Search results for: clinical heterogeneity

Authors: Rim Frikha, Nouha Bouayed Abdelmoula, Afifa Sellami, Salima Daoud, Tarek Rebai

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Klippel-Feil Syndrome (KFS) is characterized by congenital vertebral fusion of the cervical spine resulting from faulty segmentation along the embryo's developing axis. A wide spectrum of associated anomalies may be present. This heterogeneity has complicated elucidation of the genetic etiology and management of the syndrome. We report a case of an isolated Klippel-Feil Syndrome with C5-C6 fusion on the cervical spine. It‘s the rarest form of congenital fused cervical vertebrae which is predisposed to the risk of spinal cord injury and neurologic problems. The aim of this paper was to review clinical heterogeneity; radiographic abnormalities and genetic etiology in Klippel-Feil Syndrome. We insist in comprehensive evaluation and delineation of diagnostic and prognostic classes.

Keywords: Klippel–Feil anomaly, genetic, clinical heterogeneity, radiographic abnormalities

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Authors: Dimitrios Binas, Marianna Konidari, Charis Bourgioti, Lia Angela Moulopoulou, Theodore Economopoulos, George Matsopoulos

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High grade ovarian epithelial cancer (OEC) is fatal gynecological cancer and the poor prognosis of this entity is closely related to considerable intratumoral genetic heterogeneity. By examining imaging data, it is possible to assess the heterogeneity of tumorous tissue. This study proposes a methodology for aligning, segmenting and finally visualizing information from various magnetic resonance imaging series in order to construct 3D models of heterogeneity maps from the same tumor in OEC patients. The proposed system may be used as an adjunct digital tool by health professionals for personalized medicine, as it allows for an easy visual assessment of the heterogeneity of the examined tumor.

Keywords: image segmentation, ovarian epithelial cancer, quantitative characteristics, image registration, tumor visualization

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Authors: Majid Samavatian, Reza Gholamipour, Vahid Samavatian

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This study addresses the role of rejuvenation on the fluctuation of atomic-level stresses and nanoscale topological heterogeneity in ZrCuNiAl bulk metallic glass (BMG). Based on atomic force microscopy (AFM) results, the rejuvenation process leads to an increase in nanoscale spatial heterogeneity manifested by the intensification of the local viscoelastic response of the BMG nanostructure. It means that the rejuvenation process induces more loose-packing structures which behave towards an external load in a viscoelastic way. Hence, it is suggested that the alteration of such heterogeneity may be attributed to the variation of positional atomic rearrangement during the evolution of structural rejuvenation. On the other side, the synchrotron X-ray diffraction (XRD) results indicate that the rejuvenation intensifies the variation of internal stresses at the atomic level. This conclusion unfolds that the increase of atomic-level stresses during rejuvenation induces structural disordering and nanoscale heterogeneity in the amorphous material.

Keywords: bulk metallic glass, heterogeneity, rejuvenation, nanostructure

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Authors: Maha Salah, Hanaa Hashem, Mahmoud M. Alsagheir, Mohammed Salah

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Acute respiratory distress syndrome (ARDS) represents a complex clinical syndrome and carries a high risk for mortality. The severity of the clinical course, the uncertainty of the outcome, and the reliance on the full spectrum of critical care resources for treatment mean that the entire health care team is challenged. Researchers and clinicians have investigated the nature of the pathological process and explored treatment options with the goal of improving outcome. Through this application of research to practice, we know that some previous strategies have been ineffective, and innovations in mechanical ventilation, sedation, nutrition, and pharmacological intervention remain important research initiatives. Developed Clinical pathway is multidisciplinary plans of best clinical practice for this specified groups of patients that aid in the coordination and delivery of high quality care. They are a documented sequence of clinical interventions that help a patient to move, progressively through a clinical experience to a desired outcome. Although there is a lot of heterogeneity in patients with ARDS, this suggested developed clinical pathway with alternatives was built depended on a lot of researches and evidence based medicine and nursing practices which may be helping these patients to improve outcomes, quality of life and decrease mortality.

Keywords: acute respiratory distress syndrome (ARDS), clinical pathway, clinical syndrome

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Authors: Rui Xing, Baolin Ye, Nan Zhou, Guohong Wang

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Drawing upon a perspective of cognitive interaction, this study explores the relationship between team cognitive heterogeneity and team strategic decision-making flexibility, treating the transactive memory system as a mediator and task complexity as a moderator. The hypotheses were tested in linear regression models by using data gathered from 67 strategic decision-making teams in the new-energy vehicle industry. It is found that team cognitive heterogeneity has a positive impact on strategic decision-making flexibility through the mediation of specialization and coordination of the transactive memory system, which is positively moderated by task complexity.

