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Results for “Spatial heterogeneity”

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PubMed2000

Fractal analysis of nuclear medicine images for the diagnosis of pulmonary emphysema: interpretations, implications, and limitations.

OBJECTIVE: The purpose of this study was to investigate, on images obtained in nuclear medicine examinations, the physical meanings and consequent implications of fractal analysis developed in a recent study that was reported to be effective in quantifying the heterogeneous distribution of carbon particle radioaerosol in the lungs. MATERIALS AND METHODS: Fractal dimensions were computed for 108 sets of radionuclide imaging data from 28 patients according to the methods in a previous report, and were then correlated with the ratio of tissue areas segmented at two thresholds (15% and 35% of maximal radioactivity). RESULTS: Fractal dimension was found to linearly correlate with the ratio natural logarithm of tissue areas segmented at two different threshold levels (n = 108, r = 0.999), with regression slope accurately predicted (error = 0.06%). Bland-Altman analysis showed that fractal dimensions ranging from 0.2 to 1.9 can be explained by this area ratio with disagreement of only 5.13% at two standard deviations; thus, fractal dimension seems to be an over-simplified parameter unrelated to spatial heterogeneity of radioaerosol distribution. CONCLUSION: The analysis of this study suggested that the fractal dimension defined in a previous report was limited to the indication of the percentage area of low-radioactivity regions with respect to total tissue area in the image. Because the fractal dimension partially reflects, but is not specific to, a certain degree of focal spots of low radioactivity, we suggest using fractal analysis in clinical practice only with careful control and thorough understanding of the physical meanings.

Fractals↗

PubMed1988

Mechanisms of heterogeneous distribution of monoclonal antibodies and other macromolecules in tumors: significance of elevated interstitial pressure.

The therapeutic efficacy of monoclonal antibodies (MAbs), bound to radionuclides, chemotherapeutic agents, toxins, growth factors, or effector antibodies, depends upon their ability to reach their target in vivo in adequate quantities. Despite the high vascular permeability and interstitial transport coefficients in tumor tissue compared to several normal tissues, MAbs and their fragments do not distribute homogeneously in a tumor. Heterogeneity of tumor-associated antigen expression alone cannot explain this maldistribution of MAbs in tumors. We propose that in addition to the heterogeneous blood perfusion, hindered diffusion in the interstitium, and extravascular binding of MAbs, elevated interstitial pressure is responsible for the poor penetration of MAbs into tumors. Elevated interstitial pressure principally reduces the driving force for extravasation of fluid and macromolecules in tumors, and also leads to an experimentally verifiable, radially outward convection which opposes the inward diffusion. We present here mathematical models for transport of fluid and macromolecules in a tumor. To illustrate the significance of elevated interstitial pressure, these models are used to describe the interstitial pressure, interstitial fluid velocity, and concentration of nonbinding macromolecules as a function of radial position in a uniformly perfused tumor. The key result of these models is that the filtration of fluid from blood vessels in a uniformly perfused tumor is (a) spatially heterogeneous, (b) a result of elevated interstitial pressure, and (c) sufficient to explain the heterogeneous distribution of macromolecules in tumors. Nonuniform blood flow, and extravascular binding would enhance this heterogeneity in the solute distribution considerably. The results of the models also agree with the following experimental data: (a) tumor interstitial pressure is low in the periphery and it increases toward the center of the tumor; (b) the radially outward fluid velocity at the tumor periphery predicted by the model is of the same order of magnitude as measured in tissue-isolated tumors; and (c) immediately after bolus injection, the concentration of macromolecules is higher in the periphery than in the center; however, at later time periods the peripheral concentration is lower than in the center. These results have significant implications not only for MAbs and their fragments, but for other biologically useful macromolecules (e.g., cytokines) produced by genetic engineering for cancer diagnosis and treatment.

