The quenching of cluster satellite galaxies is inextricably linked to the suppression of their cold interstellar medium (ISM) by environmental mechanisms. While the removal of neutral atomic hydrogen (H i) at large radii is well studied, how the environment impacts the remaining gas in the centres of galaxies, which are dominated by molecular gas, is less clear. Using new observations from the Virgo Environment traced in CO survey (VERTICO) and archival H i data, we study the H i and molecular gas within the optical discs of Virgo cluster galaxies on 1.2-kpc scales with spatially resolved scaling relations between stellar ($\Sigma_{\star}$), H i ($\Sigma_{\text{H}\,{\small\text{I}}}$), and molecular gas ($\Sigma_{\text{mol}}$) surface densities. Adopting H i deficiency as a measure of environmental impact, we find evidence that, in addition to removing the H i at large radii, the cluster processes also lower the average $\Sigma_{\text{H}\,{\small\text{I}}}$ of the remaining gas even in the central $1.2\,$kpc. The impact on molecular gas is comparatively weaker than on the H i, and we show that the lower $\Sigma_{\text{mol}}$ gas is removed first. In the most H i-deficient galaxies, however, we find evidence that environmental processes reduce the typical $\Sigma_{\text{mol}}$ of the remaining gas by nearly a factor of 3. We find no evidence for environment-driven elevation of $\Sigma_{\text{H}\,{\small\text{I}}}$ or $\Sigma_{\text{mol}}$ in H i-deficient galaxies. Using the ratio of $\Sigma_{\text{mol}}$-to-$\Sigma_{\text{H}\,{\small\text{I}}}$ in individual regions, we show that changes in the ISM physical conditions, estimated using the total gas surface density and midplane hydrostatic pressure, cannot explain the observed reduction in molecular gas content. Instead, we suggest that direct stripping of the molecular gas is required to explain our results.

Remote sensing survey in southern Jordan has identified at least three Roman temporary camps that indicate a probable undocumented military campaign into what is today Saudi Arabia, and which we conjecture is linked to the Roman annexation of the Nabataean kingdom in AD 106.

Many decisions in everyday life involve a choice between exploring options that are currently unknown and exploiting options that are already known to be rewarding. Previous work has suggested that humans solve such “explore-exploit” dilemmas using a mixture of two strategies: directed exploration, in which information seeking drives exploration by choice, and random exploration, in which behavioral variability drives exploration by chance. One limitation of this previous work was that, like most studies on explore-exploit decision making, it focused exclusively on the domain of gains, where the goal was to maximize reward. In many real-world decisions, however, the goal is to minimize losses and it is well known from Prospect Theory that behavior can be quite different in this domain. In this study, we compared explore-exploit behavior of human subjects under conditions of gain and loss. We found that people use both directed and random exploration regardless of whether they are exploring to maximize gains or minimize losses and that there is quantitative agreement between the exploration parameters across domains. Our results also revealed an overall bias towards the more uncertain option in the domain of losses. While this bias towards uncertainty was qualitatively consistent with the predictions of Prospect Theory, quantitatively we found that the bias was better described by a Bayesian account, in which subjects had a prior that was optimistic for losses and pessimistic for gains. Taken together, our results suggest that explore-exploit decisions are driven by three independent processes: directed and random exploration, and a baseline uncertainty seeking that is driven by a prior.

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

Background: Hospitalized patients with COVID-19 often receive antimicrobial therapies due to concerns for bacterial and fungal coinfections. We analyzed patients admitted with COVID-19 to our VA facility to understand antimicrobial use, frequency of coinfections, and outcomes in our population. Methods: This retrospective study included veterans who were 18 years or older and hospitalized with COVID-19 from March 10, 2020, to March 9, 2021 at the Louis Stokes VA Medical Center in Cleveland, Ohio. We identified antimicrobials administered and coinfections with bacterial or fungal pathogens. Patients were deemed to have coinfection if there was supporting microbiological data and a consistent clinical course upon review of clinical records. Urinary tract infections were excluded because of difficulty determining infection. Odds ratios (ORs) and 95% confidence intervals (CIs) for 30-day mortality were derived using multivariate logistic regression models that included age, Charlson comorbidity index (CCI), corticosteroid use, and time of infection. Results: In our cohort of 312 patients, the median age was 70 years and 97% of the patients were male. The mean CCI was 3.7 (SD, 3.0), and 111 patients (35.6%) had a score ≥5. Oxygen was administered to 250 patients (80.1%), and 20 (6.4%) required mechanical ventilation. Antimicrobials were administered to 164 patients (52.6%) (Fig. 1). Of 20 patients (6.4%) with coinfection, 11 (3.5%) had a bloodstream infection (BSI) and 9 (2.9%) had bacterial pneumonia (Fig. 2). The overall 30-day mortality rate was 12.5% (39 of 312). Among patients with coinfection, the 30-day mortality rate was 45% (9 of 20). Diagnoses of BSI (OR, 6.35; 95% CI, 1.41–26.30) and bacterial pneumonia (OR, 9.34; 95% CI, 2.01–46.34) were associated with increased mortality. Of the data available, 12 (63%) of 19 patients with coinfection had elevated procalcitonin levels (ie, >0.50). At the time of COVID-19 diagnosis, the median absolute lymphocyte count in patients who died was 0.7 K/mm3 (95% CI, 0.6–1.12) in comparison to 1 K/mm3 (95% CI, 0.7–1.4) in patients who survived at 30 days. Conclusions: Our analysis of hospitalized COVID-19 patients with advanced age and underlying comorbid conditions demonstrated that coinfections were infrequent but that they were independently associated with increased mortality. This finding highlights the need for better tools to diagnose the presence or absence of bacterial and fungal coinfection in COVID-19 patients. Our findings also emphasize the need for judicious use of antimicrobials while discerning which patients are at risk of critical illness and mortality.

