Numerical simulations suggest asteroids (101955) Bennu and (162173) Ryugu are likely second or later generation rubble piles.

Rubble pile asteroids are widely understood to be composed of reaccumulated debris following a catastrophic collision between asteroids in the main asteroid belt, where each disruption can make a family of new asteroids. Near-Earth asteroids Ryugu and Bennu have been linked to collisional families in the main asteroid belt, but surface age analyses of each asteroid suggest these bodies are substantially younger than their putative families. Here we show, through a coupled collisional and dynamical evolution of members of these families, that neither asteroid was likely to have been created at the same time as the original family breakups, but rather are likely remnants of later disruptions of original family members, making them second, or later, generation remnants. Our model finds about 80% and 60% of asteroids currently being delivered to near-Earth orbits from the respective families of New Polana and Eulalia are second or later generation. These asteroids delivered today in the 0.5-1 km size range have median ages since their last disruption that are substantially younger than the family age, reconciling their measured crater retention ages with membership in these families.

Spectral Characterization of Bennu Analogs Using PASCALE: A New Experimental Set-Up for Simulating the Near-Surface Conditions of Airless Bodies.

We describe the capabilities, radiometric stability, and calibration of a custom vacuum environment chamber capable of simulating the near-surface conditions of airless bodies. Here we demonstrate the collection of spectral measurements of a suite of fine particulate asteroid analogs made using the Planetary Analogue Surface Chamber for Asteroid and Lunar Environments (PASCALE) under conditions like those found on Earth and on airless bodies. The sample suite includes anhydrous and hydrated physical mixtures, and chondritic meteorites (CM, CI, CV, CR, and L5) previously characterized under Earth- and asteroid-like conditions. And for the first time, we measure the terrestrial and extra-terrestrial mineral end members used in the olivine- and phyllosilicate-dominated physical mixtures under the same conditions as the mixtures and meteorites allowing us better understand how minerals combine spectrally when mixed intimately. Our measurements highlight the sensitivity of thermal infrared emissivity spectra to small amounts of low albedo materials and the composition of the sample materials. As the albedo of the sample decreases, we observe smaller differences between Earth- and asteroid-like spectra, which results from a reduced thermal gradient in the upper hundreds of microns in the sample. These spectral measurements can be compared to thermal infrared emissivity spectra of asteroid (101955) Bennu's surface in regions where similarly fine particulate materials may be observed to infer surface compositions.

Bright carbonate veins on asteroid (101955) Bennu: Implications for aqueous alteration history.

The composition of asteroids and their connection to meteorites provide insight into geologic processes that occurred in the early Solar System. We present spectra of the Nightingale crater region on near-Earth asteroid Bennu with a distinct infrared absorption around 3.4 micrometers. Corresponding images of boulders show centimeters-thick, roughly meter-long bright veins. We interpret the veins as being composed of carbonates, similar to those found in aqueously altered carbonaceous chondrite meteorites. If the veins on Bennu are carbonates, fluid flow and hydrothermal deposition on Bennu's parent body would have occurred on kilometer scales for thousands to millions of years. This suggests large-scale, open-system hydrothermal alteration of carbonaceous asteroids in the early Solar System.

Observations, Meteorites, and Models: A Preflight Assessment of the Composition and Formation of (16) Psyche.

Some years ago, the consensus was that asteroid (16) Psyche was almost entirely metal. New data on density, radar properties, and spectral signatures indicate that the asteroid is something perhaps even more enigmatic: a mixed metal and silicate world. Here we combine observations of Psyche with data from meteorites and models for planetesimal formation to produce the best current hypotheses for Psyche's properties and provenance. Psyche's bulk density appears to be between 3,400 and 4,100 kg m-3. Psyche is thus predicted to have between ~30 and ~60 vol% metal, with the remainder likely low-iron silicate rock and not more than ~20% porosity. Though their density is similar, mesosiderites are an unlikely analog to bulk Psyche because mesosiderites have far more iron-rich silicates than Psyche appears to have. CB chondrites match both Psyche's density and spectral properties, as can some pallasites, although typical pallasitic olivine contains too much iron to be consistent with the reflectance spectra. Final answers, as well as resolution of contradictions in the data set of Psyche physical properties, for example, the thermal inertia measurements, may not be resolved until the NASA Psyche mission arrives in orbit at the asteroid. Despite the range of compositions and formation processes for Psyche allowed by the current data, the science payload of the Psyche mission (magnetometers, multispectral imagers, neutron spectrometer, and a gamma-ray spectrometer) will produce data sets that distinguish among the models.

