bluuebunny/crossref_metadata_2025 huggingface dataset:
Color image representation model and its application based on an improved FRQI
Authors: Li Panchi , Liu Xiande
Published: December 2017

To address quantum description for color images, an improved FRQI model called FRQCI is proposed in this paper. In our model, the qubit has two-phase parameters [Formula: see text] and [Formula: see text], and the primary color R is stored in [Formula: see text], the primary colors G and B are stored in [Formula: see text]. We provide several simple image processing operators, including color change and geometric transformation. Next, we focus on an encryption algorithm, which includes two parts: position scrambling and color transformation. All operations involved in this paper are implemented by the rotation of the qubit on the Bloch sphere. The simulation results on classical computer show the effectiveness of the proposed method.
On the Derivation of the GKLS Equation for Weakly Coupled Systems
Authors: Facchi Paolo , Ligabò Marilena , Yuasa Kazuya
Published: December 2017

We consider the reduced dynamics of a small quantum system in interaction with a reservoir when the initial state is factorized. We present a rigorous derivation of a GKLS master equation in the weak-coupling limit for a generic bath, which is not assumed to have a bosonic or fermionic nature, and whose reference state is not necessarily thermal. The crucial assumption is a reservoir state endowed with a mixing property: the n-point connected correlation function of the interaction must be asymptotically bounded by the product of two-point functions (clustering property).
Non-Markovianity over Ensemble Averages in Quantum Complex Networks
Authors: Nokkala Johannes , Maniscalco Sabrina , Piilo Jyrki
Published: December 2017

We consider bosonic quantum complex networks as structured finite environments for a quantum harmonic oscillator and investigate the interplay between the network structure and its spectral density, excitation transport properties and non-Markovianity. After a review of the formalism used, we demonstrate how even small changes to the network structure can have a large impact on the transport of excitations. We then consider the non-Markovianity over ensemble averages of several different types of random networks of identical oscillators and uniform coupling strength. Our results show that increasing the number of interactions in the network tends to suppress the average non-Markovianity. This suggests that tree networks are the random networks optimizing this quantity.
Optical properties of mesoporous photonic crystals, filled with dielectrics, ferroelectrics and piezoelectrics
Authors: Gorelik V. S. , Bi Dongxue , Fei Guang Tao
Published: December 2017

At present, it is very important to create new types of mirrors, nonlinear light frequency transformers and optical filters with controlled optical properties. In this connection, it is of great interest to study photonic crystals. Their dielectric permittivity varies periodically in space with a period permitting Bragg diffraction of light. In this paper, we have investigated the optical properties of mesoporous three-dimensional (3D) opal-type and one-dimensional (1D) anodic alumina photonic crystals, filled with different dielectrics, ferroelectrics and piezoelectrics. We have compared the optical properties of initial mesoporous photonic crystals and filled with different substances. The possibility of mesoporous photonic crystals using selective narrow-band light filters in Raman scattering experiments and nonlinear mirrors has been analyzed. The electromagnetic field enhancing in the case of exciting light frequency close to the stop band edges has been established. The optical harmonics and subharmonics generation in mesoporous crystals, filled with ferroelectrics and piezoelectrics was proposed.
Groundwater Chemistry and Overpressure Evidences in Cerro Prieto Geothermal Field
Authors: Morales-Arredondo Ivan , Armienta María Aurora , Segovia Nuria
Published: December 2017

In order to understand the geological and hydrogeological processes influencing the hydrogeochemical behavior of the Cerro Prieto Geothermal Field (CP) aquifer, Mexico, a characterization of the water samples collected from geothermal wells was carried out. Different hydrochemical diagrams were used to evaluate brine evolution of the aquifer. To determine pressure conditions at depth, a calculation was performed using hydrostatic and lithostatic properties from CP, considering geological characteristics of the study area, and theoretical information about some basin environments. Groundwater shows hydrogeochemical and geological evidences of the diagenetic evolution that indicate overpressure conditions. Some physical, chemical, textural, and mineralogical properties reported in the lithological column from CP are explained understanding the evolutionary process of the sedimentary material that composes the aquifer.
Efficacy of Once Daily versus Divided Daily Administration of Low Daily Dosage (15 mg/Day) of Methimazole in the Induction of Euthyroidism in Graves’ Hyperthyroidism: A Randomized Controlled Study
Authors: Sriussadaporn Sutin , Pumchumpol Wanwaroon , Lertwattanarak Raweewan , Kunavisarut Tada
Published: December 2017

Background. Previous studies used unequal or high daily dosages of methimazole (MMI) to compare the efficacy of once daily dose regimen (OD-MMI) with that of divided daily doses regimen (DD-MMI) in inducing euthyroidism. Objectives. To compare the efficacy of OD-MMI to that of DD-MMI using low daily dosage of MMI in inducing euthyroidism. Methods. Fifty patients with clinically nonsevere Graves’ hyperthyroidism were randomized to be treated with 15 mg/day OD-MMI or 15 mg/day DD-MMI. Results. 21 cases (84%) in OD-MMI and 23 cases (92%) in DD-MMI were eligible for analyses. During the treatment, there was no difference in baseline characteristics, serum FT3 and FT4 reductions, and cumulative rate of achieving euthyroidism (4.8% versus 4.3%, 28.6% versus 34.8%, 71.4% versus 82.6%, and 85.7% versus 87.0% at 2, 4, 8, and 12 weeks, resp.) between both regimens. Hypothyroidism developed in DD-MMI significantly more than in OD-MMI (17.4% versus 0%, p<0.05). Conclusions. Treatment with MMI at a low daily dosage of 15 mg/day OD-MMI is as effective as DD-MMI in the reduction of serum thyroid hormone levels and induction of euthyroidism. The OD-MMI regimen is preferable to the DD-MMI regimen in the treatment of clinically nonsevere Graves’ hyperthyroidism. This trial is registered with Thai Clinical Trials Registry: TCTR20170529001.
Safety Criteria and Standards for Bearing Capacity of Foundation
Authors: Li Yanlong , Fan Wangtao , Chen Xuguang , Liu Yunhe , Chen Bo
Published: December 2017

