We provide an assessment of the Infinity Two fusion pilot plant (FPP) baseline plasma physics design. Infinity Two is a four-field period, aspect ratio $A = 10$, quasi-isodynamic stellarator with improved confinement appealing to a max-$J$ approach, elevated plasma density and high magnetic fields ($ \langle B\rangle = 9$ T). Here $J$ denotes the second adiabatic invariant. At the envisioned operating point ($800$ MW deuterium-tritium (DT) fusion), the configuration has robust magnetic surfaces based on magnetohydrodynamic (MHD) equilibrium calculations and is stable to both local and global MHD instabilities. The configuration has excellent confinement properties with small neoclassical transport and low bootstrap current ($|I_{bootstrap}| \sim 2$ kA). Calculations of collisional alpha-particle confinement in a DT FPP scenario show small energy losses to the first wall (${\lt}1.5 \,\%$) and stable energetic particle/Alfvén eigenmodes at high ion density. Low turbulent transport is produced using a combination of density profile control consistent with pellet fueling and reduced stiffness to turbulent transport via three-dimensional shaping. Transport simulations with the T3D-GX-SFINCS code suite with self-consistent turbulent and neoclassical transport predict that the DT fusion power$P_{{fus}}=800$ MW operating point is attainable with high fusion gain ($Q=40$) at volume-averaged electron densities $n_e\approx 2 \times 10^{20}$ m$^{-3}$, below the Sudo density limit. Additional transport calculations show that an ignited ($Q=\infty$) solution is available at slightly higher density ($2.2 \times 10^{20}$ m$^{-3}$) with $P_{{fus}}=1.5$ GW. The magnetic configuration is defined by a magnetic coil set with sufficient room for an island divertor, shielding and blanket solutions with tritium breeding ratios (TBR) above unity. An optimistic estimate for the gas-cooled solid breeder designed helium-cooled pebble bed is TBR $\sim 1.3$. Infinity Two satisfies the physics requirements of a stellarator fusion pilot plant.

In this work, we present a detailed assessment of fusion-born alpha-particle confinement, their wall loads and stability of Alfvén eigenmodes driven by these energetic particles in the Infinity Two Fusion Pilot Plant baseline plasma design, a four-field-period quasi-isodynamic stellarator to operate in deuterium–tritium fusion conditions. Using the Monte Carlo codes, SIMPLE, ASCOT5 and KORC-T, we study the collisionless and collisional dynamics of guiding-centre and full-orbit alpha-particles in the core plasma. We find that core energy losses to the wall are less than 4 %. Our simulations shows that peak power loads on the wall of this configuration are approximately 2.5 MW m-$^2$ and are spatially localised, toroidally and poloidaly, in the vicinity of x-points of the magnetic island chain $n/m = 4/5$ outside the plasma volume. Also, an exploratory analysis using various simplified walls shows that shaping and distance of the wall from the plasma volume can help reduce peak power loads. Our stability assessment of Alfvén eigenmodes using the STELLGAP and FAR3d codes shows the absence of unstable modes driven by alpha-particles in Infinity Two due to the relatively low alpha-particle beta at the envisioned 800 MW operating scenario.

The magnetohydrodynamic (MHD) equilibrium and stability properties of the Infinity Two fusion pilot plant baseline plasma physics design are presented. The configuration is a four-field period, aspect ratio $A = 10$ quasi-isodynamic stellarator optimised for excellent confinement at elevated density and high magnetic field $B = 9\,T$. Magnetic surfaces exist in the plasma core in vacuum and retain good equilibrium surface integrity from vacuum to an operational $\beta = 1.6 \,\%$, the ratio of the volume average of the plasma and magnetic pressures, corresponding to $800\ \textrm{MW}$ deuterium–tritium fusion operation. Neoclassical calculations show that a self-consistent bootstrap current of the order of ${\sim} 1\ \textrm{kA}$ slightly increases the rotational transform profile by less than 0.001. The configuration has a magnetic well across its entire radius. From vacuum to the operating point, the configuration exhibits good ballooning stability characteristics, exhibits good Mercier stability across most of its minor radius and it is stable against global low-n MHD instabilities up to $\beta = 3.2\,\%$.