Keywords: strategic decision-making flexibility, team cognitive heterogeneity, transactive memory system, task complexity

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Authors: Chansheng He, Zhongfu Wang, Xiao Bai, Jie Tian, Xin Jin

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Heterogeneity of soil hydraulic properties directly affects hydrological processes at different scales. Understanding heterogeneity of soil hydraulic properties such as soil moisture is therefore essential for modeling watershed ecohydrological processes, particularly in hard to access, topographically complex mountainous watersheds. This study maps spatial variations of soil moisture by in situ observation network that consists of sampling points, zones, and tributaries, and monitors corresponding hydrological variables of air and soil temperatures, evapotranspiration, infiltration, and runoff in the Upper Reach of the Heihe River Watershed, a second largest inland river (terminal lake) with a drainage area of over 128,000 km² in Northwest China. Subsequently, the study uses a hydrological model, SWAT (Soil and Water Assessment Tool) to simulate the effects of heterogeneity of soil moisture on watershed hydrological processes. The spatial clustering method, Full-Order-CLK was employed to derive five soil heterogeneous zones (Configuration 97, 80, 65, 40, and 20) for soil input to SWAT. Results show the simulations by the SWAT model with the spatially clustered soil hydraulic information from the field sampling data had much better representation of the soil heterogeneity and more accurate performance than the model using the average soil property values for each soil type derived from the coarse soil datasets. Thus, incorporating detailed field sampling soil heterogeneity data greatly improves performance in hydrologic modeling.

Keywords: heterogeneity, soil moisture, SWAT, up-scaling

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Authors: Umut Erksan Senalp

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The aim of this study is to examine the link between firm level productivity heterogeneity and firm’s decision to export. Thus, we test the self selection hypothesis which suggests only more productive firms self select themselves to export markets. We analyze UK manufacturing sector by using firm-level data for the period 2003-2011. Although our preliminary results suggest that exporters outperform non-exporters when we pool all manufacturing industries, when we examine each industry individually, we find that self-selection hypothesis does not hold for each industries.

Keywords: total factor productivity, firm heterogeneity, international trade, decision to export

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Authors: Xianglu Tang, Zhenxue Jiang, Zhuo Li

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Characterization of shale multi scale heterogeneity is an important part to evaluate size and space distribution of shale gas reservoirs in sedimentary basins. The origin of shale heterogeneity has always been a hot research topic for it determines shale micro characteristics description and macro quality reservoir prediction. Shale multi scale heterogeneity was discussed based on thin section observation, FIB-SEM, QEMSCAN, TOC, XRD, mercury intrusion porosimetry (MIP), and nitrogen adsorption analysis from 30 core samples in Silurian Longmaxi formation. Results show that shale heterogeneity can be characterized by pore structure and mineral composition. The heterogeneity of shale pore is showed by different size pores at nm-μm scale. Macropores (pore diameter > 50 nm) have a large percentage of pore volume than mesopores (pore diameter between 2~ 50 nm) and micropores (pore diameter < 2nm). However, they have a low specific surface area than mesopores and micropores. Fractal dimensions of the pores from nitrogen adsorption data are higher than 2.7, what are higher than 2.8 from MIP data, showing extremely complex pore structure. This complexity in pore structure is mainly due to the organic matter and clay minerals with complex pore network structures, and diagenesis makes it more complicated. The heterogeneity of shale minerals is showed by mineral grains, lamina, and different lithology at nm-km scale under the continuous changing horizon. Through analyzing the change of mineral composition at each scale, random arrangement of mineral equal proportion, seasonal climate changes, large changes of sedimentary environment, and provenance supply are considered to be the main reasons that cause shale minerals heterogeneity from microcosmic to macroscopic. Due to scale effect, the change of shale multi scale heterogeneity is a discontinuous process, and there is a transformation boundary between homogeneous and in homogeneous. Therefore, a shale multi scale heterogeneity changing model is established by defining four types of homogeneous unit at different scales, which can be used to guide the prediction of shale gas distribution from micro scale to macro scale.

Keywords: heterogeneity, homogeneous unit, multiscale, shale

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Authors: Chang Liu, Rui Xing, Liyan Tang, Guohong Wang

