Characterizing the structure and composition of clay minerals on the surface of Mars is important for reconstructing past aqueous processes and environments. Data from the CheMin X-ray diffraction (XRD) instrument on the Mars Science Laboratory Curiosity rover demonstrate a ubiquitous presence of collapsed smectite (basal spacing of 10 Å) in ~3.6-billion-year-old lacustrine mudstone in Gale crater, except for expanded smectite (basal spacing of 13.5 Å) at the base of the stratigraphic section in a location called Yellowknife Bay. Hypotheses to explain expanded smectite include partial chloritization by Mg(OH)2 or solvation-shell H2O molecules associated with interlayer Mg2+. The objective of this work is to test these hypotheses by measuring partially chloritized and Mg-saturated smectite using laboratory instruments that are analogous to those on Mars rovers and orbiters. This work presents Mars-analog XRD, evolved gas analysis (EGA), and visible/shortwave-infrared (VSWIR) data from three smectite standards that were Mg-saturated and partially and fully chloritized with Mg(OH)2. Laboratory data are compared with XRD and EGA data collected from Yellowknife Bay by the Curiosity rover to examine whether the expanded smectite can be explained by partial chloritization and what this implies about the diagenetic history of Gale crater. Spectral signatures of partial chloritization by hydroxy-Mg are investigated that may allow the identification of partially chloritized smectite in Martian VSWIR reflectance spectra collected from orbit or in situ by the SuperCam instrument suite on the Mars 2020 Perseverance rover. Laboratory XRD and EGA data of partially chloritized saponite are consistent with data collected from Curiosity. The presence of partially chloritized (with Mg(OH)2) saponite in Gale crater suggests brief interactions between diagenetic alkaline Mg2+-bearing fluids and some of the mudstone exposed at Yellowknife Bay, but not in other parts of the stratigraphic section. The location of Yellowknife Bay at the base of the stratigraphic section may explain the presence of alkaline Mg2+-bearing fluids here but not in other areas of Gale crater investigated by Curiosity. Early diagenetic fluids may have had a sufficiently long residence time in a closed system to equilibrate with basaltic minerals, creating an elevated pH, whereas diagenetic environments higher in the section may have been in an open system, therefore preventing fluid pH from becoming alkaline.

Current clinical guidelines for people at risk of heart disease in Australia recommend nutrition intervention in conjunction with pharmacotherapy(1). However, Australians living in rural and remote regions have less access to medical nutritional therapy (MNT) provided by Accredited Practising Dietitians (APDs) than their urban counterparts(2). The aim of the HealthyRHearts study was to trial the delivery of MNT by APDs using telehealth to eligible patients of General Practitioners (GPs) located in small to large rural towns in the Hunter New England region(3) of New South Wales, Australia. The study design was a 12-month pragmatic randomised controlled trial. The key outcome was reduced total cholesterol. The study was place-based, meaning many of the research team and APDs were based rurally, to ensure the context of the GPs and patients was already known. Eligible participants were those assessed as moderate-to-high risk of CVD by their GP. People in the intervention group received five MNT consults (totalling two hours) delivered via telehealth by APDs, and also answered a personalised nutrition questionnaire to guide their priorities and to support personalised dietary behaviour change during the counselling. Both intervention and control groups received usual care from their GP and were provided access to the Australian Eating Survey (Heart version), a 242-item online food frequency questionnaire with technology-supported personalised nutrition reports that evaluated intake relative to heart healthy eating principles. Of the 192 people who consented to participate, 132 were eligible due to their moderate-to-high risk. Pre-post participant medication use with a registered indication(4) for hypercholesterolemia, hypertension and glycemic control were documented according to class and strength (defined daily dose: DDD)(5). Nine GP practices (with 91 participants recruited) were randomised to the intervention group and seven practices (41 participants) were randomised to control. Intervention participants attended 4.3 ± 1.4 out of 5 dietetic consultations offered. Of the132 people with baseline clinical chemistry, 103 also provided a 12-month sample. Mean total cholesterol at baseline was 4.97 ± 1.13 mmol/L for both groups, with 12-m reduction of 0.26 ± 0.77 for intervention and 0.28 ± 0.79 for control (p = 0.90, unadjusted value). Median (IQR) number of medications for the intervention group was 2 (1–3) at both baseline and 12 months (p = 0.78) with 2 (1–3) and 3 (2–3) for the control group respectively. Combined DDD of all medications was 2.1 (0.5–3.8) and 2.5 (0.75–4.4) at baseline and 12 months (p = 0.77) for the intervention group and 2.7 (1.5–4.0) and 3.0 (2.0–4.5) for the control group (p = 0.30). Results suggest that medications were a significant contributor to the management of total cholesterol. Further analysis is required to evaluate changes in total cholesterol attributable to medication prescription relative to the MNT counselling received by the intervention group.

