The magnetic cage.

The Spherical Tokamak for Energy Production (STEP) requires high-field magnet designs and has therefore adopted the REBCO-based high-temperature superconductor (HTS) as its current carrier. The HTS enables the toroidal field (TF) coils to be remountable, which unlocks STEP's vertical maintenance approach; however, remountable joints, approximately 18 GJ of stored energy and limited space down the centre of a spherical tokamak, make the TF coils the most challenging. STEP has pursued a passive approach to TF coil quench protection in order to limit coil terminal voltage. Initial results suggest that a solution may rely on tuning internal coil resistance coupled with actively powered heaters. The pre-conceptual inter-coil structure demonstrates acceptable stresses and deflections under steady-state operating conditions and preliminary fault scenarios, and loads are distributed to limit the tensile force on the TF centre rod. Finally, the HTS must operate reliably in a high radiation environment and endure high neutron fluences, ensuring commercially relevant magnet lifetimes. Initial experiments indicate that instantaneous gamma irradiation of HTS has no negative impact on current carrying capacity. Experimental programmes are underway to cold irradiate HTS to fusion-relevant fluences and to develop a method of assuring tape irradiation tolerance using oxygen ions as an analogue for neutrons.This article is part of the theme issue 'Delivering Fusion Energy - The Spherical Tokamak for Energy Production (STEP)'.

Percutaneous coronary intervention in a 3-year-old with hypoplastic left heart syndrome.

Mortality outcomes associated with surgical palliation for hypoplastic left heart syndrome (HLHS) have continued to improve with time. Despite these advances, interstage mortality continues to be difficult to predict and prevent. This case report details a 3-year-old boy with HLHS palliated with a Glenn shunt who presented with acute myocardial infarction due to near total occlusion of the distal right coronary artery. He was treated by thrombus aspiration with good clinical response. This is the first report of thrombus aspiration in complex pediatric congenital heart disease and demonstrates the utility of collaboration between congenital and adult cardiologists.

Repurposing the Microsoft Kinect for Windows v2 for external head motion tracking for brain PET.

Medical imaging systems such as those used in positron emission tomography (PET) are capable of spatial resolutions that enable the imaging of small, functionally important brain structures. However, the quality of data from PET brain studies is often limited by subject motion during acquisition. This is particularly challenging for patients with neurological disorders or with dynamic research studies that can last 90 min or more. Restraining head movement during the scan does not eliminate motion entirely and can be unpleasant for the subject. Head motion can be detected and measured using a variety of techniques that either use the PET data itself or an external tracking system. Advances in computer vision arising from the video gaming industry could offer significant benefits when re-purposed for medical applications. A method for measuring rigid body type head motion using the Microsoft Kinect v2 is described with results presenting ⩽0.5 mm spatial accuracy. Motion data is measured in real-time at 30 Hz using the KinectFusion algorithm. Non-rigid motion is detected using the residual alignment energy data of the KinectFusion algorithm allowing for unreliable motion to be discarded. Motion data is aligned to PET listmode data using injected pulse sequences into the PET/CT gantry allowing for correction of rigid body motion. Pilot data from a clinical dynamic PET/CT examination is shown.

Topical bioavailability of a potential anti-acne agent (SC-23110) as determined by cumulative excretion and areas under plasma concentration time curves.

The topical bioavailability of a potential anti-acne agent ([14C]-SC-23110) was determined in the rhesus monkey, an animal model relevant to man. By the method of cumulative excretion in urine and feces the percutaneous absorption of 21 microgram/cm2 of the free base form was determined to be 0.58 +/- 0.16 (SD) percent of the applied dose. The mean areas under the plasma concentration time curves (AUC) following topical and intravenous administration were also determined. The ratior of the AUC's following topical and iv administration gave a bioavailability of 0.49% of the applied dose, a value in good agreement with the 0.58% obtained by cumulative excretion. Plasma AUC curves can be used to determined the percutaneous absorption (bioavailability) of compounds. Percutaneous absorption of [14C]-SC-23110 (80 microgram/cm2) when topically applied as the salt or free base form was compared. Twice the amount of compound was absorbed as the free base (0.34%) than as the salt (0.17%).

Variable glyceryl dinitrate formation as a function of route of nitroglycerin administration.

