Evidence of Toroidally Localized Turbulence with Applied 3D Fields in the DIII-D Tokamak.

New evidence indicates that there is significant 3D variation in density fluctuations near the boundary of weakly 3D tokamak plasmas when resonant magnetic perturbations are applied to suppress transient edge instabilities. The increase in fluctuations is concomitant with an increase in the measured density gradient, suggesting that this toroidally localized gradient increase could be a mechanism for turbulence destabilization in localized flux tubes. Two-fluid magnetohydrodynamic simulations find that, although changes to the magnetic field topology are small, there is a significant 3D variation of the density gradient within the flux surfaces that is extended along field lines. This modeling agrees qualitatively with the measurements. The observed gradient and fluctuation asymmetries are proposed as a mechanism by which global profile gradients in the pedestal could be relaxed due to a local change in the 3D equilibrium. These processes may play an important role in pedestal and scrape-off layer transport in ITER and other future tokamak devices with small applied 3D fields.

PAR-1 antagonist vorapaxar favorably improves global thrombotic status in patients with coronary disease.

To assess the effect of vorapaxar on global thrombotic and thrombolytic status. The propensity for thrombus formation is determined by the balance between prothrombotic factors and endogenous thrombolysis. Impaired thrombolytic status increases cardiovascular risk. Vorapaxar is a novel, oral, protease-activated receptor-1 antagonist that inhibits thrombin-induced platelet activation. In the TRACER and TRA 2°P-TIMI 50 studies, patients with acute coronary syndromes and established atherosclerosis were randomized to vorapaxar 2.5 mg daily or placebo, in addition to standard care. In 57 patients enrolled in a single center, blood was tested with the point-of-care global thrombosis test, on and off treatment. This automated test employs non-anticoagulated blood to assess thrombotic and thrombolytic status, measuring the time required to form a shear-induced thrombus under physiological conditions (occlusion time, OT), and subsequently, the time to achieve endogenous lysis of the thrombus (lysis time, LT). Patients on vorapaxar exhibited longer OT on vs. off treatment [median 561 s (interquartile range 422-654) vs. 372 s(338-454), P = 0.003] and shorter LT on treatment than off [1,158 s(746-1,492) vs. 1,733 s(1,388-2,230), P = 0.016]. Patients on placebo showed no difference in OT [419 s(343-514) vs. 411 s(346-535), P = 0.658] or LT [1,236 s(985-1,594) vs. 1,400 s(1,092-1,686), P = 0.524] on and off treatment. During treatment, OT was longer in patients taking vorapaxar [561 s(422-654) vs. 419 s(343-514), P = 0.009], but LT was similar in vorapaxar and placebo arms [1,158 s(746-1,492) vs. 1,236 s(985-1,594), P = 0.277]. Vorapaxar prolongs OT and shortens LT, with favorable effects on thrombotic and thrombolytic status. In addition to its antiplatelet effect, vorapaxar may enhance endogenous thrombolysis, which is frequently impaired in coronary disease.

Methane emissions among individual dairy cows during milking quantified by eructation peaks or ratio with carbon dioxide.

The aims of this study were to compare methods for examining measurements of CH4 and CO2 emissions of dairy cows during milking and to assess repeatability and variation of CH4 emissions among individual dairy cows. Measurements of CH4 and CO2 emissions from 36 cows were collected in 3 consecutive feeding periods. In the first period, cows were fed a commercial partial mixed ration (PMR) containing 69% forage. In the second and third periods, the same 36 cows were fed a high-forage PMR ration containing 75% forage, with either a high grass silage or high maize silage content. Emissions of CH4 during each milking were examined using 2 methods. First, peaks in CH4 concentration due to eructations during milking were quantified. Second, ratios of CH4 and CO2 average concentrations during milking were calculated. A linear mixed model was used to assess differences between PMR. Variation in CH4 emissions was observed among cows after adjusting for effects of lactation number, week of lactation, diet, individual cow, and feeding period, with coefficients of variation estimated from variance components ranging from 11 to 14% across diets and methods of quantifying emissions. No significant difference was detected between the 3 PMR in CH4 emissions estimated by either method. Emissions of CH4 calculated from eructation peaks or as CH4 to CO2 ratio were positively associated with forage dry matter intake. Ranking of cows according to CH4 emissions on different diets was correlated for both methods, although rank correlations and repeatability were greater for CH4 concentration from eructation peaks than for CH4-to-CO2 ratio. We conclude that quantifying enteric CH4 emissions either using eructation peaks in concentration or as CH4-to-CO2 ratio can provide highly repeatable phenotypes for ranking cows on CH4 output.

