63 research outputs found
Bifurcation Boundary Conditions for Switching DC-DC Converters Under Constant On-Time Control
Sampled-data analysis and harmonic balance analysis are applied to analyze
switching DC-DC converters under constant on-time control. Design-oriented
boundary conditions for the period-doubling bifurcation and the saddle-node
bifurcation are derived. The required ramp slope to avoid the bifurcations and
the assigned pole locations associated with the ramp are also derived. The
derived boundary conditions are more general and accurate than those recently
obtained. Those recently obtained boundary conditions become special cases
under the general modeling approach presented in this paper. Different analyses
give different perspectives on the system dynamics and complement each other.
Under the sampled-data analysis, the boundary conditions are expressed in terms
of signal slopes and the ramp slope. Under the harmonic balance analysis, the
boundary conditions are expressed in terms of signal harmonics. The derived
boundary conditions are useful for a designer to design a converter to avoid
the occurrence of the period-doubling bifurcation and the saddle-node
bifurcation.Comment: Submitted to International Journal of Circuit Theory and Applications
on August 10, 2011; Manuscript ID: CTA-11-016
A short purification process for quantitative isolation of PrP(Sc) from naturally occurring and experimental transmissible spongiform encephalopathies
BACKGROUND: Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases affecting both humans and animals. They are associated with post-translational conversion of the normal cellular prion protein (PrP(C)) into a heat- and protease-resistant abnormal isoform (PrP(Sc)). Detection of PrP(Sc) in individuals is widely utilized for the diagnosis of prion diseases. METHODS: TSE brain tissue samples have been processed in order to quantitatively isolate PrP(Sc). The protocol includes an initial homogenization, digestion with proteinase K and salt precipitation. RESULTS: Here we show that over 97 percent of the PrP(Sc) present can be precipitated from infected brain material using this simple salting-out procedure for proteins. No chemically harsh conditions are used during the process in order to conserve the native quality of the isolated protein. CONCLUSION: The resulting PrP(Sc)-enriched preparation should provide a suitable substrate for analyzing the structure of the prion agent and for scavenging for other molecules with which it may associate. In comparison with most methods that exist today, the one described in this study is rapid, cost-effective and does not demand expensive laboratory equipment
The Conselice Study of Brain Ageing
Among the age-related diseases, the development of cognitive impairments, in particular dementia, is the most devastating for the individual and has great social and healthcare costs. Accurate information is needed about the prevalence and incidence of cognitive disorders and the physiology of the ageing brain. In particular, only scant data are available about the relationship between ageing, cognitive status and nutritional factors. In order to address these issues we planned the Conselice Study of Brain Ageing, a longitudinal study of physiologic and pathologic brain ageing. The center involved in the study was the municipality of Conselice, Ravenna province, in the Northern Italian region Emilia-Romagna. A total of 1016 subjects aged 65 and over was enrolled at baseline. Information about cognitive status at 4-years of follow-up was collected for 940 of them. These data have been used to estimate prevalence and incidence of dementia in the elderly Italian population and to investigate the possible role of baseline blood homocysteine as risk factors for dementia
Monitoring the early signs of cognitive decline in elderly by computer games: an MRI study
BACKGROUND: It is anticipated that current and future preventive therapies will likely be more effective in the early stages of dementia, when everyday functioning is not affected. Accordingly the early identification of people at risk is particularly important. In most cases, when subjects visit an expert and are examined using neuropsychological tests, the disease has already been developed. Contrary to this cognitive games are played by healthy, well functioning elderly people, subjects who should be monitored for early signs. Further advantages of cognitive games are their accessibility and their cost-effectiveness. PURPOSE: The aim of the investigation was to show that computer games can help to identify those who are at risk. In order to validate games analysis was completed which measured the correlations between results of the 'Find the Pairs' memory game and the volumes of the temporal brain regions previously found to be good predictors of later cognitive decline. PARTICIPANTS AND METHODS: 34 healthy elderly subjects were enrolled in the study. The volume of the cerebral structures was measured by MRI. Cortical reconstruction and volumetric segmentation were performed by Freesurfer. RESULTS: There was a correlation between the number of attempts and the time required to complete the memory game and the volume of the entorhinal cortex, the temporal pole, and the hippocampus. There was also a correlation between the results of the Paired Associates Learning (PAL) test and the memory game. CONCLUSIONS: The results gathered support the initial hypothesis that healthy elderly subjects achieving lower scores in the memory game have increased level of atrophy in the temporal brain structures and showed a decreased performance in the PAL test. Based on these results it can be concluded that memory games may be useful in early screening for cognitive decline
A development study and randomised feasibility trial of a tailored intervention to improve activity and reduce falls in older adults with mild cognitive impairment and mild dementia
Background:
People with dementia progressively lose abilities and are prone to falling. Exercise- and activity-based interventions hold the prospect of increasing abilities, reducing falls, and slowing decline in cognition. Current falls prevention approaches are poorly suited to people with dementia, however, and are of uncertain effectiveness. We used multiple sources, and a co-production approach, to develop a new intervention, which we will evaluate in a feasibility randomised controlled trial (RCT), with embedded adherence, process and economic analyses.
