Spatial patterns of the pathological changes in the cerebellar cortex in sporadic Creutzfeldt-Jakob disease (sCJD)

The spatial patterns of the vacuolation ("spongiform change"), surviving cells, and prion protein (PrP) deposition were studied in the various cell laminae of the cerebellar cortex in 11 cases of sporadic Creutzfeldt-Jakob disease (sCJD). Clustering of the histological features, with the clusters regularly distributed along the folia, was evident in all cell laminae. In the molecular layer, clusters of vacuoles coincided with the surviving Purkinje cells. In the granule cell layer, however, the spatial relationship between the vacuoles and surviving cells was more complex and varied between cases. PrP deposition was not spatially correlated with either the vacuoles or the surviving cells in any of the cerebellar laminae in the majority of cases. In some cases, there were spatial relationships between th histological features in the molecular and granule cell layers. The data suggest that degeneration of the cerebellar cortex in sCJD may occur in a topographic pattern consistent with the spread of prion pathology along anatomical pathways. The development of the vacuolation may be an early stage of the pathology in the cerebellum preceding the appearance of the PrP deposits. In addition, there is evidence that the pathological changes may spread across the different laminae of the cerebellar cortex.

The spatial patterns of prion protein deposits in cases of variant Creutzfeldt-Jakob disease

The spatial patterns of the prion protein (PrP) deposits were studied in immunostained sections of areas of the cerebral cortex, hippocampus, dentate gyrus, and the molecular layer of the cerebellum in 11 cases of variant Creutzfeldt-Jakob disease (vCJD). Clustering of PrP deposits, with a regular distribution of the clusters parallel to the tissue boundary, was the most common spatial pattern observed. Two morphological types of PrP deposit were recognised, those consisting of a condensed core (florid deposits) and those deposits lacking a condensed core (non-florid deposits). The florid and non-florid PrP deposits exhibited a different profile of spatial patterns. First, the florid deposits exhibited a regularly distributed pattern of clusters more frequently than the non-florid deposits. Second, the florid deposits formed larger clusters (greater than1,600 µm in diameter) less frequently than the non-florid deposits. In the areas of the cerebral cortex that exhibited a regular distribution of PrP deposit clusters, the cluster size of the deposits approximated that of the groups of cells of the cortico-cortical pathway origin in only 12% of analyses. No significant differences in the frequency of the different types of spatial pattern were observed in different brain regions, or in the cerebral cortex between the upper and lower laminae. It was concluded that the spatial patterns of the PrP deposits in the cerebral cortex in vCJD are unlikely to reflect the degeneration of the cortico-cortical pathways as has been reported in sporadic CJD (sCJD). In addition, different factors could be involved in the development of the deposits with and without a condensed core.

The spatial patterns of beta-amyloid deposits and neurofibrillary tangles in the cerebral cortex in Alzheimer's disease

In Alzheimer's disease (AD) brain, beta-amyloid (Abeta) deposits and neurofibrillary tangles (NFT) are not randomly distributed but exhibit a spatial pattern, i.e., a departure from randomness towards regularity or clustering. Studies of the spatial pattern of a lesion may contribute to an understanding of its pathogenesis and therefore, of AD itself. This article describes the statistical methods most commonly used to detect the spatial patterns of brain lesions and the types of spatial patterns exhibited by ß-amyloid deposits and NFT in the cerebral cortex in AD. These studies suggest that within the cerebral cortex, Abeta deposits and NFT exhibit a similar spatial pattern, i.e., an aggregation of individual lesions into clusters which are regularly distributed parallel to the pia mater. The location, size and distribution of these clusters supports the hypothesis that AD is a 'disconnection syndrome' in which degeneration of specific cortical pathways results in the formation of clusters of NFT and Abeta deposits. In addition, a model to explain the development of the pathology within the cerebral cortex is proposed.

