Objectives/Goals: Injury to the medial knee ligaments (sMCL, dMCL, POL) and anterior cruciate ligament (ACL) can cause anteromedial rotatory instability (AMRI). AMRI can cause knee instability and ACL graft failure, but it is unclear how the sMCL, dMCL, POL, and ACL resist AMRI. We aimed to characterize the in-situ forces of the sMCL, dMCL, POL, and ACL under loading conditions involved with AMRI. Methods/Study Population: We characterized the in situ forces of the sMCL, dMCL, POL, and ACL under 1) isolated external tibial rotation torque (ER), 2) isolated anterior tibial force (Ant), and 3) combined ER+Ant loading. Twenty-eight human cadaveric knees (18 male; mean age, 48±13; 21–65 years) were tested on a robotic manipulator with force sensing. Tibiofemoral kinematics were recorded under isolated ER (4Nm, 0–90°), isolated Ant (134N at 0–90°), and combined ER+Ant (4Nm+100N at 15, 30, 90°). The sMCL, dMCL, POL, and ACL were dissected in random order. The in situ force (N) in the sMCL, dMCL, POL, and ACL at the peak applied load for each loading condition was calculated using superposition and compared with Kruskal–Wallis tests with post hoc pairwise testing using a Bonferroni–Holm correction for multiple comparisons (α = 0.05). Results/Anticipated Results: Under isolated ER, the force in the sMCL (32–52N) from 0°-90° exceeded that of the ACL, dMCL, and POL at each flexion angle (p0.05). Force in the ACL was the second highest (26–6N from 0°-90°). Force in the dMCL and POL was low (≤12N). Under isolated Ant, the ACL carried the highest force at all flexion angles (≥113N) (p0.05), but at 90° the sMCL carried the highest force of all ligaments (p0.05). At 90°, force in the dMCL diminished (Discussion/Significance of Impact: We show that the sMCL is the major stabilizer to external rotation torques and combined anterior and external loading conditions related to anteromedial rotatory instability across the arc of knee flexion, while the dMCL, POL, and ACL play a less prominent role, with the exception of the ACL and dMCL near full extension.

This work presents visual morphological and dynamical classifications for 637 spatially resolved galaxies, most of which are at intermediate redshift (z ∼ 0.3), in the Middle-Ages Galaxy Properties with Integral field spectroscopy (MAGPI) Survey. For each galaxy, we obtain a minimum of 11 independent visual classifications by knowledgeable classifiers. We use an extension of the standard Dawid-Skene Bayesian model introducing classifier-specific confidence parameters and galaxy-specific difficulty parameters to quantify classifier confidence and infer reliable statistical confidence estimates. Selecting sub-samples of 86 bright (r < 20 mag) high-confidence (> 0.98) morphological classifications at redshifts (0.2 ≤ z ≤ 0.4), we confirm the full range of morphological types is represented in MAGPI as intended in the survey design. Similarly, with a sub-sample of 82 bright high-confidence stellar kinematic classifications, we find that the rotating and non-rotating galaxies seen at low redshift are already in place at intermediate redshifts. We do not find evidence that the kinematic morphology-density relation seen at z ∼ 0 is established at z ∼ 0.3. We suggest that galaxies without obvious stellar rotation are dynamically pre-processed sometime before z ∼ 0.3 within lower mass groups before joining denser environments.

China's green energy shift is now attracting increasing attention, as its strategic implications become clearer. In a recent article in Foreign Affairs, Amy Myers Jaffe has argued that China is effecting a “pivot” to green and clean energy that puts the country on a superior footing in international competition – particularly competition with the United States, that remains committed to its fossil fuel industries. Jaffe cites a number of statistics and trends, such as the shift to green power generation and the shift to electric vehicles (EVs) – but she does not offer any definitive demonstration of China's greening. We tackle this central issue in this article, and offer fresh evidence that in a fundamental sense, China is indeed greening its total energy system. What we do is construct a picture of China's total fossil fuel consumption over the past decade where coal, oil and gas consumption are aggregated not just in terms of coal-equivalent or oil-equivalent but in electric power-equivalent (in TWh) – so that a direct comparison can be made between burning of fossil fuels in aggregate and generation of electric power from renewable sources (i.e. from water, wind and sun). What we show is that in each of the past six years, from 2012 to 2017, China's increase in fossil fuel burning in aggregate has been exceeded by the generation of green electric power. In this precise sense, where “blackening” is defined as the increase in fossil fuel consumption in aggregate (across the entire economy), and “greening” is defined as green electric power generation, we can demonstrate that in each of the past six years, China's greening has outpaced its blackening – as shown in Fig. 1.

