bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive Resource Allocation for Computation Offloading
Authors: Avgeris Marios , Dechouniotis Dimitrios , Athanasopoulos Nikolaos , Papavassiliou Symeon
Published: April 2019

Although mobile devices today have powerful hardware and networking capabilities, they fall short when it comes to executing compute-intensive applications. Computation offloading (i.e., delegating resource-consuming tasks to servers located at the edge of the network) contributes toward moving to a mobile cloud computing paradigm. In this work, a two-level resource allocation and admission control mechanism for a cluster of edge servers offers an alternative choice to mobile users for executing their tasks. At the lower level, the behavior of edge servers is modeled by a set of linear systems, and linear controllers are designed to meet the system’s constraints and quality of service metrics, whereas at the upper level, an optimizer tackles the problems of load balancing and application placement toward the maximization of the number the offloaded requests. The evaluation illustrates the effectiveness of the proposed offloading mechanism regarding the performance indicators, such as application average response time, and the optimal utilization of the computational resources of edge servers.
Lower bounds for Sum and Sum of Products of Read-once Formulas
Authors: Ramya C. , Rao B. V. Raghavendra
Published: April 2019

We study limitations of polynomials computed by depth-2 circuits built over read-once formulas (ROFs). In particular:

• We prove a 2

Ω(
n
)

lower bound for the sum of ROFs computing the 2
n
-variate polynomial in VP defined by Raz and Yehudayoff [21].

• We obtain a 2

Ω(√
n
)

lower bound on the size of Σ Π

[
n
1/15
]

arithmetic circuits built over restricted ROFs of unbounded depth computing the permanent of an
n
×
n
matrix (superscripts on gates denote bound on the fan-in). The restriction is that the number of variables with + gates as a parent in a proper sub formula of the ROF has to be bounded by √
n
. This proves an exponential lower bound for a subclass of possibly non-multilinear formulas of unbounded depth computing the permanent polynomial.

• We also show an exponential lower bound for the above model against a polynomial in VP.

• Finally, we observe that the techniques developed yield an exponential lower bound on the size of ΣΠ

[
N
1/30
]

arithmetic circuits built over syntactically multi-linear ΣΠΣ

[
N
1/4
]

arithmetic circuits computing a product of variable disjoint linear forms on
N
variables, where the superscripts on gates denote bound on the fan-in.

Our proof techniques are built on the measure developed by Kumar et al. [14] and are based on a non-trivial analysis of ROFs under random partitions. Further, our results exhibit strengths and provide more insight into the lower bound techniques introduced by Raz [19].
SSA-AC
Authors: Metwalli Sara Ayman , Hara-Azumi Yuko
Published: April 2019

Recently, the quest to reduce energy consumption in digital systems has been the subject of a number of ongoing studies. One of the most researched focuses is
approximate computing (AC)
. AC is a new computing paradigm in both hardware and software designs that aim to achieve energy-efficient digital systems. Although a variety of AC techniques have been studied so far, the main question,
“How (in which section) can a program or a circuit be approximated?,”
has not been answered yet. This work addresses the above issue by developing a software framework Static Significance Analysis for Approximate Computing (SSA-AC) to analyze the target application program and guide the designers to identify parts of the program to which approximation can or cannot be applied. SSA-AC statically analyzes the significance of variables in the precise version of the program and thus needs no trial-and-error evaluation or specific test data. Experimental results show that SSA-AC can successfully extract the significance ranking of inputs/variables to be approximated in much shorter time than existing statistical works that are inevitably data dependent.
Effects of PDE5 inhibition on dystrophic muscle following an acute bout of downhill running and endurance training
Authors: Batra Abhinandan , Vohra Ravneet S. , Chrzanowski Steve M. , Hammers David W. , Lott Donovan J. , Vandenborne Krista , Walter Glenn A. , Forbes Sean C.
Published: April 2019

Lack of sarcolemma-localized neuronal nitric oxide synthase mu (nNOSμ) contributes to muscle damage and fatigue in dystrophic muscle. In this study, we examined the effects of compensating for lack of nNOSμ with a phosphodiesterase type 5 (PDE5) inhibitor in mdx mice following downhill running and endurance training. Dystrophic mice ( mdx) were treated with sildenafil citrate and compared with untreated mdx and wild-type mice after an acute bout of downhill running and during a progressive low-intensity treadmill running program (5 days/wk, 4 wk). Magnetic resonance imaging (MRI) and spectroscopy (MRS) transverse relaxation time constant (T2) of hindlimb and forelimb muscles were measured as a marker of muscle damage after downhill running and throughout training. The MRI blood oxygenation level dependence (BOLD) response and 31phosphorus MRS (31P-MRS) data were acquired after stimulated muscle contractions. After downhill running, the increase in T2 was attenuated ( P < 0.05) in treated mdx and wild-type mice compared with untreated mdx. During training, resting T2 values did not change in wild-type and mdx mice from baseline values; however, the running distance completed during training was greater ( P < 0.05) in treated mdx (>90% of target distance) and wild-type (100%) than untreated mdx (60%). The post-contractile BOLD response was greater ( P < 0.05) in treated mdx that trained than untreated mdx, with no differences in muscle oxidative capacity, as measured by 31P-MRS. Our findings indicate that PDE5 inhibition reduces muscle damage after a single bout of downhill running and improves performance during endurance training in dystrophic mice, possibly because of enhanced microvascular function.

