Quantification of pathological lesions in the frontal and temporal lobe of ten patients diagnosed with Pick's disease

The densities of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) in the frontal and temporal lobe were determined in ten patients diagnosed with Pick's disease (PD). The density of PB was significantly higher in the dentate gyrus granule cells compared with the cortex and the CA sectors of the hippocampus. Within the hippocampus, the highest densities of PB were observed in sector CA1. PC were absent in the dentate gyrus and no significant differences in PC density were observed in the remaining brain regions. With the exception of two patients, the densities of SP and NFT were low with no significant differences in mean densities between cortical regions. In the hippocampus, the density of NFT was greatest in sector CA1. PB and PC densities were positively correlated in the frontal cortex but no correlations were observed between the PD and AD lesions. A principal components analysis (PCA) of the neuropathological variables suggested that variations in the densities of SP in the frontal cortex, temporal cortex and hippocampus were the most important sources of heterogeneity within the patient group. Variations in the densities of PB and NFT in the temporal cortex and hippocampus were of secondary importance. In addition, the PCA suggested that two of the ten patients were atypical. One patient had a higher than average density of SP and one familial patient had a higher density of NFT but few SP.

Is neuropathological heterogeneity in Alzheimer’s disease related to apolipoprotein genotype?

The abundance of senile plaques (SP) and neurofibrillary tangles (NFT) was studied in cortical and subcortical regions from 30 patients with Alzheimer’s disease (AD) expressing different apolipoprotein E (apoE) genotypes. Principal components analysis (PCA) was used to identify the most important neuropathological variations between individual patients and to determine whether these variations were related to apoE genotype. The first two principal components (PC) accounted for 60% and 40% of the total variance of the SP and NFT data respectively. The abundance of SP in the frontal and occipital cortex and NFT in the frontal cortex, amygdala and substantia nigra were positively correlated with the first principal component (PC1). Analysis of the SP data revealed that the apoE score of the patient (the sum of the two alleles) was positively correlated with PC1 while analysis of the NFT data revealed no significant correlations between apoE score and the PC. The data suggest that apoE genotype was more closely related to variations in the distribution and abundance of SP than of NFT. In addition, a more rapid spread of SP into the frontal and occipital cortex may occur in patients with a high apoE score.

Relationships between morphological types of plaque in Alzheimer’s disease as revealed in silver and immunostained preparations

The objective of this study was to determine the possible relationships between the morphological types of plaque revealed in silver and immunostained sections of Alzheimer’s disease (AD) tissue. The density of cored and uncored senile plaques in Glees and Marsland preparations, and of diffuse, primitive, classic and compact beta/A4 deposits in immunostained preparations were estimated. A principal components analysis (PCA) of the data suggested that three uncorrelated principal components accounted for 80% of the variation in lesion density in the tissues. This suggested that thee processes lead independently to the formation of: (1) the uncored Glees plaques; (2) the primitive beta/A4 deposits and most of the classic beta/A4 deposits and (3) the compact beta/A4 deposits and the remaining classic deposits. Hence, the uncored plaques revealed by the Glees stain and the primitive beta/A4 deposits represented distinct plaque populations. In addition, the classic beta/A4 deposits did not appear to represent a uniform plaque population but to originate from at least two pathological processes. The uncored Glees plaques appeared to the only plaque population closely related to the diffuse beta/A4 deposits.

Exploratory database visualisation: the application and assessment of data and dimensionality reduction

