bluuebunny/crossref_metadata_2025 huggingface dataset:
Conductive PVDF-HFP/CNT composites for strain sensing
Authors: Hu Bin , Liu Yaolu , Hu Ning , Wu Liangke , Ning Huiming , Zhang Jianyu , Fu Shaoyun , Tang Shang , Xu Chaohe , Liu Feng , Alamusi  , Yuan Weifeng
Published: January 2016

A strain sensor based on the composites of poly (vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) filled by multi-walled carbon nanotube (MWNT) was prepared using a proposed fabrication process. Three kinds of MWNT loadings, i.e., 1.0[Formula: see text]wt.%, 2.0[Formula: see text]wt.% and 3.0[Formula: see text]wt.% were employed. Due to good dispersion state of MWNT in PVDF-HFP matrix, which was characterized by scanning electron microscope (SEM), this sensor was found to be of high sensitivity and stable performance. The sensor’s piezoresistivity varied in a weak nonlinear pattern, which was probably caused by the tunneling effect among neighboring MWNTs. The gauge factor of the sensor of 1.0[Formula: see text]wt.% MWNT loading was identified to be the highest, i.e., 33. This sensor gauge factor decreased gradually with the increase of addition amount of MWNT, which was 5 for the sensor of 3.0[Formula: see text]wt.% MWNT loading. This gauge factor was still higher than that of conventional metal-foil strain sensors. The electrical conductivity of PVDF-HFP/MWNT composites was also studied. It was found that with the increase of the addition amount of MWNT, the electrical conductivity of the PVDF-HFP/MWNT composites varied in a perfect percolation pattern with a very low percolation threshold, i.e., 0.77 vol.%, further indicating the very good dispersion of MWNT in the PVDF-HFP matrix.
User-Centric Adaptation Analysis of Multi-Tenant Services
Authors: García-galán Jesús , Pasquale Liliana , Trinidad Pablo , Ruiz-Cortés Antonio
Published: January 2016

Multi-tenancy is a key pillar of cloud services. It allows different users to share computing and virtual resources transparently, meanwhile guaranteeing substantial cost savings. Due to the tradeoff between scalability and customization, one of the major drawbacks of multi-tenancy is limited configurability. Since users may often have conflicting configuration preferences, offering the best user experience is an open challenge for service providers. In addition, the users, their preferences, and the operational environment may change during the service operation, thus jeopardizing the satisfaction of user preferences. In this article, we present an approach to support user-centric adaptation of multi-tenant services. We describe how to engineer the activities of the Monitoring, Analysis, Planning, Execution (MAPE) loop to support user-centric adaptation, and we focus on adaptation analysis. Our analysis computes a service configuration that optimizes user satisfaction, complies with infrastructural constraints, and minimizes reconfiguration obtrusiveness when user- or service-related changes take place. To support our analysis, we model multi-tenant services and user preferences by using feature and preference models, respectively. We illustrate our approach by utilizing different cases of virtual desktops. Our results demonstrate the effectiveness of the analysis in improving user preferences satisfaction in negligible time.
Self-Stabilized Fast Gossiping Algorithms
Authors: Dulman Stefan , Pauwels Eric
Published: January 2016

In this article, we explore the topic of extending aggregate computation in distributed networks with self-stabilizing properties to withstand network dynamics. Existing research suggests that fast gossiping algorithms, based on the properties of order statistics applied to families of exponential random variables, are a viable solution for computing functions of the values stored in the network. We focus on the specific case in which network changes and failures occur in batches with a minimum frequency in the order of the diameter of the network. Our contribution consists in two self-stabilizing mechanisms, allowing fast gossiping algorithms to be applicable to dynamic networks with minor increase in resources usage. The resulting algorithms can be deployed in networks exhibiting churn, node stop-failures and resets, and random topological changes. The theoretical results are verified with simulations on synthetic data, showcasing desirable properties for large-scale network designers such as scalability, lack of single points of failure, and anonymity.
Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation
Authors: Rigg Rachel A. , Healy Laura D. , Nowak Marie S. , Mallet Jérémy , Thierheimer Marisa L. D. , Pang Jiaqing , McCarty Owen J. T. , Aslan Joseph E.
Published: January 2016

Molecular chaperones that support protein quality control, including heat shock protein 70 (Hsp70), participate in diverse aspects of cellular and physiological function. Recent studies have reported roles for specific chaperone activities in blood platelets in maintaining hemostasis; however, the functions of Hsp70 in platelet physiology remain uninvestigated. Here we characterize roles for Hsp70 activity in platelet activation and function. In vitro biochemical, microscopy, flow cytometry, and aggregometry assays of platelet function, as well as ex vivo analyses of platelet aggregate formation in whole blood under shear, were carried out under Hsp70-inhibited conditions. Inhibition of platelet Hsp70 blocked platelet aggregation and granule secretion in response to collagen-related peptide (CRP), which engages the immunoreceptor tyrosine-based activation motif-bearing collagen receptor glycoprotein VI (GPVI)-Fc receptor-γ chain complex. Hsp70 inhibition also reduced platelet integrin-αIIbβ3 activation downstream of GPVI, as Hsp70-inhibited platelets showed reduced PAC-1 and fibrinogen binding. Ex vivo, pharmacological inhibition of Hsp70 in human whole blood prevented the formation of platelet aggregates on collagen under shear. Biochemical studies supported a role for Hsp70 in maintaining the assembly of the linker for activation of T cells signalosome, which couples GPVI-initiated signaling to integrin activation, secretion, and platelet function. Together, our results suggest that Hsp70 regulates platelet activation and function by supporting linker for activation of T cells-associated signaling events downstream of platelet GPVI engagement, suggesting a role for Hsp70 in the intracellular organization of signaling systems that mediate platelet secretion, “inside-out” activation of platelet integrin-αIIbβ3, platelet-platelet aggregation, and, ultimately, hemostatic plug and thrombus formation.
Tactile texture signals in primate primary somatosensory cortex and their relation to subjective roughness intensity
Authors: Bourgeon Stéphanie , Dépeault Alexandra , Meftah El-Mehdi , Chapman C. Elaine
Published: January 2016