NEW & NOTEWORTHY This study examined the combined effects of PDE5 inhibition and exercise in dystrophic muscle using high-resolution magnetic resonance imaging and spectroscopy. Our findings demonstrated that sildenafil citrate reduces muscle damage after a single bout of downhill running, improves endurance-training performance, and enhances microvascular function in dystrophic muscle. Collectively, the results support the combination of exercise and PDE5 inhibition as a therapeutic approach in muscular dystrophies lacking nNOSμ.
Mechanical properties, physiological behavior, and function of aponeurosis and tendon
Authors: Bojsen-Møller Jens , Magnusson S. Peter
Published: April 2019

During human movement, the muscle and tendinous structures interact as a mechanical system in which forces are generated and transmitted to the bone and energy is stored and released to optimize function and economy of movement and/or to reduce risk of injury. The present review addresses certain aspects of how the anatomical design and mechanical and material properties of the force-transmitting tissues contribute to the function of the muscle-tendon unit and thus overall human function. The force-bearing tissues are examined from a structural macroscopic point of view down to the nanoscale level of the collagen fibril. In recent years, the understanding of in vivo mechanical function of the force-bearing tissues has increased, and it has become clear that these tissues adapt to loading and unloading and furthermore that force transmission mechanics is more complex than previously thought. Future investigations of the force-transmitting tissues in three dimensions will enable a greater understanding of the complex functional interplay between muscle and tendon, with relevance for performance, injury mechanisms, and rehabilitation strategies.
Angiotensin II suppresses autophagy and disrupts ultrastructural morphology and function of mitochondria in mouse skeletal muscle
Authors: Silva Kleiton Augusto Santos , Ghiarone Thaysa , Schreiber Kathy , Grant DeAna , White Tommi , Frisard Madlyn I. , Sukhanov Sergiy , Chandrasekar Bysani , Delafontaine Patrice , Yoshida Tadashi
Published: April 2019

Angiotensin II (ANG II)-induced skeletal muscle wasting is characterized by activation of the ubiquitin-proteasome system. However, the potential involvement of proteolytic system macroautophagy/autophagy in this wasting process remains elusive. Autophagy is precisely regulated to maintain cell survival and homeostasis; thus its dysregulation (i.e., overactivation or persistent suppression) could lead to detrimental outcomes in skeletal muscle. Here we show that infusion of ANG II for 7 days in male FVB mice suppressed autophagy in skeletal muscle. ANG II blunted microtubule-associated protein 1 light chain 3B (LC3B)-I-to-LC3B-II conversion (an autophagosome marker), increased p62/SQSTM1 (an autophagy cargo receptor) protein expression, and decreased the number of autophagic vacuoles. ANG II inhibited UNC-51-like kinase 1 via inhibition of 5′-AMP-activated kinase and activation of mechanistic target of rapamycin complex 1, leading to reduced phosphorylation of beclin-1Ser14 and Autophagy-related protein 14Ser29, suggesting that ANG II impairs autophagosome formation in skeletal muscle. In line with ANG II-mediated suppression of autophagy, ANG II promoted accumulation of abnormal/damaged mitochondria, characterized by swelling and disorganized cristae and matrix dissolution, with associated increase in PTEN-induced kinase 1 protein expression. ANG II also reduced mitochondrial respiration, indicative of mitochondrial dysfunction. Together, these results demonstrate that ANG II reduces autophagic activity and disrupts mitochondrial ultrastructure and function, likely contributing to skeletal muscle wasting. Therefore, strategies that activate autophagy in skeletal muscle have the potential to prevent or blunt ANG II-induced skeletal muscle wasting in chronic diseases.

NEW & NOTEWORTHY Our study identified a novel mechanism whereby angiotensin II (ANG II) impairs mitochondrial energy metabolism in skeletal muscle. ANG II suppressed autophagosome formation by inhibiting the UNC-51-like kinase 1(ULK1)-beclin-1 axis, resulting in accumulation of abnormal/damaged and dysfunctional mitochondria and reduced mitochondrial respiratory capacity. Therapeutic strategies that activate the ULK1-beclin-1 axis have the potential to delay or reverse skeletal muscle wasting in chronic diseases characterized by increased systemic ANG II levels.
Firing rate models for gamma oscillations
Authors: Keeley Stephen , Byrne Áine , Fenton André , Rinzel John
Published: April 2019

Gamma oscillations are readily observed in a variety of brain regions during both waking and sleeping states. Computational models of gamma oscillations typically involve simulations of large networks of synaptically coupled spiking units. These networks can exhibit strongly synchronized gamma behavior, whereby neurons fire in near synchrony on every cycle, or weakly modulated gamma behavior, corresponding to stochastic, sparse firing of the individual units on each cycle of the population gamma rhythm. These spiking models offer valuable biophysical descriptions of gamma oscillations; however, because they involve many individual neuronal units they are limited in their ability to communicate general network-level dynamics. Here we demonstrate that few-variable firing rate models with established synaptic timescales can account for both strongly synchronized and weakly modulated gamma oscillations. These models go beyond the classical formulations of rate models by including at least two dynamic variables per population: firing rate and synaptic activation. The models’ flexibility to capture the broad range of gamma behavior depends directly on the timescales that represent recruitment of the excitatory and inhibitory firing rates. In particular, we find that weakly modulated gamma oscillations occur robustly when the recruitment timescale of inhibition is faster than that of excitation. We present our findings by using an extended Wilson-Cowan model and a rate model derived from a network of quadratic integrate-and-fire neurons. These biophysical rate models capture the range of weakly modulated and coherent gamma oscillations observed in spiking network models, while additionally allowing for greater tractability and systems analysis.

