Objectives/Goals: The creatine (Cr) system is impaired in Alzheimer’s disease (AD). Data show that creatine monohydrate (CrM) supplementation may improve AD symptoms in AD mouse models, but no human studies have been reported. Thus, we investigated whether an eight-week CrM supplementation was feasible and associated with increased brain creatine in patients with AD. Methods/Study Population: Twenty participants with probable AD were allocated to an open-label, eight-week intervention of 20 g/day CrM. Fasting blood draws were taken at baseline, 4-, and 8-week visits to measure serum creatine (Quest Diagnostics). 1H magnetic resonance spectroscopy was performed at baseline and 8-week visits to measure brain Cr as a ratio to unsuppressed water. Self-reported compliance (with assistance from study partners) was assessed with daily CrM trackers. The mean compliance percentage across all participants was used to describe overall compliance with the intervention. We used paired t-tests to analyze the mean changes in serum Cr levels from baseline to 4- and 8-week visits and the mean change in brain Cr from baseline to 8-week visits. Statistical significance was set at p<0.05. Results/Anticipated Results: Participants were 65% male with a mean age of 73.1±6.3 years. All participants completed the study, with 19 out of 20 achieving the dose compliance target of ≥80%. The mean self-reported dose intake was 90%. Serum Cr levels were significantly increased at 4- and 8-week visits compared to baseline (0.6±0.4 mg/dL vs. 14.0±9.9 mg/dL and 15.0±13.6 mg/dL, respectively; p<0.001). Brain Cr levels also significantly increased (330.5±36.80 i.u. vs. 366.9±57.52 i.u., p<0.001). Discussion/Significance of Impact: We are the first to demonstrate that 20 g/day of CrM for eight weeks is feasible and associated with increased brain Cr in patients with AD. Our findings support further investigation of brain target engagement of CrM and its efficacy in AD. With AD cases expected to rise, CrM could serve as an effective, affordable therapeutic to slow AD progression.

Objectives/Goals: Community-based practices have limited research opportunities for providers. As a rural community-based health system, Mayo Clinic Health System (MCHS) sought to create intramural funding mechanisms to help early-stage researchers conduct pilot research so they are more competitive to compete for more robust extramural funding opportunities. Methods/Study Population: We created a Research Seed Grant Program infrastructure across our four MCHS regions (Southwest and Southeast Minnesota, Northwest and Southwest Wisconsin). This model program featured an initial research funding announcement call based on 6 prioritized programs (AI Validation & Stewardship, Cancer, Health Equity, Population Health, Rural Health, Learning Healthcare System [LHS]), with submissions uploaded to a central electronic repository. Proposal review and ranking was organized on a regional basis, with ranking of all proposals by at least 2 clinical scientist reviewers according to the NIH domain-specific framework (i.e., 1.0 best > 9.0 worst). Awards were competitively selected by conformity to prioritized research areas and through ranking of most competitive overall application scores. Results/Anticipated Results: For our inaugural RFA, we received 55 grant application submissions across the MCHS regions. Fifteen of the most highly ranked applications were selected for awards on a per region basis, providing direct funding as well as protected investigator research time of 10% for up to six months. The selected projects address several research priorities including improving access, reducing health disparities, improving behavioral health in our communities, increasing cancer screening and prevention, and community-based pragmatic trials and interventions. Outcomes from these now completed pilot projects remain pending at this time. Funding for this seed grant program was supported by philanthropy, Mayo Clinic Research Administration, Mayo Clinic Comprehensive Cancer Center, and the Mayo Clinic CCaTS Rural Core. Discussion/Significance of Impact: We present this framework for a LHS-focused Seed Grant program model for consideration of adoption by other national/international LHS. Future plans include tracking of outcome metrics (e.g., published peer review articles, extramural grant applications) of this initial cycle and future expansion of this program to support the goals of our LHS.

