bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiobjective Programming Problems Involving Fuzzy Coefficients, Random Variable Coefficients and Fuzzy Random Variable Coefficients
Authors: Yano Hitoshi
Published: August 2015

In this paper, we propose an interactive method for multiobjective linear programming problems, in which fuzzy coefficients, random variable coefficients and fuzzy random variable coefficients are involved in the objective functions respectively. In the proposed method, it is assumed that the decision maker has a fuzzy goal for each objective function, and such a fuzzy goal can be quantified by eliciting the membership function. Through a possibility measure and a fractile optimization model, the original problem is transformed to the well-defined multiobjective programming problem. Then, a generalized Pareto optimal concept is defined, and an interactive algorithm is proposed to obtain a satisfactory solution from among a generalized Pareto optimal solution set.
Multivalued Dependencies in Fuzzy Multivalued Relational Databases Using Fuzzy Functions
Authors: Tayal Devendra K. , Saxena P. C.
Published: August 2015

In this paper we discuss an important integrity constraint called multivalued dependency (mvd), which occurs as a result of the first normal form, in the framework of a newly proposed model called fuzzy multivalued relational data model. The fuzzy multivalued relational data model proposed in this paper accommodates a wider class of ambiguities by representing the domain of attributes as a “set of fuzzy subsets”. We show that our model is able to represent multiple types of impreciseness occurring in the real world. To compute the equality of two fuzzy sets/values (which occur as tuple-values), we use the concept of fuzzy functions. So the main objective of this paper is to extend the mvds in context of fuzzy multivalued relational model so that a wider class of impreciseness can be captured. Since the mvds may not exist in isolation, a complete axiomatization for a set of fuzzy functional dependencies (ffds) and mvds in fuzzy multivalued relational schema is provided and the role of fmvds in obtaining the lossless join decomposition is discussed. We also provide a set of sound Inference Rules for the fmvds and derive the conditions for these Inference Rules to be complete. We also derive the conditions for obtaining the lossless join decomposition of a fuzzy multivalued relational schema in the presence of the fmvds. Finally we extend the ABU's Algorithm to find the lossless join decomposition in context of fuzzy multivalued relational databases. We apply all of the concepts of fmvds developed by us to a real world application of “Technical Institute” and demonstrate that how the concepts fit well to capture the multiple types of impreciseness.
R&D CONSORTIA AS BOUNDARY ORGANISATIONS: MISALIGNMENT AND ASYMMETRY OF BOUNDARY MANAGEMENT
Authors: OMIDVAR OMID , KISLOV ROMAN
Published: August 2015

The paper presents a qualitative multiple case study of three multilateral public–private R&D consortia representing different industrial sectors. Using the practice-based view as a theoretical lens, we explore the interplay between the deliberate and emergent practices of boundary management across the following three dimensions: (1) Boundary bridging focus; (2) boundary crossing arrangements; and (3) collaborative governance arrangements. Drawing on interviews, documentary analysis and observational data, we describe the misalignment between the deliberate and emergent aspects of boundary management, which can be caused by the funders’ reporting requirements, power differentials between collaborators and lack of contextual understanding. These factors, accompanied by path-dependency and confidentiality issues, may result in asymmetrical boundary management, whereby a selective focus on a specific boundary (or set of boundaries) combined with an unequal development of boundary bridges within the collaboration may lead to the crossing of some boundaries being prioritised at the expense of others.
A Predictive Model for the Elastic Properties of a Collagen-Hydroxyapatite Porous Scaffold for Multi-Layer Osteochondral Substitutes
Authors: Gastaldi Dario , Parisi Gianluca , Lucchini Riccardo , Contro Roberto , Bignozzi Simone , Ginestra Paola S. , Filardo Giuseppe , Kon Elisaveta , Vena Pasquale
Published: August 2015

Damaged articular cartilage can be substituted by porous scaffolds exhibiting tailored mechanical properties and with a suited layer-based design. Reliable predictive models are able to provide a structure–property relationship in the design phase is still an open issue which is of prominent relevance. In this paper, a bottom-up homogenization approach is presented having the purpose to determine the elastic properties of each single layer of a osteochondral porous three-layers scaffold: a top cartilage chondral layer and two mineralized layers: an intermediate and a subchondral bone layer. For the cartilage top layer, dry and wet conditions are considered; while, for intermediate and bone layers only dry conditions are considered. The homogenization model is based on the porosity of each layer and on the elastic properties of the constituent materials, i.e., water, hydroxyapatite (HA) and collagen. The elastic moduli predicted for the mineralized layers are compared with available literature results. The model results obtained on the cartilage layers are validated through flat punch micro-indentation tests carried out on wet and dry samples.