Spatial pattern analysis of beta-amyloid (A beta) deposits in Alzheimer disease by linear regression

The spatial patterns of discrete beta-amyloid (Abeta) deposits in brain tissue from patients with Alzheimer disease (AD) were studied using a statistical method based on linear regression, the results being compared with the more conventional variance/mean (V/M) method. Both methods suggested that Abeta deposits occurred in clusters (400 to <12,800 mu m in diameter) in all but 1 of the 42 tissues examined. In many tissues, a regular periodicity of the Abeta deposit clusters parallel to the tissue boundary was observed. In 23 of 42 (55%) tissues, the two methods revealed essentially the same spatial patterns of Abeta deposits; in 15 of 42 (36%), the regression method indicated the presence of clusters at a scale not revealed by the V/M method; and in 4 of 42 (9%), there was no agreement between the two methods. Perceived advantages of the regression method are that there is a greater probability of detecting clustering at multiple scales, the dimension of larger Abeta clusters can be estimated more accurately, and the spacing between the clusters may be estimated. However, both methods may be useful, with the regression method providing greater resolution and the V/M method providing greater simplicity and ease of interpretation. Estimates of the distance between regularly spaced Abeta clusters were in the range 2,200-11,800 mu m, depending on tissue and cluster size. The regular periodicity of Abeta deposit clusters in many tissues would be consistent with their development in relation to clusters of neurons that give rise to specific neuronal projections.

The spatial patterns of beta-amyloid (Abeta) deposits in elderly non-demented patients and patients with Alzheimer’s disease

The spatial patterns of diffuse, primitive, classic and compact beta-amyloid (Abeta) deposits were studied in the medial temporal lobe in 14 elderly, non-demented patients (ND) and in nine patients with Alzheimer’s disease (AD). In both patient groups, Abeta deposits were clustered and in a number of tissues, a regular periodicity of Abeta deposit clusters was observed parallel to the tissue boundary. The primitive deposit clusters were significantly larger in the AD cases but there were no differences in the sizes of the diffuse and classic deposit clusters between patient groups. In AD, the relationship between Abeta deposit cluster size and density in the tissue was non-linear. This suggested that cluster size increased with increasing Abeta deposit density in some tissues while in others, Abeta deposit density was high but contained within smaller clusters. It was concluded that the formation of large clusters of primitive deposits could be a factor in the development of AD.

The usefulness of spatial pattern analysis in understanding the pathogenesis of neurodegenerative disorders, with particular reference to plaque formation in Alzheimer's disease

Discrete, microscopic lesions are developed in the brain in a number of neurodegenerative diseases. These lesions may not be randomly distributed in the tissue but exhibit a spatial pattern, i.e., a departure from randomness towards regularlity or clustering. The spatial pattern of a lesion may reflect its development in relation to other brain lesions or to neuroanatomical structures. Hence, a study of spatial pattern may help to elucidate the pathogenesis of a lesion. A number of statistical methods can be used to study the spatial patterns of brain lesions. They range from simple tests of whether the distribution of a lesion departs from random to more complex methods which can detect clustering and the size, distribution and spacing of clusters. This paper reviews the uses and limitations of these methods as applied to neurodegenerative disorders, and in particular to senile plaque formation in Alzheimer's disease.

The development of collaborative skills in young children

This thesis examines young children's early collaborative development when engaged in joint tasks with both a peer and a parent. It begins by examining how the term "collaborative" has been applied and researched in previous literature. As collaboration is found to usually require dialogue, and intersubjectivity is seen as an important component in the construction of both collaboration and dialogue, the ability to construct intersubjectivity is the subject of the rest of the chapter. The chapter concludes by introducing the research questions that underpin the experiments that follow. A number of experiments are then described. Experiments 1 and 2 investigate age differences in interaction styles and the communication strategies used by similar aged dyads. Experiments 3 and 4 investigate differences due to the age of the child and/or the status of the information giver (either parent or child) in the styles of interaction and the communication strategies used by parent and child dyads. Experiment 5 investigates the benefits of collaborating with a parent, and finally, Experiment 6 examines the collaborative ability of pre-schools. The thesis identifies a series of skills required for successful collaboration. These include recognition of a joint goal and the need to suppress individual desires, the ability to structure joint interaction, moving from role-based to a negotiating style, and communicative skills, for example, asking for clarification. Other reasons for children's failure in collaborative tasks involve task-related skills, such as the development of spatial terms, and failure to recognise the need for accuracy. The findings support Vygotsky's theory that when working with an adult, children perform at a higher level than when working with a peer. Evidence was also found of parents scaffolding the interaction for their children. However, further research is necessary to establish that such scaffolding skills affect the child's development of collaborative interactive skills.