This paper focuses on the evaluation standards of factor of safety for foundation stability analysis. The problem of foundation stability is analyzed via the methods of risk analysis of engineering structures and reliability‐based design, and the factor of safety for foundation stability is determined by using bearing capacity safety‐factor method (BSFM) and strength safety‐factor method (SSFM). Based on a typical example, the admissible factors of safety were calibrated with a target reliability index specified in relevant standards. Two safety criteria and their standards of bearing capacity of foundation for these two methods (BSFM and SSFM) were established. The universality of the safety criteria and their standards for foundation reliability was verified based on the concept of the ratio of safety margin (RSM).
Inhibiting Interleukin 17 Can Ameliorate the Demyelination Caused by A. cantonensis via iNOS Inhibition
Authors: Ying Feng , Cunjing Zheng , Feng Feng , Shuo Wan , Xin Zeng , Fukang Xie , Zhongdao Wu
Published: December 2017

Angiostrongylus cantonensis (A. cantonensis) is an important food-borne parasitic disease. Previous study showed that A. cantonensis infection can cause demyelination in the central nerve system, but the mechanism of action has not been understood. To explore the mechanism and to look for effective therapeutic methods, interleukin 17A (IL-17A) and iNOS expressions were detected during A. cantonensis infection. In addition, IL-17A-neutralizing antibody was applied to treat A. cantonensis-infected mice. In our results, we found that IL-17A and iNOS RNA expressions increased gradually in the process of A. cantonensis infection. When infected mice were treated with IL-17A-neutralizing antibody, the pathologic changes of demyelination alleviated obviously, followed with the elevation of myelin basic protein (MBP) in the brain. In addition, the iNOS expression of the brain in infected animals also showed a decrease in astrocytes. Our study provided evidence that IL-17A may take part in the demyelination caused by A. cantonensis and inhibiting IL-17A expression can ameliorate the pathologic changes of demyelination. Moreover, the decreasing of iNOS expression may be the key reason for the effect of IL-17A inhibition on demyelination caused by A. cantonensis.
Color Distribution Pattern Metric for Person Reidentification
Authors: Ye Yingsheng , Zhang Xingming , Ng Wing W. Y.
Published: December 2017

Accompanying the growth of surveillance infrastructures, surveillance IP cameras mount up rapidly, crowding Internet of Things (IoT) with countless surveillance frames and increasing the need of person reidentification (Re-ID) in video searching for surveillance and forensic fields. In real scenarios, performance of current proposed Re-ID methods suffers from pose and viewpoint variations due to feature extraction containing background pixels and fixed feature selection strategy for pose and viewpoint variations. To deal with pose and viewpoint variations, we propose the color distribution pattern metric (CDPM) method, employing color distribution pattern (CDP) for feature representation and SVM for classification. Different from other methods, CDP does not extract features over a certain number of dense blocks and is free from varied pedestrian image resolutions and resizing distortion. Moreover, it provides more precise features with less background influences under different body types, severe pose variations, and viewpoint variations. Experimental results show that our CDPM method achieves state-of-the-art performance on both 3DPeS dataset and ImageLab Pedestrian Recognition dataset with 68.8% and 79.8% rank 1 accuracy, respectively, under the single-shot experimental setting.
Yangyin Runchang Decoction Improves Intestinal Motility in Mice with Atropine/Diphenoxylate‐Induced Slow‐Transit Constipation
Authors: Jiang Feng , Zhou Jin-Yong , Wu Jian , Tian Fang , Zhu Xuan-Xuan , Zhu Chang-Le , Yang Bo-Lin , Chen Yu-Gen
Published: December 2017

This study assessed the efficacy and mechanism of action of Yangyin Runchang decoction (YRD) in the treatment of slow‐transit constipation (STC). ICR mice were randomly divided into four groups (n = 10/group) and treated with saline (normal control; NC), atropine/diphenoxylate (model control; MC; 20 mg/kg), or atropine/diphenoxylate plus low‐dose YRD (L‐YRD; 29.6 g/kg) or high‐dose YRD (H‐YRD; 59.2 g/kg). Intestinal motility was assessed by evaluating feces and the intestinal transit rate (ITR). The serum level of stem cell factor (SCF) and changes in interstitial cells of Cajal (ICCs) were also evaluated. Additionally, the expression of SCF and c‐kit and the intracellular Ca2+ concentration [Ca2+]I were investigated. Fecal volume and ITR were greater in the L‐YRD and H‐YRD groups than in the MC group. The serum SCF level was lower in the MC group than in the NC group; this effect was ameliorated in the YRD‐treated mice. Additionally, YRD‐treated mice had more ICCs and elevated expression of c‐kit and membrane‐bound SCF, and YRD also increased [Ca2+]I in vitro in isolated ICCs. YRD treatment in this STC mouse model was effective, possibly via the restoration of the SCF/c‐kit pathway, increase in the ICC count, and enhancement of ICC function by increasing [Ca2+]i.
Primary Resonance of van der Pol Oscillator under Fractional-Order Delayed Feedback and Forced Excitation
Authors: Chen Jufeng , Li Xianghong , Tang Jianhua , Liu Yafeng
Published: December 2017