Methods:
We will recruit people with mild cognitive impairment or mild dementia from memory assessment clinics, and a family member or carer. We will randomise participants between a therapy programme with high intensity supervision over 12 months, a therapy programme with moderate intensity supervision over 3 months, and brief falls assessment and advice as a control intervention. The therapy programmes will be delivered at home by mental health specialist therapists and therapy assistants. We will measure activities of daily living, falls and a battery of intermediate and distal health status outcomes, including activity, balance, cognition, mood and quality of life. The main aim is to test recruitment and retention, intervention delivery, data collection and other trial processes in advance of a planned definitive RCT. We will also study motivation and adherence, and conduct a process evaluation to help understand why results occurred using mixed methods, including a qualitative interview study and scales measuring psychological, motivation and communication variables. We will undertake an economic study, including modelling of future impact and cost to end-of-life, and a social return on investment analysis.
Discussion:
In this study, we aim to better understand the practicalities of both intervention and research delivery, and to generate substantial new knowledge on motivation, adherence and the approach to economic analysis. This will enable us to refine a novel intervention to promote activity and safety after a diagnosis of dementia, which will be evaluated in a definitive randomised controlled trial.\ud
Trial registration:
ClinicalTrials.gov: NCT02874300; ISRCTN 10550694
Listeria monocytogenes in Milk Products
peer-reviewedMilk and milk products are frequently identified as vectors for transmission of Listeria monocytogenes. Milk can be contaminated at farm level either by indirect external contamination from the farm environment or less frequently by direct contamination of the milk from infection in the animal. Pasteurisation of milk will kill L. monocytogenes, but post-pasteurisation contamination, consumption of unpasteurised milk and manufacture of unpasteurised milk products can lead to milk being the cause of outbreaks of listeriosis. Therefore, there is a concern that L. monocytogenes in milk could lead to a public health risk. To protect against this risk, there is a need for awareness surrounding the issues, hygienic practices to reduce the risk and adequate sampling and analysis to verify that the risk is controlled. This review will highlight the issues surrounding L. monocytogenes in milk and milk products, including possible control measures. It will therefore create awareness about L. monocytogenes, contributing to protection of public health
Treadmill training as an augmentation treatment for Alzheimer?s disease: a pilot randomized controlled study
Comparing recruitment, retention, and safety reporting among geographic regions in multinational Alzheimer’s disease clinical trials
INTRODUCTION: Most Alzheimer’s disease (AD) clinical trials enroll participants multinationally. Yet, few data exist to guide investigators and sponsors regarding the types of patients enrolled in these studies and whether participant characteristics vary by region. METHODS: We used data derived from four multinational phase III trials in mild to moderate AD to examine whether regional differences exist with regard to participant demographics, safety reporting, and baseline scores on the Mini Mental State Examination (MMSE), the 11-item Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-cog11), the Clinical Dementia Rating scale Sum of Boxes (CDR-SB), the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Inventory (ADCS-ADL), and the Neuropsychiatric Inventory (NPI). We assigned 31 participating nations to 7 geographic regions: North America, South America/Mexico, Western Europe/Israel, Eastern Europe/Russia, Australia/South Africa, Asia, and Japan. RESULTS: North America, Western Europe/Israel, and Australia/South Africa enrolled similar proportions of men, apolipoprotein E ε4 carriers, and participants with spouse study partners, whereas Asia, Eastern Europe/Russia, and South America/Mexico had lower proportions for these variables. North America and South America/Mexico enrolled older subjects, whereas Asia and South America/Mexico enrolled less-educated participants than the remaining regions. Approved AD therapy use differed among regions (range: 73% to 92%) and was highest in North America, Western Europe/Israel, and Japan. Dual therapy was most frequent in North America (48%). On the MMSE, North America, Western Europe/Israel, Japan, and Australia/South Africa had higher (better) scores, and Asia, South America/Mexico, and Eastern Europe/Russia had lower scores. Eastern Europe/Russia had more impaired ADAS-cog11 scores than all other regions. Eastern Europe/Russia and South America/Mexico had more impaired scores for the ADCS-ADL and the CDR-SB. Mean scores for the CDR-SB in Asia were milder than all regions except Japan. NPI scores were lower in Asia and Japan than in all other regions. Participants in North America and Western Europe/Israel reported more adverse events than those in Eastern Europe/Russia and Japan. CONCLUSIONS: These findings suggest that trial populations differ across geographic regions on most baseline characteristics and that multinational enrollment is associated with sample heterogeneity. The data provide initial guidance with regard to the regional differences that contribute to this heterogeneity and are important to consider when planning global trials
Measures of frailty in population-based studies: An overview
Although research productivity in the field of frailty has risen exponentially in recent years, there remains a lack of consensus regarding the measurement of this syndrome. This overview offers three services: first, we provide a comprehensive catalogue of current frailty measures; second, we evaluate their reliability and validity; third, we report on their popularity of use
Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis
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