Application of a mixture DOE for the prediction of formulation critical temperatures during lyophilisation process optimisation.

During lyophilisation cycle design, primary drying parameters (chamber pressure and shelf temperature) are adjusted to maximize the sublimation rate and prevent cake collapse, by maintaining the product continuously below its critical temperatures. The objective of this study was to employ mixture design of experiments to generate empirical models capable of predicting glass transition of the maximally freeze concentrated solution (Tg') and collapse temperature (Tc) of amorphous protein (BSA and IgG1) formulations. Additionally, the models developed aid the design of high concentration protein formulations with maximised critical temperatures to obtain shorter and more cost-effective lyophilisation cycles. Formulations contain sucrose as cryo/lyo-protectant and arginine/arginine-HCl as multifunctional excipient (e.g. solubility enhancer, viscosity and aggregation suppressor). The impact of formulation components at varied ratios on critical temperatures was evaluated; the amorphous excipients decrease critical temperatures, on the contrary, the protein increases critical temperatures. The robustness of the empirical models generated with BSA formulations was verified with BSA and IgG1 formulations. The models showed greater accuracy in predicting Tg' than the Fox-Flory equation. For the first time, empirical models are reported to predict both critical temperatures. Finally, unconventional collapse events observed for formulations with and without arginine/arginine-HCl at different protein concentrations are also discussed.

Evidence for widespread hydrated minerals on asteroid (101955) Bennu.

Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7 µm and thermal infrared spectral features that are most similar to those of aqueously altered CM carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of meters observed to date. In the visible and near-infrared (0.4 to 2.4 µm) Bennu's spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth.

Bartonella spp. as a Possible Cause or Cofactor of Feline Endomyocarditis-Left Ventricular Endocardial Fibrosis Complex.

Endomyocarditis is a commonly detected post-mortem finding in domestic cats presenting for sudden onset cardiovascular death, yet the aetiology remains unresolved. Cats are documented reservoir hosts for Bartonella henselae, the infectious cause of cat scratch disease in man. Various Bartonella spp. have been associated with culture-negative endocarditis, myocarditis and sudden death in man and animals. We hypothesized that Bartonella spp. DNA could be amplified more often from the hearts of cats with feline endomyocarditis-left ventricular endocardial fibrosis (FEMC-LVEF) complex compared with cats with hypertrophic cardiomyopathy (HCM) or cats with grossly and microscopically unremarkable hearts (designated non-cardiac disease controls). Formalin-fixed and paraffin wax-embedded, cardiac tissues from 60 domestic and purebred cats aged 3 months to 18 years were examined, and histological features were recorded. Cardiac tissue sections were tested for Bartonella DNA using multiple 16-23S intergenic transcribed spacer region polymerase chain reaction (PCR) primer sets, including two Bartonella genera, a Bartonella koehlerae species-specific and a Bartonella vinsonii subsp. berkhoffii-specific assay, followed by DNA sequence confirmation of the species or genotype. Special precautions were taken to avoid DNA cross-contamination between tissues. Bartonella spp. DNA was amplified by PCR and sequenced from 18 of 36 cats (50%) with FEMC-LVEF and 1/12 (8.3%) cats with HCM. Bartonella spp. DNA was not amplified from any non-cardiac disease control hearts. Based on PCR/DNA sequencing, one Bartonella spp. was amplified from 10 cats, while the remaining eight were coinfected with more than one Bartonella spp. To our knowledge, this study represents the first documentation of B. vinsonii subsp. berkhoffii genotype I infection in cats (n = 11). Fluorescence in-situ hybridization testing facilitated visualization of Bartonella bacteria within the myocardium of four of seven PCR-positive FEMC-LVEF hearts. Collectively, these findings support the hypothesis that Bartonella spp. may play a primary role or act as a cofactor in the pathogenesis of FEMC-LVEF. Studies involving cats from other geographical regions and definitive demonstration of Bartonella spp. within regions of inflammation are needed to confirm an association between Bartonella spp. and FEMC-LVEF induced morbidity and mortality in cats.

