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Optical imaging of epileptiform events in visual cortex in response to patterned photic stimulation.

In a subset of patients with epilepsy, patterned visual stimuli can trigger clinical seizures. The etiology of this phenomenon, and the complex interaction between functional architecture and epilepsy, were investigated in ferret visual cortex. Optical imaging of intrinsic signals was used to visualize maps of orientation, ocular dominance and spatial frequency. Acute interictal spike foci were then induced within V1 using focal iontophoresis of bicuculline methiodide and optically mapped during presentation of patterned visual stimuli. We found that specific orientations and spatial frequencies could preferentially trigger epileptiform events, depending on the location of the epicenter of the epileptic focus within the columnar architecture of visual cortex. These data support a cortical etiology of the clinical phenomenon of pattern-sensitive epilepsy. We were not able to demonstrate a spatial correlation between the functional architecture maps and the topography of the epileptic focus. These findings implicate short-range rather than long-range horizontal excitatory connections in the lateral spread of interictal spikes, which may be specific to the epilepsy model of acute focal disinhibition. Orientation and spatial frequency maps were severely disturbed in the region of the focus but were unaltered in the surrounding cortex. Thus, optical imaging of intrinsic signals can be used to simultaneously map epilepsy and normal functional anatomy with high spatial resolution.

Action Potentials↗

Spatial dynamics of pertussis in a small region of Senegal.

Extended time-series analysis of infectious diseases raises two issues: the spread of disease, and its persistence in space and time. Most studies are based on both data and models, corresponding to conditions encountered in developed countries. The present work sought to determine the impact of local heterogeneity on these two issues, regarding pertussis in tropical conditions. First, we tested the 'cities and villages' model in a small community of 30 villages in rural Senegal. Second, we focused on the impact of population size and density, as well as geographic distance, on population dynamics of pertussis. Results showed that pertussis initially arrived in urban centres, and then spread to surrounding areas. Both population size and density are implicated in the persistence of pertussis within the study area, whereas geographical distance between villages is not. This is the first study on pertussis in a developing country carried out on a very fine spatial scale. Furthermore, it confirms previous results for measles in England and Wales.

Bordetella pertussis↗

A spatiotemporal stochastic process model for species spread.

We use a spatiotemporal Markov process to model the spread of an ecological population through its environment over time. Available habitat is divided into sites, and a parametric function of spatial variables is used to model the probability that one site is colonized from another. This allows us both to make predictions about the future spread of a population, and to determine which are the important factors governing colonizations. The model evolves in discrete time, allowing the population distribution to change seasonally in accordance with breeding patterns. Discrete time formulations are natural for ecological populations, but are problematic due to difficulties of fitting and predicting over irregular time intervals. The model described here can accommodate years of missing data and can therefore fit and predict at irregular intervals. Two methods of approximating the likelihood are described and applied to ornithological survey data for the woodlark, Lullula arborea, from Thetford Forest in the U.K.

Animals↗

Leishmania/HIV co-infections: epidemiology in Europe.

As the AIDS pandemic spreads to rural areas and human visceral leishmaniasis (VL) becomes more common in suburban areas, there is an ever greater degree of overlap between the geographical distributions of the two diseases and, in consequence, an increasing incidence of Leishmania/HIV co-infection. Cases of the co-infection have been reported from 35 countries around the world but most have been recorded in south-western Europe. There has been a total of 1911 cases detected in Spain, France, Italy and Portugal. The incidence of Leishmania/HIV co-infection is expected to continue increasing in eastern Africa but to fall in south-western Europe as increasing numbers of HIV-positives in the latter region are given the new, highly active, antiretroviral therapy (HAART). In 1998, a world-wide network of surveillance for the co-infection, which now includes 28 member institutions, was established by the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS). In south-western Europe, the surveillance system is based on 16 institutions and is already well established. The systematic use of standardized and recently computerized case-report forms, a central international registry at the WHO's headquarters in Geneva, and the use of a geographical information system (GIS) for mapping and monitoring the co-infections have together improved the overall quality of the epidemiological data-gathering. All member institutions of the global network report to the WHO on an annual basis. The data collected are then analysed and periodically disseminated through international publications. The GIS allows the relevant epidemiological and demographic data-sets to be integrated and permits all detected cases of co-infection to be mapped down to locality level. The system also allows the spatial distribution of cases to be visualised and analysed and the geographical spread of the co-infection to be monitored over time. The risk posed by co-infected patients, as a source of Leishmania infection for the sandflies feeding on them, has recently been confirmed. The parasites and HIV may also be transmitted as the result of needle-sharing among intravenous-drug users.

AIDS-Related Opportunistic Infections↗

Scaling of spreading in models unidirectionally coupled to source particles.