Calibration improvements expand filterscope diagnostic use.

The filterscope diagnostic on DIII-D utilizes photomultiplier tubes to measure visible light emission from the plasma. The system has undergone a substantial upgrade since previous attempts to cross-calibrate the filterscope with other spectroscopic diagnostics were unsuccessful. The optics now utilize a dichroic mirror to initially split the light at nearly 99% transmission or reflectance for light below or above 550 nm. This allows the system to measure Dα emission without degrading visible light emission from the plasma for wavelengths below 550 nm (to measure Dß, Dγ, W-I, C-III, etc.). Additional optimization of the optical components and calibration techniques reduce the error in the signal up to 10% in some channels compared to previous methods. Cross-calibration measurements with two other high resolution spectroscopic diagnostics now show excellent agreement for the first time. This expands the capabilities of the filterscope system allowing measurement of divertor detachment, emission profiles, edge-localized mode behavior, and plasma-wall interactions. It also enables direct comparisons against calculations from boundary plasma simulations. These were not possible before.

Highest fusion performance without harmful edge energy bursts in tokamak.

The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.

The natural history of anal transition zone inflammation and possible relationship to pouchitis: a long-term longitudinal study.

AIM: Reservoir ileitis (pouchitis) is the most common complication after pelvic pouch surgery for ulcerative colitis and the aetiology remains largely unknown. The anal transition zone (ATZ) contains the only remaining colonic epithelium after ileal pouch anal anastomosis (IPAA) and may provide important clues as to whether ulcerative colitis and pouchitis share a common pathogenesis. The aim of this study was to evaluate longitudinally the long-term histological changes in the ATZ and their relationship to the incidence of pouchitis. METHOD: Patients with a double-stapled IPAA for ulcerative colitis at an academic medical centre with at least 10 years of clinical and histological follow-up were identified from a prospective database. Annual ATZ and pouch biopsies were taken and interpreted by two expert gastrointestinal pathologists. ATZ histological variability score, the incidence of pouchitis, and function were correlated over time. ATZ biopsies were scored from one to three based on the extent of inflammation. RESULTS: Sixteen of the 114 patients having IPAA fulfilled the criteria for admission to the study. There were 179 biopsies of the ATZ. All exhibited variability in ATZ histology over time and 81% had a 2-unit change in their inflammatory score. There was no correlation between pouchitis and histological severity score of the ATZ. Similarly, function over time did not vary with the intensity of ATZ inflammation. CONCLUSION: ATZ inflammation varies substantially over time in most patients. But these changes from year to year did not correlate with function or the occurrence of pouchitis.

Using Statistical Shape and Appearance Modelling to characterise the 3D shape and material properties of human lumbar vertebrae: A proof of concept study.

