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The objective of this study was to compare the effectiveness of a second tumor necrosis factor inhibitor (TNFi) versus a non‐TNFi biologic following discontinuation of a TNFi for patients with polyarticular‐course juvenile idiopathic arthritis (pJIA). Using the Childhood Arthritis and Rheumatology Research Alliance Registry, patients with pJIA who started receiving a second biologic following a first TNFi were identified. Patients were required to have no active uveitis on the index date and a visit six months after the index date. Outcome measures included Clinical Juvenile Arthritis Disease Activity Score with a maximum of 10 active joints (cJADAS10), cJADAS10 inactive disease (ID; ≤2.5) and cJADAS10 minimal disease activity (MiDA; ≤5). Multiple imputation was used to account for missing data. Adjusted odds ratios (aORs) were calculated using propensity score quintiles to compare outcomes at six months following second biologic initiation. There were 216 patients included, 84% initially received etanercept, and most patients stopped receiving it because of its ineffectiveness (74%). A total of 183 (85%) started receiving a second TNFi, and 33 (15%) started receiving a non‐TNFi. Adalimumab was the most common second biologic received (71% overall, 84% of second TNFi), and tocilizumab was the most common non‐TNFi second biologic received (9% overall, 58% of non‐TNFi). There was no difference between receiving TNFi versus non‐TNFi in cJADAS10 ID (29% vs 25%; aOR 1.23, 95% confidence interval [CI] 0.47–3.20) or at least MiDA (43% vs 39%; aOR 1.11, 95% CI 0.47–2.62) at six months. Most patients with pJIA started receiving TNFi rather than non‐TNFi as their second biologic, and there were no differences in disease activity at six months.

Asteroids with diameters less than about 5 km have complex histories because they are small enough for radiative torques (that is, YORP, short for the Yarkovsky–O’Keefe–Radzievskii–Paddack effect)1to be a notable factor in their evolution2. (152830) Dinkinesh is a small asteroid orbiting the Sun near the inner edge of the main asteroid belt with a heliocentric semimajor axis of 2.19 au; its S-type spectrum3,4is typical of bodies in this part of the main belt5. Here we report observations by the Lucy spacecraft6,7as it passed within 431 km of Dinkinesh. Lucy revealed Dinkinesh, which has an effective diameter of only 720 m, to be unexpectedly complex. Of particular note is the presence of a prominent longitudinal trough overlain by a substantial equatorial ridge and the discovery of the first confirmed contact binary satellite, now named (152830) Dinkinesh I Selam. Selam consists of two near-equal-sized lobes with diameters of 210 m and 230 m. It orbits Dinkinesh at a distance of 3.1 km with an orbital period of about 52.7 h and is tidally locked. The dynamical state, angular momentum and geomorphologic observations of the system lead us to infer that the ridge and trough of Dinkinesh are probably the result of mass failure resulting from spin-up by YORP followed by the partial reaccretion of the shed material. Selam probably accreted from material shed by this event.

Health disparities in childhood‐onset systemic lupus erythematosus (SLE) disproportionately impact marginalized populations. Socioeconomically patterned missing data can magnify existing health inequities by supporting inferences that may misrepresent populations of interest. Our objective was to assess missing data and subsequent health equity implications among participants with childhood‐onset SLE enrolled in a large pediatric rheumatology registry. We evaluated co‐missingness of 12 variables representing demographics, socioeconomic position, and clinical factors (e.g., disease‐related indices) using Childhood Arthritis and Rheumatology Research Alliance Registry childhood‐onset SLE enrollment data (2015–2022; n = 766). We performed logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) for missing disease‐related indices at enrollment (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI‐2K] and/or Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]) associated with data missingness. We used linear regression to assess the association between socioeconomic factors and SLEDAI‐2K at enrollment using 3 analytic methods for missing data: complete case analysis, multiple imputation, and nonprobabilistic bias analyses, with missing values imputed to represent extreme low or high disadvantage. On average, participants were missing 6.2% of data, with over 50% of participants missing at least 1 variable. Missing data correlated most closely with variables within data categories (i.e., demographic). Government‐assisted health insurance was associated with missing SLEDAI‐2K and/or SDI scores compared to private health insurance (OR 2.04 [95% CI 1.22, 3.41]). The different analytic approaches resulted in varying analytic sample sizes and fundamentally conflicting estimated associations. Our results support intentional evaluation of missing data to inform effect estimate interpretation and critical assessment of causal statements that might otherwise misrepresent health inequities.

The goal was to characterize short‐term kidney status and describe variation in early care utilization in a multicenter cohort of patients with childhood‐onset systemic lupus erythematosus (cSLE) and nephritis. We analyzed previously collected prospective data from North American patients with cSLE with kidney biopsy‐proven nephritis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry from March 2017 through December 2019. We determined the proportion of patients with abnormal kidney status at the most recent registry visit and applied generalized linear mixed models to identify associated factors. We also calculated frequency of medication use, both during induction and ever recorded. We identified 222 patients with kidney biopsy–proven nephritis, with 64% class III/IV nephritis on initial biopsy. At the most recent registry visit at median (interquartile range) of 17 (8–29) months from initial kidney biopsy, 58 of 106 patients (55%) with available data had abnormal kidney status. This finding was associated with male sex (odds ratio [OR] 3.88, 95% confidence interval [95% CI] 1.21–12.46) and age at cSLE diagnosis (OR 1.23, 95% CI 1.01–1.49). Patients with class IV nephritis were more likely than class III to receive cyclophosphamide and rituximab during induction. There was substantial variation in mycophenolate, cyclophosphamide, and rituximab ever use patterns across rheumatology centers. In this cohort with predominately class III/IV nephritis, male sex and older age at cSLE diagnosis were associated with abnormal short‐term kidney status. We also observed substantial variation in contemporary medication use for pediatric lupus nephritis between pediatric rheumatology centers. Additional studies are needed to better understand the impact of this variation on long‐term kidney outcomes.