NEW & NOTEWORTHY Here we develop simple and tractable models of gamma oscillations, a dynamic feature observed throughout much of the brain with significant correlates to behavior and cognitive performance in a variety of experimental contexts. Our models depend on only a few dynamic variables per population, but despite this they qualitatively capture features observed in previous biophysical models of gamma oscillations that involve many individual spiking units.
Electrocatalytic Properties of Calcium Titanate, Strontium Titanate, and Strontium Calcium Titanate Powders Synthesized by Solution Combustion Technique
Authors: Jongprateep Oratai , Sato Nicha , Techapiesancharoenkij Ratchatee , Surawathanawises Krissada
Published: April 2019

Calcium titanate (CaTiO3), strontium titanate (SrTiO3), and strontium calcium titanate (SrxCa1−xTiO3) are widely recognized and utilized as dielectric materials. Their electrocatalytic properties, however, have not been extensively examined. The aim of this research is to explore the electrocatalytic performance of calcium titanate, strontium titanate, and strontium calcium titanate, as potential sensing materials. Experimental results revealed that CaTiO3, SrTiO3, and Sr0.5Ca0.5TiO3 powders synthesized by the solution combustion technique consisted of submicrometer-sized particles with specific surface areas ranging from 4.19 to 5.98 m2/g. Optical bandgap results indicated that while CaTiO3 and SrTiO3 had bandgap energies close to 3 eV, Sr0.5Ca0.5TiO3 yielded a lower bandgap energy of 2.6 eV. Cyclic voltammetry tests, measured in 0.1 M sodium nitrite, showed oxidation peaks occurring at 0.58 V applied voltage. The highest peak current was observed in Sr0.5Ca0.5TiO3 powder. The superior electrocatalytic performance of Sr0.5Ca0.5TiO3 might be attributed to lower bandgap energy, which consequently facilitates higher electron transfer. Electrocatalytic performance of Sr0.5Ca0.5TiO3 was subsequently reexamined in a wider concentration range of sodium nitrite. The results revealed that the material responded linearly to nitrite solution in the range of 0.1 mM to 0.1 M and exhibited sensitivity ranging from 3.117 to 0.040 μA/mM, in the entire tested nitrite concentrations. The results suggest that Sr0.5Ca0.5TiO3 could also be used for nitrite detection.
Chitosan-Based Nanogel Enhances Chemotherapeutic Efficacy of 10-Hydroxycamptothecin against Human Breast Cancer Cells
Authors: Guo Hui , Li Faping , Qiu Heping , Zheng Qi , Yang Chao , Tang Chao , Hou Yuchuan
Published: April 2019

Chitosan (CS), the second most abundant polysaccharide in nature, has been widely developed as a nanoscopic drug delivery vehicle due to its intriguing characteristics. In this work, a positively charged CS-based nanogel was designed and synthesized to inhibit the proliferation of breast cancer cell lines. The model drug of 10-hydroxycamptothecin (HCPT) was entrapped into the core via a facile diffusion to form CS/HCPT. The characteristics of CS/HCPT were evaluated by assessing particle size, drug loading content, and drug loading efficiency. Furthermore, cell internalization, cytotoxicity, and apoptosis of CS/HCPT were also investigated in vitro. The present investigation indicated that the positively charged CS-based nanogel could be potentially used as a promising drug delivery system.
Comparison of Self-Rated Health among Characteristic Groups of Vegetable Greenhouse Farmers Based on Exposure to Pesticide Residuals: A Latent Profile Analysis
Authors: Li Jiangping , Li Honghui , He Shulan , Xue Min , Tian Danian , Zhou Jian , Xie Yongxin , Yang Huifang
Published: April 2019

Objective. The current study was aimed at using a latent profile analysis (LPA) model to classify greenhouse farmers into a potential cluster according to their exposure to pesticide residuals. Further, the association between self-rated health (SRH) and the cluster exposed to pesticide residual was explored. Methods. Four hundred sixty-four farmers from vegetable greenhouses were selected, their SRH information was gathered through questionnaires from the “Self-Rated Health Measurement Scale (SRHMS)” Version 1.0, and the corresponding pesticide residuals were detected in a laboratory. The linear mixed regression model was employed for association assessment. Results. Two latent clusters were extracted as samples, and the results showed that a high amount of pesticide residual accounted for poor physical health, but did not show statistical significance. In addition, an inverse significant association was observed between psychosocial symptoms and negative emotion and pesticide residual level. Furthermore, a diversity of significant relationship was observed in social health and its corresponding dimensions with latent cluster. Conclusions. LPA offers a holistic and parsimonious method to identify high-risk health clusters of greenhouse workers in various health aspects and allows for a personality-targeted intervention by a local health department.
The Solution of the Optimal Insurance Problem with Background Risk
Authors: Fan Yulian
Published: April 2019

This paper proves the existence and uniqueness of the solution of the optimal insurance problem with background risk and presents the explicit form of the optimal solution.
Lowering Emissivity of Concrete Roof Tile’s Underside Cuts Down Heat Entry to the Building
Authors: Chen Xuejun , Wang Lei , Liu Zhikui , Qin Yinghong , Bao Ting
Published: April 2019