The results have shown that the elastic modulus of the mineralized layers is of the order of magnitude of few GPa; whereas, the elastic modulus of the cartilage layer which exhibits porosity higher than 90% is as low as 50 kPa and 300 kPa in wet and dry conditions, respectively. The above results show that the knowledge of the mechanical properties of the basic constituents which are universally known and the porosity of the layers are sufficient information to obtain a reliable prediction of the elastic properties of both mineralized layers and of cartilage layers.
Characterization of Electro-Active Paper Vibration Sensor by Impact Testing and Random Excitation
Authors: Abas Zafar , Yang Dong Ho , Kim Heung Soo , Kwak Moon Kyu , Kim Jaehwan
Published: August 2015

We characterized a vibration sensor made of piezoelectric paper by measuring the frequency response function of an aluminum cantilever that was subjected to impulse loading and random excitation. The dynamic characteristics of the device were measured by recording the transient response of the smart cantilever beam with a pair of electro-active paper (EAPap) and polyvinylidene fluoride (PVDF) sensors located at a 5 mm distance from the clamped end as well as from a second pair of piezoelectric sensors located at a distance of 140 mm. The responses were measured by impacting the cantilever at its tip and at its mid-point. A fast Fourier transform was applied on the time domain data to measure the resonant frequencies of the vibrating structure. Both the EAPap and the PVDF sensors were observed to be very sensitive to varying levels of dynamic strain. The EAPap sensor showed a low strain sensitivity that was found to be desirable due to the inherent piezoelectricity and eco-friendly behavior of the material. The results revealed that the dynamic sensing ability of the EAPap at a low frequency range was quite comparable to that of PVDF when monitoring structural vibrations. The frequency response function was also measured via random excitation, piezoelectricity of the EAPap sensor shows potential for sensing vibrations with a dynamic response.
Modeling Signaling Networks to Advance New Cancer Therapies
Authors: Saez-Rodriguez Julio , MacNamara Aidan , Cook Simon
Published: August 2015

Cell signaling pathways control cells' responses to their environment through an intricate network of proteins and small molecules partitioned by intracellular structures, such as the cytoskeleton and nucleus. Our understanding of these pathways has been revised recently with the advent of more advanced experimental techniques; no longer are signaling pathways viewed as linear cascades of information flowing from membrane-bound receptors to the nucleus. Instead, such pathways must be understood in the context of networks, and studying such networks requires an integration of computational and experimental approaches. This understanding is becoming more important in designing novel therapies for diseases such as cancer. Using the MAPK (mitogen-activated protein kinase) and PI3K (class I phosphoinositide-3′ kinase) pathways as case studies of cellular signaling, we give an overview of these pathways and their functions. We then describe, using a number of case studies, how computational modeling has aided in understanding these pathways' deregulation in cancer, and how such understanding can be used to optimally tailor current therapies or help design new therapies against cancer.
Approaching the Econo-Socio-Legal
Authors: Perry-Kessaris Amanda
Published: August 2015

This article offers a systematic introduction to a body of historical and contemporary research that is distinctive in its commitment to the observations that the economy and the law are mutually constitutive, and that both are in turn mutually constitutive of wider social life, including that part of social life relating to how we think and communicate about the econo-socio-legal. The aim is to offer a framework for approaching econo-socio-legal thinking and practice from the past, present, and future.
Justice and Negotiation
Authors: Druckman Daniel , Wagner Lynn M.
Published: August 2015

This review article examines the literature regarding the role played by principles of justice in negotiation. Laboratory experiments and high-stakes negotiations reveal that justice is a complex concept, both in relation to attaining just outcomes and to establishing just processes. We focus on how justice preferences guide the process and outcome of negotiated exchanges. Focusing primarily on the two types of principles that have received the most attention, distributive justice (outcomes of negotiation) and procedural justice (process of negotiation), we introduce the topic by reviewing the most relevant experimental and field or archival research on the roles played by these justice principles in negotiation. A discussion of the methods used in these studies precedes a review organized in terms of a framework that highlights the concept of negotiating stages. We also develop hypotheses based on the existing literature to point the way forward for further research on this topic.
β-Blocker Use and Risk of Recurrence in Patients with Early Breast Cancer
Authors: Sakellakis Minas , Kostaki Anastasia , Starakis Ioannis , Koutras Angelos
Published: August 2015

Aim: We evaluated whether the concurrent β-blocker use in early breast cancer patients influenced the outcome in terms of preventing tumor recurrence after adjuvant chemotherapy. Methods: We retrospectively reviewed the medical records of 610 patients with breast cancer. Thereafter, we compared overall disease-free survival (DFS) between β-blocker users and nonusers. Results: Those not receiving β-blockers had a relatively longer mean DFS (10.8 vs. 9.7 years), although the difference did not reach statistical significance (p = 0.651). When the survival analysis was adjusted for age, tumor stage, hormone receptor status and HER2 status, the results remained unaltered, suggesting that β-blocker use did not significantly improve overall DFS (HR, 0.849; 95% CI, 0.537-1.343; p = 0.485). Conclusion: Our findings failed to confirm previous results indicating a potential antitumor effect of β-blockers.
The Essential Oil from Origanum vulgare L. and Its Individual Constituents Carvacrol and Thymol Enhance the Effect of Tetracycline against Staphylococcus aureus
Authors: Cirino Isis Caroline S. , Menezes-Silva Suellen Maria P. , Silva Helena Tainá D. , de Souza Evandro Leite , Siqueira-Júnior José P.
Published: August 2015