Antibodies, Monoclonal↗

PubMed1997

Beat-to-beat QT interval variability: novel evidence for repolarization lability in ischemic and nonischemic dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is associated with a high incidence of malignant ventricular arrhythmias and sudden death. Abnormalities in repolarization of ventricular myocardium have been implicated in the development of these arrhythmias. Spatial heterogeneity in repolarization has been studied in DCM, but temporal fluctuations in repolarization in this setting have been largely ignored. We sought to test the hypothesis that beat-to-beat QT interval variability is increased in DCM patients compared with control subjects. METHODS AND RESULTS: Eighty-three patients with ischemic and nonischemic DCM and 60 control subjects served as the study population. Beat-to-beat QT interval variability was measured by automated analysis on the basis of 256-second records of the surface ECG. A QT variability index (QTVI) was calculated for each subject as the logarithm of the ratio of normalized QT variance to heart rate variance. The coherence between heart rate and QT interval fluctuations was determined by spectral analysis. In patients, ejection fractions were assessed by echocardiography or ventriculography, and spatial QT dispersion was determined from the standard 12-lead ECG. DCM patients had greater QT variance than control subjects (60.4+/-63.1 versus 25.7+/-24.8 ms2, P<.0001) despite reduced heart rate variance (6.7+/-7.8 versus 10.5+/-10.4 bpm2, P=.01). The QTVI was higher in DCM patients than in control subjects, with a high degree of significance (-0.43+/-0.71 versus -1.29+/-0.51, P<10[-12]). QTVI did not correlate with ejection fraction or spatial QT dispersion but did depend on New York Heart Association functional class. QTVI did not differ between DCM patients with ischemic and those with nonischemic origin. Coherence between heart rate and QT interval fluctuations at physiological frequencies was lower in DCM patients compared with control subjects (0.28+/-0.14 versus 0.39+/-0.18, P<.0001). CONCLUSIONS: DCM is associated with beat-to-beat fluctuations in QT interval that are larger than normal and uncoupled from variations in heart rate. QT interval variability increases with worsening functional class but is independent of ejection fraction. These data indicate that DCM leads to temporal lability in ventricular repolarization.

Adult↗

PubMed1980

Intracellular filament bundles in whole mounts of chick and human myoblasts extracted with triton X-100.

The method of Triton X-100 extraction and critical point drying of whole mounts of cultured chick and human myoblasts was used to study the presence of intracellular bundles of filaments within these cells. Observation by means of transmission and scanning electron microscopy demonstrated a complex system of filament bundles which appeared morphologically and spatially heterogeneous. Most obvious were long dense bundles of cables traversing along the ventral surface of developing myoblasts, presumably the 'stress fibers' seen in light microscopy. Other bundle types occurred which were composed of loose aggregates of filaments coursing through the remnant cell body. A prominent accumulation of filaments was also seen at the lateral edges of these myoblasts. These lateral edge cables were thicker and denser than any other type of filament bundle observed in the myoblasts. Reaction of unextracted myoblasts directly to human antiplatelet myosin conjugated to rhodamine demonstrated that the most intense reaction also occurred along the lateral edges of both human and chick myoblasts. During development of chick myoblasts the filament bundles became oriented parallel to the cell axis giving the cell a fusiform morphology. It is possible that the various filament bundle structures and their differing structural and spatial dispositions could be related to functional differences among the diverse population of intracellular bundles of filaments.

Animals↗

PubMed2004

Dynamic heterogeneous spatio-temporal pattern formation in host-parasitoid systems with synchronised generations.

In this paper we develop a general mathematical model describing the spatio-temporal dynamics of host-parasitoid systems with forced generational synchronisation, for example seasonally induced diapause. The model itself may be described as an individual-based stochastic model with the individual movement rules derived from an underlying continuum PDE model. This approach permits direct comparison between the discrete model and the continuum model. The model includes both within-generation and between-generation mechanisms for population regulation and focuses on the interactions between immobile juvenile hosts, adult hosts and adult parasitoids in a two-dimensional domain. These interactions are mediated, as they are in many such host-parasitoid systems, by the presence of a volatile semio-chemical (kairomone) emitted by the hosts or the hosts' food plant. The model investigates the effects on population dynamics for different host versus parasitoid movement strategies as well as the transient dynamics leading to steady states. Despite some agreement between the individual and continuum models for certain motility parameter ranges, the model dynamics diverge when host and parasitoid motilities are unequal. The individual-based model maintains spatially heterogeneous oscillatory dynamics when the continuum model predicts a homogeneous steady state. We discuss the implications of these results for mechanistic models of phenotype evolution.

