bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Asperity Interactions and Mesh Resolution on Friction Coefficient
Authors: Jourani Abdeljalil
Published: December 2016

Few models are devoted to explain the effect of surface roughness on the friction coefficient. Most of them use statistical approaches and do not incorporate the transition from elastic deformation to fully plastic flow. In this paper, a three-dimensional (3D) deterministic model is developed by considering different deformation modes of surface roughness which range from fully elastic through elastic–plastic to fully plastic contact interface. The simulations show that the increase in the surface roughness and mesh resolution lead to the increase in the static friction coefficient. For surfaces which present a low roughness, the static friction coefficient increases with increase in the normal load. The transition from elastic to plastic deformation is responsible for the increase of the friction coefficient with normal load. The comparison between experimental and numerical results reveals that the experimental friction coefficient is slightly larger than the calculated one. This difference does not exceed 10%. The multiscale roughness and the simplified geometry used to describe the shape of the surface roughness can explain the gap between experimental and numerical results in terms of friction coefficient.
Fracture Analysis in the Continuum Theory of Stress Gradient Plasticity
Authors: Shishvan Siamak Soleymani , Ghoddousifar Mirsalim
Published: December 2016

Plastic deformation around a stationary mode I crack in an isotropic material is studied within the continuum theory of stress gradient plasticity ([Formula: see text]GP). This model, as a lower-order plasticity theory, has been quite successful in predicting the size-dependent plastic behavior in micro-torsion as well as micro-bending. However, its application to a problem involving a complex stress state reveals here that it has to be modified with a proper measure of stress gradient in the continuum context. To this end, a new measure of stress gradient is proposed and assessed appropriately. It is then employed to investigate crack tip stress fields within the [Formula: see text]GP theory. Analyses show that a higher stress level is predicted near the crack tip using the [Formula: see text]GP theory when compared with the classical plasticity predictions. The increase of stress level due to stress gradient effects is predicted around 35% which is enough for cleavage cracking. However, relatively higher stress levels were expected due to large stress gradients near the crack tip. Therefore, either a higher-order formulation or involving higher-order spatial gradients of stress is required to study fracture with the [Formula: see text] GP theory.
Parametric Thermally Induced Vibration of an Electrostatically Deflected FGM Micro-Beam
Authors: Jafarsadeghi-Pournaki Ilgar , Rezazadeh Ghader , Zamanzadeh Mohammadreza , Shabani Rasoul
Published: December 2016

The present paper deals with the study of nonlinear vibration of a functionally graded cantilever micro-beam imposed on a bias DC voltage and superimposed on a sinusoidal heat source. The governing equation of motion is derived extremizing the Lagrange’s equation and Hamilton’s principal under the assumption of Euler–Bernoulli beam theory. The thermo-elastic equation is obtained utilizing the first law of thermodynamics under the assumption of the classical Fourier heat conduction model. Due to the displacement dependency of the electrostatic force and time variability of the heat source, the governing differential equations of the system are nonlinear implicitly parametrically electro-thermo-elastic coupled equations. To evaluate the dynamic response of the micro-beam, the coupled equations are discretized applying a Galerkin-based reduced order model and then integrated numerically by the Runge–Kutta method. By solving the equations, the stable and unstable regions at different bias DC voltages are identified. By picking some special points from these regions and depicting the time history and phase portrait diagrams, their behaviors are investigated in detail. In addition to the classical dynamic pull-in, in which a homoclinic orbit separates stable periodic orbits from the unbounded solutions, a new kind of dynamic pull-in is presented, which separates unstable solutions, due to parametric resonance response, from unbounded rapidly growing solutions owing to the existence of saddle and singular fixed points in the system.
A Modified Fourier Solution for Free Damped Vibration Analysis of Sandwich Viscoelastic-Core Conical Shells and Annular Plates with Arbitrary Restraints
Authors: Yang Chuanmeng , Jin Guoyong , Xu Weijian , Liu Zhigang
Published: December 2016

In this paper, arbitrary boundary conditions including classical and elastic ones are considered in analyzing the vibration and damping characteristics of the sandwich conical shells and annular plates using a simple and efficient modified Fourier solution. The displacement field is expressed as the linear combination of a standard Fourier series and several supplementary terms. The addition of these terms make the Fourier series expansion applicable to any boundary conditions, and the Fourier series expansions improved drastically regarding its accuracy and convergence. Instead of adopting conventional differentiation procedure, a Rayleigh–Ritz technique based on the energy function is conducted which leads to a set of algebraic equations. Then natural frequencies and loss factors can be obtained by solving the algebraic equations. Accuracy and reliability of the current method are checked by comparing the present results with the existing solutions. Influences of some vital parameters on the free vibration and damping performance of sandwich shells and plates are discussed. The detailed effect of restraints from different directions on the frequencies and loss factors is investigated. So, the method can provide a guide to design sandwich structures with desired vibration characteristic and well damping performance by reasonably adjusting the boundary condition. Some new numerical results are presented for future validation of various approximate/numerical methods.
Modeling transmission dynamics of Ebola virus disease
Authors: Imran Mudassar , Khan Adnan , Ansari Ali R. , Shah Syed Touqeer Hussain
Published: December 2016