Children with well‐controlled juvenile idiopathic arthritis (JIA) frequently experience flares after medication discontinuation, but the outcomes of these flares have not been well described. The objective of this study was to characterize the rates and predictors of disease recapture among children with JIA who restarted medication to treat disease flare. Children with JIA who discontinued conventional synthetic or biologic disease‐modifying antirheumatic drugs for well‐controlled disease but subsequently experienced a flare and restarted medication were identified from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. The primary outcome was inactive disease (ID) (physician global assessment <1 and active joint count = 0) 6 months after flare. A total of 333 patients had complete data for ID at 6 months after flare. The recapture rate for the cohort was 55%, ranging from 47% (persistent oligoarthritis) to 69% (systemic arthritis) (P= 0.4). Approximately 67% of children achieved ID by 12 months. In the multivariable model, history and reinitiation of biologic drugs were associated with increased odds of successful recapture (odds ratio [OR] 4.79 [95% confidence interval (95% CI) 1.22–18.78] and OR 2.74 [95% CI 1.62–4.63], respectively). Number of joints with limited range of motion was associated with decreased odds (OR 0.83 per 1 joint increase [95% CI 0.72–0.95]). Approximately half of JIA flares post‐discontinuation were recaptured within 6 months, but rates of recapture varied across JIA categories. These findings inform shared decision‐making for patients, families, and clinicians regarding the risks and benefits of medication discontinuation. Better understanding of biologic predictors of successful recapture in JIA are needed.

After introducing IL-1/IL-6 inhibitors, some patients with Still and Still-like disease developed unusual, often fatal, pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease.

Down syndrome–associated arthritis (DA) is underrecognized, and current therapies used for juvenile idiopathic arthritis (JIA) appear to be poorly tolerated and less effective in patients with DA. The objective of this study was to characterize clinical manifestations and therapeutic preferences in DA compared to JIA, using the new Childhood Arthritis and Rheumatology Research Alliance (nCARRA) registry. In a case–control study, between July 2015 and March 2019, patients with a diagnosis of JIA and Down syndrome (DS) were identified and matched by age, sex, and JIA subtype to patients who have JIA without DS. Collected data included demographic characteristics, disease characteristics, laboratory results, treatment exposure, and outcome measures. A total of 36 children with DA and 165 with JIA were identified. Most patients presented with polyarticular rheumatoid factor–negative disease. At entry into the nCARRA registry, there were minimal differences between the groups, and at the last visit there were significant differences (P< 0.05) for multiple outcome measures. Patients with DA and those with JIA had similar therapeutic exposure to disease‐modifying antirheumatic drugs (DMARDs) and biologics, but those with DA had more DMARD‐related adverse events (93% versus 25%) and biologic therapy ineffectiveness (60% versus 17%). There was little difference between patients with DA and those with JIA at baseline, and similar therapy was implemented for those in the nCARRA registry; however, at the last visit, the patients with DA had greater disease burden. Additionally, there were more DMARD‐related adverse events and biologic ineffectiveness for those patients with DA. More research is needed to determine differences in pathophysiology and optimal therapeutic approaches.

To describe characteristics of children with enthesitis‐related arthritis (ERA) and juvenile psoriatic arthritis (PsA) who were enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. All children with ERA and those with juvenile PsA were identified. Demographic characteristics, clinical characteristics, and treatments were described. The children with sacroiliitis and those without sacroiliitis were compared. In the children with sacroiliitis, the first visit with clinically active sacroiliitis (which came first in 72% of cases) was compared to the first visit without clinically active sacroiliitis. A total of 902 children with ERA or juvenile PsA were identified. Children with ERA were older at diagnosis (ages 10.8 years versus 8.2 years; P< 0.01) and were more likely to be male (56% versus 38%; P< 0.01). Polyarticular involvement was reported in 57% of children with ERA and in 72% of those with juvenile PsA. Of the children tested, HLA–B27 was positive in 38% of those in the ERA group and in 12% of those in the juvenile PsA group. At least 1 biologic was taken by 72% of those with ERA and 64% of those with juvenile PsA. Sacroiliitis (diagnosed clinically and/or by imaging) was reported in 28% of the children (40% of those with ERA and 12% of those with juvenile PsA). Of these, 54% of the children were female, 36% were HLA–B27 positive, and 81% took at least 1 biologic. In children with sacroiliitis, scores according to the physician global assessment of disease activity, parent/patient global assessment of well‐being, and clinical Juvenile Arthritis Disease Activity Score 10 were all significantly worse at the first visit with clinically active sacroiliitis versus the first visit without active sacroiliitis. In this registry, there are more than 900 children with ERA or juvenile PsA. There was high biologic use in this population, especially in those with sacroiliitis. Further, there was equal sex representation in those children with sacroiliitis.

Acquiring and processing astrometric measurements of a spacecraft’s target using on-board images, generically referred to as optical navigation, is an integral function of the orbit determination and navigation of NASA’s New Horizons spacecraft. Since New Horizons’ reconnaissance of the Pluto system in July 2015, many preparations have been completed to further enhance the optical navigation system and prepare for the reconnaissance of New Horizons’ next target, Kuiper Belt Object (486958) 2014 MU69(unofficially nicknamed Ultima Thule). Due to its low relative brightness compared to most planetary exploration targets, Ultima Thule presents several unique challenges to the optical navigation system. The optical navigation system design, imaging schedule, and technical algorithms that were developed and tailored to these challenges are explored in detail. Additionally, several operational readiness tests, simulation methods, and test results are presented and analyzed to assess the optical navigation system performance and implications to flight operations. Lastly, a first look at Ultima as viewed from the New Horizons LORRI imager is presented.

Pluto is thought to possess a present-day ocean beneath a thick ice shell. It has generally been assumed that Pluto accreted from cold material and then later developed its ocean due to warming from radioactive decay; in this ‘cold start’ scenario, the ice shell would have experienced early compression and more recent extension. Here we compare thermal model simulations with geological observations from the New Horizons mission to suggest that Pluto was instead relatively hot when it formed, with an early subsurface ocean. Such a ‘hot start’ Pluto produces an early, rapid phase of extension, followed by a more prolonged extensional phase, which totals ~0.5% linear strain over the last 3.5 Gyr. The amount of second-phase extension is consistent with that inferred from extensional faults on Pluto; we suggest that an enigmatic ridge–trough system recently identified on Pluto is indicative of early extensional tectonics. A hot initial start can be achieved with the gravitational energy released during accretion if the final stage of Pluto’s accretion is rapid (<30 kyr). A fast final stage of growth is in agreement with models of the formation of Kuiper belt objects via gravitational collapse followed by pebble accretion, and implies that early oceans may have been common in the interiors of large Kuiper belt objects.