Plasma concentrations of 1,2- and 1,3-glyceryl dinitrates were measured in each of four healthy volunteers who received intravenous infusions (10, 20, and 40 micrograms/min), topical ointment (20 mg/200 cm2), and oral solution (6.5 mg) doses of nitroglycerin and from two subjects who received sublingual (0.4 mg) nitroglycerin. The ratio of 1,2-glyceryl dinitrate to 1,3-glyceryl dinitrate (dinitrate ratio) was determined for each subject after each dose and was found to vary with route of administration. Dinitrate ratios were 7.36, 4.60, 3.86, and 1.99 for intravenous, sublingual, topical, and oral doses, respectively. Nonspecific metabolism of nitroglycerin would result in twice as much of the 1,2-dinitrate as the 1,3-dinitrate (i.e., a dinitrate ratio of 2.0, such as that produced after oral administration). A high ratio (e.g., after intravenous administration) indicates that the metabolism was more specific. These results indicate that metabolite formation depends on route of administration, implying different metabolic specificity of enzymes in the gut, liver, skin, sublingual mucosa, and blood vessels.

Regional subacute cranial neuropathies following internal carotid cisplatin infusion.

The inferolateral trunk arises from the internal carotid artery at C-4 and provides vascular supply to cranial nerves III to VI. We report a patient who developed neuropathies of cranial nerves III, V1-3, and VI, 48 hours after infusion of cisplatin into the right internal carotid artery for an anaplastic oligoastrocytoma. The clinical and radiographic findings implicated direct toxicity to nerves in the distribution of the inferolateral trunk. We found additional cases by review of published brain tumor chemotherapy trials, thus identifying a novel, toxic neurovascular mechanism for injury to cranial nerves III to VI.

Incomplete and delayed bioavailability of sublingual nitroglycerin.

Eight healthy male volunteers received 16 doses of sublingual nitroglycerin tablets (0.4 mg). After 8 minutes, each subject rinsed out his mouth to halt the drug absorption process. The mouth rinses were assayed by high-performance liquid chromatography for residual nitroglycerin content. Each subject also received intravenous infusions of nitroglycerin so that the absolute bioavailability could be evaluated. Plasma nitroglycerin concentrations were determined using a specific and sensitive capillary gas chromatographic method capable of quantifying 25 pg/ml of nitroglycerin. The mean bioavailability (+/- standard deviation) of sublingual nitroglycerin, estimated from plasma concentrations, was 36.2 +/- 24.9% (range 2.6 to 113%). The amount of drug not absorbed after 8 minutes, as determined from the analysis of the mouth rinses, varied from 2.7 to 65.8% (mean 31.4 +/- 18.9%) of the administered sublingual dose. Mean nitroglycerin peak concentrations of 1.89 +/- 1.64 ng/ml were obtained at a mean peak time of 5.3 +/- 2.3 minutes. Thus, sublingual absorption is not instantaneous and can be relatively slow, with peak times of as long as 10 minutes. These data indicate that nitroglycerin pharmacokinetic values should not be estimated only from sublingual doses. Additionally, attempts to correlate pharmacodynamic measurements to sublingual doses must take into account the low and variable bioavailability and the potentially long peak times after sublingual nitroglycerin administration to patients.

Adaptive plasticity and diurnal rhythm in the primate spinal stretch reflex are independent phenomena.

Recent studies have revealed two phenomena producing considerable variation in amplitude of the initial, purely segmental, largely monosynaptic, response to sudden muscle stretch, the spinal stretch reflex (SSR), without change in background EMG activity or initial muscle length. The first is small and short-term, a modest diurnal rhythm in SSR amplitude. The second is large and long-term, marked adaptive change in SSR amplitude which occurs gradually over weeks and months when animals are rewarded for such change. This second phenomenon may involve persistent segmental alteration, and, if so, could constitute a technically accessible substrate of memory. The present study compared the two phenomena and sought evidence of interaction between them. The diurnal rhythm persisted, without change in phase and with only minimal change in amplitude, despite the occurrence of marked adaptive change. Animals did not utilize the rhythm to increase reward percentage by altering daily performance schedules. These results suggest that the mechanisms of the diurnal rhythm and of adaptive plasticity in SSR amplitude are separate and independent. The diurnal rhythm's effect on movement was not altered by adaptive change in SSR amplitude. This effect was comparable to adaptive change's effect on movement when both were expressed as change in movement/change in SSR amplitude.