This study investigated the hypothesis that a simple intensive code, based on mean firing rate, could explain the cortical representation of subjective roughness intensity and its invariance with scanning speed. We examined the sensitivity of neurons in the cutaneous, finger representation of primary somatosensory cortex (S1) to a wide range of textures [1 mm high, raised-dot surfaces; spatial periods (SPs), 1.5–8.5 mm], scanned under the digit tips at different speeds (40–115 mm/s). Since subjective roughness estimates show a monotonic increase over this range and are independent of speed, we predicted that the mean firing rate of a subgroup of S1 neurons would share these properties. Single-unit recordings were made in four alert macaques (areas 3b, 1 and 2). Cells whose discharge rate showed a monotonic increase with SP, independent of speed, were particularly concentrated in area 3b. Area 2 was characterized by a high proportion of cells sensitive to speed, with or without texture sensitivity. Area 1 had intermediate properties. We suggest that area 3b and most likely area 1 play a key role in signaling roughness intensity, and that a mean rate code, signaled by both slowly and rapidly adapting neurons, is present at the level of area 3b. Finally, the substantial proportion of neurons that showed a monotonic change in discharge limited to a small range of SPs (often independent of response saturation) could play a role in discriminating smaller changes in SP.
A quantitative confidence signal detection model: 1. Fitting psychometric functions
Authors: Yi Yongwoo , Merfeld Daniel M.
Published: January 2016

Perceptual thresholds are commonly assayed in the laboratory and clinic. When precision and accuracy are required, thresholds are quantified by fitting a psychometric function to forced-choice data. The primary shortcoming of this approach is that it typically requires 100 trials or more to yield accurate (i.e., small bias) and precise (i.e., small variance) psychometric parameter estimates. We show that confidence probability judgments combined with a model of confidence can yield psychometric parameter estimates that are markedly more precise and/or markedly more efficient than conventional methods. Specifically, both human data and simulations show that including confidence probability judgments for just 20 trials can yield psychometric parameter estimates that match the precision of those obtained from 100 trials using conventional analyses. Such an efficiency advantage would be especially beneficial for tasks (e.g., taste, smell, and vestibular assays) that require more than a few seconds for each trial, but this potential benefit could accrue for many other tasks.
Functional connectivity as a means to delineate differences between treatment-resistant and treatment-responsive schizophrenia
Authors: Paul Sara , Sharfman Nathan
Published: January 2016

It has been estimated that one-third of schizophrenia patients are treatment resistant (TRS). Recent studies have shown that functional connectivity (FC) can be used for measuring connections between brain regions in diseased states. White, Wigton, Joyce, Collier, Fornito, and Shergill ( Neuropsychopharmacology. First published September 9, 2015; doi:10.1038/npp.2015.277) used FC to identify differences between schizophrenia patients responding to antipsychotic treatment and TRS patients. Their results support the idea that the groups differ not only in treatment response but also neurophysiologically through differences in FC.
Rodent models for resolving extremes of exercise and health
Authors: Garton Fleur C. , North Kathryn N. , Koch Lauren G. , Britton Steven L. , Nogales-Gadea Gisela , Lucia Alejandro
Published: January 2016

The extremes of exercise capacity and health are considered a complex interplay between genes and the environment. In general, the study of animal models has proven critical for deep mechanistic exploration that provides guidance for focused and hypothesis-driven discovery in humans. Hypotheses underlying molecular mechanisms of disease and gene/tissue function can be tested in rodents to generate sufficient evidence to resolve and progress our understanding of human biology. Here we provide examples of three alternative uses of rodent models that have been applied successfully to advance knowledge that bridges our understanding of the connection between exercise capacity and health status. First we review the strong association between exercise capacity and all-cause morbidity and mortality in humans through artificial selection on low and high exercise performance in the rat and the consequent generation of the “energy transfer hypothesis.” Second we review specific transgenic and knockout mouse models that replicate the human disease condition and performance. This includes human glycogen storage diseases (McArdle and Pompe) and α-actinin-3 deficiency. Together these rodent models provide an overview of the advancements of molecular knowledge required for clinical translation. Continued study of these models in conjunction with human association studies will be critical to resolving the complex gene-environment interplay linking exercise capacity, health, and disease.
Sports genetics moving forward: lessons learned from medical research
Authors: Mattsson C. Mikael , Wheeler Matthew T. , Waggott Daryl , Caleshu Colleen , Ashley Euan A.
Published: January 2016