Buildings in Southern China widely use a double-skin roof to reduce heat entry through the roof to the building interior during summertime. Concrete roof tiles are preferably installed as the outmost layer of the double-skin roof due to their resistance to hail and wind damages and their attractive price. However, after construction, the tile’s top tends to be darkened by dust deposit and algae growth, increasing the heat entry through the roof to the building. Here, we show that this heat entry can be curtailed by lowering the emissivity at the tile’s underside. Temperatures and heat fluxes at different elevations of a double-skin roof with concrete tiles as the outmost layer of the roof are monitored. The underside of each concrete tile is coated with a specific paint to get a unique emissivity. Observations reveal that lowering the emissivity of concrete roof tiles could cut down the summer heat gain of buildings in tropical regions.
Behavioral and Cognitive Impacts of Mindfulness-Based Interventions on Adults with Attention-Deficit Hyperactivity Disorder: A Systematic Review
Authors: Poissant Hélène , Mendrek Adrianna , Talbot Nadine , Khoury Bassam , Nolan Jennifer
Published: April 2019

Mindfulness-based interventions (MBIs) are becoming increasingly popular as treatments for physical and psychological problems. Recently, several studies have suggested that MBIs may also be effective in reducing symptoms of attention-deficit hyperactivity disorder (ADHD). Most studies have examined the effectiveness in children, but there are now a sufficient number of individual treatment trials to consider a systematic review in adults. Majority of existing systematic reviews and meta-analyses only consider ADHD symptoms as an outcome, and most of them do not fully report potential biases of included studies, thus limiting considerably their conclusions. This is an important facet because some studies could be found ineligible to be included in future analysis due to their low quality. In this systematic review, we followed the PRISMA/PICO criteria and we thoroughly assessed the risks of bias for each of the selected studies according to Cochrane guidelines. We searched the available literature concerning MBIs in adult participants with ADHD using PsycINFO, PubMed, Scopus, and ERIC databases. In total, 13 studies conducted with 753 adults (mean age of 35.1 years) were identified as eligible. Potential moderators such as participants’ age, ADHD subtypes, medication status, comorbidity, intervention length, mindfulness techniques, homework amount, and training of therapists were carefully described. Aside from measuring the symptoms of ADHD, outcome measures were categorized into executive/cognitive functioning, emotional disturbances, quality of life, mindfulness, and grade point average at school. According to presented descriptive results, all the studies (100%) showed improvement of ADHD symptoms. In addition, mindfulness meditation training improves some aspects of executive function and emotion dysregulation. Although these are promising findings to support treatment efficacy of MBIs for ADHD, various biases such as absence of randomization and lack of a control group may affect the actual clinical value and implications of the studies. Moreover, the relatively low quality of selection and performance criteria in several studies, as well as relatively high attrition bias across studies, call for caution before considering conducting further analysis.
Road Tunnel Axial Fan Performance In Situ Test: Taking Qinling Zhongnan Mountain Highway Tunnel as an Example
Authors: Wang Yongdong , Han Xingbo , Zhou Tianyue , He Zhiwei , Tian Feilong , Zheng Zhuoqi , Zhao Haiping
Published: April 2019

Axial fans play a pivotal role in the road tunnel ventilation system. Qualified performance of the axial fan is important for both safety and air quality maintenance reasons. Axial fans performance in situ test of Qinling Zhongnan Mountain highway tunnel, the second longest road tunnel in the world, is presented in this research. Performance test items and the qualification criterion, as well as a general framework for the road tunnel axial fan assessment, are recommended. Log‐Tchebycheff method is suggested to confirm the location for the measuring lines and points. The precision of the log‐Tchebycheff method in air flow rate measuring is verified by comparing with the biharmonic spline interpolation fitting result. The research shows that the log‐Tchebycheff method has high precision and good efficiency in the air flow rate measurement of the road tunnel air duct. What is more, the biharmonic spline interpolation fitting method can be applied to obtain a more accurate result. The number of interpolation points of the biharmonic spline interpolation fitting method should be bigger than 2000 to provide quality results.
Assessment of Overactive Bladder after Laparoscopic Lateral Suspension for Pelvic Organ Prolapse
Authors: Malanowska Ewelina , Starczewski Andrzej , Bielewicz Włodzimierz , Balzarro Matteo
Published: April 2019

Background. Pelvic organ prolapses (POP) and overactive bladder (OAB) may coexist and both negatively impact quality of life in women. The correlation between POP and OAB remains unclear, but these patients may have the OAB resolution after the surgical treatment of POP. Aim of our study was to assess the anatomical results and the effect on OAB symptoms in women who underwent laparoscopic lateral suspension for POP. Materials and Methods. This prospective study included all women with apical POP who underwent surgical repair with laparoscopic uterine lateral suspension from January 2016 to December 2017. The baseline and the 1-year follow-up included post-void residual measurement, urinalysis, vaginal examination, OAB symptoms evaluation, and administration of questionnaires (PFDI-20, UDI 6). Results. 64 women underwent laparoscopic lateral suspension for uterine prolapse and 78.1% had concomitant anterior vaginal wall defect. At 1-year follow-up the anatomic success rates were 84.4% for the apical and 76.2% for the anterior compartment. The comparison between OAB symptoms before and after the surgical procedure showed the resolution of OAB in 76% of the women, while de novo OAB was present in 2.6%. With the questionnaires 95.3% (61/64) of our patients were satisfied after the POP repair. We documented a trend in ameliorating of OAB regardless of the POP-Q stage. However, the Pearson test showed this correlation as statistically significant only in women with anterior vaginal wall defect stage III and apical stage II. No patient had vaginal exposure of the polypropylene mesh. Conclusion. Our data show how laparoscopic lateral suspension is an effective procedure for apical and anterior vaginal wall defects. This study provides further evidence for the concept that OAB in women with POP >II stage improves after a successful POP surgery. These women may benefit from a resolution of OAB and POP symptoms with the improvement of patient’s quality of life.
Generalized Numerical Index of Function Algebras
Authors: Lee Han Ju
Published: April 2019