Background: In an ongoing project to evaluate essential oils as modulators of antibiotic resistance, the essential oil from Origanum vulgare L. (OVEO), as well as its individual constituents carvacrol (CAR) and thymol (THY), were investigated using Staphylococcus aureus strains possessing efflux mechanisms of resistance to norfloxacin, erythromycin and tetracycline. Methods: The minimum inhibitory concentration (MIC) values of the antibiotics were determined by agar dilution method, in the absence and in the presence of subinhibitory concentrations of OVEO, CAR or THY. Results: Along with relevant antistaphylococcal activity, OVEO, CAR and THY modulated the activity of tetracycline, i.e. in combination with antibiotics a reduction in the MIC was observed (up to fourfold). Conclusions: The results presented here represent, as far as we know, the first report of OVEO, CAR and THY as putative efflux pump inhibitors. Broadly, these findings indicate that essential oils could serve as potential sources of compounds capable of modulating drug resistance.
Identification of Amino Acid Residues in Angiotensin II Type 1 Receptor Sensing Mechanical Stretch and Function in Cardiomyocyte Hypertrophy
Authors: Jiang Guoliang , Gong Hui , Niu Yuhong , Yang Chunjie , Wang Shijun , Chen Zhidan , Ye Yong , Zhou Ning , Zhang Guoping , Ge Junbo , Zou Yunzeng
Published: August 2015

Background/Aims: Angiotensin II (AngII) type 1 receptor (AT1R) could be activated by mechanical stress without the involvement of AngII during the development of cardiac hypertrophy. We aimed to identify sensing sites of AT1R for activation by mechanical stretch. Methods: We constructed several site-directed mutations of AT1R (AT1RK199Q, AT1RL212F, AT1RQ257A and AT1RC289A), transfected them respectively into COS7 cells or angiotensinogen knockout cardiomyocytes (ATG−/−-CMs), and observed cellular events after mechanical stretch. Results: AngII-induced phosphorylation of ERKs and Jak2, and redistribution of Gαq11 in AT1RWT- COS7 or -ATG−/−-CMs were dramatically decreased in AT1RK199Q- or AT1RQ257A- COS7 cells or -ATG−/−-CMs, while those effects induced by mechanical stretch were greatly suppressed in COS7 cells or ATG−/−-CMs expressing AT1RL212F, AT1RQ257A or AT1RC289A compared with these cells expressing AT1RWT. AngII-induced hypertrophic responses (the increase in hypertrophic genes expression and cross-sectional area) in AT1RWT- ATG−/−-CMs were partly abolished in AT1RK199Q-ATG−/−-CMs or AT1RQ257A-ATG−/−-CMs, while these responses induced by mechanical stretch were greatly inhibited in ATG−/−-CMs overexpressing AT1RL212F, AT1RQ257A or AT1RC289A. Conclusion: These results indicated that Leu212, Gln257 and Cys289 in AT1R are not only sensing sites for mechanical stretch but also functional amino residues for activation of the receptor and cardiomyocytes hypertrophy induced by mechanical stretch.
In vitro Cytotoxicity of Bisphenol A in Monocytes Cell Line
Authors: Neri Mauro , Virzì Grazia Maria , Brocca Alessandra , Garzotto Francesco , Kim Jeong Chul , Ramponi Francesco , de Cal Massimo , Lorenzin Anna , Brendolan Alessandra , Nalesso Federico , Zanella Monica , Ronco Claudio
Published: August 2015

Background/Aim: Bisphenol A (BPA) is used in the production of many plastics, which are used to build biomaterials that sometimes are in direct contact with blood. It is believed that the release of BPA into bloodstream may give rise to cytotoxic events for blood components. The aim of the present study was to perform an in vitro investigation of the observable cytotoxic effect of BPA, at increasing concentrations, on the monocyte cell line. Methods: We incubated in vitro monocyte cells (U937) for 24 h in cell line medium samples (RPMI 1640) at different concentrations of BPA. We then generated curves to evaluate viability, necrosis and apoptosis of monocytes against increasing concentrations of BPA. Results: The percentage values of concentrations of BPA corresponding to 50% of the viability and necrosis of the monocytes were 1.39 and 1.48 ng/ml, respectively. Based on our observations, we reported an increasing cytotoxic effect for higher concentrations. The apoptotic effect reached the maximum value at BPA concentration of 1.5 ng/ml; at still higher concentrations, we observed a predominantly necrotic cell death. Conclusion: Viability, necrosis and apoptosis of monocytes are strongly and positively correlated with BPA concentration. A direct contact of such compound with biological components of blood may lead to high levels of cytotoxicity, and require us to evaluate additional factors while judging the bio-incompatibility of BPA.
Time Savings with Once-Monthly C.E.R.A.: A Time and Motion Study Conducted in 13 Haemodialysis Centres in Italy
Authors: De Cock Erwin , Kritikou Persefoni , Ravera Simona , Filippini Armando
Published: August 2015

Background: We sought to document the time required by health care professionals to administer erythropoiesis-stimulating agents (ESAs) and continuous erythropoiesis receptor activator (C.E.R.A.) in the management of renal anaemia. Methods: A Time and Motion study was conducted in 13 centres in Italy. The time spent on preparation, distribution, and injection for both ESA and C.E.R.A. groups was measured. A multilevel model was run to account for the centre-clustering effect. Results: The average number of ESA injections/patient/year was 89. The average uptake of C.E.R.A. was 26%. The average time per session was 1.54 min for ESA (95% CI 1.21-1.86) vs. 1.64 min for C.E.R.A. (95% CI 1.31-1.97). Estimated time/patient/year was 137 min for ESA and 20 min for C.E.R.A. Assuming a 100% uptake of C.E.R.A., annual time savings/centre would be 84% (194 h). Conclusions: Substantial annual time savings on frequent anaemia management-related tasks were found when a switchover was made from ESAs to C.E.R.A.
Tumor Suppressor in Lung Cancer-1 Is a Prognostic Predictor for the Recurrence and Progression of Non-Muscle-Invasive Bladder Cancer
Authors: Chen Yegang , Yang Yongjiao , Liu Li , Wang Shangren , Song Hong , Liu Xiaoqiang
Published: August 2015

