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.

In this paper, we construct operator fractional Lévy motion (ofLm), a broad class of infinitely divisible stochastic processes that are covariance operator self-similar and have wide-sense stationary increments. The ofLm class generalizes the univariate fractional Lévy motion as well as the multivariate operator fractional Brownian motion (ofBm). OfLm can be divided into two types, namely, moving average (maofLm) and real harmonizable (rhofLm), both of which share the covariance structure of ofBm under assumptions. We show that maofLm and rhofLm admit stochastic integral representations in the time and Fourier domains, and establish their distinct small- and large-scale limiting behavior. We also characterize time-reversibility for ofLm through parametric conditions related to its Lévy measure. In particular, we show that, under non-Gaussianity, the parametric conditions for time-reversibility are generally more restrictive than those for the Gaussian case (ofBm).

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.

Postprandial glycaemia and insulinaemia are important risk factors for type 2 diabetes. The prevalence of insulin resistance in adolescents is increasing, but it is unknown how adolescent participant characteristics such as BMI, waist circumference, fitness and maturity offset may explain responses to a standard meal. The aim of the present study was to examine how such participant characteristics affect the postprandial glycaemic and insulinaemic responses to an ecologically valid mixed meal. Data from the control trials of three separate randomised, crossover experiments were pooled, resulting in a total of 108 participants (fifty-two boys, fifty-six girls; aged 12·5 (SD 0·6) years; BMI 19·05 (SD 2·66) kg/m2). A fasting blood sample was taken for the calculation of fasting insulin resistance, using the homoeostatic model assessment of insulin resistance (HOMA-IR). Further capillary blood samples were taken before and 30, 60 and 120 min after a standardised lunch, providing 1·5 g/kg body mass of carbohydrate, for the quantification of blood glucose and plasma insulin total AUC (tAUC). Hierarchical multiple linear regression demonstrated significant predictors for plasma insulin tAUC were waist circumference, physical fitness and HOMA-IR (F(3,98) = 36·78, P < 0·001, adjusted R2 = 0·515). The variance in blood glucose tAUC was not significantly explained by the predictors used (F(7,94) = 1·44, P = 0·198). Significant predictors for HOMA-IR were BMI and maturity offset (F(2,102) = 14·06, P < 0·001, adjusted R2 = 0·021). In summary, the key findings of the study are that waist circumference, followed by physical fitness, best explained the insulinaemic response to an ecologically valid standardised meal in adolescents. This has important behavioural consequences because these variables can be modified.

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.

We observed the 2 July 2019 total solar eclipse with a variety of imaging and spectroscopic instruments recording from three sites in mainland Chile: on the centerline at La Higuera, from the Cerro Tololo Inter-American Observatory, and from La Serena, as well as from a chartered flight at peak totality in mid-Pacific. Our spectroscopy monitored Fe X, Fe XIV, and Ar X lines, and we imaged Ar X with a Lyot filter adjusted from its original H-alpha bandpass. Our composite imaging has been compared with predictions based on modeling using magnetic-field measurements from the pre-eclipse month. Our time-differenced sites will be used to measure motions in coronal streamers.

Plumes generated by vertically distributed sources of buoyancy have been observed to have substantially lower entrainment coefficients than their equivalent-geometry constant buoyancy flux plumes. Two differences between distributed and localized sources of buoyancy are the presence of a wall shear stress at the source and that non-ideal source conditions are distributed over the whole height of the enclosure for a vertically distributed source. Herein the impact of non-ideal source and boundary conditions on vertically distributed plumes is analysed. It is shown that, at small heights, the plume volume flow rate is significantly influenced by the wall-source volume flux. At larger heights the wall-source buoyancy is greater than the mean plume buoyancy, creating a non-self-similar horizontal buoyancy distribution within the plume. Recent experiments into the behaviour of a vertically distributed source of buoyancy in a confined region have also shown that the plume partially detrains in the stratified region of the enclosure. This detrainment has not been observed for constant buoyancy flux plumes in a confined region. Although models have been proposed to quantify the detrainment process, it is still unclear why vertically distributed buoyancy sources detrain while constant buoyancy flux plumes do not in the same physical geometry. The impact of source and boundary effects on previously published experiments on vertically distributed plumes are reviewed and the possible implications for plume entrainment and detrainment are discussed.

Childrenite (Fe,Mn)AlPO4,(OH)2.2H2O, the iron-rich end-member of the childrenite-eosphorite diadochic series, was first discovered by Brooke (1823) on specimens from near Tavistock in Devon. Subsequently it has been recorded from a small number of other British localities, mostly in the Tavistock area, and also from near St. Austell in Cornwall, and from one locality in Cumbria. The Sir Arthur Russell collection, now in the British Museum (Nat. Hist.), has specimens from a few additional localities, all near Tavistock, and the Geological Museum, Institute of Geological Sciences, has a specimen from Wheal Jane, near Truro.

The depletion of neutral helium atoms has been studied in an unmagnetised spherical plasma created by DC discharge in a multidipole confinement field. Knowing the neutral density profile is critical to predicting the equilibrium flow of such plasmas. A model of the emissivity due to electron-impact excitation of neutral atoms in the plasma has been derived and used to fit radiance measurements of several neutral transitions to extract the radial profile of neutral density for plasmas of varying temperature and density. We report a depletion of the core neutral density varying between negligible levels to 80 % of the edge neutral density depending on the input power and fuelling. The corresponding ionisation fraction varies between 30–80 % in the plasma core. A simple neutral diffusion model is sufficient to describe the shape of neutral density profile implied by the radiance measurements. We have used the measurements to include a drag force due to neutral charge-exchange collisions in simulations of driven plasma flow. The simulation predicts a better fit to Mach probe flow measurements when this neutral drag is accounted for. This work shows that accounting for a realistic neutral profile is important to predict the plasma flow geometry and its magnetohydrodynamics (MHD) stability.

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.