Patient variation affects the outcomes of a range of spinal interventions, from disc replacement to vertebral fixation and vertebroplasty. Statistical Shape and Appearance Modelling (SSAM) can be used to describe anatomical variation and pathological differences within the population. To better understand how bone density and shape variation affect load transfer with respect to surgical treatments, Finite Element (FE) models can be generated from a SSAM. The aim for this study is to understand whether geometric and density variation as well as multiple vertebral levels can be incorporated into a single SSAM and whether this can be used to investigate the relationships between, and effects of, the various modes of variation. FE models of 14 human lumbar vertebrae that had been µCT imaged and validated through experimental testing were used as input specimens for a SSAM. The validity of the SSAM was evaluated by using principal component analysis to identify the primary modes of geometric and bone density variation and comparing to those in the input set. FE models were generated from the SSAM to examine the response to loading. The mean error between the input set and generated models for volume, mean density and FE compressive stiffness were 10%, 3% and 10% respectively. Principal Component (PC) 1 captured the majority of the bone density variation. The remaining PCs described specific geometric variation. The FE models generated from the SSAM showed the variations in vertebral stiffness as a result of complex relationships between bone density and shape. The SSAM created has limited data for its input set, however, it acts as a proof of concept for the novel combination of material and shape variation into a single shape model. This approach and the tools developed can be applied to wider patient groups and treatment scenarios to improve patient stratification and to optimise treatments.

High-density lipoprotein-cholesterol and not HbA1c was directly related to cardiovascular outcome in PROactive.

AIM: In PROactive, pioglitazone reduced the incidence of death, myocardial infarction and stroke, and significantly improved HbA1c, systolic blood pressure (SBP), triglycerides and high-density lipoprotein (HDL)-cholesterol relative to placebo. As these glycaemic and lipid parameters are major cardiovascular (CV) risk factors, we assessed their separate contribution to the reduced incidence of CV outcomes. METHODS: Patients (n = 5238) with type 2 diabetes and macrovascular disease were randomized to 45 mg pioglitazone or placebo. Relationships among treatment, outcome (time to first event of all-cause mortality, myocardial infarction and stroke) and 10 laboratory measurements and vital signs were investigated using log-linear models. Continuous variable measurements (percent changes from baseline to average of all postbaseline values prior to censoring) were made discrete by categorizing into tertiles. Log-linear models were fitted to multiway tables of discrete data and analysis of deviance used to summarize sources of variation in the data. RESULTS: Although pioglitazone treatment was associated with a decrease in HbA1c and an increase in HDL-cholesterol (HDL-C), only the change from baseline HDL-C predicted the outcome (χ(2) = 28.89, p < 0.0001). No other variables, including HbA1c, triglycerides and systolic blood pressure, showed significant direct associations with outcome. When the analysis was extended to include baseline statin use, this was associated with an improved outcome independently of HDL-C changes. CONCLUSIONS: This post hoc analysis suggests that HDL-C, but probably not HbA1c, is a driver of pioglitazone's favourable influence on CV outcome.

Review of in vitro mechanical testing for intervertebral disc injectable biomaterials.

Many early stage interventions for intervertebral disc degeneration are under development involving injection of a biomaterial into the affected tissue. Due to the complex mechanical behaviour of the intervertebral disc, there are challenges in comprehensively evaluating the performance of these injectable biomaterials in vitro. The aim of this review was to examine the different methods that have been developed to mechanically test injectable intervertebral disc biomaterials in an in vitro disc model. Testing methods were examined with emphasis on overall protocol, artificial degeneration method, mechanical testing regimes and injection delivery. Specifically, the effects of these factors on the evaluation of different aspects of device performance was assessed. Broad testing protocols varied between studies and enabled evaluation of different aspects of an injectable treatment. Studies employed artificial degeneration methodologies which were either on a macro scale through mechanical means or on a microscale with biochemical means. Mechanical loading regimes differed greatly across studies, with load being either held constant, ramped to failure, or applied cyclically, with large variability on all loading parameters. Evaluation of the risk of herniation was possible by utilising ramped loading, whereas cyclic loading enabled the examination of the restoration of mechanical behaviour for initial screening of biomaterials and surgical technique optimisation studies. However, there are large variations in the duration or tests, and further work is needed to define an appropriate number of cycles to standardise this type of testing. Biomaterial delivery was controlled by set volume or haptic feedback, and future investigations should generate evidence applying physiological loading during injection and normalisation of injection parameters based on disc size. Based on the reviewed articles and considering clinical risks, a series of recommendations have been made for future intervertebral disc mechanical testing.

