Shoe-stiffening inserts for first metatarsophalangeal joint osteoarthritis: a randomised trial.

OBJECTIVE: To evaluate the efficacy of carbon-fibre shoe-stiffening inserts in individuals with first metatarsophalangeal joint osteoarthritis. DESIGN: This was a randomised, sham-controlled, participant- and assessor-blinded trial. One hundred participants with first metatarsophalangeal joint osteoarthritis received rehabilitation therapy and were randomised to receive either carbon fibre shoe-stiffening inserts (n = 49) or sham inserts (n = 51). The primary outcome measure was the Foot Health Status Questionnaire (FHSQ) pain domain assessed at 12 weeks. RESULTS: All 100 randomised participants (mean age 57.5 (SD 10.3) years; 55 (55%) women) were included in the analysis of the primary outcome. At the 12 week primary endpoint, there were 13 drop-outs (7 in the sham insert group and 6 in the shoe-stiffening insert group), giving completion rates of 86 and 88%, respectively. Both groups demonstrated improvements in the FHSQ pain domain score at each follow-up period, and there was a significant between-group difference in favour of the shoe-stiffening insert group (adjusted mean difference of 6.66 points, 95% CI 0.65 to 12.67, P = 0.030). There were no between-group differences for the secondary outcomes, although global improvement was more common in the shoe-stiffening insert group compared to the sham insert group (61 vs 34%, RR 1.73, 95% CI 1.05 to 2.88, P = 0.033; number needed to treat 4, 95% CI 2 to 16). CONCLUSION: Carbon-fibre shoe-stiffening inserts were more effective at reducing foot pain than sham inserts at 12 weeks. These results support the use of shoe-stiffening inserts for the management of this condition, although due to the uncertainty around the effect on the primary outcome, some individuals may not experience a clinically worthwhile improvement.

Fatty-acid biomarkers and tissue-specific turnover: validation from a controlled feeding study in juvenile Atlantic croaker Micropogonias undulatus.

Fatty-acid (FA) profiles of liver and muscle tissue from juvenile Atlantic croaker Micropogonias undulatus were examined over a 15 week diet-switch experiment to establish calibration coefficients (CC) and improve understanding of consumer-diet relationships for field applications. Essential FAs [docosahexaenoic acid (DHA), 22:6n-3 and eicosapentaenoic acid (EPA) , 20:5n-3] decreased and 18:2n-6 increased in tissues of M. undulatus fed diets with increasing proportions of terrestrial v. marine lipid sources. Non-linear models used to estimate the incorporation rate and days to saturation of per cent 18:2n-6 in tissues showed that livers incorporated 18:2n-6 faster than muscle, but the proportions of 18:2n-6 in muscle were higher. CCs were established to determine proportions of FA deposition in tissues relative to diet. Many CCs were consistent amongst diet treatments, despite growth and dietary differences. The CCs can be used to discern FA modification and retention within tissues and as tools for future quantitative estimates of diet histories. Incorporation rates and CCs of 18:2n-6 were applied to a sub-set of field samples of wild M. undulatus to understand habitat use and feeding ecology. Altogether, these results suggest that FAs provide a time-integrated measure of diet in aquatic food webs and are affected by tissue type, growth rate and the influence of mixed diets.

A multichannel feature-based approach for longitudinal lung CT registration in the presence of radiation induced lung damage.