This thesis describes the development of a complete data visualisation system for large tabular databases, such as those commonly found in a business environment. A state-of-the-art 'cyberspace cell' data visualisation technique was investigated and a powerful visualisation system using it was implemented. Although allowing databases to be explored and conclusions drawn, it had several drawbacks, the majority of which were due to the three-dimensional nature of the visualisation. A novel two-dimensional generic visualisation system, known as MADEN, was then developed and implemented, based upon a 2-D matrix of 'density plots'. MADEN allows an entire high-dimensional database to be visualised in one window, while permitting close analysis in 'enlargement' windows. Selections of records can be made and examined, and dependencies between fields can be investigated in detail. MADEN was used as a tool for investigating and assessing many data processing algorithms, firstly data-reducing (clustering) methods, then dimensionality-reducing techniques. These included a new 'directed' form of principal components analysis, several novel applications of artificial neural networks, and discriminant analysis techniques which illustrated how groups within a database can be separated. To illustrate the power of the system, MADEN was used to explore customer databases from two financial institutions, resulting in a number of discoveries which would be of interest to a marketing manager. Finally, the database of results from the 1992 UK Research Assessment Exercise was analysed. Using MADEN allowed both universities and disciplines to be graphically compared, and supplied some startling revelations, including empirical evidence of the 'Oxbridge factor'.

Addressing missing data in geochemistry: a non-linear approach

Exploratory analysis of petroleum geochemical data seeks to find common patterns to help distinguish between different source rocks, oils and gases, and to explain their source, maturity and any intra-reservoir alteration. However, at the outset, one is typically faced with (a) a large matrix of samples, each with a range of molecular and isotopic properties, (b) a spatially and temporally unrepresentative sampling pattern, (c) noisy data and (d) often, a large number of missing values. This inhibits analysis using conventional statistical methods. Typically, visualisation methods like principal components analysis are used, but these methods are not easily able to deal with missing data nor can they capture non-linear structure in the data. One approach to discovering complex, non-linear structure in the data is through the use of linked plots, or brushing, while ignoring the missing data. In this paper we introduce a complementary approach based on a non-linear probabilistic model. Generative topographic mapping enables the visualisation of the effects of very many variables on a single plot, while also dealing with missing data. We show how using generative topographic mapping also provides an optimal method with which to replace missing values in two geochemical datasets, particularly where a large proportion of the data is missing.

TDP-43-Immunoreactive pathology in frontotemporal lobar degeneration with TDP proteinopathy (FTLD-TDP) with and without associated motor neuron disease

A proportion of patients with motor neuron disease (MND) exhibit frontotemporal dementia (FTD) and some patients with FTD develop the clinical features of MND. Frontotemporal lobar degeneration (FTLD) is the pathological substrate of FTD and some forms of this disease (referred to as FTLD-U) share with MND the common feature of ubiquitin-immunoreactive, tau-negative cellular inclusions in the cerebral cortex and hippocampus. Recently, the transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) has been found to be a major protein of the inclusions of FTLD-U with or without MND and these cases are referred to as FTLD with TDP-43 proteinopathy (FTLD-TDP). To clarify the relationship between MND and FTLD-TDP, TDP-43 pathology was studied in nine cases of FTLD-MND and compared with cases of familial and sporadic FTLD–TDP without associated MND. A principal components analysis (PCA) of the nine FTLD-MND cases suggested that variations in the density of surviving neurons in the frontal cortex and neuronal cytoplasmic inclusions (NCI) in the dentate gyrus (DG) were the major histological differences between cases. The density of surviving neurons in FTLD-MND was significantly less than in FTLD-TDP cases without MND, and there were greater densities of NCI but fewer neuronal intranuclear inclusions (NII) in some brain regions in FTLD-MND. A PCA of all FTLD-TDP cases, based on TDP-43 pathology alone, suggested that neuropathological heterogeneity was essentially continuously distributed. The FTLD-MND cases exhibited consistently high loadings on PC2 and overlapped with subtypes 2 and 3 of FTLD-TDP. The data suggest: (1) FTLD-MND cases have a consistent pathology, variations in the density of NCI in the DG being the major TDP-43-immunoreactive difference between cases, (2) there are considerable similarities in the neuropathology of FTLD-TDP with and without MND, but with greater neuronal loss in FTLD-MND, and (3) FTLD-MND cases are part of the FTLD-TDP ‘continuum’ overlapping with FTLD-TDP disease subtypes 2 and 3.