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Entrepreneurial actions are based on entrepreneurial decisions. The quality of decisions influences entrepreneurial activities and subsequent new venture performance. Uncertainty of surroundings put heightened demands on the team as a whole, and each team member. Diverse team composition provides rich information, which a team can draw when making complex decisions. However, team heterogeneity may cause emotional conflicts, which is adverse to team outcomes. Thus, the effects of team heterogeneity on team outcomes are complex. Although team heterogeneity is an essential factor influencing entrepreneurial decision-making, there is a lack of empirical analysis on under what conditions team heterogeneity plays a positive role in promoting decision-making quality. Entrepreneurial teams always struggle with complex tasks. How a team shapes its teamwork is key in resolving constant issues. As a collective regulatory process, team reflexivity is characterized by continuous joint evaluation and discussion of team goals, strategies, and processes, and adapt them to current or anticipated circumstances. It enables diversified information to be shared and overtly discussed. Instead of hostile interpretation of opposite opinions team members take them as useful insights from different perspectives. Team reflexivity leads to better integration of expertise to avoid the interference of negative emotions and conflict. Therefore, we propose that team reflexivity is a conditional factor that influences the impact of team heterogeneity on high-quality entrepreneurial decisions. In this study, we identify team heterogeneity as a crucial determinant of entrepreneurial decision quality. Integrating the literature on decision-making and team heterogeneity, we investigate the relationship between team heterogeneity and entrepreneurial decision-making quality, treating team reflexivity as a moderator. We tested our hypotheses using the hierarchical regression method and the data gathered from 63 teams and 205 individual members from 45 new firms in China's first-tier cities such as Beijing, Shanghai, and Shenzhen. This research found that both teams' education heterogeneity and teams' functional background heterogeneity were significantly positively related to entrepreneurial decision-making quality, and the positive relation was stronger in teams with a high level of team reflexivity. While teams' specialization of education heterogeneity was negatively related to decision-making quality, and the negative relationship was weaker in teams with a high level of team reflexivity. We offer two contributions to decision-making and entrepreneurial team literatures. Firstly, our study enriches the understanding of the role of entrepreneurial team heterogeneity in entrepreneurial decision-making quality. Different from previous entrepreneurial decision-making literatures, which focus more on decision-making modes of entrepreneurs and the top management team, this study is a significant attempt to highlight that entrepreneurial team heterogeneity makes a unique contribution to generating high-quality entrepreneurial decisions. Secondly, this study introduced team reflexivity as the moderating variable, to explore the boundary conditions under which the entrepreneurial team heterogeneity play their roles.

Keywords: decision-making quality, entrepreneurial teams, education heterogeneity, functional background heterogeneity, specialization of education heterogeneity

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Authors: Fahrudin Nugroho, Halim Hamadi, Yusril Yusuf, Pekik Nurwantoro, Ari Setiawan, Yoshiki Hidaka

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We investigate the Nikolaevskiy equation numerically using exponential time differencing method and pseudo-spectral method. This equation develops a long-wavelength modulation that behaves as a Nambu–Goldstone mode, and short-wavelength instability and exhibit turbulence. Using the autocorrelation analysis, the statistical properties of the turbulence governed by the equation are investigated. The autocorrelation then has been fitted with The Kohlrausch– Williams–Watts (KWW) expression. By varying the control parameter, we show a transition from compressed to stretched exponential for the auto-correlation function of Nikolaevskiy turbulence. The compressed exponential is an indicator of the existence of dynamical heterogeneity while the stretched indicates aging process. Thereby, we revealed the existence of dynamical heterogeneity and aging in the turbulence governed by Nikolaevskiy equation.

Keywords: compressed exponential, dynamical heterogeneity, Nikolaevskiy equation, stretched exponential, turbulence

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Authors: Chevonne Reynolds, Robert J. Fletcher, Jr, Celine M. Carneiro, Nicole Jennings, Alison Ke, Michael C. LaScaleia, Mbhekeni B. Lukhele, Mnqobi L. Mamba, Muzi D. Sibiya, James D. Austin, Cebisile N. Magagula, Themba’alilahlwa Mahlaba, Ara Monadjem, Samantha M. Wisely, Robert A. McCleery

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A key challenge for the developing world is reconciling biodiversity conservation with the growing demand for food. In these regions, agriculture is typically interspersed among other land-uses creating heterogeneous landscapes. A primary hypothesis for promoting biodiversity in agricultural landscapes is the habitat heterogeneity hypothesis. While there is evidence that landscape heterogeneity positively influences biodiversity, the application of this hypothesis is hindered by a need to determine which components of landscape heterogeneity drive these effects and at what spatial scale(s). Additionally, whether diverse taxonomic groups are similarly affected is central for determining the applicability of this hypothesis as a general conservation strategy in agricultural mosaics. Two major components of landscape heterogeneity are compositional and configurational heterogeneity. Disentangling the roles of each component is important for biodiversity conservation because each represents different mechanisms underpinning variation in biodiversity. We identified a priori independent gradients of compositional and configurational landscape heterogeneity within an extensive agricultural mosaic in north-eastern Swaziland. We then tested how bird, dung beetle, ant and meso-carnivore diversity responded to compositional and configurational heterogeneity across six different spatial scales. To determine if a general trend could be observed across multiple taxa, we also tested which component and spatial scale was most influential across all taxonomic groups combined, Compositional, not configurational, heterogeneity explained diversity in each taxonomic group, with the exception of meso-carnivores. Bird and ant diversity was positively correlated with compositional heterogeneity at fine spatial scales < 1000 m, whilst dung beetle diversity was negatively correlated to compositional heterogeneity at broader spatial scales > 1500 m. Importantly, because of these contrasting effects across taxa, there was no effect of either component of heterogeneity on the combined taxonomic diversity at any spatial scale. The contrasting responses across taxonomic groups exemplify the difficulty in implementing effective conservation strategies that meet the requirements of diverse taxa. To promote diverse communities across a range of taxa, conservation strategies must be multi-scaled and may involve different strategies at varying scales to offset the contrasting influences of compositional heterogeneity. A diversity of strategies are likely key to conserving biodiversity in agricultural mosaics, and we have demonstrated that a landscape management strategy that only manages for heterogeneity at one particular scale will likely fall short of management objectives.

