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Clustering of giardiosis among AIDS patients in Los Angeles County.

The purpose of this study was to determine the mode of the spread of the enteric parasitic infections among HIV+/AIDS patients attending the AIDS clinic of the King/Drew Medical Center in Los Angeles. Two hundred forty three patients diagnosed with HIV+/AIDS agreed to participate. The study was conducted by several interviews, questionnaires and stool sample collections over a one year period. Stool samples were processed for protozoan cysts and Helminth Ova using standard stool concentration and staining techniques. An indirect immunofluorescence monoclonal antibody technique was also used as an alternate to detect the parasites in samples. Forty three cases were positive for Giardia Lamblia (17.7%) and 10 cases were positive for Cryptosporidium (4%). No Helminth Ova were detected. The majority of the participants were African-American (72.6%) and 27.6% were Hispanic. Clustering studies were performed to determine the mechanism of spread of the parasites among the population study. The Nearest Neighbor Clustering Technique (NNT) was used to determine if there was spatial clustering of positive cases. Geocoding with the MapInfo Program was performed to determine the precise coordinates of the residence of the subjects. Application of the NNT showed a high degree of clustering for Giardia. The NNT statistic for Giardia was significant with the p value for 0.020 using the Simes multiple comparisons correction. Examination of the map plots indicated that there were two areas with high Giardia prevalence, one in Hollywood region, the other in South-Central Los Angeles. The odds ratio for sexual orientation was 14.2 (for homosexuals vs heterosexuals) with a p value of less than 0.001. These findings strongly suggest that male homosexual contact was the main mode of transmission of observed Giardia cases.

Acquired Immunodeficiency Syndrome↗

Local signaling by the EGF receptor.

Differing spatial scales of signaling cascades are critical for cell orientation during chemotactic responses. We used biotin EGF bound to streptavidin-coupled magnetic beads to locally stimulate cells overexpressing the EGF receptor. We have found that EGF-induced actin polymerization remains localized even under conditions of receptor overexpression. Conversely, EGF-induced ERK activation spreads throughout the cell body after EGF bead stimulation. The localized actin polymerization is independent of PI3-kinase and rho protein activity and requires Arp2/3 complex and cofilin function. Thus, we find differing spatial scales of signaling from the EGF receptor, supporting models of chemotaxis that integrate short- and long-range signaling.

Actin Depolymerizing Factors↗

Quartz crystal microbalance studies of polymer gels and solutions in liquid environments.

Spreading of liquids and soft solids on a rigid surface in a surrounding liquid medium is investigated by utilizing the lateral sensitivity of the quartz crystal microbalance (QCM). While the QCM has been used extensively to study systems with spatial variations in the direction normal to the crystal's electrodes, few studies have exploited the QCM's ability to sense changes in loading in the plane of the electrodes. We propose equations to describe the predicted response of the QCM to a generalized viscoelastic material spreading at the QCM surface at the expense of the surrounding liquid medium. Several experimental examples are given in order to support the validity of the proposed equations, including situations where the spreading material is a Newtonian liquid, a viscoelastic liquid, or one of two viscoelastic solids. The first viscoelastic solid is a physically cross-linked gel based on a styrene/ethylene-butene/styrene triblock copolymer in mineral oil, and the second is a cross-linked poly(ethylene glycol) hydrogel.

Crystallization↗

A gradual spread of attention during mental curve tracing.

The visual system has to segregate objects that are relevant to behavior from other objects and the background, if they are embedded in a visual scene. This segregation process can be time consuming, especially if the relevant object is spatially extended and overlaps with other image components, but the cause of the delays is presently not well understood. In the present study, we used a curve-tracing task to investigate processing delays during the grouping of contour segments into elongated curves. Our results indicate that contour segments that need to be grouped together are labeled with visual attention. Attention gradually spreads from contour segments that were labeled previously to other contours that are colinear and connected to them. The contour-grouping task is completed as soon as attention is directed to the entire curve. We conclude that processing delays during contour grouping are caused by a time-consuming spread of visual attention.

Adult↗

Three-dimensional spatial tuning of neck muscle activation in humans.