Animals↗

PubMed2005

Temporal autocorrelation can enhance the persistence and abundance of metapopulations comprised of coupled sinks.

In spatially heterogeneous landscapes, some habitats may be persistent sources, providing immigrants to sustain populations in unfavorable sink habitats (where extinction is inevitable without immigration). Recent theoretical and empirical studies of source-sink systems demonstrate that temporally variable local growth rates in sinks can substantially increase average abundance of a persisting population, provided that the variation is positively autocorrelated--in effect, temporal variation inflates average abundance. Here we extend these results to a metapopulation in which all habitat patches are sinks. Using numerical studies of a population with discrete generations (buttressed by analytic results), we show that temporal variation and moderate dispersal can jointly permit indefinite persistence of the metapopulation and that positive autocorrelation both lowers the magnitude of variation required for persistence and increases the average abundance of persisting metapopulations. These effects are weakened--but not destroyed--if variation in local growth rates is spatially synchronized and dispersal is localized. We show that the inflationary effect is robust to a number of extensions of the basic model, including demographic stochasticity and density dependence. Because ecological and environmental processes contributing to temporally variable growth rates in natural populations are typically autocorrelated, these observations may have important implications for species persistence.

Ecosystem↗

PubMed2006

Diversity of Planctomycetes in soil in relation to soil history and environmental heterogeneity.

Members of the Planctomycetes, which were once thought to occur primarily in aquatic environments, have been discovered in soils on five continents, revealing that these Bacteria are a widespread and numerically abundant component of microbial communities in soil. We examined the diversity of Planctomycetes in soil samples obtained from experimental plots at an agricultural site in order to assess the extent of Planctomycetes diversity in soil, to determine whether management effects such as past land cover and compost addition affected the composition of the Planctomycetes community, and to determine whether the observations made could provide insight into the ecological distribution of these organisms. Analysis of Planctomycetes 16S rRNA gene sequences revealed a total of 312 +/- 35 unique phylotypes in the soil at the site examined. The majority of these Planctomycetes sequences were unique, and the sequences had phylogenetic affiliations that included all major lineages in the Planctomycetaceae, as well as several novel groups of deeply divergent Planctomycetes. Both soil management history and compost amendment had significant effects on the Planctomycetes diversity, and variations in soil organic matter, Ca2+ content, and pH were associated with variations in the Planctomycetes community composition. In addition, Planctomycetes richness increased in proportion to the area sampled and was correlated with the spatial heterogeneity of nitrate, which was associated with the soil management history at the orchard site examined. This report provides the first systematic assessment of the diversity of Planctomycetes in soil and also provides evidence that the diversity of this group increases with area as defined by the general power law description of the taxon-area relationship.

Agriculture↗

PubMed1991

Capillary recruitment and heterogeneity of perfused capillary distribution in dog myocardium.

To estimate functional diffusion distances, the distribution of perfused capillaries was calculated in dog myocardium. A fluorescent dye was injected via a femoral vein in 6 anesthetized, open-chest dogs, and passed once through the coronary circulation (23 +/- 3 s). In 6 animals the dye circulated 4-20 min. In 6 animals the dye circulated for one pass following 2-3 min of asphyxia. The heart was then removed and frozen. Frozen sections from the left ventricule were cut, illuminated to excite the dye to fluoresce, and photographed. They were then stained by silver methenamine to mark all capillaries. The density of all capillaries was compared to that of capillaries containing fluorescent label. The distributions of capillaries were estimated by morphometry. In one pass of the normoxic coronary circulation, 66(+/- 4 SE)% of subepicardial and 60(+/- 4)% of subendocardial capillaries were detectably labeled. Their distribution approached a random pattern, and maximal distances to the nearest labeled capillary were lengthened by 50% compared to all capillaries. With multiple passes of the dye, or with asphyxia 76-79% of the capillaries were detectably labeled and their distribution approached the ordered pattern of the total capillary bed. We speculated that the unlabeled capillaries represented a spatially heterogeneous blood flow reserve.

Animals↗

PubMed2003

Spontaneous initiation and termination of complex rhythms in cardiac cell culture.

