Learning-based Ensemble Average Propagator Estimation

By capturing the anisotropic water diffusion in tissue, diffusion magnetic resonance imaging (dMRI) provides a unique tool for noninvasively probing the tissue microstructure and orientation in the human brain. The diffusion profile can be described by the ensemble average propagator (EAP), which is inferred from observed diffusion signals. However, accurate EAP estimation using the number of diffusion gradients that is clinically practical can be challenging. In this work, we propose a deep learning algorithm for EAP estimation, which is named learning-based ensemble average propagator estimation (LEAPE). The EAP is commonly represented by a basis and its associated coefficients, and here we choose the SHORE basis and design a deep network to estimate the coefficients. The network comprises two cascaded components. The first component is a multiple layer perceptron (MLP) that simultaneously predicts the unknown coefficients. However, typical training loss functions, such as mean squared errors, may not properly represent the geometry of the possibly non-Euclidean space of the coefficients, which in particular causes problems for the extraction of directional information from the EAP. Therefore, to regularize the training, in the second component we compute an auxiliary output of approximated fiber orientation (FO) errors with the aid of a second MLP that is trained separately. We performed experiments using dMRI data that resemble clinically achievable $q$-space sampling, and observed promising results compared with the conventional EAP estimation method.Comment: Accepted by MICCAI 201

Caring for the patient, caring for the record: an ethnographic study of 'back office' work in upholding quality of care in general practice

© 2015 Swinglehurst and Greenhalgh; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Additional file 1: Box 1. Field notes on summarising (Clover Surgery). Box 2. Extract of document prepared for GPs by summarisers at Clover Surgery. Box 3. Fieldnotes on coding incoming post, Clover (original notes edited for brevity).This work was funded by a research grant from the UK Medical Research Council (Healthcare Electronic Records in Organisations 07/133) and a National Institute of Health Research doctoral fellowship award for DS (RDA/03/07/076). The funders were not involved in the selection or analysis of data nor did they make any contribution to the content of the final manuscript

The effect of Tai Chi Chuan in reducing falls among elderly people: design of a randomized clinical trial in the Netherlands [ISRCTN98840266]

BACKGROUND: Falls are a significant public health problem. Thirty to fifty percent of the elderly of 65 years and older fall each year. Falls are the most common type of accident in this age group and can result in fractures and subsequent disabilities, increased fear of falling, social isolation, decreased mobility, and even an increased mortality. Several forms of exercise have been associated with a reduced risk of falling and with a wide range of physiological as well as psychosocial health benefits. Tai Chi Chuan seems to be the most promising form of exercise in the elderly, but the evidence is still controversial. In this article the design of a randomized clinical trial is presented. The trial evaluates the effect of Tai Chi Chuan on fall prevention and physical and psychological function in older adults. METHODS/DESIGN: 270 people of seventy years and older living at home will be identified in the files of the participating general practitioners. People will be asked to participate when meeting the following inclusion criteria: have experienced a fall in the preceding year or suffer from two of the following risk factors: disturbed balance, mobility problems, dizziness, or the use of benzodiazepines or diuretics. People will be randomly allocated to either the Tai Chi Chuan group (13 weeks, twice a week) or the no treatment control group. The primary outcome measure is the number of new falls, measured with a diary. The secondary outcome measures are balance, fear of falling, blood pressure, heart rate, lung function parameters, physical activity, functional status, quality of life, mental health, use of walking devices, medication, use of health care services, adjustments to the house, severity of fall incidents and subsequent injuries. Process parameters will be measured to evaluate the Tai Chi Chuan intervention. A cost-effectiveness analysis will be carried out alongside the evaluation of the clinical results. Follow-up measurements will be collected at 3, 6 and 12 months after randomization. DISCUSSION: As far as we know this is the first trial in Europe considering Tai Chi Chuan and fall prevention. This project will answer a pragmatic research question regarding the efficacy of Tai Chi Chuan regarding fall reduction