A quantitative study of α-synuclein pathology in fifteen cases of dementia associated with Parkinson disease

The α-synuclein-immunoreactive pathology of dementia associated with Parkinson disease (DPD) comprises Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG). The densities of LB, LN, LG together with vacuoles, neurons, abnormally enlarged neurons (EN), and glial cell nuclei were measured in fifteen cases of DPD. Densities of LN and LG were up to 19 and 70 times those of LB, respectively, depending on region. Densities were significantly greater in amygdala, entorhinal cortex (EC), and sectors CA2/CA3 of the hippocampus, whereas middle frontal gyrus, sector CA1, and dentate gyrus were least affected. Low densities of vacuoles and EN were recorded in most regions. There were differences in the numerical density of neurons between regions, but no statistical difference between patients and controls. In the cortex, the density of LB and vacuoles was similar in upper and lower laminae, while the densities of LN and LG were greater in upper cortex. The densities of LB, LN, and LG were positively correlated. Principal components analysis suggested that DPD cases were heterogeneous with pathology primarily affecting either hippocampus or cortex. The data suggest in DPD: (1) ratio of LN and LG to LB varies between regions, (2) low densities of vacuoles and EN are present in most brain regions, (3) degeneration occurs across cortical laminae, upper laminae being particularly affected, (4) LB, LN and LG may represent degeneration of the same neurons, and (5) disease heterogeneity may result from variation in anatomical pathway affected by cell-to-cell transfer of α-synuclein. © 2013 Springer-Verlag Wien.

Properties of intention:component structure and consequences for behavior, information processing and resistance

Three studies tested the impact of properties of behavioral intention on intention-behavior consistency, information processing, and resistance. Principal components analysis showed that properties of intention formed distinct factors. Study 1 demonstrated that temporal stability, but not the other intention attributes, moderated intention-behavior consistency. Study 2 found that greater stability of intention was associated with improved memory performance. In Study 3, participants were confronted with a rating scale manipulation designed to alter their intention scores. Findings showed that stable intentions were able to withstand attack. Overall, the present research findings suggest that different properties of intention are not simply manifestations of a single underlying construct ("intention strength"), and that temporal stability exhibits superior resistance and impact compared to other intention attributes. © 2013 Wiley Periodicals, Inc.

Singapore's online retail deviants:analyzing the rise of blogshops' power

Geography, retailing, and power are institutionally bound up together. Within these, the authors situate their research in Clegg's work on power. Online shopping offers a growing challenge to the apparent hegemony of traditional physical retail stores' format. While novel e-formats appear regularly, blogshops in Singapore are enjoying astonishing success that has taken the large retailers by surprise. Even though there are well-developed theoretical frameworks for understanding the role of institutional entrepreneurs and other major stakeholders in bringing about change and innovation, much less attention has been paid to the role of unorganized, nonstrategic actors-such as blogshops-in catalyzing retail change. The authors explore how blogshops are perceived by consumers and how they challenge the power of other shopping formats. They use Principal Components Analysis to analyze results from a survey of 349 blogshops users. While the results show that blogshops stay true to traditional online shopping attributes, deviations occur on the concept of value. Furthermore, consumer power is counter intuitively found to be strongly present in the areas related to cultural ties, excitement, and search for individualist novelty (as opposed to mass-production), thereby encouraging researchers to think critically about emerging power behavior in media practices.

Comparative quantitative study of ‘signature’ pathological lesions in the hippocampus and adjacent gyri of 12 neurodegenerative disorders

