512 resultados para UNIFYING HYPOTHESIS
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What is ‘transmedia’? This chapter attempts to understand what this phenomenon is from a transhistorical perspective. The transhistorical nature of media combinations is interrogated in light of media specificity and in relation to the key phenomena of Intermedia. Transmedia is argued to be a transhistorical urge towards unifying that which has been artificially estranged.
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We develop a hybrid cellular automata model to describe the effect of the immune system and chemokines on a growing tumor. The hybrid cellular automata model consists of partial differential equations to model chemokine concentrations, and discrete cellular automata to model cell–cell interactions and changes. The computational implementation overlays these two components on the same spatial region. We present representative simulations of the model and show that increasing the number of immature dendritic cells (DCs) in the domain causes a decrease in the number of tumor cells. This result strongly supports the hypothesis that DCs can be used as a cancer treatment. Furthermore, we also use the hybrid cellular automata model to investigate the growth of a tumor in a number of computational “cancer patients.” Using these virtual patients, the model can explain that increasing the number of DCs in the domain causes longer “survival.” Not surprisingly, the model also reflects the fact that the parameter related to tumor division rate plays an important role in tumor metastasis.
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This paper introduces the smooth transition logit (STL) model that is designed to detect and model situations in which there is structural change in the behaviour underlying the latent index from which the binary dependent variable is constructed. The maximum likelihood estimators of the parameters of the model are derived along with their asymptotic properties, together with a Lagrange multiplier test of the null hypothesis of linearity in the underlying latent index. The development of the STL model is motivated by the desire to assess the impact of deregulation in the Queensland electricity market and ascertain whether increased competition has resulted in significant changes in the behaviour of the spot price of electricity, specifically with respect to the occurrence of periodic abnormally high prices. The model allows the timing of any change to be endogenously determined and also market participants' behaviour to change gradually over time. The main results provide clear evidence in support of a structural change in the nature of price events, and the endogenously determined timing of the change is consistent with the process of deregulation in Queensland.
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Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= −0.0452, p=0.024) as well as COPD (β= −0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10−7), FVC (p=2.07×10−5), and FEV1/FVC (p=5.27×10−3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.
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Despite much scholarly fascination with the question of whether great minds appear in cycles, together with some empirical evidence that historical cycles exist, prior studies mostly disregard the ‘‘great minds’’ hypothesis as it relates to scientists. Rather, researchers assume a linear relation based on the argument that science is allied with the development of technology. To probe this issue further, this study uses a ranking of over 5600 scientists based on number of appearances in Google Books over a period of 200 years (1800–2000). The results point to several peak periods, particularly for scientists born in the 1850–1859, 1897–1906, or 1900–1909 periods, suggesting overall cycles of around 8 years and a positive trend in distinction that lasts around 100 years. Nevertheless,a non-parametric test to determine whether randomness can be rejected indicates that nonrandomness is less apparent, although once we analyse the greatest minds overall, rejection is more likely.
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Increased concentrations of biomarkers reflecting myocardial stress such as cardiac troponin I and T and brain natriuretic peptide (BNP) have been observed following strenuous, long-lasting endurance exercise. The pathophysiological mechanisms are still not fully elucidated and the interpretations of increased post-exercise concentrations range from (i) evidence for exercise-induced myocardial damage to (ii) non-relevant spurious troponin elevations, presumably caused by assay imprecision or heterophilic antibodies. Several lines of evidence suggest that inflammatory processes or oxidative stress could be involved in the rise of NT-proBNP and Troponin observed in critically ill patients with sepsis or burn injury. We tested the hypothesis that inflammatory or oxidative stress is also responsible for exercise-induced cardiomyocyte strain in a large cohort of triathletes following an Ironman triathlon. However, the post-race increase in cardiac troponin T and NT-proBNP was not associated with several markers of exercise-induced inflammation, oxidative stress or antioxidant vitamins. Therefore, we clearly need more studies with other inflammatory markers and different designs to elucidate the scientific background for increases in myocardial stress markers following strenuous endurance events.