Sports genetics can take advantage of lessons learned from human disease genetics. By righting past mistakes and increasing scientific rigor, we can magnify the breadth and depth of knowledge in the field. We present an outline of challenges facing sports genetics in the light of experiences from medical research. Sports performance is complex, resulting from a combination of a wide variety of different traits and attributes. Improving sports genetics will foremost require analyses based on detailed phenotyping. To find widely valid, reproducible common variants associated with athletic phenotypes, study sample sizes must be dramatically increased. One paradox is that in order to confirm relevance, replications in specific populations must be undertaken. Family studies of athletes may facilitate the discovery of rare variants with large effects on athletic phenotypes. The complexity of the human genome, combined with the complexity of athletic phenotypes, will require additional metadata and biological validation to identify a comprehensive set of genes involved. Analysis of personal genetic and multiomic profiles contribute to our conceptualization of precision medicine; the same will be the case in precision sports science. In the refinement of sports genetics it is essential to evaluate similarities and differences between sexes and among ethnicities. Sports genetics to date have been hampered by small sample sizes and biased methodology, which can lead to erroneous associations and overestimation of effect sizes. Consequently, currently available genetic tests based on these inherently limited data cannot predict athletic performance with any accuracy.
Probable Levofloxacin-Induced Thrombocytopenia in a Patient Previously on Ciprofloxacin: A Case Report and Literature Review
Authors: Landi A. Justine , Burkes Robert
Published: January 2016

Drug-induced thrombocytopenia is a poorly understood, yet common phenomenon widely encountered in clinical practice. We present a case of suspected levofloxacin-induced thrombocytopenia, a rare side effect of a ubiquitous antibiotic, in a patient without similar effect to ciprofloxacin. This report builds upon other isolated case reports of fluoroquinolone-induced thrombocytopenia and demonstrates our algorithmic approach to the issue as well as a literature review pertaining to fluoroquinolone-induced thrombocytopenia.
Study of Exhaled Nitric Oxide in Subjects with Suspected Obstructive Sleep Apnea: A Pilot Study in Vietnam
Authors: Duong-Quy Sy , Hua-Huy Thong , Tran-Mai-Thi Huyen-Tran , Le-Dong Nhat-Nam , Craig Timothy J. , Dinh-Xuan Anh-Tuan
Published: January 2016

Background and Objective. The concentration of exhaled nitric oxide (eNO), reflecting the activity of inducible NO synthase in airway epithelium, has been found to increase in patients with obstructive sleep apnea (OSA). This study aimed to measure eNO concentration in patients with suspected OSA and to correlate different eNO parameters with clinical and sleep apnea characteristics.Methods. In this cross-sectional study, all patients underwent in-lab overnight polysomnography (PSG) and eNO measurement using a method of multiple flow rates before and after PSG (pre- and post-PSG).Results. According to the result of PSG, 82 persons were divided into two groups: control subjects (n=30;54±14years) and patients with OSA defined as apnea-hypopnea index (AHI) ≥ 5/hour (n=52;53±12years). Body mass index (BMI) and neck and abdomen circumferences of OSA patients were significantly higher than those from control subjects. In OSA group, post-PSG alveolar NO concentration (CANO) (5.3±1.9 ppb) was significantly higher than pre-PSG CANO (4.0±1.7 ppb;P<0.001). Significant correlations have been found between CANO and AHI (P<0.001) and between CANO and nadir SpO2(P<0.05). The daytime CANO value of more than 4.1 ppb can be used to screen symptomatic subjects for the presence of OSA with a high specificity of 93.3%.Conclusion. Our findings indicate CANO as a surrogate marker for OSA in persons with suggestive symptoms.
Subzero Temperature Dip-Coating of Sol-Gel Vanadium Pentoxide: Effect of the Deposition Temperature on the Film Structure, Morphology, and Electrochromic Properties
Authors: Almoabadi Afaf , Alsawafta Mohammed , Badilescu Simona , Stancovski Victor , Sharma Tanu , Brüning Ralf , Truong Vo-Van
Published: January 2016

Vanadium pentoxide sol-gel prepared thin films were deposited on indium-tin-oxide (ITO) substrates by dip-coating at a subzero temperature (−10°C). The structure, morphology, and optical and electrochromic properties of dense and porous vanadium oxide films coated at low temperature were determined and compared to those of the corresponding films deposited under room-temperature conditions. The results indicated that, in the films coated at −10°C, a residual compressive stress exists that would originate from the formation of microvoids during the deposition. These microvoids are preserved during the heat treatment of the films. The microvoid morphology would favor the formation of nanostructures that would be responsible for the improved electrochromic properties of the subzero dip-coated films. Low-temperature coated films, heated at 450°C for several hours, undergo the transformation from a layered to a highly uniform nanorod structure that would be an important feature for different applications.
Prediction Accuracy in Multivariate Repeated-Measures Bayesian Forecasting Models with Examples Drawn from Research on Sleep and Circadian Rhythms
Authors: Kogan Clark , Kalachev Leonid , Van Dongen Hans P. A.
Published: January 2016