Volcanic lightning—a near ubiquitous feature of explosive volcanic eruptions—possesses great potential for the analysis of volcanic plume dynamics. To date, the lack of quantitative knowledge on the relationships between plume characteristics hinders efficient data analysis and application of the resulting parameterizations. We use a shock‐tube apparatus for rapid decompression experiments to produce particle‐laden jets. We have systematically and independently varied the water content (0–27 wt%) and the temperature (25–320 °C) of the particle‐gas mixture. The addition of a few weight percent of water is sufficient to reduce the observed electrification by an order of magnitude. With increasing temperature, a larger number of smaller discharges are observed, with the overall amount of electrification staying similar. Changes in jet dynamics are proposed as the cause of the temperature‐dependence, while multiple factors (including the higher conductivity of wet ash) can be seen responsible for the decreased electrification in wet experiments. Volcanic explosive eruptions are accompanied by lightning strikes generated from the volcanic dust cloud. Here we have experimentally studied the effects of atmospheric water and plume temperature on the frequency and intensity of the lightning strikes. The results will feed a model for the use of volcanic lightning strikes to estimate plume contents and intensity. Natural observations on the influence of temperature and water content on volcanic lightning have been modelled in laboratory experiments.The magnitude of electrification and discharging in plumes decreases significantly with added water.At higher temperatures a decrease in magnitude of individual discharges is observed, while the total neutralized charge stays similar.

Pluto energies of a few kiloelectron volts and suprathermal ions with tens of kiloelectron volts and above. We measure this population using the Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) instrument on board the New Horizons spacecraft that flew by Pluto in 2015. Even though the measured ions have gyroradii larger than the size of Pluto and the cross section of its magnetosphere, we find that the boundary of the magnetosphere is depleting the energetic ion intensities by about an order of magnitude close to Pluto. The intensity is increasing exponentially with distance to Pluto and reaches nominal levels of the interplanetary medium at about 190RPdistance. Inside the wake of Pluto, we observe oscillations of the ion intensities with a periodicity of about 0.2 hr. We show that these can be quantitatively explained by the electric field of an ultralow‐frequency wave and discuss possible physical drivers for such a field. We find no evidence for the presence of plutogenic ions in the considered energy range. Space around Pluto is not entirely empty but filled with solar wind plasma and ions that originate from interstellar space and are pushed outward by the solar wind. All planetary bodies interact with their surrounding medium. In the case of a magnetized body like Earth, this interaction is strong and creates a magnetosphere. Unmagnetized bodies like that of the dwarf planet Pluto have a much weaker interaction. What makes Pluto special is that it is far outside in our solar system and therefore embedded in relatively high intensities of interstellar ions. When New Horizons passed Pluto and measured the distribution of these ions, we found that Pluto is forming a wake in the interstellar ion flow. It is more difficult to deflect the motion of the relatively fast‐moving interstellar ions than it is to deflect the lower‐energy solar wind. Therefore, it was not obvious that we would observe this. Even Pluto's wake is not entirely empty because some interstellar ions do manage to enter. Another finding was that a wave is propagating within the tenuous medium of the wake. This wave modulates the ion intensities resembling a sound wave propagating through air and modulating the gas density. Pluto forms a wake for energetic heliospheric ionsWaves cause ion intensity oscillations in the wake

New Horizons did not carry a magnetometer, so there is no direct way to know the strength of the Interplanetary Magnetic Field (IMF) at the time of the flyby. Using a hybrid model together with a detailed model of the Solar Wind Around Pluto (SWAP) instrument (McComas et al., 2007, https://doi.org/10.1007/s11214-007-9205-3) we have identified three observables that are sensitive to IMF strength: the width of Pluto's heavy ion tail, the energy of heavy ions, and the profile of thermal pressure along the New Horizons trajectory. By comparing simulation to data we infer that the IMF strength was most likely near or below ∼0.1 nT. We also show that the shell distribution of Interstellar Pickup Ions is important for reproducing these observations due to its effect on global pressure balance. Numerical experiments suggest that an IMF strength near or below 0.1 nT is consistent with New Horizons dataHigh plasma beta in the wake adequately explains the broad heavy ion tail that was observedThe shell distribution of interplanetary pickup ions is important for understanding Pluto's plasma wake

Geologic mapping has been used for over 200 years as a technique to synthesize a complicated surface into a more simplified product, identifying similar types of surface features, and placing them into a relative stratigraphy. Geomorphologic mapping has applied those principles to other terrestrial bodies throughout the solar system and has formed an important product set to understand these surfaces, plan future exploration, and conduct different scientific endeavors. We created a geomorphologic map of the New Horizonsencounter hemisphere of Pluto's binary companion, Charon. Ten primary geomorphologic unit categories were identified, covering approximately 35% of Charon's surface, and we used lower resolution data to speculate about other regions of Charon. Over 1,000 linear features were mapped, nearly 90% of them are tectonic in nature, and we use these to provide evidence of Charon being active in its past. Additionally, we placed the mapped features into a chronostratigraphic sequence, and we present a possible surface history for the body. The northern terrain typified by large crustal blocks is the oldest, having fractured early in Charon's history, and potentially similar blocks were submerged in a cryoflow of which the now solid surface of Vulcan Planitia is the remnant today. Planetary scientists will create geologic maps of a surface to perform different kinds of studies. Geologic maps identify features of different types and help to distill many different kinds of data into an easier to use format from which scientific investigations can be done. We have created such a map for Pluto's largest companion, Charon, imaged during the flyby of New Horizonsin July 2015. This geologic map covers approximately 35% of the best‐imaged region of Charon, and we mapped 16 different geologic units, over 1,000 linear features, and a variety of albedo features. We developed a chronology that places these features in time‐order, and we provide potential interpretations of the different features that we mapped. We found that Charon has potentially one of the most convincing examples of possible large cryoflow(s) of any heretofore imaged body in the solar system. We present a new geomorphologic map of New Horizons' encounter hemisphere of Charon, showing units, linear features, and albedo featuresWe introduce a chronostratigraphic system to place features and units in a historic sequence and contextWe interpret units and features in local, regional, and global context, pulling from knowledge of other solar system bodies