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Five significant problems hinder advances in understanding of the volcanology of kimberlites: (1) kimberlite geology is very model driven; (2) a highly genetic terminology drives deposit or facies interpretation; (3) the effects of alteration on preserved depositional textures have been grossly underestimated; (4) the level of understanding of the physical process significance of preserved textures is limited; and, (5) some inferred processes and deposits are not based on actual, modern volcanological processes. These issues need to be addressed in order to advance understanding of kimberlite volcanological pipe forming processes and deposits. The traditional, steep-sided southern African pipe model (Class I) consists of a steep tapering pipe with a deep root zone, a middle diatreme zone and an upper crater zone (if preserved). Each zone is thought to be dominated by distinctive facies, respectively: hypabyssal kimberlite (HK, descriptively called here massive coherent porphyritic kimberlite), tuffisitic kimberlite breccia (TKB, descriptively here called massive, poorly sorted lapilli tuff) and crater zone facies, which include variably bedded pyroclastic kimberlite and resedimented and reworked volcaniclastic kimberlite (RVK). Porphyritic coherent kimberlite may, however, also be emplaced at different levels in the pipe, as later stage intrusions, as well as dykes in the surrounding country rock. The relationship between HK and TKB is not always clear. Sub-terranean fluidisation as an emplacement process is a largely unsubstantiated hypothesis; modern in-vent volcanological processes should initially be considered to explain observed deposits. Crater zone volcaniclastic deposits can occur within the diatreme zone of some pipes, indicating that the pipe was largely empty at the end of the eruption, and subsequently began to fill-in largely through resedimentation and sourcing of pyroclastic deposits from nearby vents. Classes II and III Canadian kimberlite models have a more factual, descriptive basis, but are still inadequately documented given the recency of their discovery. The diversity amongst kimberlite bodies suggests that a three-model classification is an over-simplification. Every kimberlite is altered to varying degrees, which is an intrinsic consequence of the ultrabasic composition of kimberlite and the in-vent context; few preserve original textures. The effects of syn- to post-emplacement alteration on original textures have not been adequately considered to date, and should be back-stripped to identify original textural elements and configurations. Applying sedimentological textural configurations as a guide to emplacement processes would be useful. The traditional terminology has many connotations about spatial position in pipe and of process. Perhaps the traditional terminology can be retained in the industrial situation as a general lithofacies-mining terminological scheme because it is so entrenched. However, for research purposes a more descriptive lithofacies terminology should be adopted to facilitate detailed understanding of deposit characteristics, important variations in these, and the process origins. For example every deposit of TKB is different in componentry, texture, or depositional structure. However, because so many deposits in many different pipes are called TKB, there is an implication that they are all similar and that similar processes were involved, which is far from clear.
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Introduction & Aims Optimising fracture treatments requires a sound understanding of relationships between stability, callus development and healing outcomes. This has been the goal of computational modelling, but discrepancies remain between simulations and experimental results. We compared healing patterns vs fixation stiffness between a novel computational callus growth model and corresponding experimental data. Hypothesis We hypothesised that callus growth is stimulated by diffusible signals, whose production is in turn regulated by mechanical conditions at the fracture site. We proposed that introducing this scheme into computational models would better replicate the observed tissue patterns and the inverse relationship between callus size and fixation stiffness. Method Finite element models of bone healing under stiff and flexible fixation were constructed, based on the parameters of a parallel rat femoral osteotomy study. An iterative procedure was implemented, to simulate the development of callus and its mechanical regulation. Tissue changes were regulated according to published mechano-biological criteria. Predictions of healing patterns were compared between standard models, with a pre-defined domain for callus development, and a novel approach, in which periosteal callus growth is driven by a diffusible signal. Production of this signal was driven by local mechanical conditions. Finally, each model’s predictions were compared to the corresponding histological data. Results Models in which healing progressed within a prescribed callus domain predicted that greater interfragmentary movements would displace early periosteal bone formation further from the fracture. This results from artificially large distortional strains predicted near the fracture edge. While experiments showed increased hard callus size under flexible fixation, this was not reflected in the standard models. Allowing the callus to grow from a thin soft tissue layer, in response to a mechanically stimulated diffusible signal, results in a callus shape and tissue distribution closer to those observed histologically. Importantly, the callus volume increased with increasing interfragmentary movement. Conclusions A novel method to incorporate callus growth into computational models of fracture healing allowed us to successfully capture the relationship between callus size and fixation stability observed in our rat experiments. This approach expands our toolkit for understanding the influence of different fixation strategies on healing outcomes.