The complex structure of the neck musculoskeletal system poses challenges to understanding central nervous system (CNS) control strategies. Examining muscle activation patterns in relation to musculoskeletal geometry and three-dimensional mechanics may reveal organizing principles. We analyzed the spatial tuning of neck muscle electromyographic (EMG) activity while subjects generated moments in three dimensions. EMG tuning curves were characterized by their orientation (mean direction) and focus (spread of activity). For the four muscles that were studied (sternocleidomastoid, splenius capitis, semispinalis capitis and trapezius), EMG tuning curves exhibited directional preference, with consistent orientation and focus among 12 subjects. However, the directional preference (orientation) of three of the four neck muscles did not correspond to the muscle's moment arm, indicating that maximizing a muscle's mechanical advantage is not the only factor in determining muscle activation. The focus of muscle tuning did not change with moment magnitude, demonstrating that co-contraction did not increase with load. Axial rotation was found to have a strong influence on neck muscle spatial tuning. The uniform results among subjects indicate that the CNS has consistent strategies for selecting neck muscle activations to generate moments in specific directions; however, these strategies depend on three-dimensional mechanics in a complex manner.

Adult↗

Genomic signatures of adaptation across a landscape of crickets following the introduction of a parasitoid fly.

Novel species interactions provide an opportunity to assess the earliest stages of genetic adaptation. We combined population genomics and field selection surveys to explore the genomic and geographic landscape of adaptation in small, fragmented Hawaiian cricket populations, which are parasitized by larvae of an introduced fly that targets singing males. Multiple protective male-silencing cricket morphs have recently spread under this novel selection pressure, despite song's important roles in mate attraction. We find evidence of sharp declines in cricket effective population sizes following the fly's introduction and identify regions under spatially varying selection mediated by infestation risk, which are linked to an adaptive morph and other genes implicating in resisting infestation. Despite repeated bottlenecks, genetic variation is dominated by structural variant polymorphisms seemingly maintained under balancing selection. Our study illustrates pervasive consequences of abrupt changes in selection on small populations. Fly-mediated selection remains strong despite the spread of adaptive male-silencing phenotypes, which also reduce male fitness in the context of mate attraction.

Animals↗

Spatial resolution and count density requirements in brain SPECT imaging.

A set of simulations has been performed to investigate the spatial resolution and count density requirements for brain SPECT imaging. Projections were drawn from a matrix representation of the Hoffman brain phantom. These projections were convolved with realistic point spread functions and Poisson noise was added to simulate a wide range of imaging situations normalized to a fixed imaging time. The projections were optimally smoothed with a Wiener filter and were reconstructed with a ramp filter. The quality of the reconstructed images was determined objectively from the normalized mean square between the simulated data and the true distribution. This ranking was validated against the preferences of a group of trained observers. The results from this study indicate that the optimal choice of spatial resolution (collimation) depends on the available count density. As the count density (normalized to 10 mm resolution) increases by a factor of 2.7, results from the simulations indicate that the optimal spatial resolution improves by 1 mm. For brain studies in which the administered activity is limited (such as 123I IMP), the optimal spatial resolution is approximately 8 to 9 mm. With 99Tcm labelled brain agents the amount of administered radioactivity can be increased six-fold and the optimal spatial resolution is predicted to fall to about 6 to 7 mm. If sensitivity is further increased by the use of a dedicated SPECT unit with multiple detectors, the optimal spatial resolution will be on the order of 4 to 5 mm.

Brain↗

The spread of attention across modalities and space in a multisensory object.

Attending to a stimulus is known to enhance the neural responses to that stimulus. Recent experiments on visual attention have shown that this modulation can have object-based characteristics, such that, when certain parts of a visual object are attended, other parts automatically also receive enhanced processing. Here, we investigated whether visual attention can modulate neural responses to other components of a multisensory object defined by synchronous, but spatially disparate, auditory and visual stimuli. The audiovisual integration of such multisensory stimuli typically leads to mislocalization of the sound toward the visual stimulus (ventriloquism illusion). Using event-related potentials and functional MRI, we found that the brain's response to task-irrelevant sounds occurring synchronously with a visual stimulus from a different location was larger when that accompanying visual stimulus was attended versus unattended. The event-related potential effect consisted of sustained, frontally distributed, brain activity that emerged relatively late in processing, an effect resembling attention-related enhancements seen at earlier latencies during intramodal auditory attention. Moreover, the functional MRI data confirmed that the effect included specific enhancement of activity in auditory cortex. These findings indicate that attention to one sensory modality can spread to encompass simultaneous signals from another modality, even when they are task-irrelevant and from a different location. This cross-modal attentional spread appears to reflect an object-based, late selection process wherein spatially discrepant auditory stimulation is grouped with synchronous attended visual input into a multisensory object, resulting in the auditory information being pulled into the attentional spotlight and bestowed with enhanced processing.