Effect of salicylic acid on the percutaneous absorption of hydrocortisone. In vivo studies in the rhesus monkey.

To document the effect of salicylic acid on hydrocortisone penetration in vivo in the rhesus monkey, hydrocortisone 14C, with and without salicylic acid, was applied in acetone and the solvent evaporated. The compounds also were applied in a formulation (60% ethanol, 5% propylene glycol, 5% glycerin, 30% water) in which salicylic acid enhances penetration in vitro. There was a difference in the kinetics of hydrocortisone absorption with the two formulations. In acetone, excretion of 14C peaked at 48 hours and then declined. With the other formulation, excretion peaked at 48 hours, maintained to 72 hours, and then declined. There was no statistical difference in the percutaneous absorption of hydrocortisone with the addition of salicylic acid. These in vivo data are in contrast to the reported enhancing effect of salicylic acid obtained with in vitro studies.

Percutaneous absorption of hydrocortisone increases with long-term administration. In vivo studies in the rhesus monkey.

This study compares percutaneous absorption of hydrocortisone after short and long-term administration. The experimental design was to first apply 14C-hydrocortisone. This was followed by long-term administration of nonradioactive hydrocortisone. Then 14C-hydrocortisone was applied again when urinary excretion of radioactivity from the first application reached minimum detectable levels. Short- (first 14C-hydrocortisone application) and long-term (second 14C-hydrocortisone application) penetrations were compared. The level of absorption of hydrocortisone significantly increased during long-term administration, whether applied in an acetone vehicle or in a 0.9% emulsion ointment base (Eucerin). A placebo study in which only an acetone vehicle was applied for a long period followed by 14C-hydrocortisone application showed no enhanced penetration. It is suggested that long-term application of hydrocortisone alters the penetration barrier, resulting in enhanced penetration. The relevance of this long-term corticosteroid use in man is possibly of great importance.

Frequency of application on percutaneous absorption of hydrocortisone.

This study determines the percutaneous absorption of hydrocortisone when applied as a single dose or on a repetitive basis. Application was to the shaved ventral forearm of the rhesus monkey, an animal model in which some relevance to man has been shown. Absorption was quantified by measuring 14C in aliquots of urine over five days. There was no substantial difference in total absorption when 13.3 microng/sq cm was applied as a single dose or when the 13.3 microng/sq cm was applied three times, totaling 40 microng/sq cm. However, when 40 microng/sq cm was applied as a single dose, absorption was substantially increased over 13.3 microng/sq cm applied either once or three times. Additionally, when the skin was washed between applications to remove previously applied material in the three application experiment, there was a statistically significant increase over not washing the skin. The clinical importance of these results to man will await appropriate clinical studies.

Pilot study for the development of a monitoring device for ventilated children.

Airway pressure and air flow were measured at the endotracheal tube in 13 children on a variety of ventilators. These signals were stored for analysis on a computer. Further data sets were obtained after 24 hours or following major interventions. Air flow rate was integrated to give volume. Pulmonary resistance and elastance were obtained by multiple linear regression. Pressure-volume, pressure-flow and flow-volume loops were plotted. "Closed" pressure-volume and pressure-flow loops (by subtraction of the resistive or elastic pressure components, respectively) were also displayed, giving compliance and resistance loops. The loops from the initial data set were taken as the baseline, and loops from later data sets were superimposed to provide visual comparisons. Change in clinical status was reflected by the change in slope of compliance and resistance loops. A 30% change in compliance or resistance was easily observed. There was minimal interference with patient care. This pilot study demonstrates that changes in respiratory mechanics can be displayed safely and easily in ventilated patients using resistance and compliance loops. Further work is necessary to confirm the usefulness of real time of these displays.

Variations in percutaneous absorption of testosterone in the rhesus monkey due to anatomic site of application and frequency of application.