The primary resonance of van der Pol oscillator under fractional-order delayed negative feedback and forced excitation is studied. Firstly, the approximate analytical solution is obtained based on the averaging method, and it could be found that the fractional-order delayed feedback has not only the property of delayed velocity feedback but also that of delayed displacement feedback. Moreover, the amplitude-frequency equation for the steady-state solution is established, and its stability conditions are also obtained. Then, the results of the approximate analytical solution and numerical integration are compared and analyzed. The agreement between the two methods is very high, so that the correctness and accuracy of the approximate analytical solution are verified. Finally, the effects of all the parameters in the fractional-order delayed feedback on the amplitude-frequency curves are analyzed. It could be concluded that fractional-order delayed feedback has important influences on the dynamical behavior of van der Pol oscillator, which is very significant to the optimization and control of a similar system.
Cancer in ANCA-Associated Glomerulonephritis: A Registry-Based Cohort Study
Authors: Sriskandarajah Sanjeevan , Bostad Leif , Myklebust Tor Åge , Møller Bjørn , Skrede Steinar , Bjørneklett Rune
Published: December 2017

Background. Immunosuppressive therapy for antineutrophil cytoplasmic antibody-associated vasculitis has been associated with increased malignancy risk.Objectives. To quantify the cancer risk associated with contemporary cyclophosphamide-sparing protocols.Methods. Patients from the Norwegian Kidney Biopsy Registry between 1988 and 2012 who had biopsy-verified pauci-immune glomerulonephritis and positive antineutrophil cytoplasmic antibody (ANCA) serology were included. Standardised incidence ratios (SIRs) were calculated to compare the study cohort with the general population.Results. The study cohort included 419 patients. During 3010 person-years, cancer developed in 41 patients (9.79%); the expected number of cancer cases was 37.5 (8.95%). The cohort had SIRs as follows: 1.09, all cancer types (95% CI, 0.81 to 1.49); 0.96, all types except nonmelanoma skin cancer (95% CI, 0.69 to 1.34); 3.40, nonmelanoma skin cancer (95% CI, 1.62 to 7.14); 3.52, hematologic cancer (95% CI, 1.32 to 9.37); 2.12, posttransplant cancer (95% CI, 1.01 to 4.44); and 1.53, during the 1–5-year follow-up after diagnosis (95% CI, 1.01 to 2.32).Conclusions. Cancer risk did not increase significantly in this cohort with ANCA-associated glomerulonephritis. However, increased risk of nonmelanoma skin cancer, posttransplant cancer, and hematologic cancer indicates an association between immunosuppression and malignancy.
Asynchronous Bilateral Ovarian Torsion: Three Cases, Three Lessons
Authors: Lucchetti M. C. , Orazi C. , Lais A. , Capitanucci M. L. , Caione P. , Bakhsh H.
Published: December 2017

Background. Ovarian torsion (OT) is a serious condition, and delay in surgical intervention may result in loss of the ovary. Children and adolescents who have suffered from ovarian torsion may be at risk for asynchronous torsion of the contralateral ovary. Study objective. Three cases of asynchronous bilateral ovarian torsion were reported to analyse clinical history of three patients, to review the current literature, and to draw a conclusion for future treatment. Design. Case reports and review of the literature. Result. When a prepubertal girl presents with an ovarian torsion, several considerations have to be taken in account in order to preserve her future fertility; in particular, the pediatric surgeon/gynecologist has to preserve as much as possible the twisted ovary in addition to considering the fate of the contralateral ovary. Summary and Conclusions. Pelvic pain in a young girl has always raised the clinical suspect of an ovarian torsion; the possibility of asynchronous bilateral ovarian torsion is rare, but it is described in the literature and has catastrophic consequences; this condition has to be known and treated in the proper way by pediatric surgeons as well as by gynecologists in order to maximize the future fertility of the young patients.
Correlation Analysis of Water Demand and Predictive Variables for Short‐Term Forecasting Models
Authors: Brentan B. M. , Meirelles G. , Herrera M. , Luvizotto E. , Izquierdo J.
Published: December 2017

Operational and economic aspects of water distribution make water demand forecasting paramount for water distribution systems (WDSs) management. However, water demand introduces high levels of uncertainty in WDS hydraulic models. As a result, there is growing interest in developing accurate methodologies for water demand forecasting. Several mathematical models can serve this purpose. One crucial aspect is the use of suitable predictive variables. The most used predictive variables involve weather and social aspects. To improve the interrelation knowledge between water demand and various predictive variables, this study applies three algorithms, namely, classical Principal Component Analysis (PCA) and machine learning powerful algorithms such as Self‐Organizing Maps (SOMs) and Random Forest (RF). We show that these last algorithms help corroborate the results found by PCA, while they are able to unveil hidden features for PCA, due to their ability to cope with nonlinearities. This paper presents a correlation study of three district metered areas (DMAs) from Franca, a Brazilian city, exploring weather and social variables to improve the knowledge of residential demand for water. For the three DMAs, temperature, relative humidity, and hour of the day appear to be the most important predictive variables to build an accurate regression model.
Tumor-Like Reaction to Polypropylene Mesh from a Mid-Urethral Sling Material Resembling Giant Cell Tumor of Vagina
Authors: Azadi Ali , Bradley James A. , O’Connor Dennis M. , Azadi Amir , Ostergard Donald R.
Published: December 2017