Ebola virus disease (EVD) has emerged as a rapidly spreading potentially fatal disease. Several studies have been performed recently to investigate the dynamics of EVD. In this paper, we study the transmission dynamics of EVD by formulating an SEIR-type transmission model that includes isolated individuals as well as dead individuals that are not yet buried. Dynamical systems analysis of the model is performed, and it is consequently shown that the disease-free steady state is globally asymptotically stable when the basic reproduction number, [Formula: see text] is less than unity. It is also shown that there exists a unique endemic equilibrium when [Formula: see text]. Using optimal control theory, we propose control strategies, which will help to eliminate the Ebola disease. We use data fitting on models, with and without isolation, to estimate the basic reproductive numbers for the 2014 outbreak of EVD in Liberia and Sierra Leone.
Geometric aspects of CR-warped product submanifolds of T-manifolds
Authors: Ali Akram , Mior Othman Wan Ainun
Published: December 2016

In this paper, we study CR-warped product submanifolds of [Formula: see text]-manifolds. We prove that the CR-warped product submanifolds with invariant fiber are trivial warped products and provide a characterization theorem of CR-warped products with anti-invariant fiber of [Formula: see text]-manifolds. Moreover, we develop an inequality of CR-warped product submanifolds for the second fundamental form in terms of warping function and the equality cases are considered. Also, we find a necessary and sufficient condition for compact oriented CR-warped products turning into CR-products of [Formula: see text]-space forms.
Automated Task Load Detection with Electroencephalography: Towards Passive Brain–Computer Interfacing in Robotic Surgery
Authors: Zander Thorsten O. , Shetty Kunal , Lorenz Romy , Leff Daniel R. , Krol Laurens R. , Darzi Ara W. , Gramann Klaus , Yang Guang-Zhong
Published: December 2016

Automatic detection of the current task load of a surgeon in the theatre in real time could provide helpful information, to be used in supportive systems. For example, such information may enable the system to automatically support the surgeon when critical or stressful periods are detected, or to communicate to others when a surgeon is engaged in a complex maneuver and should not be disturbed. Passive brain–computer interfaces (BCI) infer changes in cognitive and affective state by monitoring and interpreting ongoing brain activity recorded via an electroencephalogram. The resulting information can then be used to automatically adapt a technological system to the human user. So far, passive BCI have mostly been investigated in laboratory settings, even though they are intended to be applied in real-world settings. In this study, a passive BCI was used to assess changes in task load of skilled surgeons performing both simple and complex surgical training tasks. Results indicate that the introduced methodology can reliably and continuously detect changes in task load in this realistic environment.
Common pitfalls in customer journey maps
Authors: Thompson Michael
Published: December 2016

This forum addresses conceptual, methodological, and professional issues that arise in the UX field's continuing effort to contribute robust information about users to product planning and design.
--- David Siegel and Susan Dray, Editors
Effects of exogenous desmopressin on a model of heat stress nephropathy in mice
Authors: Roncal-Jimenez Carlos A. , Milagres Tamara , Andres-Hernando Ana , Kuwabara Masanari , Jensen Thomas , Song Zhilin , Bjornstad Petter , Garcia Gabriela E. , Sato Yuka , Sanchez-Lozada Laura G. , Lanaspa Miguel A. , Johnson Richard J.
Published: December 2016

Recurrent heat stress and dehydration have recently been shown experimentally to cause chronic kidney disease (CKD). One potential mediator may be vasopressin, acting via the type 2 vasopressin receptor (V2receptor). We tested the hypothesis that desmopressin accelerates CKD in mice subjected to heat stress and recurrent dehydration. Recurrent exposure to heat with limited water availability was performed in male mice over a 5-wk period, with one group receiving desmopressin two times daily and the other group receiving vehicle. Two additional control groups were not exposed to heat or dehydration and received vehicle or desmopressin. The effects of the treatment on renal injury were assessed. Heat stress and recurrent dehydration induced functional changes (albuminuria, elevated urinary neutrophil gelatinase-associated protein), glomerular changes (mesangiolysis, matrix expansion), and tubulointerstitial changes (fibrosis, inflammation). Desmopressin also induced albuminuria, glomerular changes, and tubulointerstitial fibrosis in normal animals and also exacerbated injury in mice with heat stress nephropathy. Both heat stress and/or desmopressin were also associated with activation of the polyol pathway in the renal cortex, likely due to increased interstitial osmolarity. Our studies document both glomerular and tubulointerstitial injury and inflammation in heat stress nephropathy and may be clinically relevant to the pathogenesis of Mesoamerican nephropathy. Our data also suggest that vasopressin may play a role in the pathogenesis of the renal injury of heat stress nephropathy, likely via a V2receptor-dependent pathway.
Proximal-distal differences in movement smoothness reflect differences in biomechanics
Authors: Salmond Layne H. , Davidson Andrew D. , Charles Steven K.
Published: December 2016

Smoothness is a hallmark of healthy movement. Past research indicates that smoothness may be a side product of a control strategy that minimizes error. However, this is not the only reason for smooth movements. Our musculoskeletal system itself contributes to movement smoothness: the mechanical impedance (inertia, damping, and stiffness) of our limbs and joints resists sudden change, resulting in a natural smoothing effect. How the biomechanics and neural control interact to result in an observed level of smoothness is not clear. The purpose of this study is to 1) characterize the smoothness of wrist rotations, 2) compare it with the smoothness of planar shoulder-elbow (reaching) movements, and 3) determine the cause of observed differences in smoothness. Ten healthy subjects performed wrist and reaching movements involving different targets, directions, and speeds. We found wrist movements to be significantly less smooth than reaching movements and to vary in smoothness with movement direction. To identify the causes underlying these observations, we tested a number of hypotheses involving differences in bandwidth, signal-dependent noise, speed, impedance anisotropy, and movement duration. Our simulations revealed that proximal-distal differences in smoothness reflect proximal-distal differences in biomechanics: the greater impedance of the shoulder-elbow filters neural noise more than the wrist. In contrast, differences in signal-dependent noise and speed were not sufficiently large to recreate the observed differences in smoothness. We also found that the variation in wrist movement smoothness with direction appear to be caused by, or at least correlated with, differences in movement duration, not impedance anisotropy.