In study designs with repeated measures for multiple subjects, population models capturing within- and between-subjects variances enable efficient individualized prediction of outcome measures (response variables) by incorporating individuals response data through Bayesian forecasting. When measurement constraints preclude reasonable levels of prediction accuracy, additional (secondary) response variables measured alongside the primary response may help to increase prediction accuracy. We investigate this for the case of substantial between-subjects correlation between primary and secondary response variables, assuming negligible within-subjects correlation. We show how to determine the accuracy of primary response predictions as a function of secondary response observations. Given measurement costs for primary and secondary variables, we determine the number of observations that produces, with minimal cost, a fixed average prediction accuracy for a model of subject means. We illustrate this with estimation of subject-specific sleep parameters using polysomnography and wrist actigraphy. We also consider prediction accuracy in an example time-dependent, linear model and derive equations for the optimal timing of measurements to achieve, on average, the best prediction accuracy. Finally, we examine an example involving a circadian rhythm model and show numerically that secondary variables can improve individualized predictions in this time-dependent nonlinear model as well.
Pulmonary Disease Secondary to Reflux Mimicking Interstitial Pneumonia in Systemic Sclerosis: Case Report and Literature Review
Authors: Montes Ricardo Azêdo de Luca , Mazolli Veiga Nathalia , Lanzieri Pedro Gemal , Mocarzel Luis Otávio Cardoso
Published: January 2016

Systemic sclerosis is a complex disease due to the variety of clinical presentations, often superimposed on other conditions, related or not to the connective tissue. We report a 43-year-old Brazilian woman with limited systemic sclerosis and pulmonary symptoms secondary to gastroesophageal reflux disease, with a clinical presentation similar to a diffuse interstitial lung disease. Because of the frequency of interstitial lung injury due to systemic sclerosis, this was an important differential diagnosis, which could be excluded after optimized treatment of reflux disease, with clinical and radiological improvement. Clinical management of patients with collagen diseases requires clinician skills to identify the natural history and understand its nuances. This is a common situation in clinical practice, but with a few discussions in international literature.
Biliary Adenofibroma with Invasive Carcinoma: Case Report and Review of the Literature
Authors: Godambe Anjali , Brunt Elizabeth M. , Fulling Keith H. , Reza Kermanshahi Taher
Published: January 2016

We report a case of biliary adenofibroma with an invasive carcinoma in a 71-year-old female who presented with bilateral upper abdominal pain. Imaging revealed a 6.3 cm heterogeneously enhancing mass in the left lateral segment of the liver. Histologically, the adenofibroma showed the characteristic components as previously described of biliary adenofibromata, namely, cystic and tubular structures lined by cuboidal to low columnar biliary type epithelium and a dense fibrous stroma composed of spindled cells. Intimately admixed with the adenofibroma was a distinct tumor composed of malignant clear cells which demonstrated stromal and vascular invasion. Although mitotic figures were inconspicuous, Ki67 was brisk and p53 demonstrated 25–50%positivity. Sections also showed a von Meyenberg complex located adjacent to the tumor. This case expands the understanding of this rare tumor and proves two important assertions from previous case reports. First, the presence of an associated von Meyenberg complex with similar morphology and immunohistochemical staining pattern suggests that biliary adenofibromata and von Meyenberg complexes may share related histogenesis. Second, biliary adenofibromata harbor malignant potential and may show malignant transformation. Furthermore, this case highlights the need for these rare tumors to be followed aggressively, as their biological behavior is poorly understood.
One-Year Outcome of Geriatric Hip-Fracture Patients following Prolonged ICU Treatment
Authors: Eschbach Daphne , Bliemel Christopher , Oberkircher Ludwig , Aigner Rene , Hack Juliana , Bockmann Benjamin , Ruchholtz Steffen , Buecking Benjamin
Published: January 2016

Purpose. Incidence of geriatric fractures is increasing. Knowledge of outcome data for hip-fracture patients undergoing intensive-care unit (ICU) treatment, including invasive ventilatory management (IVM) and hemodiafiltration (CVVHDF), is sparse.Methods. Single-center prospective observational study including 402 geriatric hip-fracture patients. Age, gender, the American Society of Anesthesiologists (ASA) classification, and the Barthel index (BI) were documented. Underlying reasons for prolonged ICU stay were registered, as well as assessed procedures like IVM and CVVHDF. Outcome parameters were in-hospital, 6-month, and 1-year mortality and need for nursing care.Results. 15% were treated > 3 days and 68% < 3 days in ICU. Both cohorts had similar ASA, BI, and age. In-hospital, 6-month, and 12-month mortality of ICU > 3d cohort were significantly increased (p=0.001). Most frequent indications were cardiocirculatory pathology followed by respiratory failure, renal impairment, and infection. 18% of patients needed CVVHDF and 41% IVM. In these cohorts, 6-month mortality ranged > 80% and 12-month mortality > 90%. 100% needed nursing care after 6 and 12 months.Conclusions. ICU treatment > 3 days showed considerable difference in mortality and nursing care needed after 6 and 12 months. Particularly, patients requiring CVVHDF or IVM had disastrous long-term results. Our study may add one further element in complex decision making serving this vulnerable patient cohort.
High Output Cardiac Failure Resolving after Repair of AV Fistula in a Six-Month-Old
Authors: Teomete Uygar , Gugol Rubee Anne , Neville Holly , Dandin Ozgur , Young Ming-Lon
Published: January 2016