The influence of a 16-week exercise program, APOE status, and age on executive function task performance: A randomized trial.

Previous research has shown beneficial cognitive changes following exercise training in older adults. However, the work on the potential moderating effects of Apoliprotein E (APOE) ε4 carrier status has been mixed, and the role of exercise intensity remains largely unexplored. The present study sought to examine the influence of APOE ε4 status and exercise intensity on measures of cognitive performance in a group of older adults. Cross-sectional comparisons between a group of younger inactive adults (n = 44, age = 28.86 ± 0.473 SD, 60.5% female) and a group of older inactive adults (n = 142, age = 67.8 ± 5.4, 62.7% female) were made on baseline measurements of APOE ε4 status, VO2peak, and cognitive performance in the domain of executive functioning. The older adults also participated in a randomized controlled exercise trial, exercising three times per week for 16-weeks in either a low-intensity continuous training (LICT) group or a moderate-intensity continuous training plus interval training (MICT+IT) group at the Center for Health and Neuroscience, Genes, and Environment (CUChange) Exercise Laboratory. Follow-up measurements of VO2peak and cognitive performance were collected on the older adults after the exercise intervention. Cross-sectional comparisons between the older and younger adults demonstrated significant impairments among older adults in Stroop effect on error and time, Category Switch mixing effects, and Keep Track task. This impairment was not moderated by APOE ε4 carrier status. Improvements from pre- to post-exercise intervention were observed in both exercise groups in Stroop effect on error ([F (1, 256) = 9.381, p < 0.01, η2 = 0.031]) and Category Switch switching effect reaction time ([F(1, 274) = 4.442, p < 0.05, η2 = 0.020]), with no difference between exercise groups. The moderating effects of APOE ε4 carrier status were mixed. Exercise did not improve the Stroop effect on error among ε4 carriers assigned to MICT+IT when improvements were seen in all other groups. Further research is needed to examine the mechanisms of action by which exercise impacts cognitive task performance, and possible moderators such as genetic variability and exercise intensity.

Time-resolved pump-probe experiments at the LCLS.

The first time-resolved x-ray/optical pump-probe experiments at the SLAC Linac Coherent Light Source (LCLS) used a combination of feedback methods and post-analysis binning techniques to synchronize an ultrafast optical laser to the linac-based x-ray laser. Transient molecular nitrogen alignment revival features were resolved in time-dependent x-ray-induced fragmentation spectra. These alignment features were used to find the temporal overlap of the pump and probe pulses. The strong-field dissociation of x-ray generated quasi-bound molecular dications was used to establish the residual timing jitter. This analysis shows that the relative arrival time of the Ti:Sapphire laser and the x-ray pulses had a distribution with a standard deviation of approximately 120 fs. The largest contribution to the jitter noise spectrum was the locking of the laser oscillator to the reference RF of the accelerator, which suggests that simple technical improvements could reduce the jitter to better than 50 fs.

Optimisation of the mechanical and handling properties of an injectable calcium phosphate cement.

Calcium phosphate cements have the potential to be successful in minimally invasive surgical techniques, like that of vertebroplasty, due to their ability to be injected into a specific bone cavity. These bone cements set to produce a material similar to that of the natural mineral component in bone. Due to the ceramic nature of these materials they are highly brittle and it has been found that they are difficult to inject. This study was carried out to determine the factors that have the greatest effect on the mechanical and handling properties of an apatitic calcium phosphate cement with the use of a Design of Experiments (DoE) approach. The properties of the cement were predominantly influenced by the liquid:powder ratio and weight percent of di-sodium hydrogen phosphate within the liquid phase. An optimum cement composition was hypothesised and tested. The mechanical properties of the optimised cement were within the clinical range for vertebroplasty, however, the handling properties still require improvement.

Modelling cement augmentation: a comparative experimental and finite element study at the continuum level.

