Progress at JET in integrating ITER-relevant core and edge plasmas within the constraints of an ITER-like wall

This paper reports the progress made at JET-ILW on integrating the requirements of the reference ITER baseline scenario with normalized confinement factor of 1, at a normalized pressure of 1.8 together with partially detached divertor whilst maintaining these conditions over many energy confinement times. The 2.5 MA high triangularity ELMy H-modes are studied with two different divertor configurations with D-gas injection and nitrogen seeding. The power load reduction with N seeding is reported. The relationship between an increase in energy confinement and pedestal pressure with triangularity is investigated. The operational space of both plasma configurations is studied together with the ELM energy losses and stability of the pedestal of unseeded and seeded plasmas. The achievement of stationary plasma conditions over many energy confinement times is also reported.

A diode for ferroelectric domain-wall motion

For over a decade, controlling domain wall injection, motion and annihilation along nanowires has been the preserve of the nanomagnetics research community. Revolutionary technologies have resulted, like race-track memory and domain wall logic. Until recently, equivalent research in analogous ferroic materials did not seem important. However, with the discovery of sheet conduction, the control of domain walls in ferroelectrics has become vital for the future of what has been termed “domain wall electronics”. Here we report the creation of a ferroelectric domain wall diode, which allows a single direction of motion for all domain walls, irrespective of their polarity, under a series of alternating electric field pulses. The diode’s saw-tooth morphology is central to its function. Domain walls can move readily in the direction in which thickness increases gradually, but are prevented from moving in the other direction by the sudden thickness increase at the saw-tooth edge.

Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation

Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g. chronic mountain sickness) and methodological issues. We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged (∼2 weeks) exposure to high altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders (Sherpa; 33 ± 14 years) we assessed brachial endothelium-dependent flow-mediated dilatation (FMD), endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid intima–media thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite (NO₂^–) and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3–4 (acute high altitude) and 12–14 (chronic high altitude) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlanders’ FMD (7.9 ± 0.4 vs. 6.8 ± 0.4%; P = 0.004) and GTN-induced dilatation (16.6 ± 0.9 vs. 14.5 ± 0.8%; P = 0.006), and raised central PWV (6.0 ± 0.2vs. 6.6 ± 0.3 m s⁻¹; P = 0.001). These changes persisted at days 12–14, and after allometrically scaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall:lumen ratio (∼19%, P ≤ 0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and NO₂^– increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN-induced dilatation evident during acute (n = 11, r = −0.53) and chronic (n = 7, r = −0.69; P ≤ 0.01) exposure to 5050 m. In a follow-up, placebo-controlled experiment (n = 11 healthy lowlanders) conducted in a normobaric hypoxic chamber (inspired O₂ fraction () = 0.11; 6 h), a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline (5.7 ± 1.6 vs. 8.0 ±1.3%; P < 0.01); this decline in FMD was largely reversed following α₁-adrenoreceptor blockade. In conclusion, high-altitude exposure in lowlanders caused persistent impairment in vascular function, which was mediated partially via oxidative stress and sympathoexcitation. Although a lifetime of high-altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure, chronic high-altitude exposure appears to be associated with arterial remodelling.

Endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE C282Y homozygotes

Purpose: This pilot study was aimed to establish techniques for assessing and observing trends in endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE haemochromatosis during the first year of venesection.

Patients/methods: Untreated newly diagnosed HFE haemochromatosis patients were tested for baseline liver function, iron indices, lipid profile, markers of endothelial function, anti-oxidant status and vascular compliance. Following baseline assessment, subjects attended at 6-weeks and at 3, 6, 9 and 12-months for follow-up studies.

Results: Ten patients were recruited (M = 8, F = 2, mean age = 51 years). Venesection significantly increased high density lipoproteins at 12-months (1.25 mmol/L vs. 1.37 mmol/L, p = 0.01). However, venesection did not significantly affect lipid hydroperoxides, intracellular and vascular cell adhesion molecules or high sensitivity C-reactive protein (0.57 mu mol/L vs. 0.51 mu mol/L, p = 0.45, 427.4 ng/ml vs. 307.22 ng/ml, p = 0.54, 517.70 ng/ml vs. 377.50 ng/ml, p = 0.51 and 290.75 mu g/dL vs. 224.26 mu g/dL, p = 0.25). There was also no significant effect of venesection on anti-oxidant status or pulse wave velocity (9.65 m/s vs. 8.74 m/s, p = 0.34).

Conclusions: Venesection significantly reduced high density lipoproteins but was not associated with significant changes in endothelial function, anti-oxidant status or vascular compliance. Larger studies using this established methodology are required to clarify this relationship further. 

