Quantitative MRI in myositis patients: comparison with healthy volunteers and radiological visual assessment.

AIM: To assess whether magnetic resonance imaging (MRI)-based measurements of T2, fat fraction, diffusion tensor imaging, and muscle volume can detect differences between the muscles of myositis patients and healthy controls, and to identify how they compare with semi-quantitative MRI diagnosis. MATERIALS AND METHODS: Sixteen myositis patients and 16 age- and gender-matched healthy controls underwent MRI of their thigh. Quantitative MRI measurements and radiologists' semi-quantitative scores were assessed. Strength was assessed using an isokinetic dynamometer. RESULTS: Fat fraction and T2 values were higher in myositis patients whereas muscle volume was lower compared to healthy controls. There was no difference in diffusion. Muscle strength was lower in myositis patients compared to healthy controls. In a subgroup of eight patients, scored as unaffected by radiologists, T2 values were still significantly higher in myositis patients. CONCLUSIONS: Quantitative MRI measurements can detect differences between myositis patients and healthy controls. Changes in the muscles of myositis patients, undetected by visual, semi-quantitative scoring, can be detected using quantitative T2 measurements. This suggests that MRI T2 values may be useful for the management of myositis patients.

The effect of ageing on skeletal muscle as assessed by quantitative MR imaging: an association with frailty and muscle strength.

BACKGROUND: Skeletal muscles undergo changes with ageing which can cause sarcopenia that can result in frailty. Quantitative MRI may detect the muscle-deficit component of frailty which could help improve the understanding of ageing muscles. AIMS: To investigate whether quantitative MRI measures of T2, fat fraction (FF), diffusion tensor imaging and muscle volume can detect differences within the muscles between three age groups, and to assess how these measures compare with frailty index, gait speed and muscle power. METHODS: 18 'young' (18-30 years), 18 'middle-aged' (31-68 years) and 18 'older' (> 69 years) healthy participants were recruited. Participants had an MRI of their dominant thigh. Knee extension and flexion power and handgrip strength were measured. Frailty (English Longitudinal Study of Ageing frailty index) and gait speed were measured in the older participants. RESULTS: Young participants had a lower muscle MRI T2, FF and mean diffusivity than middle-aged and older participants; middle-aged participants had lower values than older participants. Young participants had greater muscle flexion and extension power, muscle volume and stronger hand grip than middle-aged and older participants; middle-aged participants had greater values than the older participants. Quantitative MRI measurements correlated with frailty index, gait speed, grip strength and muscle power. DISCUSSION: Quantitative MRI and strength measurements can detect muscle differences due to ageing. Older participants had raised T2, FF and mean diffusivity and lower muscle volume, grip strength and muscle power. CONCLUSIONS: Quantitative MRI measurements correlate with frailty and muscle function and could be used for identifying differences across age groups within muscle.

Structure prediction of nanoclusters; a direct or a pre-screened search on the DFT energy landscape?

The atomic structure of inorganic nanoclusters obtained via a search for low lying minima on energy landscapes, or hypersurfaces, is reported for inorganic binary compounds: zinc oxide (ZnO)n, magnesium oxide (MgO)n, cadmium selenide (CdSe)n, and potassium fluoride (KF)n, where n = 1-12 formula units. The computational cost of each search is dominated by the effort to evaluate each sample point on the energy landscape and the number of required sample points. The effect of changing the balance between these two factors on the success of the search is investigated. The choice of sample points will also affect the number of required data points and therefore the efficiency of the search. Monte Carlo based global optimisation routines (evolutionary and stochastic quenching algorithms) within a new software package, viz. Knowledge Led Master Code (KLMC), are employed to search both directly and after pre-screening on the DFT energy landscape. Pre-screening includes structural relaxation to minimise a cheaper energy function - based on interatomic potentials - and is found to improve significantly the search efficiency, and typically reduces the number of DFT calculations required to locate the local minima by more than an order of magnitude. Although the choice of functional form is important, the approach is robust to small changes to the interatomic potential parameters. The computational cost of initial DFT calculations of each structure is reduced by employing Gaussian smearing to the electronic energy levels. Larger (KF)n nanoclusters are predicted to form cuboid cuts from the rock-salt phase, but also share many structural motifs with (MgO)n for smaller clusters. The transition from 2D rings to 3D (bubble, or fullerene-like) structures occur at a larger cluster size for (ZnO)n and (CdSe)n. Differences between the HOMO and LUMO energies, for all the compounds apart from KF, are in the visible region of the optical spectrum (2-3 eV); KF lies deep in the UV region at 5 eV and shows little variation. Extrapolating the electron affinities found for the clusters with respect to size results in the qualitatively correct work functions for the respective bulk materials.