Background. Acquired AVF in pediatrics are commonly caused by iatrogenic means, including arterial or venous punctures. These fistulae can cause great hemodynamic stress on the heart as soon as they are created.Case. A six-month-old 25-week gestation infant was referred for respiratory distress. Initial exam revealed tachypnea, tachycardia, and hypertension. There was a bruit noted on her left arm. An ultrasound showed an arteriovenous fistula. Its location, however, precluded intervention because of the high risk for limb-loss. An echocardiogram showed evidence of pulmonary hypertension that was treated with sildenafil and furosemide. However, no improvement was seen. On temporary manual occlusion of the fistula, the patient was noted to have increased her blood pressure and decreased her heart rate, suggesting significant hemodynamic effect of the fistula. The fistula was subsequently ligated and the patient clinically and echocardiographically improved.Conclusion. A patient in high output cardiac failure or pulmonary artery hypertension, especially prematüre patients with preexisting lung disease, should be probed for history of multiple punctures, trauma, or surgery and should have prompt evaluation for AVF. If it can be diagnosed and repaired, most of the cases have been shown to decrease the stress on the heart and reverse the pathologic hemodynamics.
Formation of Renal Cysts and Tumors in Vhl/Trp53-Deficient Mice Requires HIF1α and HIF2α
Authors: Schönenberger Désirée , Harlander Sabine , Rajski Michal , Jacobs Robert A. , Lundby Anne-Kristine , Adlesic Mojca , Hejhal Tomas , Wild Peter J. , Lundby Carsten , Frew Ian J.
Published: January 2016

The von Hippel–Lindau (VHL) tumor suppressor gene is inactivated in the majority of clear cell renal cell carcinomas (ccRCC), but genetic ablation of Vhl alone in mouse models is insufficient to recapitulate human tumorigenesis. One function of pVHL is to regulate the stability of the hypoxia-inducible factors (HIF), which become constitutively activated in the absence of pVHL. In established ccRCC, HIF1α has been implicated as a renal tumor suppressor, whereas HIF2α is considered an oncoprotein. In this study, we investigated the contributions of HIF1α and HIF2α to ccRCC initiation in the context of Vhl deficiency. We found that deleting Vhl plus Hif1a or Hif2a specifically in the renal epithelium did not induce tumor formation. However, HIF1α and HIF2α differentially regulated cell proliferation, mitochondrial abundance and oxidative capacity, glycogen accumulation, and acquisition of a clear cell phenotype in Vhl-deficient renal epithelial cells. HIF1α, but not HIF2α, induced Warburg-like metabolism characterized by increased glycolysis, decreased oxygen consumption, and decreased ATP production in mouse embryonic fibroblasts, providing insights into the cellular changes potentially occurring in Vhl mutant renal cells before ccRCC formation. Importantly, deletion of either Hif1a or Hif2a completely prevented the formation of renal cysts and tumors in Vhl/Trp53 mutant mice. These findings argue that both HIF1α and HIF2α exert protumorigenic functions during the earliest stages of cyst and tumor formation in the kidney. Cancer Res; 76(7); 2025–36. ©2016 AACR.
Endometrial Carcinomas with POLE Exonuclease Domain Mutations Have a Favorable Prognosis
Authors: McConechy Melissa K. , Talhouk Aline , Leung Samuel , Chiu Derek , Yang Winnie , Senz Janine , Reha-Krantz Linda J. , Lee Cheng-Han , Huntsman David G. , Gilks C. Blake , McAlpine Jessica N.
Published: January 2016

Purpose: The aim of this study was to confirm the prognostic significance of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients. In addition, the effect of treatment on POLE-mutated tumors was assessed.

Experimental Design: A retrospective patient cohort of 496 endometrial carcinoma patients was identified for targeted sequencing of the POLE exonuclease domain, yielding 406 evaluable tumors. Univariable and multivariable analyses were performed to determine the effect of POLE mutation status on progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). Combining results from eight studies in a meta-analysis, we computed pooled HR for PFS, DSS, and OS.

Results: POLEEDMs were identified in 39 of 406 (9.6%) endometrial carcinomas. Women with POLE-mutated endometrial carcinomas were younger, with stage I (92%) tumors, grade 3 (62%), endometrioid histology (82%), and frequent (49%) lymphovascular invasion. In univariable analysis, POLE-mutated endometrial carcinomas had significantly improved outcomes compared with patients with no EDMs for PFS, DSS, and OS. In multivariable analysis, POLE EDMs were only significantly associated with improved PFS. The effect of adjuvant treatment on POLE-mutated cases could not be determined conclusively; however, both treated and untreated patients with POLE EDMs had good outcomes. Meta-analysis revealed an association between POLE EDMs and improved PFS and DSS with pooled HRs 0.34 [95% confidence interval (CI), 0.15–0.73] and 0.35 (95% CI, 0.13–0.92), respectively.

Conclusions: POLE EDMs are prognostic markers associated with excellent outcomes for endometrial carcinoma patients. Further investigation is needed to conclusively determine if treatment is necessary for this group of women. Clin Cancer Res; 22(12); 2865–73. ©2016 AACR.
Tumor-Infiltrating Plasma Cells Are Associated with Tertiary Lymphoid Structures, Cytolytic T-Cell Responses, and Superior Prognosis in Ovarian Cancer
Authors: Kroeger David R. , Milne Katy , Nelson Brad H.
Published: January 2016

Purpose: CD8+ tumor-infiltrating lymphocytes (TIL) are key mediators of antitumor immunity and are strongly associated with survival in virtually all solid tumors. However, the prognostic effect of CD8+ TIL is markedly higher in the presence of CD20+ B cells, suggesting that cooperative interactions between these lymphocyte subsets lead to more potent antitumor immunity.

Experimental Design: We assessed the colocalization patterns, phenotypes, and gene expression profiles of tumor-associated T- and B-lineage cells in high-grade serous ovarian cancer (HGSC) by multicolor IHC, flow cytometry, and bioinformatic analysis of gene expression data from The Cancer Genome Atlas.