Keywords: agriculture, biodiversity, composition, configuration, heterogeneity

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Authors: H. Khanfari, M. Johari Fard

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Dealing with carbonate reservoirs can be mind-boggling for the reservoir engineers due to various digenetic processes that cause a variety of properties through the reservoir. A good estimation of the reservoir heterogeneity which is defined as the quality of variation in rock properties with location in a reservoir or formation, can better help modeling the reservoir and thus can offer better understanding of the behavior of that reservoir. Most of reservoirs are heterogeneous formations whose mineralogy, organic content, natural fractures, and other properties vary from place to place. Over years, reservoir engineers have tried to establish methods to describe the heterogeneity, because heterogeneity is important in modeling the reservoir flow and in well testing. Geological methods are used to describe the variations in the rock properties because of the similarities of environments in which different beds have deposited in. To illustrate the heterogeneity of a reservoir vertically, two methods are generally used in petroleum work: Dykstra-Parsons permeability variations (V) and Lorenz coefficient (L) that are reviewed briefly in this paper. The concept of Lorenz is based on statistics and has been used in petroleum from that point of view. In this paper, we correlated the statistical-based Lorenz method to a petroleum concept, i.e. Kozeny-Carman equation and derived the straight line plot of Lorenz graph for a homogeneous system. Finally, we applied the two methods on a heterogeneous field in South Iran and discussed each, separately, with numbers and figures. As expected, these methods show great departure from homogeneity. Therefore, for future investment, the reservoir needs to be treated carefully.

Keywords: carbonate reservoirs, heterogeneity, homogeneous system, Dykstra-Parsons permeability variations (V), Lorenz coefficient (L)

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Authors: Syeda Sahra, Abdullah Jahangir, Rachelle Hamadi, Ahmad Jahangir, Allison Glaser

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Background: Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (H.A.B.P.), and ventilator-associated bacterial pneumonia (V.A.B.P.). Objective: We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. Search Strategy: We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. Selection Criteria: We included randomized clinical trials (R.C.T.s) with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. Analysis: For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A p-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. Results: The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups. Conclusion: Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, H.A.B.P., V.A.B.P.).

Keywords: bacterial pneumonia, complicated intra-abdominal infections, complicated urinary tract infection, Imipenem, cilastatin, relebactam

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Authors: Tamphasana Wairokpam

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Inflammatory myopathies (IMs) have long been recognised as a heterogenous family of myopathies with acute, subacute, and sometimes chronic presentation and are potentially treatable. Necrotizing autoimmune myopathies (NAM) are a relatively new subset of myopathies. Patients generally present with subacute onset of proximal myopathy and significantly elevated creatinine kinase (CK) levels. It is being increasingly recognised that there are limitations to the independent diagnostic utility of muscle biopsy. Immunohistochemistry tests may reveal important information in these cases. The traditional classification of IMs failed to recognise NAM as a separate entity and did not adequately emphasize the diversity of IMs. This review and case report on NAM aims to highlight the heterogeneity of this entity and focus on the distinct clinical presentation, biopsy findings, specific auto-antibodies implicated, and available treatment options with prognosis. This article is a meta-analysis of literatures on NAM and a case report illustrating the clinical course, investigation and biopsy findings, antibodies implicated, and management of a patient with NAM. The main databases used for the search were Pubmed, Google Scholar, and Cochrane Library. Altogether, 67 publications have been taken as references. Two biomarkers, anti-signal recognition protein (SRP) and anti- hydroxyl methylglutaryl-coenzyme A reductase (HMGCR) Abs, have been found to have an association with NAM in about 2/3rd of cases. Interestingly, anti-SRP associated NAM appears to be more aggressive in its clinical course when compared to its anti-HMGCR associated counterpart. Biopsy shows muscle fibre necrosis without inflammation. There are reports of statin-induced NAM where progression of myopathy has been seen even after discontinuation of statins, pointing towards an underlying immune mechanism. Diagnosisng NAM is essential as it requires more aggressive immunotherapy than other types of IMs. Most cases are refractory to corticosteroid monotherapy. Immunosuppressive therapy with other immunotherapeutic agents such as IVIg, rituximab, mycophenolate mofetil, azathioprine has been explored and found to have a role in the treatment of NAM. In conclusion,given the heterogeneity of NAM, it appears that NAM is not just a single entity but consists of many different forms, despite the similarities in presentation and its classification remains an evolving field. A thorough understanding of underlying mechanism and the clinical correlation with antibodies associated with NAM is essential for efficacious management and disease prognostication.

