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We present an analysis of an unusual pattern of water vapor emission from the $\sim$2 Myr-old low-mass binary system VV CrA, as observed in infrared spectra obtained with VLT-CRIRES, VLT-VISIR, and Spitzer-IRS. Each component of the binary shows emission from water vapor in both the L ($\sim3\,\mu$m) and N ($\sim 12\,\mu$m) bands. The N-band and Spitzer spectra are similar to those previously observed from young stars with disks, and are consistent with emission from an extended protoplanetary disk. Conversely, the CRIRES L-band data of VV CrA A show an unusual spectrum, which requires the presence of a water reservoir with high temperature ($T\gtrsim1500$ K), column density ($N_\mathrm{H2O}\sim 3\times10^{20}\ \mathrm{cm}^{-2}$), and turbulent broadening ($v\sim 10$ km s$^{-1}$), but very small emitting area ($A\lesssim0.005$ AU$^2$). Similarity with previously observed water emission from V1331 Cyg (Doppmann et al. 2011) and SVS 13 (Carr et al. 2004) suggests that the presence of such a reservoir may be linked to evolutionary state, perhaps related to the presence of high accretion rates or winds. While the inner disk may harbor such a reservoir, simple Keplerian models do not match well with emitting line shapes, and alternative velocity fields must be considered. We also present a new idea, that the unusual emission could arise in a circumplanetary disk, embedded within the larger VV CrA A protoplanetary disk. Additional data are likely required to determine the true physical origin of this unusual spectral pattern., Comment: 32 pages, 17 figures, 5 appendix figures, 2 tables. Accepted for publication in ApJ

Patients with atrial fibrillation (AF) are frequently admitted from the emergency department (ED), and when discharged, are not reliably prescribed indicated anticoagulation. We report the impact of a novel computerized ED AF pathway orderset on discharge rate and risk-appropriate anticoagulation in patients with primary AF.The orderset included options for rate and rhythm control of primary AF, structured risk assessment for thrombotic complications, recommendations for anticoagulation as appropriate, and follow up with an electrophysiologist. All patients discharged from the ED in whom the AF orderset was utilized over an 18-month period comprised the primary study population. The primary outcome was the rate of appropriate anticoagulation or not according to confirmed CHADS-VASC and HASBLED scores. Additionally, the percentage of primary AF patients discharged directly from the ED was compared in the 18-month periods before and after introduction of the orderset.A total of 56 patients, average age 57.8 years and average initial heart rate 126 beats/minute, were included in the primary analysis. All 56 (100%; 95% confidence interval, 94-100) received guideline-concordant anticoagulation. The discharge rates in the pre- and postorderset implementation periods were 29% and 41%, respectively (95% confidence interval for 12% difference, 5-18).Our novel AF pathway orderset was associated with 100% guideline-concordant anticoagulation in patients discharged from the ED. Availability of the orderset was associated with a significant increase in the proportion of ED AF patients discharged.

High angular resolution observations of discs at mm wavelengths (on scales of a few au) are now commonplace, but there is a current lack of a comparable angular resolution for observations at cm wavelengths. This presents a significant barrier to improving our understanding of planet formation, in particular how dust grains grow from mm to cm sizes. In this paper, we examine the ability of the Square Kilometre Array (SKA) to observe dust substructure in a young, planet-forming disc at cm wavelengths. We use dusty hydrodynamics and continuum radiative transfer to predict the distribution and emission of 1 cm dust grains (or pebbles) within the disc, and simulate continuum observations with the current SKA1-MID design baseline at frequencies of 12.5 GHz (Band 5b, ~2.4 cm) on 5-10 au scales. The SKA will provide high-fidelity observations of the cm dust emission substructure in discs for integration times totalling 100's of hours. Radial structure can be obtained at a sufficient resolution and S/N from shorter (10's of hours) integration times by azimuthal averaging in the image plane. By modelling the intensity distribution directly in the visibility plane, it is possible to recover a similar level of (axisymmetric) structural detail from observations with integration times 1-2 orders of magnitude lower than required for high-fidelity imaging. Our results demonstrate that SKA1-MID will provide crucial constraints on the distribution and morphology of the raw material for building planets, the pebbles in protoplanetary discs., Comment: 12 pages, 8 figures, accepted for publication in MNRAS

Diabetes mellitus (DM) is a highly prevalent, chronic condition in adults worldwide. Little is known about the potential role of diabetes as an effect modifier of vaccine protective responses.We conducted a literature review of the immunogenicity, efficacy and effectiveness of immunization in individuals, in studies that compared subjects with DM (DM+) and without DM (DM-). We found few published studies, which were only for vaccines against hepatitis B, influenza, pneumococcal disease, or varicela zoster. Except for a consistent attenuation of the immune response to hepatitis B vaccine among DM+ individuals, we found little other consistent evidence for DM as an effect modifier of vaccine responses.There are substantial gaps in our knowledge of the impact of DM on the immune response to immunization or effect of vaccination.