FRENKEL-KONTOROVA DOMAIN-WALL PHASE-TRANSITIONS IN AN ADSORBED LAYER - POTASSIUM ON CO(10(1)OVER-BAR-0)

As the potassium fractional coverage of a cobalt {1010BAR} surface is increased over the range 0.2 to 0.6 monolayer the adlayer passes through a series of phase transitions. A commensurate phase is formed at exactly 0.5 monolayer, and corresponds to adatoms bonded in high-symmetry hollow sites on the unreconstructed cobalt surface, with an effective adatom radius lying between the ionic and covalent radii of potassium. A detailed structural study shows that the structural transitions can be characterised within a one-dimensional Frenkel-Kontorova model, with small lateral displacements of adatoms away from hollow sites in the low and high coverage phases. The low coverage phases progress from a distributed vacancy structure to a low density domain-wall structure; while the high coverage phase formed above half a monolayer is a high density asymmetric domain-wall structure.

Epigenetic Changes in Endothelial Progenitors as a Possible Cellular Basis for Glycemic Memory in Diabetic Vascular Complications

The vascular complications of diabetes significantly impact the quality of life and mortality in diabetic patients. Extensive evidence from various human clinical trials has clearly established that a period of poor glycemic control early in the disease process carries negative consequences, such as an increase in the development and progression of vascular complications that becomes evident many years later. Importantly, intensive glycemic control established later in the disease process cannot reverse or slow down the onset or progression of diabetic vasculopathy. This has been named the glycemic memory phenomenon. Scientists have successfully modelled glycemic memory using various in vitro and in vivo systems. This review emphasizes that oxidative stress and accumulation of advanced glycation end products are key factors driving glycemic memory in endothelial cells. Furthermore, various epigenetic marks have been proposed to closely associate with vascular glycemic memory. In addition, we comment on the importance of endothelial progenitors and their role as endogenous vasoreparative cells that are negatively impacted by the diabetic milieu and may constitute a "carrier" of glycemic memory. Considering the potential of endothelial progenitor-based cytotherapies, future studies on their glycemic memory are warranted to develop epigenetics-based therapeutics targeting diabetic vascular complications.

Ultrasound entropy may be a new non-invasive measure of pre-clinical vascular damage in young hypertensive patients

Background: The identification of pre-clinical microvascular damage in hypertension by non-invasive techniques has proved frustrating for clinicians. This proof of concept study investigated whether entropy, a novel summary measure for characterizing blood velocity waveforms, is altered in participants with hypertension and may therefore be useful in risk stratification.

Methods: Doppler ultrasound waveforms were obtained from the carotid and retrobulbar circulation in 42 participants with uncomplicated grade 1 hypertension (mean systolic/diastolic blood pressure (BP) 142/92 mmHg), and 26 healthy controls (mean systolic/diastolic BP 116/69 mmHg). Mean wavelet entropy was derived from flow-velocity data and compared with traditional haemodynamic measures of microvascular function, namely the resistive and pulsatility indices.

Results: Entropy, was significantly higher in control participants in the central retinal artery (CRA) (differential mean 0.11 (standard error 0.05 cms(-1)), CI 0.009 to 0.219, p 0.017) and ophthalmic artery (0.12 (0.05), CI 0.004 to 0.215, p 0.04). In comparison, the resistive index (0.12 (0.05), CI 0.005 to 0.226, p 0.029) and pulsatility index (0.96 (0.38), CI 0.19 to 1.72, p 0.015) showed significant differences between groups in the CRA alone. Regression analysis indicated that entropy was significantly influenced by age and systolic blood pressure (r values 0.4-0.6). None of the measures were significantly altered in the larger conduit vessel.

Conclusion: This is the first application of entropy to human blood velocity waveform analysis and shows that this new technique has the ability to discriminate health from early hypertensive disease, thereby promoting the early identification of cardiovascular disease in a young hypertensive population.

Predictors of Chest Wall Toxicity after Lung Stereotactic Ablative Radiotherapy

AIMS: To determine the incidence and predictive factors of rib fracture and chest wall pain after lung stereotactic ablative radiotherapy (SABR).

MATERIALS AND METHODS: Patients were treated with lung SABR of 48-60 Gy in four to five fractions. The treatment plan and follow-up computed tomography scans of 289 tumours in 239 patients were reviewed. Dose-volume histogram (DVH) metrics and clinical factors were evaluated as potential predictors of chest wall toxicity.

RESULTS: The median follow-up was 21.0 months (range 6.2-52.1). Seventeen per cent (50/289) developed a rib fracture, 44% (22/50) were symptomatic; the median time to fracture was 16.4 months. On univariate analysis, female gender, osteoporosis, tumours adjacent (within 5 mm) to the chest wall and all of the chest wall DVH metrics predicted for rib fracture, but only tumour location adjacent to the chest wall remained significant on the multivariate model (P < 0.01). The 2 year fracture-free probability for those adjacent to the chest wall was 65.6%. Among those tumours adjacent to the chest wall, only osteoporosis (P = 0.02) predicted for fracture, whereas none of the chest wall DVH metrics were predictive. Eight per cent (24/289) experienced chest wall pain without fracture.

CONCLUSIONS: None of the chest wall DVH metrics independently predicted for SABR-induced rib fracture when tumour location is taken into account. Patients with tumours adjacent (within 5 mm) to the chest wall are at greater risk of rib fracture after lung SABR, and among these, an additional risk was observed in osteoporotic patients.