Keywords: inflammatory myopathies, necrotising autoimmune myopathies, anti-SRP antibody, anti-HMGCR antibody, statin induced myopathy

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Authors: Charles-Olivier Amédée-Manesme, Benoit Faye, Eric Le Fur

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In this paper, the heterogeneity of the Bordeaux Legends 50 wine market price segment is addressed. For this purpose, quantile regression is applied – with market segmentation based on wine bottle price quantile – and the hedonic price of wine attributes is computed for various price segments of the market. The approach is applied to a major privately held data set which consists of approximately 30,000 transactions over the 2003–2014 period. The findings suggest that the relative hedonic prices of several wine attributes differ significantly among deciles. In particular, the elasticity coefficient of the expert ratings shows strong variation among prices. If - as suggested in the literature - expert ratings have a positive influence on wine price on average, they have a clearly decreasing impact over the quantiles. Finally, the lower the wine price, the higher the potential for price appreciation over time. Other variables such as chateaux or vintage are also shown to vary across the distribution of wine prices. While enhancing our understanding of the complex market dynamics that underlie Bordeaux wines’ price, this research provides empirical evidence that the QR approach adequately captures heterogeneity among wine price ranges, which simultaneously applies to wine stock, vintage and auctions’ house.

Keywords: hedonics, market segmentation, quantile regression, heterogeneity, wine economics

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Authors: Qiuyue Peng, Vladimir Zachar

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The application of adipose-derived stromal/stem cells (ASCs) in regenerative medicine is gaining more awareness due to their advanced translational potential and abundant source preparations. However, ASC-based translation has been confounded by high subpopulation heterogeneity, causing ambiguity about its precise therapeutic value. Some phenotypes defined by a unique combination of positive and negative surface markers have been found beneficial to the required roles. Therefore, the immunophenotypic repertoires of cultured ASCs and temporal changes of distinct subsets were investigated in this study. ASCs from three donors undergoing cosmetic liposuction were cultured in standard culturing methods, and the co-expression patterns based on the combination of selected markers at passages 1, 4, and 8 were analyzed by multi-chromatic flow cytometry. The results showed that the level of heterogeneity of subpopulations of ASCs became lower by in vitro expansion. After a few passages, most of the CD166⁺/CD274⁺/CD271⁺ based subpopulations converged to CD166 single positive cells. Meanwhile, these CD29⁺CD201⁺ double-positive cells, in combination with CD36/Stro-1 expression or without, feathered only the major epitopes and maintained prevailing throughout the whole process. This study suggested that, upon in vitro expansion, the phenotype repertoire of ASCs redistributed and stabilized in a way that cells co-expressing exclusively the strong markers remained dominant. These preliminary findings provide a general overview of the distribution of heterogeneous subsets residents within human ASCs during expansion in vitro. It is a critical step to fully characterize ASCs before clinical application, although the biological effects of heterogeneous subpopulations still need to be clarified.

Keywords: adipose-derived stromal/stem cells, heterogeneity, immunophenotype, subpopulations

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Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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Authors: Simone Tedeschi, Francesco Crespi, Paolo Liberati, Massimo Paradiso, Antonio Sciala

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This paper aims at contributing to the understanding of smokers’ responses to cigarette prices increases with a focus on heterogeneity, both across individuals and price levels. To do this, a stated preference quasi-experimental design grounded in a random utility framework is proposed to evaluate the effect on smokers’ utility of the price level and variation, along with social conditioning and health impact perception. The analysis is based on individual-level data drawn from a unique survey gathering very detailed information on Italian smokers’ habits. In particular, qualitative information on the individual reactions triggered by changes in prices of different magnitude and composition are exploited. The main findings stemming from the analysis are the following; the average price elasticity of cigarette consumption is comparable with previous estimates for advanced economies (-.32). However, the decomposition of this result across five latent-classes of smokers, reveals extreme heterogeneity in terms of price responsiveness, implying a potential price elasticity that ranges between 0.05 to almost 1. Such heterogeneity is in part explained by observable characteristics such as age, income, gender, education as well as (current and lagged) smoking intensity. Moreover, price responsiveness is far from being independent from the size of the prospected price increase. Finally, by comparing even and uneven price variations, it is shown that uniform across-brand price increases are able to limit the scope of product substitutions and downgrade. Estimated price-response heterogeneity has significant implications for tax policy. Among them, first, it provides evidence and a rationale for why the aggregate price elasticity is likely to follow a strictly increasing pattern as a function of the experienced price variation. This information is crucial for forecasting the effect of a given tax-driven price change on tax revenue. Second, it provides some guidance on how to design excise tax reforms to balance public health and revenue goals.