Observations of systems hosting close in ($, 15 pages, 8 figures, accepted for publication in MNRAS

Introduction: The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in childhood immunization programs reduced antimicrobial-resistant pneumococcal infections by vaccine serotypes. However, emerging antimicrobial-resistant non-vaccine serotypes, particularly serotype 19A, attenuated the overall effect. In 2010, higher-valent PCVs became available containing serotypes that are prone to become antimicrobial-resistant, like serotype 7F in PCV10 and PCV13, and serotype 19A in PCV13. Areas covered: This review evaluated literature published between June 1, 2008 and June 1, 2017 reporting on the effect of PCV10 or PCV13 implementation in routine infant immunization schedules on antimicrobial-resistant invasive pneumococcal disease (IPD), otitis media (OM), and nasopharyngeal carriage (NPC) in children and adults. Expert opinion: In countries with relatively high prior pneumococcal antimicrobial resistance (AMR), PCV13 childhood vaccination programs have reduced antimicrobial-resistant IPD, OM, and NPC in children and IPD in adults. The effectiveness of PCV13 against serotype 19A is likely an important contributing factor. Only few studies have documented the impact of PCV10 on AMR. Multiple factors may influence observed decreases in pneumococcal AMR including antimicrobial stewardship, case definition, time since PCV10/13 introduction, and pre-PCV10/13 AMR levels. This review emphasizes the importance of including impact on AMR when evaluating the full public health of pneumococcal vaccination programs.

Modeling analyses have attempted to quantify the global impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal disease (PD), however these pediatric models face several challenges in obtaining comprehensive impact measurements. We present several measurement challenges and discuss examples from recently published pediatric modeling evaluations. Challenges include estimating the number of infants fully or partially vaccinated with PCVs, inclusion of indirect effects of vaccination, accounting for various dosing schedules, capturing effect of PCVs on nonspecific, noninvasive PD, and inclusion of adult PCV use. The true impact of PCVs has been consistently underestimated in published analyses due to multiple measurement challenges. Nearly 100 million adults are estimated to have received PCV13 over the last decade globally, potentially preventing up to 662 thousand cases of PD. Approximately 4.1 million cases of invasive PD alone may have been averted through indirect protection. Estimates of PCV impact on noninvasive PD remain a challenge due to altered epidemiology. Program switches, incomplete vaccination, and private market uptake among children also confound PD impact estimates. Taken together, the number of averted PD cases from PCV use in the last ten years may be up to three times higher than estimated in previous studies.

The observed sub-structures, like annular gaps, in dust emissions from protoplanetary disk, are often interpreted as signatures of embedded planets. Fitting a model of planetary gaps to these observed features using customized simulations or empirical relations can reveal the characteristics of the hidden planets. However, customized fitting is often impractical owing to the increasing sample size and the complexity of disk-planet interaction. In this paper we introduce the architecture of DPNNet-2.0, second in the series after DPNNet \citep{aud20}, designed using a Convolutional Neural Network ( CNN, here specifically ResNet50) for predicting exoplanet masses directly from simulated images of protoplanetary disks hosting a single planet. DPNNet-2.0 additionally consists of a multi-input framework that uses both a CNN and multi-layer perceptron (a class of artificial neural network) for processing image and disk parameters simultaneously. This enables DPNNet-2.0 to be trained using images directly, with the added option of considering disk parameters (disk viscosities, disk temperatures, disk surface density profiles, dust abundances, and particle Stokes numbers) generated from disk-planet hydrodynamic simulations as inputs. This work provides the required framework and is the first step towards the use of computer vision (implementing CNN) to directly extract mass of an exoplanet from planetary gaps observed in dust-surface density maps by telescopes such as the Atacama Large (sub-)Millimeter Array., 15 pages, 10 figures, to appear in ApJ

Recent multi-wavelength ALMA observations of the protoplanetary disk orbiting around Elias 2-27 revealed a two armed spiral structure. The observed morphology together with the young age of the star and the disk-to-star mass ratio estimated from dust continuum emission make this system a perfect laboratory to investigate the role of self-gravity in the early phases of star formation. This is particularly interesting if we consider that gravitational instabilities could be a fundamental first step for the formation of planetesimals and planets. In this Letter, we model the rotation curve obtained by CO data of Elias 2-27 with a theoretical rotation curve including both the disk self-gravity and the star contribution to the gravitational potential. We compare this model with a purely Keplerian one and with a simple power-law function. We find that (especially for the $^{13}$CO isotopologue) the rotation curve is better described by considering not only the star, but also the disk self-gravity. We are thus able to obtain for the first time a dynamical estimate of the disk mass of $0.08\pm0.04\,M_{\odot}$ and the star mass of $0.46\pm0.03\,M_{\odot}$ (in the more general case), the latter being comparable with previous estimates. From these values, we derive that the disk is 17$\%$ of the star mass, meaning that it could be prone to gravitational instabilities. This result would strongly support the hypothesis that the two spiral arms are generated by gravitational instabilities., Comment: 14 pages, 9 figures, 2 tables, accepted for publication on ApJL

It is likely that young protostellar disks undergo a self-gravitating phase. Such systems are characterized by the presence of a spiral pattern that can be either in a quasi-steady state or in a nonlinear unstable condition. This spiral wave affects both the gas dynamics and kinematics, resulting in deviations from the Keplerian rotation. Recently, a lot of attention has been devoted to kinematic studies of planet-forming environments, and we are now able to measure even small perturbations of velocity field ($\lesssim 1 \%$ of the Keplerian speed) thanks to high spatial and spectral resolution observations of protostellar disks. In this work, we investigate the kinematic signatures of gravitational instability: we perform an analytical study of the linear response of a self-gravitating disk to a spiral-like perturbation, focusing our attention on the velocity field perturbations. We show that unstable disks have clear kinematic imprints into the gas component across the entire disk extent, due to the GI spiral wave perturbation, resulting in deviations from Keplerian rotation. The shape of these signatures depends on several parameters, but they are significantly affected by the cooling factor: by detecting these features, we can put constraints on protoplanetary disk cooling., Comment: Accepted for publication in APJL, 13 pages, 4 figures