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This research identifies the commuting mode choice behaviour of 3537 adults living in different types of transit oriented development (TOD) in Brisbane by disentangling the effects of their “evil twin” transit adjacent developments (TADs), and by also controlling for residential self-selection, travel attitudes and preferences, and socio-demographic effects. A TwoStep cluster analysis was conducted to identify the natural groupings of respondents’ living environment based on six built environment indicators. The analysis resulted in five types of neighbourhoods: urban TODs, activity centre TODs, potential TODs, TADs, and traditional suburbs. HABITAT survey data were used to derive the commute mode choice behaviour of people living in these neighbourhoods. In addition, statements reflecting both respondents’ travel attitudes and living preferences were also collected as part of the survey. Factor analyses were conducted based on these statements and these derived factors were then used to control for residential self-selection. Four binary logistic regression models were estimated, one for each of the travel modes used (e.g. public transport, active transport, less sustainable transport such as the car/taxi, and other), to differentiate between the commuting behaviour of people living in the five types of neighbourhoods. The findings verify that urban TODs enhance the use of public transport and reduce car usage. No significant difference was found in the commuting behaviour between respondents living in traditional suburbs and TADs. The results confirm the hypothesis that TADs are the “evil twin” of TODs. The data indicates that TADs and the mode choices of residents in these neighbourhoods is a missed transport policy opportunity. Further policy efforts are required for a successive transition of TADs into TODs in order to realise the full benefits of these. TOD policy should also be integrated with context specific TOD design principles.
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In estuaries and natural water channels, the estimate of velocity and dispersion coefficients is critical to the knowledge of scalar transport and mixing. This estimate is rarely available experimentally at sub-tidal time scale in shallow water channels where high frequency is required to capture its spatio-temporal variation. This study estimates Lagrangian integral scales and autocorrelation curves, which are key parameters for obtaining velocity fluctuations and dispersion coefficients, and their spatio-temporal variability from deployments of Lagrangian drifters sampled at 10 Hz for a 4-hour period. The power spectral densities of the velocities between 0.0001 and 0.8 Hz were well fitted with a slope of 5/3 predicted by Kolmogorov’s similarity hypothesis within the inertial subrange, and were similar to the Eulerian power spectral previously observed within the estuary. The result showed that large velocity fluctuations determine the magnitude of the integral time scale, TL. Overlapping of short segments improved the stability of the estimate of TL by taking advantage of the redundant data included in the autocorrelation function. The integral time scales were about 20 s and varied by up to a factor of 8. These results are essential inputs for spatial binning of velocities, Lagrangian stochastic modelling and single particle analysis of the tidal estuary.