Keywords: smoking behaviour, preference heterogeneity, price responsiveness, cigarette taxation, random utility models

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Authors: Yu Cheng-Yu

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‘Heterotopia’, ‘Visual Cultural Art Education’ and ‘New Media’ of these three subjects seemingly are irrelevant. In fact, there are synchronicity and intertextuality inside. In addition to visual culture, art education inspires students the ability to reflect on popular culture image through visual culture teaching strategies in school. We should get involved in the community to construct the learning environment that conveys visual culture art. This thesis attempts to probe the heterogeneity of space and value from Michel Foucault and to research sustainable development strategy in ‘New Media Art Village’ heterogeneity from Jean Baudrillard, Marshall McLuhan's media culture theory and social construction ideology. It is possible to find a new media group that can convey ‘Visual Culture Art Education’ around the National Taipei University of Technology in this commercial district that combines intelligent technology, fashion, media, entertainment, art education, and marketing network. Let the imagination and innovation of ‘New Media Art Village’ become ‘implementable’ and new media Heterotopia of inter-subjectivity with the engagement of big data and digital media. Visual culture art education will also bring aesthetics into the community by New Media Art Village.

Keywords: social construction, heterogeneity, new media, big data, visual culture art education

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Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

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Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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Authors: S. A. Naeini, A. Mahigir

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Naturally occurring cohesive soil deposits are inherently anisotropic with respect to different properties amongst which is the shear strength. The anisotropy is primary due to the process of sedimentation followed by predominantly one-dimensional consolidation. However, most soils in their natural states exhibit some anisotropy with respect to shear strength and some non-homogeneity with respect to depth. In this paper the standard Mohr-Coulomb yield criterion was modified to consider the anisotropic shear strength properties. The term non-homogeneity used in this paper refers to only the cohesion intercept which is assumed to vary linearly with depth. The effect of both anisotropy and deterministic non-homogeneity on bearing capacity of shallow foundation was investigated using finite difference method. Result of numerical analysis indicates that the cohesion anisotropy has a significant effect on bearing capacity of shallow foundation. Furthermore, the linear and bilinear heterogeneity affects the bearing capacity in a similar way although the anisotropy issue emerges to be more important as far as shallow foundations are considered.

Keywords: anisotropic ratio, finite difference analysis, bearing capacity, heterogeneity

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Authors: Lei Qin

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As shared accommodation has become one of the most important market developments in the tourism industry, numerous contributions have emerged on travelers’ motivations to choose shared accommodation. A debated question, however, resides in the heterogeneity of travelers based on motivations. This paper aims to reconcile opposing perspectives by comparing motivation segmentation at two distinct phases of innovation adoption of this new hospitality option: (i) before the first travel – potential users showing interest (n=420) and (ii) after the first travel – users (n=420). Interestingly, we find that travelers (including pre-and-post adopters) have a stronger agreement in experiential motivations than practical motivations. However, the heterogeneity of motivations among travelers is significantly higher in users, increasing from two to six clusters, which means travelers cluster into more and distinct motivation groups after adoption. Rather than invalidating specific assumptions used in the literature in terms of motivation heterogeneity, this paper reconciles opposing findings by putting them along with one another in the process of innovation adoption. A subsequent tourists’ segmentation based on motivations were conducted according to their innovation adoption stages.

Keywords: motivation, pre-and-post adoption, shared accommodation, segmentation

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Authors: Eyup Dogan

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This empirical aims to analyze the impacts of real income and biomass energy consumption on the level of emissions in the EKC model for the panel of biomass-consuming countries over the period 1980-2011. Because we detect the presence of cross-sectional dependence and heterogeneity across countries for the analyzed data, we use panel estimation methods robust to cross-sectional dependence and heterogeneity. The CADF and the CIPS panel unit root tests indicate that carbon emissions, real income and biomass energy consumption are stationary at the first-differences. The LM bootstrap panel cointegration test shows that the analyzed variables are cointegrated. Results from the panel group-mean DOLS and the panel group-mean FMOLS estimators show that increase in biomass energy consumption decreases CO2 emissions and the EKC hypothesis is validated. Therefore, countries are advised to boost their production and increase the use of biomass energy for lower level of emissions.