NEW & NOTEWORTHY This article presents the first thorough characterization of the smoothness of wrist rotations (flexion-extension and radial-ulnar deviation) and comparison with the smoothness of reaching (shoulder-elbow) movements. We found wrist rotations to be significantly less smooth than reaching movements and determined that this difference reflects proximal-distal differences in biomechanics: the greater impedance (inertia, damping, stiffness) of the shoulder-elbow filters noise in the command signal more than the impedance of the wrist.
Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery
Authors: Kovacs Christopher S.
Published: December 2016

During pregnancy and lactation, female physiology adapts to meet the added nutritional demands of fetuses and neonates. An average full-term fetus contains ∼30 g calcium, 20 g phosphorus, and 0.8 g magnesium. About 80% of mineral is accreted during the third trimester; calcium transfers at 300-350 mg/day during the final 6 wk. The neonate requires 200 mg calcium daily from milk during the first 6 mo, and 120 mg calcium from milk during the second 6 mo (additional calcium comes from solid foods). Calcium transfers can be more than double and triple these values, respectively, in women who nurse twins and triplets. About 25% of dietary calcium is normally absorbed in healthy adults. Average maternal calcium intakes in American and Canadian women are insufficient to meet the fetal and neonatal calcium requirements if normal efficiency of intestinal calcium absorption is relied upon. However, several adaptations are invoked to meet the fetal and neonatal demands for mineral without requiring increased intakes by the mother. During pregnancy the efficiency of intestinal calcium absorption doubles, whereas during lactation the maternal skeleton is resorbed to provide calcium for milk. This review addresses our current knowledge regarding maternal adaptations in mineral and skeletal homeostasis that occur during pregnancy, lactation, and post-weaning recovery. Also considered are the impacts that these adaptations have on biochemical and hormonal parameters of mineral homeostasis, the consequences for long-term skeletal health, and the presentation and management of disorders of mineral and bone metabolism.
Parathyroid Hormone-Related Protein, Its Regulation of Cartilage and Bone Development, and Role in Treating Bone Diseases
Authors: Martin T. John
Published: December 2016

Although parathyroid hormone-related protein (PTHrP) was discovered as a cancer-derived hormone, it has been revealed as an important paracrine/autocrine regulator in many tissues, where its effects are context dependent. Thus its location and action in the vasculature explained decades-long observations that injection of PTH into animals rapidly lowered blood pressure by producing vasodilatation. Its roles have been specified in development and maturity in cartilage and bone as a crucial regulator of endochondral bone formation and bone remodeling, respectively. Although it shares actions with parathyroid hormone (PTH) through the use of their common receptor, PTHR1, PTHrP has other actions mediated by regions within the molecule beyond the amino-terminal sequence that resembles PTH, including the ability to promote placental transfer of calcium from mother to fetus. A striking feature of the physiology of PTHrP is that it possesses structural features that equip it to be transported in and out of the nucleus, and makes use of a specific nuclear import mechanism to do so. Evidence from mouse genetic experiments shows that PTHrP generated locally in bone is essential for normal bone remodeling. Whereas the main physiological function of PTH is the hormonal regulation of calcium metabolism, locally generated PTHrP is the important physiological mediator of bone remodeling postnatally. Thus the use of intermittent injection of PTH as an anabolic therapy for bone appears to be a pharmacological application of the physiological function of PTHrP. There is much current interest in the possibility of developing PTHrP analogs that might enhance the therapeutic anabolic effects.
Electropolished Titanium Implants with a Mirror-Like Surface Support Osseointegration and Bone Remodelling
Authors: Larsson Wexell Cecilia , Shah Furqan A. , Ericson Lars , Matic Aleksandar , Palmquist Anders , Thomsen Peter
Published: December 2016

This work characterises the ultrastructural composition of the interfacial tissue adjacent to electropolished, commercially pure titanium implants with and without subsequent anodisation, and it investigates whether a smooth electropolished surface can support bone formation in a manner similar to surfaces with a considerably thicker surface oxide layer. Screw-shaped implants were electropolished to remove all topographical remnants of the machining process, resulting in a thin spontaneously formed surface oxide layer and a smooth surface. Half of the implants were subsequently anodically oxidised to develop a thickened surface oxide layer and increased surface roughness. Despite substantial differences in the surface physicochemical properties, the microarchitecture and the composition of the newly formed bone were similar for both implant surfaces after 12 weeks of healing in rabbit tibia. A close spatial relationship was observed between osteocyte canaliculi and both implant surfaces. On the ultrastructural level, the merely electropolished surface showed the various stages of bone formation, for example, matrix deposition and mineralisation, entrapment of osteoblasts within the mineralised matrix, and their morphological transformation into osteocytes. The results demonstrate that titanium implants with a mirror-like surface and a thin, spontaneously formed oxide layer are able to support bone formation and remodelling.
Change in Free Radical and Antioxidant Enzyme Levels in the Patients Undergoing Open Heart Surgery with Cardiopulmonary Bypass
Authors: Türker Fevzi Sarper , Doğan Ayşe , Ozan Gonca , Kıbar Kurtuluş , Erışır Mine
Published: December 2016

