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The formation and evolution of the South Pole‐Aitken (SPA) basin is critical to relating large impact basin formation and modification to lunar geophysical evolution. Most prior models of the SPA impact were conducted in 2D, making it difficult to compare model output to the 3D crustal structure and ejecta distribution. In order to better constrain the parameters of the SPA impactor and the expected post impact distribution of crust and ejecta, we conducted numerical simulations of the SPA impact in 3D. We tested a wide range of impact parameters and constrained model results with recent geophysical data. We found the crustal structure of the SPA basin is best fit by an oblique impact (30–45°) of a 350–400 km diameter projectile impacting at 12–16 km/s. The impact excavated material from as deep as 80–120 km, and ejecta was deposited in a butterfly pattern with a forbidden region uprange of the impact. Plain Language Summary The South Pole‐Aitken (SPA) basin is the largest impact‐generated structure on the Moon. The large size of the basin (approximately 1,500–2,000 km in diameter) implies the impact that generated the basin globally influenced the early evolution of the Moon. In order to constrain the type of impact that formed the basin, we ran computer simulations of large projectiles (300–400 km in diameter) impacting the early lunar surface. We found the structure of the crust surrounding the basin best matches an impact of a 350–400 km diameter projectile (similar in scale to Saturn's moon Mimas) impacting the Moon with a velocity of 12–16 km per second. Our computer models show that the collision that generated the basin would have formed a non‐symmetrical distribution of impact ejecta, and excavated material from the lower crust and upper mantle. Our results constrain the type of impact that formed the SPA basin, and suggest that ejecta from the impact is prevalent at sites of current and future lunar exploration. Key Points 3D simulations constrain the South Pole‐Aitken (SPA) impactor to 350–400 km diameter impacting at 12–16 km/s and 30–45° The SPA impact excavated lower crust and upper mantle lunar materials, and emplaced ejecta in a butterfly type ejecta pattern The thick crustal annulus present in model results requires further modeling of basin collapse and post‐impact relaxation

Understanding the longevity of Mars’s dynamo is key to interpreting the planet’s atmospheric loss history and the properties of its deep interior. Satellite data showing magnetic lows above many large impact basins formed 4.1-3.7 billion years ago (Ga) have been interpreted as evidence that Mars’s dynamo terminated before 4.1 Ga—at least 0.4 Gy before intense late Noachian/early Hesperian hydrological activity. However, evidence for a longer-lived, reversing dynamo from young volcanics and the Martian meteorite ALH 84001 supports an alternative interpretation of Mars’s apparently demagnetized basins. To understand how a reversing dynamo would affect basin fields, here we model the cooling and magnetization of 200-2200 km diameter impact basins under a range of Earth-like reversal frequencies. We find that magnetic reversals efficiently reduce field strengths above large basins. In particular, if the magnetic properties of the Martian mantle are similar to most Martian meteorites and late remagnetization of the near surface is widespread, >90% of large ( > 800 km diameter) basins would appear demagnetized at spacecraft altitudes. This ultimately implies that Mars’s apparently demagnetized basins do not require an early dynamo cessation. A long-lived and reversing dynamo, unlike alternative scenarios, satisfies all available constraints on Mars’s magnetic history. Weak magnetic fields above Mars’s large impact basins are often interpreted as a signature of the dynamo’s early cessation. Here, the authors demonstrate that these weakly magnetic basins may instead have formed in a long-lived but reversing dynamo.