The New Horizonsencounter with the cold classical Kuiper Belt object 2014 MU69(informally named “Ultima Thule,” hereafter Ultima) on 1 January 2019 will be the first time a spacecraft has ever closely observed one of the free‐orbiting small denizens of the Kuiper Belt. Related to but not thought to have formed in the same region of the solar system as the comets that been explored so far, it will also be the most distant, and most primitive body yet visited by spacecraft. In this letter we begin with a brief overview of cold classical Kuiper Belt objects, of which Ultima is a prime example. We give a short preview of our encounter plans. We note what is currently known about Ultima from Earth‐based observations. We then review our expectations and capabilities to evaluate Ultima's composition, surface geology, structure, near space environment, small moons, rings, and the search for activity. The letter discusses the current state‐of‐knowledge for the cold classical Kuiper Belt object 2014 MU69, the target of a close encounter by NASA's New Horizon spacecraft on 1 January 2019. We also review our encounter plans and make broad speculative predictions as to might be revealed by our observations. New Horizons will fly to within 3,500 km of 2014 MU69(informally named “Ultima Thule”), acquiring images with pixel scale resolutions significantly better than 100 m/pixel). We plan to obtain topography derived from stereo imaging and body shape. Our spectroscopic observations potentially could detect H2O, CH4, N2, CH3OH, and NH3, depending on their brightness and abundance on the surface. We will also search for evidence of outgassing, small moons, and rings. This exploration will transform Kuiper Belt and Kuiper Belt object science from a purely astronomical regime, to a geological and geophysical regime, which radically changed paradigms when the same happened to asteroids and comets in past decades. New Horizons will fly to within 3,500 km of 2014 MU69, acquiring images with pixel scale resolutions significantly better than 100 m/pixelOur spectroscopic observations potentially could detect H2O, CH4, N2, CH3OH, and NH3, depending on their brightness and abundanceWe will evaluate Ultima's composition, surface geology, structure, near space environment, and the search for small moons, rings, and activity

Recent observations of interplanetary medium atomic hydrogen Lyman‐α emission in the outer solar system, made with the Alice ultraviolet spectrograph on New Horizons, are presented. The observations include regularly spaced great circle scans of the sky and pointed observations near the downstream and upstream flow directions of interstellar H atoms. The New Horizons Alice data agree very well with the much earlier Voyager UVS results, after these are reduced by a factor of 2.4 in brightness, in accordance with recent reanalyses. In particular, the falloff of interplanetary medium Lyman‐α brightness in the upstream‐looking direction as a function of spacecraft distance from the Sun is well matched by an expected 1/rdependence, but with an added constant brightness of ~40 Rayleighs. This additional brightness is a possible signature of the hydrogen wall at the heliopause or of a more distant background. Ongoing observations are planned at a cadence of roughly twice per year. Long‐term observations made with the Alice instrument on the New Horizons spacecraft confirm measurements made 30 years earlier with the Voyager spacecraft. Both sets of data are best explained if the observed ultraviolet light is not only a result of the scattering of sunlight by hydrogen atoms within the solar system but includes a substantial contribution from a distant source. This distant source could be the signature of a “wall” of hydrogen, formed near where the interstellar wind encounters the solar wind, or could be more distant. Similar future observations from New Horizons are planned about twice each year. New Horizons Alice observations of interplanetary medium Lyman alpha are presentedThe observed brightness falloff with distance from the Sun matches well with Voyager results and indicates a substantial external background contribution

Bipolar disorder (BD) is a progressive psychiatric disorder with more than 3% prevalence worldwide. Affected individuals experience recurrent episodes of depression and mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and genetic heterogeneity of psychiatric disorders have challenged the development of animal and cellular models. We recently reported that hippocampal dentate gyrus (DG) neurons differentiated from induced pluripotent stem cell (iPSC)-derived fibroblasts of BD patients are electrophysiologically hyperexcitable. Here we used iPSCs derived from Epstein–Barr virus-immortalized B-lymphocytes to verify that the hyperexcitability of DG-like neurons is reproduced in this different cohort of patients and cells. Lymphocytes are readily available for research with a large number of banked lines with associated patient clinical description. We used whole-cell patch-clamp recordings of over 460 neurons to characterize neurons derived from control individuals and BD patients. Extensive functional analysis showed that intrinsic cell parameters are very different between the two groups of BD neurons, those derived from lithium (Li)-responsive (LR) patients and those derived from Li-non-responsive (NR) patients, which led us to partition our BD neurons into two sub-populations of cells and suggested two different subdisorders. Training a Naïve Bayes classifier with the electrophysiological features of patients whose responses to Li are known allows for accurate classification with more than 92% success rate for a new patient whose response to Li is unknown. Despite their very different functional profiles, both populations of neurons share a large, fast after-hyperpolarization (AHP). We therefore suggest that the large, fast AHP is a key feature of BD and a main contributor to the fast, sustained spiking abilities of BD neurons. Confirming our previous report with fibroblast-derived DG neurons, chronic Li treatment reduced the hyperexcitability in the lymphoblast-derived LR group but not in the NR group, strengthening the validity and utility of this new human cellular model of BD.