Subject-specific computational models of anatomical components can now be generated from image data and used in the assessment of orthopaedic interventions. However, little work has been undertaken to model cement-augmented bone using these methods. The purpose of this study was to investigate different methods of representing a trabecular-like material (open-cell polyurethane foam, Sawbone, Sweden) augmented with poly(methyl methacrylate) (PMMA) bone cement in a finite element (FE) model. Three sets of specimens (untreated, fully augmented with cement, partially augmented with cement) were imaged using micro computed tomography (microCT) and tested under axial compression. Subject-specific continuum level FE models were built based on the microCT images. Using the first two sets of models, the material conversion factors between image greyscale and mechanical properties for the pure synthetic bone and cement-augmented composite were determined iteratively by matching the FE predictions to the experimental measurements. By applying these greyscale related mechanical properties to the FE models of the partially augmented specimens, the predicted stiffness was found to be more accurate (approximately 5 per cent error) than using homogeneous properties for the augmented and synthetic bone regions (approximately 18 per cent error). It was also found that the predicted stiffness using the modulus of pure cement to define the augmented region was overestimated, and generally the apparent elastic modulus was dominated by the properties of the synthetic bone.

Sex Discrimination in Gerris remigis: Role of a Surface Wave Signal.

Even when blinded with masks, adult male water striders (Gerris remigis) accurately ascertain the sex of other adult water striders in the laboratory. Freely moving females that were artificially made to play back computer-generated male surface wave and body-contact signals of about 90 waves per second were treated as males by the masked males and as females when no such playbacks were made. Thus, the males can use presence or absence of the male signal as the sole means for sex discrimination.

Crisis management: some opportunities.

Modern crises present decision makers with many agonizing management choices. Very often a crisis manager is confronted with a plethora of conflicting information and given very little time to choose an appropriate course of action. Although contemporary methods of systems analysis have been used in attempts to organize data and clarify options, they have generally been of little use in presenting an accurate picture of an opponent's values and perceptions. Thus it is clear that we must now make use of the improved communications and technological devices at our disposal if crises are to be avoided or resolved with minimum damage. Our proposal to establish international model-oriented computer-assisted conferences is designed to promote greater cooperation and understanding among scientists and crisis managers of differing nations by enabling them to share images of themselves and one another. With better information and more rational options available, the chances of catastrophic misunderstanding or miscalculation can be meaningfully reduced. We have proposed a possible scenario for the initial implementation of such a system to combat famine, and hope that the same approach might be used in other areas over time. The ultimate goal is a system by which specialists of all persuasions cooperate so that international crises will be resolved on the bases of mutual benefits without resort to armed conflict.

Hashimoto's encephalopathy masquerading as acute psychosis.

Hashimoto's encephalopathy (HE) is a relapsing, but exquisitely corticosteroid-responsive encephalopathy associated with autoimmune thyroiditis. Although a rare disease, with just over 100 cases reported, it may be under-recognised. Its presentation can be protean with prominent neuropsychiatric features, stroke-like episodes, seizures and myoclonic jerks. Prompt corticosteroid treatment usually leads to rapid recovery. Here we report a patient with HE, initially presenting with florid neuropsychiatric symptoms. Recent developments in the understanding of this condition are discussed.

Development of specimen-specific finite element models of human vertebrae for the analysis of vertebroplasty.

The aim of this study was to determine the accuracy of specimen-specific finite element models of untreated and cement-augmented vertebrae by direct comparison with experimental results. Eleven single cadaveric vertebrae were imaged using micro computed tomography (microCT) and tested to failure in axial compression in the laboratory. Four of the specimens were first augmented with PMMA cement to simulate a prophylactic vertebroplasty. Specimen-specific finite element models were then generated using semi-automated methods. An initial set of three untreated models was used to determine the optimum conversion factors from the image data to the bone material properties. Using these factors, the predicted stiffness and strength were determined for the remaining specimens (four untreated, four augmented). The model predictions were compared with the corresponding experimental data. Good agreement was found with the non-augmented specimens in terms of stiffness (root-mean-square (r.m.s.) error 12.9 per cent) and strength (r.m.s. error 14.4 per cent). With the augmented specimens, the models consistently overestimated both stiffness and strength (r.m.s. errors 65 and 68 per cent). The results indicate that this method has the potential to provide accurate predictions of vertebral behaviour prior to augmentation. However, modelling the augmented bone with bulk material properties is inadequate, and more detailed modelling of the cement region is required to capture the bone-cement interactions if the models are to be used to predict the behaviour following vertebroplasty.