Impacts may have had a significant effect on the atmospheric chemistry of the early Earth. Reduced phases in the impactor (e.g., metallic iron) can reduce the planet's H\\(_2\\)O inventory to produce massive atmospheres rich in H\\(_2\\). Whilst previous studies have focused on the interactions between the impactor and atmosphere in such scenarios, we investigate two further effects, 1) the distribution of the impactor's iron inventory during impact between the target interior, target atmosphere, and escaping the target, and 2) interactions between the post-impact atmosphere and the impact-generated melt phase. We find that these two effects can potentially counterbalance each other, with the melt-atmosphere interactions acting to restore reducing power to the atmosphere that was initially accreted by the melt phase. For a \\(\\sim10^{22}\\,\\mathrm{kg}\\) impactor, when the iron accreted by the melt phase is fully available to reduce this melt, we find an equilibrium atmosphere with H\\(_2\\) column density \\(\\sim10^4\\,\\mathrm{moles\\,cm^{-2}}\\) (\\(p\\mathrm{H2}\\sim120\\,\\mathrm{bars}\\mathrm{,}~X_\\mathrm{H2}\\sim0.77\\)), consistent with previous estimates. However, when the iron is not available to reduce the melt (e.g., sinking out in large diameter blobs), we find significantly less H\\(_2\\) (\\(7\\times10^2-5\\times10^3\\,\\mathrm{moles\\,cm^{-2}}\\), \\(p\\mathrm{H2}\\lesssim60\\,\\mathrm{bars}\\mathrm{,}~X_\\mathrm{H2}\\lesssim0.41\\)). These lower H\\(_2\\) abundances are sufficiently high that species important to prebiotic chemistry can form (e.g., NH3, HCN), but sufficiently low that the greenhouse heating effects associated with highly reducing atmospheres, which are problematic to such chemistry, are suppressed. The manner in which iron is accreted by the impact-generated melt phase is critical in determining the reducing power of the atmosphere and re-solidified melt pool in the aftermath of impact.

We use MasterCode to perform a frequentist analysis of the constraints on a phenomenological MSSM model with 11 parameters, the pMSSM11, including constraints from ∼36/fb of LHC data at 13 TeV and PICO, XENON1T and PandaX-II searches for dark matter scattering, as well as previous accelerator and astrophysical measurements, presenting fits both with and without the (g-2)μ constraint. The pMSSM11 is specified by the following parameters: 3 gaugino masses M1,2,3, a common mass for the first-and second-generation squarks mq~ and a distinct third-generation squark mass mq~3, a common mass for the first-and second-generation sleptons mℓ~ and a distinct third-generation slepton mass mτ~, a common trilinear mixing parameter A, the Higgs mixing parameter μ, the pseudoscalar Higgs mass MA and tanβ. In the fit including (g-2)μ, a Bino-like χ~10 is preferred, whereas a Higgsino-like χ~10 is mildly favoured when the (g-2)μ constraint is dropped. We identify the mechanisms that operate in different regions of the pMSSM11 parameter space to bring the relic density of the lightest neutralino, χ~10, into the range indicated by cosmological data. In the fit including (g-2)μ, coannihilations with χ~20 and the Wino-like χ~1± or with nearly-degenerate first- and second-generation sleptons are active, whereas coannihilations with the χ~20 and the Higgsino-like χ~1± or with first- and second-generation squarks may be important when the (g-2)μ constraint is dropped. In the two cases, we present χ2 functions in two-dimensional mass planes as well as their one-dimensional profile projections and best-fit spectra. Prospects remain for discovering strongly-interacting sparticles at the LHC, in both the scenarios with and without the (g-2)μ constraint, as well as for discovering electroweakly-interacting sparticles at a future linear e+e- collider such as the ILC or CLIC.

Respiratory syncytial virus (RSV) infection is the leading cause of hospitalization and infant mortality under six months of age worldwide; therefore, the prevention of RSV infection in all infants represents a significant unmet medical need. Here we report the isolation of a potent and broadly neutralizing RSV monoclonal antibody derived from a human memory B-cell. This antibody, RB1, is equipotent on RSV A and B subtypes, potently neutralizes a diverse panel of clinical isolates in vitro and demonstrates in vivo protection. It binds to a highly conserved epitope in antigenic site IV of the RSV fusion glycoprotein. RB1 is the parental antibody to MK-1654 which is currently in clinical development for the prevention of RSV infection in infants. Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization. Here, the authors isolate a human monoclonal antibody that binds to a highly conserved epitope on the RSV fusion protein, neutralizes RSV A and B subtypes equipotently and is protective in the cotton rat model.

