A comparison of beta-amyloid deposition in the medial temporal lobe in sporadic Alzheimer's disease, Down's syndrome and normal elderly brains

The density of beta-amyloid (A beta) deposits was studied in the medial temporal lobe in non-demented individuals and in sporadic Alzheimer's disease (SAD) and Down's syndrome (DS). No A beta deposits were recorded in six of the non-demented cases, while in a further eight cases, these were confined to either the lateral occipitotemporal or parahippocampal gyrus. The mean density of A beta deposits in the cortex was greater in SAD and DS than in non-demented cases but with overlap between patient groups. The mean density of A beta deposits was greater in DS than SAD consistent with a gene dosage effect. The ratio of primitive to diffuse A beta deposits was greater in DS and in non-demented cases than in SAD and the ratio of classic to diffuse deposits was lowest in DS. In all groups, A beta deposits occurred in clusters which were often regularly distributed. In the cortex, the dimension of the A beta clusters was greater in SAD than in the non-demented cases and DS. The data suggest that the development of A beta pathology in the hippocampus could be a factor in the development of DS and SAD. Furthermore, the high density of A beta deposits, and in particular the high proportion of primitive type deposits, may be important in DS while the development of large clusters of A beta deposits may be a factor in SAD.

Separate influences of acoustic AM and FM sensitivity on the phonological decoding skills of impaired and normal readers

Developmental dyslexia is associated with deficits in the processing of basic auditory stimuli. Yet it is unclear how these sensory impairments might contribute to poor reading skills. This study better characterizes the relationship between phonological decoding skills, the lack of which is generally accepted to comprise the core deficit in reading disabilities, and auditory sensitivity to amplitude modulation (AM) and frequency modulation (FM). Thirty-eight adult subjects, 17 of whom had a history of developmental dyslexia, completed a battery, of psychophysical measures of sensitivity to FM and AM at different modulation rates, along with a measure of pseudoword reading accuracy and standardized assessments of literacy and cognitive skills. The subjects with a history of dyslexia were significantly less sensitive than controls to 2-Hz FM and 20-Hz AM only. The absence of a significant group difference for 2-Hz AM shows that the dyslexics do not have a general deficit in detecting all slow modulations. Thresholds for detecting 2-Hz and 240-Hz FM and 20-Hz AM correlated significantly with pseudoword reading accuracy. After accounting for various cognitive skills, however, multiple regression analyses showed that detection thresholds for both 2-Hz FM and 20-Hz AM were significant and independent predictors of pseudoword reading ability in the entire sample. Thresholds for 2-Hz AM and 240-Hz FM did not explain significant additional variance in pseudoword reading skill, it is therefore possible that certain components of auditory processing of modulations are related to phonological decoding skills, whereas others are not.

Long-term statin therapy in patients with systolic heart failure and normal cholesterol:effects on elevated serum markers of collagen turnover, inflammation, and B-type natriuretic peptide

BACKGROUND: The role of statin therapy in heart failure (HF) is unclear. The amino-terminal propeptide of procollagen type III (PIIINP) predicts outcome in HF, and yet there are conflicting reports of statin therapy effects on PIIINP.

OBJECTIVES: This study determined whether there was an increase in serum markers of inflammation, fibrosis (including PIIINP), and B-type natriuretic peptide (BNP) in patients with systolic HF and normal total cholesterol and determined the effects of long-term treatment with atorvastatin on these markers.

METHODS: Fifty-six white patients with systolic HF and normal cholesterol levels (age 72 [13] years; 68% male; body mass index 27.0 [7.3] kg/m(2); ejection fraction 35 [13]%; 46% with history of smoking) were randomly allocated to atorvastatin treatment for 6 months, titrated to 40 mg/d (A group) or not (C group). Age- and/or sex-matched subjects without HF (N group) were also recruited. Biomarkers were measured at baseline (all groups) and 6 months (A and C groups).