INTRODUCTION: Complex cardiac arrhythmias often start and stop spontaneously. These poorly understood behaviors frequently are associated with pathologic modification of the structural heterogeneity and functional connectivity of the myocardium. To evaluate underlying mechanisms, we modify heterogeneity by varying the confluence of embryonic chick monolayer cultures that display complex bursting behaviors. A simple mathematical model was developed that reproduces the experimental behaviors and reveals possible generic mechanisms for bursting dynamics in heterogeneous excitable systems. METHODS AND RESULTS: Wave propagation was mapped in embryonic chick myocytes monolayers using calcium-sensitive dyes. Monolayer confluence was varied by plating cultures with different cell densities and by varying times in culture. At high plating densities, waves propagate without breaks, whereas monolayers plated at low densities display spirals with frequent breaks and irregular activation fronts. Monolayers at intermediate densities display bursting rhythms in which there is paroxysmal starting and stopping of spiral waves of activity. Similar spatiotemporal patterns of activity were also observed as a function of the time in culture; irregular activity dominates the first 30 hours, followed by repetitive bursting dynamics until 54 hours, after which periodic target patterns or stable spirals prevail. In some quiescent cultures derived from older embryos, it was possible to trigger pacemaker activity following a single activation. We are able to reproduce all of these behaviors by introducing spatial heterogeneity and varying neighborhood size, equivalent to cell connectivity, in a spontaneous cellular automaton model containing a rate-dependent fatigue term. CONCLUSION: We observe transitions from irregular propagating waves, to spiral waves that spontaneously start and stop, to target waves originating from localized pacemakers in cell culture and a simple theoretical model of heterogeneous excitable media. The results show how physiologic properties of spontaneous activity, heterogeneity, and fatigue can give rise to a wide range of different complex dynamic behaviors similar to clinically observed cardiac arrhythmias.

Algorithms↗

PubMed1991

Effects of spatial dispersion of acetylcholine release on AV conduction responses to vagal stimulation in dogs.

We determined the effects on atrioventricular (AV) conduction of changing the spatial dispersion of acetylcholine (ACh) release from vagal nerve fibers in anesthetized dogs. We paced the atria at a constant rate and stimulated the vagus nerves with one stimulus burst per cardiac cycle. We varied the spatial heterogeneity of ACh release in the cardiac tissues by changing the stimulus voltage, and we varied the quantity of ACh release from each excited nerve fiber by changing the number of pulses per stimulus burst. We slightly changed the stimulus timing with each heartbeat to scan the entire cardiac cycle. We constructed phase-response curves (PRCs) by plotting the changes in AV conduction time as a function of the timing of vagal stimulation. We found that the amplitude of the PRC varied directly with average AV conduction time (AV), whereas the minimum-to-maximum phase difference of the PRC varied inversely with AV. However, for any given change in AV, the specific characteristics of the PRCs did not depend on whether we varied the number of pulses per burst or the stimulus voltage. Therefore, the phase-dependent characteristics of the dromotropic responses appear to be unaffected by the spatial dispersion of ACh release from the vagal nerve endings. The effects of vagal activity on the AV conduction time are determined by those conducting fibers that are the least restrained by neurally released ACh.

Acetylcholine↗

PubMed2002

Evolutionary branching of dispersal strategies in structured metapopulations.

Dispersal polymorphism and evolutionary branching of dispersal strategies has been found in several metapopulation models. The mechanism behind those findings has been temporal variation caused by cyclic or chaotic local dynamics, or temporally and spatially varying carrying capacities. We present a new mechanism: spatial heterogeneity in the sense of different patch types with sufficient proportions, and temporal variation caused by catastrophes. The model where this occurs is a generalization of the model by Gyllenberg and Metz (2001). Their model is a size-structured metapopulation model with infinitely many identical patches. We present a generalized version of their metapopulation model allowing for different types of patches. In structured population models, defining and computing fitness in polymorphic situations is, in general, difficult. We present an efficient method, which can be applied also to other structured population or metapopulation models.

Biological Evolution↗

PubMed1998

Heterogeneity of trabecular bone structure in the calcaneus using magnetic resonance imaging.

