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Aims/hypothesis Sudden nocturnal death in type 1 diabetes ('dead in bed' syndrome) is thought to be due to ECG QT prolongation with subsequent ventricular tachyarrhythmia in response to nocturnal hypoglycaemia. We investigated this theoretical mechanism using continuous ECG and continuous glucose monitoring in a group of patients with type 1 diabetes. Methods Twenty-five patients with type 1 diabetes (age 20-50 years) underwent two separate 24 h ECG and continuous glucose monitoring periods. Patients were fully ambulant and carried out normal daily activities. Results There were 13 episodes (26% of recordings) of nocturnal hypoglycaemia, eight of <2.2 mmol/l and five of 2.2-3.4 mmol/l. Corrected QT interval (QTc) was longer during nocturnal hypoglycaemia compared with normoglycaemic control periods (445 ± 40 vs 415 ± 23 ms; p = 0.037). Cardiac rate and rhythm disturbances (excluding sinus tachycardia) were seen in eight of the 13 nocturnal hypoglycaemia episodes (62%). These were sinus bradycardia (<40 beats/min; three episodes), ventricular ectopics (three episodes), atrial ectopics (one) and P wave abnormalities (one). Conclusions/interpretation This study demonstrates QTc prolongation and cardiac rate/rhythm disturbances in response to episodes of nocturnal hypoglycaemia in ambulant patients with type 1 diabetes. This may support an arrhythmic basis for the 'dead in bed' syndrome.

The isotope dependence of plasma transport will have a significant impact on the performance of future D-T experiments in JET and ITER and eventually on the fusion gain and economics of future reactors. In preparation for future D-T operation on JET, dedicated experiments and comprehensive transport analyses were performed in H, D and H-D mixed plasmas. The analysis of the data has demonstrated an unexpectedly strong and favourable dependence of the global confinement of energy, momentum and particles in ELMy H-mode plasmas on the atomic mass of the main ion species, the energy confinement time scaling as ${\\tau _E}\\sim {A^{0.5}}$ (Maggi et al., Plasma Phys. Control. Fusion, vol. 60, 2018, 014045; JET Team, Nucl. Fusion, vol. 39, 1999, pp. 1227–1244), i.e. opposite to the expectations based only on local gyro-Bohm (GB) scaling, ${\\tau _E}\\sim {A^{ - 0.5}}$, and stronger than in the commonly used H-mode scaling for the energy confinement (Saibene et al., Nucl. Fusion, vol. 39, 1999, 1133; ITER Physics Basis, Nucl. Fusion, vol. 39, 1999, 2175). The scaling of momentum transport and particle confinement with isotope mass is very similar to that of energy transport. Nonlinear local GENE gyrokinetic analysis shows that the observed anti-GB heat flux is accounted for if collisions, E × B shear and plasma dilution with low-Z impurities (9Be) are included in the analysis (E and B are, respectively the electric and magnetic fields). For L-mode plasmas a weaker positive isotope scaling ${\\tau _E}\\sim {A^{0.14}}$ has been found in JET (Maggi et al., Plasma Phys. Control. Fusion, vol. 60, 2018, 014045), similar to ITER97-L scaling (Kaye et al., Nucl. Fusion, vol. 37, 1997, 1303). Flux-driven quasi-linear gyrofluid calculations using JETTO-TGLF in L-mode show that local GB scaling is not followed when stiff transport (as is generally the case for ion temperature gradient modes) is combined with an imposed boundary condition taken from the experiment, in this case predicting no isotope dependence. A dimensionless identity plasma pair in hydrogen and deuterium L-mode plasmas has demonstrated scale invariance, confirming that core transport physics is governed, as expected, by the 4 dimensionless parameters ρ*, ν*, β, q (normalised ion Larmor radius, collisionality, plasma pressure and safety factor) consistently with global quasi-linear gyrokinetic TGLF calculations (Maggi et al., Nucl. Fusion, vol. 59, 2019, 076028). We compare findings in JET with those in different devices and discuss the possible reasons for the different isotope scalings reported from different devices. The diversity of observations suggests that the differences may result not only from differences affecting the core, e.g. heating schemes, but are to a large part due to differences in device-specific edge and wall conditions, pointing to the importance of better understanding and controlling pedestal and edge processes.