Let X be a complex Banach space and Cb(Ω:X) be the Banach space of all bounded continuous functions from a Hausdorff space Ω to X, equipped with sup norm. A closed subspace A of Cb(Ω:X) is said to be an X-valued function algebra if it satisfies the following three conditions: (i) A≔{x⁎∘f:f∈A,  x⁎∈X⁎} is a closed subalgebra of Cb(Ω), the Banach space of all bounded complex-valued continuous functions; (ii) ϕ⊗x∈A for all ϕ∈A and x∈X; and (iii) ϕf∈A for every ϕ∈A and for every f∈A. It is shown that k-homogeneous polynomial and analytic numerical index of certain X-valued function algebras are the same as those of X.
Endocan Is an Independent Predictor of Heart Failure-Related Mortality and Hospitalizations in Patients with Chronic Stable Heart Failure
Authors: Kosir Gorazd , Jug Borut , Novakovic Marko , Mijovski Mojca Bozic , Ksela Jus
Published: April 2019

Background. Heart failure (HF) is characterized by unfavorable prognosis. Disease trajectory of HF, however, may vary, and risk assessment of patients remains elusive. In our study, we sought to determine the prognostic impact of endocan—a novel biomarker of endothelial dysfunction and low-grade inflammation—in patients with heart failure. Methods. In outpatients with chronic HF, baseline values of endocan were determined and clinical follow-up for a minimum of 18 months obtained. A multivariate Cox proportional hazard model was built for HF-related death or hospitalization requiring inotropic support. Results. A total of 120 patients (mean age 71 years, 64% male, mean LVEF 36%) were included. During a mean follow-up of 656±109 days, 50 patients (41.6%) experienced an event. On Cox multivariate analysis, endocan values emerged as an independent predictor of HF prognosis (HR, 1.471 CI 95% 1.183-1.829, p=0.001, for each 1 ng/mL increase) even after adjustment for age, gender, HF etiology, LVEF, NYHA class, NT-proBNP, and exercise tolerance. Conclusions. Endocan is an independent predictor of HF-related events in chronic HF individuals and represents a promising tool for risk assessment of HF patients.
A Review of Self-Expanding Esophageal Stents for the Palliation Therapy of Inoperable Esophageal Malignancies
Authors: Kang Yunqing
Published: April 2019

Esophageal cancer is a very deadly disease, killing more than 15,000 people in the United States annually. Almost 400,000 new cases happen in the worldwide every year. More than 50% esophageal cancer patients are diagnosed at an advanced stage when they need an esophageal stent to open the blocked esophagus for feeding and drinking. Esophageal stents have evolved in stages over the years. Current clinically used stents commonly include stainless steel or nitinol self-expandable metallic stent (SEMS) and self-expandable plastic stent (SEPS). There are many choices of different types of stents and sizes, with fierce competition among manufacturers. However, current stent technology, whether uncovered, partially covered, fully covered SEMS or SEPS, has their own advantages to solve the dysphagia, stricture, and fistula problems, but they also cause some clinical complications. The ideal stent remains elusive. New 3D printing technique may bring new promising potential to manufacturing personalized esophageal stents. Drug-eluting stents could be the new avenue to do more than just pry open a stricture or cover a defect in the esophageal lumen, a possibility of proving local anticancer therapy simultaneously. Additionally, the lack of esophageal cancer animal models also hinders the progress of stent development. This paper reviews these topics for a comprehensive understanding of this field. In a conclusion, the ultimate goal of the future esophageal stent would have multifunction to treat the underlying conditions and restore esophageal function to near normal.
Genome-wide Analysis of Common Copy Number Variation and Epithelial Ovarian Cancer Risk
Authors: Reid Brett M. , Permuth Jennifer B. , Chen Y. Ann , Fridley Brooke L. , Iversen Edwin S. , Chen Zhihua , Jim Heather , Vierkant Robert A. , Cunningham Julie M. , Barnholtz-Sloan Jill S. , Narod Steven , Risch Harvey , Schildkraut Joellen M. , Goode Ellen L. , Monteiro Alvaro N. , Sellers Thomas A.
Published: April 2019

Background:

Germline DNA copy number variation (CNV) is a ubiquitous source of genetic variation and remains largely unexplored in association with epithelial ovarian cancer (EOC) risk.

Methods:

CNV was quantified in the DNA of approximately 3,500 cases and controls genotyped with the Illumina 610k and HumanOmni2.5M arrays. We performed a genome-wide association study of common (>1%) CNV regions (CNVRs) with EOC and high-grade serous (HGSOC) risk and, using The Cancer Genome Atlas (TCGA), performed in silico analyses of tumor-gene expression.