Recent observations of the protoplanetary disc surrounding AB Aurigae have revealed the possible presence of two giant planets in the process of forming. The young measured age of $1-4$Myr for this system allows us to place strict time constraints on the formation histories of the observed planets. Hence we may be able to make a crucial distinction between formation through core accretion (CA) or the gravitational instability (GI), as CA formation timescales are typically Myrs whilst formation through GI will occur within the first $\approx10^4-10^5$yrs of disc evolution. We focus our analysis on the $4-13$M$_{\rm Jup}$ planet observed at $R\approx30$AU. We find CA formation timescales for such a massive planet typically exceed the system's age. The planet's high mass and wide orbit may instead be indicative of formation through GI. We use smoothed particle hydrodynamic simulations to determine the system's critical disc mass for fragmentation, finding $M_{\rm d,crit}=0.3$M$_{\odot}$. Viscous evolution models of the disc's mass history indicate that it was likely massive enough to exceed $M_{\rm d,crit}$ in the recent past, thus it is possible that a young AB Aurigae disc may have fragmented to form multiple giant gaseous protoplanets. Calculations of the Jeans mass in an AB Aurigae-like disc find that fragments may initially form with masses $1.6-13.3$M$_{\rm Jup}$, consistent with the planets which have been observed. We therefore propose that the inferred planets in the disc surrounding AB Aurigae may be evidence of planet formation through GI., Comment: 12 pages, 5 figures

We present a 3D semi-analytic model of self-gravitating discs, and include a prescription for dust trapping in the disc spiral arms. Using Monte-Carlo radiative transfer we produce synthetic ALMA observations of these discs. In doing so we demonstrate that our model is capable of producing observational predictions, and able to model real image data of potentially self-gravitating discs. For a disc to generate spiral structure that would be observable with ALMA requires that the disc's dust mass budget is dominated by millimetre and centimetre-sized grains. Discs in which grains have grown to the grain fragmentation threshold may satisfy this criterion, thus we predict that signatures of gravitational instability may be detectable in discs of lower mass than has previously been suggested. For example, we find that discs with disc-to-star mass ratios as low as $0.10$ are capable of driving observable spiral arms. Substructure becomes challenging to detect in discs where no grain growth has occurred or in which grain growth has proceeded well beyond the grain fragmentation threshold. We demonstrate how we can use our model to retrieve information about dust trapping and grain growth through multi-wavelength observations of discs, and using estimates of the opacity spectral index. Applying our disc model to the Elias 27, WaOph 6 and IM Lup systems we find gravitational instability to be a plausible explanation for the observed substructure in all 3 discs, if sufficient grain growth has indeed occurred., 19 pages, 21 figures, accepted for publication in MNRAS

Searches for young gas giant planets at wide separations have so far focused on techniques appropriate for compact (Jupiter sized) planets. Here we point out that protoplanets born through Gravitational Instability (GI) may remain in an initial pre-collapse phase for as long as the first $ 10^5-10^7$ years after formation. These objects are hundreds of times larger than Jupiter and their atmospheres are too cold ($T\sim$ tens of K) to emit in the NIR or H$\alpha$ via accretion shocks. However, it is possible that their dust emission can be detected with ALMA, even around Class I and II protoplanetary discs. In this paper we produce synthetic observations of these protoplanets. We find that making a detection in a disc at 140 parsecs would require a few hundred minutes of ALMA band 6 observation time. Protoplanets with masses of 3-5 $M_J$ have the highest chance of being detected; less massive objects require unreasonably long observation times (1000 minutes) while more massive ones collapse into giant planets before $10^5$ years. We propose that high resolution surveys of young ($10^5-10^6$ years), massive and face on discs offer the best chance for observing protoplanets. Such a detection would help to place constraints on the protoplanet mass spectrum, explain the turnover in the occurrence frequency of gas giants with system metallicity and constrain the prevalence of GI as a planet formation mechanism. Consistent lack of detection would be evidence against GI as a common planet formation mechanism., Comment: 15 pages, 13 figures, accepted to MNRAS

Observations with the Atacama Large Millimeter/Submillimeter array (ALMA) have dramatically improved our understanding of the site of exoplanet formation: protoplanetary discs. However, many basic properties of these discs are not well-understood. The most fundamental of these is the total disc mass, which sets the mass budget for planet formation. Discs with sufficiently high masses can excite gravitational instability and drive spiral arms that are detectable with ALMA . Although spirals have been detected in ALMA observations of the dust , their association with gravitational instability, and high disc masses, is far from clear. Here we report a prediction for kinematic evidence of gravitational instability. Using hydrodynamics simulations coupled with radiative transfer calculations, we show that a disc undergoing such instability has clear kinematic signatures in molecular line observations across the entire disc azimuth and radius which are independent of viewing angle. If these signatures are detected, it will provide the clearest evidence for the occurrence of gravitational instability in planet-forming discs, and provide a crucial way to measure disc masses., 10 pages, 7 figures, accepted to The Astrophysical Journal