Background. Polypropylene material is widely used in gynecological surgery. There are few reports regarding its carcinogenic potential. There is lack of evidence supporting tumor formation directly attributed to the use of polypropylene material. Case. This patient is a 49-year-old woman with a history of stress urinary incontinence which required a MiniArc® Sling who presented with a hard, tender, immobile mass on the anterior vaginal wall. Pathological analysis of the mass revealed a tumor-like reaction to the polypropylene material that resembled a giant cell tumor of soft tissue. Conclusion. The use of polypropylene in surgery is ubiquitous across disciplines; thus consideration for a tumor-like reaction to the material should exist for patients who present with a mass near the surgical site.
Efficient Iris Localization via Optimization Model
Authors: Wang Qi , Liu Zhipeng , Tong Shu , Yang Yuqi , Zhang Xiangde
Published: December 2017

Iris localization is one of the most important processes in iris recognition. Because of different kinds of noises in iris image, the localization result may be wrong. Besides this, localization process is time‐consuming. To solve these problems, this paper develops an efficient iris localization algorithm via optimization model. Firstly, the localization problem is modeled by an optimization model. Then SIFT feature is selected to represent the characteristic information of iris outer boundary and eyelid for localization. And SDM (Supervised Descent Method) algorithm is employed to solve the final points of outer boundary and eyelids. Finally, IRLS (Iterative Reweighted Least‐Square) is used to obtain the parameters of outer boundary and upper and lower eyelids. Experimental result indicates that the proposed algorithm is efficient and effective.
The Principle of Social Scaling
Authors: dos Santos Paulo L.
Published: December 2017

This paper identifies a general class of economic processes capable of generating the first-moment constraints implicit in the observed cross-sectional distributions of a number of economic variables: processes of social scaling. Across a variety of settings, the outcomes of economic competition reflect the normalization of individual values of certain economic quantities by average or social measures of themselves. The resulting socioreferential processes establish systematic interdependences among individual values of important economic variables, which under certain conditions take the form of emergent first-moment constraints on their distributions. The paper postulates a principle describing this systemic regulation of socially scaled variables and illustrates its empirical purchase by showing how capital- and labor-market competition can give rise to patterns of social scaling that help account for the observed distributions of Tobin’s q and wage income. The paper’s discussion embodies a distinctive approach to understanding and investigating empirically the relationship between individual agency and structural determinations in complex economic systems and motivates the development of observational foundations for aggregative, macrolevel economic analysis.
The Topography of Stuttering in Cantonese
Authors: Law Thomas , Packman Ann , Onslow Mark , To Carol K.-S. , Tong Michael C.-F. , Lee Kathy Y.-S.
Published: December 2017

Objective: This is the first study to investigate the behavioral nature (topography) of stuttering in Cantonese. Cantonese, a Sino-Tibetan language, is both tonal and syllable-timed. Previous studies of stuttering topography have mainly been in Western languages, which are mainly stress-timed. Methods: Conversational speech samples were collected from 24 native Cantonese-speaking adults who stuttered. Six consecutive stuttering moments from each participant were analyzed using the Lidcombe behavioral data language (LBDL). A complexity analysis based on the LBDL was developed to indicate the proportion of multiple-behavior stuttering moments for each participant. Results: There was no significant difference in the frequency of the 7 LBDL behaviors. Almost half the stuttering moments across participants were reported as complex, containing more than 1 stuttering behavior, and stuttering complexity correlated significantly with stuttering severity. Conclusions: These preliminary findings require replication because of their important theoretical and clinical implications. Differences in topography across languages have the potential to contribute to our understanding of the nature of stuttering. Clinically, the recognition of such differences may assist practitioners in identifying stuttering, for example when screening for early stuttering. The LBDL complexity score developed in this study has the potential to be used in other languages.
Herpes Encephalitis: A Mortal Complication in a Patient Treated with Immunosuppressive Drugs because of Immune-Related Adverse Events after Ipilimumab Treatment
Authors: van Montfort Lieke , Loos Caroline M. , Anten Monique , Jansen Rob L.H.
Published: December 2017

Until a few years ago, metastatic melanoma had a poor prognosis with limited treatment options. These therapeutics options and thereby median survival have increased obviously over 5 years with the arrival of immunotherapeutic drugs like ipilimumab, nivolumab, and pembrolizumab. Nowadays, ipilimumab is often used in patients with metastatic melanoma. In this paper, we report a case of a 68-year-old man who developed, and eventually died of, herpes encephalitis after introducing ipilimumab as treatment for metastatic melanoma. To our knowledge, this is the first report in which herpes encephalitis as a complication after ipilimumab and infliximab treatment is described and we would like to make physicians aware of this possible serious neurological complication, especially when a patient has a history of herpes simplex infection.
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Nalbuphine ER Tablets for Uremic Pruritus
Authors: Mathur Vandana S. , Kumar Jayant , Crawford Paul W. , Hait Howard , Sciascia Thomas ,   for the TR02 Study Investigators
Published: December 2017