Double bubbles: a new structural motif for enhanced electron-hole separation in solids.

Electron-hole separation for novel composite systems comprised of secondary building units formed from different compounds is investigated with the aim of finding suitable materials for photocatalysis. Pure and mixed SOD and LTA superlattices of (ZnO)12 and (GaN)12, single-shell bubbles are constructed as well as core@shell single component frameworks composed of larger (ZnO)48 and (GaN)48 bubbles with each containing one smaller bubble. Enthalpies of formation for all systems are comparable with fullerenes. Hole and electron separation is achieved most efficiently by the edge sharing framework composed of (GaN)12@(ZnO)48 double bubbles, with the hole localised on the nitrogen within the smaller bubbles and the excited electron on zinc within the larger cages.

Pushing through the Barriers: Peer Advice to Increase Physical Activity and Reduce Dementia Risk from Participants in a Massive Open Online Alzheimer's Focused Course.

BACKGROUND: Engagement in physical activity is associated with reduced dementia risk but insufficient physical activity is a global trend. OBJECTIVES: We aimed to explore what advice might be offered to others to increase physical activity and to identify enablers and barriers to physical activity for adults interested in dementia prevention and participating in a massive open online course. PARTICIPANTS: Two thousand, one hundred and thirty-two participants contributed to an online discussion forum. DESIGN: Analysis was conducted using Topic modelling analysis followed by thematic analysis. RESULTS: The themes generated from the discussion posts included time constraints, poor health and lack of motivation as barriers to physical activity, and social interaction, incidental activities, and dog ownership as enablers. Peer advice was frequently suggested around scheduling physical activity into the day and joining a friend or organised activity. CONCLUSION: This online discussion forum uniquely captured ideas from a large, diverse group of participants. Future research may benefit from further examining the role of discussion forums and peer advice in dementia risk reduction initiatives.

Repeatability of quantitative MRI in patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) affects 1% of the population and is principally associated with joint inflammation. It is suggested however that muscle involvement may be one of the earliest clinical features of RA. It is therefore important that techniques exist to accurately assess muscle health in those with RA to enable successful treatment. This study assesses the inter-rater and intra-rater repeatability of Diffusion Tensor MRI (DTI), 2-Point Dixon fat fraction, and T2 relaxation of the thigh muscle in patients with RA using manual regions of interest (ROI). METHODS: Nineteen patients (10/19 males; mean age 59; range 18-85) diagnosed with RA had an MRI scan of their hamstrings and quadriceps muscles to obtain fat fraction (FF), mean diffusivity (MD), fractional anisotropy (FA), and T2 quantitative measurements. Two raters DB & MF independently contoured ROIs for each patient. DB repeated the ROI for the same 19 patients after a 6-month hiatus to assess intra-rater repeatability. Inter-rater and intra-rater repeatability for the ROI measurements were compared using Inter Class Correlation (ICC) and Bland-Altman plots. RESULTS: There was excellent agreement for both inter-rater and intra-rater repeatability. ICC results ranged from 0.900 to 0.998 (P < 0.001), and intra-rater ICC results ranged from 0.977 to 0.999 (P < 0.001). Bland-Altman plots also showed excellent agreement. CONCLUSIONS: ICC measurements and Bland-Altman plots showed excellent repeatability and agreement with no statistically significant differences when assessing the inter-rater and intra-rater repeatability of FF, MD, FA, and T2 relaxation of the thigh muscle using manual regions of interest in patients with RA. IMPLICATIONS FOR PRACTICE: Manual ROI drawing does not introduce significant errors obtaining FF, MD, FA, and T2 MRI measurements in an RA population.

Atomistic molecular dynamics simulations of shock compressed quartz.

