Neuropathological heterogeneity in Alzheimer's disease:A study of 80 cases using principal components analysis

Three hypotheses have been proposed to explain neuropathological heterogeneity in Alzheimer's disease (AD): the presence of distinct subtypes ('subtype hypothesis'), variation in the stage of the disease ('phase hypothesis') and variation in the origin and progression of the disease ('compensation hypothesis'). To test these hypotheses, variation in the distribution and severity of senile plaques (SP) and neurofibrillary tangles (NFT) was studied in 80 cases of AD using principal components analysis (PCA). Principal components analysis using the cases as variables (Q-type analysis) suggested that individual differences between patients were continuously distributed rather than the cases being clustered into distinct subtypes. In addition, PCA using the abundances of SP and NFT as variables (R-type analysis) suggested that variations in the presence and abundance of lesions in the frontal and occipital lobes, the cingulate gyrus and the posterior parahippocampal gyrus were the most important sources of heterogeneity consistent with the presence of different stages of the disease. In addition, in a subgroup of patients, individual differences were related to apolipoprotein E (ApoE) genotype, the presence and severity of SP in the frontal and occipital cortex being significantly increased in patients expressing apolipoprotein (Apo)E allele ε4. It was concluded that some of the neuropathological heterogeneity in our AD cases may be consistent with the 'phase hypothesis'. A major factor determining this variation in late-onset cases was ApoE genotype with accelerated rates of spread of the pathology in patients expressing allele ε4.

What does endogenous growth theory tell about regional economies? Empirics of R&D worker-based productivity growth

What does endogenous growth theory tell about regional economies? Empirics of R&D worker-based productivity growth, Regional Studies. Endogenous growth theory emerged in the 1990s as ‘new growth theory’ accounting for technical progress in the growth process. This paper examines the role of research and development (R&D) workers underlying the Romer model (1990) and its subsequent modifications, and compares it with a model based on the accumulation of human capital engaged in R&D. Cross-section estimates of the models against productivity growth of European regions in the 1990s suggest that each R&D worker has a unique set of knowledge while his/her contributions are enhanced by knowledge sharing within a region as well as spillovers from other regions in proximity.

Languaging the worker:globalized governmentalities in/of language in peripheral spaces

In the introduction to the special issue “Languaging the worker: globalized governmentalities in/of language in peripheral spaces”, we take up the notion of governmentality as a means to interrogate the complex relationship between language, labor, power and subjectivity in peripheral multilingual spaces. Our aim here is to argue for the study of governmentality as a viable and growing approach in critical sociolinguistic research. As such, in this introduction, we first discuss key concepts germane to our interrogations, including the notions of governmentality, languaging, peripherality and language worker. We proceed to map out five ethnographically and discourse-analytically informed case studies. These examine diverse actors in different settings pertaining to the domain of work. Finally we chart how the case studies construe the issue of languaging the worker through a governmentality frame.

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.

Neuropathological heterogeneity in frontotemporal lobar degeneration with TDP-43 proteinopathy: a quantitative study of 94 cases using principal components analysis

Studies suggest that frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy (FTLD-TDP) is heterogeneous with division into four or five subtypes. To determine the degree of heterogeneity and the validity of the subtypes, we studied neuropathological variation within the frontal and temporal lobes of 94 cases of FTLD-TDP using quantitative estimates of density and principal components analysis (PCA). A PCA based on the density of TDP-43 immunoreactive neuronal cytoplasmic inclusions (NCI), oligodendroglial inclusions (GI), neuronal intranuclear inclusions (NII), and dystrophic neurites (DN), surviving neurons, enlarged neurons (EN), and vacuolation suggested that cases were not segregated into distinct subtypes. Variation in the density of the vacuoles was the greatest source of variation between cases. A PCA based on TDP-43 pathology alone suggested that cases of FTLD-TDP with progranulin (GRN) mutation segregated to some degree. The pathological phenotype of all four subtypes overlapped but subtypes 1 and 4 were the most distinctive. Cases with coexisting motor neuron disease (MND) or hippocampal sclerosis (HS) also appeared to segregate to some extent. We suggest: 1) pathological variation in FTLD-TDP is best described as a ‘continuum’ without clearly distinct subtypes, 2) vacuolation was the single greatest source of variation and reflects the ‘stage’ of the disease, and 3) within the FTLD-TDP ‘continuum’ cases with GRN mutation and with coexisting MND or HS may have a more distinctive pathology.

Using empirical evidence of variations in worker performance to extend the capabilities of discrete event simulations in manufacturing

Discrete event simulation of manufacturing systems has become widely accepted as an important tool to aid the design of such systems. Often, however, it is applied by practitioners in a manner which largely ignores an important element of industry; namely, the workforce. Workers are usually represented as simple resources, often with deterministic performance values. This approach ignores the potentially large effect that human performance variation can have on a system. A long-term data collection exercise is described with the aim of quantifying the performance variation of workers in a typical automotive assembly plant. The data are presented in a histogram form which is immediately usable in simulations to improve the accuracy of design assessment. The results show levels of skewness and range which are far larger than anticipated by current researchers and practitioners in the field.

Productivity in China's high technology industry:regional heterogeneity and R&D

This paper analyzes the impact of Research and Development (R&D) on the productivity of China's high technology industry. In order to capture important differences in the effect of R&D on output that arise from geographic and socioeconomic differences across three major regions in China, we use a novel semiparametric approach that allows us to model heterogeneities across provinces and time. Using a unique provincial level panel dataset spanning the period 2000–2007, we find that the impact of R&D on output varies substantially in terms of magnitude and significance across different regions. Results show that the eastern region benefits the most from R&D investments, however it benefits the least from technical progress, while the western region benefits the least from R&D investments, but enjoys the highest benefits from technical progress. The central region benefits from R&D investments more than the western region and benefits from technical progress more than the eastern region. Our results suggest that R&D investments would significantly increase output in both the eastern and central regions, however technical progress in the central region may further compound the effects of R&D on output within the region.

Overcoming schema heterogeneity between linked semantic repositories to improve coreference resolution

Schema heterogeneity issues often represent an obstacle for discovering coreference links between individuals in semantic data repositories. In this paper we present an approach, which performs ontology schema matching in order to improve instance coreference resolution performance. A novel feature of the approach is its use of existing instance-level coreference links defined in third-party repositories as background knowledge for schema matching techniques. In our tests of this approach we obtained encouraging results, in particular, a substantial increase in recall in comparison with existing sets of coreference links.