Quantifying parenchymal tissue changes in the lungs is imperative in furthering the study of radiation induced lung damage (RILD). Registering lung images from different time-points is a key step of this process. Traditional intensity-based registration approaches fail this task due to the considerable anatomical changes that occur between timepoints. This work proposes a novel method to successfully register longitudinal pre- and post-radiotherapy (RT) lung computed tomography (CT) scans that exhibit large changes due to RILD, by extracting consistent anatomical features from CT (lung boundaries, main airways, vessels) and using these features to optimise the registrations. Pre-RT and 12 month post-RT CT pairs from fifteen lung cancer patients were used for this study, all with varying degrees of RILD, ranging from mild parenchymal change to extensive consolidation and collapse. For each CT, signed distance transforms from segmentations of the lungs and main airways were generated, and the Frangi vesselness map was calculated. These were concatenated into multi-channel images and diffeomorphic multichannel registration was performed for each image pair using NiftyReg. Traditional intensity-based registrations were also performed for comparison purposes. For the evaluation, the pre- and post-registration landmark distance was calculated for all patients, using an average of 44 manually identified landmark pairs per patient. The mean (standard deviation) distance for all datasets decreased from 15.95 (8.09) mm pre-registration to 4.56 (5.70) mm post-registration, compared to 7.90 (8.97) mm for the intensity-based registrations. Qualitative improvements in image alignment were observed for all patient datasets. For four representative subjects, registrations were performed for three additional follow-up timepoints up to 48 months post-RT and similar accuracy was achieved. We have demonstrated that our novel multichannel registration method can successfully align longitudinal scans from RILD patients in the presence of large anatomical changes such as consolidation and atelectasis, outperforming the traditional registration approach both quantitatively and through thorough visual inspection.

Impact ionization-induced bistability in CMOS transistors at cryogenic temperatures for capacitorless memory applications.

Cryogenic operation of complementary metal oxide semiconductor (CMOS) silicon transistors is crucial for quantum information science, but it brings deviations from standard transistor operation. Here, we report on sharp current jumps and stable hysteretic loops in the drain current as a function of gate voltage V G for both n- and p-type commercial-foundry 180-nm-process CMOS transistors when operated at voltages exceeding 1.3 V at cryogenic temperatures. The physical mechanism responsible for the device bistability is impact ionization charging of the transistor body, which leads to effective back-gating of the inversion channel. This mechanism is verified by independent measurements of the body potential. The hysteretic loops, which have a >107 ratio of high to low drain current states at the same V G, can be used for a compact capacitorless single-transistor memory at cryogenic temperatures with long retention times.

In Silico Ventilation Within the Dose-Volume is Predictive of Lung Function Post-radiation Therapy in Patients with Lung Cancer.

Lung cancer is a leading cause of death worldwide. Radiation therapy (RT) is one method to treat this disease. A common side effect of RT for lung cancer is radiation-induced lung damage (RILD) which leads to loss of lung function. RILD often compounds pre-existing smoking-related regional lung function impairment. It is difficult to predict patient outcomes due to large variability in individual response to RT. In this study, the capability of image-based modelling of regional ventilation in lung cancer patients to predict lung function post-RT was investigated. Twenty-five patient-based models were created using CT images to define the airway geometry, size and location of tumour, and distribution of emphysema. Simulated ventilation within the 20 Gy isodose volume showed a statistically significant negative correlation with the change in forced expiratory volume in 1 s 12-months post-RT (p = 0.001, R = - 0.61). Patients with higher simulated ventilation within the 20 Gy isodose volume had a greater loss in lung function post-RT and vice versa. This relationship was only evident with the combined impact of tumour and emphysema, with the location of the emphysema relative to the dose-volume being important. Our results suggest that model-based ventilation measures can be used in the prediction of patient lung function post-RT.

Perception of letters in words: seek not and ye shall find.

Subjects perceive a letter in a briefly presented word more accurately when they attend to the whole word than when they focus their attention on just the letter they want to see.

Laser-focused atomic deposition.

The ability to fabricate nanometer-sized structures that are stable in air has the potential to contribute significantly to the advancement of new nanotechnologies and our understanding of nanoscale systems. Laser light can be used to control the motion of atoms on a nanoscopic scale. Chromium atoms were focused by a standing-wave laser field as they deposited onto a silicon substrate. The resulting nanostructure consisted of a series of narrow lines covering 0.4 millimeter by 1 millimeter. Atomic force microscopy measurements showed a line width of 65 +/- 6 nanometers, a spacing of 212.78 nanometers, and a height of 34 +/-+ 10 nanometers. The observed line widths and shapes are compared with the predictions of a semiclassical atom optical model.

