The pathogenesis of Alzheimer's disease: a reevaluation of the "amyloid cascade hypothesis"

The most influential theory to explain the pathogenesis of Alzheimer's disease (AD) has been the "Amyloid Cascade Hypothesis" (ACH) first formulated in 1992. The ACH proposes that the deposition of ß-amyloid (Aß) is the initial pathological event in AD leading to the formation of senile plaques (SPs) and then to neurofibrillary tangles (NFTs) death of neurons, and ultimately dementia. This paper examines two questions regarding the ACH: (1) is there a relationship between the pathogenesis of SPs and NFTs, and (2) what is the relationship of these lesions to disease pathogenesis? These questions are examined in relation to studies of the morphology and molecular determinants of SPs and NFTs, the effects of gene mutation, degeneration induced by head injury, the effects of experimentally induced brain lesions, transgenic studies, and the degeneration of anatomical pathways. It was concluded that SPs and NFTs develop independently and may be the products rather than the causes of neurodegeneration in AD. A modification to the ACH is proposed which may better explain the pathogenesis of AD, especially of late-onset cases of the disease.

A reevaluation of achromatic spatio-temporal vision: nonoriented filters are monocular, they adapt, and can be used for decision making at high flicker speeds

Masking, adaptation, and summation paradigms have been used to investigate the characteristics of early spatio-temporal vision. Each has been taken to provide evidence for (i) oriented and (ii) nonoriented spatial-filtering mechanisms. However, subsequent findings suggest that the evidence for nonoriented mechanisms has been misinterpreted: those experiments might have revealed the characteristics of suppression (eg, gain control), not excitation, or merely the isotropic subunits of the oriented detecting mechanisms. To shed light on this, we used all three paradigms to focus on the ‘high-speed’ corner of spatio-temporal vision (low spatial frequency, high temporal frequency), where cross-oriented achromatic effects are greatest. We used flickering Gabor patches as targets and a 2IFC procedure for monocular, binocular, and dichoptic stimulus presentations. To account for our results, we devised a simple model involving an isotropic monocular filter-stage feeding orientation-tuned binocular filters. Both filter stages are adaptable, and their outputs are available to the decision stage following nonlinear contrast transduction. However, the monocular isotropic filters (i) adapt only to high-speed stimuli—consistent with a magnocellular subcortical substrate—and (ii) benefit decision making only for high-speed stimuli (ie, isotropic monocular outputs are available only for high-speed stimuli). According to this model, the visual processes revealed by masking, adaptation, and summation are related but not identical.

Beyond all reason:spaces of hope in the struggle for England’s universities

This essay examines how academics and students in England have been primed to comply with a political agenda of “deep” neoliberalization through cumulative processes of institutional and subjective undermining and considers what might be an appropriate logic of critical response. It first describes how the embedding of principles and mechanisms of market governance within academic life has depoliticized methods for critically theorizing and collectively resisting these processes and then explores the work of recent student-led opposition to the British government’s new policies, teasing out some theoretical implications of the logic of occupation being cultivated there. It suggests that by fusing a determination for autonomy with a transgressive cultivation of new forms of thinking and social practice, the occupations illustrate new critical-experimental work in the politics of possibility. The underlying logic thus offers some resources for reimagining modalities of resistance to processes of deep neoliberalization; however, becoming receptive to them may also require a critique of professional academic subjectivities and reevaluation of attachments to existing forms of the university itself.

State-of-the-art of ‘Lean’ in the aviation maintenance, repair, and overhaul industry

The increasing need for maintenance, repair, and overhaul (MRO) organizations to meet customers' demands in quality and reduced lead times is key to its survival within the aviation industry. Furthermore, with the unpredictability in the global market and difficulties with forecasting characteristic of the MRO industry there is an increased need for the reevaluation of the operation models of organizations within this sector. However, severe economic turmoil and ever-increasing global competition introduce the opportunity for the adoption of a resilient, tried, and tested business operation model such as 'Lean'. In order to understand this concept, its long-term viability, and its application within the aerospace MRO sector fully, this paper presents the state-of-the-art in terms of the adoption of Lean within the MRO industry by carrying out a systematic review of the literature. This paper establishes the common perception of Lean by the MRO industry and the measurable progress that has been made on the subject. Some issues and challenges are also highlighted including the misconceptions that arise from the direct transference of the perception of Lean from other industrial sectors into the aerospace MRO industry. The 'enablers and inhibitors' of Lean within the aviation industry are also discussed. This paper exposes the scarcity of the literature and the general lagging behind of the industry to the adoption of the Lean paradigm and thus highlights areas where further research is required. © 2011 Authors.