RESULTS: Serum markers of collagen turnover, inflammation, and BNP were significantly elevated in HF patients compared with normal participants (all P < 0.05). There were correlations between these markers in HF patients but not in normal subjects. Atorvastatin treatment for 6 months caused a significant reduction in the following biomarkers compared with baseline: BNP, from median (interquartile range) 268 (190-441) pg/mL to 185 (144-344) pg/mL; high-sensitivity C-reactive protein (hs-CRP), from 5.26 (1.95 -9.29) mg/L to 3.70 (2.34-6.81) mg/L; and PIIINP, from 4.65 (1.86) to 4.09 (1.25) pg/mL (all P < 0.05 baseline vs 6 months). Between-group differences were significant for PIIINP only (P = 0.027). There was a positive interaction between atorvastatin effects and baseline hs-CRP and PIIINP (P < 0.01).

CONCLUSIONS: Long-term statin therapy reduced PIIINP in this small, selected HF population with elevated baseline levels. Further evaluation of statin therapy in the management of HF patients with elevated PIIINP is warranted.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Iowa Construction and Maintenance Traffic Control Handbook, 1976

This Handbook has been prepared by the Iowa DOT as a guide and supplement to the MUTCD. It provides in one document a large number of illustrations which can be easily adapted to specific conditions by field personnel. It is intended to supersede all previous non-conforming standards now being used throughout the state and to provide uniform guidelines for all agencies, public and private, who must conduct construction and maintenance activities on the streets and highways of the state. The illustrations contained herein serve as a quick reference for field personnel to follow, however, no amount of detailed instructions can adequately cover every situation. For this reason, sound judgment is required in using these illustrations to cover actual field conditions.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Equilibrium Assignments in Competitive and Cooperative Traffic Flow Routing

Part 18: Optimization in Collaborative Networks

Retail centers for community : addressing both pedestrian and car traffic

The purpose of this thesis was to redesign a commercial center in Miami, Florida in a manner that incorporates the needs of pedestrians as well as the automobile. In my research, I studied projects that had been successful at integrating cars in retail design. I applied the strategies learned from this research to the design of a center that creates a positive interaction of pedestrian and car traffic, addressing the needs of the surrounding community. I designed a master plan that includes a mix of residential, retail, commercial and parking space. The parking is designed so that the retail center is not dominated by surface parking. Rather, the automobile is introduced into the different layers of the proposed buildings. The design focused on connecting pedestrian plazas and parking areas beneath them through the introduction of light and greenery. The findings show how a shopping center might transform the area around it by including spaces for residential, civic, cultural and social functions, as well as for the automotive infrastructure that make those functions possible.

Dendritic Cells for Anomaly Detection

Artificial immune systems, more specifically the negative selection algorithm, have previously been applied to intrusion detection. The aim of this research is to develop an intrusion detection system based on a novel concept in immunology, the Danger Theory. Dendritic Cells (DCs) are antigen presenting cells and key to the activation of the human immune system. DCs perform the vital role of combining signals from the host tissue and correlate these signals with proteins known as antigens. In algorithmic terms, individual DCs perform multi-sensor data fusion based on time-windows. The whole population of DCs asynchronously correlates the fused signals with a secondary data stream. The behaviour of human DCs is abstracted to form the DC Algorithm (DCA), which is implemented using an immune inspired framework, libtissue. This system is used to detect context switching for a basic machine learning dataset and to detect outgoing portscans in real-time. Experimental results show a significant difference between an outgoing portscan and normal traffic.