Background: Sex and gender are related but distinct determinants of disease, treatment response, and research reproducibility whose consideration is increasingly required for research funding. Nevertheless, the quality of sex and gender reporting in neurological randomized controlled trials (RCTs) remains unknown. Methods: This ongoing study of RCTs associated with Food and Drug Administration neurological drug approvals aims to determine the frequency of accurate reporting of RCT participants’ sex and gender. Secondary outcomes include changes in reporting over time and RCT design characteristics. Results: Preliminary analysis included 145 RCTs (153,410 participants) associated with 77 medications approved in 1985-2023, most commonly for epilepsy (19%), migraine (16%), and multiple sclerosis (16%). Sixty-six RCTs (45.5%) used sex-related terms appropriately. Nine RCTs (6.2%) reported gender accurately. Fifty-three RCTs (37%) used sex- or gender-related terms interchangeably. There are no statistically significant differences in the proportions of studies reporting sex and/or gender accurately when comparing those published until versus after 2017. No RCT reported sex or gender collection methods, definitions of sex or gender, or including sex or gender minority participants. Conclusions: Preliminary results suggest shortcomings in reporting sex and, especially, gender accurately and inclusively among neurological drug RCTs and no significant improvement thereof in recent years.

We present and evaluate the prospects for detecting coherent radio counterparts to gravitational wave (GW) events using Murchison Widefield Array (MWA) triggered observations. The MWA rapid-response system, combined with its buffering mode ($\sim$4 min negative latency), enables us to catch any radio signals produced from seconds prior to hours after a binary neutron star (BNS) merger. The large field of view of the MWA ($\sim$$1\,000\,\textrm{deg}^2$ at 120 MHz) and its location under the high sensitivity sky region of the LIGO-Virgo-KAGRA (LVK) detector network, forecast a high chance of being on-target for a GW event. We consider three observing configurations for the MWA to follow up GW BNS merger events, including a single dipole per tile, the full array, and four sub-arrays. We then perform a population synthesis of BNS systems to predict the radio detectable fraction of GW events using these configurations. We find that the configuration with four sub-arrays is the best compromise between sky coverage and sensitivity as it is capable of placing meaningful constraints on the radio emission from 12.6% of GW BNS detections. Based on the timescales of four BNS merger coherent radio emission models, we propose an observing strategy that involves triggering the buffering mode to target coherent signals emitted prior to, during or shortly following the merger, which is then followed by continued recording for up to three hours to target later time post-merger emission. We expect MWA to trigger on $\sim$$5-22$ BNS merger events during the LVK O4 observing run, which could potentially result in two detections of predicted coherent emission.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

The cornerstone of obesity treatment is behavioural weight management, resulting in significant improvements in cardio-metabolic and psychosocial health. However, there is ongoing concern that dietary interventions used for weight management may precipitate the development of eating disorders. Systematic reviews demonstrate that, while for most participants medically supervised obesity treatment improves risk scores related to eating disorders, a subset of people who undergo obesity treatment may have poor outcomes for eating disorders. This review summarises the background and rationale for the formation of the Eating Disorders In weight-related Therapy (EDIT) Collaboration. The EDIT Collaboration will explore the complex risk factor interactions that precede changes to eating disorder risk following weight management. In this review, we also outline the programme of work and design of studies for the EDIT Collaboration, including expected knowledge gains. The EDIT studies explore risk factors and the interactions between them using individual-level data from international weight management trials. Combining all available data on eating disorder risk from weight management trials will allow sufficient sample size to interrogate our hypothesis: that individuals undertaking weight management interventions will vary in their eating disorder risk profile, on the basis of personal characteristics and intervention strategies available to them. The collaboration includes the integration of health consumers in project development and translation. An important knowledge gain from this project is a comprehensive understanding of the impact of weight management interventions on eating disorder risk.