We investigate the spreading behavior of evolving clusters using unidirectionally coupled two-level hierarchies in one spatial dimension. In the hierarchy, while only two source particles (A) hop away from each other without branching its offspring on the bottom level, different species of particles (B) evolve according to given dynamics belonging to one of known universality classes on the top level. Two levels are unidirectionally coupled from the bottom to the top level by the branching A-->A+2B. We derive the spreading exponent zU of the uncoupled region of size RU(t) approximately tzU up to the first order correction in terms of the spreading exponent of source particles (zA) and that of given dynamics of the top level (zo) as zU=(1--zA)zo/(1-zo). From the relation, zA and zU always satisfy the inequality zU< or =zA for zA> or =zo. The inequality confirms that the scaling of the spreading in the slave level should follow the scaling of the source in unidirectionally coupled systems. We numerically confirm the relation for three different B-particle dynamics; annihilating random walks, branching annihilating random walks with one and two offspring which belong to the directed percolation, and the parity conserving universality class respectively.

Journal Article↗

Spatial distribution of human and canine visceral leishmaniasis in Belo Horizonte, Minas Gerais State, Brasil, 1994-1997.

In this paper, we present spatial analysis of the association between all incidents cases of human Visceral Leishmaniasis and seropositive dogs, from 1994 to 1997 in Belo Horizonte, a large Brazilian city. We geocoded 158 human cases and 11,048 seropositive dogs and compared canine prevalence rates with Human Bayesian Incidence rates in the same areas. We also used Knox's test to evaluate the hypothesis of space-time clustering of human cases in the period. Additionally, we used Kernel's maps for seropositive dogs distribution and located the human cases in the resulting smooth maps. We concluded that human and dog rates are correlated. Also, the Visceral Leishmaniasis in Belo Horizonte spread quickly, but apart from the rates' magnitude, it has kept the same spatial pattern through time. We believe it is possible to use this technique to choose areas to implement control measures against Visceral Leishmaniasis in a more efficient way.

Animals↗

Spatial dynamics and molecular ecology of North American rabies.

Rabies, caused by a single-stranded RNA virus, is arguably the most important viral zoonotic disease worldwide. Although endemic throughout many regions for millennia, rabies is also undergoing epidemic expansion, often quite rapid, among wildlife populations across regions of Europe and North America. A current rabies epizootic in North America is largely attributable to the accidental introduction of a particularly well-adapted virus variant into a naive raccoon population along the Virginia/West Virginia border in the mid-1970s. We have used the extant database on the spatial and temporal occurrence of rabid raccoons across the eastern United States to construct predictive models of disease spread and have tied patterns of emergence to local environmental variables, genetic heterogeneity, and host specificity. Rabies will continue to be a remarkable model system for exploring basic issues in the temporal and spatial dynamics of expanding infectious diseases and examining ties between disease population ecology and evolutionary genetics at both micro- and macro-evolutionary time scales.

Algorithms↗

Epidemiological models for the spread of anti-malarial resistance.

BACKGROUND: The spread of drug resistance is making malaria control increasingly difficult. Mathematical models for the transmission dynamics of drug sensitive and resistant strains can be a useful tool to help to understand the factors that influence the spread of drug resistance, and they can therefore help in the design of rational strategies for the control of drug resistance. METHODS: We present an epidemiological framework to investigate the spread of anti-malarial resistance. Several mathematical models, based on the familiar Macdonald-Ross model of malaria transmission, enable us to examine the processes and parameters that are critical in determining the spread of resistance. RESULTS: In our simplest model, resistance does not spread if the fraction of infected individuals treated is less than a threshold value; if drug treatment exceeds this threshold, resistance will eventually become fixed in the population. The threshold value is determined only by the rates of infection and the infectious periods of resistant and sensitive parasites in untreated and treated hosts, whereas the intensity of transmission has no influence on the threshold value. In more complex models, where hosts can be infected by multiple parasite strains or where treatment varies spatially, resistance is generally not fixed, but rather some level of sensitivity is often maintained in the population. CONCLUSIONS: The models developed in this paper are a first step in understanding the epidemiology of anti-malarial resistance and evaluating strategies to reduce the spread of resistance. However, specific recommendations for the management of resistance need to wait until we have more data on the critical parameters underlying the spread of resistance: drug use, spatial variability of treatment and parasite migration among areas, and perhaps most importantly, cost of resistance.

Alleles↗

Tree diseases and landscape processes: the challenge of landscape pathology.