Microlithography by using neutral metastable atoms and self-assembled monolayers.

Lithography can be performed with beams of neutral atoms in metastable excited states to pattern self-assembled monolayers (SAMs) of alkanethiolates on gold. An estimated exposure of a SAM of dodecanethiolate (DDT) to 15 to 20 metastable argon atoms per DDT molecule damaged the SAM sufficiently to allow penetration of an aqueous solution of ferricyanide to the surface of the gold. This solution etched the gold and transformed the patterns in the SAMs into structures of gold; these structures had edge resolution of less than 100 nanometers. Regions of SAMs as large as 2 square centimeters were patterned by exposure to a beam of metastable argon atoms. These observations suggest that this system may be useful in new forms of micro- and nanolithography.

Characterization of a high-brightness, laser-cooled Li+ ion source.

Ion sources based on laser cooling have recently provided new pathways to high-resolution microscopy, ion milling, and ion implantation. Here, we present the design and detailed characterization of a 7Li magneto-optical trap ion source (MOTIS) with a peak brightness of (1.2 ± 0.2) × 105 A m-2 sr-1 eV-1 and a maximum continuous current over 1 nA. These values significantly surpass previous Li MOTIS performance benchmarks. Using simple models, we discuss how the performance of this system relates to fundamental operating limits. This source will support a range of projects using lithium ion beams for surface microscopy and nanostructure characterization, including Li+ implantation for studies of ionic transport in energy storage materials.

Between session reliability of intramuscular electromyography for segments of gluteus medius and minimus during gait and stepping tasks.

Between-session reliability of electromyographic data is important for confidence in interpreting the role of muscles in functional tasks but critical if these data are to be compared before and after an intervention that seeks to change pathological patterns of muscle activity. The gluteus medius (GMed) and minimus (GMin) are known to have functionally discrete segments that are highly active during stance phase of gait and stepping tasks. This study measured the between-session reliability of activity patterns, mean amplitudes and time to peak (TTP) activity of these muscle segments. Intramuscular electrodes were placed in 3 segments of GMed and 2 segments of GMin in 10 healthy young adults for each of two testing sessions held two weeks apart. Participants completed six repetitions of comfortable speed walking trials, step-up and step-down tasks with activity patterns for each muscle segment time- and amplitude-normalized and averaged across trials. Re-test reliability for was high for activity patterns (coefficient of mean correlation ranging from 0.890 to 0.998) across all tasks and muscle segments and only two pairwise comparisons showing differences in amplitude between sessions. With standardized data collection and analysis procedures, GMed and GMin muscle segment activity patterns show good between-session reliability for weightbearing tasks.

In-school eyecare in special education settings has measurable benefits for children's vision and behaviour.

OBJECTIVES: To determine whether implementation of comprehensive in-school eyecare results in measurable benefits for children and young people in terms of visual status, classroom behaviours and how well their visual needs are met. DESIGN: School-based observational study. PARTICIPANTS & METHODS: 200 pupils [mean age 10 years 9 months, 70% male, majority moderate (40%) or severe (35%) learning difficulty] of a special education school in the UK. A sector-agreed in-school eyecare framework including full eye examination and cycloplegic refraction, dispensing of spectacles (as appropriate) and written reporting of outcomes to parents/teachers was applied. Classroom behaviours were observed and recorded prior to, and after, the in-school eyecare. Surveys were employed to obtain visual histories from parents/teachers. School records and statutory documents were reviewed for diagnostic and learning disability classifications. Visual function and ocular health were profiled at baseline and significant visual deficits identified. Where such deficits were previously unrecognised, untreated or not compensated for (e.g. correction of refractive error, enlargement of educational material) they were recorded as 'unmet visual need'. At follow-up, 2-5 months after initial (baseline) measures, eye examinations, parent/teacher surveys and behaviour observations were repeated. Follow-up measures were used to determine if measurable improvements were evident in visual function, ocular health, the level of unmet need and classroom behaviour following implementation of in-school eyecare. RESULTS: 199 participants completed baseline and follow-up measures. 122 (61%) participants presented with at least one significant visual or ocular health deficit and 90 (45%) participants had at least one unmet visual need. Younger pupils and those with no previous history of eyecare were more likely to demonstrate unmet visual needs at baseline (OR 1.12 95% CI 1.03 to 1.21) p = 0.012; (OR 4.44 95% CI 1.38 to 14.29 p = 0.007 respectively). On follow-up, the number of pupils with unmet visual needs dropped significantly to 36 (18%) (McNemar's test p<0.001). Visual and behavioural metrics of participants without significant visual deficits or whose visual needs were adequately addressed at baseline remained relatively unchanged between baseline and follow-up (Wilcoxon signed rank p>0.05). Where significant refractive deficits were corrected at follow-up, near visual acuity improved significantly (Wilcoxon signed rank p = 0.013), however, poor spectacle compliance was a persistent cause of unmet visual need. Off-task behaviour reduced significantly after actions to address unmet visual needs were communicated to parents and teachers (Wilcoxon signed rank p = 0.035). CONCLUSIONS: The present study demonstrates for the first time measurable visual and behaviour benefits to children in special education settings when they receive comprehensive in-school eye examinations, on-site spectacle dispensing and jargon-free reporting of outcomes to teachers and parents.