On the moon and other airless bodies, ballistically emplaced ejecta transitions from a thinning, continuous inner deposit to become discontinuous beyond approximately one crater radius from the crater rim and can further break into discrete rays and secondary craters. In contrast, on Mars, ejecta often form continuous, distinct, and sometimes thick deposits that transition to a low ridge or escarpment that may be circular or lobate. The Martian ejecta type has been variously termed pancake, rampart, lobate, or layered, and in this work we refer to it as “abrupt termini” ejecta (ATE). Two main formation mechanisms have been proposed, one requiring interaction of the ejecta with the atmosphere and the other mobilization of near‐surface volatiles. ATE morphologies are also unambiguously seen on Ganymede, Europa, Dione, and Tethys, but they are not as common as on Mars. We have identified up to 38 craters on Charon that show signs of ATE, including possible distal ramparts and lobate margins. These ejecta show morphologic and morphometric similarities with other moons in the solar system, which are a subset of the properties observed on Mars. From comparison of these ejecta on Charon and other solar system bodies, we find the strongest support for subsurface volatile mobilization and ejecta fluidization as the main formation mechanism for the ATE, at least on airless, icy worlds. This conclusion comes from the bodies on which they are found, an apparent preference for certain terrains, and the observation that craters with ATE can be near to similarly sized craters that only have gradational ejecta. Report discovery of Charon abrupt termini ejecta cratersDescribe properties of Charon abrupt termini ejecta and their host craters in context of other bodiesConstrain formation mechanisms for these ejecta blankets

The unusual dark red coloration of Charon’s northern polar cap is shown to be produced from hydrocarbons that are cold-trapped from Pluto’s escaping atmosphere during winter.

The vast, deep, volatile-ice-filled basin informally named Sputnik Planum is central to Pluto’s vigorous geological activity. Composed of molecular nitrogen, methane, and carbon monoxide ices, but dominated by nitrogen ice, this layer is organized into cells or polygons, typically about 10 to 40 kilometres across, that resemble the surface manifestation of solid-state convection. Here we report, on the basis of available rheological measurements, that solid layers of nitrogen ice with a thickness in excess of about one kilometre should undergo convection for estimated present-day heat-flow conditions on Pluto. More importantly, we show numerically that convective overturn in a several-kilometre-thick layer of solid nitrogen can explain the great lateral width of the cells. The temperature dependence of nitrogen-ice viscosity implies that the ice layer convects in the so-called sluggish lid regime, a unique convective mode not previously definitively observed in the Solar System. Average surface horizontal velocities of a few centimetres a year imply surface transport or renewal times of about 500,000 years, well under the ten-million-year upper-limit crater retention age for Sputnik Planum. Similar convective surface renewal may also occur on other dwarf planets in the Kuiper belt, which may help to explain the high albedos shown by some of these bodies.

This study provides the first observations of Plutogenic ions and their unique interaction with the solar wind. We find ~20% solar wind slowing that maps to a point only ~4.5 RPupstream of Pluto and a bow shock most likely produced by comet‐like mass loading. The Pluto obstacle is a region of dense heavy ions bounded by a “Plutopause” where the solar wind is largely excluded and which extends back >100 RPinto a heavy ion tail. The upstream standoff distance is at only ~2.5 RP. The heavy ion tail contains considerable structure, may still be partially threaded by the interplanetary magnetic field (IMF), and is surrounded by a light ion sheath. The heavy ions (presumably CH4+) have average speed, density, and temperature of ~90 km s−1, ~0.009 cm−3, and ~7 × 105K, with significant variability, slightly increasing speed/temperature with distance, and are N‐S asymmetric. Density and temperature are roughly anticorrelated yielding a pressure ~2 × 10−2pPa, roughly in balance with the interstellar pickup ions at ~33 AU. We set an upper bound of <30 nT surface field at Pluto and argue that the obstacle is largely produced by atmospheric thermal pressure like Venus and Mars; we also show that the loss rate down the tail (~5 × 1023s−1) is only ~1% of the expected total CH4loss rate from Pluto. Finally, we observe a burst of heavy ions upstream from the bow shock as they are becoming picked up and tentatively identify an IMF outward sector at the time of the NH flyby. First observations of heavy ions from Pluto and their unique interaction with the solar windDiscovery of a Plutopause with an upstream standoff distance at two and a half Pluto radiiDiscovery of heavy ion tail behind Pluto losing 5 × 1023ions per second

Evidence from Arrokoth and comets strongly suggests a very low density for this and similar small Kuiper belt objects. Plausible compositions imply high porosities, in excess of 70%, and low compaction crush strengths. If so, impact craters on Arrokoth (especially Sky, its largest) formed largely by compaction of pore space and material displacement. This is consistent with geological evidence from New Horizonsimaging. High porosity reduces cratering efficiency in the gravity regime whereas compaction moves it toward crush strength scaling and increased efficiency. Compaction also guarantees that most impactor kinetic energy is taken up as waste heat near the impact point, with momentum transferred to the rest of the body by elastic waves only. Monte Carlo simulations of Sky‐forming conditions indicate that the momentum imparted likely separated Arrokoth's two lobes, but displacement was limited by dissipation at the neck between them. Unusual strength properties are not required to preserve Arrokoth's bilobate configuration. It has become apparent over the last few years that small asteroids and comets are very underdense compared with the materials they are made of. This means that their total porosities are likely quite high, in excess of 70%, both as tiny voids within particles (so‐called microscopic porosity) and spaces between particles (macroscopic porosity). But none are likely as porous as the distant denizens of the Kuiper belt such as Arrokoth (visited by the New Horizonsspacecraft in 2019). This paper concerns impact craters on Arrokoth and similar small bodies, and the rather unusual effects expected. Imagine a fluffy (fine powder) snowball striking a much larger fluffy snowball, only that the snow is not pure ice but a mixture of porous icy, rocky, and carbon‐rich particles. Even at high velocities (>100 s of m/s) craters should mostly form by compacting pore space and pushing material away from the impact point, not the traditional blasting of ejecta back into space. Similar to crush‐up of an automobile bumper, compaction helps to protect from the potentially catastrophic effects of large impacts, such as complete disruption of the target or breakup of bilobate bodies like Arrokoth, and should be incorporated in future collisional evolution studies. Arrokoth is likely a low density, highly porous, contact binary planetesimalImpact craters on Arrokoth, and particularly its largest, likely formed as compaction craters, with modest or little ejectaHigh porosity acted to protect Arrokoth from catastrophic disruption, ejecta recoil, and lobe dislocation and rearrangement Arrokoth is likely a low density, highly porous, contact binary planetesimal Impact craters on Arrokoth, and particularly its largest, likely formed as compaction craters, with modest or little ejecta High porosity acted to protect Arrokoth from catastrophic disruption, ejecta recoil, and lobe dislocation and rearrangement