Atomistic non-equilibrium molecular dynamics simulations of shock wave compression of quartz have been performed using the so-called BKS semi-empirical potential of van Beest, Kramer, and van Santen [Phys. Rev. B 43, 5068 (1991)] to construct the Hugoniot of quartz. Our scheme mimics the real world experimental set up by using a flyer-plate impactor to initiate the shock wave and is the first shock wave simulation that uses a geometry optimised system of a polar slab in a three-dimensional system employing periodic boundary conditions. Our scheme also includes the relaxation of the surface dipole in the polar quartz slab which is an essential pre-requisite to a stable simulation. The original BKS potential is unsuited to shock wave calculations and so we propose a simple modification. With this modification, we find that our calculated Hugoniot is in good agreement with experimental shock wave data up to 25 GPa, but significantly diverges beyond this point. We conclude that our modified BKS potential is suitable for quartz under representative pressure conditions of the Earth core, but unsuitable for high-pressure shock wave simulations. We also find that the BKS potential incorrectly prefers the ß-quartz phase over the α-quartz phase at zero-temperature, and that there is a ß â†’ α phase-transition at 6 GPa.

Functional connectivity of the prefrontal cortex in Huntington's disease.

BACKGROUND: Huntington's disease is a progressive neurodegenerative disorder that results in deterioration and atrophy of various brain regions. AIM: To assess the functional connectivity between prefrontal brain regions in patients with Huntington's disease, compared with normal controls, using functional magnetic resonance imaging. PATIENTS AND METHODS: 20 patients with Huntington's disease and 17 matched controls performed a Simon task that is known to activate lateral prefrontal and anterior cingulate cortical regions. The functional connectivity was hypothesised to be impaired in patients with Huntington's disease between prefrontal regions of interest, selected from both hemispheres, in the anterior cingulate and dorsal lateral prefrontal cortex. RESULTS: Controls showed a dynamic increase in interhemispheric functional connectivity during task performance, compared with the baseline state; patients with Huntington's disease, however, showed no such increase in prefrontal connectivity. Overall, patients with Huntington's disease showed significantly impaired functional connectivity between anterior cingulate and lateral prefrontal regions in both hemispheres compared with controls. Furthermore, poor task performance was predicted by reduced connectivity in patients with Huntington's disease between the left anterior cingulate and prefrontal regions. CONCLUSIONS: This finding represents a loss of synchrony in activity between prefrontal regions in patients with Huntington's disease when engaged in the task, which predicted poor task performance. Results show that functional interactions between critical prefrontal regions, necessary for cognitive performance, are compromised in Huntington's disease. It is speculated whether significantly greater levels of activation in patients with Huntington's disease (compared with controls) observed in several brain regions partially compensate for the otherwise compromised interactions between cortical regions.

Functional brain electrical activity mapping in boys with attention-deficit/hyperactivity disorder.

BACKGROUND: Symptoms of attention-deficit/hyperactivity disorder (ADHD) have been associated with frontal lobe deficits. We used a novel brain electrical imaging method to investigate rapid and continuous changes in brain activity during the continuous performance task (CPT) in normal boys and in boys with ADHD. The amplitude and latency topography of the steady-state visually evoked potential (SSVEP) were examined while subjects performed the "X" version of the CPT (CPT-X; the reference task) and the "A-X" version of the CPT (CPT-AX). METHODS: Seventeen boys meeting DSM-III-R criteria for ADHD and 17 age-matched controls participated in the study. Brain electrical activity was recorded from 64 scalp sites. During the reference task, subjects pressed a microswitch on the unpredictable appearance of the letter X. During the CPT-AX, subjects were required to press the microswitch on the appearance of the letter X only if an A had preceded it. RESULTS: In the interval between the appearances of the A and the X of the correct trials of the CPT-AX, control boys showed transient reductions in SSVEP latency at right prefrontal sites. By contrast, boys with ADHD showed no change or an increase in prefrontal SSVEP latency at right prefrontal sites. CONCLUSION: Our results suggest increased speed of prefrontal neural processing in children without ADHD following a priming stimulus, and a deficit in such processes in children with ADHD.

Working memory in ADHD: prefrontal/parietal connections.