Sunglasses, traffic signals, and color vision deficiencies

Purpose: To determine (a) the effect of different sunglass tint colorations on traffic signal detection and recognition for color normal and color deficient observers, and (b) the adequacy of coloration requirements in current sunglass standards. Methods: Twenty color-normals and 49 color-deficient males performed a tracking task while wearing sunglasses of different colorations (clear, gray, green, yellow-green, yellow-brown, red-brown). At random intervals, simulated traffic light signals were presented against a white background at 5° to the right or left and observers were instructed to identify signal color (red/yellow/green) by pressing a response button as quickly as possible; response times and response errors were recorded. Results: Signal color and sunglass tint had significant effects on response times and error rates (p < 0.05), with significant between-color group differences and interaction effects. Response times for color deficient people were considerably slower than color normals for both red and yellow signals for all sunglass tints, but for green signals they were only noticeably slower with the green and yellow-green lenses. For most of the color deficient groups, there were recognition errors for yellow signals combined with the yellow-green and green tints. In addition, deuteranopes had problems for red signals combined with red-brown and yellow-brown tints, and protanopes had problems for green signals combined with the green tint and for red signals combined with the red-brown tint. Conclusions: Many sunglass tints currently permitted for drivers and riders cause a measurable decrement in the ability of color deficient observers to detect and recognize traffic signals. In general, combinations of signals and sunglasses of similar colors are of particular concern. This is prima facie evidence of a risk in the use of these tints for driving and cautions against the relaxation of coloration limits in sunglasses beyond those represented in the study.

The impacts of traffic and rainfall characteristics on heavy metals build-up and wash-off from urban roads

An investigation into the effects of changes in urban traffic characteristics due to rapid urbanisation and the predicted changes in rainfall characteristics due to climate change on the build-up and wash-off of heavy metals was carried out in Gold Coast, Australia. The study sites encompassed three different urban land uses. Nine heavy metals commonly associated with traffic emissions were selected. The results were interpreted using multivariate data analysis and decision making tools, such as principal component analysis (PCA), fuzzy clustering (FC), PROMETHEE and GAIA. Initial analyses established high, low and moderate traffic scenarios as well as low, low to moderate, moderate, high and extreme rainfall scenarios for build-up and wash-off investigations. GAIA analyses established that moderate to high traffic scenarios could affect the build-up while moderate to high rainfall scenarios could affect the wash-off of heavy metals under changed conditions. However, in wash-off, metal concentrations in 1-75µm fraction were found to be independent of the changes to rainfall characteristics. In build-up, high traffic activities in commercial and industrial areas influenced the accumulation of heavy metal concentrations in particulate size range from 75 - >300 µm, whereas metal concentrations in finer size range of <1-75 µm were not affected. As practical implications, solids <1 µm and organic matter from 1 - >300 µm can be targeted for removal of Ni, Cu, Pb, Cd, Cr and Zn from build-up whilst organic matter from <1 - >300 µm can be targeted for removal of Cd, Cr, Pb and Ni from wash-off. Cu and Zn need to be removed as free ions from most fractions in wash-off.

Freeway traffic oscillations : microscopic analysis of formations and propagations using Wavelet Transform

In this paper we identify the origins of stop-and-go (or slow-and-go) driving and measure microscopic features of their propagations by analyzing vehicle trajectories via Wavelet Transform. Based on 53 oscillation cases analyzed, we find that oscillations can be originated by either lane-changing maneuvers (LCMs) or car-following behavior (CF). LCMs were predominantly responsible for oscillation formations in the absence of considerable horizontal or vertical curves, whereas oscillations formed spontaneously near roadside work on an uphill segment. Regardless of the trigger, the features of oscillation propagations were similar in terms of propagation speed, oscillation duration, and amplitude. All observed cases initially exhibited a precursor phase, in which slow-and-go motions were localized. Some of them eventually transitioned into a well developed phase, in which oscillations propagated upstream in queue. LCMs were primarily responsible for the transition, although some transitions occurred without LCMs. Our findings also suggest that an oscillation has a regressive effect on car following behavior: a deceleration wave of an oscillation affects a timid driver (with larger response time and minimum spacing) to become less timid and an aggressive driver less aggressive, although this change may be short-lived. An extended framework of Newell’s CF is able to describe the regressive effects with two additional parameters with reasonable accuracy, as verified using vehicle trajectory data.