Dark rings with bright rims are the indirect signposts of planets embedded in protoplanetary discs. In a recent first, an azimuthally elongated AU-scale blob, possibly a planet, was resolved with ALMA in TW Hya. The blob is at the edge of a cliff-like rollover in the dust disc rather than inside a dark ring. Here we build time-dependent models of TW Hya disc. We find that the classical paradigm cannot account for the morphology of the disc and the blob. We propose that ALMA-discovered blob hides a Neptune mass planet losing gas and dust. We show that radial drift of mm-sized dust particles naturally explains why the blob is located on the edge of the dust disc. Dust particles leaving the planet perform a characteristic U-turn relative to it, producing an azimuthally elongated blob-like emission feature. This scenario also explains why a 10 Myr old disc is so bright in dust continuum. Two scenarios for the dust-losing planet are presented. In the first, a dusty pre-runaway gas envelope of about 40 Earth mass Core Accretion planet is disrupted, e.g., as a result of a catastrophic encounter. In the second, a massive dusty pre-collapse gas giant planet formed by Gravitational Instability is disrupted by the energy released in its massive core. Future modelling may discriminate between these scenarios and allow us to study planet formation in an entirely new way -- by analysing the flows of dust and gas recently belonging to planets, informing us about the structure of pre-disruption planetary envelopes., Comment: Typos fixed, references and author list updated

We use a suite of SPH simulations to investigate the susceptibility of protoplanetary discs to the effects of self-gravity as a function of star-disc properties. We also include passive irradiation from the host star using different models for the stellar luminosities. The critical disc-to-star mass ratio for axisymmetry (for which we produce criteria) increases significantly for low-mass stars. This could have important consequences for increasing the potential mass reservoir in a proto Trappist-1 system, since even the efficient Ormel et al. (2017) formation model will be influenced by processes like external photoevaporation, which can rapidly and dramatically deplete the dust reservoir. The aforementioned scaling of the critical $M_d/M_*$ for axisymmetry occurs in part because the Toomre $Q$ parameter has a linear dependence on surface density (which promotes instability) and only an $M_*^{1/2}$ dependence on shear (which reduces instability), but also occurs because, for a given $M_d/M_*$, the thermal evolution depends on the host star mass. The early phase stellar irradiation of the disc (for which the luminosity is much higher than at the zero age main sequence, particularly at low stellar masses) can also play a key role in significantly reducing the role of self-gravity, meaning that even Solar mass stars could support axisymmetric discs a factor two higher in mass than usually considered possible. We apply our criteria to the DSHARP discs with spirals, finding that self-gravity can explain the observed spirals so long as the discs are optically thick to the host star irradiation., Comment: 21 pages, Accepted for publication MNRAS

Background Background incidence rates (IRs) of potential safety outcomes among vaccine eligible individuals can inform assessment of vaccine safety. Vaccine safety surveillance often uses claims databases, but the impact of outcome definitions on background IR estimates is largely unexplored. Using two definitions for each outcome, we estimated background IRs of 32 cardiac, metabolic, allergic, autoimmune, neurologic, hematologic and nephrologic outcomes among individuals eligible to receive pneumococcal vaccination. Methods We defined a cohort of individuals aged 6–100 years in US commercial health plans who had ≥12 months of health plan enrollment between January 2007 and August 2014 and no previous record of conjugate or simple polysaccharide pneumococcal vaccination. We developed a sensitive and a specific definition for each outcome, with the specific definition requiring evidence of additional care consistent with the outcome. IRs per 100,000 person-years for each outcome were presented overall and stratified by age, gender, and invasive pneumococcal disease (IPD) risk category. Results We followed 19.9 million individuals for a median of 2.5 years. Wide variation was seen in IRs across different definitions of the 32 outcomes, with 19 (59%) outcomes having a specific definition IR less than half of the sensitive definition IR. IRs were particularly variable by definition for outcomes categorized as either hematologic/nephrologic or neurologic (mean ratio of specific IR to sensitive IR = 0.26 and 0.30, respectively). Across definitions, the IRs of the 32 outcomes were often highest in females, adults ≥65, and those at higher IPD risk. Conclusions Background IRs of safety outcomes relevant to populations indicated for pneumococcal vaccine varied by outcome definitions and population subgroups in this large US commercially-insured population. Given large differences in estimated IRs using sensitive versus specific case definitions, neurologic, and hematologic/nephrologic safety outcomes as compared to allergic and autoimmune outcomes may warrant more refined definitions and medical record validation.

Background Individuals with certain chronic medical conditions are at higher risk of developing pneumonia and pneumococcal disease than those without. Using data from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), this post hoc analysis assessed the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥65 years with at-risk conditions. Methods The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) was a double-blind, parallel-group, randomized, placebo-controlled study in the Netherlands in which adults aged ≥65 years received either PCV13 or placebo. Outcomes of interest were identified using prespecified clinical criteria, radiographic confirmation, routine microbiologic testing, and a serotype-specific urinary antigen detection assay. In this post hoc analysis, participants were classified by at-risk status based on self-reporting of any of the following chronic medical conditions: heart disease, lung disease, asthma, diabetes, liver disease, and smoking. The objective of this analysis was to assess PCV13 vaccine efficacy (VE) against a first episode of vaccine-serotype community-acquired pneumonia (VT-CAP) in at-risk participants. Results Of the 84,496 adults enrolled in the study, 41,385 (49.2%) were considered at risk owing to chronic medical conditions. Of the 139 VT-CAP cases, 115 (82.7%) occurred in these participants. VE of PCV13 against a first episode of VT-CAP among participants with at-risk conditions was 40.3% (95.2% CI: 11.4%, 60.2%). Average duration of follow-up since vaccination was 3.95 years for at-risk participants; protection did not wane over the study period. Conclusions This post hoc analysis of the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) showed significant and persistent efficacy of PCV13 against VT-CAP in at-risk older adults. ClinicalTrials.gov identifier: NCT00744263 .