Objective: To investigate the relationship between the expression of tumor suppressor in lung cancer-1 (TSLC1) and clinicopathological characteristics of patients with non-muscle-invasive bladder cancer (NMIBC) and evaluate the prognostic significance of TSLC1. Methods: TSLC1 expression in 241 specimens of NMIBC was examined by immunohistochemistry. The correlation between TSLC1 expression and clinicopathological characteristics was evaluated using the chi-square test. The prognostic significance of TSLC1 was analyzed by univariate, multivariate analysis and Kaplan-Meier survival curves. Results: The total negative rate of TSLC1 expression was 47.3% in NMIBC. Decreased expression of TSLC1 was correlated with a higher clinical stage, higher pathological grade, the number of tumors, lager tumor size, tumor recurrence and progression. TSLC1 expression was an independent risk factor for predicting tumor recurrence (p = 0.005) and progression (p < 0.001). Conclusion: Decreased expression of TSLC1 is correlated with the malignancy of NMIBC tissues and low TSLC1 expression may serve as a predictor for bladder cancer recurrence and progression.
The Preinterventional Cystatin-Creatinine-Ratio: A Prognostic Marker for Contrast Medium-Induced Acute Kidney Injury and Long-Term All-Cause Mortality
Authors: Lüders Florian , Meyborg Matthias , Malyar Nasser , Reinecke Holger
Published: August 2015

Background/Aims: Contrast medium-induced acute kidney injury (CI-AKI) is an important iatrogenic complication following the injection of iodinated contrast media. The level of serum creatinine (SCr) is the currently accepted ‘gold standard' to diagnose CI-AKI. Cystatin C (CyC) has been detected as a more sensitive marker for renal dysfunction. Both have their limitations. Methods: The role of the preinterventional CyC-SCr ratio for evaluating the risk for CI-AKI and long-term all-cause mortality was retrospectively analyzed in the prospective single-center ‘Dialysis-versus-Diuresis trial'. CI-AKI was defined and staged according to the Acute Kidney Injury Network classification. Results: Three hundred and seventy-three patients were included (average age 67.4 ± 10.2 years, 16.4% women, 29.2% with diabetes mellitus, mean baseline glomerular filtration rate 56.3 ± 20.2 ml/min/1.73 m2 [as estimated by Chronic Kidney Disease Epidemiology Collaboration Serum Creatinine Cystatin C equation], 5.1% ejection fraction <35%). A total of 79 patients (21.2%) developed CI-AKI after elective heart catheterization, and 65 patients (17.4%) died during follow-up. Multivariate analyses by logistic regression confirmed that the preinterventional CyC-SCr ratio is independently associated with CI-AKI (OR 9.423, 95% CI 1.494-59.436, p = 0.017). Also, the Cox regression model found a high significant association between preinterventional CyC-SCr ratio and long-term all-cause mortality (mean follow-up 649 days, hazards ratio 4.096, 95% CI 1.625-10.329, p = 0.003). Conclusion: The preinterventional CyC-SCr ratio is independently associated with CI-AKI and highly significant associated with long-term mortality after heart catheterization.
The cost-utility of dabigatran etexilate compared with warfarin in treatment and extended anticoagulation of acute VTE in the UK
Authors: Jugrin Anamaria Vera , Ustyugova Anastasia , Urbich Michael , Sunderland Tom , Lamotte Mark
Published: August 2015

The relative efficacy and safety of dabigatran etexilate and warfarin have been evaluated in two head-to-head, phase III, treatment of acute venous thromboembolism (VTE) trials, and one extended prophylaxis trial, in patients with high risk of recurrent VTE. Dabigatran etexilate demonstrated similar efficacy to warfarin, and was associated with a reduced risk of major or clinically relevant bleeds. Based on results of these trials, and real-life disease prognosis following discontinuation of anticoagulation treatment, we evaluated the cost-utility of dabigatran etexilate compared with warfarin in six months anticoagulation, and in extended, up to 24 months anticoagulation, in patients with acute VTE, acute deep-vein thrombosis (DVT) or acute, symptomatic, pulmonary embolism (PE). Costs were analysed from the perspective of the National Health Services (NHS) and Public Social Services (PSS) in England and Wales. Outcomes were quantified in quality-adjusted life years (QALY). The estimated incremental, lifetime cost/QALY gain following acute, symptomatic VTE (DVT or PE) was £1,252/QALY when dabigatran etexilate or warfarin were administered for up to six months treatment. In treatment of acute, symptomatic PE and in DVT respective ratios were £1,767/QALY and £1,075/QALY. In extended, up to 24 months anticoagulation, dabigatran etexilate projected costs/QALY of £8,242/QALY, when compared with warfarin. Results obtained herein were robust across a number of sensitivity analyses and suggest dabigatran etexilate to be a cost-effective alternative to current standard of care when evaluated in six months treatment and in extended anticoagulation following acute VTE (DVT and/or PE).
Cell painting with an engineered EPCR to augment the protein C system
Authors: Bouwens Eveline A. M. , Stavenuiter Fabian , Mosnier Laurent O.
Published: August 2015