OBJECTIVES/GOALS: #NAME? METHODS/STUDY POPULATION: Cell culture & protein identification: human T cells were purified from healthy blood, then activated & cultured for 5d. CAR-T cells were collected from infusion bags of cancer patients undergoing CAR-T. Silver staining of naive & activated healthy T-cell lysates was compared; B-II spectrin was upregulated and confirmed by Western blot. Migration assays: naive & activated T-cells were imaged during migration on ICAM-1 and ICAM-1 + CXCL12 coated plates. T-cells were transfected with BII-spectrin cDNA & the chemokine dependence of migration was compared with controls. In-vivo studies: in a melanoma mouse model, BII-spectrin transfected or control T-cells were injected; tumors were followed with serial imaging. Human patient records were examined to correlate endogenous BII-spectrin levels and CAR-T response. RESULTS/ANTICIPATED RESULTS: Activated T-cells downregulate the cytoskeletal protein B-II spectrin compared to naive cells, leading to chemokine-independent migration in in vitro assays and off-target trafficking when CAR-T cells are given in vivo. Restoration of B-II spectrin levels via transfection restores chemokine-dependence of activated T-cells. In a mouse melanoma model, control mice injected with standard activated T-cells showed fewer cells in the tumor site and more cells in the off-target organs (spleen, lungs) when compared to mice injected with B-II spectrin transfected cells. Furthermore, among 3 human patients undergoing CAR-T therapy, those with higher endogenous B-II spectrin levels experienced fewer side-effects, measured by the neurotoxicity and cytokine release syndrome grades. DISCUSSION/SIGNIFICANCE: A major hurdle to widespread CAR-T therapy for cancer is significant, often fatal side-effects. Our work shows that the protein B-II spectrin is downregulated during CAR-T production, and that restoring B-II spectrin levels decreases side-effects while increasing tumor clearance--hopefully translating to better CAR-T regimens for the future.

Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.

We present a broad study of linear, clustered, noble gas puffs irradiated with the frequency doubled (527 nm) Titan laser at Lawrence Livermore National Laboratory. Pure Ar, Kr, and Xe clustered gas puffs, as well as two mixed-gas puffs consisting of KrAr and XeKrAr gases, make up the targets. Characterization experiments to determine gas-puff density show that varying the experimental parameter gas-delay timing (the delay between gas puff initialization and laser-gas-puff interaction) provides a simple control over the gas-puff density. X-ray emission (>1.4 keV) is studied as a function of gas composition, density, and delay timing. Xe gas puffs produce the strongest peak radiation in the several keV spectral region. The emitted radiation was found to be anisotropic, with smaller X-ray flux observed in the direction perpendicular to both laser beam propagation and polarization directions. The degree of anisotropy is independent of gas target type but increases with photon energy. X-ray spectroscopic measurements estimate plasma parameters and highlight their difference with previous studies. Electron beams with energy in excess of 72 keV are present in the noble gas-puff plasmas and results indicate that Ar plays a key role in their production. A drastic increase in harder X-ray emissions (X-ray flash effect) and multi-MeV electron-beam generation from Xe gas-puff plasma occurred when the laser beam was focused on the front edge of the linear gas puff.

The Square Kilometre Array will be an amazing instrument for pulsar astronomy. While the full SKA will be sensitive enough to detect all pulsars in the Galaxy visible from Earth, already with SKA1, pulsar searches will discover enough pulsars to increase the currently known population by a factor of four, no doubt including a range of amazing unknown sources. Real time processing is needed to deal with the 60 PB of pulsar search data collected per day, using a signal processing pipeline required to perform more than 10 POps. Here we present the suggested design of the pulsar search engine for the SKA and discuss challenges and solutions to the pulsar search venture.