Objectives/Goals: Acute myeloid leukemia (AML) is the second most common leukemia among pediatric populations. Approximately 15% of pediatric AML cases have KMT2A gene rearrangements (KMT2A-r), which confers a worse prognosis. Our goal is to better characterize the biologic landscape of KMT2A-r pediatric AML. Methods/Study Population: This study utilizes deidentified peripheral blood and/or bone marrow samples banked in the Children’s Mercy Tumor Bank Biorepository. We investigated four KMT2A-r pediatric AML patients and six patients with other AML subtypes using samples collected at diagnosis and remission that were stored in the “tumor bank.” In addition, we assessed 47 tumor bank samples from patients with other leukemia subtypes. We performed differential expression (DE) analysis on bulk RNA sequencing comparing KMT2A-r and all other AML subtypes, as well as single-cell RNA sequencing and proteomic analysis on the larger cohort. We then coalesced these data to better identify processes and pathways that are dysregulated in KMT2A-r AML, specifically aiming to find those that were contributing to leukemogenesis. Results/Anticipated Results: Transcriptomic analysis showed that HOXA10 and MEIS1, two genes associated with immature myeloid populations and KMT2A-r leukemias, were more highly transcribed in AMLs than other leukemias. In addition, our DE analysis showed significantly higher transcription of ITGA7, a gene shown to correlate with poorer prognosis in AML, in our KMT2A-r samples when compared to other AML subtypes. FAM46C, a tumor suppressor gene contributing to mRNA stabilization, was less highly expressed in KMT2A-r AML when compared to other AML subtypes. Of note, low expression of FAM46C is associated with poorer survival and treatment response in multiple myeloma, and our findings suggest it may also be relevant to AML. Proteomic analysis is currently in process. Discussion/Significance of Impact: Transcriptomic analysis identifies unique molecular features of pediatric KMT2A-r AML. We anticipate that our proteomic data will do the same and will also corroborate our RNA findings. Taken in combination, these results will provide a more complete picture of the specific mechanisms contributing to this aggressive leukemic subtype.

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.

Interpersonal Psychotherapy (IPT) is an evidence-based treatment for adolescent depression. However, since it does not work for all adolescents in all settings, more research on its heterogeneous effects is needed. Using a realist approach, we aimed to generate hypotheses about mechanisms and contextual contingencies in adolescent group IPT in Nepal. We analysed 26 transcripts from qualitative interviews with IPT participants aged 13–19, facilitators, supervisors and trainers. We analysed data using the Framework Method. The qualitative analytical framework was based on the VICTORE checklist, a realist tool to explore intervention complexity. Sharing, problem-solving, giving and receiving support, managing emotions and negotiating emerged as mechanisms through which adolescents improved their depression. Participants perceived that girls and older adolescents benefitted most from IPT. Girls had less family support than boys and therefore benefitted most from the group support. Older adolescents found it easier than younger ones to share problems and manage emotions. Adolescents exposed to violence and parental alcoholism struggled to overcome problems without family and school support. We formulated hypotheses on group IPT mechanisms and contextual interpersonal and school-level factors. Research is needed to test these hypotheses to better understand for whom IPT works and in what circumstances.

The consent process for research studies can be burdensome for potential participants due to complex information and lengthy consent forms. This pragmatic study aimed to improve the consent experience and evaluate its impact on participant decision making, study knowledge, and satisfaction with the In Our DNA SC program, a population-based genomic screening initiative. We compared two consent procedures: standard consent (SC) involving a PDF document and enhanced consent (EC) incorporating a pictograph and true or false questions. Decision-making control, study knowledge, satisfaction, and time to consent were assessed. We analyzed data for 109 individuals who completed the SC and 96 who completed the EC. Results indicated strong decision-making control and high levels of knowledge and satisfaction in both groups. While no significant differences were found between the two groups, the EC experience took longer for participants to complete. Future modifications include incorporating video modules and launching a Spanish version of the consent experience. Overall, this study contributes to the growing literature on consent improvements and highlights the need to assess salient components and explore participant preferences for receiving consent information.

Next generation high-power laser facilities are expected to generate hundreds-of-MeV proton beams and operate at multi-Hz repetition rates, presenting opportunities for medical, industrial and scientific applications requiring bright pulses of energetic ions. Characterizing the spectro-spatial profile of these ions at high repetition rates in the harsh radiation environments created by laser–plasma interactions remains challenging but is paramount for further source development. To address this, we present a compact scintillating fiber imaging spectrometer based on the tomographic reconstruction of proton energy deposition in a layered fiber array. Modeling indicates that spatial resolution of approximately 1 mm and energy resolution of less than 10% at proton energies of more than 20 MeV are readily achievable with existing 100 μm diameter fibers. Measurements with a prototype beam-profile monitor using 500 μm fibers demonstrate active readouts with invulnerability to electromagnetic pulses, and less than 100 Gy sensitivity. The performance of the full instrument concept is explored with Monte Carlo simulations, accurately reconstructing a proton beam with a multiple-component spectro-spatial profile.

Functional decline following hospitalization remains an important problem in health care, especially for frail older adults. Modifiable factors related to reduction in harms of hospitalization are not well described. One particularly pervasive factor is emergency department (ED) boarding time; time waiting from decision to admit, until transfer to an in-patient medical unit. We sought to investigate how the functional status of frail older adults correlated with the length of time spent boarded in the ED. We found that patients who waited for 24 hours or more exhibited functional decline in both the Barthel Index and Hierarchical Assessment of Balance and Mobility and an increase in the Clinical Frailty Scale from discharge to 6 months post discharge. In conclusion, there is a need for additional investigation into ED focused interventions to reduce ED boarding time for this population or to improve access to specialized geriatric services within the ED.