The protein C (PC) system conveys beneficial anticoagulant and cytoprotective effects in numerous in vivo disease models. The endothelial protein C receptor (EPCR) plays a central role in these pathways as cofactor for PC activation and by enhancing activated protein C (APC)-mediated protease-activated receptor (PAR) activation. During inflammatory disease, expression of EPCR on cell membranes is often diminished thereby limiting PC activation and APC’s effects on cells. Here a caveolae-targeting glycosylphosphatidylinositol (GPI)-anchored EPCR (EPCR-GPI) was engineered to restore EPCR’s bioavailability via “cell painting.” The painting efficiency of EPCR-GPI on EPCR-depleted endothelial cells was time- and dose-dependent. The EPCR-GPI bioavailability after painting was long lasting since EPCR surface levels reached 400 % of wild-type cells after 2 hours and remained > 200 % for 24 hours. EPCR-GPI painting conveyed APC binding to EPCR-depleted endothelial cells where EPCR was lost due to shedding or shRNA. EPCR painting normalised PC activation on EPCR-depleted cells indicating that EPCR-GPI is functional active on painted cells. Caveolin-1 lipid rafts were enriched in EPCR after painting due to the GPI-anchor targeting caveolae. Accordingly, EPCR painting supported PAR1 and PAR3 cleavage by APC and augmented PAR1-dependent Akt phosphorylation by APC. Thus, EPCR-GPI painting achieved physiological relevant surface levels on endothelial cells, restored APC binding to EPCR-depleted cells, supported PC activation, and enhanced APC-mediated PAR cleavage and cytoprotective signalling. Therefore, EPCRGPI provides a novel tool to restore the bioavailability and functionality of EPCR on EPCR- depleted and -deficient cells.
Gallstone Disease and the Risk of Ischemic Heart Disease
Authors: Lv Jun , Qi Lu , Yu Canqing , Guo Yu , Bian Zheng , Chen Yiping , Yang Ling , Shen Jie , Wang Shanqing , Li Mingqiang , Liu Yongmei , Zhang Libo , Chen Junshi , Chen Zhengming , Li Liming
Published: August 2015

Objective—

Gallstone disease (GSD) is related to multiple cardiovascular risk factors; the present study was to prospectively examine the association between GSD and ischemic heart disease (IHD).

Approach and Results—

We examined the association of GSD with IHD among 199 292 men and 288 081 women aged 30−79 years in the China Kadoorie Biobank study. Participants with cancer, heart disease, and stroke at baseline were excluded. Cox proportional hazards regression model was used to estimate the association of GSD with IHD. The prevalence of self-reported GSD was 3.7% in men and 7.3% in women at baseline. During 3 431 124 person-years of follow-up between 2004 and 2013 (median, 7.2 years), we documented 10 245 incident IHD cases in men and 14 714 in women. As compared with men without GSD at baseline, the multivariate-adjusted hazard ratio for IHD was 1.11 (95% confidence interval, 1.02−1.22) for men with GSD; the respective hazard ratio was 1.27 (95% confidence interval, 1.20−1.34) in women and 1.23 (95% confidence interval, 1.17−1.28) in the whole cohort. The sex difference in IHD risk associated with GSD was statistically significant (
P
=0.009 for interaction with sex). In addition, we found that the association between GSD and IHD was stronger in nonhypertensive than in hypertensive women (
P
<0.001 for interaction).

Conclusions—

In this large prospective study, the presence of GSD was associated with an increased risk of incident IHD, independent of other risk factors of cardiovascular disease. Our findings suggest novel prevention strategy to mitigate heart disease through improvement of gastrointestinal health.
Multisite Thrombus Imaging and Fibrin Content Estimation With a Single Whole-Body PET Scan in Rats
Authors: Blasi Francesco , Oliveira Bruno L. , Rietz Tyson A. , Rotile Nicholas J. , Naha Pratap C. , Cormode David P. , Izquierdo-Garcia David , Catana Ciprian , Caravan Peter
Published: August 2015

Objective—

Thrombosis is a leading cause of morbidity and mortality worldwide. Current diagnostic strategies rely on imaging modalities that are specific for distinct vascular territories, but a thrombus-specific whole-body imaging approach is still missing. Moreover, imaging techniques to assess thrombus composition are underdeveloped, although therapeutic strategies may benefit from such technology. Therefore, our goal was to test whether positron emission tomography (PET) with the fibrin-binding probe
64
Cu-FBP8 allows multisite thrombus detection and fibrin content estimation.

Approach and Results—

Thrombosis was induced in Sprague-Dawley rats (n=32) by ferric chloride application on both carotid artery and femoral vein.
64
Cu-FBP8-PET/CT imaging was performed 1, 3, or 7 days after thrombosis to detect thrombus location and to evaluate age-dependent changes in target uptake. Ex vivo biodistribution, autoradiography, and histopathology were performed to validate imaging results. Arterial and venous thrombi were localized on fused PET/CT images with high accuracy (97.6%; 95% confidence interval, 92–100). A single whole-body PET/MR imaging session was sufficient to reveal the location of both arterial and venous thrombi after
64
Cu-FBP8 administration. PET imaging showed that probe uptake was greater in younger clots than in older ones for both arterial and venous thrombosis (
P
<0.0001). Quantitative histopathology revealed an age-dependent reduction of thrombus fibrin content (
P
<0.001), consistent with PET results. Biodistribution and autoradiography further confirmed the imaging findings.