Human respiratory syncytial virus (RSV) causes a substantial proportion of respiratory tract infections worldwide. Although RSV reinfections occur throughout life, older adults, particularly those with underlying comorbidities, are at risk for severe complications from RSV. There is no RSV vaccine available to date, and treatment of RSV in adults is largely supportive. A correlate of protection for RSV has not yet been established, but antibodies targeting the pre-fusion conformation of the RSV F glycoprotein play an important role in RSV neutralization. We previously reported a Phase 1 study of an mRNA-based vaccine (V171) expressing a pre-fusion-stabilized RSV F protein (mDS-Cav1) in healthy adults. Here, we evaluated an mRNA-based vaccine (V172) expressing a further stabilized RSV pre-fusion F protein (mVRC1). mVRC1 is a single chain version of RSV F with interprotomer disulfides in addition to the stabilizing mutations present in the mDS-Cav1 antigen. The immunogenicity of the two mRNA-based vaccines encoding mVRC1 (V172) or a sequence-optimized version of mDS-Cav1 to improve transcriptional fidelity (V171.2) were compared in RSV-naïve and RSV-experienced African green monkeys (AGMs). V172 induced higher neutralizing antibody titers than V171.2 and demonstrated protection in the AGM challenge model. We conducted a Phase 1, randomized, placebo-controlled, clinical trial of 25 μg, 100 μg, 200 μg, or 300 μg of V172 in healthy older adults (60–79 years old; N = 112) and 100 μg, 200 μg, or 300 μg of V172 in healthy younger adults (18–49 years old; N = 48). The primary clinical objectives were to evaluate the safety and tolerability of V172, and the secondary objective was to evaluate RSV serum neutralization titers. The most commonly reported solicited adverse events were injection-site pain, injection-site swelling, headache, and tiredness. V172 was generally well tolerated in older and younger adults and increased serum neutralizing antibody titers, pre-fusion F-specific competing antibody titers, and RSV F-specific T-cell responses.

Antibiotics have broad off-target effects on the gut microbiome. When the microbial community is unable to recover from antibiotics, it can lead to increased susceptibility to gastrointestinal infections and increased risk of immunological and metabolic diseases. In this study, we work to better understand how the gut microbiota recovers from antibiotics by employing a recent technology to image the entire bacterial community at once. Through this approach, we characterize the spatial changes in the gut microbiota after treatment with model antibiotics in both the cecum and colon of mice. We find antibiotic- and biogeographic-dependent spatial changes between bacterial species and that many of these spatial colocalizations do not recover to baseline levels even 35 days after antibiotic administration.

Influenza HA is the primary target of neutralizing antibodies during infection, and its sequence undergoes genetic drift and shift in response to immune pressure. The receptor binding HA1 subunit of HA shows much higher sequence variability relative to the metastable, fusion-active HA2 subunit, presumably because neutralizing antibodies are primarily targeted against the former in natural infection. We have designed an HA2-based immunogen using a protein minimization approach that incorporates designed mutations to destabilize the low pH conformation of HA2. The resulting construct (HA6) was expressed in Escherichia coli and refolded from inclusion bodies. Biophysical studies and mutational analysis of the protein indicate that it is folded into the desired neutral pH conformation competent to bind the broadly neutralizing HA2 directed monoclonal 12D1, not the low pH conformation observed in previous studies. HA6 was highly immunogenic in mice and the mice were protected against lethal challenge by the homologous A/HK/68 mouse-adapted virus. An HA6-like construct from another H3 strain (A/Phil/2/82) also protected mice against A/HK/68 challenge. Regions included in HA6 are highly conserved within a subtype and are fairly well conserved within a clade. Targeting the highly conserved HA2 subunit with a bacterially produced immunogen is a vaccine strategy that may aid in pandemic preparedness.

We perform a likelihood analysis of the minimal anomaly-mediated supersymmetry-breaking (mAMSB) model using constraints from cosmology and accelerator experiments. We find that either a wino-like or a Higgsino-like neutralino LSP, χ ~ 1 0 , may provide the cold dark matter (DM), both with similar likelihoods. The upper limit on the DM density from Planck and other experiments enforces m χ ~ 1 0 ≲ 3 TeV after the inclusion of Sommerfeld enhancement in its annihilations. If most of the cold DM density is provided by the χ ~ 1 0 , the measured value of the Higgs mass favours a limited range of tan β ∼ 5 (and also for tan β ∼ 45 if μ > 0 ) but the scalar mass m 0 is poorly constrained. In the wino-LSP case, m 3 / 2 is constrained to about 900 TeV and m χ ~ 1 0 to 2.9 ± 0.1 TeV , whereas in the Higgsino-LSP case m 3 / 2 has just a lower limit ≳ 650 TeV ( ≳ 480 TeV ) and m χ ~ 1 0 is constrained to 1.12 ( 1.13 ) ± 0.02 TeV in the μ > 0 ( μ < 0 ) scenario. In neither case can the anomalous magnetic moment of the muon, ( g - 2 ) μ , be improved significantly relative to its Standard Model (SM) value, nor do flavour measurements constrain the model significantly, and there are poor prospects for discovering supersymmetric particles at the LHC, though there are some prospects for direct DM detection. On the other hand, if the χ ~ 1 0 contributes only a fraction of the cold DM density, future LHC -based searches for gluinos, squarks and heavier chargino and neutralino states as well as disappearing track searches in the wino-like LSP region will be relevant, and interference effects enable BR ( B s , d → μ + μ - ) to agree with the data better than in the SM in the case of wino-like DM with μ > 0 .