This study determines if the anatomic region affected percutaneous absorption in the rhesus monkey, an animal model with some relevance to man. Percutaneous absorption of testosterone (13.3 microgram/cm2) from the ventral forearm was 8.8 +/- 2.5%. Absorption from the chest was slightly less (5.3 +/- 0.6%) while that from the cheek was about the same (9.6 +/- 0.2%). Absorption from the scalp was greatly increased (20.4 +/- 2.7%), that from the vagina was the greatest (63.1 +/- 2.6%). As previously noted in man, anatomic variation in skin absorption exists in the rhesus. The ratio of scalp absorption to ventral forearm absorption in the rhesus was similar to that in man. The next objective was to determine the percutaneous absorption of testosterone when applied as a single dose or on a repetitive basis. There was no substantial difference in total absorption when 13.3 microgram/cm2 was applied as a single dose or when the 13.3 microgram/cm2 was applied three times, totaling 40 microgram/cm2. However, when 40 microgram/cm2 was applied as a single dose, absorption was substantially increased over 13.3 microgram/cm2 applied either once or three times. These results confirm previously reported results done with single versus repetitive doses of hydrocortisone.

The bioavailability of oral nitroglycerin.

In the 1970's, the efficacy of oral nitroglycerin therapy was seriously challenged, primarily on the basis of animal studies showing complete first-pass hepatic metabolism of nitroglycerin. Today, it is generally accepted that high oral doses of nitroglycerin do show antianginal efficacy. It has been suggested that this efficacy results from saturation of hepatic metabolism by the large oral doses administered, although the experimental evidence in humans purporting to support this may be questioned. In the present investigation, the bioavailability of oral nitroglycerin when administered in a capsule dosage form and as a solution was determined. Oral doses of nitroglycerin were less than 1% bioavailable. However, substantially high concentrations of the relatively low activity dinitrate metabolites were measured in plasma. We hypothesize that the activity of oral nitroglycerin preparations may result from high concentrations of the dinitrate metabolites, although this was not directly tested in the bioavailability studies described here.

Determination of picogram nitroglycerin plasma concentrations using capillary gas chromatography with on-column injection.

A specific, sensitive, and precise capillary gas chromatographic (GC) assay capable of analyzing picogram concentrations of nitroglycerin in human plasma was developed. The analytical procedure involves a double extraction of 1 mL of plasma with pentane, after the addition of internal standard (1 ng of 2,6-dinitrotoluene), followed by evaporation and reconstitution in 50 microL of heptane. The extract (1 microL) was injected onto a capillary column using the on-column injection technique. The GC oven temperature was programmed from 120 degrees C to 180 degrees C at a rate of 5 degrees C/min. The oven temperature was then programmed to 250 degrees C and was maintained for 10 min. The nitroglycerin and internal standard retention times were 8.6 and 11.4 min, respectively. The position of the end of the capillary column inside the detector is a critical determinant of sensitivity: the column exit must be positioned such that nitroglycerin adsorption to the detector is minimized (i.e., sensitivity maximized). The assay limit of quantitation was 25 pg/mL (CV = 7.6%) using 1 mL of plasma. This GC assay, specific for nitroglycerin in the presence of its metabolites, isosorbide dinitrate, and several other drugs, may be used to quantitate plasma levels obtained after therapeutic nitroglycerin doses.

Pharmacokinetics and bioavailability of intravenous and topical nitroglycerin in the rhesus monkey: estimate of percutaneous first-pass metabolism.

[14C]Nitroglycerin was administered intravenously and topically to three rhesus monkeys and the pharmacokinetics were determined. The rhesus monkey is an animal model for which percutaneous absorption is similar to that in the human. After intravenous administration the decline in plasma nitroglycerin concentration was biexponential with an initial half-life of 0.8 min (2-5 min postadministration) and a terminal half-life of 18 min (5-60 min postadministration). After topical application in an ointment, plasma concentrations of unchanged nitroglycerin were first detectable at 0.25 hr postapplication. Peak plasma nitroglycerin concentrations occurred between 4-6 hr, and nitroglycerin was still detectable at 24 hr postapplication. Plasma levels fit a biexponential curve with an alpha-phase half-life of 3.0 hr, a beta-phase half-life of 4.3 hr, and a lag time of 0.5 hr. The absolute bioavailability of topical nitroglycerin was 56.6 +/- 5.8%. The differences in bioavailability estimates between unchanged nitroglycerin and total carbon-14 is considered to be the amount of nitroglycerin which is metabolized as it is absorbed through the skin (percutaneous first-pass effect). This value for topical nitroglycerin was quite small, only 16-21% depending on the method of comparison.

