221 research outputs found
Optimal Cerebral Perfusion Pressure During Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage
OBJECTIVES: The recommendation of induced hypertension for delayed cerebral ischemia treatment after aneurysmal subarachnoid hemorrhage has been challenged recently and ideal pressure targets are missing. A new concept advocates an individual cerebral perfusion pressure where cerebral autoregulation functions best to ensure optimal global perfusion. We characterized optimal cerebral perfusion pressure at time of delayed cerebral ischemia and tested the conformity of induced hypertension with this target value. DESIGN: Retrospective analysis of prospectively collected data. SETTING: University hospital neurocritical care unit. PATIENTS: Thirty-nine aneurysmal subarachnoid hemorrhage patients with invasive neuromonitoring (20 with delayed cerebral ischemia, 19 without delayed cerebral ischemia). INTERVENTIONS: Induced hypertension greater than 180 mm Hg systolic blood pressure. MEASUREMENTS AND MAIN RESULTS: Changepoint analysis was used to calculate significant changes in cerebral perfusion pressure, optimal cerebral perfusion pressure, and the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure 48 hours before delayed cerebral ischemia diagnosis. Optimal cerebral perfusion pressure increased 30 hours before the onset of delayed cerebral ischemia from 82.8 +/- 12.5 to 86.3 +/- 11.4 mm Hg (p < 0.05). Three hours before delayed cerebral ischemia, a changepoint was also found in the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure (decrease from -0.2 +/- 11.2 to -7.7 +/- 7.6 mm Hg; p < 0.05) with a corresponding increase in pressure reactivity index (0.09 +/- 0.33 to 0.19 +/- 0.37; p < 0.05). Cerebral perfusion pressure at time of delayed cerebral ischemia was lower than in patients without delayed cerebral ischemia in a comparable time frame (cerebral perfusion pressure delayed cerebral ischemia 81.4 +/- 8.3 mm Hg, no delayed cerebral ischemia 90.4 +/- 10.5 mm Hg; p < 0.05). Inducing hypertension resulted in a cerebral perfusion pressure above optimal cerebral perfusion pressure (+12.4 +/- 8.3 mm Hg; p < 0.0001). Treatment response (improvement of delayed cerebral ischemia: induced hypertension(+) [n = 15] or progression of delayed cerebral ischemia: induced hypertension(-) [n = 5]) did not correlate to either absolute values of cerebral perfusion pressure or optimal cerebral perfusion pressure, nor the resulting difference (cerebral perfusion pressure [p = 0.69]; optimal cerebral perfusion pressure [p = 0.97]; and the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure [p = 0.51]). CONCLUSIONS: At the time of delayed cerebral ischemia occurrence, there is a significant discrepancy between cerebral perfusion pressure and optimal cerebral perfusion pressure with worsening of autoregulation, implying inadequate but identifiable individual perfusion. Standardized induction of hypertension resulted in cerebral perfusion pressures that exceeded individual optimal cerebral perfusion pressure in delayed cerebral ischemia patients. The potential benefit of individual blood pressure management guided by autoregulation-based optimal cerebral perfusion pressure should be explored in future intervention studies
Optimal cerebral perfusion pressure for DCI after aneurysmal subarachnoid hemorrhage - a prospective observational study in the context of induced hypertension
Optimal cerebral perfusion pressure for DCI after aneurysmal subarachnoid hemorrhage - a prospective observational study in the context of induced hypertension
Identifying Trends in Masterplanning: A Typological Classification System
This document is the Accepted Manuscript version of the following article: Robert Adam, and Claire Jamieson, ‘Identifying trends in masterplanning: A typological classification system’, URBAN DESIGN International, Vol. 19 (4): 274-290, December 2014. The final publication is available at Springer via https://doi.org/10.1057/udi.2013.24.This article reports research carried out to develop a new typological method for the analysis of masterplans. This quantitative method of analysis can be used to produce comparative data that will help in the comparison of urban design typologies and their development over time. This article sets out the research to date, describing how the initial aims have developed from simple analysis to the creation of an analytical tool with wide applications. Comprising a detailed taxonomy of urban design features gathered from a wide database of recent and emerging masterplans, the system provides opportunities for further study such as trends, qualitative comparison against quantitative measurement, and comparison of aims and outcomes. This article will describe the methodology and process of research, while elaborating on the potential of the tool.Peer reviewedFinal Accepted Versio
Towards analytical typologies of plot systems: quantitative profile of five European cities
The importance of the plot (also referred to as ‘property’) as one of the fundamental elements of urban form is well recognized within the field of urban morphology. Despite the fact that it is often described as the basic element in the pattern of land divisions, which are essential as organizational frameworks for urban form, studies offering comprehensive descriptions and classifications of plot systems are quite scant. The aim of the paper is to introduce a classification of plot systems into typologies based on five European cities, in order to distinguish particular spatial differences and similarities in terms of their plot structure. The proposed typologies are developed using unsupervised k-means cluster analysis based on numeric attributes derived from central theories in urban morphology. The introduced typologies are essentially configurational, allowing collective systematic properties of plot systems to be captured. Numeric attributes include plot differentiation (or plot size), plot frontage and compactness ratio, corresponding to essential qualities of plot systems such as the capacity to carry differences in space, the ability to operate as interface between street and building and providing a framework for evolution of built form over time. All three attributes are translated into configurational measures in order to capture the context of the plot system, rather than the parameters of individual plots. The combination of these deductively defined variables with algorithmically defined classification methods results in seven plot types that can be used to scale up traditional urban morphological analysis to whole city regions and conduct substantial comparison of patterns within, but also between these regions. Further, it also makes it possible to describe commonly recognized plot patterns and discover new ones