Results:

Three CNVRs were associated (P < 0.01) with EOC risk: two large (∼100 kb) regions within the 610k set and one small (<5 kb) region with the higher resolution 2.5M data. Large CNVRs included a duplication at LILRA6 (OR = 2.57; P = 0.001) and a deletion at CYP2A7 (OR = 1.90; P = 0.007) that were strongly associated with HGSOC risk (OR = 3.02; P = 8.98 × 10−5). Somatic CYP2A7 alterations correlated with EGLN2 expression in tumors (P = 2.94 × 10−47). An intronic ERBB4/HER4 deletion was associated with reduced EOC risk (OR = 0.33; P = 9.5 × 10−2), and somatic deletions correlated with ERBB4 downregulation (P = 7.05 × 10−5). Five CNVRs were associated with HGSOC, including two reduced-risk deletions: one at 1p36.33 (OR = 0.28; P = 0.001) that correlated with lower CDKIIA expression in TCGA tumors (P = 2.7 × 10−7), and another at 8p21.2 (OR = 0.52; P = 0.002) that was present somatically where it correlated with lower GNRH1 expression (P = 5.9 × 10−5).

Conclusions:

Though CNV appears to not contribute largely to EOC susceptibility, a number of low-to-common frequency variants may influence the risk of EOC and tumor-gene expression.

Impact:

Further research on CNV and EOC susceptibility is warranted, particularly with CNVs estimated from high-density arrays.
Role of Ancillary Techniques in Thyroid Cytology Specimens
Authors: Nishino Michiya , Krane Jeffrey F.
Published: April 2019

Ancillary molecular testing has emerged as a promising way to refine the preoperative risk stratification of thyroid nodules with indeterminate fine needle aspiration (FNA) biopsy results. Commercially available molecular tests for thyroid FNAs include those that analyze samples for mutations and gene fusions, gene expression alterations, microRNA expression alterations, chromosomal copy number alterations, or a combination thereof. This review summarizes the performance characteristics of the most current iterations of three tests currently marketed for cytologically indeterminate thyroid nodules: ThyroSeq v3, ThyGeNEXT/ThyraMIR, and Afirma Gene Sequencing Classifier.
Pediatric Brainstem Gliomas: A Retrospective Study of 180 Patients from the SEER Database
Authors: Khalid Syed I. , Kelly Ryan , Adogwa Owoicho , Carlton Adam , Tam Edric , Naqvi Salik , Kushkuley Jacob , Ahmad Shahjehan , Woodward Josha , Khanna Ryan , Davison Mark , Munoz Lorenzo , Byrne Richard
Published: April 2019

Background/Aims: Large population-based studies are needed to assess the epidemiology and survival risk factors associated with pediatric brainstem gliomas. This retrospective study explores factors that may influence survival in this population. Methods: Utilizing the SEER database, the authors retrospectively assessed survival in histologically confirmed brainstem gliomas in patients aged 17 and younger. Survival was described with Kaplan-Meyer curves and multivariate regression analysis. Results: This analysis of 180 cases showed that age (hazard ratio [HR] 1.04, 95% CI 0.96–1.14, p = 0.34), non-white race (HR 1.00, 95% CI 0.35–2.85 p > 0.99), distant or invasive extension of the tumor (HR 0.4, 95% CI 0.08–2.53, p = 0.37), and radiation therapy (HR 1.27, 95% CI 0.52–3.11, p = 0.61) were not associated with decreased survival. High-grade tumor status (HR 8.64, 95% CI 3.49–21.41, p < 0.001) was associated with decreased survival. Partial resection (HR 0.11, 95% CI 0.04–0.30, p < 0.001) and gross-total resection (HR 0.03, 95% CI 0.01–0.14, p < 0.001) were associated with improved survival. Conclusions: High-grade brainstem gliomas have a worse prognosis. Early diagnosis and surgery appear to be associated with improved survival, while the role of radiation is unclear.
ЕКСТРЕНА ПРОФІЛАКТИКА ЗАРАЖЕННЯ HCV – РЕАЛЬНІСТЬ І ПЕРСПЕКТИВИ
Authors: Bondarenko A. M.
Published: April 2019

Проаналізовано стан проблеми екстреної профілактики HCV-інфекції при парентеральному контакті потерпілого з джерелом збудника в результаті «нещасного випадку» або «аварії» на виробництві (в медичній установі). Зазначено, що ця проблема не вирішується вже протягом майже 20 років, а екстрена профілактика HCV-інфекції взагалі заперечується або фактично забороняється, що відображено в офіційних нормативних документах сучасної адміністративної медицини більшості країн навіть з розвиненою економікою. Досі навіть не простежується тенденції до вирішення цієї проблеми, незважаючи на усю її актуальність, високий ризик серйозних наслідків і те, що ця проблема передусім безпосередньо стосується медичних працівників, які складають більшість потерпілих і виявляються заручниками ситуації, залишаючись наодинці з проблемою інфікування і розвитку гострої HCV-інфекції. Замість реальної допомоги потерпілим офіційною медициною пропонується просто «пильно очікувати» розвитку гострої HCV-інфекції з ризиком хронізації на рівні 50-90 %! Фактично це усвідомлена й узаконена бездіяльність.

Але також протягом більше 20 років невирішеною залишається і проблема лікування гострої HCV-інфекції, навіть незважаючи на появу в останні декілька років високоефективних противірусних препаратів прямої дії та їх комбінацій. Стан проблеми досі перебуває на стадії «серйозної стурбованості» без яких-небудь практичних рішень. Є тільки рекомендації, що зводяться в основному до офіційно узаконеного очікування «самовільного одужання» або ж очікування розвитку хронічної HCV-інфекції. Наявність уривчастих і розпливчатих рекомендацій з етіотропної терапії гострого гепатиту С також не вирішує проблему і наполегливо рекомендує потерпілому, а тепер вже пацієнтові, самостійно чи разом з його лікарем вирішити питання про індивідуальну противірусну терапію. І тут офіційна медицина, медичні установи, де сталися «нещасні випадки», і страхові компанії знову залишаються збоку і вже постраждалий медпрацівник як пацієнт повинен вирішувати проблему також самостійно! Тому в той же час дивною виглядає і пасивність самих медпрацівників, і їх «мовчазна згода» замість активної позиції в ініціації вирішення проблеми, що безпосередньо стосується їх здоров’я і, правда у віддаленій перспективі, – навіть життя.