Relative bioavailability of a new transdermal nitroglycerin delivery system.

The purpose of this study was to measure the bioavailability of nitroglycerin from a new transdermal delivery system, Nitro-Dur II, relative to that of Nitro-Dur. Twenty-four healthy male volunteers completed a two-way crossover study. Each subject randomly received Nitro-Dur (I) and Nitro-Dur II (II) for a 24-h period. Both transdermal systems had an active surface area of 20 cm2. Blood samples were collected immediately before treatment, at 0.5, 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after topical application of the units, and 30 min after the units were removed. Nitroglycerin was determined with an analytical sensitivity of 50 pg/mL using gas chromatography with electron capture detection (GC-EC). Mean steady-state concentrations of nitroglycerin were 182 and 224 pg/mL for I and II, respectively. There were no statistical differences between I and II in the pharmacokinetic parameters measured (Css, AUC, Cmax, % fluctuation). Residual nitroglycerin content was measured in each transdermal unit after application to each of the 24 volunteers. The amounts of nitroglycerin delivered by I and II were 9.78 +/- 4.11 and 10.67 +/- 4.78 mg, respectively, or approximately 10 mg in 24 h. Statistical analysis of these data using an analysis of variance indicated no significant difference between these treatments (p = 0.27). Since there were also no differences in the plasma concentrations and pharmacokinetic parameters calculated after treatment with I and II, the bioequivalence of the two delivery systems was established.

Nurses' perceptions of pain assessment and treatment in the cognitively impaired elderly. It's not a guessing game.

The purpose of the study was to describe nurses' perceptions regarding the assessment and treatment of pain in patients with late-stage dementia. Thirty nurses from six long-term care facilities were interviewed using a semistructured format for this qualitative study. Initial results were presented to a second group for validation and refinement of findings. The most commonly cited behaviors used to indicate discomfort were facial grimacing, restless body movement, change in behavior, moaning, and tense muscles. Psychotropic drugs were perceived to be commonly misused because behavior changes were seen as a psychiatric problem rather than a representation of the patient's unmet need. Nurses had positive feelings about using both narcotics and nonnarcotic analgesics with this population but believed both types of analgesics were underused. The most common concerns regarding the administration of narcotic analgesics to this population were falls, sedation, and constipation.

Single scan parameterization of space-variant point spread functions in image space via a printed array: the impact for two PET/CT scanners.

Incorporation of a resolution model during statistical image reconstruction often produces images of improved resolution and signal-to-noise ratio. A novel and practical methodology to rapidly and accurately determine the overall emission and detection blurring component of the system matrix using a printed point source array within a custom-made Perspex phantom is presented. The array was scanned at different positions and orientations within the field of view (FOV) to examine the feasibility of extrapolating the measured point source blurring to other locations in the FOV and the robustness of measurements from a single point source array scan. We measured the spatially-variant image-based blurring on two PET/CT scanners, the B-Hi-Rez and the TruePoint TrueV. These measured spatially-variant kernels and the spatially-invariant kernel at the FOV centre were then incorporated within an ordinary Poisson ordered subset expectation maximization (OP-OSEM) algorithm and compared to the manufacturer's implementation using projection space resolution modelling (RM). Comparisons were based on a point source array, the NEMA IEC image quality phantom, the Cologne resolution phantom and two clinical studies (carbon-11 labelled anti-sense oligonucleotide [(11)C]-ASO and fluorine-18 labelled fluoro-l-thymidine [(18)F]-FLT). Robust and accurate measurements of spatially-variant image blurring were successfully obtained from a single scan. Spatially-variant resolution modelling resulted in notable resolution improvements away from the centre of the FOV. Comparison between spatially-variant image-space methods and the projection-space approach (the first such report, using a range of studies) demonstrated very similar performance with our image-based implementation producing slightly better contrast recovery (CR) for the same level of image roughness (IR). These results demonstrate that image-based resolution modelling within reconstruction is a valid alternative to projection-based modelling, and that, when using the proposed practical methodology, the necessary resolution measurements can be obtained from a single scan. This approach avoids the relatively time-consuming and involved procedures previously proposed in the literature.