Parenteral protein formulations: An overview of approved products within the European Union.

The study presented is a comprehensive overview of commercial parenteral protein formulations, approved by the European Medicines Agency (EMA), 1995-2018. The objective of this overview was to analyse current trends in the design of commercial parenteral protein products and thereby support formulation scientists in the design of new formulations. The main data source was the publicly available European Public Assessment Reports (EPARs) published by the EMA for each authorised product. An analysis of the percentage of formulations in a liquid and lyophilised form was conducted. In addition, the number of products containing individual excipients, classified into functional categories is provided. Finally, the overview includes comprehensive details of product compositions obtained from EMA, US Food and Drug Administration (FDA) and product Marketing Authorisation Holder. Data analysis highlighted trends in the number of products approved, and the higher percentage of liquid parenteral protein formulations (66%) compared to lyophilised formulations (34%). This overview identifies the most commonly incorporated excipients employed as buffering agents, stabilisers/bulking agents, surfactants, preservatives and tonicifiers, including their concentration ranges of use in both liquid and lyophilised formulation approaches. Finally, antibody-based formulations were a particular focus of this overview. The relationship between parenteral routes of administration and antibody concentrations in approved products was also investigated.

Cytochrome P450 interactions are common and consequential in Massachusetts hospital discharges.

Despite the recognition that drug-drug interactions contribute substantially to preventable health-care costs, the prevalence of such interactions related to the cytochrome P450 system in clinical practice remains poorly characterized. This study drew retrospective hospital discharge cohorts from a large health claims data set and a large health system data set. For every hospital discharge, frequency of co-occurrence of substrates and inducers or inhibitors at cytochrome P450 2D6, 2C19, 3A4 and 1A2 were determined. A total of 124 520 individuals in the state of Massachusetts (health claims cohort) and 77 026 individuals in two large academic medical centers (electronic health record (EHR) cohort) were examined. In the claims cohort, 35 157 (28.2%) exhibited at least one CYP450 drug-drug interaction at hospital discharge, whereas in the EHR cohort, 36 750 (47.7%) had at least one interaction. The most commonly affected CYP450 systems were 2C19 and 2D6, with putative interactions observed in at least 10% of individuals at discharge in each cohort. Odds of hospital readmission within 90 days among those discharged with at least one interaction were 10-16% greater, with mean health-care cost $574/month greater over the subsequent year, after adjusting for age, sex, insurance type, total number of medications prescribed, Charlson comorbidity score and presence or absence of a psychiatric diagnosis. These two distinct clinical data types show that CYP450 drug-drug interactions are prevalent and associated with greater probability of early hospital readmission and greater health-care cost, despite the widespread availability and application of drug-drug interaction checking software.

Polygenic loading for major depression is associated with specific medical comorbidity.

Major depressive disorder frequently co-occurs with medical disorders, raising the possibility of shared genetic liability. Recent identification of 15 novel genetic loci associated with depression allows direct investigation of this question. In cohorts of individuals participating in biobanks at two academic medical centers, we calculated polygenic loading for risk loci reported to be associated with depression. We then examined the association between such loading and 50 groups of clinical diagnoses, or topics, drawn from these patients' electronic health records, determined using a novel application of latent Dirichilet allocation. Three topics showed experiment-wide association with the depression liability score; these included diagnostic groups representing greater prevalence of mood and anxiety disorders, greater prevalence of cardiac ischemia, and a decreased prevalence of heart failure. The latter two associations persisted even among individuals with no mood disorder diagnosis. This application of a novel method for grouping related diagnoses in biobanks indicate shared genetic risk for depression and cardiac disease, with a pattern suggesting greater ischemic risk and diminished heart failure risk.

Prevalence and implications of cytochrome P450 substrates in Massachusetts hospital discharges.