In this paper, we model the chemical evolution of a 0.25 M$_{\odot}$ protoplanetary disc surrounding a 1 M$_{\odot}$ star that undergoes fragmentation due to self-gravity. We use Smoothed Particle Hydrodynamics including a radiative transfer scheme, along with time-dependent chemical evolution code to follow the composition of the disc and resulting fragments over approximately 4000 yrs. Initially, four quasi-stable fragments are formed, of which two are eventually disrupted by tidal torques in the disc. From the results of our chemical modelling, we identify species that are abundant in the fragments (e.g. H$_{\rm 2}$O, H$_{\rm 2}$S, HNO, N$_{\rm 2}$, NH$_{\rm 3}$, OCS, SO), species that are abundant in the spiral shocks within the disc (e.g. CO, CH$_{\rm 4}$, CN, CS, H$_{\rm 2}$CO), and species which are abundant in the circumfragmentary material (e.g. HCO$^{\rm +}$). Our models suggest that in some fragments it is plausible for grains to sediment to the core before releasing their volatiles into the planetary envelope, leading to changes in, e.g., the C/O ratio of the gas and ice components. We would therefore predict that the atmospheric composition of planets generated by gravitational instability should not necessarily follow the bulk chemical composition of the local disc material., 17 pages, 7 figures, accepted for publication in MNRAS

Background Antimicrobial resistance (AMR) is a global threat to effective prevention and treatment of an ever-increasing range of infections. Pneumococcal conjugate vaccines (PCV) used in infant national immunization programs have been shown to decrease AMR pneumococci. Cost-effectiveness models evaluating the value for money of PCV programs have not considered the economic impact of reducing antimicrobial prescribing or prolonged infections due to treatment failures. Standardized frameworks are needed for models to address outcomes and impact on health resource utilization related to AMR. Methods We developed a conceptual modeling methodology suitable for a health economic evaluation of an infant PCV program. We considered impact of PCVs on pneumococcal disease (PD) specifically related to clinical management of AMR-PD, including AMR epidemiology, antibiotic prescribing patterns, and healthcare resource utilization. Model inputs were evaluated regarding optimal and available data sources considering the complex nature of AMR at the national, regional, and global level. Results The proposed framework considers impact of PCVs on antimicrobial prescribing due to invasive pneumococcal disease (IPD), community acquired pneumonia (CAP), and acute otitis media (AOM) across 3 pathways (Figure 1). The population and pathogen-level pathway describe epidemiology and vaccine impact. The care level pathway describes clinical disease management. The health outcomes pathway characterizes resistant or successfully treated PD costs and quality of life. Conceptual Economic Model Methodology Conclusion We present a generalizable methodology to quantify impact of PCVs on cases and outcomes of PD related to AMR. Modelling vaccine-preventable burden of AMR-PD requires data extrapolations and assumptions due to the myriad of interconnected pathways (i.e. microbiology, epidemiology, environment, health systems). Further work is needed to validate assumptions and linkages across incomplete data sources. Disclosures Raymond Farkouh, PhD, Pfizer (Employee) Arianna Nevo, MPH, Pfizer, Inc. (Other Financial or Material Support, I am an employee of IQVIA. IQVIA received funding from Pfizer to carry out the project.) Jennifer Uyei, PhD, MPH, Pfizer, Inc. (Other Financial or Material Support, I am an employee of IQVIA. IQVIA received funding from Pfizer to carry out the project.) Cassandra Hall-Murray, PharmD, Pfizer, Inc. (Employee) Joseph Lewnard, PhD, Pfizer, Inc. (Consultant, Grant/Research Support, Advisor or Review Panel member) Matthew Wasserman, MSc., Pfizer Inc. (Employee)

We investigate how a protoplanetary disc's susceptibility to gravitational instabilities and fragmentation depends on the mass of its host star. We use 1D disc models in conjunction with 3D SPH simulations to determine the critical disc-to-star mass ratios at which discs become unstable against fragmentation, finding that discs become increasingly prone to the effects of self-gravity as we increase the host star mass. The actual limit for stability is sensitive to the disc temperature, so if the disc is optically thin stellar irradiation can dramatically stabilise discs against gravitational instability. However, even when this is the case we find that discs around $2$M$_{\odot}$ stars are prone to fragmentation, which will act to produce wide-orbit giant planets and brown dwarfs. The consequences of this work are two-fold: that low mass stars could in principle support high disc-to-star mass ratios, and that higher mass stars have discs that are more prone to fragmentation, which is qualitatively consistent with observations that favour high-mass wide-orbit planets around higher mass stars. We also find that the initial masses of these planets depends on the temperature in the disc at large radii, which itself depends on the level of stellar irradiation., Comment: Accepted for publication in MNRAS

Advocacy and public policy have made higher education more accessible for youth with intellectual disability than ever before. This chapter illustrates an exemplary model of inclusive higher education (IHE), successfully being implemented at Vanderbilt University, USA, through the Next Steps at Vanderbilt program. This program provides college students with intellectual disability the opportunity to learn and grow alongside their typically developing peers in a rich and diverse academic environment. This chapter provides insight into several core components of high-quality IHE programs and how these components are implemented on a college campus. Recommendations for adopting inclusive college practices are also addressed.