Background Emergency and essential surgical, obstetric and anaesthesia (SOA) care are now recognized components of universal health coverage, necessary for a functional health system. To improve surgical care at a national level, strategic planning addressing the six domains of a surgical system is needed. This paper details a process for development of a national surgical, obstetric and anaesthesia plan (NSOAP) based on the experiences of frontline providers, Ministry of Health officials, WHO leaders, and consultants. Methods Development of a NSOAP involves eight key steps: Ministry support and ownership; situation analysis and baseline assessments; stakeholder engagement and priority setting; drafting and validation; monitoring and evaluation; costing; governance; and implementation. Drafting a NSOAP involves defining the current gaps in care, synthesizing and prioritizing solutions, and providing an implementation and monitoring plan with a projected cost for the six domains of a surgical system: infrastructure, service delivery, workforce, information management, finance and governance. Results To date, four countries have completed NSOAPs and 23 more have committed to development. Lessons learned from these previous NSOAP processes are described in detail. Conclusion There is global movement to address the burden of surgical disease, improving quality and access to SOA care. The development of a strategic plan to address gaps across the SOA system systematically is a critical first step to ensuring countrywide scale‐up of surgical system‐strengthening activities. Antecedentes En la actualidad, se reconoce que la atención quirúrgica, obstétrica y anestésica urgente y esencial (surgical, obstetric, and anaesthesia, SOA) es uno de los componentes de la cobertura sanitaria universal y un elemento necesario para el funcionamiento de un sistema de salud. Para mejorar la atención quirúrgica a nivel nacional, se necesita una planificación estratégica que aborde los seis dominios de un sistema quirúrgico. En este artículo, se detalla el proceso para el desarrollo de un plan nacional de cirugía, obstetricia y anestesia (national surgical, obstetric, and anaesthesia plan, NSOAP) basado en las experiencias de los principales proveedores, los funcionarios del Ministerio de Salud, los líderes de la Organización Mundial de la Salud y consultores. Métodos El desarrollo de un NSOAP incluye ocho pasos clave: (1) apoyo y dependencia del ministerio, (2) análisis de la situación y evaluaciones de referencia, (3) compromiso de los agentes implicados y establecimiento de prioridades, (4) redacción y validación, (5) seguimiento y evaluación, (6) análisis de costes, (7) gobernanza y (8) implementación. Redactar un NSOAP implica definir los déficits actuales en la atención, sintetizar y priorizar soluciones, y proporcionar un plan de implementación y seguimiento con unos costes proyectados para los seis dominios de un sistema quirúrgico: infraestructura, prestación de servicios, personal, gestión de la información, finanzas y gobernanza. Resultados Hasta la fecha, cuatro países han completado un NSOAP y 23 más se han comprometido con su desarrollo. Las lecciones aprendidas de estos procesos previos de NSOAP se describen con detalle. Conclusiones Existe un movimiento global para abordar la carga de las enfermedades que precisan cirugía, mejorar la calidad y el acceso a la atención SOA. El desarrollo de un plan estratégico para la aproximación sistemáticamente los déficits en todo el sistema SOA es un primer paso crítico para garantizar la ampliación a nivel nacional de las actividades de fortalecimiento del sistema quirúrgico. This article describes a possible skeleton process for developing a national surgical, obstetric and anaesthesia plan (NSOAP) from the authors' experiences of developing some of the world's first NSOAPs in low‐ and middle‐income countries. It discusses the specific challenges encountered and highlights lessons learned from navigating this process. Reproducible framework for improving global surgical care