Objective. The purpose of this study is to determine the changes in oxidative damage and antioxidant parameters in open heart surgeries with cardiopulmonary bypass (CPB) in preoperative and early postoperative periods. Methods. A total of three consecutive arterial blood samples were obtained from the patients in the study group, in preoperative, early postoperative, and postoperative periods, respectively. Oxidative damage indicator (MDA) and antioxidant indicators (GPx, GSH, CAT, and SOD) were examined. Results. A statistically significant increase was observed in MDA level in postoperative period compared to preoperative and early postoperative periods. GSH levels and CAT activities increased significantly in early postoperative and postoperative periods. Analyses revealed an increase in GPx and SOD enzyme activities only in the postoperative period. Conclusion. Even though the increase in MDA level was suppressed by the increased GSH level and CAT activity like in early postoperative period, efficiency can be brought for the increases in insufficient significant antioxidant parameters in postoperative period by administering antioxidant supplements to the patients and thus the increase in MDA in postoperative period can be significantly suppressed.
Nile Red and 2-NBDG Are Incompatible for the Simultaneous Detection of Lipid and Glucose Accumulation
Authors: Hogan Andrew M. , Swaminathan Viswanathan , Pallegar Nikitha K. , Christian Sherri L.
Published: December 2016

Glucose is the universal energy source and a critical substrate for lipid synthesis in mammalian cells. Analysis of both glucose and lipid in cells is important for the understanding of the regulation of lipid synthesis in many cell types, but especially adipocytes, the major storage cell for fat in mammals. The fluorescent 7-nitrobenz-2-oxa-1,3-diazole (NBD) derivative of glucose, 2-NBDG, is used to monitor glucose uptake and the lipid-selective fluorophore Nile red is used to monitor lipid accumulation. Previous reports have used NBD-based fluorophores and Nile red simultaneously despite the possibility of spectral overlap. In this study, we determined if these fluorophores were experimentally compatible in preadipocytes and adipocytes stained with 2-NBDG and Nile red separately or costained. We found that Nile red is detectable in the wavelengths necessary to excite and detect 2-NBDG. This interference was further increased by the solvatochromic effect of lipid-localized Nile red. In addition, we found a synergistic increase in fluorescent intensity when both fluorophores were present. Unfortunately, even fine control of the excitation or emission wavelengths did not identify wavelengths suitable for selective detection when cells were costained. Therefore, 2-NBDG and Nile red cannot be used simultaneously—but can likely be used sequentially—to assess glucose uptake and lipid accumulation in lipid-laden cells.
Interacting Dark Matter andq-Deformed Dark Energy Nonminimally Coupled to Gravity
Authors: Dil Emre
Published: December 2016

In this paper, we propose a new approach to study the dark sector of the universe by considering the dark energy as an emergingq-deformed bosonic scalar field which is not only interacting with the dark matter, but also nonminimally coupled to gravity, in the framework of standard Einsteinian gravity. In order to analyze the dynamic of the system, we first give the quantum field theoretical description of theq-deformed scalar field dark energy and then construct the action and the dynamical structure of this interacting and nonminimally coupled dark sector. As a second issue, we perform the phase-space analysis of the model to check the reliability of our proposal by searching the stable attractor solutions implying the late-time accelerating expansion phase of the universe.
Isolation of an ES‐Derived Cardiovascular Multipotent Cell Population Based on VE‐Cadherin Promoter Activity
Authors: Maltabe Violetta A. , Barka Eleonora , Kontonika Marianthi , Florou Dimitra , Kouvara-Pritsouli Maria , Roumpi Maria , Agathopoulos Simeon , Kolettis Theofilos M. , Kouklis Panos
Published: December 2016

Embryonic Stem (ES) or induced Pluripotent Stem (iPS) cells are important sources for cardiomyocyte generation, targeted for regenerative therapies. Several in vitro protocols are currently utilized for their differentiation, but the value of cell‐based approaches remains unclear. Here, we characterized a cardiovascular progenitor population derived during ES differentiation, after selection based on VE‐cadherin promoter (Pvec) activity. ESCs were genetically modified with an episomal vector, allowing the expression of puromycin resistance gene, under Pvec activity. Puromycin‐surviving cells displayed cardiac and endothelial progenitor cells characteristics. Expansion and self‐renewal of this cardiac and endothelial dual‐progenitor population (CEDP) were achieved by Wnt/β‐catenin pathway activation. CEDPs express early cardiac developmental stage‐specific markers but not markers of differentiated cardiomyocytes. Similarly, CEDPs express endothelial markers. However, CEDPs can undergo differentiation predominantly to cTnT+ (~47%) and VE‐cadherin+ (~28%) cells. Transplantation of CEDPs in the left heart ventricle of adult rats showed that CEDPs‐derived cells survive and differentiate in vivo for at least 14 days after transplantation. A novel, dual‐progenitor population was isolated during ESCs differentiation, based on Pvec activity. This lineage can self‐renew, permitting its maintenance as a source of cardiovascular progenitor cells and constitutes a useful source for regenerative approaches.
Clinical Application of the Cardio-Ankle Vascular Index in Asymptomatic Healthy Koreans
Authors: Choi Su-Yeon
Published: December 2016