Spatiotemporal in vivo tracking of polyclonal human regulatory T cells (Tregs) reveals a role for innate immune cells in Treg transplant recruitment

Supplemental information is available online at: https://www.sciencedirect.com/science/article/pii/S2329050120302515#appsec2 .Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs has been shown preclinically to protect from graft rejection, and the safety of Treg therapy has been demonstrated in clinical trials. Despite these successes, the in vivo distribution and persistence of adoptively transferred Tregs remained elusive, which hampers clinical translation. Here we isolated human Tregs using a GMP-compatible protocol and lentivirally transduced them with the human sodium iodide symporter to render them traceable in vivo by radionuclide imaging. Engineered human Tregs were characterized for phenotype, survival, suppressive capacity, and reporter function. To study their trafficking behavior, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nano-single-photon emission computed tomography (nanoSPECT)/computed tomography (CT) for up to 40 days, and the results were validated ex vivo. Using this approach, we demonstrated that Treg trafficking to skin grafts was regulated by the presence of recipient Gr-1+ innate immune cells. We demonstrated the utility of radionuclide reporter gene-afforded quantitative Treg in vivo tracking, addressing a fundamental need in Treg therapy development and offering a clinically compatible methodology for future Treg therapy imaging in humans.This work was supported by the British Heart Foundation (RG/13/12/30395), the MRC Centre for Transplantation at King's College London (MR/J006742/1), Cancer Research UK (C48390/A21153), and the Wellcome/EPSRC Centre for Medical Engineering (WT203148/Z/16/Z). This research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility

Bacterial Chemotaxis in an Optical Trap

An optical trapping technique is implemented to investigate the chemotactic behavior of a marine bacterial strain Vibrio alginolyticus. The technique takes the advantage that the bacterium has only a single polar flagellum, which can rotate either in the counter-clock-wise or clock-wise direction. The two rotation states of the motor can be readily and instantaneously resolved in the optical trap, allowing the flagellar motor switching rate to be measured under different chemical stimulations. In this paper the focus will be on the bacterial response to an impulsive change of chemoattractant serine. Despite different propulsion apparati and motility patterns, cells of V. alginolyticus apparently use a similar response as Escherichia coli to regulate their chemotactic behavior. Specifically, we found that the switching rate of the bacterial motor exhibits a biphasic behavior, showing a fast initial response followed by a slow relaxation to the steady-state switching rate . The measured can be mimicked by a model that has been recently proposed for chemotaxis in E. coli. The similarity in the response to the brief chemical stimulation in these two different bacteria is striking, suggesting that the biphasic response may be evolutionarily conserved. This study also demonstrated that optical tweezers can be a useful tool for chemotaxis studies and should be applicable to other polarly flagellated bacteria

Examining links between anxiety, reinvestment and walking when talking by older adults during adaptive gait

Falls by older adults often result in reduced quality of life and debilitating fear of further falls. Stopping walking when talking (SWWT) is a significant predictor of future falls by older adults and is thought to reflect age-related increases in attentional demands of walking. We examine whether SWWT is associated with use of explicit movement cues during locomotion, and evaluate if conscious control (i.e., movement specific reinvestment) is causally linked to falls-related anxiety during a complex walking task. We observed whether twenty-four older adults stopped walking when talking when asked a question during an adaptive gait task. After certain trials, participants completed a visual-spatial recall task regarding walkway features, or answered questions about their movements during the walk. In a subsequent experimental condition, participants completed the walking task under conditions of raised postural threat. Compared to a control group, participants who SWWT reported higher scores for aspects of reinvestment relating to conscious motor processing but not movement self-consciousness. The higher scores for conscious motor processing were preserved when scores representing cognitive function were included as a covariate. There were no group differences in measures of general cognitive function, visual spatial working memory or balance confidence. However, the SWWT group reported higher scores on a test of external awareness when walking, indicating allocation of attention away from task-relevant environmental features. Under conditions of increased threat, participants self-reported significantly greater state anxiety and reinvestment and displayed more accurate responses about their movements during the task. SWWT is not associated solely with age-related cognitive decline or generic increases in age-related attentional demands of walking. SWWT may be caused by competition for phonological resources of working memory associated with consciously processing motor actions and appears to be causally linked with fall-related anxiety and increased vigilance.This research was supported by The Royal Society (IE131576) and British Academy (SG132820)