Results: T cells and B cells colocalized in four types of lymphoid aggregate, ranging from small, diffuse clusters to large, well-organized tertiary lymphoid structures (TLS) resembling activated lymph nodes. TLS were frequently surrounded by dense infiltrates of plasma cells (PC), which comprised up to 90% of tumor stroma. PCs expressed mature, oligoclonal IgG transcripts, indicative of antigen-specific responses. PCs were associated with the highest levels of CD8+, CD4+, and CD20+ TIL, as well as numerous cytotoxicity-related gene products. CD8+ TIL carried prognostic benefit only in the presence of PCs and these other TIL subsets. PCs were independent of mutation load, BRCA1/2 status, and differentiation antigens but positively associated with cancer–testis antigens.

Conclusions: PCs are associated with the most robust, prognostically favorable CD8+ TIL responses in HGSC. We propose that TLS facilitate coordinated antitumor responses involving the combined actions of cytolytic T cells and antibody-producing PCs. Clin Cancer Res; 22(12); 3005–15. ©2016 AACR.
Exemestane Use in Postmenopausal Women at High Risk for Invasive Breast Cancer: Evaluating Biomarkers of Efficacy and Safety
Authors: Gatti-Mays Margaret E. , Venzon David , Galbo Claudia E. , Singer Andrea , Reynolds James , Makariou Erini , Kallakury Bhaskar , Heckman-Stoddard Brandy M. , Korde Larissa , Isaacs Claudine , Warren Robert , Gallagher Ann , Eng-Wong Jennifer
Published: January 2016

This phase II trial evaluated clinical markers of efficacy and safety of exemestane in postmenopausal women at increased risk for breast cancer. Postmenopausal women (n = 42) at risk for invasive breast cancer received 25 mg exemestane daily for 2 years along with calcium and vitamin D. The primary outcome was change in mammographic density (MD) after one year. Secondary outcomes included change in serum steroid hormones as well as change in trefoil protein 1 (TFF1) and proliferating cell nuclear antigen (PCNA) in breast tissue. Safety and tolerability were also assessed. MD decreased at 1 year and was significant at 2 years [mean change = −4.1%; 95% confidence intervals (CI), −7.2 to −1.1; P = 0.009]. Serum estradiol and testosterone levels significantly decreased at 3 months and remained suppressed at 12 months. After 1 year of treatment, TFF1 intensity decreased (mean change −1.32; 95% CI, −1.87 to −0.76; P < 0.001). Exemestane was safe and well tolerated. Exemestane decreased MD and expression of breast tissue TFF1. It was well tolerated with few clinically relevant side effects. MD and breast tissue TFF1 are potential biomarkers of breast cancer–preventive effects of exemestane in high-risk postmenopausal women. Cancer Prev Res; 9(3); 225–33. ©2016 AACR.
Inside-Out Signaling Pathways from Nuclear Reactive Oxygen Species Control Pulmonary Innate Immunity
Authors: Choudhary Sanjeev , Boldogh Istvan , Brasier Allan R.
Published: January 2016

The airway mucosa is responsible for mounting a robust innate immune response (IIR) upon encountering pathogen-associated molecular patterns. The IIR produces protective gene networks that stimulate neighboring epithelia and components of the immune system to trigger adaptive immunity. Little is currently known about how cellular reactive oxygen species (ROS) signaling is produced and cooperates in the IIR. We discuss recent discoveries about 2 nuclear ROS signaling pathways controlling innate immunity. Nuclear ROS oxidize guanine bases to produce mutagenic 8-oxoguanine, a lesion excised by 8-oxoguanine DNA glycosylase1/AP-lyase (OGG1). OGG1 forms a complex with the excised base, inducing its nuclear export. The cytoplasmic OGG1:8-oxoG complex functions as a guanine nucleotide exchange factor, triggering small GTPase signaling and activating phosphorylation of the nuclear factor (NF)κB/RelA transcription factor to induce immediate early gene expression. In parallel, nuclear ROS are detected by ataxia telangiectasia mutated (ATM), a PI3 kinase activated by ROS, triggering its nuclear export. ATM forms a scaffold with ribosomal S6 kinases, inducing RelA phosphorylation and resulting in transcription-coupled synthesis of type I and type III interferons and CC and CXC chemokines. We propose that ATM and OGG1 are endogenous nuclear ROS sensors that transmit nuclear signals that coordinate with outside-in pattern recognition receptor signaling, regulating the IIR.
Frameless Stereotactic Ommaya Reservoir Placement: Efficacy and Complication Comparison with Frame-Based Technique
Authors: Kennedy Benjamin C. , Brown Lauren T. , Komotar Ricardo J. , McKhann 2nd Guy M.
Published: January 2016