The acute adaptations of normal and pathological human Achilles tendons to eccentric and concentric exercise

Eccentric exercise is the conservative treatment of choice for mid-portion Achilles tendinopathy. While there is a growing body of evidence supporting the medium to long term efficacy of eccentric exercise in Achilles tendinopathy treatment, very few studies have investigated the short term response of the tendon to eccentric exercise. Moreover, the mechanisms through which tendinopathy symptom resolution occurs remain to be established. The primary purpose of this thesis was to investigate the acute adaptations of the Achilles tendon to, and the biomechanical characteristics of, the eccentric exercise protocol used for Achilles tendinopathy rehabilitation and a concentric equivalent. The research was conducted with an orientation towards exploring potential mechanisms through which eccentric exercise may bring about a resolution of tendinopathy symptoms. Specifically, the morphology of tendinopathic and normal Achilles tendons was monitored using high resolution sonography prior to and following eccentric and concentric exercise, to facilitate comparison between the treatment of choice and a similar alternative. To date, the only proposed mechanism through which eccentric exercise is thought to result in symptom resolution is the increased variability in motor output force observed during eccentric exercise. This thesis expanded upon prior work by investigating the variability in motor output force recorded during eccentric and concentric exercises, when performed at two different knee joint angles, by limbs with and without symptomatic tendinopathy. The methodological phase of the research focused on establishing the reliability of measures of tendon thickness, tendon echogenicity, electromyography (EMG) of the Triceps Surae and the standard deviation (SD) and power spectral density (PSD) of the vertical ground reaction force (VGRF). These analyses facilitated comparison between the error in the measurements and experimental differences identified as statistically significant, so that the importance and meaning of the experimental differences could be established. One potential limitation of monitoring the morphological response of the Achilles tendon to exercise loading is that the Achilles tendon is continually exposed to additional loading as participants complete the walking required to carry out their necessary daily tasks. The specific purpose of the last experiment in the methodological phase was to evaluate the effect of incidental walking activity on Achilles tendon morphology. The results of this study indicated that walking activity could decrease Achilles tendon thickness (negative diametral strain) and that the decrease in thickness was dependent on both the amount of walking completed and the proximity of walking activity to the sonographic examination. Thus, incidental walking activity was identified as a potentially confounding factor for future experiments which endeavoured to monitor changes in tendon thickness with exercise loading. In the experimental phase of this thesis the thickness of Achilles tendons was monitored prior to and following isolated eccentric and concentric exercise. The initial pilot study demonstrated that eccentric exercise resulted in a greater acute decrease in Achilles tendon thickness (greater diametral strain) compared to an equivalent concentric exercise, in participants with no history of Achilles tendon pain. This experiment was then expanded to incorporate participants with unilateral Achilles tendinopathy. The major finding of this experiment was that the acute decrease in Achilles tendon thickness observed following eccentric exercise was modified by the presence of tendinopathy, with a smaller decrease (less diametral strain) noted for tendinopathic compared to healthy control tendon. Based on in vitro evidence a decrease in tendon thickness is believed to reflect extrusion of fluid from the tendon with loading. This process would appear to be limited by the presence of pathology and is hypothesised to be a result of the changes in tendon structure associated with tendinopathy. Load induced fluid movement may be important to the maintenance of tendon homeostasis and structure as it has the potential to enhance molecular movement and stimulate tendon remodelling. On this basis eccentric exercise may be more beneficial to the tendon than concentric exercise. Finally, EMG and motor output force variability (SD and PSD of VGRF) were investigated while participants with and without tendinopathy performed the eccentric and concentric exercises. Although between condition differences were identified as statistically significant for a number of force variability parameters, the differences were not greater than the limits of agreement for repeated measures. Consequently the meaning and importance of these findings were questioned. Interestingly, the EMG amplitude of all three Triceps Surae muscles did not vary with knee joint angle during the performance of eccentric exercise. This raises questions pertaining to the functional importance of performing the eccentric exercise protocol at each of the two knee joint angles as it is currently prescribed. EMG amplitude was significantly greater during concentric compared to eccentric muscle actions. Differences in the muscle activation patterns may result in different stress distributions within the tendon and be related to the different diametral strain responses observed for eccentric and concentric muscle actions.