NASA's New Horizonsmission performed the first flyby of a small Kuiper Belt Object (KBO), (486958) Arrokoth on 1 January 2019. The fast flyby revealed a fascinating, flattened, contact binary replete with a variety of unexpected geologic terrains. However, the irregular shape and constraints imposed by the fast flyby makes it a challenge to understand these features. Here we use the latest New Horizonsshape models of Arrokoth to investigate its geophysical environment, including its surface slopes, gravity field, and moments of inertia—which are critical context for understanding Arrokoth's formation, evolution, and peculiar geology. We find that Arrokoth's surface features have a complicated relationship to its geophysical environment. For example, bright material tends to be concentrated in geopotential lows (like the neck), consistent with mass wasting—however, this trend is not consistently observed across Arrokoth. Mass wasting may naturally explain some aspects of Arrokoth's geology, but the actual dynamics of material transport may be complicated owing to Arrokoth's unique shape, spin‐rate, and inferred density. While New Horizons's fast and distant flyby precluded directly measuring Arrokoth's mass, we used techniques previously pioneered for comets and asteroids to infer its density. We find that Arrokoth has a low bulk density of ρ= 235 kg/m3(1σrange: 155–600 kg/m3). This density is low compared to previously explored small bodies, but is comparable to comets, select binary KBOs, and the ring‐moons of Saturn. This low density may be a critical data‐point for understanding the formation of planetesimals at the dawn of the Solar System. NASA's New Horizonsmission performed the first flyby of a small Kuiper Belt Object (KBO), (486958) Arrokoth on 1 January 2019. Arrokoth is a ∼30‐km long, peanut shaped, icy body in the Kuiper Belt—a reservoir of small bodies left over from the Solar System's formation. Arrokoth is the most distant, and likely the least evolved object, ever explored by a spacecraft. Arrokoth's unusual shape makes it challenging to determine how material moves across its surface. We use the latest shape models to calculate Arrokoth's gravity field. Bright material tends to collect in Arrokoth's lowest locations, perhaps indicating material can move downslope. While New Horizonswas not able to measure the density of Arrokoth, we are able to infer it using techniques pioneered for studying asteroids and comets. We find that Arrokoth's density is extremely low—more akin to fluffy snow on Earth. If correct, this would be one of the lowest density objects ever explored, closer to the densities of some of the comets and small moons within Saturn's rings. Arrokoth's low density may suggests that the building blocks of planets were assembled very gently in the outer Solar System, in the first few million years of Solar System formation. We present new models for the geophysical environment of (486958) Arrokoth based on the latest New Horizonsshape modelsMany (but not all) of Arrokoth's enigmatic surface markings are correlated with its geophysical environmentAnalysis of Arrokoth's shape suggests that it has a low density of 235 kg/m3(1σrange: 155–600 kg/m3) We present new models for the geophysical environment of (486958) Arrokoth based on the latest New Horizonsshape models Many (but not all) of Arrokoth's enigmatic surface markings are correlated with its geophysical environment Analysis of Arrokoth's shape suggests that it has a low density of 235 kg/m3(1σrange: 155–600 kg/m3)

To explain the position of the Sputnik Planitia basin on Pluto, the feature would need to have formed via impact and Pluto would need to have a subsurface ocean.

Modelling suggests that the icy region on Pluto known as Sputnik Planitia formed shortly after Charon did and has since been stable, with its latitude corresponding to a minimum in annual solar illumination and its longitude determined by tidal forces from Charon.

The orientation and morphology of the bilobate, cold classical Kuiper belt object (486958) Arrokoth (formerly 2014 MU69) is consistent with a slow, tidal merger of a close binary. However, the discrepancy between Arrokoth's present‐day rotation (15.9 hr) and synchronous rotation for nominal cometary densities near ∼500 kg/m3implies reduction (up to 30%) in post‐merger spin angular momentum. We investigate how collisions with dynamically cold and hot classical Kuiper belt objects might have affected Arrokoth's post‐merger spin. Using a dynamically equivalent triaxial ellipsoid, 5000 Monte Carlo simulations of 100 impacts each, consistent with Arrokoth's cratering record, were carried out. Starting from the assumption of critical, synchronous rotation for a given density, these simulations rarely reproduce Arrokoth's present spin period, unless its true density is near 250 kg/m3. We explore in greater depth the effects of formation of Arrokoth's largest crater (now officially named Sky, previously informally named Maryland). We adopt point‐source scaling and randomly select impact parameters that lead to the crater, using Arrokoth's full bilobate shape. Results from Sky's formation alone are similar to those considering a full range of impactor sizes, unless we adopt low cratering efficiency due to high porosity, which implies substantially larger Sky‐forming impactors. Overall, results imply that the probability of substantial angular momentum change due to impacts alone over Solar System history is unlikely, and spindown from a synchronous, tidal rotation rate to a 15.9‐hr period unlikely unless Arrokoth itself was and is a very low density object (∼250 kg/m3), though we cannot statistically rule out densities up to 400 kg/m3. Both lobes of the cold classical Kuiper belt object Arrokoth were likely in a close spin‐synchronous orbit before they gently merged to form the bilobate body we see today. This spin‐synchronous orbital period depends on density, however, and Arrokoth's observed spin period implies that it either has an extremely low density (much lower than typical cometary values) or underwent significant despinning after the merger. Here we study the spin‐altering effects of impacts by other, small Kuiper belt objects over time and address the likelihood of the required despinning by impacts, with implications for Arrokoth's bulk density. We use a Monte Carlo impact simulation to investigate Arrokoth's rotational response over its impact history, with special attention to the largest recognized crater (Sky). Our results indicate that: (a) Small impacts alone are not capable of altering Arrokoth's spin by much; (b) The likelihood of geophysically significant impact despinning on Arrokoth is low, if it has a typical cometary density of ∼500 kg m−3; (c) Arrokoth's bulk density may actually be quite low, ∼250 kg m−3, implying substantial porosity. Impacts of classical Kuiper belt objects consistent with Arrokoth's observed craters caused at best modest spin changesThe formation of the largest craters would have had a larger effect, especially if cratering efficiency is reduced by substantial porosityThe most consistent interpretation of Arrokoth' shape and slow spin is that its bulk density is low, between 250 and 400 kg m−3 Impacts of classical Kuiper belt objects consistent with Arrokoth's observed craters caused at best modest spin changes The formation of the largest craters would have had a larger effect, especially if cratering efficiency is reduced by substantial porosity The most consistent interpretation of Arrokoth' shape and slow spin is that its bulk density is low, between 250 and 400 kg m−3