Background: Ommaya reservoirs are ventricular access devices used primarily for the administration of intrathecal antineoplastic chemotherapy. In patients with low or normal ventricular volume, stereotaxy can improve accuracy of catheter placement with minimal morbidity. Frameless stereotaxy has become an increasingly popular alternative to frame-based stereotaxy. Relative rates of successful catheter placement between these two techniques are not described in the literature. Objectives: To compare a large series of frameless to frame-based stereotactic catheter placements for Ommaya reservoirs, with an aim to compare accuracy and complication rate between the two procedures. Methods: A consecutive series of 41 frame-based and 68 frameless Ommaya reservoir placement procedures performed at our institution from 1998 to 2013 was reviewed. Patient demographics, operative accuracy and complication rates for the two techniques were compared. Results: Characteristics of the two groups were similar in diagnoses, age and other related factors. Comparison of frameless to frame-based stereotactic Ommaya catheter placement did not show significant differences in accuracy of placement, overall morbidity or mortality, or in any subcategory of complications. Conclusions: These findings suggest that frameless stereotactic Ommaya reservoir placement is as safe and accurate as the frame-based technique.
Laparoscopic Management of Vaginal Vault Prolapse Recurring after Pelvic Organ Prolapse Surgery
Authors: Mearini Luigi , Nunzi Elisabetta , Di Biase Manuel , Costantini Elisabetta
Published: January 2016

Introduction: Despite the increasing success of surgery for pelvic organ prolapse, recurrent vaginal vault prolapse is not rare. We present a step-by-step laparoscopic approach with a sacral colpopexy (SC) for treatment of recurrent vault prolapse. Materials and Methods: From 2006, 25 women presenting with symptomatic recurrent vault prolapse were prospectively evaluated and treated with laparoscopic SC. This article briefly describes all of the steps that are required to conduct a proper surgery in such cases. Results: After previous abdominal sacropexy, both the dissection of adherences and restoration of normal pelvic anatomy were challenging. As result, the overall operating time was longer in patients who had undergone abdominal sacropexy vs. vaginal route, p = 0.032. No significant peri- or postoperative complications were observed. At a mean follow-up of 41 months, all women presented with less than stage 2 prolapse and high levels of satisfaction. Conclusions: Despite the need for an intraoperative step-by-step surgical safety checklist, the laparoscopic repair of recurrent vault prolapse is technically feasible, safe and effective.
Carboxiterminal pro-endothelin-1 as an endothelial cell biomarker in thrombotic thrombocytopenic purpura
Authors: Sinkovits György , Farkas Péter , Csuka Dorottya , Rázsó Katalin , Réti Marienn , Radványi Gáspár , Demeter Judit , Prohászka Zoltán , Mikes Bálint
Published: January 2016

Thrombotic thrombocytopenic purpura (TTP) is characterised by the deficiency of the von Willebrand factor (VWF) cleaving protease (ADAMTS-13). Although several observations indicate an important role of endothelial activation in the pathogenesis of TTP, no reliable endothelial activation markers are available in the clinical management of TTP. Our aim was to investigate the presence of endothelial activation in TTP and to determine its connections with disease activity, therapy and complement activation. We enrolled 54 patients (median age 40.5; 44 females) and 57 healthy controls (median age 34; 30 females),VWF antigen, carboxiterminal-pro-endothelin-1 (CT-proET-1), complement Factor H and complement activation products (C3bBbP and SC5b-9) were measured. In both the acute and remission phase of TTP we found increased CT-proET-1 and VWF levels, while Factor H levels decreased compared with healthy controls. In remission, however, the elevated CT-proET-1 levels showed 22 % decrease when compared with the acute phase in paired samples (p=0.0031), whereas no changes for VWF and Factor H levels were observed. We also found positive correlations between CT-proET-1 levels and alternative pathway activation markers (C3bBbP; p=0.0360; r=0.4299). The data we present here demonstrate a role of endothelium activation in patients with acute TTP. The finding that CT-proET-1 levels decreased in remission compared with the acute phase further supports endothelial involvement. In addition, we show that endothelial activation also correlated with the activation of the alternative complement pathway. The data suggest that complement and endothelium activation jointly contribute to the development of TTP episodes in patients with predisposition to TTP.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Processo de Formatação de Atrativos Turísticos Sustentáveis
Authors: Oliveira Cassio dos Santos e , Minasse Maria Henriqueta Sperandio Garcia Gimenes , Marques Sílvio César Moral
Published: January 2016

Este artigo parte do pressuposto que o planejamento do destino turístico, com base nas premissas do desenvolvimento sustentável, deve focar e ressaltar seus atrativos turísticos, uma vez que esses elementos são responsáveis por promover o deslocamento de visitantes. Assim, a organização dos atrativos turísticos impacta na competitividade do destino no mercado turístico. Este estudo tem como objetivo o desenvolvimento de um processo de formatação de atrativos turísticos sustentáveis. Os dados que subsidiam as reflexões aqui apresentadas foram coletados a partir de pesquisa bibliográfica e documental. O resultado final é a apresentação de um processo de formatação de atrativos turísticos, com uma abordagem prática e operacional no formato de auto solução, onde o proprietário e/ou gestor de atrativos turísticos, bem como os técnicos de projetos de turismo do SEBRAE-SP sejam capazes de implementar os procedimentos propostos neste trabalho. Este processo de formatação é composto por três etapas de desenvolvimento de atrativos turísticos (interpretação, diagnóstico e intervenção) que está alicerçado em cinco eixos estratégicos de análise (características do produto; estrutura física; segurança; gestão; promoção e comercialização). Espera-se que, ao contribuir para a análise da formatação de atrativos turísticos sustentáveis, possa-se criar subsídios para o processo de planejamento de destinos turísticos, no sentido de incrementar a qualidade das atividades de lazer e as experiências oferecidas, bem como orientar os profissionais que atuam diretamente na gestão desses equipamentos turísticos.
Shoreline: Image and Representation of the Seacoast and Contemporary Art
Authors: Dias Geraldo Souza
Published: January 2016