Keywords: biomass energy, CO2 emissions, EKC model, heterogeneity, cross-sectional dependence

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Authors: S. Mondal, L. M. Olsen-Kettle, L. Gross

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Fracture propagation and damage evolution are extremely important for many industrial applications including mining industry, composite materials, earthquake simulations, hydraulic fracturing. The influence of pre-existing flaws and rock heterogeneity on the processes and mechanisms of rock fracture has important ramifications in many mining and reservoir engineering applications. We simulate the damage evolution and fracture propagation in an isotropic sandstone specimen containing a pre-existing 3-D surface flaw in different configurations under uniaxial compression. We apply a damage model based on the unified strength theory and solve the solid deformation and damage evolution equations using the Finite Element Method (FEM) with tetrahedron elements on unstructured meshes through the simulation software, eScript. Unstructured meshes provide higher geometrical flexibility and allow a more accurate way to model the varying flaw depth, angle, and length through locally adapted FEM meshes. The heterogeneity of rock is considered by initializing material properties using a Weibull distribution sampled over a cubic grid. In our model, we introduce a length scale related to the rock heterogeneity which is independent of the mesh size. We investigate the effect of parameters including the heterogeneity of the elastic moduli and geometry of the single flaw in the stress strain response. The generation of three typical surface cracking patterns, called wing cracks, anti-wing cracks and far-field cracks were identified, and these depend on the geometry of the pre-existing surface flaw. This model results help to advance our understanding of fracture and damage growth in heterogeneous rock with the aim to develop fracture simulators for different industry applications.

Keywords: finite element method, heterogeneity, isotropic damage, uniaxial compression

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Authors: Mette Kjerholt, Thora Grothe Thomsen, Connie Bøttcher Berthelsen, Bibi Hølge Hazelton

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Academic nursing is a relatively new phenomenon in Denmark. Leadership and management training in nursing does not prepare Danish nurse leaders to become leaders for nurses with academic background, and some leaders may feel estranged with including this kind of nursing staff in clinical settings. Currently there is a debate regarding what academic nurses can contribute with in clinical practice, and some managers express concern regarding whether this will lead to less focus on clinical practice and more focus on theoretical issues that may not seem so relevant in a busy everyday clinical setting. The paper will present the experiences of integrating three advanced nurse practitioners with Ph.D. degrees (ANP) in three different clinical departments at a regional hospital in Denmark with no prior experiences with such profiles among its staff.

Keywords: leadership, advanced nurse practitioners, clinical practice, academic nursing

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Authors: Khaled M. Alhawiti

Abstract:

This paper investigates the future of medicine and the use of Natural language processing. The importance of having correct clinical information available online is remarkable; improving patient care at affordable costs could be achieved using automated applications to use the online clinical information. The major challenge towards the retrieval of such vital information is to have it appropriately coded. Majority of the online patient reports are not found to be coded and not accessible as its recorded in natural language text. The use of Natural Language processing provides a feasible solution by retrieving and organizing clinical information, available in text and transforming clinical data that is available for use. Systems used in NLP are rather complex to construct, as they entail considerable knowledge, however significant development has been made. Newly formed NLP systems have been tested and have established performance that is promising and considered as practical clinical applications.

Keywords: clinical information, information retrieval, natural language processing, automated applications

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Authors: Venkataraman Sankaranarayanan, Sougata Ray

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While extant research has examined many aspects of differential corporate environmental outcomes and behavior, a holistic and integrated view of heterogeneity in corporate environment sustainability (CES) practices remains a puzzle to be fully unraveled – its extent and nature, its relationship to macro or micro level influences, or strategic orientations. Such a perspective would be meaningful for the field given notable strides in CES practices and the corporate social responsibility agenda over the last two decades, in the backdrop of altered global socio-political sensitivities and technological advances. To partly address this gap, this exploratory research adopted a content analysis approach to code patterns in the sustainability disclosures of the 160 largest global firms spread over 8 years. The sample of firms spanned seven industries, nine countries and three continents thereby presenting data rich and diverse enough in several dimensions to be representative of global heterogeneity in CES practices. Through a factor analysis of the coded data, four strategic CES orientations were extracted through the analysis, that effectively straddles most of the variation observed in current CES practices – one that seeks to reduce environmental damage on account of the firm’s operations, another that prioritizes minimalism, a third that focuses on broader ecological status quo, and a final one that champions the ‘business of green’, extending the CES agenda beyond the firm’s boundaries. These environment sustainability strategy orientations are further examined to elicit prominent patterns and explore plausible antecedents.