The purpose of this study was to quantify the heterogeneity in the trabecular bone structure in the calcaneus. Magnetic resonance (MR) images of the calcaneus were obtained in the sagittal plane at an in-plane resolution of 195 microns and a slice thickness of 1000 microns in 12 young normal subjects. Regions of interest (ROI) were selected to cover the calcaneus using a grid of square boxes (10 mm per side). A thresholding technique based on the regional intensity histogram was used to segment the images into trabecular bone and marrow phases and to calculate measures such as apparent trabecular bone area fraction, apparent trabecular spacing, apparent trabecular thickness and apparent trabecular number. Bone mineral density (BMD) of the calcaneus was assessed using dual-energy X-ray absorptiometry (DXA). Histological sections of three calcanei were also analyzed using transmission light illumination, and the results used to calibrate our computational software. For a relatively narrow inter-subject variation in posterior BMD, a significant inter-subject variation was seen in MRI-derived structural parameters. Furthermore, the spatial heterogeneity of the structural parameters in the posterior region was as high as 40%. Thus, the posterior tuberosity of the calcaneus, a typical site for BMD and single-point ultrasound assessments, can demonstrate significant regional variation in trabecular bone structure.

Absorptiometry, Photon↗

PubMed1997

Transit time heterogeneity in canine small intestine: significance for oxygen transport.

We previously found that local O2 extraction efficacy in isolated pump-perfused intestine was enhanced when systemic reflex vasoconstriction was stimulated by hypovolemia (Samsel, R.W., and P.T. Schumacker. 1994. J. Appl. Physiol. 77: 2291-2298). The microvascular mechanism underlying this beneficial effect could involve a redistribution of flow between mucosa and serosa, or an adjustment in the heterogeneity of perfusion within those regions. We measured regional blood flows and distributions of flow and capillary erythrocyte transit times in two segments of small intestine in anesthetized dogs (n = 10). Each vascularly isolated segment of intestine was pump-perfused under high flow (O2 supply-independent VO2) and low flow (O2 supply-dependent) conditions. During the first gut segment, the animal was kept normovolemic using i.v. fluids to minimize reflex vasoconstriction. During the second, the animal was hemorrhaged to augment vasoconstriction (n = 7), or kept normovolemic to control for the effects of time (n = 3). Blood flow distributions were measured using 15 microm radiolabeled microspheres. Tissue blood volume was measured using 99mTc-labeled red blood cells. Capillary volume was determined as the product of tissue blood volume and the histologically derived fraction of vascular volume in the capillaries. Transit times were calculated as the ratio of capillary volume to flow. Each gut segment was fixed and sectioned into 350 approximately 100 mg tissue pieces for analysis. Data revealed significant spatial heterogeneity of blood flow and capillary transit times in both mucosa and muscularis, with relative dispersions (SD/Mean) ranging from 23 to 97%. Hypovolemia caused an increase in flow heterogeneity in muscularis at both high and low flow states, and in mucosa under high flow conditions. However, hypovolemia also elicited changes in capillary volume, such that transit time heterogeneity remained unchanged. Augmentation of vasoconstrictor tone caused a redistribution of flow toward mucosa (P < 0.003) under high and low flow conditions. This redistribution correlated with the improvements in O2 extraction ratio (P = 0.022). Thus, the improvement in gut O2 extraction efficacy seen with increased vasoconstriction may be explained mostly by an intramural redistribution of flow between mucosa and muscularis. Capillary transit time heterogeneity remained unchanged, suggesting that this variable is tightly regulated.

Animals↗

PubMed1998

Spatial distribution patterns of Echinococcus multilocularis (Leuckart 1863) (Cestoda: Cyclophyllidea: Taeniidae) among red foxes in an endemic focus in Brandenburg, Germany.