Funding: None

Disclosures: None

Background:Pseudomonas aeruginosa is an important pathogen in the hospital setting; it has the ability to cause severe disease and a high mortality rate. Its increasing ability to elude even novel antimicrobial mechanisms of action is a significant cause for concern. More effective treatment options and increasing understanding of this pathogen likely effect P. aeruginosa incidence and severity; however, longer-term studies are lacking. The Veterans’ Health Administration (VHA) population is a socially, demographically, and medically distinct entity, representing a rich source of data for studying contributing factors to P. aeruginosa infection and mortality. We sought to identify the system-wide case count and mortality rate of P. aeruginosa bacteremia and the rate of resistance to antipseudomonal agents over the course of several years. We described trends observed over the study period. Methods: We utilized the nationwide VHA database to identify all inpatients with a positive blood culture for P. aeruginosa treated between January 1, 2009, and December 31, 2020. We identified the annual count of bacteremia cases and associated 30-day mortality rate. Additionally, we determined rates of resistance to antipseudomonal agents. Results: In total, 7,480 cases of P. aeruginosa bacteremia were identified. The total case count of P. aeruginosa bacteremia decreased from 774 in 2009 to 519 in 2014, then remained relatively stable. The 30-day mortality rate decreased from 26.5 in 2009 to 19.3 in 2019, but this rate increased to 23.6 in 2020 (Fig. 1). The fluoroquinolone class had the highest resistance rate at 23%, followed by ceftazidime, cefepime, and the carbapenem class with rates of ~15%–16%. All classes were noted to have decreased resistance over time (Fig. 2). Conclusions: Occurrences, mortality rate, and associated resistance of P. aeruginosa bacteremia across the VHA system generally decreased during the study period. Potential explanations for these observations include improved infection control measures, more effective therapeutic agents, and enhanced antimicrobial stewardship efforts. The increased mortality in 2020 could be related to concomitant COVID-19 or the result of delayed medical care in the pandemic setting. Limitations of this study include inability to identify causative factors for observed trends and potential variability between labs affecting the rates of observed resistance. Additionally, VHA data may not be representative of entire adult population. Future studies could explore the relationship between P. aeruginosa bacteremia and infection prevention and antimicrobial stewardship efforts and could describe associations between P. aeruginosa and COVID-19 and identify risk factors associated with P. aeruginosa bacteremia and mortality.

Funding: None

Disclosures: None

OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.

World-renowned for having made a totally new kind of theatre, director-designer Robert Wilson first astonished international audiences in Paris in 1971 with Le Regard du sourd (Deafman Glance) and then with his twenty-four-hour Ouverture at the first edition of the Festival d’Automne in 1972. He also refers in this Conversation to Einstein on the Beach, premiered at the Avignon Festival in 1976, as another example among more of France offering him a home before he eventually founded the Watermill Center in 1992 on Long Island in the State of New York. Watermill, a laboratory for multidisciplinary creativity, opened its doors to the public in 2006 and is a focal point of the Conversation as a whole. Wilson’s immediately pre-Covid-pandemic production of The Messiah by Mozart was premiered at the Mozartwoche Salzburg in February 2020 and performed subsequently in Paris during a brief Covid ‘lull’ in September of that year. Discussion of this pivotal work leads to reflections on the opera productions that he had staged not so long before it, emphasizing the elements fundamental to his compositions – light, time, space, architecture, and silence. The Conversation, followed by audience questions addressed to Wilson, took place live online and on Facebook on 4 December 2020 as a prelude to the Festival Internacional Santiago a Mil in Chile, which opened on 3 January 2021. This was the Festival’s twenty-eighth year, but in a significantly restricted form due to Covid-19. A sequel to the Santiago interchange, also online but this time located in Paris, occurred on 17 September 2021. It resumes dialogue mainly on the Watermill Center’s broader cultural and social goals in the present and for the future, noting as well Wilson’s then current activities in Paris: a heavy schedule of four productions from the beginning of September to the end of December 2021, and a sound installation planned for 2022.