Background: Pruritus is a distressing hallmark of the uremic condition, affecting approximately 60% of hemodialysis patients. Abnormal endogenous opioid ligand activity at μ and κ-opioid receptors has been postulated as a mechanism in uremic pruritus. Nalbuphine is a μ-opioid antagonist and κ-opioid agonist. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 373 hemodialysis patients with moderate or severe uremic pruritus were randomized in a 1: 1:1 ratio to nalbuphine extended-release tablets 120 mg (NAL 120), 60 mg (NAL 60), or placebo and treated for 8 weeks. Three hundred seventy-one were analyzed for efficacy. The primary endpoint was the change from baseline to treatment weeks 7 and 8 in itching intensity on a Numerical Rating Scale (NRS, 0 [no itching]; 10 [worst possible itching]) using an intent-to-treat approach. The aim was to evaluate the safety and antipruritic efficacy of NAL. Results: The mean duration of itching was 3.2 years. From a baseline NRS of 6.9 (1.5), the mean NRS declined by 3.5 (2.4) and by 2.8 (2.2) in NAL 120 mg and the placebo groups, respectively (p = 0.017). There was no evidence of tolerance. A trend for less sleep disruption due to itching (p = 0.062, NAL 120 vs. placebo) was also observed. There were no significant differences between NAL 60 vs. placebo. Serious adverse events occurred in 6.7, 12.7, and 15.4% in the NAL 120, NAL 60, and placebo groups respectively. Conclusions: In this largest-to-date randomized controlled trial in uremic pruritus, NAL 120 durably and significantly reduced the itching intensity among hemodialysis patients.
Recurrent Stroke in a Young Woman with a Single Pulmonary Arteriovenous Fistula: An Unusual Association
Authors: Sousa Sandra , Vasco Costa Nuno , Carmona Cátia , Coimbra Élia , Pita Fernando
Published: December 2017

Introduction: Cryptogenic stroke is present in about 40% of ischemic stroke patients. Extracardiac shunt related to pulmonary arteriovenous fistula (PAVF) could be a rare potential risk factor for embolic stroke. Most PAVFs are multiple, congenital, and associated with hereditary conditions. On the other hand, isolated PAVFs are rare conditions and an uncommon cause of cryptogenic stoke. Case Report: We describe a case of a young woman without history of respiratory diseases or vascular risk factors, who presented with acute onset of transitory aphasia and right hemiplegia. She had a history of a transient ischemic attack, 3 years before, and migraine headaches. Brain MRI showed an acute cortical ischemic lesion and a chronic ischemic lesion. Diagnostic workup with transcranial Doppler ultrasonography revealed a significant right-to-left shunt with curtain pattern, and echocardiogram did not show structural abnormalities. An isolated small PAVF was diagnosed on pulmonary angiogram. Despite the rare association between isolated small PAVF and stroke, we decided to treat it with coil embolization because of recurrence of stroke, cortical lesions suggestive of embolic source, significant right-left shunt, and risk of future complications. Conclusions: This case highlights the importance of search, identification, and interpretation of causes of cryptogenic strokes to better choose therapy to reduce the stroke recurrence risk. Although unusual, PAVF detection is a treatable cause of stroke and the therapeutic decisions should take into account the characteristics of the PAVF and the degree of suspicion regarding the cause-effect relationship between PAVF and stroke.
Potential of Moringa oleifera in the Treatment of Benign Prostate Hyperplasia: Role of Antioxidant Defence Systems
Authors: Ishola Ismail O. , Yemitan Kayode O. , Afolayan Olasunmbo O. , Anunobi Charles C. , Durojaiye Tobi E.
Published: December 2017

Objective: This study sought to evaluate the protective effect of ethanolic leaf extract of Moringa oleifera on testosterone-induced benign prostatic hyperplasia (BPH) in male Sprague-Dawley rats. Materials and Methods: BPH was induced in rats by the administration of testosterone propionate (3 mg/kg, s.c., in olive oil) for 4 weeks. M. oleifera (50, 100, or 200 mg/kg), celecoxib (20 mg/kg), or M. oleifera (50 mg/kg) + celecoxib (20 mg/kg) were orally administered daily 15 min before testosterone. On day 29, blood was collected to measure the levels of serum testosterone and prostate-specific antigen before the animals were sacrificed. The prostates were weighed, assayed, and histologically examined. Results: M. oleifera significantly reduced the testosterone-induced increase in prostate weight (20.16%), prostate index (65.85%), serum testosterone (72.86%), and prostate-specific antigen (48.49%). Testosterone caused a significant increase in malondialdehyde (73%) as well as a reduction in glutathione (62.5%), superoxide dismutase (50%), and catalase (64%) activities which were attenuated by M. oleifera with a peak effect obtained at 100 mg/kg. The disruption of prostate histoarchitecture by testosterone was also ameliorated by M. oleifera. Conclusion: M. oleifera prevented testosterone-induced BPH through enhancement of antioxidant defence mechanisms, and hence could be used as an adjunct in the treatment of BPH.
Renal Function, Time in Therapeutic Range and Outcomes in Warfarin-Treated Atrial Fibrillation Patients: A Retrospective Analysis of Nationwide Registries
Authors: Bonde Anders , Lip Gregory , Kamper Anne-Lise , Staerk Laila , Torp-Pedersen Christian , Gislason Gunnar , Olesen Jonas
Published: December 2017

Patients with severely reduced renal function have been excluded from randomized controlled trials of oral anticoagulation in atrial fibrillation (AF). Warfarin treatment in this population is controversial and data on anticoagulation control and the impact on adverse outcomes are needed. By individual-level linkage of nationwide registries, we identified all patients discharged from hospitals with AF in Denmark between 1997 and 2011. Patients with available serum creatinine tests were categorized according to the estimated glomerular filtration rate (eGFR). Time in therapeutic range (TTR) was calculated using the Rosendaal method. The risk of stroke and bleeding was estimated using multivariable Cox regression analyses with eGFR and TTR estimated time dependently throughout follow-up. We identified 10,423 warfarin-treated AF patients with available international normalized ratio and creatinine tests; 5,527 with eGFR > 60 mL/min/1.73 m2, 4,524 with eGFR 30–60 mL/min/1.73 m2 and 372 with eGFR < 30 mL/min/1.73 m2. Median TTR was 66.7, 61.2 and 49.7% in patients with eGFR > 60, 30–59 and <30 mL/min/1.73 m2, respectively. A TTR < 70% was associated with a higher risk of stroke/thromboembolism (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.20–1.60) and bleeding (HR: 1.22; 95% CI: 1.05–1.42) among patients with eGFR of 30 to 59 and a trend towards higher risk of stroke/thromboembolism (HR: 1.24; 95% CI: 0.86–1.80) and bleeding (HR: 1.17; 95% CI: 0.83–1.65) among patients with eGFR < 30 mL/min/1.73 m2. In conclusion, warfarin-treated AF patients with reduced renal function have suboptimal anticoagulation control which was related to the risk of adverse outcomes.
Low-Dose Aspirin after an Episode of Haemorrhagic Stroke Is Associated with Improved Survival
Authors: González-Pérez Antonio , Gaist David , de Abajo Francisco , Sáez María , García Rodríguez Luis
Published: December 2017