Objectives/Goals: The Standards for Reporting Implementation Studies (StaRI) are the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network 27-item checklist for Implementation Science. This study quantifies StaRI adherence among self-defined Implementation Science studies in published Learning Health Systems (LHS) research. Methods/Study Population: A medical librarian-designed a search strategy identified original Implementation Science research published in one of the top 20 Implementation Science journals between 2017 and 2021. Inclusion criteria included studies or protocols describing the implementation of any intervention in healthcare settings. Exclusion criteria included concept papers, non-implementation research, or editorials. Full-text documents were reviewed by two investigators to abstract and judge StaRI implementation and intervention adherence, partial adherence, or non-adherence. Results/Anticipated Results: A total of 330 documents were screened, 97 met inclusion criteria, and 47 were abstracted including 30 research studies and 17 protocols. Adherence to individual StaRI reporting items ranged from 13% to 100%. Most StaRI items were reported in >60% of manuscripts and protocols. The lowest adherence in research studies was noted around economic evaluation reporting for implementation (16%) or intervention (13%) strategies, harms (13%), contextual changes (30%), or fidelity of either the intervention (34%) or implementation (53%) approach. Subgroup analyses were infrequently contemplated or reported (43%). In protocols, the implications of the implementation strategy (41%) or intervention approach (47%) were not commonly reported. Discussion/Significance of Impact: When leveraging implementation science to report reproducible and sustainable practice change initiatives, LHS researchers will need to include assessments of economics, harms, context, and fidelity in order to attain higher levels of adherence to EQUATOR’s StaRI checklist.

Young stellar objects (YSOs) are protostars that exhibit bipolar outflows fed by accretion disks. Theories of the transition between disk and outflow often involve a complex magnetic field structure thought to be created by the disk coiling field lines at the jet base; however, due to limited resolution, these theories cannot be confirmed with observation and thus may benefit from laboratory astrophysics studies. We create a dynamically similar laboratory system by driving a $\sim$1 MA current pulse with a 200 ns rise through a $\approx$2 mm-tall Al cylindrical wire array mounted to a three-dimensional (3-D)-printed, stainless steel scaffolding. This system creates a plasma that converges on the centre axis and ejects cm-scale bipolar outflows. Depending on the chosen 3-D-printed load path, the system may be designed to push the ablated plasma flow radially inwards or off-axis to make rotation. In this paper, we present results from the simplest iteration of the load which generates radially converging streams that launch non-rotating jets. The temperature, velocity and density of the radial inflows and axial outflows are characterized using interferometry, gated optical and ultraviolet imaging, and Thomson scattering diagnostics. We show that experimental measurements of the Reynolds number and sonic Mach number in three different stages of the experiment scale favourably to the observed properties of YSO jets with $Re\sim 10^5\unicode{x2013}10^9$ and $M\sim 1\unicode{x2013}10$, while our magnetic Reynolds number of $Re_M\sim 1\unicode{x2013}15$ indicates that the magnetic field diffuses out of our plasma over multiple hydrodynamical time scales. We compare our results with 3-D numerical simulations in the PERSEUS extended magnetohydrodynamics code.

The United Kingdom’s National Referral Mechanism (NRM) is a framework for identifying potential victims of modern slavery (slavery, servitude, forced labour or human trafficking) and ensuring that they receive adequate care. This research explores differences in referrals and outcomes of potential modern slavery victims within the NRM on the basis of individual attributes, geography and first responder. Findings are based on exploratory analysis of data on 55,000 cases released by the Home Office in spring 2022 plus data from four Freedom of Information requests. Findings confirm that there are significant differences in rates of positive outcomes between native and immigrant groups, with native populations more likely to receive positive conclusive grounds (CG) decisions. Our key contribution is in identification of the role of the first responder in negatively influencing outcomes for victims of particular forms of exploitation. We suggest the differences in outcomes may be explained by the dual role played by first responders within the immigration system in identifying victims and implementing immigration control measures. We situate this finding within a broader critical migration literature on polymorphous borders pointing to the NRM as one mechanism through which bodies are differentially excluded from territorial access and associated rights or benefits.

We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.

The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.