We analyze high-resolution (dv= 10$^{-8}$ Msun/yr) while LVCs are found in sources with low Macc, low [OI] luminosity, and large infrared spectral index (n13-31). Interestingly, the [NeII] and [OI] LVC luminosities display an opposite behaviour with n13-31: as the inner dust disk depletes (higher n13-31) the [NeII] luminosity increases while the [OI] weakens. The [NeII] and [OI] HVC profiles are generally similar with centroids and FWHMs showing the expected behaviour from shocked gas in micro-jets. In contrast, the [NeII] LVC profiles are typically more blueshifted and narrower than the [OI] profiles. The FWHM and centroid vs. disk inclination suggest that the [NeII] LVC predominantly traces unbound gas from a slow, wide-angle wind that has not lost completely the Keplerian signature from its launching region. We sketch an evolutionary scenario that could explain the combined [OI] and [NeII] results and includes screening of hard (~1keV) X-rays in inner, mostly molecular, MHD winds., Accepted for publication in The Astrophysical Journal

Recent observations of protoplanetary discs reveal disc substructures potentially caused by embedded planets. We investigate how the gas surface density in discs changes the observed morphology in scattered light and dust continuum emission. Assuming that disc substructures are due to embedded protoplanets, we combine hydrodynamical modelling with radiative transfer simulations of dusty protoplanetary discs hosting planets. The response of different dust species to the gravitational perturbation induced by a planet depends on the drag stopping time - a function of the generally unknown local gas density. Small dust grains, being stuck to the gas, show spirals. Larger grains decouple, showing progressively more axisymmetric (ring-like) substructure as decoupling increases with grain size or with the inverse of the gas disc mass. We show that simultaneous modelling of scattered light and dust continuum emission is able to constrain the Stokes number, ${\rm St}$. Hence, if the dust properties are known, this constrains the local gas surface density, $\Sigma_{\rm gas}$, at the location of the structure, and hence the total gas mass. In particular, we found that observing ring-like structures in mm-emitting grains requires ${\rm St} \gtrsim 0.4$ and therefore $\Sigma_{\rm gas} \lesssim 0.4\,\textrm{g/cm}^{2}$. We apply this idea to observed protoplanetary discs showing substructures both in scattered light and in the dust continuum., Comment: Accepted for publication on MNRAS, 12 pages, 6 figures

A recent ALMA observation of the Elias 2-27 system revealed a two-armed structure extending out to ~300 au in radius. The protostellar disc surrounding the central star is unusually massive, raising the possibility that the system is gravitationally unstable. Recent work has shown that the observed morphology of the system can be explained by disc self-gravity, so we examine the physical properties of the disc necessary to detect self-gravitating spiral waves. Using three-dimensional Smoothed Particle Hydrodynamics, coupled with radiative transfer and synthetic ALMA imaging, we find that observable spiral structure can only be explained by self-gravity if the disc has a low opacity (and therefore efficient cooling), and is minimally supported by external irradiation. This corresponds to a very narrow region of parameter space, suggesting that, although it is possible for the spiral structure to be due to disc self-gravity, other explanations, such as an external perturbation, may be preferred., 12 pages, 5 figures

We present Atacama Large Millimeter/sub-millimeter Array (ALMA) Cycle 2 observations of the 1.3 mm dust continuum emission of the protoplanetary disc surrounding the T Tauri star Elias 24 with an angular resolution of $\sim 0.2"$ ($\sim 28$ au). The dust continuum emission map reveals a dark ring at a radial distance of $0.47"$ ($\sim 65$ au) from the central star, surrounded by a bright ring at $0.58"$ ($\sim 81$ au). In the outer disc, the radial intensity profile shows two inflection points at $0.71"$ and $0.87"$ ($\sim 99$ and $121$ au respectively). We perform global three-dimensional smoothed particle hydrodynamic gas/dust simulations of discs hosting a migrating and accreting planet. Combining the dust density maps of small and large grains with three dimensional radiative transfer calculations, we produce synthetic ALMA observations of a variety of disc models in order to reproduce the gap- and ring-like features observed in Elias 24. We find that the dust emission across the disc is consistent with the presence of an embedded planet with a mass of $\sim 0.7\, \mathrm{M_{\mathrm{J}}}$ at an orbital radius of $\sim$ 60 au. Our model suggests that the two inflection points in the radial intensity profile are due to the inward radial motion of large dust grains from the outer disc. The surface brightness map of our disc model provides a reasonable match to the gap- and ring-like structures observed in Elias 24, with an average discrepancy of $\sim$ 5% of the observed fluxes around the gap region., Comment: 17 pages, 11 figures. Accepted for publication in MNRAS