Conclusions—

We demonstrated that
64
Cu-FBP8-PET is a feasible approach for whole-body thrombus detection and that molecular imaging of fibrin can provide, noninvasively, insight into clot composition.
Differential Genetic Effects on Statin-Induced Changes Across Low-Density Lipoprotein–Related Measures
Authors: Chu Audrey Y. , Giulianini Franco , Barratt Bryan J. , Ding Bo , Nyberg Fredrik , Mora Samia , Ridker Paul M. , Chasman Daniel I.
Published: August 2015

Background—

Statin therapy influences not only low-density lipoprotein (LDL) cholesterol levels but also LDL-related biomarkers, including non–high-density lipoprotein cholesterol (non–HDL-C), apolipoprotein B, total number of LDL particles, and mean LDL particle size. Recent studies have identified many genetic loci influencing circulating lipid levels and statin-induced LDL cholesterol reduction. However, it is unknown how these genetic variants influence statin-induced changes in LDL subfractions and non–HDL-C.

Methods and Results—

One hundred sixty candidate single-nucleotide polymorphisms for effects on circulating lipid levels or statin-induced LDL-cholesterol lowering were tested for association with response of LDL subfractions and non–HDL-C to rosuvastatin or placebo for 1 year among 7046 participants from the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Of the 51 single-nucleotide polymorphisms associated with statin response for ≥1 of the LDL subfractions or non–HDL-C, 20 single-nucleotide polymorphisms could be clustered according to effects predominantly on LDL particle size, predominantly on LDL particle number, and on apolipoprotein B but not on LDL cholesterol or non–HDL-C.

Conclusions—

These differential associations point to pathways of LDL response to statin therapy and possibly to mechanisms of statin-dependent cardiovascular disease risk reduction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00239681.
Effect of High‐Calcium Diet on Coronary Artery Disease in Ossabaw Miniature Swine With Metabolic Syndrome
Authors: Phillips‐Eakley Alyssa K. , McKenney‐Drake Mikaela L. , Bahls Martin , Newcomer Sean C. , Radcliffe John S. , Wastney Meryl E. , Van Alstine William G. , Jackson George , Alloosh Mouhamad , Martin Berdine R. , Sturek Michael , Weaver Connie M.
Published: August 2015

Background

Calcium is a shortfall essential nutrient that has been a mainstay of osteoporosis management. Recent and limited findings have prompted concern about the contribution of calcium supplementation to cardiovascular risk. A proposed mechanism is through the acceleration of coronary artery calcification. Determining causality between calcium intake and coronary artery calcification has been hindered by a lack of sensitive methodology to monitor early vascular calcium accumulation. The primary study aim was to assess the impact of high calcium intake on coronary artery calcification using innovative calcium tracer kinetic modeling in Ossabaw swine with diet‐induced metabolic syndrome. Secondary end points (in vitro wire myography, histopathology, intravascular ultrasound) assessed coronary disease.

Methods and Results

Pigs (n=24; aged ≈15 months) were fed an atherogenic diet with adequate calcium (0.33% by weight) or high calcium (1.90% from calcium carbonate or dairy) for 6 months. Following 5 months of feeding, all pigs were dosed intravenously with
41
Ca, a rare isotope that can be measured in serum and tissues at a sensitivity of 10
−18
 mol/L by accelerator mass spectrometry. Kinetic modeling evaluated early coronary artery calcification using
41
Ca values measured in serial blood samples (collected over 27 days) and coronary artery samples obtained at sacrifice. Serum disappearance of
41
Ca and total coronary artery
41
Ca accumulation did not differ among groups. Secondary end points demonstrated no treatment differences in coronary artery disease or function.

Conclusion

There was no detectable effect of high calcium diets (from dairy or calcium carbonate) on coronary artery calcium deposition in metabolic syndrome swine.
Point-of-Care Testing of Coagulation in Patients Treated With Non–Vitamin K Antagonist Oral Anticoagulants
Authors: Ebner Matthias , Peter Andreas , Spencer Charlotte , Härtig Florian , Birschmann Ingvild , Kuhn Joachim , Wolf Martin , Winter Natalie , Russo Francesca , Zuern Christine S. , Blumenstock Gunnar , Ziemann Ulf , Poli Sven
Published: August 2015

Background and Purpose—

Specific coagulation assays for non–vitamin K antagonist oral anticoagulants (NOAC) are relatively slow and often lack availability. Although specific point-of-care tests (POCT) are currently not available, NOAC are known to affect established coagulation POCT. This study aimed at determining the diagnostic accuracy of the CoaguChek POCT to rule out relevant concentrations of rivaroxaban, apixaban, and dabigatran in real-life patients.

Methods—

We consecutively enrolled 60 ischemic stroke patients newly started on NOAC treatment and obtained blood samples at 6 prespecified time points. Samples were tested using the CoaguChek POCT, laboratory-based coagulation assays (prothrombin time and activated partial thromboplastin time, anti-Xa test and Hemoclot), and liquid chromatography–tandem mass spectrometry for direct determination of NOAC concentrations.

Results—

Three hundred fifty-six blood samples were collected. The CoaguChek POCT strongly correlated (
r
=0.82
P
<0.001) with rivaroxaban concentrations but did not accurately detect dabigatran or apixaban. If used to estimate the presence of low rivaroxaban concentrations, POCT was superior to predictions based on normal prothrombin time and activated partial thromboplastin time values even if sensitive reagents were used. POCT-results ≤1.0 predicted rivaroxaban concentrations <32 and <100 ng/mL with a specificity of 90% and 96%, respectively.

