeostasis model assessment index values (
r
=0.34–0.36,
P
<0.05). Plasma norepinephrine and heart rate values were not significantly different in the 3 groups. These data provide evidence that the marked sympathetic activation and baroreflex dysfunction detected in RHT is not present in ARHT, which displays a sympathetic and baroreflex profile superimposable to that seen in HT. These differences in the neurogenic function may have important clinical and therapeutic implications.