A quasi-linear reduced transport model is developed from a database of high-$\\beta$ electromagnetic nonlinear gyrokinetic simulations performed with spherical tokamak for energy production (STEP) relevant parameters. The quasi-linear model is fully electromagnetic and accounts for the effect of equilibrium flow shear using a novel approach. Its flux predictions are shown to agree quantitatively with predictions from local nonlinear gyrokinetic simulations across a broad range of STEP-relevant local equilibria. This reduced transport model is implemented in the T3D transport solver that is used to perform the first flux-driven simulations for STEP to account for transport from hybrid kinetic ballooning mode turbulence, which dominates over a wide region of the core plasma. Nonlinear gyrokinetic simulations of the final transport steady state from T3D return turbulent fluxes that are consistent with the reduced model, indicating that the quasi-linear model may also be appropriate for describing the transport steady state. Within the assumption considered here, our simulations support the existence of a transport steady state in STEP with a fusion power comparable to that in the burning flat top of the conceptual design, but do not demonstrate how this state can be accessed.

Aims: To determine the prevalence of overweight and obesity among patients with type 1 and type 2 diabetes mellitus attending a secondary care diabetes clinic in the United Kingdom, and to assess the impact of overweight and obesity on glycaemic control and cardiovascular risk factors in patients with type 2 diabetes. Methods: 3637 patients with diabetes were identified from the hospital electronic diabetes register, 916 with type 1 diabetes (mean (SD) age 40.4 (15.1) years, 496 male) and 2721 with type 2 diabetes (mean (SD) age 62.5 (11.8) years, 1436 male). Data on body mass index (BMI), glycaemic control, lipid profiles, and blood pressure were extracted. Results: Of patients with type 1 diabetes, 55.3% were overweight (BMI ⩾25 kg/m2), 16.6% were obese (BMI ⩾30 kg/m2), and 0.4% had morbid obesity (BMI ⩾40 kg/m2). In contrast, 86% of patients with type 2 diabetes were overweight or obese, 52% were obese, and 8.1% had morbid obesity. Obese patients with type 2 diabetes were younger, had poorer glycaemic control, higher blood pressures, worse lipid profiles, and were more likely to be receiving antihypertensive and lipid lowering drugs compared with patients with BMI <30 kg/m2. Conclusions: Obesity is the rule among patients attending this hospital diabetes clinic, with 86% of those with type 2 diabetes overweight or obese. Obesity is associated with significantly worse cardiovascular risk factors in this patient group, suggesting that more active interventions to control weight gain would be appropriate.

Abstract Objective: To monitor pregnancies in women with pre-existent insulin dependent diabetes for pregnancy loss, congenital malformations, and fetal growth in a geographically defined area of north west England. Design: Population cohort study. Setting: 10 maternity units in Cheshire, Lancashire, and Merseyside which had no regional guidelines for the management of pregnancy in diabetic women. Subjects: 462 pregnancies in 355 women with insulin dependent diabetes from the 10 centres over five years (1990-4 inclusive). Main outcome measures: Numbers and rates of miscarriages, stillbirths, and neonatal and postneonatal deaths; prevalence of congenital malformations; birth weight in relation to gestational age. Results: Among 462 pregnancies, 351 (76%) resulted in a liveborn infant, 78 (17%) aborted spontaneously, nine (2%) resulted in stillbirth, and 24 (5%) were terminated. Of the terminations, nine were for congenital malformation. The stillbirth rate was 25.0/1000 total births (95% confidence interval 8.9 to 41.1) compared with a population rate of 5.0/1000, and infant mortality was 19.9/1000 live births (5.3 to 34.6) compared with 6.8/1000. The prevalence of congenital malformations was 94.0/1000 live births (63.5 to 124.5) compared with 9.7/1000 in the general population. When corrected for gestational age, mean birth weight in the sample was 1.3 standard deviations greater than that of infants of non-diabetic mothers. Infants with congenital malformations weighed less than those without. Conclusion: In an unselected population the infants of women with pre-existent insulin dependent diabetes mellitus have a 10-fold greater risk of a congenital malformation and a fivefold greater risk of being stillborn than infants in the general population. Further improvements in the management of pregnancy in diabetic women are needed if target of the St Vincent declaration of 1989 is to be met. Key messages Infants of women with established insulin dependent diabetes mellitus have 10 times the population risk of congenital malformations and five times the stillbirth rate Excess mortality among infants of women with pre-existent insulin dependent diabetes mellitus is predominantly due to congenital malformations The birth prevalence of congenital malformations can be reduced by good periconceptional glycaemic control, but the challenge remains to implement this on a population basis Macrosomia remains a problem among infants of women with established insulin dependent diabetes mellitus

Electron cyclotron waves injected from an antenna located in the upper part of the vessel will be employed in ITER to controlMHD instabilities, particularly neoclassical tearingmodes (NTMs). The derivation of the NTM stabilization criteria used up to now to guide the optimization of the launcher is reviewed in this paper and their range of validity elucidated. Possible effects leading to a deterioration of the predicted performance through a broadening of the EC deposition profile are discussed. The most detrimental effect will likely be the scattering of the EC beams from density fluctuations, resulting in a beam broadening in the 100% range. The combined impact of these effects with that of beam misalignment (with respect to the targeted surface) is discussed for a time slice of the standard Q = 10 H-mode scenario.