The article presents a reflection on the systematic practice (research?) developed at ECA/USP in partnership with the Oceanographic Institute of USP in the last years focused on the representation and imagination of the seascape in Cananéia (South seashore of the State of Sao Paulo) and suggests a survey on the several studies and/or artistic practices developed in other seashore areas of Brazil with the purpose of producing a future mapping of such researches and its artistic, didactic and sociocultural unfolding.
Expanded fields of sculpture in landscape and urban rehabilitation: an example of public art and collaborative practices
Authors: Piteira Susana , Charréu Leonardo
Published: January 2016

We seek to discuss the sculpture insertion as qualitative element in urban and landscape rehabilitation project of an old country road, developed and implemented in Belver, a small rural town in central Portugal. We highlight the impact and the conceptual debate that was generated by the project – supported with EU funds – over who participated in it, as well as collaborative practices between politicians, architects and artists (sculptors) we consider to be relatively rare in similar contexts. They permeated the principles and processes in which the work was performed, and therefore they seemed worthy of study and attention
Effect of Left Atrial Ablation Process and Strategy on Microemboli Formation During Irrigated Radiofrequency Catheter Ablation in an In Vivo Model
Authors: Takami Mitsuru , Lehmann H. Immo , Parker Kay D. , Welker Kirk M. , Johnson Susan B. , Packer Douglas L.
Published: January 2016

Background—

Formation of microemboli during catheter ablation has been suggested as a cause for asymptomatic cerebral emboli. However, it is unknown which part of the process and ablation setting/strategy is most strongly related to this occurrence.

Methods and Results—

A total of 27 pigs were used. Catheter/sheath manipulations in left atrium were performed in 25 of 27 pigs outfitted with microemboli monitoring systems. Ablations using open-irrigated radiofrequency catheters were performed in 18 of 25 pigs. Two of 27 pigs did not undergo left atrial procedures and were injected with microembolic materials in the carotid artery to serve as positive controls. In total, 334 sheath/catheter manipulations (transseptal puncture, sheath flushing, catheter insertion, pulmonary vein venography, and sheath exchange) and 333 radiofrequency applications (power setting, 30/50 W; point-by-point/drag ablations) were analyzed. High microbubble volume in the extracorporeal circulation loop and a high number of microembolic signals in carotid artery were observed during sheath/catheter manipulations especially in saline/contrast injections at fast speed and ablations with steam pop. Fast sheath flushing produced significantly higher microbubble volume than slow sheath flushing (median, 12 200 versus 121 nL;
P
<0.0001). A total of 44 of 126 (35%) blood filters in the circulation loop showed microparticles (thrombus/coagulum and tissue). Most of them were seen after radiofrequency application especially in 50-W ablations, drag ablations, and steam pop. Brain magnetic resonance imaging showed positive-embolic lesions in control pigs.

Conclusions—

Formation of microbubbles was the greatest during fast saline/contrast injections and steam pops, whereas high-power radiofrequency applications, drag ablations, and steam pops produced most of the microparticles.
Cortical Sparing in Preterm Ischemic Arterial Stroke
Authors: van der Aa Niek E. , Benders Manon J.N.L. , Nikkels Peter G. , Groenendaal Floris , de Vries Linda S.
Published: January 2016

Background and Purpose—

Residual injury after perinatal arterial ischemic stroke in the middle cerebral artery territory usually involves the loss of cortical gray matter and subcortical white matter. In this article, we describe a different pattern of residual injury after middle cerebral artery stroke in preterm-born infants, in which the cortex is spared.

Methods—

Magnetic resonance imaging scans of 40 infants (12 preterm and 28 full-term infants) with a large middle cerebral artery stroke were reviewed and correlated with outcome.

Results—

Complete sparing of the cortex with cavitation of the underlying white matter was observed in 3 preterm infants, and partial sparing was noted in another 4 late preterm–born infants. One full-term infant had partial cortical sparing, and all others showed no sparing. Overall, 86% developed a hemiplegia and 30% had a developmental quotient below 85, but this did not vary between the different types of cortical injury.

Conclusions—

The pattern of cortical injury after middle cerebral artery stroke changes with gestational age and may be related to maturational changes of the vascular system. Outcome did not vary between the different patterns of cortical injury.
ERP Evidence for Implicit Priming of Top–Down Control of Attention
Authors: Blais Chris , Hubbard Emily , Mangun George R.
Published: January 2016

Proportion congruency effects are the observation that the magnitude of the Stroop effect increases as the proportion of congruent trials in a block increases. Contemporary work shows that proportion effects can be specific to a particular context. For example, in a Simon task in which items appearing above fixation are mostly congruent and items appearing below fixation are mostly incongruent, the Simon effect is larger for the items appearing at the top. There is disagreement as to whether these context-specific effects result from simple associative learning or, instead, a type of conflict-mediated associative learning. Here, we address this question in an ERP study using a Simon task in which the proportion congruency effect was context-specific, manipulating the proportion of congruent trials based on location (upper vs. lower visual field). We found significant behavioral proportion congruency effects that varied with the specific contexts. In addition, we observed that the N2 response of the ERPs to the stimuli was larger in amplitude for the high congruent (high conflict) versus low congruent (low conflict) conditions/contexts. Because the N2 is known to be greater in amplitude also for trials where conflict is high and is believed to be an electrical signal related to conflict detection in the medial frontal cortex, this supports the idea that conflict-mediated associative learning is involved in the proportion congruency effect.