Associations of sedentary behaviour, physical activity, blood pressure and anthropometric measures with cardiorespiratory fitness in children with cerebral palsy

Background - Children with cerebral palsy (CP) have poor cardiorespiratory fitness in comparison to their peers with typical development, which may be due to low levels of physical activity. Poor cardiorespiratory fitness may contribute to increased cardiometabolic risk. Purpose - The aim of this study was to determine the association between sedentary behaviour, physical activity and cardiorespiratory fitness in children with CP. An objective was to determine the association between cardiorespiratory fitness, anthropometric measures and blood pressure in children with CP. Methods- This study included 55 ambulatory children with CP [mean (SD) age 11.3 (0.2) yr, range 6-17 yr; Gross Motor Function Classification System (GMFCS) levels I and II]. Anthropometric measures (BMI, waist circumference and waist-height ratio) and blood pressure were taken. Cardiorespiratory fitness was measured using a 10 m shuttle run test. Children were classified as low, middle and high fitness according to level achieved on the test using reference curves. Physical activity was measured by accelerometry over 7 days. In addition to total activity, time in sedentary behaviour and light, moderate, vigorous, and sustained moderate-to-vigorous activity (≥10 min bouts) were calculated. Results - Multiple regression analyses revealed that vigorous activity (β = 0.339, p<0.01), sustained moderate-to-vigorous activity (β = 0.250, p<0.05) and total activity (β = 0.238, p<0.05) were associated with level achieved on the shuttle run test after adjustment for age, sex and GMFCS level. Children with high fitness spent more time in vigorous activity than children with middle fitness (p<0.05). Shuttle run test level was negatively associated with BMI (r2 = -0.451, p<0.01), waist circumference (r2 = -0.560, p<0.001), waist-height ratio (r2 = -0.560, p<0.001) and systolic blood pressure (r2 = -0.306, p<0.05) after adjustment for age, sex and GMFCS level. Conclusions - Participation in physical activity, particularly at a vigorous intensity, is associated with high cardiorespiratory fitness in children with CP. Low cardiorespiratory fitness is associated with increased cardiometabolic risk

Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus

Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory

MRI in multiple myeloma : a pictorial review of diagnostic and post-treatment findings

Magnetic resonance imaging (MRI) is increasingly being used in the diagnostic work-up of patients with multiple myeloma. Since 2014, MRI findings are included in the new diagnostic criteria proposed by the International Myeloma Working Group. Patients with smouldering myeloma presenting with more than one unequivocal focal lesion in the bone marrow on MRI are considered having symptomatic myeloma requiring treatment, regardless of the presence of lytic bone lesions. However, bone marrow evaluation with MRI offers more than only morphological information regarding the detection of focal lesions in patients with MM. The overall performance of MRI is enhanced by applying dynamic contrast-enhanced MRI and diffusion weighted imaging sequences, providing additional functional information on bone marrow vascularization and cellularity. This pictorial review provides an overview of the most important imaging findings in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma, by performing a 'total' MRI investigation with implications for the diagnosis, staging and response assessment. Main message aEuro cent Conventional MRI diagnoses multiple myeloma by assessing the infiltration pattern. aEuro cent Dynamic contrast-enhanced MRI diagnoses multiple myeloma by assessing vascularization and perfusion. aEuro cent Diffusion weighted imaging evaluates bone marrow composition and cellularity in multiple myeloma. aEuro cent Combined morphological and functional MRI provides optimal bone marrow assessment for staging. aEuro cent Combined morphological and functional MRI is of considerable value in treatment follow-up