The hippocampus (HC) and adjacent gyri are implicated in dementia in several neurodegenerative disorders. To compare HC pathology among disorders, densities of ‘signature’ pathological lesions were measured at a standard location in eight brain regions of 12 disorders. Principal components analysis of the data suggested that the disorders could be divided into three groups: (1) Alzheimer’s disease (AD), Down’s syndrome (DS), sporadic Creutzfeldt–Jakob disease, and variant Creutzfeldt–Jakob disease in which either β-amyloid (Aβ) or prion protein deposits were distributed in all sectors of the HC and adjacent gyri, with high densities being recorded in the parahippocampal gyrus and subiculum; (2) Pick’s disease, sporadic frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions, and neuronal intermediate filament inclusion disease in which relatively high densities of neuronal cytoplasmic inclusions were present in the dentate gyrus (DG) granule cells; and (3) Parkinson’s disease dementia, dementia with Lewy bodies, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy in which densities of signature lesions were relatively low. Variation in density of signature lesions in DG granule cells and CA1 were the most important sources of neuropathological variation among disorders. Hence, HC and adjacent gyri are differentially affected in dementia reflecting either variation in vulnerability of hippocampal neurons to specific molecular pathologies or in the spread of pathological proteins to the HC. Information regarding the distribution of pathology could ultimately help to explain variations in different cognitive domains, such as memory, observed in various disorders.

Quantitative pathological changes in the cerebellum of multiple system atrophy

Multiple system atrophy (MSA) is a rare neurodegenerative disorder associated with parkinsonism, ataxia, and autonomic dysfunction. Its pathology is primarily subcortical comprising vacuolation, neuronal loss, gliosis, and α-synuclein-immunoreactive glial cytoplasmic inclusions (GO). To quantify cerebellar pathology in MSA, the density and spatial pattern of the pathological changes were studied in α-synuclein-immunolabelled sections of the cerebellar hemisphere in 10 MSA and 10 control cases. In MSA, densities of Purkinje cells (PC) were decreased and vacuoles in the granule cell layer (GL) increased compared with controls. In six MSA cases, GCI were present in cerebellar white matter. In the molecular layer (ML) and GL of MSA, vacuoles were clustered, the clusters exhibiting a regular distribution parallel to the edge of the folia. Purkinje cells were randomly or regularly distributed with large gaps between surviving cells. Densities of glial cells and surviving neurons in the ML and surviving cells and vacuoles in the GL were negatively correlated consistent with gliosis and vacuolation in response to neuronal loss. Principal components analysis (PCA) suggested vacuole densities in the ML and vacuole density and cell losses in the GL were the main source of neuropathological variation among cases. The data suggest that: (1) cell losses and vacuolation of the GCL and loss of PC were the most significant pathological changes in the cases studied, (2) pathological changes were topographically distributed, and (3) cerebellar pathology could influence cerebral function in MSA via the cerebello-dentato-thalamic tract.

TDP-43-immunoreactive pathology in frontotemporal lobar degeneration with TDP proteinopathy (FTLD-TDP) with and without associated motor neuron disease (MND)

A proportion of patients with motor neuron disease (MND) exhibit frontotemporal dementia (FTD) and some patients with FTD develop the clinical features of MND. Frontotemporal lobar degeneration (FTLD) is the pathological substrate of FTD and some forms of this disease (referred to as FTLD-U) share with MND the common feature of ubiquitin-immunoreactive, tau-negative cellular inclusions in the cerebral cortex and hippocampus. Recently, the transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) has been found to be a major protein of the inclusions of FTLD-U with or without MND and these cases are referred to as FTLD with TDP-43 proteinopathy (FTLD-TDP). To clarify the relationship between MND and FTLD-TDP, TDP-43 pathology was studied in nine cases of FTLD-MND and compared with cases of familial and sporadic FTLD-TDP without associated MND. A principal components analysis (PCA) of the nine FTLD-MND cases suggested that variations in the density of surviving neurons in the frontal cortex and neuronal cytoplasmic inclusions (NCI) in the dentate gyrus (DG) were the major histological differences between cases. The density of surviving neurons in FTLD-MND was significantly less than in FTLD-TDP cases without MND, and there were greater densities of NCI but fewer neuronal intranuclear inclusions (NII) in some brain regions in FTLD-MND. A PCA of all FTLD-TDP cases, based on TDP-43 pathology alone, suggested that neuropathological heterogeneity was essentially continuously distributed. The FTLD-MND cases exhibited consistently high loadings on PC2 and overlapped with subtypes 2 and 3 of FTLD-TDP. The data suggest: (1) FTLD-MND cases have a consistent pathology, variations in the density of NCI in the DG being the major TDP-43-immunoreactive difference between cases, (2) there are considerable similarities in the neuropathology of FTLD-TDP with and without MND, but with greater neuronal loss in FTLD-MND, and (3) FTLD-MND cases are part of the FTLD-TDP 'continuum' overlapping with FTLD-TDP disease subtypes 2 and 3. © 2012 Nova Science Publishers, Inc. All rights reserved.