Conclusions—

If anti-Xa test is not available, we propose the use of the CoaguChek POCT to guide thrombolysis decisions after individual risk assessment in rivaroxaban-treated patients having acute ischemic stroke.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02371044.
Prognostic Factors for Cognitive Decline After Intracerebral Hemorrhage
Authors: Benedictus Marije R. , Hochart Anaïs , Rossi Costanza , Boulouis Gregoire , Hénon Hilde , van der Flier Wiesje M. , Cordonnier Charlotte
Published: August 2015

Background and Purpose—

Stroke and dementia are closely related, but no prospective study ever focused on poststroke cognitive decline in patients with intracerebral hemorrhage (ICH). We aimed to determine prognostic factors for cognitive decline in patients with ICH.

Methods—

We prospectively included 167 consecutive ICH survivors without preexisting dementia from the Prognosis of Intra-Cerebral Hemorrhage (PITCH) cohort. Median follow-up was 4 years (interquartile range, 2.3–5.4). We explored factors associated with cognitive decline using linear mixed models. Cognitive decline was determined based on repeated mini-mental state examination. We investigated each prognostic factor separately in univariate models. Next, we constructed clinical and radiological multivariable models. In a sensitivity analysis, we excluded patients with preexisting cognitive impairment.

Results—

Median age was 64 (interquartile range, 53–75) years, 69 (41%) patients were women, and median mini-mental state examination at 6 months was 27 (interquartile range, 23–29). Overall, 37% of the patients declined during follow-up. Factors associated with cognitive decline in univariate analyses were previous stroke or transient ischemic attack, preexisting cognitive impairment, microbleed presence, severity of white matter hyperintensities, and severity of cortical atrophy. In multivariable analyses, previous stroke or transient ischemic attack (β [SE], −0.55 [0.23];
P
<0.05), preexisting cognitive impairment (β [SE], −0.56 [0.25];
P
<0.01), and severity of cortical atrophy (β [SE], −0.50 [0.19];
P
<0.01) remained independent prognostic factors. In patients without preexisting cognitive impairment (n=139), severity of cortical atrophy (β [SE], −0.38 [0.17];
P
<0.05) was the only prognostic factor for future cognitive decline.

Conclusions—

Prognostic factors for cognitive decline after ICH are already present when ICH occurs, suggesting a process of ongoing cognitive impairment instead of new-onset decline induced by the ICH itself.
Strategies of Inhibition: U.S. Grand Strategy, the Nuclear Revolution, and Nonproliferation
Authors: Gavin Francis J.
Published: August 2015

The United States has gone to extraordinary lengths since the beginning of the nuclear age to inhibit—that is, to slow, halt, and reverse—the spread of nuclear weapons and, when unsuccessful, to mitigate the consequences. To accomplish this end, the United States has developed and implemented a wide range of tools, applied in a variety of combinations. These “strategies of inhibition” employ different policies rarely seen as connected to one another, from treaties and norms to alliances and security guarantees, to sanctions and preventive military action. The United States has applied these measures to friend and foe alike, often regardless of political orientation, economic system, or alliance status, to secure protection from nuclear attack and maintain freedom of action. Collectively, these linked strategies of inhibition have been an independent and driving feature of U.S. national security policy for more than seven decades, to an extent rarely documented or fully understood. The strategies of inhibition make sense of puzzles that neither containment nor openness strategies can explain, while providing critical insights into post–World War II history, theory, the causes of nuclear proliferation, and debates over the past, present, and future trajectory of U.S. grand strategy.
Barriers to Entry: Who Builds Fortified Boundaries and Why?
Authors: Hassner Ron E. , Wittenberg Jason
Published: August 2015

Fortified boundaries are asymmetrical, physical barriers placed along borders. These boundaries are more formidable in structure than conventional boundary lines, but less robust than militarized boundaries. Their goal is to impose costs on infiltrators and in so doing deter or impede infiltration. A novel dataset of all such boundaries worldwide shows that states are constructing these barriers at an accelerating rate. More than half of barrier builders are Muslim-majority states, and so are the vast majority of targets. A multivariate analysis demonstrates that, contrary to conventional wisdom, states that construct such barriers do not tend to suffer disproportionately from terrorism, nor are they apt to be involved in a significant number of territorial disputes. Instead, differences in state wealth and migration rates are the best predictors of barrier construction. Qualitative case studies suggest that the most effective fortified boundaries are found where the initiating state controls the territory beyond a boundary that blocks the only access route into the state.
Soft Balancing in the Americas: Latin American Opposition to U.S. Intervention, 1898–1936
Authors: Friedman Max Paul , Long Tom
Published: August 2015

In the aftermath of the 2003 U.S.-led invasion of Iraq, scholars of international relations debated how to best characterize the rising tide of global opposition. The concept of “soft balancing” emerged as an influential, though contested, explanation of a new phenomenon in a unipolar world: states seeking to constrain the ability of the United States to deploy military force by using multinational organizations, international law, and coalition building. Soft balancing can also be observed in regional unipolar systems. Multinational archival research reveals how Argentina, Mexico, and other Latin American countries responded to expanding U.S. power and military assertiveness in the early twentieth century through coordinated diplomatic maneuvering that provides a strong example of soft balancing. Examination of this earlier case makes an empirical contribution to the emerging soft-balancing literature and suggests that soft balancing need not lead to hard balancing or open conflict.
Imperial Crisis and Muslim-Christian Relations in Ottoman Syria and Palestine, c. 1770-1830
Authors: Grehan James
Published: August 2015