Among outpatients with coronavirus disease 2019 (COVID-19) due to the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) δ (delta) variant who did and did not receive 2 vaccine doses at 7 days after symptom onset, there was no difference in viral shedding (cycle threshold difference 0.59, 95% CI, −4.68 to 3.50; P = .77) with SARS-CoV-2 cultured from 2 (7%) of 28 and 1 (4%) of 26 outpatients, respectively.

We establish sharp bounds for the second moment of symmetric-square L-functions attached to Hecke Maass cusp forms $u_j$ with spectral parameter $t_j$, where the second moment is a sum over $t_j$ in a short interval. At the central point $s=1/2$ of the L-function, our interval is smaller than previous known results. More specifically, for $\left \lvert t_j\right \rvert $ of size T, our interval is of size $T^{1/5}$, whereas the previous best was $T^{1/3}$, from work of Lam. A little higher up on the critical line, our second moment yields a subconvexity bound for the symmetric-square L-function. More specifically, we get subconvexity at $s=1/2+it$ provided $\left \lvert t_j\right \rvert ^{6/7+\delta }\le \lvert t\rvert \le (2-\delta )\left \lvert t_j\right \rvert $ for any fixed $\delta>0$. Since $\lvert t\rvert $ can be taken significantly smaller than $\left \lvert t_j\right \rvert $, this may be viewed as an approximation to the notorious subconvexity problem for the symmetric-square L-function in the spectral aspect at $s=1/2$.

Scanning transmission X-ray microscopy is a powerful method for mapping chemical phases in nano-materials. The point spread function (PSF) of a conventional zone-plate-based microscope limits the achievable spatial resolution and also results in spatially resolved spectra that do not accurately reflect the spatial heterogeneity of the samples when the scale of the detail approaches the probe size. X-ray ptychography, a coherent-scattering-based imaging scheme that effectively removes the probe from the image data, returns accurate spectra from regions smaller than the probe size. We show through simulation how the long tails on the PSF of an x-ray optic can cause spectral distortion near a boundary between two spectrally distinct regions. The resulting apparent point spectra can appear mixed, with the species on one side of the boundary seeming to be present on the other even at a distance from the boundary equal to several times the spatial resolution. We further demonstrate the effect experimentally and show that ptychographic microscopy can return the expected spectra from a model system, whereas conventional microscopy does not.

High-temperature differential scanning calorimetry was used to understand the thermal properties of Si-rich metal–silicon alloys. Insoluble metals (A and B) were found to produce an alloy with discrete ASi2 and BSi2 dispersed phases. In contrast, metals that form a solid solution result in a dispersed phase that has a composition of AxB1−xSi2, where x varies continuously across each inclusion. This complex composition distribution is putatively caused by differences in the solidification temperatures of ASi2 versus BSi2. Though this behavior was observed for several different combinations of metals, we focus here specifically on the Cr/V/Si system. To better understand the range and most probable element concentrations in the dispersed silicide domains, a method was devised to generate histograms of their Cr and V concentrations from energy-dispersive X-ray spectroscopy hyperspectral images. Varying the Cr/V/Si ratio was found to change the shape of the element histograms, indicating that the distribution of silicide compositions that form is controlled by the input composition. Adding aluminum was found to result in dispersed phases that had a single composition rather than a range of Cr and V concentrations. This demonstrates that aluminum can be an effective additive for altering solidification kinetics in silicon alloys.

The purpose of this paper is to build on personal engagement and role theory to develop a conceptual definition of engagement to different organizational roles (job, organization, supervisor, and coworkers) and create and validate the Role-Based Engagement Scale (RBES). Data were collected from four samples (n = 1,302) of employees, including three from multiple organizations and one from an aircraft manufacturer. Results across three studies consistently support the four dimension structure of the RBES, its internal consistency, convergent, discriminant, and predictive validity based on a series of confirmatory factor analyses. The RBES is a psychometrically sound instrument that measures engagement to job, organization, supervisor, and coworkers. This instrument will provide more targeted information for human resource management (HRM) professionals tasked with developing training methods and processes to improve low-scoring dimensions of engagement, optimizing HRM interventions.