Keywords: corporate social responsibility, corporate sustainability, environmental management, heterogeneity, strategic orientation

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Authors: Hamza Ikhlaq, Stephen Franks

Abstract:

Background: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. The aetiology behind PCOS is poorly understood but influencing ethnic, environmental, and genetic factors have been recognised. However, literature examining the impact of ethnicity is scarce. We hypothesised Body Mass Index (BMI) and ethnicity influence the clinical, metabolic, and biochemical presentations of PCOS, with an interaction between these factors. Methods: A database of 1081 women with PCOS and a control group of 72 women were analysed. BMIs were grouped using the World Health Organisation classification into normal weight, overweight and obese groups. Ethnicities were classified into European, South Asian, and Afro-Caribbean groups. Biochemical and clinical presentations were compared amongst these groups, and statistical analyses were performed to assess significance. Results: This study revealed ethnicity significantly influences biochemical and clinical presentations of PCOS. A greater proportion of South Asian women are impacted by menstrual cycle disturbances and hirsutism than European and Afro-Caribbean women. South Asian and Afro-Caribbean women show greater measures of insulin resistance and weight gain when compared to their European peers. Women with increased BMI are shown to have an increased prevalence of PCOS phenotypes alongside increased levels of insulin resistance and testosterone. Furthermore, significantly different relationships between the waist-hip ratio and measures of insulin and glucose control for Afro-Caribbean women were identified compared to other ethnic groups. Conclusions: The findings of this study show ethnicity significantly influence the phenotypic and biochemical presentations of PCOS, with an interaction between body habitus and ethnicity found. Furthermore, we provide further data on the influences of BMI on the manifestations of PCOS. Therefore, we highlight the need to consider these factors when reviewing diagnostic criteria and delivering clinical care for these groups.

Keywords: PCOS, ethnicity, BMI, clinical

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Authors: Cecilia Moreira, Rita Paiva, Daniela Macedo, Leonor Ribeiro, Isabel Fernandes, Luis Costa

Abstract:

Background: Head and neck paragangliomas are a rare group of tumors with a large spectrum of clinical manifestations. The approach to evaluate and treat these lesions has evolved over the last years. Surgery was the standard for the approach of these patients, but nowadays new techniques of imaging and radiation therapy changed that paradigm. Despite advances in treating, the growth potential and clinical outcome of individual cases remain largely unpredictable. Objectives: Characterization of our institutional experience with clinical management of these tumors. Methods: This was a cross-sectional study of patients followed in our institution between 01 January and 31 December 2017 with paragangliomas of the head and neck and cranial base. Data on tumor location, catecholamine levels, and specific imaging modalities employed in diagnostic workup, treatment modality, tumor control and recurrence, complications of treatment and hereditary status were collected and summarized. Results: A total of four female patients were followed between 01 January and 31 December 2017 in our institution. The mean age of our cohort was 53 (± 16.1) years. The primary locations were at the level of the tympanic jug (n=2, 50%) and carotid body (n=2, 50%), and only one of the tumors of the carotid body presented pulmonary metastasis at the time of diagnosis. None of the lesions were catecholamine-secreting. Two patients underwent genetic testing, with no mutations identified. The initial clinical presentation was variable highlighting the decrease of visual acuity and headache as symptoms present in all patients. In one of the cases, loss of all teeth of the lower jaw was the presenting symptomatology. Observation with serial imaging, surgical extirpation, radiation, and stereotactic radiosurgery were employed as treatment approaches according to anatomical location and resectability of lesions. As post-therapeutic sequels the persistence of tinnitus and disabling pain stands out, presenting one of the patients neuralgia of the glossopharyngeal. Currently, all patients are under regular surveillance with a median follow up of 10 months. Conclusion: Ultimately, clinical management of these tumors remains challenging owing to heterogeneity in clinical presentation, the existence of multiple treatment alternatives, and potential to cause serious detriment to critical functions and consequently interference with the quality of life of the patients.

Keywords: clinical outcomes, head and neck, management, paragangliomas

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Authors: Yue Huang, Hongcheng Gan

Abstract:

The new urbanization pattern has led to a rapid growth in demand for short-distance intercity travel, and the emergence of new travel modes has also increased the variety of intercity travel options. In previous studies on intercity travel mode choice behavior, the impact of functional amenities of travel mode and travelers’ long-term personality characteristics has rarely been considered, and empirical results have typically been calibrated using revealed preference (RP) or stated preference (SP) data. This study designed a questionnaire that combines the RP and SP experiment from the perspective of a trip chain combining inner-city and intercity mobility, with consideration for the actual condition of the Huainan-Hefei traffic corridor. On the basis of RP/SP fusion data, a hybrid choice model considering both random taste heterogeneity and psychological characteristics was established to investigate travelers’ mode choice behavior for traditional train, high-speed rail, intercity bus, private car, and intercity online car-hailing. The findings show that intercity time and cost exert the greatest influence on mode choice, with significant heterogeneity across the population. Although inner-city cost does not demonstrate a significant influence, inner-city time plays an important role. Service attributes of travel mode, such as catering and hygiene services, as well as free wireless network supply, only play a minor role in mode selection. Finally, our study demonstrates that safety-seeking tendency, hedonism, and introversion all have differential and significant effects on intercity travel mode choice.

Keywords: intercity travel mode choice, stated preference survey, hybrid choice model, RP/SP fusion data, psychological latent variable, heterogeneity

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