It is likely that most protostellar systems undergo a brief phase where the protostellar disc is self-gravitating. If these discs are prone to fragmentation, then they are able to rapidly form objects that are initially of several Jupiter masses and larger. The fate of these disc fragments (and the fate of planetary bodies formed afterwards via core accretion) depends sensitively not only on the fragment's interaction with the disc, but with its neighbouring fragments. We return to and revise our population synthesis model of self-gravitating disc fragmentation and tidal downsizing. Amongst other improvements, the model now directly incorporates fragment-fragment interactions while the disc is still present. We find that fragment-fragment scattering dominates the orbital evolution, even when we enforce rapid migration and inefficient gap formation. Compared to our previous model, we see a small increase in the number of terrestrial-type objects being formed, although their survival under tidal evolution is at best unclear. We also see evidence for disrupted fragments with evolved grain populations - this is circumstantial evidence for the formation of planetesimal belts, a phenomenon not seen in runs where fragment-fragment interactions are ignored. In spite of intense dynamical evolution, our population is dominated by massive giant planets and brown dwarfs at large semimajor axis, which direct imaging surveys should, but only rarely, detect. Finally, disc fragmentation is shown to be an efficient manufacturer of free floating planetary mass objects, and the typical multiplicity of systems formed via gravitational instability will be low., 14 pages, 17 figures, accepted for publication in MNRAS

Recent high-sensitivity observations carried out with ALMA have revealed the presence of complex organic molecules (COMs) such as methyl cyanide (CH$_{\rm 3}$CN) and methanol (CH$_{\rm 3}$OH) in relatively evolved protoplanetary discs. The behaviour and abundance of COMs in earlier phases of disc evolution remains unclear. Here we combine a smoothed particle hydrodynamics simulation of a fragmenting, gravitationally unstable disc with a gas-grain chemical code. We use this to investigate the evolution of formamide (NH$_{\rm 2}$CHO), a pre-biotic species, in both the disc and in the fragments that form within it. Our results show that formamide remains frozen onto grains in the majority of the disc where the temperatures are $, Comment: 10 pages, 5 figures, accepted for publication in ApJ

Adults, particularly those with underlying chronic conditions, eg, cardiovascular, liver, and pulmonary diseases and diabetes mellitus, have a persistent pneumococcal disease burden. Thirteen-valent pneumococcal conjugate vaccine (PCV13) is recommended in the United States for all adults aged ≥65 years and immunocompromised adults aged65 years to protect against vaccine-serotype (VT) invasive pneumococcal disease (IPD) and pneumonia. PCV13 is not recommended for immunocompetent adults aged ≥18 years with comorbidities associated with increased pneumococcal disease risk.This US-focused review summarizes PCV13-type IPD and community-acquired pneumonia burden in adults aged50 years, PCV13 immunogenicity and safety in this population, and adult pneumococcal vaccination recommendations.Considering (i) PCV13 has demonstrated efficacy against VT-IPD and pneumonia in adults aged ≥65 years (with or without underlying chronic conditions), and (ii) immune responses to PCV13 in younger adults are comparable or better than in older adults, PCV13 would likely have similar efficacy in adults aged50 years. Recommending PCV13 for at-risk adults aged50 years would provide direct immunologic benefit of a conjugate vaccine and could address an important unmet medical need for pneumococcal pneumonia prevention. Although not directly addressed here, this benefit would likely extend to at-risk adults aged 50-64 years.

We consider the problem of estimating the sparse initial condition of a solution to the advection-diffusion equation based on line integrals of the solution at a later time. We propose models for locating a single and multiple point sources. We also propose algorithms for the efficient implementation of these models. In practice, the models are relevant also for reconstructing the solution of the PDE at the observation time from a very sparse Radon transform; in this case, our models improve on more standard Radon inversion techniques by utilizing the specialized information about how the observed function was generated.

We use a simple, self-consistent, self-gravitating semi-analytic disc model to conduct an examination of the parameter space in which self-gravitating discs may exist. We then use Monte-Carlo radiative transfer to generate synthetic ALMA images of these self-gravitating discs to determine the subset of this parameter space in which they generate non-axisymmetric structure that is potentially detectable by ALMA. Recently, several transition discs have been observed to have non-axisymmetric structure that extends out to large radii. It has been suggested that one possible origin of these asymmetries could be spiral density waves induced by disc self-gravity. We use our simple model to see if these discs exist in the region of parameter space where self-gravity could feasibly explain these spiral features. We find that for self-gravity to play a role in these systems typically requires a disc mass around an order of magnitude higher than the observed disc masses for the systems. The spiral amplitudes produced by self-gravity in the local approximation are relatively weak when compared to amplitudes produced by tidal interactions, or spirals launched at Lindblad resonances due to embedded planets in the disc. As such, we ultimately caution against diagnosing spiral features as being due to self-gravity, unless the disc exists in the very narrow region of parameter space where the spiral wave amplitudes are large enough to produce detectable features, but not so large as to cause the disc to fragment., 13 pages, 9 figures

Combining 3D smoothed-particle hydrodynamics and Monte Carlo radiative transfer calculations, we examine the morphology of spiral density waves induced by gravitational instability (GI) in protoplanetary disks, as they would appear in direct images at near-infrared (NIR) wavelengths. We find that systems with disk-to-star-mass ratios q=M_disk/M_star that are ~0.25 or more may produce prominent spiral arms in NIR imaging, remarkably resembling features observed in the MWC 758 and SAO 206462 systems. The contrast of GI-induced arms at NIR wavelengths can reach a factor of ~3, and their pitch angles are about 10-15 degree. The dominant azimuthal wavenumber of GI-induced spiral arms roughly obeys m~1/q in the range 2~0.25; and that the accretion rate Mdot be high, on the order of 1e-6 solar mass per year., Comment: 18 pages, 4 figures, 1 table, ApJ Letter accepted

Because all important assumptions used in the model are simultaneously biased toward PCV10, the model results are erroneous and misleading. Routine infant pneumococcal vaccination in Japan would undoubtedly bring substantial reductions in morbidity and mortality. However, given the current epidemiologic landscape in Japan and the current evidence, the clinical and economic gains from the use of PCV13 would, undoubtedly, far exceed those potentially observed from the use of PCV10. We urge those who conduct, critique, and consider cost-effectiveness studies to evaluate the strength of the evidence of clinical claims for the products and the influence these assumptions have on the overall findings. In addition, when performing economic predictive modeling, it is critical to provide a balanced perspective by weighing the strengths and weaknesses of all available data to construct the base case analysis.