Organised for inward investment? Development agencies, local government, and firms in the inward investment process

Inward investment promotion and aftercare remain central aspects of local economic development for English Regional Development Agencies, Scottish and Welsh development bodies, and local authorities in Britain. In many cases, partnership and consultation mechanisms have become integral to attracting inward investment and providing aftercare. Inward investment is thus an important area in which to explore interinstitutional relations between agents operating along diverse spatial boundaries and with different responsibilities. In this paper we analyse the local and regional institutional structures and relations characterising the inward investment process in Britain using new survey data from local authorities, regional bodies, and inward investors. We find that promotional activities have clearly defined structures which are chiefly led by the regional level. Aftercare is characterised by more collaborative arrangements involving both regional bodies and local government. However, many bodies are little used, with competition and tension between partners remaining frequent within English regions, regardless of recent institutional changes designed to reduce such problems. In Scotland and Wales, however, their national institutions are not only widely used, but they create high levels of satisfaction from firms. Hence, England has yet to respond to the effective challenges of Scotland and Wales. The analysis also highlights the limited importance of all national, regional, and local public institutions in attracting inward investors and their subsequent aftercare. The critical inputs to business decisions appear to be driven chiefly by more general supply-side conditions (for example, general skills versus local public packages) and the general attractions of a particular location.

Spatial-spectral flexible optical networking:enabling switching solutions for a simplified and efficient SDM network platform

The traffic carried by core optical networks grows at a steady but remarkable pace of 30-40% year-over-year. Optical transmissions and networking advancements continue to satisfy the traffic requirements by delivering the content over the network infrastructure in a cost and energy efficient manner. Such core optical networks serve the information traffic demands in a dynamic way, in response to requirements for shifting of traffics demands, both temporally (day/night) and spatially (business district/residential). However as we are approaching fundamental spectral efficiency limits of singlemode fibers, the scientific community is pursuing recently the development of an innovative, all-optical network architecture introducing the spatial degree of freedom when designing/operating future transport networks. Spacedivision- multiplexing through the use of bundled single mode fibers, and/or multi-core fibers and/or few-mode fibers can offer up to 100-fold capacity increase in future optical networks. The EU INSPACE project is working on the development of a complete spatial-spectral flexible optical networking solution, offering the network ultra-high capacity, flexibility and energy efficiency required to meet the challenges of delivering exponentially growing traffic demands in the internet over the next twenty years. In this paper we will present the motivation and main research activities of the INSPACE consortium towards the realization of the overall project solution. © 2014 Copyright SPIE.

A method for enhancing digital information displayed to computer users with visual refractive errors via spatial and spectral processing

This research pursued the conceptualization, implementation, and verification of a system that enhances digital information displayed on an LCD panel to users with visual refractive errors. The target user groups for this system are individuals who have moderate to severe visual aberrations for which conventional means of compensation, such as glasses or contact lenses, does not improve their vision. This research is based on a priori knowledge of the user's visual aberration, as measured by a wavefront analyzer. With this information it is possible to generate images that, when displayed to this user, will counteract his/her visual aberration. The method described in this dissertation advances the development of techniques for providing such compensation by integrating spatial information in the image as a means to eliminate some of the shortcomings inherent in using display devices such as monitors or LCD panels. Additionally, physiological considerations are discussed and integrated into the method for providing said compensation. In order to provide a realistic sense of the performance of the methods described, they were tested by mathematical simulation in software, as well as by using a single-lens high resolution CCD camera that models an aberrated eye, and finally with human subjects having various forms of visual aberrations. Experiments were conducted on these systems and the data collected from these experiments was evaluated using statistical analysis. The experimental results revealed that the pre-compensation method resulted in a statistically significant improvement in vision for all of the systems. Although significant, the improvement was not as large as expected for the human subject tests. Further analysis suggest that even under the controlled conditions employed for testing with human subjects, the characterization of the eye may be changing. This would require real-time monitoring of relevant variables (e.g. pupil diameter) and continuous adjustment in the pre-compensation process to yield maximum viewing enhancement.