Over a period of 40 months, 4374 foxes were randomly sampled from an area located in northwestern Brandenburg, Germany, and examined parasitologically for infections with Echinococcus multilocularis. Spatial analysis of the origin of infected animals identified two (one central and one southeastern) high-endemic foci with an estimated prevalence of 23.8%. By contrast, a prevalence of 4.9% was found in the remaining (low-endemic) area. The prevalences among juvenile and adult foxes were compared in the high-endemic and the low-endemic areas. To analyse the central high-endemic focus further, the random sample was stratified by zones representing concentric circles with a radius of 13 km (zone 1) or x(n-1) + 7 km for the remaining three zones from the apparent centre of this focus (anchor point). Prevalences calculated for each zone showed a decrease from zone 1 (18.8%) to zone 4 (2.4%) with significant differences for all zones but zones 3 and 4. The relative risk of an infection decreased rapidly in a distance range of 26 km around the high-endemic focus, whereas the relative risk remained unchanged within a distance of 5 km around the anchor point. The importance of heterogeneous spatial distribution patterns for the diagnosis and epidemiology of the infection is discussed.

Age Distribution↗

PubMed1999

[Heterogeneities of ventricular repolarization and vulnerability to arrhythmia. How to detect them with noninvasive methods?].

Vulnerability to arrhythmias can be influenced by two conditions: a dynamic (beat-to-beat) variation of repolarization sequence, and a state of heterogeneity of repolarization, i.e. a greater than normal dispersion of recovery time. The first condition is well reflected by T-wave alternans, a phenomenon characterized by alternation on every other beat basis of amplitude and morphology of T waves. Experimental studies provided evidences of close temporal correlations between ischemia-induced alternans, dispersion of repolarization and susceptibility to ventricular fibrillation. Gross T-wave alternans can be occasionally observed in patients with long QT syndrome or during acute ischemia before the onset of arrhythmias. Recent studies have demonstrated that measurement of microvolt level T-wave alternans at rest and during exercise is a promising technique for the identification of patients at risk of ventricular arrhythmias and sudden death. A state of repolarization inhomogeneity can be revealed by methods which analyze a single cardiac beat. The QT dispersion, defined as the difference between maximum and minimum QT interval measured at 12 lead ECG, is the most simple and widely used index of repolarization inhomogeneity. The major limitation is that this measure cannot be related to the actual spatial heterogeneity of repolarization, since each surface lead reflects, in different degree, the electrical activity of the whole heart. The majority of studies reported that, in various pathological conditions, the QT dispersion is higher in patients with than without ventricular arrhythmias. On the other hand, a recent large prospective study in post-myocardial infarction patients failed to demonstrate the predictive value of QT dispersion, even when measured with the best available methodology. Body surface potential mapping has proven to be a useful method for detecting repolarization inhomogeneities not revealed by the analysis of conventional ECG leads. Different methods of analysis of the potential maps have been used. By applying principal component analysis of the ST-T waves, we computed the similarity index, defined as the ratio of the first principal component to the sum of all remaining components. A low value of similarity index suggests a high degree of repolarization inhomogeneity. The similarity index was found significantly lower in patients with idiopathic long QT syndrome and in patients with arrhythmogenic right ventricular dysplasia with episodes of ventricular tachycardia than in normal subjects. Future researches should aim at identifying novel reliable indices of repolarization inhomogeneity, first deduced from extensive body surface mapping, then possibly computed from digital recording of the 12 conventional leads.

Arrhythmias, Cardiac↗

PubMed1994

Spatiotemporal dynamics of intracellular [Ca2+]i oscillations during the growth and meiotic maturation of mouse oocytes.

Calcium oscillations occur during meiotic maturation of mouse oocytes. They also trigger activation at fertilization. We have monitored [Ca2+]i in oocytes at different stages of growth and maturation to examine how the calcium release mechanisms alter during oogenesis. Spontaneous calcium oscillations occur every 2-3 minutes in the majority of fully grown (but immature) mouse oocytes released from antral follicles and resuming meiosis. The oscillations last for 2-4 hours after release from the follicle and take the form of global synchronous [Ca2+]i increases throughout the cell. Rapid image acquisition or cooling the bath temperature from 28 degrees C to 16 degrees C did not reveal any wave-like spatial heterogeneity in the [Ca2+]i signal. Calcium appears to reach highest levels in the germinal vesicle but this apparent difference of [Ca2+] in nucleus and cytoplasm is an artifact of dye loading. Smaller, growing immature oocytes are less competent: about 40% are able to resume meiosis and a similar proportion of these oocytes show spontaneous calcium oscillations. [Ca2+]i transients are not seen in oocytes that do not resume meiosis spontaneously in vitro. Nonetheless, these oocytes are capable of [Ca2+]i oscillations since they show them in response to the addition of carbachol or thimerosal. To examine how the properties of calcium release change during meiotic maturation, a calcium-releasing factor from sperm was microinjected into fully grown immature and mature oocytes. The sperm-factor-induced oscillations were about two-fold larger and longer in mature oocytes compared to immature oocytes. Calcium waves travelling at 40-60 microns/second were generated in mature oocytes, but not in immature oocytes. In some mature oocytes, successive calcium waves had different sites of origin. The modifications in the size and spatial organization of calcium transients during oocyte maturation may be a necessary prerequisite for normal fertilization.