We aimed at investigating how antiplatelet drug use affected mortality in patients with a history of haemorrhagic stroke (HS). Thus, starting 30 days after an HS episode, we followed 1,004 patients with intracerebral haemorrhage (ICH) and 929 patients with subarachnoid haemorrhage (SAH) for a median of 6.4 years. We estimated the effect of time-dependent exposure to antiplatelets after HS on all-cause mortality. Cox proportional hazard models were used to compute adjusted hazard ratios (aHRs) and 95% confidence intervals (CI).

We found that current use of low-dose aspirin was associated with a 32% improved survival (aHR = 0.68; 95% CI: 0.53–0.88), with a similar association among ICH (aHR = 0.66; 95% CI: 0.49–0.89) and SAH (aHR = 0.61; 95% CI: 0.36–1.04) patients. A statistically significant improved survival associated with current use of low-dose aspirin during follow-up was only observed among individuals who used antithrombotic drugs in the year before the HS (prior use: aHR = 0.56; 95% CI: 0.39–0.80; non-prior use: aHR = 0.87; 95% CI: 0.61–1.24). Current use of clopidogrel was not associated with survival (aHR = 1.35; 95% CI: 0.88–2.08). Statin use was associated with improved survival (aHR = 0.38; 95% CI: 0.31–0.47). On the other hand, discontinuation of statins (aHR = 1.31; 95% CI: 1.02–1.68) or low-dose aspirin (aHR = 1.54; 95% CI: 1.21–1.97) was associated with decreased survival. In our study, use of low-dose aspirin after an episode of HS to reduce vascular risks is safe, particularly in patients who were on antithrombotic therapy before the episode. Our results suggest an improved survival associated with low-dose aspirin. This finding must be interpreted with care due to the observational nature of the study, and warrants further studies.
Erythrocyte Membrane Fluidity Alterations in Sudden Sensorineural Hearing Loss Patients: The Role of Oxidative Stress
Authors: Becatti Matteo , Marcucci Rossella , Mannucci Amanda , Gori Anna , Giusti Betti , Sofi Francesco , Mannini Lucia , Cellai Anna , Alessandrello Liotta Agatina , Mugnaini Marco , Emmi Giacomo , Prisco Domenico , Taddei Niccolò , Fiorillo Claudia
Published: December 2017

Introduction Sudden sensorineural hearing loss (SSNHL) involves an acute unexplained hearing loss, nearly always unilateral, that occurs over less than a 72-hour period. SSNHL pathogenesis is not yet fully understood. Cochlear vascular occlusion has been proposed as a potential mechanism of hearing damage and cochlear ischaemia has been related to alterations of cochlear microvessels. In addition, some researchers have focused their attention on the rheological alterations and blood hyperviscosity. Erythrocyte deformability plays a key role in determining blood viscosity, and it is critical to cochlear perfusion. It has been shown that oxidative stress-induced erythrocyte membrane fluidity alterations are linked to the progression of cardiovascular diseases.

Methods To determine whether erythrocytes from SSNHL patients show signs of oxidative stress, and whether this condition can modify the haemorheologic profile in these patients, we analysed haemorheologic profile and erythrocyte oxidative stress in 35 SSNHL patients and 35 healthy subjects, matched for age and sex. Fluorescence anisotropy was used to evaluate the fluidity of erythrocyte membranes.

Results Our results show a significant structural and functional involvement of erythrocyte membrane alterations in SSNHL, as well as elevated levels of membrane lipid peroxidation and intracellular reactive oxygen species (ROS) production. In addition, erythrocyte-derived ROS and erythrocyte lipid peroxidation positively correlated with whole blood viscosity and erythrocyte deformability. Moreover, in vitro experiments demonstrated that ROS display a key role in erythrocyte membrane fluidity.

Conclusion These findings indicate that erythrocyte oxidative stress plays a key role in the pathogenesis of SSNHL and pave the way to new therapeutic interventions.
Developmental Stage–Specific Manifestations of Absent TPO/c-MPL Signalling in Newborn Mice
Authors: Lorenz Viola , Ramsey Haley , Liu Zhi-Jian , Italiano Joseph , Hoffmeister Karin , Bihorel Sihem , Mager Donald , Hu Zhongbo , Slayton William , Kile Benjamin , Sola-Visner Martha , Ferrer-Marin Francisca
Published: December 2017