During puberty young people undergo significant hormonal changes which affect metabolism and, subsequently, health. Evidence suggests there is a period of transient pubertal insulin resistance, with this effect greater in girls than boys. However, the response to everyday high and low glycaemic index (GI) meals remains unknown. Following ethical approval, forty adolescents consumed a high GI or low GI breakfast, in a randomised cross-over design. Capillary blood samples were taken during a 2-h postprandial period, examining the glycaemic and insulinaemic responses. Maturity offset and homoeostatic model assessment (HOMA) were also calculated. The glycaemic response to the breakfasts was similar between boys and girls, as shown by similar peak blood glucose concentrations and incremental AUC (IAUC) following both high and low GI breakfasts (all P>0·05). Girls exhibited a higher peak plasma insulin concentration 30 min post-breakfast following both high GI (P=0·043, g=0·69) and low GI (P=0·010, g=0·84) breakfasts, as well as a greater IAUC following high GI (P=0·041, g=0·66) and low GI (P=0·041, g=0·66) breakfasts. HOMA was positively correlated with the insulinaemic responses (all P<0·0005) and maturity offset (P=0·037). The findings of the present study suggest that pubertal insulin resistance affects the postprandial insulinaemic responses to both high and low GI meals. Specifically, girls exhibit a greater insulinaemic response than boys to both meals, despite similar glycaemic responses. This study is the first to report the glycaemic and insulinaemic responses to everyday meals in boys and girls, supporting the recommendation for young people to base their diet on low GI carbohydrates.

This paper presents a comparison of linear and non-linear methods for the analysis of aeroelastic behaviour and flutter boundary prediction. The methods in question include NASTRAN and ZAERO, based on linear aerodynamics, and the non-linear coupled CFD-CSD methods RANSMB and PMB, developed at the Universities of Bristol and Glasgow respectively. The test cases used for this comparison are the MDO and AGARD 445.6 weakened wing. In general, it was found that the non-linear methods demonstrate excellent agreement with respect to pressure distributions, deflections, dynamic behaviour, and flutter boundary locations for both cases. This is in contrast to previous studies involving similar methods, where notable differences across the MDO span were found, and is taken to imply good performance of the CFD-CSD interpolation schemes employed here. While the linear methods produce similar flutter boundaries to the coupled codes for the aerodynamically simple AGARD 445.6 wing, results for the transonic ‘rooftop’ MDO wing design did not agree as well.

Novel free boundary magnetohydrodynamic equilibrium states with spontaneous three-dimensional (3-D) deformations of the plasma–vacuum interface are computed. The structures obtained look like saturated ideal external kink/peeling modes. Large edge pressure gradients yield toroidal mode number $n=1$ distortions when the edge bootstrap current is large and higher $n$ corrugations when this current is small. Linear ideal MHD stability analyses confirm the nonlinear saturated ideal kink equilibrium states produced and we can identify the Pfirsch–Schlüter current as the main linear instability driving mechanism when the edge pressure gradient is large. The dominant non-axisymmetric component of this Pfirsch–Schlüter current drives a near resonant helical parallel current density ribbon that aligns with the near vanishing magnetic shear region caused by the edge bootstrap current. This current ribbon is a manifestation of the outer mode previously found on JET (Solano 2010). We claim that the equilibrium corrugations describe structures that are commonly observed in quiescent H-mode tokamak discharges.

A large area nanogap electrode fabrication method combinig conventional lithography patterning with the of focused ion beam (FIB) is presented. Lithography and a lift-off process were used to pattern 50 nm thick platinum pads having an area of 300 μm × 300 μm. A range of 30-300 nm wide nanogaps (length from 300 μm to 10 mm ) were then etched using an FIB of Ga+ at an acceleration voltage of 30 kV at various beam currents. An investigation of Ga+ beam current ranging between 1-50 pA was undertaken to optimise the process for the current fabrication method. In this study, we used Monte Carlo simulation to calculate the damage depth in various materials by the Ga+. Calculation of the recoil cascades of the substrate atoms are also presented. The nanogap electrodes fabricated in this study were found to have empty gap resistances exceeding several hundred MΩ. A comparison of the gap length versus electrical resistance on glass substrates is presented. The results thus outline some important issues in low-conductance measurements. The proposed nanogap fabrication method can be extended to various sensor applications, such as chemical sensing, that employ the nanogap platform. This method may be used as a prototype technique for large-scale fabrication due to its simple, fast and reliable features.