Connecting visual and analytic reasoning to improve students' spatial visualization abilities: A constructivist approach

Current reform initiatives recommend that school geometry teaching and learning include the study of three-dimensional geometric objects and provide students with opportunities to use spatial abilities in mathematical tasks. Two ways of using Geometer's Sketchpad (GSP), a dynamic and interactive computer program, in conjunction with manipulatives enable students to investigate and explore geometric concepts, especially when used in a constructivist setting. Research on spatial abilities has focused on visual reasoning to improve visualization skills. This dissertation investigated the hypothesis that connecting visual and analytic reasoning may better improve students' spatial visualization abilities as compared to instruction that makes little or no use of the connection of the two. Data were collected using the Purdue Spatial Visualization Tests (PSVT) administered as a pretest and posttest to a control and two experimental groups. Sixty-four 10th grade students in three geometry classrooms participated in the study during 6 weeks. Research questions were answered using statistical procedures. An analysis of covariance was used for a quantitative analysis, whereas a description of students' visual-analytic processing strategies was presented using qualitative methods. The quantitative results indicated that there were significant differences in gender, but not in the group factor. However, when analyzing a sub sample of 33 participants with pretest scores below the 50th percentile, males in one of the experimental groups significantly benefited from the treatment. A review of previous research also indicated that students with low visualization skills benefited more than those with higher visualization skills. The qualitative results showed that girls were more sophisticated in their visual-analytic processing strategies to solve three-dimensional tasks. It is recommended that the teaching and learning of spatial visualization start in the middle school, prior to students' more rigorous mathematics exposure in high school. A duration longer than 6 weeks for treatments in similar future research studies is also recommended.

Investigation of molecular mechanisms of LKB1 function in Dictyostelium development and stress responses and the function of superoxide dismutase C (SodC) in chemotaxis

The serine/threonine kinase LKB1 is a regulator of critical events including development and stress responses in metazoans. The current study was undertaken to determine the function of LKB1 in Dictyostelium . During multicellular development and in response to stress insult, an apparent increase in the DdLKB1 kinase activity was observed. Depletion of DdLKB1 with a knockdown construct led to aberrant development; a severe reduction in prespore cell differentiation and a precocious induction of prestalk cells, which were reminiscent of cells lacking GSK3, a well known cell-fate switch. Furthermore, DdLKB1 depleted cells displayed lower GSK3 activity than wild type cells in response to cAMP stimulation during development and failed to activate AMPK, a well known LKB1 target in mammals, in response to cAMP and stress insults. These results suggest that DdLKB1 positively regulates both GSK3 and AMPK during Dictyostelium development, and DdLKB1 is necessary for AMPK activation during stress response regulation. No apparent GSK3 activation was observed in response to stress insults. Spatial and temporal regulation of phosphatidylinositol-(3,4,5)-triphosphate (PIP3) along the membrane of polarized cells is important for efficient chemotaxis. A REMI screen for PIP3 suppressors in the absence of stimulation led to the identification of SodC as PIP3 regulator. Consistent with their higher PIP3 levels, sodC− cells showed defects in chemotaxis and exhibited higher intra-cellular superoxide levels. Protein localization studies along with observations from GPI specific PI-PLC treatment of wild-type cells suggested that SodC is a GPI anchored outer-membrane protein. SodC showed superoxide dismutase activity in vitro, and motility defects of sodC− cells can be rescued by expressing the intact SodC but not by the mutant SodC, which has point mutations that affect its dismutase function. Treatment of sodC− cells with LY294002, a pharmacological inhibitor of PI3K, partially rescued the polarization and chemoattractant sensing defects but not motility defects. Consistent with increased intracellular superoxide levels, sodC − cells also exhibited higher basal Ras activity, an upstream regulator of PI3K, which can be suppressed by a cell permeable superoxide scavenger, XTT, indicating that SodC is important in regulation of intracellular superoxide levels thereby regulating the Ras activity and PIP3 levels at the membrane.