Background: Arterial stiffness has been established as a surrogate marker for the prognosis of cardiovascular disease. Arterial stiffness is also a predictor of future cardiovascular events, and is the earliest detectable manifestation of adverse structural and functional changes to blood vessel walls. Summary and Key Messages: The cardio-ankle vascular index (CAVI) is an index representing the stiffness of the entire arterial segments from the aorta to the ankle independent of the blood pressure at the time of the measurement. This paper provides an overview of the clinical application of arterial stiffness measurement by CAVI in asymptomatic Koreans. It includes the association between cardiometabolic risk factors and CAVI, and the relation between CAVI and asymptomatic coronary artery disease.
Cardiorenal Syndrome Type 5 in Sepsis: Role of Endotoxin in Cell Death Pathways and Inflammation
Authors: Virzì Grazia Maria , Clementi Anna , Brocca Alessandra , de Cal Massimo , Marcante Stefano , Ronco Claudio
Published: December 2016

Background/Aims: Cardiorenal Syndrome Type 5 (CRS Type 5) is characterized by concomitant cardiac and renal dysfunction in the setting of different systemic disorders, such as sepsis. In this study, we investigated the possible relationship between endotoxin levels, renal cell death and inflammation in septic patients with CRS Type 5. Methods: We enrolled 11 patients with CRS Type 5. CRS Type 5 was defined according to the current classification system. AKI was defined by Acute Kidney Injury Network (AKIN) criteria. Acute cardiac dysfunction was documented by echocardiography as acute left and/or right ventricular dysfunction leading to decreased ejection fraction. Endotoxin activity was measured by the Endotoxin Activity Assay (EAA). Plasma from CRS Type 5 patients was incubated with renal tubular cells (RTCs) and cell death levels were evaluated. Plasma cytokines levels were measured as well. Results: Accordingly to EAA levels, patients were divided into two groups: 45.4% of patients had low endotoxin activity level (negative EAA), while 54.5% of patients showed high endotoxin activity (positive EAA). RTCs incubated with plasma from EAA positive patients showed significantly higher apoptosis levels and higher caspase-3 activation compared to cells incubated with plasma from EAA negative patients, and a significant positive correlation was observed between EAA levels and RTC apoptosis levels. Furthermore, IL-6 and IFN-γ levels were significantly higher in CRS Type 5 patients with positive EAA. Conclusion: Our data suggest a possible relationship between endotoxin levels and renal cell death in septic patients with CRS Type 5. Furthermore, this study highlights the presence of renal apoptosis, the immune deregulation and the strong inflammation in CRS Type 5 patients, especially in those with high endotoxin activity.
Lemierre Syndrome: A Retrospective Study of the Role of Anticoagulation and Thrombosis Outcomes
Authors: Cupit-Link Margaret C. , Nageswara Rao Amulya , Warad Deepti M. , Rodriguez Vilmarie
Published: December 2016

Lemierre syndrome (LS) is a multisystemic infection beginning in the oropharynx and leading to thrombosis of the internal jugular vein (IJV) with septic emboli and potential thrombotic extension to the central nervous system. Although patient outcomes have improved with early initiation of antimicrobial therapies, there is no consensus regarding the role of anticoagulation in LS. To better define the role of anticoagulation therapy in LS and determine whether anticoagulation improves thrombosis outcomes, we conducted a retrospective chart review of pediatric and adult patients diagnosed with LS and managed at our institution from January 1998 to December 2014. Eighteen patients (9 females and 9 males) were included in this analysis, 6 of whom received ≥4 weeks of anticoagulation therapy (median 23.1 weeks, range 6.9-32.9 weeks). Six patients were in the pediatric age group (<18 years). All patients received broad-spectrum antibiotics. All patients had improvement in their thrombi by 3 months (nonanticoagulated patient group: complete response [CR], n = 9; partial response [PR], n = 3; anticoagulated patient group: CR, n = 2; PR, n = 4). No patient developed recurrent thrombosis or progression during the follow-up period, regardless of anticoagulation status. Our study suggests that anticoagulation in LS may not affect thrombosis outcomes.
Is Overexpression of Ki-67 a Prognostic Biomarker of Upper Tract Urinary Carcinoma? A Retrospective Cohort Study and Meta-Analysis
Authors: Fan Bo , Zhang Hongshuo , Jin Huidan , Gai Yu , Wang Honglong , Zong Huafeng , Jin Mingyu , Yang Hao , Wan Shuping , Zhu Jiabin , Xu Siyao , Wang Jianbo , Yang Deyong , Song Xishuang
Published: December 2016