Acoustic Stimulation↗

Use of a spread sheet to calculate the current-density distribution produced in human and rat models by low-frequency electric fields.

The current-density distribution produced inside irregularly shaped, homogeneous human and rat models by low-frequency electric fields is obtained by a two-stage finite-difference procedure. In the first stage the model is assumed to be equipotential. Laplace's equation is solved by iteration in the external region to obtain the capacitive-current densities at the model's surface elements. These values then provide the boundary conditions for the second-stage relaxation solution, which yields the internal current-density distribution. Calculations were performed with the Excel spread-sheet program on a Macintosh-II microcomputer. A spread sheet is a two-dimensional array of cells. Each cell of the sheet can represent a square element of space. Equations relating the values of the cells can represent the relationships between the potentials in the corresponding spatial elements. Extension to three dimensions is readily made. Good agreement was obtained with current densities measured on human models with both, one, or no legs grounded and on rat models in four different grounding configurations. The results also compared well with predictions of more sophisticated numerical analyses. Spread sheets can provide an inexpensive and relatively simple means to perform good, approximate dosimetric calculations on irregularly shaped objects.

Animals↗

Possible roles of vertebrate neuroglia in potassium dynamics, spreading depression and migraine.

The membranes of glial cells are highly selectively permeable to potassium. The implications of this and the possible reasons for it are discussed. Glial cells may contribute to buffering the extracellular K+ concentration of brain tissue through several mechanisms. However, the only one that benefits from the K+ selective permeability is the so-called 'spatial' buffer mechanism, which acts more effectively than extracellular diffusion in many situations to speed the dispersal of local accumulations of potassium. The role of glial cells in buffering the extracellular K+ concentration may help to prevent the occurrence of a phenomenon called Leão's spreading depression (SD). A K+-induced K+ efflux from neurones, occurring when the EC K+ concentration rises above critical levels, is probably crucial in causing SD. The models that have been proposed to describe this process are discussed and related. Spreading depression is not known definitely to occur in man. It seems probable, however, that it occurs during attacks of 'classical' migraine, associated with neurological symptoms. These neurological symptoms have often been attributed to vasoconstriction rather than to SD since certain vasodilators can relieve the symptoms. Experiments with SD in anaesthetized rats show that at least one of these vasodilator interventions (administration of a CO2/O2 mixture) stops also the propagation of a wave of SD. This strengthens the evidence for a possible relationship between migraine and SD. The involvement of SD in migraine probably deserves more critical attention than has hitherto been devoted to it.

Animals↗

Dynamics of prey moving through a predator field: a model of migrating juvenile salmon.

The migration of a patch of prey through a field of relatively stationary predators is a situation that occurs frequently in nature. Making quantitative predictions concerning such phenomena may be difficult, however, because factors such as the number of the prey in the patch, the spatial length and velocity of the patch, and the feeding rate and satiation of the predators all interact in a complex way. However, such problems are of great practical importance in many management situations; e.g., calculating the mortality of juvenile salmon (smolts) swimming down a river or reservoir containing many predators. Salmon smolts often move downstream in patches short compared with the length of the reservoir. To take into account the spatial dependence of the interaction, we used a spatially-explicit, individual-based modeling approach. We found that the mortality of prey depends strongly on the number of prey in the patch, the downstream velocity of prey in the patch, and the dispersion or spread of the patch in size through time. Some counterintuitive phenomena are predicted, such as predators downstream capturing more prey per predator than those upstream, even though the number of prey may be greatly depleted by the time the prey patch reaches the downstream predators. Individual-based models may be necessary for complex spatial situations, such as salmonid migration, where processes such as schooling occur at fine scales and affect system predictions. We compare some results to predictions from other salmonid models.

Animals↗

Spatial control of rabies on heterogeneous landscapes.

