A novel extension of active appearance models (AAMs) for automated border detection in echocardiographic image sequences is reported. The active appearance motion model (AAMM) technique allows fully automated robust and time-continuous delineation of left ventricular (LV) endocardial contours over the full heart cycle with good results. Nonlinear intensity normalization was developed and employed to accommodate ultrasound-specific intensity distributions. The method was trained and tested on 16-frame phase-normalized transthoracic four-chamber sequences of 129 unselected infarct patients, split randomly into a training set (n = 65) and a test set (n = 64). Borders were compared to expert drawn endocardial contours. On the test set, fully automated AAMM performed well in 97% of the cases (average distance between manual and automatic landmark points was 3.3 mm, comparable to human interobserver variabilities). The ultrasound-specific intensity normalization proved to be of great value for good results in echocardiograms. The AAMM was significantly more accurate than an equivalent set of two-dimensional AAMs.
Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5–15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer’s disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI.
Trimethylaminuria is a rare metabolic disorder that is associated with abnormal amounts of the dietary-derived trimethylamine. Excess unmetabolized trimethylamine in the urine, sweat and other body secretions confers a strong, foul body odor that can affect the individual's ability to work or engage in social activities. This review summarizes the biochemical aspects of the condition and the classification of the disorder into: 1) primary genetic form, 2) acquired form, 3) childhood forms, 4) transient form associated with menstruation, 5) precursor overload and 6) disease states. The genetic variability of the flavin-containing monooxygenase (form 3) that is responsible for detoxication and deodoration of trimethylamine is discussed and put in context with other variant forms of the flavin-containing monooxygenase (forms 1-5). The temporal-selective expression of flavin-containing monooxygenase forms 1 and 3 is discussed in terms of an explanation for childhood trimethylaminuria. Information as to whether variants of the flavin-containing monooxygenase form 3 contributes to hypertension and/or other diseases are presented. Discussion is provided outlining recent bioanalytical approaches to quantify urinary trimethylamine and trimethylamine N-oxide and plasma choline as well as data on self-reporting individuals tested for trimethylaminuria. Finally, trimethylaminuria treatment strategies and nutritional support are described including dietary sources of trimethylamine, vitamin supplementation and drug treatment and issues related to trimethylaminuria in pregnancy and lactation are discussed. The remarkable progress in the biochemical, genetic, clinical basis for understanding the trimethylaminuria condition is summarized and points to needs in the treatment of individuals suffering from trimethylaminuria.
BACKGROUNDWe examine why dementia prevention and risk reduction are relatively underfunded and suggest potential remediation strategies. The paper is aimed at researchers, funders and policy-makers, both within dementia and also the wider health prevention field.METHODSA discussion-led workshop, attended by 58 academics, clinicians, funders and policy-makers.RESULTSThe key barriers identified were the gaps in understanding the basic science of dementia; the complex interplay between individual risk factors; variations in study methodology; disincentives to collaboration; a lack of research capacity and leadership and the broader stigma of the condition. Recommendations were made to encourage strategic leadership, provide greater support for grant applications, promote collaboration and support randomized control trials for the research field.CONCLUSIONHaving identified the barriers, the key challenge is how to implement the potential solutions. This will require engagement with decision-makers within funding, policy and research to ensure that action takes place.
Medical faculty, blood center directors, and technologists were surveyed to assess current opinions of knowledge deficiencies in transfusion medicine among medical school graduates, housestaff, and practicing physicians. Over 90% of those responding believed additional training in transfusion medicine was needed. Nine categories of deficiencies were identified, with more than 40% of respondents' comments reflecting concern about the lack of knowledge of the use of blood and blood components. Clinical faculty and blood bankers differed in their assessments of the knowledge deficiencies in two of the nine categories. Information obtained in this survey is relevant to educational development in transfusion medicine.
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