Background: Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. The Ki-67 antigen is a classic marker of cellular proliferation, but there is still controversy regarding the significance and importance of Ki-67 in tumor progression. Methods: In this study, we first detected Ki-67 expression in UTUC patients by immunohistochemistry (IHC). Subsequently, we quantitatively combined the results with those from the published literature in a meta-analysis after searching several databases. Results: IHC results demonstrated that patients with muscle-invasive tumors (T2-T4) had higher Ki-67 expression than those with non-muscle-invasive tumors (Tis-T1), suggesting that high Ki-67 expression may be associated with the aggressive form of UTUC. Kaplan-Meier curves showed that patients with high Ki-67 expression had significantly poorer cancer-specific survival (CSS) and disease-free survival (DFS). Furthermore, multivariate analysis suggested that Ki-67 expression was an independent prognostic factor for CSS (hazard ratio, HR=3.196) and DFS (HR=3.517) in UTUC patients. Then, a meta-analysis of the published literature investigating Ki-67 expression and its effects on UTUC prognosis was conducted. After searching the PubMed, Medline, Embase, Cochrane Library and Scopus databases, 12 articles met the eligibility criteria for this analysis. The eligible studies included a total of 1740 patients with a mean number of 82 patients per study (range, 38-475). The combined results showed that increased Ki-67 levels were associated with poor survival and disease progression, with a pooled HR estimate of 2.081 and 2.791, respectively. In subgroup analysis, the pooled HR was statistically significant for cancer-specific survival (HR=2.276), metastasis-free survival (HR=3.008) and disease-free survival (HR=6.336). Conclusions: In conclusion, high Ki-67 expression was associated with poor survival in patients with UTUC, as well as a high risk of disease progression, although these findings need to be interpreted with caution. Large-scale, adequately designed, prospective trials are needed to further confirm the value of Ki-67 in prognosis of UTUC patients.
Allogeneic Compact Bone-Derived Mesenchymal Stem Cell Transplantation Attenuates the Severity of Idiopathic Pneumonia Syndrome in a Murine Bone Marrow Transplantation Model
Authors: Qiao Shu-kai , Ren Han-yun , Shi Yong-jin , Liu Wei
Published: December 2016

Background/Aims: Idiopathic pneumonia syndrome (IPS) is a serious and life-threatening lung complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and currently no effective therapies exist. This study was designed to determine whether transplantation of allogeneic murine compact bone derived- mesenchymal stem cells (CB-MSCs) could prevent the development of IPS. Methods: We tested the effects of CB-MSCs transplantation on IPS using an established murine model of C57BL/6 (H-2b)→BALB/c (H-2d). Survival rates, body weight change, clinical GVHD scores, lung histological changes were assessed after IPS induction. Mechanistically, concentrations of cytokines (TNF-α, IFN-γ and IL-4) and chemokines (CCL5, CXCL9 and CXCL10) in bronchoalveolar lavage fluid (BALF) from the recipient mice were measured at different time point post-transplantation. CD4+CD25+Foxp3+ regulatory T cell (Treg) percentage, CCR5, CXCR3 and CCR7 expression on CD3+ T cells, and lung CXCR3, CCR5, CCR7, T-bet and GATA-3 mRNA levels were also evaluated at different time point post-transplantation. Results: Co-transplantation of CB-MSCs significantly attenuated the severity of lung injuries and increased survival rate of mice compared to non-cotransplanted mice. A higher Treg percentage, reduction of TNF-α, IFN-γ, CCL5, CXCL9 and CXCL10 levels, down-regulation of CXCR3 and CCR5, as well as up-regulation of CCR7, were observed in MSCs co-transplantation mice. Also, the prophylactic effect of CB-MSCs was associated with a shift of Th1/Th2 balance toward anti-inflammatory Th2 polarization. Conclusions: Allogeneic CB-MSCs effectively controlled the occurrence of IPS due to its profound immunomodulatory capacity. This may offer a novel prophylactic approach for IPS after allo-HSCT.
Cellular Innate Immunity: An Old Game with New Players
Authors: Gasteiger Georg , D'Osualdo Andrea , Schubert David A. , Weber Alexander , Bruscia Emanuela M. , Hartl Dominik
Published: December 2016

Innate immunity is a rapidly evolving field with novel cell types and molecular pathways being discovered and paradigms changing continuously. Innate and adaptive immune responses are traditionally viewed as separate from each other, but emerging evidence suggests that they overlap and mutually interact. Recently discovered cell types, particularly innate lymphoid cells and myeloid-derived suppressor cells, are gaining increasing attention. Here, we summarize and highlight current concepts in the field, focusing on innate immune cells as well as the inflammasome and DNA sensing which appear to be critical for the activation and orchestration of innate immunity, and may provide novel therapeutic opportunities for treating autoimmune, autoinflammatory, and infectious diseases.
A Systematic Review and Meta-Analysis of the Effects on Dutasteride Treatment for Reducing Surgical Blood Loss during Transurethral Resection of the Prostate
Authors: Ren Jian , Lai Shicong , Jiang Zhaoqiang , Xu Xin , Diao Tongxiang , Thiruchelvam Nikesh , Zhang Guan
Published: December 2016

Objective: This systematic review and meta-analysis were performed to evaluate the efficacy of preoperative dutasteride treatment for reducing surgical blood loss in patients undergoing transurethral resection of the prostate (TURP). Methods: A systematic search was performed from the electronic databases including PubMed, EMBASE, and Cochrane Library by May 2016. We followed the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analysis statement when examining the literature. Identified articles were strictly appraised for quality and relevance. Results: Five randomized controlled trials (RCTs) and 5 retrospective cohort studies involving 1,022 patients with benign prostate hyperplasia were analyzed based on the inclusion criteria. Pooled analysis revealed that preoperative treatment with dutasteride had a significantly smaller decrease in hemoglobin (weighted mean difference [WMD] -0.47, 95% CI -0.70 to -0.24, p < 0.0001) and hematocrit levels (WMD -1.03, 95% CI -1.73 to -0.33, p = 0.004); However, no signiﬁcant difference has been found in terms of the total blood loss during TURP and blood loos per gram of resected prostatic tissue, the weight of resected prostate tissue, the microvessel density of the prostate, and the transfusion rate between the dutasteride and the control group. Conclusions: This systematic review and meta-analysis indicate that preoperative treatment with dutasteride could reduce surgical bleeding during TURP, but the findings of this study should be further confirmed by well-designed prospective RCTs with a larger patient series.
Cardiometabolic Risks in Polycystic Ovary Syndrome: Non-Traditional Risk Factors and the Impact of Obesity
Authors: Chiu Wei-Ling , Boyle Jacqueline , Vincent Amanda , Teede Helena , Moran Lisa J.
Published: December 2016