Current theories of dopaminergic and noradrenergic mechanisms, which are thought to be of importance in the regulation of attention are reviewed. A biphasic model of dopaminergic function is described, in which tonic dopamine exerts a suppressive influence on subcortical dopamine systems by altering tonic/phasic dopaminergic relationships. Noradrenergic mechanisms are of importance in modulating sensory processing at the prefrontal cortical level. The work of Silberstein and colleagues utilizing Steady-State Visually Evoked Potential, during the course of an A-X Continuous Performance Task enables examination of the spatial distribution and dynamics of electrical brain activity during the task. The maintenance of activation in the interval between A and X provides a measure of working memory, thought to be related to prefrontal-parietal activation, which is facilitated by administration of methylphenidate to children with ADHD, suggesting that working memory may be a core deficiency in children with ADHD. While tonic dopamine activity in ventral striatum/accumbens gates inhibitory activity, dorsolateral prefrontal-parietal connections allow maintenance of working memory required for goal completion.

Evaluation of anticoagulant control in a pharmacist operated anticoagulant clinic.

AIMS: To compare the quality of outpatient anticoagulant control before and after the transfer of dosing responsibility to designated trained pharmacists from rotating junior medical staff. METHODS: All International Normalised Ratio (INR) values for an eight month period either side of the staff changeover were assessed for precision of therapeutic control according to described standards. Allowing for patient associated effects, observed and expected frequencies of "successful" control for the two staff groups were compared under the hypothesis of no association. RESULTS: INR results (n = 2219) for 382 patients were analysed. For patients in stable therapeutic control, there was no significant difference in performance between the two staff groups. Patients with an INR result "out" of control limits were more likely to be returned "in" to control at their next visit by the pharmacists than by the doctors. CONCLUSIONS: The quality of anticoagulant control in outpatient clinics benefits from dedicated trained staff using standard protocols.

Natural transformation of Streptococcus crista.

Over the years Streptococcus gordonii (sanguis) Challis has become the workhorse of genetic manipulations for the sanguis group of oral streptococci. This is because strain Challis was shown in early studies to be highly naturally competent for transformation. However, Challis is not usually the most appropriate strain to use in studies which focus on oral microbial adherence. We report that other members of the newly reorganized sanguis group, particularly within the species S. crista, display reasonable transformation frequencies, with both plasmid and chromosomal DNA, if transformed at the appropriate time during the growth curve. The ability to transform S. crista may be especially important for genetic studies of biological properties that appear to be limited to these specific streptococcal strains.

The pattern of variation in centipede segment number as an example of developmental constraint in evolution

The range of animal morphologies observed in nature is partly determined by natural selection. However, there is no agreement yet regarding whether it is also partly determined by developmental constraint. Testing for the effects of constraint has been difficult due to the lack of both an appropriate null model and a sufficiently simple system capable of yielding unambiguous results regarding the model's plausibility. Here we examine the case of variation in segment number in geophilomorph centipedes. Curiously, while this ranges between 29 and 191, there are no species in which an even number of segments is observed, in contrast to about 1000 species with odd numbers of segments. It seems unlikely that this distribution of character values is determined by selection alone. Using an approach based on Bayesian inference, we attempt to quantify the probability of obtaining the observed distribution of values given a null model in which developmental constraint is absent. Since this probability is in the region of 10(-20), we conclude that constraint must be involved. We discuss various implications of this conclusion, and comment on the unexpected absence of neoteny and progenesis in centipede evolution. Copyright 1999 Academic Press.

An evaluation of the host-mediated assay and body fluid analysis. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

The methodologies and status of the Host-Mediated Assay were reviewed using the published literature available up to June 1980. The Working Group reviewed 274 documents, including abstracts, research articles, review articles, and publicly available contracts and grant final reports. From this group, abstracts and reviews were rejected from critical evaluation. 77 documents were accepted and reviewed by the Working Group and the test results summarized. These selected documents yielded 208 chemicals that were evaluated in th host-mediated assay. Of these chemicals, 133 were mutagenic in this assay with one or more indicators. 76 chemicals, several of which are not considered to be carcinogenic, were not detected by any of the indicators. Of the 208 chemicals, 125 had been tested in carcinogenicity assay in rodents. 90, or 71%, of the carcinogens were detected as mutagens in the Host-Mediated Assay. In several cases, those carcinogens not detected may have been negative because of improper selection of the indicator. The Working Group concluded that the Host-Mediated Assay is an important test in mutagenicity/carcinogenicity research and that, by proper selection of protocols and indicators, valuable information can be gained that otherwise would be overlooked strict, in vitro assays.