The influence of zinc bacitracin (ZB) and of Bacillus licheniformison host microbial-related functions in young piglets was investigated by applying the concept of microflora-associated characteristics. Six biochemical parameters were determined before and after weaning in faecal samples from piglets in four litters having access to a diet containing ZB, to a diet containing B. licheniformis, to a diet with both additives, or to a diet with no additives, from 3 weeks of age. Statistically significant differences were found in three of the intestinal functions investigated: formation of short-chain fatty acids (at 7 and 10 weeks of age), degradation of mucin (at 7 and 10 weeks of age) and conversion of bilirubin to urobilins (at 7 weeks of age). We also found age-dependent influences on the formation of short-chain fatty acids, on conversion of cholesterol to coprostanol and on conversion of bilirubin to urobilins. We conclude that a functional approach is appropriate for measuring exogenous influence(s) on the microbial intestinal metabolisms in weaned piglets.

Like all low- and moderate-mass stars, the Sun will burn as a red giant during its later evolution, generating of solar luminosities for some tens of millions of years. During this post-main sequence phase, the habitable (i.e., liquid water) thermal zone of our Solar System will lie in the region where Triton, Pluto-Charon, and Kuiper Belt objects orbit. Compared with the 1 AU habitable zone where Earth resides, this "delayed gratification habitable zone" (DGHZ) will enjoy a far less biologically hazardous environment - with lower harmful radiation levels from the Sun, and a far less destructive collisional environment. Objects like Triton, Pluto-Charon, and Kuiper Belt objects, which are known to be rich in both water and organics, will then become possible sites for biochemical and perhaps even biological evolution. The Kuiper Belt, with >105 objects ≥50 km in radius and more than three times the combined surface area of the four terrestrial planets, provides numerous sites for possible evolution once the Sun's DGHZ reaches it. The Sun's DGHZ might be thought to only be of academic interest owing to its great separation from us in time. However, ~109 Milky Way stars burn as luminous red giants today. Thus, if icy-organic objects are common in the 20-50 AU zones of these stars, as they are in our Solar System (and as inferred in numerous main sequence stellar disk systems), then DGHZs may form a niche type of habitable zone that is likely to be numerically common in the Galaxy.

We investigate the hypothesis that the so-called Late Heavy Bombardment (LHB) of the Moon was triggered by the formation of Uranus and Neptune. As Uranus and Neptune formed, which we assume occurred at the epoch of the LHB, they scattered neighboring icy planetesimals throughout the Solar System. Some of these objects hit the Moon. Our integrations show that the Moon would have accreted about 6×1021 g, if we assume that the Uranus–Neptune region initially contained 5 times the current mass of these planets in the form of small solid objects. In addition, Mars would have accumulated ∼6×1022 g of icy material, which could have supplied its putative early massive atmosphere. However, Earth would likely have accreted only ∼7×1022 g of water, or ∼5% of its oceans, through the mechanisms studied here. The numerical experiment that we have performed on the behavior of Uranus–Neptune planetesimals shows very good agreement with current constraints on the LHB. The influx of Uranus–Neptune planetesimals onto the Moon could have lasted for a time as short as 10 or 20 million years. The dynamical transport of the Uranus–Neptune planetesimals during this process would have caused Jupiter and Saturn to migrate. This migration, in turn, would have destabilized objects in the jovian Trojan swarms and the asteroid belt. Thus, not only would Uranus and Neptune planetesimals have struck the Moon, but asteroids would have as well. We find that the Trojan asteroids of Jupiter could not have contributed a large percentage of material to the LHB, but the asteroid belt could, in principle, have contributed to, or even dominated, the LHB. Although this model appears to explain the LHB well, it requires that fully formed Uranus and Neptune not appear in the trans-saturnian region until some 700 million years after the formation of the Earth.

We present an analysis of HST/FOC images of Triton obtained on 20–24 September 1995. Images were taken in two wavelength bands using the F278M and F410M filters in order to obtain the first mid-UV map of Triton and to place further compositional constraints on Triton's surface by imaging farther into the UV than did Voyager. Our disk-resolved images provide full (if sparse) longitudinal coverage, with image sets taken at Triton central meridian longitudes of 100°, 210°, and 330°. We compare FOC-derived lightcurves and geometric albedo maps with 1989 Voyager imaging data and 1993 HST/FOS disk-averaged albedos. We find that Triton's disk-averaged albedo has decreased at both 2780 (12%) and 4100 A˚ (8%) and that an extensive region near longitude 340° has reddened significantly, with a 4100:2780 A˚ albedo ratio that is 15% lower than average. We conclude that these changes are evidence of recent, large-scale volatile transport on Triton.

Photographic photometry of (2060) Chiron was carried out using a set of archival plates taken between 1969 and 1977. The data reveal an extensive interval of brightening, presumably due to an increase in cometary activity, when Chiron was near aphelion. This activity substantially exceeded, in both magnitude and duration, the activity observed as Chiron approached perihelion near the end of the 1980s.