Congenital amegakaryocytic thrombocytopaenia (CAMT) is a disorder caused by c-MPL mutations that impair thrombopoietin (TPO) signalling, resulting in a near absence of megakaryocytes (MKs). While this phenotype is consistent in adults, neonates with CAMT can present with severe thrombocytopaenia despite normal MK numbers. To investigate this, we characterized MKs and platelets in newborn c-MPL
–/– mice. Liver MKs in c-MPL
–/– neonates were reduced in number and size compared with wild-type (WT) age-matched MKs, and exhibited ultrastructural abnormalities not found in adult c-MPL
–/– MKs. Platelet counts were lower in c-MPL
–/– compared with WT mice at birth and did not increase over the first 2 weeks of life. In vivo biotinylation revealed a significant reduction in the platelet half-life of c-MPL
–/– newborn mice (P2) compared with age-matched WT pups, which was not associated with ultrastructural abnormalities. Genetic deletion of the pro-apoptotic Bak did not rescue the severely reduced platelet half-life of c-MPL
–/– newborn mice, suggesting that it was due to factors other than platelets entering apoptosis early. Indeed, adult GFP+ (green fluorescent protein transgenic) platelets transfused into thrombocytopenic c-MPL
–/– P2 pups also had a shortened lifespan, indicating the importance of cell-extrinsic factors. In addition, neonatal platelets from WT and c-MPL
–/– mice exhibited reduced P-selectin surface expression following stimulation compared with adult platelets of either genotype, and platelets from c-MPL
–/– neonates exhibited reduced glycoprotein IIb/IIIa (GPIIb/IIIa) activation in response to thrombin compared with age-matched WT platelets. Taken together, our findings indicate that c-MPL deficiency is associated with abnormal maturation of neonatal MKs and developmental stage-specific defects in platelet function.
Thrombus Burden of Deep Vein Thrombosis and Its Association with Thromboprophylaxis and D-Dimer Measurement: Insights from the APEX Trial
Authors: Chi Gerald , Goldhaber Samuel , Hull Russell , Hernandez Adrian , Kerneis Mathieu , Al Khalfan Fahad , Cohen Alexander , Harrington Robert , Gibson C.
Published: December 2017

Background The aim of this study was to evaluate the effect of betrixaban on the occurrence of deep vein thrombosis (DVT) and also the extent of thrombus and to assess the association of baseline D-dimer with subsequent thrombus burden.

Methods In the APEX trial (ClinicalTrials.gov: NCT01583218), 7,513 acutely ill hospitalized medical patients were randomly assigned to extended-duration betrixaban (35–42 days) or enoxaparin (10 ± 4 days). D-dimer concentration was measured at baseline, and mandatory lower-extremity compression ultrasonography (CUS) was performed at 35 to 42 days. The thrombus burden of DVT was assessed by the number of non-compressible vascular segments in six target proximal veins and compared between treatment groups and D-dimer categories (≥2 × upper limit of normal [ULN] versus <2 × ULN).

Results Compared with enoxaparin, extended-duration betrixaban reduced the DVT risk at 35 to 42 days (any-dose: relative risk [RR] = 0.76 [95% confidence interval: 0.61–0.94]; p = 0.013; full-dose: RR = 0.70 [0.55–0.90]; p = 0.005). Patients who received betrixaban were more likely to have a lower thrombus burden (p = 0.012 for any-dose and p = 0.001 for full-dose). Elevated D-dimer at baseline was independently associated with a 2.12-fold increased risk of developing DVT (p < 0.001). A greater thrombus burden was also observed in those with D-dimer ≥ 2 × ULN compared with <2 × ULN (p < 0.0001).

Conclusion Extended-duration betrixaban reduced the number of venous segments with thrombosis at 35 to 42 days compared with enoxaparin. A positive D-dimer was associated with a greater extent of thrombus burden among acutely ill medical patients who developed DVT despite receiving thromboprophylaxis.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. ClinicalTrials.gov identifier: NCT01583218.
The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study for Patients on a Direct Oral Anticoagulant Who Need an Elective Surgery or Procedure: Design and Rationale
Authors: Douketis James , Spyropoulos Alex , Anderson Julia , Arnold Donald , Bates Shannon , Blostein Mark , Carrier Marc , Caprini Joseph , Clark Nathan , Coppens Michiel , Dentali Francesco , Duncan Joanne , Gross Peter , Kassis Jeannine , Kowalski Stephen , Lee Agnes , Le Gal Gregoire , Le Templier Geneviève , Li Na , MacKay Elizabeth , Shah Vinay , Shivakumar Sudeep , Solymoss Susan , Spencer Frederick , Syed Summer , Tafur Alfonso , Vanassche Thomas , Thiele Thomas , Wu Cynthia , Yeo Erik , Schulman Sam
Published: December 2017

Background The perioperative management of patients who take a direct oral anticoagulant (DOAC) for atrial fibrillation and require treatment interruption for an elective surgery/procedure is a common clinical scenario for which best practices are uncertain. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study is designed to address this unmet clinical need. We discuss the rationale for the PAUSE design and analysis plan as well as the rationale supporting the perioperative DOAC protocol.

Methods PAUSE is a prospective study with three parallel cohorts, one for each DOAC, to assess a standardized but patient-specific perioperative management protocol for DOAC-treated patients with atrial fibrillation. The perioperative protocol accounts for DOAC type, patient's renal function and surgery/procedure-related bleeding risk. The primary study aim is to demonstrate the safety of the PAUSE protocol for the perioperative management of each DOAC. The secondary aim is to determine the effect of the pre-procedure interruption on residual anticoagulation when measured by the dilute thrombin time for dabigatran and anti-factor Xa levels for rivaroxaban and apixaban. The study hypothesis is that the perioperative management protocol for each DOAC is safe for patient care, defined by expected risks for major bleeding of 1% (80% power to exclude 2%), and for arterial thromboembolism of 0.5% (80% power to exclude 1.5%) in each DOAC group.