Covert orienting of visual spatial attention in attention deficit hyperactivity disorder: does comorbidity make a difference?

Attentional performance in children with attention deficit hyperactivity disorder (ADHD) with and without comorbid disorders was examined using the Covert Orienting of Visuospatial Attention Task (COVAT) and the Continuous Performance Task (CPT). The relationship between these two tasks was also examined. The results showed no overall differences on the attention tasks between children with ADHD alone and those with ADHD plus other disorders. Compared to non-ADHD control children, children with ADHD showed a deficit in the disengage operation of covert visuospatial attention, suggesting a difficulty in the endogenous mode of orienting. The ADHD children also showed a general performance deficit on the CPT. Although there was a general slowing on both attention tasks in the ADHD group, there was no relationship between invalid cue effect sizes on the COVAT and the CPT measures. These results indicate that these two attention tasks may be tapping both similar and independent underlying cognitive processes in ADHD.

Psychological factors associated with short-term recovery from total knee replacement.

OBJECTIVE: To identify the psychological factors that predict short-term recovery following total knee replacement. METHOD: A group of 42 patients undergoing total knee replacement received a pre-operative psychological assessment. Four self-report questionnaires were completed: the Pain Coping Strategies Questionnaire; the Short Form Social Support Questionnaire; the Recovery Locus of Control Scale; and the Brief Symptom Inventory. Post-operative outcome was assessed in terms of the number of days taken to achieve key physiotherapy milestones (straight leg raise; 90 degrees bend of the knee) and discharge. RESULTS: The three response variables were analysed separately using an ordinal regression. Internal locus of control was associated with a shorter time to achieve a straight leg raise. Larger values of catastrophizing were associated with longer times to achieve a 90 degrees bend. There was a trend towards larger values of satisfaction with social support to be associated with an earlier achievement of the 90 degrees bend. No psychological variables were found to be associated with the length of hospital stay. CONCLUSIONS: As suggested by previous studies, coping style and locus of control appear to be important in the rehabilitation process. The current data suggest that psychological variables could be usefully included in a pre-operative assessment for total knee replacement.

Assessing inhibitory control: a revised approach to the stop signal task.

The stop signal task (stop task) is designed to assess inhibitory control and is a frequently used research tool in clinical disorders such as ADHD and schizophrenia. Previous methods of setting stop signal delay and of assessing inhibitory control are problematic. The current study reports two modifications that improve the task as a measure of inhibitory control. The first modification was to set stop signal delays proportional to go mean reaction time (go MRT) to better account for inter-subject variability in go MRT. Twenty-eight normal children were tested, and all standard, stop task dependent measures were obtained when delays were set by this method. The second modification was to calculate a novel dependent measure called the area of inhibition (AOI) which provides a more complete measure of inhibitory control than the slope of the relative finishing time z-scores (ZRFT-slope). Implications for the assessment of inhibitory control in clinical populations are discussed.

Athermal photofluidization of glasses.

Azobenzene and its derivatives are among the most important organic photonic materials, with their photo-induced trans-cis isomerization leading to applications ranging from holographic data storage and photoalignment to photoactuation and nanorobotics. A key element and enduring mystery in the photophysics of azobenzenes, central to all such applications, is athermal photofluidization: illumination that produces only a sub-Kelvin increase in average temperature can reduce, by many orders of magnitude, the viscosity of an organic glassy host at temperatures more than 100 K below its thermal glass transition. Here we analyse the relaxation dynamics of a dense monolayer glass of azobenzene-based molecules to obtain a measurement of the transient local effective temperature at which a photo-isomerizing molecule attacks its orientationally confining barriers. This high temperature (T(loc)~800 K) leads directly to photofluidization, as each absorbed photon generates an event in which a local glass transition temperature is exceeded, enabling collective confining barriers to be attacked with near 100% quantum efficiency.