Maria Shevtsova gratefully thanks the Fundación Teatro a Mil and its General Director Carmen Romero for their initiative in inviting Robert Wilson with her to converse publicly as part of the Festival a Mil, and for permission to edit the transcript for publication in New Theatre Quarterly. Thanks are due to interpreters Margit Schmohl and Jorge Ramirez, and to Maria Luisa Vergara for organizing the audience participation included below, as well as to Alfonso Arenas, former Coordinator of the Education and Communities Area at the Theatre Foundation a Mil. Warmest gratitude is extended to Robert Wilson for his generosity in all sorts of ways, and not least for finding the time to continue the Conversation in Paris. Thanks for their kind support to Nuria Moreno, Production at Teatro Real Madrid, Christof Belka, Executive Director of RW Work Ltd, Clifford Allen, Director of Archives of the Watermill Center, and Leesa Kelly and Noah Khoshbin, curators of the 2021 outdoor exhibition Minneapolis Protest Murals at the Crossroads Summer Festival held at the Watermill Center. The exhibition presented 190 public artworks from the 900 boards of the Minneapolis Protest Murals which were created organically in Minneapolis following the murder of George Floyd on 25 May 2020. Special thanks for their gift of images are given to photographers Lucie Jansch, Javier del Real, Kristian Kruuser and Kaupo Kikkas, Lovik Delger Ostenrik, and Martyna Szczesna. Kunsang Kelden and Maria Shevtsova transcribed this Conversation in two parts. Shevtsova, Editor of New Theatre Quarterly and author of Robert Wilson (Routledge, 2007; updated edition, 2019) edited and annotated the combined transcript for publication.

Background: The survival of patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) is largely determined by the timely administration of effective antibiotic therapy. Guidelines for the treatment HAP and VAP recommend empiric treatment with broad-spectrum antibiotics and tailoring of antibiotic therapy once results of microbiological testing are available. Objective: We examined the influence of bacterial identification and antibiotic susceptibility testing on antibiotic therapy for patients with HAP or VAP. Methods: We used the US Veterans’ Health Administration (VHA) database to identify a retrospective cohort of patients diagnosed with HAP or VAP between fiscal year 2015 and 2018. We further analyzed patients who were started on empiric antibiotic therapy, for whom microbiological test results from a respiratory sample were available within 7 days and who were alive within 48 hours of sample collection. We used the antibiotic spectrum index (ASI) to compare antibiotics prescribed the day before and the day after availability of bacterial identification and antibiotic susceptibility testing results. Results: We identified 4,669 cases of HAP and VAP in 4,555 VHA patients. The median time from respiratory sample receipt in the laboratory to final result of bacterial identification and antibiotic susceptibility testing was 2.22 days (IQR, 1.31–3.38 days). The most common pathogen was Staphylococcus aureus (n = 994), with methicillin resistance in 58% of those isolates tested. The next most common pathogen was Pseudomonas spp (n = 946 isolates). The susceptibility of antipseudomonal antibiotics, when tested, was as follows: 64% to carbapenems, 74% to cephalosporins, 75% to β-lactam/β-lactamase inhibitors, 69% to fluoroquinolones, and 95% to amikacin. Lactose-fermenting gram-negative bacteria (296 Escherichia coli and 360 Klebsiella pneumoniae) were also common. Among the 3,094 cases who received empiric antibiotic therapy, 607 (20%) had antibiotics stopped the day after antibiotic susceptibility results became available, 920 (30%) had a decrease in ASI, 1,075 (35%) had no change in ASI, and 492 (16%) had an increase in ASI (Fig. 1). Among the 1,098 patients who were not started on empiric antibiotic therapy, only 154 (14%) were started on antibiotic therapy the day after antibiotic susceptibility results became available. Conclusions: Changes in antibiotic therapy occurred in at least two-thirds of cases the day after bacterial identification and antibiotic susceptibility results became available. These results highlight how respiratory cultures can inform the treatment and improve antibiotic stewardship for patients with HAP/VAP.

Funding: This study was supported by Accelerate Diagnostics.

Disclosures: None

Home care for older people in England is commissioned through local authorities working predominantly with independent providers of care. Commissioners operate in a market model, planning and procuring home care services for local populations. Their role involves ‘managing’ and ‘shaping’ the market to ensure an adequate supply of care providers. Another imperative, emerging from the principles of personalisation, is the drive to achieve user outcomes rather than ‘time and task’ objectives. Little formal research has investigated the way commissioners reconcile these different requirements and organise commissioning. This study investigated commissioning approaches using qualitative telephone interviews with ten commissioners from different local authorities in England. The characteristics of commissioning were analysed thematically. Findings indicated (a) commissioning involved complex systems and processes, uniquely shaped for the local context, but frequently changed, suggesting a constant need for reframing commissioning arrangements; (b) partnerships with providers were mainly transactional, with occasional examples of collaborative models, that were considered to facilitate flexible services more appropriate for commissioning for personalised outcomes; and (c) only a small number of commissioners had attempted to reconcile the competing and incompatible goals of tightly prescribed contracting and working collaboratively with providers. A better understanding of flexible contracting arrangements and the hallmarks of a trusting collaboration is required to move beyond the procedural elements of contracting and commissioning.