Forest pathology inherently involves a landscape perspective, because tree pathogens propagate according to heterogeneous spatial patterns of flow and isolation. Landscape pathology is a field that is now emerging from the transdisciplinary cooperation of forest pathologists with landscape ecologists. Here, we review recent broad-scale assessments of tree disease risk, investigations of site and host preferences for several root rot pathogens, and regional historical analyses of pathogen outbreak in plantations. Crucial topics include fragmentation effects on pathogen spread and geophysical features that predispose forest patches to disease expression. Recent methodological developments facilitate the spatially explicit analysis of reciprocal coarse-scale relationships among hosts and pathogens. Landscape pathology studies fill a significant research gap in the context of our understanding of sustainable forest management, the introduction of exotic organisms and how climate change might affect the spread of disease.

Journal Article↗

Fast Fourier imaging.

A new NMR imaging technique, aiming at a reduction of the data acquisition time, is described in detail. The method is applicable in all multidimensional imaging situations where at least one spatial coordinate is resolved. Discussed at some length are the point-spread function, the required bandwidth of the NMR spectrometer, and the sampling strategy used to diminish the loss in signal-to-noise ratio. Experiments reveal that a reduction of the data acquisition time by at least a factor of four is attainable in practice.

Head↗

Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer's disease, and vascular cognitive impairment.

In this review, the neuropsychological symptoms of different diseases in the elderly are described. After a brief explanation of relevant principles in the neuropsychological assessment of older individuals, a summary of the complex relation between ageing and cognition is presented. It may be concluded that cognitive decline is not an inevitable outcome of ageing, and may well be the result of unrecognised pathology. The term mild cognitive impairment is reserved for patients whose impairment is objectively demonstrable but is not pronounced in more than one domain of cognition and does not seriously affect activities of daily living. The initial phase of Alzheimer's disease is marked by a progressive deterioration of episodic memory. When the process advances, the impairment spreads to other functions, such as semantic memory, language and visuo-spatial ability. Vascular dementia is the second most common type of dementia; however, it is increasingly being recognised that vascular dementia is actually a heterogeneous syndrome and that several vascular pathologies can lead to cognitive deterioration. In contrast to the striking deficits produced by cortical infarcts, lesions of the subcortical white matter are mainly associated with a non-specific slowing of behaviour. Cerebrovascular disease also plays an important role in forms of cognitive decline other than dementia, and as such, it appears to be no less prevalent in old age than Alzheimer's disease. Neuropsychology is an important asset to the study and treatment of cognitive decline, but must be embedded in a multi-disciplinary context.

Aged↗

Anthelmintic resistance revisited: under-dosing, chemoprophylactic strategies, and mating probabilities.

Deterministic and stochastic models are used to examine the evolution of anthelmintic resistance among trichostrongylid parasites of domestic ruminants. We find that the relative selection pressures exerted by chemoprophylactic (preventive) control strategies, chemotherapeutic (salvage) control strategies, and regimens involving "under-dosing" are critically dependent on a variety of host and parasite parameters (particularly host immunity and grazing behaviour, parasite fecundity, and the survival of the free-living stages on the pasture). Chemoprophylactic strategies are not necessarily more likely to exert a stronger selection pressure than chemotherapeutic strategies. Similarly, as one reduces dosage levels, there is a range of dose levels where under-dosing promotes resistance and a range of dose levels where under-dosing impedes resistance. The most dangerous dose is either that necessary to kill all the susceptible homozygotes, or that necessary to kill all the susceptible homozygotes and all the heterozygotes. Which one prevails depends upon model parameters. The stochastic formulation indicates that spatial heterogeneity in transmission may be a significant force in promoting the spread of resistant genotypes--at least when infection is at low levels.

Animals↗

Spatial Mendelian games.

This paper considers complex models arising in sociobiology. These combine genetic and strategic aspects to model the effect of gene-linked strategies on the ability of individuals to survive to maturity, mate and produce offspring. Several important models considered in the literature are generalised and extended to incorporate a spatial aspect. Individuals are allowed to migrate. Contests, e.g. for food or amongst males for females, take place locally. The choice of the point at which the population structure is measured affects the complexity of the equations describing the system, although it is possible to utilise any point in the life cycle. For our spatial models the simplest approach is to measure the population structure immediately after migration. A saddle point method, developed by the authors, has previously been used to obtain results for simple discrete time spatial models. It is utilised here to obtain the speed of first spread of a new gene-linked strategy for the much more complex sociobiological models included in this paper. This demonstrates the wide-ranging applicability and power of the method.

Alleles↗

Objective evaluation of the relative modulation transfer function of densitometers for digitisation of electron micrographs.