Background Recommendations for adult pneumococcal immunization generally specify the use of PCV13 first, followed by PPSV23, when administered sequentially, for prevention of pneumococcal disease. This is supported by observations of reduced functional opsonophagocytic assay (OPA) antibody titers in subjects who received PPSV23 first compared with PCV13 first. Methods In a previously-published phase 3 study of pneumococcal vaccine–naïve adults 60–64 years of age, participants received PCV13 followed by PPSV23 one year later (PCV13/PPSV23) or PPSV23 followed by PCV13 one year later (PPSV23/PCV13). Here we report the previously unpublished clinically relevant comparisons for the 2 sequential dosing groups by showing the antibody response curve analyses by serotype. We also highlight the reverse cumulative distribution curve (RCDC) analysis by serotype for the 2 relevant sequential dosing groups. Results OPA titers for shared serotypes rose substantially from pre-vaccination to 1 month post-initial vaccination for both groups. For all serotypes, OPA titers declined over the year interval between vaccinations, but remained higher at the pre-vaccination 2 time point compared with baseline for both groups. When evaluating the antibody response curves, the OPA geometric mean titers (GMTs) were generally higher for all shared serotypes at all measured time points in the PCV13/PPSV23 group compared with the PPSV23/PCV13 group; example serotype 19F (Figure 1). RCDC analyses show that for the PCV13/PPSV23 group, OPA titers after vaccination 2 were generally higher across the full range of responses than for PPSV23/PCV13; example serotype 19F (Figure 2). Conclusion The observed immune responses, with the sequential administration of PCV13 followed by PPSV23 one year later (PCV13/PPSV23), are higher compared with responses observed with PPSV23 followed by PCV13 one year later (PPSV23/PCV13). This supports the administration of PCV13 first when use of both pneumococcal vaccines is appropriate. Limitations: This study was not designed to determine the optimal interval between PCV13 and PPSV23 doses. Disclosures E. Chilson, Pfizer Inc: Employee and Shareholder, Salary; B. Atkinson, Pfizer Inc: Shareholder, Salary; C. Hall-Murray, Pfizer, Inc.: Employee and Shareholder, Salary; V. Snow, Pfizer Inc: Employee and Shareholder, Salary; B. Schmoele-Thoma, Pfizer Inc: Shareholder, Salary; R. E. Isturiz, Pfizer, Inc.: Employee, Salary; D. A. Scott, Pfizer Inc: Shareholder, Salary

We present a new method of identifying protostellar disc fragments in a simulation based on density derivatives, and analyse our data using this and the existing CLUMPFIND method, which is based on an ordered search over all particles in gravitational potential energy. Using smoothed particle hydrodynamics, we carry out 9 simulations of a $0.25$ M$_{\odot}$ disc around a 1 M$_{\odot}$ star, all of which fragment to form at least 2 bound objects. We find that when using all particles ordered in gravitational potential space, only fragments that survive the duration of the simulation are detected. When we use the density derivative method, all fragments are detected, so the two methods are complementary, as using the two methods together allows us to identify all fragments, and to then determine those that are likely to be destroyed. We find a tentative empirical relationship between the dominant azimuthal wavenumber in the disc $m$ and the maximum semi-major axis a fragment may achieve in a simulation, such that $a_{\mathrm{max}}\propto\frac{1}{m}$. We find the fragment destruction rate to be around half that predicted from population synthesis models. This is due to fragment-fragment interactions in the early gas phase of the disc, which can cause scattering and eccentricity pumping on short timescales, and affects the fragment's internal structure. We therefore caution that measurements of eccentricity as a function of semi-major axis may not necessarily constrain the formation mechanism of giant planets and brown dwarfs., 22 pages, 22 figures

To determine the origin of the spiral structure observed in the dust continuum emission of Elias 2-27 we analyze multi-wavelength continuum ALMA data with a resolution of $\sim$0.2 arcsec ($\sim$23au) at 0.89, 1.3 and 3.3mm. We also study the kinematics of the disk with $^{13}$CO and C$^{18}$O ALMA observations in the $J=$3-2 transition. The spiral arm morphology is recovered at all wavelengths in the dust continuum observations, where we measure contrast and spectral index variations along the spiral arms and detect subtle dust-trapping signatures. We determine that the emission from the midplane is cold and interpret the optical depth results as signatures of a higher disk mass than previous constraints. From the gas data, we search for deviations from Keplerian motion and trace the morphology of the emitting surfaces and the velocity profiles. We find an azimuthally varying emission layer height in the system, large-scale emission surrounding the disk, and strong perturbations in the channel maps, co-located with the spirals. Additionally, we develop multigrain dust and gas SPH simulations of a gravitationally unstable disk and compare them to the observations. Given the large scale emission and highly perturbed gas structure, together with the comparison of continuum observations to theoretical predictions, we propose infall-triggered gravitational instabilities as origin for the observed spiral structure., Comment: Accepted for publication in ApJ, 38 pages, 23 Figures