Correction: In-school eyecare in special education settings has measurable benefits for children's vision and behaviour.

[This corrects the article DOI: 10.1371/journal.pone.0220480.].

Planning lung radiotherapy using 4D CT data and a motion model.

This work is a feasibility study to use a four-dimensional computed tomography (4D CT) dataset generated by a continuous motion model for treatment planning in lung radiotherapy. The model-based 4D CT data were derived from multiple breathing cycles. Four patients were included in this retrospective study. Treatment plans were optimized at end-exhale for each patient and the effect of respiratory motion on the dose delivery investigated. The accuracy of the delivered dose as determined by the number of intermediate respiratory phases used for the calculation was considered. The time-averaged geometry of the anatomy representing the mid-ventilation phase of the breathing cycle was generated using the motion model and a treatment plan was optimized for this phase for one patient. With respiratory motion included, the mid-ventilation plan achieved better target coverage than the plan optimized at end-exhale when standard margins were used to expand the clinical target volume (CTV) to planning target volume (PTV). Using a margin to account for set-up uncertainty only, resulted in poorer target coverage and healthy tissue sparing. For this patient cohort, the results suggest that conventional three-dimensional treatment planning was sufficient to maintain target coverage despite respiratory motion. The motion model has proved a useful tool in 4D treatment planning.

A comparison of internal target volume definition by limited four-dimensional computed tomography, the addition of patient-specific margins, or the addition of generic margins when planning radical radiotherapy for lymph node-positive non-small cell lung cancer.

AIMS: Radical radiotherapy for stage II/III non-small cell lung cancer (NSCLC) includes the primary tumour and positive mediastinal lymph nodes in the clinical target volume (CTV). These move independently of each other in magnitude and direction during respiration. To prevent a geographical miss, a generic margin is usually added to the CTV to create an internal target volume (ITV). Previous studies have investigated the use of additional breath-hold computed tomography to generate patient-specific ITVs for primary tumours alone. We used a similar technique to investigate the generation of patient-specific and generic ITVs for CTVs that include mediastinal lymph nodes. MATERIALS AND METHODS: Thirteen patients with node-positive NSCLC had two limited end-tidal breath-hold computed tomography scans in addition to their planning computed tomography. The CTV was segmented in each scan and a rigid registration was carried out on the vertebral columns to align them. Different methods for generating an ITV were then analysed. RESULTS: Generic margins provided >95% mean coverage of the reference ITV. However, with the exception of 1cm expansion margins, there were cases of inadequate coverage (<95%) for each ITV. With increasing ITV margins there was a small increase in reference ITV coverage, but at the expense of a large increase in the volume of normal tissue within the ITV. DISCUSSION: For stage II/III NSCLC, ITV generation by the addition of a generic margin is not optimal. It can result in both geographical miss and excessive irradiation of normal tissue in the same treatment plan. A simple method for producing a patient-specific ITV is to co-register end-tidal breath-hold computed tomography scans to the planning scan. CONCLUSIONS: Further work is required to determine whether end-tidal breath-hold scans are representative of the anatomy at the limits of tidal respiration. Planning strategies are also needed to account for breathing cycle variation during a course of radiotherapy.