STEP is a spherical tokamak prototype power plant that is being designed to demonstrate net electric power. The design phase involves the exploitation of plasma models to optimise fusion performance subject to satisfying various physics and engineering constraints. A modelling workflow, including integrated core plasma modelling, MHD stability analysis, SOL and pedestal modelling, coil set and free boundary equilibrium solvers, and whole plant design, has been developed to specify the design parameters and to develop viable scenarios. The integrated core plasma model JETTO is used to develop individual flat-top operating points that satisfy imposed criteria for fusion power performance within operational constraints. Key plasma parameters such as normalised beta, Greenwald density fraction, auxiliary power and radiated power have been scanned to scope the operational space and to derive a collection of candidate non-inductive flat-top points. The assumed auxiliary heating and current drive is either from electron cyclotron systems only or a combination of electron cyclotron and electron Bernstein waves. At present stages of transport modelling, there is a large uncertainty in overall confinement for relevant parameter regimes. For each of the two auxiliary heating and current drive systems scenarios, two candidate flat-top points have been developed based on different confinement assumptions, totalling to four operating points. A lower confinement assumption generally suggests operating points in high-density, high auxiliary power regimes, whereas higher confinement would allow access to a broader parameter regime in density and power while maintaining target fusion power performance.

Previous studies with first-principle-based integrated modelling suggested that ETG turbulence may lead to an anti-GyroBohm isotope scaling in JET high-performance hybrid H-mode scenarios. A dedicated comparison study against higher-fidelity turbulence modelling invalidates this claim. Ion-scale turbulence with magnetic field perturbations included, can match the power balance fluxes within temperature gradient error margins. Multiscale gyrokinetic simulations from two distinct codes produce no significant ETG heat flux, demonstrating that simple rules-of-thumb are insufficient criteria for its onset.

For the first time the pellet cycle of a multiple-isotope plasma is successfully reproduced with reduced turbulent transport modelling, within an integrated simulation framework. Future nuclear fusion reactors are likely to be fuelled by cryogenic pellet injection, due to higher penetration and faster response times. Accurate pellet cycle modelling is crucial to assess fuelling efficiency and burn control. In recent JET tokamak experiments, deuterium pellets with reactor-relevant deposition characteristics were injected into a pure hydrogen plasma. Measurements of the isotope ratio profile inferred a Deuterium penetration time comparable to the energy confinement time. The modelling successfully reproduces the plasma thermodynamic profiles and the fast deuterium penetration timescale. The predictions of the reduced turbulence model QuaLiKiz in the presence of a negative density gradient following pellet deposition are compared with GENE linear and nonlinear higher fidelity modelling. The results are encouraging with regard to reactor fuelling capability and burn control.

Core turbulent particle transport with multiple isotopes can display observable differences in behaviour between the electron and ion particle channels. Experimental observations at JET with mixed H-D plasmas and varying NBI and gas-puff sources [M. Maslov et al., Nucl. Fusion 7 076022 (2018)] inferred source dominated electron peaking, but transport dominated isotope peaking. In this work, we apply the QuaLiKiz quasilinear gyrokinetic transport model within JINTRAC flux-driven integrated modelling, for core transport validation in this multiple-isotope regime. The experiments are successfully reproduced, predicting self consistently \\( j \\), \\( n_{e} \\), \\( n_{Be} \\), \\( T_{e} \\), \\( T_{i} \\), \\(\\omega_{tor}\\) and the isotope composition. As seen in the experiments, both H and D profiles are predicted to be peaked regardless of the core isotope source. An extensive sensitivity study confirmed that this result does not depend on the specific choices made for the boundary conditions and physics settings. While kinetic profiles and electron density peaking did vary depending on the simulation parameters, the isotope ratio remained nearly invariant, and tied to the electron density profile. These findings have positive ramifications for multiple-isotope fuelling, burn control, and helium ash removal.