Conclusion The PAUSE study has the potential to establish a standard-of-care approach for the perioperative management of DOAC-treated patients. The PAUSE management protocol is designed to be easily applied in clinical practice, as it is standardized and also patient specific.
Regional Differences in Antithrombotic Treatment for Atrial Fibrillation: Insights from the GLORIA-AF Phase II Registry
Authors: Mazurek Michał , Huisman Menno , Rothman Kenneth , Paquette Miney , Teutsch Christine , Diener Hans-Christoph , Dubner Sergio , Halperin Jonathan , Ma Chang , Zint Kristina , Elsaesser Amelie , Lu Shihai , Lip Gregory ,   on behalf of the GLORIA-AF Investigators
Published: December 2017

Introduction Although guideline-adherent antithrombotic therapy (ATT) for stroke prevention in atrial fibrillation (AF) is associated with lower mortality and thromboembolism, ATT uptake shows geographic variation worldwide. We aimed to assess thromboembolic risk and baseline ATT by geographic region and identify factors associated with prescription of ATT in a large, truly global registry of patients with recently diagnosed AF.

Methods and Results Our analysis comprises 15,092 patients newly diagnosed with non-valvular AF at risk for stroke, enrolled in Phase II of Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF). Global oral anticoagulation (OAC) use was 79.9%, being highest in Europe (90.1%), followed by Africa/Middle East (87.4%) and Latin America (85.3%), North America (78.3%) and Asia (55.2%). Among OAC users, vitamin K antagonists (VKAs) have been replaced by non-VKA OACs (NOACs) as the more prevalent OAC option in all regions, with highest use in North America (66.5%) and lowest in Asia (50.2%). In Asia, OAC was 80.4% in community hospitals but only 49.8% in university hospitals and 42.6% in specialist offices, and varied from 21.0% in China to 89.7% in Japan (NOACs at 5.8% in China and 83.3% in Japan). Globally, 76.5% of low-risk patients were prescribed ATT (46.1% OAC), whereas 17.7% high-risk patients were not anticoagulated (Europe 8.8%; North America 18.9%; Asia 42.4%).

Conclusion Substantial inter- and intra-regional differences in ATT for stroke prevention in AF are evident in this global registry. While guideline-adherent ATT can be further improved, NOACs are the main contributor to high OAC use worldwide.
Blood cultures on internal medicine: utilization profile and clinical implications
Authors: Jesus Gustavo Nobre de , Nave João Trindade , Pinheiro Luís Santos , Santos João Meneses , Lucas Margarida , Victorino Rui M. M.
Published: December 2017

Introduction: recent literature suggests that excessive use of blood cultures could prolong length of stay and hospital costs. Moreover, low positive rates have been reported and positivity predictive scores have recently been proposed. Methods: we conducted an observational prospective study in an Internal Medicine department of a university reference hospital analysing data from all patients to whom BC was requested. Results: blood cultures were performed in 39.9% of 414 admissions. Patients with blood cultures had higher length of stay and underwent more laboratory and imaging diagnostic tests. Global positivity rate was of 7.5%. Patients fulfilling sepsis criteria had a higher positivity rate (21.7%) and there were no positive blood cultures in patients without sepsis, namely in cases of isolated creactive protein elevation, leucocytosis or fever. In addition, blood cultures results were not a determinant of antibiotic adjust or de-escalation. Conclusions: our data suggest that the use of BC should be done essentially in patients with sepsis criteria, reducing its unnecessary use, although more studies are required to validate such practice.
Inhibition of JAK-STAT Signaling Suppresses Pathogenic Immune Responses in Medium and Large Vessel Vasculitis
Authors: Zhang Hui , Watanabe Ryu , Berry Gerald J. , Tian Lu , Goronzy Jörg J. , Weyand Cornelia M.
Published: December 2017

Background:

Giant cell arteritis, a chronic autoimmune disease of the aorta and its large branches, is complicated by aneurysm formation, dissection, and arterial occlusions. Arterial wall dendritic cells attract CD4
+
T cells and macrophages to form prototypic granulomatous infiltrates. Vasculitic lesions contain a diverse array of effector T cells that persist despite corticosteroid therapy and sustain chronic, smoldering vasculitis. Transmural inflammation induces microvascular neoangiogenesis and results in lumen-occlusive intimal hyperplasia. We have examined whether persistent vessel wall inflammation is maintained by lesional T cells, including the newly identified tissue-resident memory T cells, and whether such T cells are sensitive to the cytokine-signaling inhibitor tofacitinib, a Janus kinase (JAK) inhibitor targeting JAK3 and JAK1.

Methods:

Vascular inflammation was induced in human arteries engrafted into immunodeficient mice that were reconstituted with T cells and monocytes from patients with giant cell arteritis. Mice carrying inflamed human arteries were treated with tofacitinib or vehicle. Vasculitic arteries were examined for gene expression (reverse transcription polymerase chain reaction), protein expression (immunohistochemistry), and infiltrating cell populations (flow cytometry).

Results:

Tofacitinib effectively suppressed innate and adaptive immunity in the vessel wall. Lesional T cells responded to tofacitinib with reduced proliferation rates (<10%) and minimal production of the effector molecules interferon-γ, interleukin-17, and interleukin-21. Tofacitinib disrupted adventitial microvascular angiogenesis, reduced outgrowth of hyperplastic intima, and minimized CD4
+
CD103
+
tissue-resident memory T cells.

Conclusions:

Cytokine signaling dependent on JAK3 and JAK1 is critically important in chronic inflammation of medium and large arteries. The JAK inhibitor tofacitinib effectively suppresses tissue-resident memory T cells and inhibits core vasculitogenic effector pathways.