We present results from our model of collision rates in the present-day Edgeworth–Kuiper Belt and Centaur region. We have updated previous results to allow for new estimates of the total disk population in order to examine surface activation and modification time scales due to cratering impacts. We extend previous results showing that the surfaces of Edgeworth–Kuiper Belt objects are not primordial and have been moderately to heavily reworked by collisions. Objects smaller than about r=2.5 km have collisional disruption lifetimes less than 3.5 Gyr in the present-day collisional environment and have probably been heavily damaged in their interiors by large collisions. In the 30- to 50-AU region, impacts of 1-km-radius comets onto individual 100-km-radius objects occur on 7×107–4×108-year time scales, cratering the surfaces of the larger objects with ∼8–54 craters 6 km in diameter over a 3.5-Gyr period. Collision time scales for impacts of 4-m-radius projectiles onto 1-km-radius comets range from 3×107, to 5×107 years. The cumulative fraction of the surface area of 1- and 100-km-radius objects cratered by projectiles with radii larger than 4 m ranges from a few to a few tens percent over 3.5 Gyr. The flux of Edgeworth–Kuiper Belt projectiles onto Pluto and Charon is also calculated and is found to be ∼3–5 times that of previous estimates. Our impact model is also applied to Centaur objects in the 5- to 30-AU region. We find that during their dynamical lifetimes within the Centaur region, objects undergo very little collisional evolution. Therefore, the collisional/cratering histories of Centaurs are dominated by the time spent in the Edgeworth–Kuiper Belt rather than the time spent on planet-crossing orbits. Further, we find that the predominant surface activity of Centaur objects like Chiron is most likely not impact-induced.

AimsTo examine the expression of HLA-DR and β₂ microglobulin in medullary carcinoma and atypical medullary carcinoma of the breast to determine if the effective presentation of tumour antigens to the immune system can differentiate between these two histopathologically similar entities.MethodsExpression of HLA-DR and β₂ microglobulin was examined by immunohistochemical methods in five samples of medullary carcinoma of the breast, which has a relatively favourable prognosis, six samples of atypical medullary carcinoma of the breast, which has a prognosis closer to that of regular invasive duct carcinoma, and 20 samples of invasive duct carcinomas, 10 with an accompanying lymphocytic infiltrate.ResultsA positive and significant correlation was found between tumour type and both HLA-DR and β₂ microglobulin expression. Expression was most prominent in medullary carcinoma, followed by atypical medullary carcinoma and invasive duct carcinoma with and without lymphocytic infiltrates. The mean intensity and percentage of HLA-DR tumour immunostaining were significantly higher in medullary carcinoma than in the other three tumour groups, as was the mean intensity of β₂ microglobulin immunostaining. Mean percentage of β₂ microglobulin immunostaining was significantly higher in medullary carcinoma than in invasive duct carcinoma without lymphocytic infiltrates, and showed a trend to increase from invasive duct carcinoma with lymphocytic infiltrates to atypical medullary carcinoma and medullary carcinoma.ConclusionsMedullary carcinoma and atypical medullary carcinoma of the breast differ in their expression of HLA-DR and β₂ microglobulin. The relatively favourable prognosis of medullary carcinoma of the breast may be related to effective tumour antigen presentation to the immune system through MHC-I and MHC-II expression. Immunotherapy aimed at MHC-I and MHC-II induction might have a beneficial effect in breast cancer.

We explore the effects of collisional evolution on putative Vulcanoid ensembles in the region between 0.06 and 0.21 AU from the Sun in order to constrain the probable population density and population structure of this region today. Dynamical studies have shown that the Vulcanoid Zone (VZ) could be populated. However, we find that the frequency and energetics of collisional evolution this close to the Sun, coupled with the efficient radiation transport of small debris out of this region, together conspire to create an active and highly intensive collisional environment that depletes any very significant population of rocky bodies placed in it, unless the bodies exhibit orbits that are circular to ∼10−3 or less or highly lossy mechanical properties that correspond to a fraction of impact energy significantly less than 10% being imparted to ejecta. The most favorable locale for residual bodies to survive in this region is in highly circular orbits near the outer edge of the dynamically stable Vulcanoid Zone (i.e., near 0.2 AU), where collisional evolution and radiation transport of small bodies and debris proceed most slowly. If the mean random orbital eccentricity in this region exceeds ∼10−3, then our work suggests it is unlikely that more than a few hundred objects with radii larger than 1 km will be found in the entire VZ; assuming the largest objects have a radius of 30 km, then the total mass of bodies in the VZ down to 0.1 km radii is likely to be no more than ∼10−6 M⊕, <10−3 the mass of the asteroid belt. A 0.01-AU-wide ring near the outer stability boundary of the VZ at 0.2 AU would likely not contain over a few tens of objects with radii larger than 1 km. Despite the dynamical stability of large objects in this region (Evans, N. W., and S. Tabachnik, 1999, Nature 399, 41–43), it is plausible that the entire region is virtually empty of kilometer-scale and larger objects.

Background & Aims: Prostaglandin production in the normal gastrointestinal tract, believed to be critical for mucosal integrity, is mediated by cyclooxygenase (COX)-1, whereas prostaglandin production at inflammatory sites seems to occur via induction of COX-2. We hypothesized that COX-2-specific inhibition with rofecoxib (25 mg once daily) in the treatment of patients with osteoarthritis would cause fewer gastroduodenal ulcers than an equally effective dose of ibuprofen (800 mg 3 times a day), a nonspecific COX inhibitor. Methods: A total of 742 osteoarthritis patients without ulcers on baseline endoscopy were randomly assigned to receive rofecoxib (25 or 50 mg once daily), ibuprofen (800 mg 3 times daily), or placebo. Endoscopy was repeated at 6, 12, and 24 weeks. At 16 weeks, by study design, 95% of the placebo group and 5% of the other groups were discontinued. Results: The cumulative incidence of gastroduodenal ulcers >=3 mm with rofecoxib (25 or 50 mg once daily) was significantly (P < 0.001) lower than with ibuprofen and was statistically equivalent to placebo at week 12 (placebo, 9.9%; 25 mg rofecoxib, 4.1%; 50 mg rofecoxib, 7.3%; and ibuprofen, 27.7%). At 24 weeks, ulcer rates were 25 mg rofecoxib, 9.6%; 50 mg rofecoxib, 14.7%; and ibuprofen, 45.8% (P < 0.001, ibuprofen vs. 25 and 50 mg rofecoxib). Conclusions: Rofecoxib, at doses 2-4 times the dose demonstrated to relieve symptoms of osteoarthritis, caused significantly less gastroduodenal ulceration than ibuprofen, with ulcer rates comparable to placebo. GASTROENTEROLOGY 1999;117:776-783