Polycystic ovary syndrome (PCOS) is a common and complex endocrinopathy with reproductive, metabolic, and psychological features and significantly increased cardiometabolic risks. PCOS is underpinned by inherent insulin resistance and hyperandrogenism. Obesity, more common in PCOS, plays an important role in the pathophysiology, exacerbating hyperinsulinaemia and hyperandrogenism, leading to recommended first-line lifestyle intervention. Significant traditional and non-traditional risk factors are implicated in PCOS in addition to obesity-exacerbated cardiometabolic risks and are explored in this review to promote the understanding of this common metabolic and reproductive condition.
Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B
Authors: Pasi K.John , Fischer Kathelijn , Ragni Margaret , Nolan Beatrice , Perry David J. , Kulkarni Roshni , Ozelo Margareth , Mahlangu Johnny , Shapiro Amy D. , Baker Ross I. , Bennett Carolyn M. , Barnes Christopher , Oldenburg Johannes , Matsushita Tadashi , Yuan Huixing , Ramirez-Santiago Alejandra , Pierce Glenn F. , Allen Geoffrey , Mei Baisong
Published: December 2016

The safety, efficacy, and prolonged half-life of recombinant factor IX Fc fusion protein (rFIXFc) were demonstrated in the Phase 3 B-LONG (adults/adolescents ≥12 years) and Kids B-LONG (children <12 years) studies of subjects with haemophilia B (≤2 IU/dl). Here, we report interim, long-term safety and efficacy data from B-YOND, the rFIXFc extension study. Eligible subjects who completed B-LONG or Kids B-LONG could enrol in B-YOND. There were four treatment groups: weekly prophylaxis (20–100 IU/kg every 7 days), individualised prophylaxis (100 IU/kg every 8–16 days), modified prophylaxis (further dosing personalisation to optimise prophylaxis), and episodic (ondemand) treatment. Subjects could change treatment groups at any point. Primary endpoint was inhibitor development. One hundred sixteen subjects enrolled in B-YOND. From the start of the parent studies to the B-YOND interim data cut, median duration of rFIXFc treatment was 39.5 months and 21.9 months among adults/adolescents and children, respectively; 68/93 (73.1 %) adults/adolescents and 9/23 (39.1 %) children had ≥100 cumulative rFIXFc exposure days. No inhibitors were observed. Median annualised bleeding rates (ABRs) were low in all prophylaxis regimens: weekly (≥12 years: 2.3; <6 years: 0.0; 6 to <12 years: 2.7), individualised (≥12 years: 2.3; 6 to <12 years: 2.4), and modified (≥12 years: 2.4). One or two infusions were sufficient to control 97 % (adults/adolescents) and 95 % (children) of bleeding episodes. Interim data from B-YOND are consistent with data from B-LONG and Kids B-LONG, and confirm the longterm safety of rFIXFc, absence of inhibitors, and maintenance of low ABRs with prophylactic dosing every 1 to 2 weeks.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Fc-saxatilin suppresses hypoxia-induced vascular leakage by regulating endothelial occludin expression
Authors: Choi Hyun-Jung , Kwon Il , Kim Na-Eun , Kim Jayoung , An Sunho , Kang Sungsoo , Hong Sung-Yu , Nam Hyo Suk , Hoe Heo Ji
Published: December 2016

Vascular leakage due to compromised integrity of the endothelial barrier is closely associated with brain damage in several neurological disorders, including ischaemic stroke. Saxatilin, a snake venom disintegrin containing the Arg-Gly-Asp (RGD) motif, exerts thrombolytic and antiplatelet effects by interacting with multiple integrins on platelets. Integrin signalling is indispensable for regulation of endothelial permeability. Saxatilin may play a role in vascular leakage after ischaemia because it has high affinity for endothelial integrins. Here, we determined whether Fc-saxatilin, an Fc-fusion protein of saxatilin, could prevent vascular leakage under hypoxic or ischaemic conditions. In mouse brain microvascular endothelial cells, hypoxia increased the permeability to FITC-dextran, and this effect was attenuated by Fc-saxatilin treatment. Fc-saxatilin also blocked vascular leakage of Evans Blue in the ischaemic brain induced by middle cerebral artery occlusion in mice. Furthermore, the expression of occludin, a tight junction protein, was reduced by hypoxia in endothelial cells. This downregulation of occludin was attenuated by Fc-saxatilin treatment. We also determined the activity of matrix metalloproteinases (MMPs) 2 and 9 because they are implicated in the degradation of occludin and of the microvascular basal lamina. Hypoxia increased MMP-9 activity, and this increase was attenuated by Fc-saxatilin treatment. Fc-saxatilin specifically bound to integrin αvβ3 of the endothelial cells and inhibited hypoxia-induced activation of FAK, a downstream signalling molecule in integrin-dependent signal transduction. Taken together, these results provide new insights into the mechanism via which Fc-saxatilin, as an integrin antagonist, prevents vascular leakage under ischemic conditions by regulating occludin expression in endothelial tight junctions.