In the middle of the nineteenth century, a wave of anti-Christian violence broke out in Ottoman Syria. Prevailing interpretations tie this social turmoil to the region’s sudden integration into the modern world economy, further aggravated by state reforms that upset long-standing political hierarchies. This paper argues that the origins of these disturbances lay not in the penetration of the modern world economy but in the extended political crisis that shook the Ottoman Empire during the late eighteenth and early nineteenth centuries. Sectarian tensions therefore need to be seen, at their root, as political reactions to the slow disintegration of the early-modern political order. In its timing and causes, this Ottoman experience helps to highlight a broader “sectarian turn” that overtook many other parts of Eurasia in the same period.
Rethinking the Economy of Mughal India: Lateral Perspectives
Authors: Guha Sumit
Published: August 2015

This article seeks to reopen the argument regarding the economic structure of the Mughal Empire. The field saw vigorous debate in the 1980s and 1990s, followed by a stalemate. I seek to move beyond this impasse, first by studying British efforts at implementing a neo-Mughal tax system. This retrospective exhibits the practical difficulties that make it unlikely that the Mughals ever fully implemented their program. I then deploy underused Marathi sources to see what well-informed contemporaries guessed about the real working of the empire and analyze the effects of regimes of power in the creation and survival of the information that constitutes our evidence. I end by connecting key aspects of my structural analysis with the expansion of international trade and with India’s political economy in the transition to British rule.
Runaways and Fugitive-Catchers during the Third Dynasty of Ur
Authors: Reid John Nicholas
Published: August 2015

The study of flight provides insight into life at the bottom of society during the Third Dynasty of Ur (c. 2100-2000bce). Examples of individual rebellion and its consequences display the perspectives of members of non-elite and elite, advancing Adams’s conclusion (2010, §6.1) that the boundaries between slaves and other lower-stratum individuals were fluid and poorly defined. This study also references the earliest known attestation of the concept of reform through detainment.
Engendering Religious Compassion
Authors: Kuah-Pearce Khun Eng
Published: August 2015

The aim of this paper is to the study of the role of women Buddhists in the delivery of Buddhist compassion and the micro-politics of volunteerism from a feminist perspective. It sets out to ask a simple question: What attracts and motivates the Chinese women Buddhists to become actively engaged in religious volunteerism and commit their time, energies and resources into doing philanthropic works for the greater needs of their local and transnational communities. Ethnographically, I want to explore how through their understanding of the Buddhist teachings, these women Buddhists interpret and integrate their status, role and actions within their local socially-engaged Buddhist community. At the same time, to understand how, in today’s globalised world, these women focus and frame themselves as performers of emotive compassion in the local and global societies. Through this study, this paper argues that using a feminist perspective will shed light on the micro-politics of women’s involvement in Buddhist volunteerism in three areas: empowerment, social visibility and emotive philanthropy.
Tzu Chi and the Philanthropy of Filipino Volunteers
Authors: Lau Arnold Lindros , Cornelio Jayeel Serrano
Published: August 2015

This paper examines how local Filipino volunteers frame their participation and membership in the Tzu Chi Foundation, a worldwide Buddhist philanthropic organisation headquartered in Taiwan. These volunteers were recruited into Tzu Chi after receiving disaster aid in the wake of Typhoon Ketsana in 2009 in the Philippines. They participate not just in philanthropic activities, but also in Buddhist religious instruction and rituals. We suggest, however, that the volunteers, who are mostly non-Chinese, urban poor, and Catholic, frame their participation in terms of personal transformation through self-discipline and self-fulfillment. These are facets that render their philanthropic participation in Tzu Chi not so much as religious as it is aspirational. In other words, participating in Tzu Chi for local Filipino volunteers is not about religion, but rather aspiration, in contrast to earlier studies that have emphasised Buddhist awareness as crucial to members of Tzu Chi. This piece contributes to the emerging literature that documents Tzu Chi as an increasingly inclusive organisation that downplays its traditionally Chinese diasporic character.
Philanthropic Organizations and Community Development
Authors: Kalapura Jose
Published: August 2015

Philanthropic organisations are engaged in diverse welfare and development works including community development in India. A substantial number of these organisations are faith-based organisations (FBOs). While religion impacts people in many ways, religious tenets and practices have shaped, and in many cases strengthened, much of philanthropic activity. This paper focuses on the socio-economic change impacted by a philanthropic organisation called Bettiah Parish Society, successively managed by two FBOs since 1745, for the development of a Christian community, located at Bettiah, West Champaran District, in the State of Bihar, eastern India. The two FBOs were the Capuchin Mission Society (1745–1921), and the Patna Jesuit Society (1921–2000). The paper explores the influence and impact of these two external, goal-oriented FBOs on the 265-year-old Bettiah Christian community in Bihar. Aside a brief discussion on the missionary agents and their religion-induced ideologies, vision and motivations that seem to have goaded them engage in philanthropic works, the main discussion will be on the second aspect, namely the impact of their philanthropic action on the recipient community. The overall impact was (1) the construction of a Christian community (the Bettiah Christians) from among disparate convert groups, formerly belonging to different Hindu castes, and (2) changes in the socio-economic structures of the community through development aid and education. I have used an inter-disciplinary method for this study, relying much on historical, sociological and anthropological data, collected during a field study in 1998, and again in 2010.