The cytochrome P450 (CYP450) system of drug-metabolizing enzymes may contribute to individual variation in drug response. We examined prevalence of CYP450 substrates at hospital discharge for patients in two cohorts: insurance claims of Massachusetts residents and the medical records of two academic medical centers. The claims cohort included 47 473 individuals (38.2%) treated with at least one CYP450 2D6, 2C19, 3A4 or 1A2 substrate. The electronic medical records cohort included 45 905 individuals (57.4%) treated with at least one substrate. In adjusted models, substrates of CYP450 2D6 and 2C19 were associated with greater risk for 90-day readmission in both cohorts (odds ratios of 1.104 and 1.128 (P<0.001), respectively). Presence of any CYP450 substrate was associated with increased monthly medical costs (+$397, P<0.003). These analyses of more than 300 000 admissions using two different cohorts and data types indicate that CYP450 substrates are associated with greater readmission rates and greater health-care cost.

Predicting early psychiatric readmission with natural language processing of narrative discharge summaries.

The ability to predict psychiatric readmission would facilitate the development of interventions to reduce this risk, a major driver of psychiatric health-care costs. The symptoms or characteristics of illness course necessary to develop reliable predictors are not available in coded billing data, but may be present in narrative electronic health record (EHR) discharge summaries. We identified a cohort of individuals admitted to a psychiatric inpatient unit between 1994 and 2012 with a principal diagnosis of major depressive disorder, and extracted inpatient psychiatric discharge narrative notes. Using these data, we trained a 75-topic Latent Dirichlet Allocation (LDA) model, a form of natural language processing, which identifies groups of words associated with topics discussed in a document collection. The cohort was randomly split to derive a training (70%) and testing (30%) data set, and we trained separate support vector machine models for baseline clinical features alone, baseline features plus common individual words and the above plus topics identified from the 75-topic LDA model. Of 4687 patients with inpatient discharge summaries, 470 were readmitted within 30 days. The 75-topic LDA model included topics linked to psychiatric symptoms (suicide, severe depression, anxiety, trauma, eating/weight and panic) and major depressive disorder comorbidities (infection, postpartum, brain tumor, diarrhea and pulmonary disease). By including LDA topics, prediction of readmission, as measured by area under receiver-operating characteristic curves in the testing data set, was improved from baseline (area under the curve 0.618) to baseline+1000 words (0.682) to baseline+75 topics (0.784). Inclusion of topics derived from narrative notes allows more accurate discrimination of individuals at high risk for psychiatric readmission in this cohort. Topic modeling and related approaches offer the potential to improve prediction using EHRs, if generalizability can be established in other clinical cohorts.

Limb lengthening in children with Russell-Silver syndrome: a comparison to other etiologies.

INTRODUCTION/BACKGROUND: Russell-Silver syndrome (RSS) is the combination of intrauterine growth retardation, difficulty feeding, and postnatal growth retardation. Leg length discrepancy (LLD) is one of four major diagnostic criteria of RSS and is present in most cases. We aimed to ascertain whether pediatric RSS patients will adequately consolidate bony regenerate following leg lengthening. MATERIALS AND METHODS: We retrospectively reviewed pediatric RSS patients who underwent limb lengthening and compared them to a similar group of patients with LLD resulting from tumor, trauma, or congenital etiology. The primary outcome measurement was the bone healing index (BHI). RESULTS: The RSS group included seven lengthened segments in five patients; the comparison group included 21 segments in 19 patients. The groups had similar lengthening amounts (3.3 vs. 3.9 cm, p = 0.507). The RSS group healed significantly faster (lower BHI) than the control group (BHI 29 vs. 43 days/cm, p = 0.028). Secondary analysis showed no difference between RSS and trauma patients in terms of the BHI (29 vs. 31); however, the BHI of the RSS group was significantly lower than both of the other congenital etiologies (29 vs. 41, p = 0.032) and tumor patients (29 vs. 66, p = 0.019). The RSS patients had fewer and less significant complications than the controls. DISCUSSION: The limb lengthening regenerate healing of RSS patients is faster than the healing of patients with other congenital etiologies and tumor patients, and is as fast as the regenerate healing of patients with posttraumatic LLD. Although all RSS patients were treated with human growth hormone (hGH), we are unable to isolate the hGH contribution to the regenerate bone healing. We conclude that RSS patients can have safe limb lengthening.