Supplementary Material to this article is available online at www.thrombosis-online.com.
The role of microRNAs in prethrombotic status associated with coronary artery disease
Authors: Gao Jie , Ma Xiaojuan , Zhang Ying , Guo Ming , Shi Dazhuo
Published: December 2016

The acute cardiovascular events following thrombus formation is a primary cause of morbidity and mortality of patients with coronary artery disease (CAD). Numerous studies have shown that a prethrombotic status, which can be defined as an imbalance between the procoagulant and anticoagulant conditions, would exist for a period of time before thrombogenesis. Therefore, early diagnosis and intervention of prethrombotic status are important for reducing acute cardiovascular events. However, none of prethrombotic indicators have been identified as golden standard for diagnosis of prethrombotic status to date. MicroRNAs (miRNAs), a class of short non-coding RNAs, have been shown to be involved in pathophysiologic processes related to prethrombotic status, such as endothelial dysfunction, platelet activation, impaired fibrinolysis and elevated procoagulant factors, etc. Owing to their multiple and fine-tuning impacts on gene expression, miRNAs raise a novel understanding in the underlying mechanism of prethrombotic status. This review aims to discuss the role of miRNAs in prethrombotic status, especially the differently expressed miRNAs in CAD, which may be meaningful for developing promising diagnostic biomarkers and therapeutic strategies for CAD patients in future.
D-dimer and the Risk of Stroke and Coronary Heart Disease
Authors: McClure Leslie A. , Judd Suzanne E. , Kissela Brett , Howard George , Safford Monika M. , Cushman Mary , Zakai Neil A.
Published: December 2016

D-dimer, a biomarker of coagulation, is higher in blacks than in whites and has been associated with stroke and coronary heart disease (CHD). It was our objective to assess the association of higher D-dimer with stroke and CHD in blacks and whites. REGARDS recruited 30,239 black and white participants across the contiguous US and measured baseline D-dimer in stroke (n=646) and CHD (n=654) cases and a cohort random sample (n=1,104). Cox models adjusting for cardiovascular risk factors determined the hazard ratio (HR) for increasing D-dimer for cardiovascular disease with bootstrapping to assess the difference in HR for CHD versus stroke by race. D-dimer was higher with increasing age, female sex, diabetes, hypertension, pre-baseline cardiovascular disease and higher C-reactive protein (CRP). Accounting for cardiovascular risk factors, each doubling of D-dimer was associated with increased stroke (hazard ratio [HR] 1.15; 95 % confidence interval [CI] 1.01, 1.31) and CHD (HR 1.27; 95 % CI 1.11, 1.45) risk. The difference in the HR between CHD and stroke was 0.20 (95 % CI >0.00, 0.58) for blacks and 0.02 (95 % CI –0.30, 0.27) for whites. CRP mediated 22 % (95 % CI 5 %, 41 %) of the association between D-dimer and CHD and none of the association with stroke. Higher D-dimer increased the risk of stroke and CHD independent of cardiovascular risk factors and CRP, with perhaps a stronger association for CHD versus stroke in blacks than whites. These findings highlight potential different pathophysiology of vascular disease by disease site and race suggesting potential further studies targeting haemostasis in primary prevention of vascular disease.
Transições canceladas: teatro e experiência no Brasil (notas para um programa de trabalho)
Authors: Azevedo José Fernando
Published: December 2016

Recorrente nos títulos da maior parte das obras clássicas de interpretação da vida cultural e social no Brasil, a ideia de formação nunca se estabeleceu como modelo de compreensão do teatro entre nós. Sinal de uma experiência feita toda de cancelamentos, essa ausência ou insuficiência impõe outras exigências interpretativas. Das relações entre forma social e forma estética, certamente emerge a experiência teatral, entre nós, como depoimento acerca do tempo presente, na ordem de um teatro mundial – desde a colônia, se quisermos, aos diversos estágios do capitalismo e seus desenvolvimentos.
A melancolia conjunta escrita com a tinta em primeira pessoa
Authors: Cosmo Matheus
Published: December 2016

Este texto nasce de uma constatação frequentemente reiterada em análises acerca da atual conjuntura política nacional: o poder, organizando-se a partir da ideia de crise, melancolizou grande parte das subjetividades emergentes. Sendo esse este um enunciado verdadeiro, busca-se aqui, por meio de preceitos advindos, em grande parte, da filosofia e da psicanálise, a redescoberta de uma potência intrínseca à melancolia, capaz de reavaliar os impasses que inflamam o Brasil atual.
Sobre uma possível morada do real na ficção
Authors: Penuela Sanches Pedro Rodrigo
Published: December 2016

Este trabalho procura revisar ideias de alguns teóricos do teatro e da dança com relação às produções cênicas realizadas a partir da década de 1960 (que têm sido nomeadas como “pós-modernas”, “pós-dramáticas”, “teatro performativo”, entre outras expressões que procuram salientar sua diferenciação com relação às artes cênicas de certa época ou conceituação anteriores), a fim de apontar limites da crítica à representação que tais teorizações pretendem realizar. Discute-se em que medida certo caminho de desconstrução da lógica da representação tende a efetuar-se sobre os mesmos fundamentos conceituais de tal lógica, e sobre um mesmo tipo de pensamento dicotômico que a estrutura. Em seguida, tomando como base ideias do filósofo Jacques Rancière, pretende-se apontar outras possibilidades de crítica da representação por meio de sua reconceituação da noção de ficção.