Rabies control in terrestrial wildlife reservoirs relies heavily on an oral rabies vaccine (ORV). In addition to direct ORV delivery to protect wildlife in natural habitats, vaccine corridors have been constructed to control the spread; these corridors are often developed around natural barriers, such as rivers, to enhance the effectiveness of vaccine deployment. However, the question of how to optimally deploy ORV around a river (or other natural barrier) to best exploit the barrier for rabies control has not been addressed using mathematical models. Given an advancing epidemic wave, should the vaccine be distributed on both sides of barrier, behind the barrier, or in front of it? Here, we introduce a new mathematical model for the dynamics of raccoon rabies on a spatially heterogeneous landscape that is both simple and realistic. We demonstrate that the vaccine should always be deployed behind a barrier to minimize the recurrence of subsequent epidemics. Although the oral rabies vaccine is sufficient to induce herd immunity inside the vaccinated area, it simultaneously creates a demographic refuge. When that refuge is in front of a natural barrier, seasonal dispersal from the vaccine corridor into an endemic region sustains epidemic oscillations of raccoon rabies. When the vaccine barrier creates a refuge behind the river, the low permeability of the barrier to host movement limits dispersal of the host population from the protected populations into the rabies endemic area and limits subsequent rabies epidemics.

Administration, Oral↗

Asymptotic properties of mathematical models of excitability.

We analyse small parameters in selected models of biological excitability, including Hodgkin-Huxley (Hodgkin & Huxley 1952 J. Physiol.117, 500-544) model of nerve axon, Noble (Noble 1962 J. Physiol.160, 317-352) model of heart Purkinje fibres and Courtemanche et al. (Courtemanche et al. 1998 Am. J. Physiol.275, H301-H321) model of human atrial cells. Some of the small parameters are responsible for differences in the characteristic time-scales of dynamic variables, as in the traditional singular perturbation approaches. Others appear in a way which makes the standard approaches inapplicable. We apply this analysis to study the behaviour of fronts of excitation waves in spatially extended cardiac models. Suppressing the excitability of the tissue leads to a decrease in the propagation speed, but only to a certain limit; further suppression blocks active propagation and leads to a passive diffusive spread of voltage. Such a dissipation may happen if a front propagates into a tissue recovering after a previous wave, e.g. re-entry. A dissipated front does not recover even when the excitability restores. This has no analogy in FitzHugh-Nagumo model and its variants, where fronts can stop and then start again. In two spatial dimensions, dissipation accounts for breakups and self-termination of re-entrant waves in excitable media with Courtemanche et al. kinetics.

Action Potentials↗

Multicomponent binary spreading process.

I investigate numerically the phase transitions of two-component generalizations of binary spreading processes in one dimension. In these models pair annihilation AA --> emptyset, BB --> emptyset, explicit particle diffusion, and binary pair production processes compete with each other. Several versions with spatially different production are explored, and it is shown that for the cases 2A --> 3A, 2B--> 3B and 2A --> 2AB, 2B--> 2BA a phase transition occurs at zero production rate (sigma=0), which belongs to the class of N-component, asymmetric branching and annihilating random walks, characterized by the order parameter exponent beta=2. In the model with particle production AB --> ABA, BA --> BAB a phase transition point can be located at sigma(c)=0.3253 which belongs to the class of one-component binary spreading processes.

Journal Article↗

Spatial and seasonal distribution of Culicoides imicola in Iberia in relation to the transmission of African horse sickness virus.

Collections of biting midges were made over 24 months from sixty sites spread across Iberia. Information on the distribution of the vector of African horse sickness virus, Culicoides imicola, from these 3119 samples showed that this species was annually present across south-western Spain as far as 3 degrees 53'W and throughout most of Portugal, up to 41 degrees 5'N. C. imicola was found in all areas where African horse sickness epizootics had occurred in 1987-90 and also in areas outside the epizootic zones. Seasonal patterns of capture success of C. imicola, from seventeen frequently sampled sites where the vector was present, usually showed a late summer-early autumn peak. At the sites furthest south there was a discrete peak, mostly in September or October, before and after which the numbers captured increased or decreased steadily. At higher latitudes peak abundances occurred as early as May or as late as November, population build up was less uniform and numbers often declined rapidly after the peak was reached. Both the distribution and seasonal abundance patterns closely matched transmission patterns of African horse sickness virus, which rose during late summer and caused most cases during the autumn months.

African Horse Sickness↗

Neutrophil leucocyte chemotaxis is not induced by a spatial gradient of chemoattractant.