Pitted terrain on Vesta and implications for the presence of volatiles.

We investigated the origin of unusual pitted terrain on asteroid Vesta, revealed in images from the Dawn spacecraft. Pitted terrain is characterized by irregular rimless depressions found in and around several impact craters, with a distinct morphology not observed on other airless bodies. Similar terrain is associated with numerous martian craters, where pits are thought to form through degassing of volatile-bearing material heated by the impact. Pitted terrain on Vesta may have formed in a similar manner, which indicates that portions of the surface contain a relatively large volatile component. Exogenic materials, such as water-rich carbonaceous chondrites, may be the source of volatiles, suggesting that impactor materials are preserved locally in relatively high abundance on Vesta and that impactor composition has played an important role in shaping the asteroid's geology.

Dawn at Vesta: testing the protoplanetary paradigm.

The Dawn spacecraft targeted 4 Vesta, believed to be a remnant intact protoplanet from the earliest epoch of solar system formation, based on analyses of howardite-eucrite-diogenite (HED) meteorites that indicate a differentiated parent body. Dawn observations reveal a giant basin at Vesta's south pole, whose excavation was sufficient to produce Vesta-family asteroids (Vestoids) and HED meteorites. The spatially resolved mineralogy of the surface reflects the composition of the HED meteorites, confirming the formation of Vesta's crust by melting of a chondritic parent body. Vesta's mass, volume, and gravitational field are consistent with a core having an average radius of 107 to 113 kilometers, indicating sufficient internal melting to segregate iron. Dawn's results confirm predictions that Vesta differentiated and support its identification as the parent body of the HEDs.

Exploration of Victoria crater by the Mars rover Opportunity.

The Mars rover Opportunity has explored Victoria crater, an approximately 750-meter eroded impact crater formed in sulfate-rich sedimentary rocks. Impact-related stratigraphy is preserved in the crater walls, and meteoritic debris is present near the crater rim. The size of hematite-rich concretions decreases up-section, documenting variation in the intensity of groundwater processes. Layering in the crater walls preserves evidence of ancient wind-blown dunes. Compositional variations with depth mimic those approximately 6 kilometers to the north and demonstrate that water-induced alteration at Meridiani Planum was regional in scope.

Detection of silica-rich deposits on Mars.

Mineral deposits on the martian surface can elucidate ancient environmental conditions on the planet. Opaline silica deposits (as much as 91 weight percent SiO2) have been found in association with volcanic materials by the Mars rover Spirit. The deposits are present both as light-toned soils and as bedrock. We interpret these materials to have formed under hydrothermal conditions and therefore to be strong indicators of a former aqueous environment. This discovery is important for understanding the past habitability of Mars because hydrothermal environments on Earth support thriving microbial ecosystems.

Ancient asteroids enriched in refractory inclusions.

Calcium- and aluminum-rich inclusions (CAIs) occur in all classes of chondritic meteorites and contain refractory minerals predicted to be the first condensates from the solar nebula. Near-infrared spectra of CAIs have strong 2-micrometer absorptions, attributed to iron oxide-bearing aluminous spinel. Similar absorptions are present in the telescopic spectra of several asteroids; modeling indicates that these contain approximately 30 +/- 10% CAIs (two to three times that of any meteorite). Survival of these undifferentiated, large (50- to 100-kilometer diameter) CAI-rich bodies suggests that they may have formed before the injection of radiogenic 26Al into the solar system. They have also experienced only modest post-accretionary alteration. Thus, these asteroids have higher concentrations of CAI material, appear less altered, and are more ancient than any known sample in our meteorite collection, making them prime candidates for sample return.

Pyroclastic activity at Home Plate in Gusev Crater, Mars.

Home Plate is a layered plateau in Gusev crater on Mars. It is composed of clastic rocks of moderately altered alkali basalt composition, enriched in some highly volatile elements. A coarsegrained lower unit lies under a finer-grained upper unit. Textural observations indicate that the lower strata were emplaced in an explosive event, and geochemical considerations favor an explosive volcanic origin over an impact origin. The lower unit likely represents accumulation of pyroclastic materials, whereas the upper unit may represent eolian reworking of the same pyroclastic materials.