Така ситуація повністю абсурдна і, навіть, злочинна, а, отже, вимагає невідкладного вирішення проблеми! За наявності широкого й ефективного арсеналу поки що досить ефективних противірусних препаратів таку бездіяльність з боку офіційної медицини і з боку самих медпрацівників можна вважати неприпустимим.
Cost effectiveness of the cancer prevention program for carriers of the BRCA1/2 mutation
Authors: Ramos Marcelo Cristiano de Azevedo , Folgueira Maria Aparecida Azevedo Koike , Maistro Simone , Campolina Alessandro Gonçalves , Soárez Patricia Coelho de , Bock Geertruida Hendrika de , Novaes Hillegonda Maria Dutilh , Diz Maria Del Pilar Estevez
Published: April 2019

OBJECTIVE: To analyze the cost effectiveness of the diagnostic program for the germline mutation in BRCA1/2 genes and of preventative strategies for the relatives of patients diagnosed with ovarian cancer associated with this mutation. METHODS: The study analyzed the cost effectiveness by developing an analysis of the Markov decision process from the perspective of the National Health System. The strategies compared reflect upon the adoption of genetic testing and preventative strategies for relatives or the usual care currently proposed. The incremental cost-effectiveness ratio was expressed in terms of cost per case avoided. The sensitivity analysis was performed in a univariate and deterministic manner. RESULTS: The study showed increments for effectiveness and for costs when performing genetic testing and adopting prophylactic measures for family members. The incremental cost-effectiveness ratio was estimated at R$908.58 per case of cancer avoided, a figure considered lower than the study’s cost-effectiveness threshold (R$7,543.50). CONCLUSIONS: The program analyzed should be considered a cost-effective strategy for the national situation. Studies in various other countries have reached similar conclusions. One possible ramification of this research might the need to perform a budgetary-impact analysis of making the program one of the country’s health policies
Device Therapy and Arrhythmia Management in Left Ventricular Assist Device Recipients: A Scientific Statement From the American Heart Association
Authors: Gopinathannair Rakesh , Cornwell William K. , Dukes Jonathan W. , Ellis Christopher R. , Hickey Kathleen T. , Joglar José A. , Pagani Francis D. , Roukoz Henri , Slaughter Mark S. , Patton Kristen K. ,   On behalf of the American Heart Association Electrocardiography and Arrhythmias Committee; Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; and Council on Cardiovascular and Stroke Nursing
Published: April 2019

Left ventricular assist devices (LVADs) are an increasingly used strategy for the management of patients with advanced heart failure with reduced ejection fraction. Although these devices effectively improve survival, atrial and ventricular arrhythmias are common, predispose these patients to additional risk, and complicate patient management. However, there is no consensus on best practices for the medical management of these arrhythmias or on the optimal timing for procedural interventions in patients with refractory arrhythmias. Although the vast majority of these patients have preexisting cardiovascular implantable electronic devices or cardiac resynchronization therapy, given the natural history of heart failure, it is common practice to maintain cardiovascular implantable electronic device detection and therapies after LVAD implantation. Available data, however, are conflicting on the efficacy of and optimal device programming after LVAD implantation. Therefore, the primary objective of this scientific statement is to review the available evidence and to provide guidance on the management of atrial and ventricular arrhythmias in this unique patient population, as well as procedural interventions and cardiovascular implantable electronic device and cardiac resynchronization therapy programming strategies, on the basis of a comprehensive literature review by electrophysiologists, heart failure cardiologists, cardiac surgeons, and cardiovascular nurse specialists with expertise in managing these patients. The structure and design of commercially available LVADs are briefly reviewed, as well as clinical indications for device implantation. The relevant physiological effects of long-term exposure to continuous-flow circulatory support are highlighted, as well as the mechanisms and clinical significance of arrhythmias in the setting of LVAD support.
Morphology and Function of the Lymphatic Vasculature in Patients With a Fontan Circulation
Authors: Mohanakumar Sheyanth , Telinius Niklas , Kelly Benjamin , Lauridsen Henrik , Boedtkjer Donna , Pedersen Michael , de Leval Marc , Hjortdal Vibeke
Published: April 2019

Background:

The Fontan procedure has revolutionized the treatment of univentricular hearts. However, it is associated with severe complications such as protein-losing enteropathy, plastic bronchitis, and peripheral edema that may involve the lymphatic circulation. We aimed to assess lymphatic function and morphology in patients with a univentricular circulation.

Methods:

The functional state of lymphatic vessels in the lower extremities of patients with a Fontan circulation (n=10) was investigated using the novel technique near-infrared fluorescence imaging and compared with an age-, sex-, and weight-matched control group of healthy volunteers (n=10). The lymphatic morphology was described using T2-weighted magnetic resonance imaging, and microvascular permeability was estimated by strain gauge plethysmography.