2-Aminophenoxazine-3-one and 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one cause cellular apoptosis by reducing higher intracellular pH in cancer cells
We examined intracellular pH (pHi) of ten cancer cell lines derived from different organs and two normal cell lines including human embryonic lung fibroblast cells (HEL) and human umbilical vein endothelial cells (HUVEC) in vitro, and found that pHi of most of these cancer cells was evidently higher (pH 7.5 to 7.7) than that of normal cells (7.32 and 7.44 for HEL and HUVEC, respectively) and that of primary leukemic cells and erythrocytes hitherto reported (≤7.2). Higher pHi in these cancer cells could be related to the Warburg effect in cancer cells with enhanced glycolytic metabolism. Since reversal of the Warburg effect may perturb intracellular homeostasis in cancer cells, we looked for compounds that cause extensive reduction of pHi, a major regulator of the glycolytic pathway and its associated metabolic pathway. We found that phenoxazine compounds, 2-aminophenoxazine-3-one (Phx-3) and 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one (Phx-1) caused a rapid and drastic dose-dependent decrease of pHi in ten different cancer cells within 30 min, though the extent of the decrease of pHi was significantly larger for Phx-3 (ΔpHi = 0.6 pH units or more for 100 µM Phx-3) than for Phx-1 (ΔpHi = 0.1 pH units or more for 100 µM Phx-1). This rapid and drastic decrease of pHi in a variety of cancer cells caused by Phx-3 and Phx-1 possibly perturbed their intracellular homeostasis, and extensively affected the subsequent cell death, because these phenoxazines exerted dose-dependent proapoptotic and cytotoxic effects on these cells during 72 h incubation, confirming a causal relationship between ΔpHi and cytotoxic effects due to Phx-3 and Phx-1. Phx-3 and Phx-1 also reduced pHi of normal cells including HEL and HUVEC, although they exerted less proapoptotic and cytotoxic effects on these cells than on cancer cells. Drugs such as Phx-3 and Phx-1 that reduce pHi and thereby induce cellular apoptosis might serve as benevolent anticancer drugs
The recent intellectual structure of geography
An active learning project in an introductory graduate course used multidimensional scaling of the name index in Geography in America at the Dawn of the 21st Century, by Gary Gaile and Cort Willmott, to reveal some features of the discipline\u27s recent intellectual structure relevant to the relationship between human and physical geography. Previous analyses, dating to the 1980s, used citation indices or Association of American Geographers spe- cialty-group rosters to conclude that either the regional or the methods and environmental subdisciplines bridge human and physical geography. The name index has advantages over those databases, and its analysis reveals that the minimal connectivity that occurs between human and physical geography has recently operated more through environmental than through either methods or regional subdisciplines
Describing the residential valorisation of urban space at the street level. The French Riviera as example
There is a growing concern regarding the use of relatively coarse units for the aggregation of various spatial information. Researchers thus suggest that the street segment might be better suited than areal units for carrying out such a task. Furthermore, the street segment has recently become one of the most prominent spatial units, for example, to study street network centrality, retail density, and urban form. In this paper, we thus propose to use the street segment as unit of analysis for calculating the residential valorisation of urban space. To be more specific, we define a protocol that characterises street segments through a measure of central tendency and one of dispersion of prices. Moreover, through Bayesian clustering, it classifies street segments according to the most probable combination house type-valuation to provide a picture of local submarkets. We apply this methodology to the housing transactions exchanged in the French Riviera, in the period 2008–2017, and observe that outputs seem to align with local specificities of the housing market of that region. We suggest that the proposed protocol can be useful as an explorative tool to question and interpret the housing market, in any metropolitan region, at a fine level of spatial granularity
Quantitative MRI radiomics in the prediction of molecular classifications of breast cancer subtypes in the TCGA/TCIA data set
Using quantitative radiomics, we demonstrate that computer-extracted magnetic resonance (MR) image-based tumor phenotypes can be predictive of the molecular classification of invasive breast cancers. Radiomics analysis was performed on 91 MRIs of biopsy-proven invasive breast cancers from National Cancer Institute’s multi-institutional TCGA/TCIA. Immunohistochemistry molecular classification was performed including estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and for 84 cases, the molecular subtype (normal-like, luminal A, luminal B, HER2-enriched, and basal-like). Computerized quantitative image analysis included: three-dimensional lesion segmentation, phenotype extraction, and leave-one-case-out cross validation involving stepwise feature selection and linear discriminant analysis. The performance of the classifier model for molecular subtyping was evaluated using receiver operating characteristic analysis. The computer-extracted tumor phenotypes were able to distinguish between molecular prognostic indicators; area under the ROC curve values of 0.89, 0.69, 0.65, and 0.67 in the tasks of distinguishing between ER+ versus ER−, PR+ versus PR−, HER2+ versus HER2−, and triple-negative versus others, respectively. Statistically significant associations between tumor phenotypes and receptor status were observed. More aggressive cancers are likely to be larger in size with more heterogeneity in their contrast enhancement. Even after controlling for tumor size, a statistically significant trend was observed within each size group (P = 0.04 for lesions ≤ 2 cm; P = 0.02 for lesions >2 to≤ 5 cm) as with the entire data set (P-value = 0.006) for the relationship between enhancement texture (entropy) and molecular subtypes (normal-like, luminal A, luminal B, HER2-enriched, basal-like). In conclusion, computer-extracted image phenotypes show promise for high-throughput discrimination of breast cancer subtypes and may yield a quantitative predictive signature for advancing precision medicine
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