A quantitative study of tau pathology in eleven cases of chronic traumatic encephalopathy

AIMS: To quantify tau pathology of chronic traumatic encephalopathy (CTE) and investigate influence of dot-like lesions (DL), brain region, co-morbidity, and sporting career length. METHODS: Densities of neurofibrillary tangles (NFT), astrocytic tangles (AT), DL, oligodendroglial inclusions (GI), neuropil threads (NT), vacuoles, neurons, and enlarged neurons (EN) were measured in tau-immunoreactive sections of upper cortical laminae of frontal and temporal lobe, hippocampus (HC), amygdala, and substantia nigra (SN) of eleven cases of CTE. RESULTS: DL were a consistent finding in CTE. Densities of NFT, NT and DL were greatest in sectors CA1 and CA2 of the HC. Densities of AT were lower than NFT, small numbers of GI were recorded in temporal lobe, and low densities of vacuoles and EN were consistently present. β-amyloid containing neuritic plaques (NP) also occurred at low density. Densities of NFT, NT, DL, and AT were greater in sulci than gyri while vacuole density was greater in gyri. Principal components analysis (PCA) suggested that sporting career length and densities of NFT in entorhinal cortex, NT in CA2 and SN, and vacuolation in the DG were significant sources of variation among cases. CONCLUSION: DL are frequent in CTE suggesting affinity with argyrophilic grain disease (AGD) and Parkinson's disease dementia (PD-Dem). Densities of AT in all regions and NT/DL in sectors CA2/4 were consistent features of CTE. The eleven cases are neuropathologically heterogeneous which may result from genetic diversity, and variation in anatomical pathways subjected to trauma. This article is protected by copyright. All rights reserved.

Forecasting Responses of Seagrass Distributions to Changing Water Quality Using Monitoring Data

Extensive data sets on water quality and seagrass distributions in Florida Bay have been assembled under complementary, but independent, monitoring programs. This paper presents the landscape-scale results from these monitoring programs and outlines a method for exploring the relationships between two such data sets. Seagrass species occurrence and abundance data were used to define eight benthic habitat classes from 677 sampling locations in Florida Bay. Water quality data from 28 monitoring stations spread across the Bay were used to construct a discriminant function model that assigned a probability of a given benthic habitat class occurring for a given combination of water quality variables. Mean salinity, salinity variability, the amount of light reaching the benthos, sediment depth, and mean nutrient concentrations were important predictor variables in the discriminant function model. Using a cross-validated classification scheme, this discriminant function identified the most likely benthic habitat type as the actual habitat type in most cases. The model predicted that the distribution of benthic habitat types in Florida Bay would likely change if water quality and water delivery were changed by human engineering of freshwater discharge from the Everglades. Specifically, an increase in the seasonal delivery of freshwater to Florida Bay should cause an expansion of seagrass beds dominated by Ruppia maritima and Halodule wrightii at the expense of the Thalassia testudinum-dominated community that now occurs in northeast Florida Bay. These statistical techniques should prove useful for predicting landscape-scale changes in community composition in diverse systems where communities are in quasi-equilibrium with environmental drivers.

Adult Curiosity Dimensionality

The need to discern the dimensions of curiosity is compelling as researchers strive to understand better the developmental implications of learning. Six hundred and two participants completed 10 curiosity scales. Scores were factored using Principal Components Analysis and a varimax solution. A threefactor interpretation of the curiosity construct was supported.