Chemotaxis and directed locomotion of neutrophil leucocytes are generally thought to be determined by the directed response of the cell to stable, spatial gradients of chemoattractants. In most cases, however, cells are also exposed to characteristic temporal changes in the attractant concentration during the lifetime of the gradient, especially as it develops. We have attempted to test whether neutrophils can respond to a spatial gradient in which these temporal changes are essentially absent. Gradients of formyl-peptides were made across a narrow barrier of agarose gel that separated two fluid reservoirs, and the cells were observed cinematographically as they moved between gel and glass. In gradients predeveloped at low temperature, at which cell motion and responses to attractant were inhibited, neutrophils showed no tendency to accumulate up-gradient when warmed to 37 degrees C. Yet their speed and turning behaviour was related to the local concentration of formyl-peptide. However, gradients that developed at 37 degrees C, whilst the cells were responsive, elicited directed locomotion. We also tested populations that were either spreading into or already evenly distributed across micropore filters to see how cells might sense directional cues. We reasoned that evenly distributed populations could accumulate in a spatial gradient only if cells were able to 'read' it. However, no redistribution occurred without an applied impulse of attractant. It seems that the oriented, temporal component of an attractant signal is essential if a directed response (i.e. non-random turning) is to occur; a spatial gradient of soluble attractant alone does not induce neutrophil accumulation or taxis. This finding has implications for the termination of the acute inflammatory response, for clinical tests of leucocyte behaviour and for morphogen signal interpretation by cells in developing tissues.

Animals↗

Characterization of a fluoroscopic imaging system for kV and MV radiography.

An on-line kilovoltage (kV) imaging system has been implemented on a medical linear accelerator to verify radiotherapy field placement. A kV x-ray tube is mounted on the accelerator at 90 degrees to the megavoltage (MV) source and shares the same isocenter. Nearly identical CCD-based fluoroscopic imagers are mounted opposite the two x-ray sources. These systems are being used in a clinical study of patient setup error that examines the advantage of kV imaging for on-line localization. In the investigation reported here, the imaging performance of the kV and MV systems are characterized to provide support to the conclusions of the studies of setup error. A spatial-frequency-dependent linear systems model is used to predict the detective quantum efficiencies (DQEs) of the two systems. Each is divided into a series of gain and spreading stages. The parameters of each stage are either measured or obtained from the literature. The model predicts the system gain to within 7% of the measured gain for the MV system and to within 10% for the kV system. The systems' noise power spectra (NPSs) and modulation transfer functions (MTFs) are measured to construct the measured DQEs. X-ray fluences are calculated using modeled polyenergetic spectra. Measured DQEs agree well with those predicted by the model. The model reveals that the MV system is well optimized, and is x-ray quantum noise limited at low spatial frequencies. The kV system is suboptimal, but for purposes of patient positioning yields images superior to those produced by the MV system. This is attributed to the kV system's higher DQE and to the inherently higher contrasts present at kV energies.

Biophysical Phenomena↗

Spatial and dynamic changes in intracellular Ca2+ measured by confocal laser-scanning microscopy in bullfrog sympathetic ganglion cells.

Confocal laser scanning microscopy (CLSM) was used to record spatial and dynamic changes in the intracellular Ca2+ [(Ca2+]i) of bullfrog sympathetic ganglion cells in excised tissue or in culture. A CLSM utilizing Ar ion laser (488 nm) and recording fluo-3 fluorescence yielded the sliced image of ganglion cells, while conventional epifluorescence microscopy provided the cell image of a convex structure. A high K+ (50 mM) solution, caffeine (3-10 mM) and electrical stimulation (10-20 Hz, 0.5-10 s) caused a homogeneous increase in fluo-3 fluorescence with or without regional differences, possibly due to intracellular organelles and other constituents. Scanning a single horizontal line across the cytoplasm with He-Cd laser (325 nm) and recording indo-1 fluorescence demonstrated that the rate of rise in [Ca2+]i following action potentials depends on the distance from the cell membrane and on the cytoplasmic constituents, showing an inward spread of 'Ca(2+)-wave' at variable speeds of 17-219 microns/s. These results suggest that heterogeneity of the cytoplasmic structures and constituents affects dynamic and spatial changes of [Ca2+]i in response to stimuli in neurones. Such heterogenic changes in [Ca2+]i would better be studied by CLSM.

Aniline Compounds↗