Digitisation of images recorded on film is a crucial part of data acquisition in electron microscopy, particularly for electron cryo-microscopy of biological specimens where the contrast and signal-to-noise ratio are low. A quantitative method to evaluate and compare the quality of densitometers, as measured by the modulation transfer function (MTF), is described here. The densitometer is modelled as a linear system, the output being the convolution of the input image and a point spread function. The MTF is the magnitude of the Fourier transform of the point spread function. The relative MTF describes the quality of signal transfer with spatial frequency. It is important that fine structural details in the micrograph are digitised with a high value for the MTF which does not vary with direction. A test pattern has been generated by projecting an electron image of a grid pattern onto film. The film is scanned and a computer program measures the intensities of the diffraction orders of the repeating pattern. Three different scanners are compared, one is a point scanner and the other two are line scanners. The test can be used to check if a scanner is set up optimally, and how it compares with another scanner.

Journal Article↗

Ensemble patterns of hippocampal CA3-CA1 neurons during sharp wave-associated population events.

Transfer of neuronal patterns from the CA3 to CA1 region was studied by simultaneous recording of neuronal ensembles in the behaving rat. A nonlinear interaction among pyramidal neurons was observed during sharp wave (SPW)-related population bursts, with stronger synchrony associated with more widespread spatial coherence. SPW bursts emerged in the CA3a-b subregions and spread to CA3c before invading the CA1 area. Synchronous discharge of >10% of the CA3 within a 100 ms window was required to exert a detectable influence on CA1 pyramidal cells. Activity of some CA3 pyramidal neurons differentially predicted the ripple-related discharge of circumscribed groups of CA1 pyramidal cells. We suggest that, in SPW behavioral state, the coherent discharge of a small group of CA3 cells is the primary cause of spiking activity in CA1 pyramidal neurons.

Action Potentials↗

Characterization of a transmission ionization beam-imager for radiotherapy verification.

A system for radiotherapy treatment verification is proposed, using an air-ionization chamber with 1600 simultaneously readable 1 cm pixels. An image of the entire beam may be used to calibrate a portal image, to verify the position of the multi-leaf collimator with respect to delivered dose (either before or during treatment) and to check beam flatness and symmetry. This study characterizes the physical behaviour of such a system. A test chamber has been constructed and its temporal and spatial resolution and noise characteristics are evaluated. Several parameters of the design are varied, and their effects assessed. Temporal resolution is adequate to allow readout between each linear accelerator pulse at 400 pulses per second. Application of low atomic-number build-up and reduction of plate separation were the most effective methods to improve spatial resolution. The full width at half maximum of the line-spread function is shown to be 4.5 mm using a pre-sampling technique. The peak pixel-signal to x-ray quantum noise ratio exceeds 100. Prototype electronics have been tested, demonstrating that electronic noise could be reduced to a level below the x-ray quantum noise. The results of the study allow the simulation of any possible application to evaluate the proposed verification system.

Algorithms↗

A method for comparative evaluation of EIT algorithms using a standard data set.

The point spread function (PSF) is the most widely used tool for quantifying the spatial resolution of imaging systems. However, prerequisites for the proper use of this tool are linearity and space invariance. Because EIT is non-linear it is only possible to compare different reconstruction algorithms using a standard data set. In this study, the FEM is used to generate simulation data, which are used to investigate the non-linear behaviour of EIT, the space dependence of its PSF and its capability of resolving nearby objects. It is found that for the case of iterative backprojection (IterB), the full width half maximum (FWHM) values of single-object perturbations for central, intermediate and peripheral high-contrast objects are 27%, 18% and 14% of the imaging region diameter respectively. For the method based on singular value decomposition of the Geselowitz lead sensitivity matrix (GS-SVD), the FWHM is not space dependent and is 12% of the imaging region diameter. Conclusions obtained using single-object PSF studies must also be checked with double-object or more complex perturbations because EIT is non-linear. For example, the GS-SVD method fails to detect two widely separated objects unless the truncation level of SVD is carefully adjusted. With more truncation, however, the resolution of the method is worsened. Based on these and similar observations a set of simulation data, which is proposed for comparative evaluation of different EIT algorithms, is specified and explained in the conclusion section.

Algorithms↗

A priori prediction of disease invasion dynamics in a novel environment.

Directly transmitted infectious diseases spread through wildlife populations as travelling waves away from the sites of original introduction. These waves often become distorted through their interaction with environmental and population heterogeneities and by long-distance translocation of infected individuals. Accurate a priori predictions of travelling waves of infection depend upon understanding and quantifying these distorting factors. We assess the effects of anisotropies arising from the orientation of rivers in relation to the direction of disease-front propagation and the damming effect of mountains on disease movement in natural populations. The model successfully predicts the local and large-scale prevaccination spread of raccoon rabies through New York State, based on a previous spatially heterogeneous model of raccoon-rabies invasion across the state of Connecticut. Use of this model provides a rare example of a priori prediction of an epidemic invasion over a naturally heterogeneous landscape. Model predictions matched to data can also be used to evaluate the most likely points of disease introduction. These results have general implications for predicting future pathogen invasions and evaluating potential containment strategies.

Animals↗