For near-future missions planed for Mars Sample Return (MSR), an international working group organized by the Committee on Space Research (COSPAR) developed the sample safety assessment framework (SSAF). For the SSAF, analytical instruments were selected by taking the practical limitations of hosting them within a facility with the highest level of biosafety precautions (biosafety level 4) and the precious nature of returned samples into account. To prepare for MSR, analytical instruments of high sensitivity need to be tested on effective Mars analogue materials. As an analogue material, we selected a rock core of basalt, a prominent rock type on the Martian surface. Two basalt samples with aqueous alteration cached in Jezero crater by the Perseverance rover are planned to be returned to Earth. Our previously published analytical procedures using destructive but spatially sensitive instruments such as nanoscale secondary ion mass spectrometry (NanoSIMS) and transmission electron microscopy coupled to energy-dispersive spectroscopy revealed microbial colonization at clay-filled fractures. With an aim to test the capability of an analytical instrument listed in SSAF, we now extend that work to conventional Fourier transform infrared (FT-IR) microscopy with a spatial resolution of 10 μm. Although Fe-rich smectite called nontronite was identified after crushing some portion of the rock core sample into powder, the application of conventional FT-IR microscopy is limited to a sample thickness of <30 μm. In order to obtain IR-based spectra without destructive preparation, a new technique called optical-photothermal infrared (O-PTIR) spectroscopy with a spatial resolution of 0.5 μm was applied to a 100 μm thick section of the rock core. By O-PTIR spectroscopic analysis of the clay-filled fracture, we obtained in-situ spectra diagnostic to microbial cells, consistent with our previously published data obtained by NanoSIMS. In addition, nontronite identification was also possible by O-PTIR spectroscopic analysis. From these results, O-PTIR spectroscopy is suggested be superior to deep ultraviolet fluorescence microscopy/μ-Raman spectroscopy, particularly for smectite identification. A simultaneous acquisition of the spatial distribution of structural motifs associated with biomolecules and smectites is critical for distinguishing biological material in samples as well as characterizing an abiotic background.

Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

Ask most oncologists (especially radiation oncologists), and you may be hard pressed to find one who professes ignorance of Madame Curie and her historic contributions to medicine. Innumerable publications and media over the past century have correctly memorialised Madame Curie as one of the most brilliant minds in world history. However, do any of us really know the woman and the true extent of her sphere of influence? How, as well, does she fit into modern life and contemporary scientific advancement? Let us try to understand and learn from this complex scientist as more than just one of the most brilliant minds in human history.

OBJECTIVES/GOALS: As mortality and morbidity from acute COVID-19 decline, the impact of COVID-19 on short- and long-term quality of life (QoL) becomes critical to address. We assessed the impact of re-purposed COVID-19 therapies on QoL as a secondary outcome measure in ACTIV-6, a decentralized platform trial. METHODS/STUDY POPULATION: Adults aged ≥30 with mild-to-moderate COVID-19 enroll in ACTIV-6 online or through a study site. Patients are randomized to a medication of interest or placebo. Medications are mailed and symptoms are tracked using electronic diaries. QoL is measured#_msocom_1 using the PROMIS-29 questionnaire. Adjusted Bayesian logistic regression models are used to measure effects of treatment on the seven PROMIS-29 QoL domains at days 7, 14, 28#_msocom_2 and 90. Covariates are treatment, age, gender, symptom duration and severity, vaccination status, geographic region, call center#_msocom_3#_msocom_4, and calendar time. Treatment effects are described using ORs, 95% credible intervals, and posterior probabilities of efficacy, P(eff). RESULTS/ANTICIPATED RESULTS: There are 5,362 patients included, representing four of the study arms in ACTIV-6. We report results where P(eff)<0.025 and P(eff)>0.975 in the table below. Table 1. Scale Day: OR* (95% credible interval, P(eff)) Therapy Physical Anxiety Depression Fatigue Sleep Social Pain Ivermectin 400 — Ivermectin 600 D7: 0.77 (0.61-0.96, 0.01) D14: 0.65 (0.49-0.85, <0.01) D28: 0.69 (0.52-0.92, 0.01) — D7: 0.79 (0.64-0.97, 0.01) — D14 0.78 (0.60-1.00, 0.02) D28: 0.66 (0.50-0.87, <0.01) Fluticasone - D14: 0.77 (0.60-0.99, 0.02) — D7: 0.76 (0.62-0.93, <0.01) D90: 0.79 (0.64-0.98, 0.01) — D7: 0.74 (0.59-0.93, 0.01) Fluvoxamine D7: 0.66 (0.51-0.84, 0.01) — D28: 1.38 (1.02, 1.85, 0.98) D7: 0.78 (0.63-0.97, 0.01) D7: 0.77 (0.62-0.95, 0.01) — *OR > 1 favors active intervention DISCUSSION/SIGNIFICANCE: Results suggest fluvoxamine may improve depression scores by day 28, while placebo is favored in several other scales across treatments. Differences between treatment and placebo are not seen at most other timepoints. This trial is ongoing and future work will include results from additional ACTIV-6 study arms.