Results:

The Fontan patients had 17% lower lymphatic pumping pressure (50±3.1 mm Hg) compared with controls (60±2.8 mm Hg;
P
=0.0341) and a 62% higher contraction frequency (0.8±0.1 min
−1
) compared with the healthy controls (0.5±0.1 min
−1
;
P
=0.0432). Velocity by which the lymph is moved and refill time after manual emptying of the lymphatic vessels showed no differences between the 2 groups. The thoracic duct was elongated 10% (
P
=0.0409) and with an abnormal course in the Fontan patients compared with normal. No difference in microvascular permeability was found between the 2 groups.

Conclusions:

Patients with a Fontan circulation have an impaired lymphatic pumping capacity and morphologically changed thoracic duct. Our results indicate a challenged lymphatic vasculature in the Fontan circulation and may play a role in the pathogenesis of the complications that are seen in Fontan patients.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03379805.
Abstract 1: Readmission Rates Across All Insurance Types After Passage of the Hospital Readmissions Reduction Program: A Nationwide Analysis
Authors: Ferro Enrico G , Secemsky Eric A , Wadhera Rishi K , Choi Eunhee , Strom Jordan B , Wasfy Jason H , Wang Yun , Shen Changyu , Yeh Robert W
Published: April 2019

Introduction:
Since implementation of the Hospital Readmission Reduction Program (HRRP), readmission rates have declined among Medicare patients hospitalized with conditions targeted by the policy - myocardial infarction, heart failure, and pneumonia. It is unknown if similar reductions occurred for other insurance types (Medicaid, private).

Methods:
We conducted a difference-in-difference analysis using the Nationwide Readmission Database. First, we calculated quarterly readmission rates for each insurance type and target condition from 2010 to 2014. Second, we compared how quarterly readmission rates for target conditions changed before (2010-2012) and after HRRP implementation (2012-2014), using changes in readmissions for non-target conditions as controls. The analysis included 3,737,589 patients with target conditions and 31,096,617 patients with non-target conditions.

Results:
Following HRRP implementation, readmission rates declined for both Medicare and Medicaid patients. Medicaid readmissions for patients with target conditions declined at a significantly greater rate compared to non-target conditions, both in aggregate (change in slope between pre- and post-HRRP periods, -0.044%/quarter [95% CI -0.061; -0.027]), and for each condition: acute myocardial infarction (-0.098 [-0.132; -0.064]), heart failure (-0.030 [-0.055; -0.005]) and pneumonia (-0.079 [-0.107;-0.051]). Composite Medicaid readmission rates, however, remained higher than Medicare. Privately-insured patients had the lowest aggregate readmission rates throughout the study period, with no additional decline after HRRP implementation.

Conclusions:
The HRRP was associated with reductions in readmissions that extended to the Medicaid population. These findings may reflect the effect of system-wide efforts to reduce readmissions in response to the policy. Medicaid readmission rates, however, remained greater compared to other insurers, and should be considered a focus for future readmission reduction initiatives. Figure. Change in Readmission Rates for All Target Conditions, Across Insurance Types

Points represent quarterly risk-adjusted readmission rates. Solid lines were generated from these points through a piecewise linear model. The dashed line separates the pre- and post-HRRP periods.
Abstract 113: Mitral Leaflet Clip Procedure Outcomes: Analysis from the National Cardiovascular Data Registry
Authors: Covas Pedro , Alzahrani Talal , McCaffrey James , Yunus Raza , Krepp Joseph , Mazhari Ramesh , Nagy Christian , Reiner Jonathan
Published: April 2019

Introduction:
Mitral regurgitation is one of the most common valvular diseases worldwide. Treatment for severe mitral regurgitation (MR) commonly involves surgical replacement of the mitral valve, but for those who are poor surgical candidates, another option has become mitral valve repair with a mitral leaflet clip procedure (MLCP). In this study, we conducted a descriptive analysis for all patients who underwent MLCP in the United States to investigate preoperative, intraoperative, and postoperative characteristics, techniques, complications, and clinical outcomes.

Methods:
The National Cardiovascular Data Registry (NCDR) was used to summarize the baseline demographics and procedural quality measures of all patients who underwent MLCP between 2014 and 2017. The change in the demographics, mortality, complications, and clinical outcomes were summarized and visualized in graphs.

Results:
The number of subjects who underwent mitral valve repair increased from 1,023 subjects in 2014 to 5,075 in 2017. The overall mortality rates are relatively unchanged (2.6% to 2.4%). However, there was an improvement in 30-day mortality (4.5% to 4.0%). The rate of patients with low STS scores increased (34% to 50%). Overall, the rate of patients with functional MR who received mitral clips are low (<10%). Of note, there has been a decrease in the number of patients who are 80 years old and older (62% to 56%). Intra-operatively, there were fewer complications (14.6% to 12.2%) including fewer clips not deployed (5.3% to 3.5%) related to a decrease in leaflets not being able to be grasped. Interestingly, there was an increase in the percentage of patients with mitral valve pressure gradient <= 5 mmHg (71.5% to 72.5%). Regarding 30-day follow-ups, our results have shown that residual mitral valve regurgitation (moderate or greater) has decreased from 39% to 5%, with a decrease in the number of clips attempted per patient. NYHA class IV symptoms at 30 days decreased from 4.2% to 3.1%. Finally, follow up echocardiograms changed in approach, with an increase in trans-thoracic (TTE) and a decrease in trans-esophageal (TEE) (86% TEE in 2014 vs. 86% TTE in 2017).

Conclusions:
Our interpretation shows a trend that MLCP continues to be a viable option for MR. The rate of procedures is expected to increase especially among younger patients with low STS scores and functional MR as results of the COAPT trial. We expect a continued decrease in complications and continued intra-operative success shown by improvement in mitral regurgitation.