Verification of Doppler coherence imaging for 2D ion velocity measurements on DIII-D.

Coherence Imaging Spectroscopy (CIS) has emerged as a powerful tool for investigating complex ion phenomena in the boundary of magnetically confined plasma devices. The combination of Fourier-transform interferometry and high-resolution fast-framing cameras has made it possible to make sensitive velocity measurements that are also spatially resolved. However, this sensitivity makes the diagnostic vulnerable to environmental effects including thermal drifts, vibration, and magnetic fields that can influence the velocity measurement. Additionally, the ability to provide an absolute calibration for these geometries can be impacted by differences in the light-collection geometry between the plasma and reference light source, spectral impurities, and the presence of thin-films on in-vessel optics. This paper discusses the mitigation of these effects and demonstration that environmental effects result in less than 0.5 km/s error on the DIII-D CIS systems. A diagnostic comparison is used to demonstrate agreement between CIS and traditional spectroscopy once tomographic artifacts are accounted for.

A multiple ligand-binding radioimmunoassay of diiodotyrosine.

A radioimmunoassay has been developed for the measurement of 3,5-diiodo-L-tyrosine (DIT) in serum. DIT was coupled to porcine thyroglobulin (PTg) with a molar ratio of 205:1. Rabbits were immunized with 1 mg of immunogen emulsified in complete Freund's adjuvant. Sera were screened for their ability to bind trace amounts of [125I]DIT. A serum that bound 40% of the tracer at a final dilution of 1:1,750 was used in the assay. Assay specificity was improved by the use of thyroxine (T4)-binding globulin as a second ligand-binding protein to decrease T4 and triiodothyronine (T3) cross-reactivity with the antibody. Double antibody and polyethylene glycol radioimmunoassays were compared. DIT present in the second antiserum shifted the double antibody assay standard curve and altered estimates of assay specificity and assay sensitivity. By using the polyethylene glycol system and butanol:ethanol extracts of serum, DIT was measured in human serum. In 35 apparently healthy young adult controls DIT levels averaged 156 ng/100 ml. Random DIT levels averaged 158 ng/100 ml in 11 untreated hyperthyroid patients and 84 ng/100 ml in 15 untreated primary hypothyroid patients. No diurnal pattern in DIT levels could be demonstrated. Thyroid-stimulating hormone administration led to a variable but small rise in DIT levels, but short term T3 suppression was not associated with a measurable fall in DIT concentrations. Paired serum samples from the carotid artery and thyroid vein of 10 euthyroid goiter patients and one patient with a toxic solitary adenoma all showed a positive transthyroidal gradient indicating the thyroidal release of DIT in each patient. Measurable DIT levels of 45, 47, 68, and 80 ng/100 ml, respectively, were found in four fasting athyrotic patients indicating that the thyroid is not the only source of serum DIT.

Two cases of Cryptococcus meningitis presenting as leukoencephalopathy prior to amphotericin therapy.

We report two patients with cryptococcal meningitis and combined immunodeficiency with unusual magnetic resonance imaging findings of gadolinium-enhancing white matter lesions, quite different from cryptococcomas and seen prior to anti-fungal treatment. The lesions resembled demyelinating plaques and resolved. In one patient, biopsy of the lesion revealed cryptococci, non-specific inflammatory changes and occasional small perivascular lymphocyte collections, but not demyelination. Leukoencephalopathy, previously rarely observed in Cryptococcal meningitis, was thought to be the sequelae of amphotericin toxicity. Our cases demonstrate cryptococcal meningitis may present with leukoencephalopathy, possibly as an immune response to the organism.