Anatomical Global Spatial Normalization

Anatomical global spatial normalization (aGSN) is presented as a method to scale high-resolution brain images to control for variability in brain size without altering the mean size of other brain structures. Two types of mean preserving scaling methods were investigated, “shape preserving” and “shape standardizing”. aGSN was tested by examining 56 brain structures from an adult brain atlas of 40 individuals (LPBA40) before and after normalization, with detailed analyses of cerebral hemispheres, all gyri collectively, cerebellum, brainstem, and left and right caudate, putamen, and hippocampus. Mean sizes of brain structures as measured by volume, distance, and area were preserved and variance reduced for both types of scale factors. An interesting finding was that scale factors derived from each of the ten brain structures were also mean preserving. However, variance was best reduced using whole brain hemispheres as the reference structure, and this reduction was related to its high average correlation with other brain structures. The fractional reduction in variance of structure volumes was directly related to ρ2, the square of the reference-to-structure correlation coefficient. The average reduction in variance in volumes by aGSN with whole brain hemispheres as the reference structure was approximately 32%. An analytical method was provided to directly convert between conventional and aGSN scale factors to support adaptation of aGSN to popular spatial normalization software packages

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

BACKGROUND: Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. METHODS: The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. DISCUSSION: The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.MRC Funding: MC_UP_1302/3 NIHR Funding: RP-PG-0610-1006

Estimation of coronary artery hyperemic blood flow based on arterial lumen volume using angiographic images

The purpose of this study is to develop a method to estimate the hyperemic blood flow in a coronary artery using the sum of the distal lumen volumes in a swine animal model. The limitations of visually assessing coronary artery disease are well known. These limitations are particularly important in intermediate coronary lesions where it is difficult to determine whether a particular lesion is the cause of ischemia. Therefore, a functional measure of stenosis severity is needed using angiographic image data. Coronary arteriography was performed in 10 swine (Yorkshire, 25–35 kg) after power injection of contrast material into the left main coronary artery. A densitometry technique was used to quantify regional flow and lumen volume in vivo after inducing hyperemia. Additionally, 3 swine hearts were casted and imaged post-mortem using cone-beam CT to obtain the lumen volume and the arterial length of corresponding coronary arteries. Using densitometry, the results showed that the stem hyperemic flow (Q) and the associated crown lumen volume (V) were related by Q = 159.08 V3/4 (r = 0.98, SEE = 10.59 ml/min). The stem hyperemic flow and the associated crown length (L) using cone-beam CT were related by Q = 2.89 L (r = 0.99, SEE = 8.72 ml/min). These results indicate that measured arterial branch lengths or lumen volumes can potentially be used to predict the expected hyperemic flow in an arterial tree. This, in conjunction with measured hyperemic flow in the presence of a stenosis, could be used to predict fractional flow reserve based entirely on angiographic data

Phylogenetic Analysis of Pelecaniformes (Aves) Based on Osteological Data: Implications for Waterbird Phylogeny and Fossil Calibration Studies

) were also assessed. The antiquity of these taxa and their purported status as stem members of extant families makes them valuable for studies of higher-level avian diversification. (sister taxon to Phalacrocoracidae). These relationships are invariant when ‘backbone’ constraints based on recent avian phylogenies are imposed.Relationships of extant pelecaniforms inferred from morphology are more congruent with molecular phylogenies than previously assumed, though notable conflicts remain. The phylogenetic position of the Plotopteridae implies that wing-propelled diving evolved independently in plotopterids and penguins, representing a remarkable case of convergent evolution. Despite robust support for the placement of fossil taxa representing key calibration points, the successive outgroup relationships of several “stem fossil + crown family” clades are variable and poorly supported across recent studies of avian phylogeny. Thus, the impact these fossils have on inferred patterns of temporal diversification depends heavily on the resolution of deep nodes in avian phylogeny