A youth vision of the city: The socio-spatial lives and exclusion of street girls in Bogota, Colombia

This dissertation documents the everyday lives and spaces of a population of youth typically constructed as out of place, and the broader urban context in which they are rendered as such. Thirty-three female and transgender street youth participated in the development of this youth-based participatory action research (YPAR) project utilizing geo-ethnographic methods, auto-photography, and archival research throughout a six-phase, eighteen-month research process in Bogotá, Colombia. ^ This dissertation details the participatory writing process that enabled the YPAR research team to destabilize dominant representations of both street girls and urban space and the participatory mapping process that enabled the development of a youth vision of the city through cartographic images. The maps display individual and aggregate spatial data indicating trends within and making comparisons between three subgroups of the research population according to nine spatial variables. These spatial data, coupled with photographic and ethnographic data, substantiate that street girls’ mobilities and activity spaces intersect with and are altered by state-sponsored urban renewal projects and paramilitary-led social cleansing killings, both efforts to clean up Bogotá by purging the city center of deviant populations and places. ^ Advancing an ethical approach to conducting research with excluded populations, this dissertation argues for the enactment of critical field praxis and care ethics within a YPAR framework to incorporate young people as principal research actors rather than merely voices represented in adultist academic discourse. Interjection of considerations of space, gender, and participation into the study of street youth produce new ways of envisioning the city and the role of young people in research. Instead of seeing the city from a panoptic view, Bogotá is revealed through the eyes of street youth who participated in the construction and feminist visualization of a new cartography and counter-map of the city grounded in embodied, situated praxis. This dissertation presents a socially responsible approach to conducting action-research with high-risk youth by documenting how street girls reclaim their right to the city on paper and in practice; through maps of their everyday exclusion in Bogotá followed by activism to fight against it.^

A spatial-temporal analysis of section 404 wetland permitting in Texas and Florida: Thirteen years of impact along the coast

Over the past 200 years, an estimated 53% (about 47 million ha) of the original wetlands in the conterminous United States have been lost, mainly as a result of various human activities. Despite the importance of wetlands (particularly along the coast), and a longstanding federal policy framework meant to protect their integrity, the cumulative impact on these natural systems over large areas is poorly understood. We address this lack of research by mapping and conducting descriptive spatial analyses of federal wetland alteration permits (pursuant to section 404 of the Clean Water Act) across 85 watersheds in Florida and coastal Texas from 1991 to 2003. Results show that more than half of the permits issued in both states (60%) fell under the Nationwide permitting category. Permits issued in Texas were typically located outside of urban areas (78%) and outside 100-year floodplains (61%). More than half of permits issued in Florida were within urban areas (57%) and outside of 100-year floodplains (51%). The most affected wetlands types were estuarine in Texas (47%) and palustrine in Florida (55%). We expect that an additional outcome of this work will be an increased awareness of the cumulative depletion of wetlands and loss of ecological services in these urbanized areas, perhaps leading to increased conservation efforts.

Patterns of phosphorus, nitrogen and δ15N along a peat development gradient in a coastal mire, Panama

Differentiation of limiting nutrients within small spatial scales has been observed in coastal mangrove forests, but research on other tropical peatlands suggests it is a more widespread phenomenon. In the Changuinola mire of coastal Panama, oligotrophy was hypothesized to increase along a gradient of peat development (peat doming). Nutrient and carbon concentration of leaf tissue, soil, and soil porewater were characterised over a successive sequence of plant communities along the gradient. Soil phosphorus (P) and nitrogen (N) concentrations decreased from 1200 μg P g−1 and 27 mg N g−1 to 377 μg P g−1 and 22 mg N g−1 within 2.7 km into the mire interior. These changes coincided with an increase in soil and average leaf N:P molar ratios from 52–128 and 24–41, respectively. Soil P was strongly related to leaf P and soil N:P to foliar N:P. There was a wide range in δ15N values for canopy (4.0 to −9.4‰), Campnosperma panamense (4.0 to −7.8‰) and understorey (4.8 to −3.1‰) species. Foliar δ15N values of canopy species were strongly related to soil N:P, soil P and leaf P. The depleted foliar δ15N values appeared to be an effect of both the N atmospheric source and P limitation. Here, P limitation is likely associated with ombrotrophic conditions that developed as hydrologic inputs became dominated by precipitation.