Aviation passenger screening has been used worldwide to mitigate the translocation risk of SARS-CoV-2. We present a model that evaluates factors in screening strategies used in air travel and assess their relative sensitivity and importance in identifying infectious passengers. We use adapted Monte Carlo simulations to produce hypothetical disease timelines for the Omicron variant of SARS-CoV-2 for travelling passengers. Screening strategy factors assessed include having one or two RT-PCR and/or antigen tests prior to departure and/or post-arrival, and quarantine length and compliance upon arrival. One or more post-arrival tests and high quarantine compliance were the most important factors in reducing pathogen translocation. Screening that combines quarantine and post-arrival testing can shorten the length of quarantine for travelers, and variability and mean testing sensitivity in post-arrival RT-PCR and antigen tests decrease and increase with the greater time between the first and second post-arrival test, respectively. This study provides insight into the role various screening strategy factors have in preventing the translocation of infectious diseases and a flexible framework adaptable to other existing or emerging diseases. Such findings may help in public health policy and decision-making in present and future evidence-based practices for passenger screening and pandemic preparedness.

Commentaries on the target article offer diverse perspectives on integrative experiment design. Our responses engage three themes: (1) Disputes of our characterization of the problem, (2) skepticism toward our proposed solution, and (3) endorsement of the solution, with accompanying discussions of its implementation in existing work and its potential for other domains. Collectively, the commentaries enhance our confidence in the promise and viability of integrative experiment design, while highlighting important considerations about how it is used.

The conversion of volcanic glass to secondary alteration products is one of the most common mineralogical transformations during low-temperature hydrothermal alteration of submarine basalts. To better understand the mechanism and kinetics of this transformation, porphyritic and formerly glassy trachybasalt, recovered from Conical Seamount, Papua New Guinea, was studied in detail. Low-temperature interaction of trachybasalt with hydrothermal fluids at this submerged volcano occurred in response to the formation of submarine epithermal-style gold mineralization. Alteration of the coherent volcanic rocks is heterogeneous with pronounced differences in alteration intensity occurring between igneous minerals and the surrounding glassy groundmass. In comparison to the volcanic glass, the crystalline phases were less prone to hydrothermal alteration with the alteration susceptibility decreasing from clinopyroxene through biotite to feldspar. Low-temperature alteration of clinopyroxene resulted in the formation of abundant saponite-like smectite with no topotactic relationship being observed between the two phases. In contrast, the conversion of biotite to smectite involved structural inheritance as the orientation of common structural blocks was maintained during alteration. Transmission and analytical electron microscopy revealed that pervasive alteration of interstitial glass in the groundmass of the trachybasalt resulted in the formation of montmorillonite- and saponite-like smectite whereby smectite composition is strongly influenced by the glass chemistry. The occurrence of poorly crystalline domains with a 0.3 to 0.4 nm layer spacing in the altered interstitial glass suggests that the transformation of glass to smectite involved the formation of a transitional alteration product. Comparison with the results of previous studies highlights the fact that the glass-to-smectite transformation can proceed through more than one reaction pathway. Reaction style and reaction progress are controlled by kinetic factors such as the mode of fluid transport triggering alteration in the low-temperature hydrothermal environment. Alteration of the trachybasalt at Conical Seamount is inferred to have taken place at a comparably low fluid-rock ratio as the low permeability and the absence of primary fractures and joints restricted fluid circulation through the coherent volcanic rocks.