Animals↗

PubMed2005

Inbreeding levels and consanguinity structure in the Basque province of Guipúzcoa (1862-1980).

This work analyzes the spatial heterogeneity of consanguinity in the Basque province of Guipúzcoa (Spain), using data provided by Catholic dispensations (1862-1980). Secular trends in consanguinity rates (%M(C)) and mean inbreeding coefficient (F) were similar in the seven Guipúzcoan regions considered, with peaks between 1881-1920 and subsequently a gradual decline. Substantial differences in consanguinity characteristics emerged when the regions were classified according to level of urbanization. Principal component analysis (accounting for more than 85% of the total variance in consanguinity variables) clearly discriminated between urbanized and less urbanized regions. The latter stand out for their high consanguinity rates (3.57-6.73%), mean inbreeding coefficient (0.00112-0.00240), and M22/M33 ratio (M22, first cousins; M33, second cousins), which ranged between 0.89-1.48. Moreover, in less urbanized regions, marital consanguinity was eminently local, and mainly conditioned by regional endogamy (71.4-85.0%). By contrast, urban subpopulations showed the lowest consanguinity rates (1.60-1.96%) and mean inbreeding coefficient (around 0.0007). In these regions, the M22/M33 ratio also exhibited high values (1.07-1.56), but this time at the expense of the contribution of the immigrant group. Discussion of the factors that could have modeled this spatial variation in consanguinity centers on: 1) demographic aspects related to the chronology and intensity of industrialization, 2) the geography of the territory and the geography of peopling, and 3) linguistic differences, expressed in the uneven distribution of Basque-speakers among the different territories considered.

Consanguinity↗

PubMed2006

Characterizing physiological heterogeneity of infarction risk in acute human ischaemic stroke using MRI.

Viable tissues at risk of infarction in acute stroke patients have been hypothesized to be detectable as volumetric mismatches between lesions on perfusion-weighted (PWI) and diffusion-weighted magnetic resonance imaging (DWI). Because tissue response to ischaemic injury and to therapeutic intervention is tissue- and patient-dependent, changes in infarct progression due to treatment may be better detected with voxel-based methods than with volumetric mismatches. Acute DWI and PWI were combined using a generalized linear model (GLM) to predict infarction risk on a voxel-wise basis for patients treated either with non-thrombolytic (Group 1; n = 11) or with thrombolytic therapy (Group 2; n = 27). Predicted infarction risk for both groups was evaluated in four ipsilateral regions of interest: tissue acutely abnormal on DWI (Core), tissue acutely abnormal on PWI but normal on DWI that either infarcts (Recruited) or does not (Salvaged), and tissue normal on both DWI and PWI that does not infarct (Normal) by follow-up imaging > or = 5 days. The performance of the models was significantly reduced for the thrombolysed group compared with the group receiving standard treatment, suggesting an alteration in natural progression of the ischaemic cascade. Average GLM-predicted infarction risk values in the four regions were different from one another for both groups. GLM-predicted infarction risk in Salvaged tissue was significantly higher (P = 0.02) for thrombolysed patients than for non-thrombolysed patients, suggesting that thrombolysis rescued tissue with higher infarction risk than typically measured in tissue that spontaneously recovered. The observed spatial heterogeneity of GLM-predicted infarction risk values probably reflects the varying degrees of tissue injury and salvageability that exist after stroke. MRI-based algorithms may therefore provide a more sensitive means for monitoring therapeutic effects on a voxel-wise basis.

Acute Disease↗