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Background An important potential clinical benefit of using capnography monitoring during procedural sedation and analgesia (PSA) is that this technology could improve patient safety by reducing serious sedation-related adverse events, such as death or permanent neurological disability, which are caused by inadequate oxygenation. The hypothesis is that earlier identification of respiratory depression using capnography leads to a change in clinical management that prevents hypoxaemia. As inadequate oxygenation/ventilation is the most common reason for injury associated with PSA, reducing episodes of hypoxaemia would indicate that using capnography would be safer than relying on standard monitoring alone. Methods/design The primary objective of this review is to determine whether using capnography during PSA in the hospital setting improves patient safety by reducing the risk of hypoxaemia (defined as an arterial partial pressure of oxygen below 60 mmHg or percentage of haemoglobin that is saturated with oxygen [SpO2] less than 90 %). A secondary objective of this review is to determine whether changes in the clinical management of sedated patients are the mediating factor for any observed impact of capnography monitoring on the rate of hypoxaemia. The potential adverse effect of capnography monitoring that will be examined in this review is the rate of inadequate sedation. Electronic databases will be searched for parallel, crossover and cluster randomised controlled trials comparing the use of capnography with standard monitoring alone during PSA that is administered in the hospital setting. Studies that included patients who received general or regional anaesthesia will be excluded from the review. Non-randomised studies will be excluded. Screening, study selection and data extraction will be performed by two reviewers. The Cochrane risk of bias tool will be used to assign a judgment about the degree of risk. Meta-analyses will be performed if suitable. Discussion This review will synthesise the evidence on an important potential clinical benefit of capnography monitoring during PSA within hospital settings. Systematic review registration: PROSPERO CRD42015023740
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Modern non-invasive brain imaging technologies, such as diffusion weighted magnetic resonance imaging (DWI), enable the mapping of neural fiber tracts in the white matter, providing a basis to reconstruct a detailed map of brain structural connectivity networks. Brain connectivity networks differ from random networks in their topology, which can be measured using small worldness, modularity, and high-degree nodes (hubs). Still, little is known about how individual differences in structural brain network properties relate to age, sex, or genetic differences. Recently, some groups have reported brain network biomarkers that enable differentiation among individuals, pairs of individuals, and groups of individuals. In addition to studying new topological features, here we provide a unifying general method to investigate topological brain networks and connectivity differences between individuals, pairs of individuals, and groups of individuals at several levels of the data hierarchy, while appropriately controlling false discovery rate (FDR) errors. We apply our new method to a large dataset of high quality brain connectivity networks obtained from High Angular Resolution Diffusion Imaging (HARDI) tractography in 303 young adult twins, siblings, and unrelated people. Our proposed approach can accurately classify brain connectivity networks based on sex (93% accuracy) and kinship (88.5% accuracy). We find statistically significant differences associated with sex and kinship both in the brain connectivity networks and in derived topological metrics, such as the clustering coefficient and the communicability matrix.
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The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA-DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18-85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/).
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The study examines the property value impacts of an announcement of a project which has potential environmental impacts as distinct from other studies that address costs associated with under-construction and the operating impacts of developments. The hypothesis is that the announcement of a proposed project with potential environmental impact creates uncertainty in the property market of the affected area, and this impact is greater on properties closer to the project than those farther from it. The results of the study confirm the hypothesis and indicate that the marginal willingness to pay for properties within a 5 km distance declined by AU$17,020 per km proximity to the proposed heavy vehicle route, after the proposed route was announced. The results support the need for more holistic measurement of cost–benefit analysis of projects and provide a basis for improved consideration by policy makers of the rights of affected parties.
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A phylogenetic hypothesis for the lepidopteran superfamily Noctuoidea was inferred based on the complete mitochondrial (mt) genomes of 12 species (six newly sequenced). The monophyly of each noctuoid family in the latest classification was well supported. Novel and robust relationships were recovered at the family level, in contrast to previous analyses using nuclear genes. Erebidae was recovered as sister to (Nolidae+(Euteliidae+Noctuidae)), while Notodontidae was sister to all these taxa (the putatively basalmost lineage Oenosandridae was not included). In order to improve phylogenetic resolution using mt genomes, various analytical approaches were tested: Bayesian inference (BI) vs. maximum likelihood (ML), excluding vs. including RNA genes (rRNA or tRNA), and Gblocks treatment. The evolutionary signal within mt genomes had low sensitivity to analytical changes. Inference methods had the most significant influence. Inclusion of tRNAs positively increased the congruence of topologies, while inclusion of rRNAs resulted in a range of phylogenetic relationships varying depending on other analytical factors. The two Gblocks parameter settings had opposite effects on nodal support between the two inference methods. The relaxed parameter (GBRA) resulted in higher support values in BI analyses, while the strict parameter (GBDH) resulted in higher support values in ML analyses.