Toward adaptive radiotherapy for lung patients: feasibility study on deforming planning CT to CBCT to assess the impact of anatomical changes on dosimetry.

Changes in lung architecture during a course of radiotherapy can alter the planned dose distribution to the extent that it becomes clinically unacceptable. This study aims to validate a quantitative method of determining whether a replan is required during the course of conformal radiotherapy. The proposed method uses deformable image registration (DIR) to flexibly map planning CT (pCT) data to the anatomy of online CBCT images. The resulting deformed CT (dCT) images are used as a basis for assessing the effect of anatomical change on dose distributions. The study used retrospective data from a sample of seven replanned lung patients. The settings of an in-house, open-source DIR algorithm were first optimised for CT-to-CBCT registrations of the anatomy of the thorax. Using these optimised parameters, each patient's pCT was deformed to the CBCT acquired immediately before the replan. Registration accuracy was rigorously validated both geometrically and dosimetrically to confirm that the dCTs could reliably be used to inform replan decisions. A retrospective evaluation of the changes in dose delivered over time was then carried out for a single patient to demonstrate the clinical application of the proposed method. The geometric analysis showed good agreement between deformed structures and those same structures manually outlined on the CBCT images. Results were consistently better than those achieved with rigid-only registration. In the dosimetric analysis, dose distributions derived from the dCTs were found to match closely to the 'gold standard' replan CT (rCT) distributions across dose volume histogram and absolute dose difference measures. The retrospective analysis of serial CBCTs of a single patient produced reliable quantitative assessment of the dose delivery. Had the proposed method been available at the time of treatment, it would have enabled a more objective replan decision. DIR is a valuable clinical tool for dose recalculation in adaptive radiotherapy protocols for lung cancer patients.

MRI-guidance for motion management in external beam radiotherapy: current status and future challenges.

High precision conformal radiotherapy requires sophisticated imaging techniques to aid in target localisation for planning and treatment, particularly when organ motion due to respiration is involved. X-ray based imaging is a well-established standard for radiotherapy treatments. Over the last few years, the ability of magnetic resonance imaging (MRI) to provide radiation-free images with high-resolution and superb soft tissue contrast has highlighted the potential of this imaging modality for radiotherapy treatment planning and motion management. In addition, these advantageous properties motivated several recent developments towards combined MRI radiation therapy treatment units, enabling in-room MRI-guidance and treatment adaptation. The aim of this review is to provide an overview of the state-of-the-art in MRI-based image guidance for organ motion management in external beam radiotherapy. Methodological aspects of MRI for organ motion management are reviewed and their application in treatment planning, in-room guidance and adaptive radiotherapy described. Finally, a roadmap for an optimal use of MRI-guidance is highlighted and future challenges are discussed.

Category learning. Learning the general but not the specific.

Amnesia patients have a normal ability to learn categories from examples, even though they fail to learn the examples themselves; computational models of brain function suggest how and why.

Tracking 'differential organ motion' with a 'breathing' multileaf collimator: magnitude of problem assessed using 4D CT data and a motion-compensation strategy.

Intrafraction tumour (e.g. lung) motion due to breathing can, in principle, be compensated for by applying identical breathing motions to the leaves of a multileaf collimator (MLC) as intensity-modulated radiation therapy is delivered by the dynamic MLC (DMLC) technique. A difficulty arising, however, is that irradiated voxels, which are in line with a bixel at one breathing phase (at which the treatment plan has been made), may move such that they cease to be in line with that breathing bixel at another phase. This is the phenomenon of differential voxel motion and existing tracking solutions have ignored this very real problem. There is absolutely no tracking solution to the problem of compensating for differential voxel motion. However, there is a strategy that can be applied in which the leaf breathing is determined to minimize the geometrical mismatch in a least-squares sense in irradiating differentially-moving voxels. A 1D formulation in very restricted circumstances is already in the literature and has been applied to some model breathing situations which can be studied analytically. These are, however, highly artificial. This paper presents the general 2D formulation of the problem including allowing different importance factors to be applied to planning target volume and organ at risk (or most generally) each voxel. The strategy also extends the literature strategy to the situation where the number of voxels connecting to a bixel is a variable. Additionally the phenomenon of 'cross-leaf-track/channel' voxel motion is formally addressed. The general equations are presented and analytic results are given for some 1D, artificially contrived, motions based on the Lujan equations of breathing motion. Further to this, 3D clinical voxel motion data have been extracted from 4D CT measurements to both assess the magnitude of the problem of 2D motion perpendicular to the beam-delivery axis in clinical practice and also to find the 2D optimum breathing-leaf strategy. Issues relating to the practical calculation of the strategy, including effects on leaf velocity and effects of different spatial-sampling frequencies, have been investigated, and unattenuated-fluence maps have been produced showing the effects of the differential motion and tracking. It was discovered that large distances between adjacent leaf-ends could cause the tracking to fail when there was tissue motion across the leaf channels. To overcome this problem the use of 'synchronized' leaf trajectories, which ensure that adjacent leaf-ends are always close enough to each other to facilitate tracking, has also been investigated.

High-brightness Cs focused ion beam from a cold-atomic-beam ion source.

We present measurements of focal spot size and brightness in a focused ion beam system utilizing a laser-cooled atomic beam source of Cs ions. Spot sizes as small as (2.1 ± 0.2) nm (one standard deviation) and reduced brightness values as high as (2.4 ± 0.1) × 107 A m-2 Sr-1 eV-1 are observed with a 10 keV beam. This measured brightness is over 24 times higher than the highest brightness observed in a Ga liquid metal ion source. The behavior of brightness as a function of beam current and the dependence of effective source temperature on ionization energy are examined. The performance is seen to be consistent with earlier predictions. Demonstration of this source with very high brightness, producing a heavy ionic species such as Cs+, promises to allow significant improvements in resolution and throughput for such applications as next-generation circuit edit and nanoscale secondary ion mass spectrometry.

Evaluation of a multi-atlas CT synthesis approach for MRI-only radiotherapy treatment planning.

BACKGROUND AND PURPOSE: Computed tomography (CT) imaging is the current gold standard for radiotherapy treatment planning (RTP). The establishment of a magnetic resonance imaging (MRI) only RTP workflow requires the generation of a synthetic CT (sCT) for dose calculation. This study evaluates the feasibility of using a multi-atlas sCT synthesis approach (sCTa) for head and neck and prostate patients. MATERIAL AND METHODS: The multi-atlas method was based on pairs of non-rigidly aligned MR and CT images. The sCTa was obtained by registering the MRI atlases to the patient's MRI and by fusing the mapped atlases according to morphological similarity to the patient. For comparison, a bulk density assignment approach (sCTbda) was also evaluated. The sCTbda was obtained by assigning density values to MRI tissue classes (air, bone and soft-tissue). After evaluating the synthesis accuracy of the sCTs (mean absolute error), sCT-based delineations were geometrically compared to the CT-based delineations. Clinical plans were re-calculated on both sCTs and a dose-volume histogram and a gamma analysis was performed using the CT dose as ground truth. RESULTS: Results showed that both sCTs were suitable to perform clinical dose calculations with mean dose differences less than 1% for both the planning target volume and the organs at risk. However, only the sCTa provided an accurate and automatic delineation of bone. CONCLUSIONS: Combining MR delineations with our multi-atlas CT synthesis method could enable MRI-only treatment planning and thus improve the dosimetric and geometric accuracy of the treatment, and reduce the number of imaging procedures.