This study examined the efficacy of a probiotic in reducing depressive symptom severity in people with subthreshold depression. In a double-blind, randomised, placebo-controlled trial, a probiotic (1 × 10^9 live cells per strain: Limosilactobacillus fermentum LF16 (DSM26956), Lacticaseibacillus rhamnosus LR06 (DSM21981), Lactiplantibacillus plantarum LP01 (LMG P-21021) and Bifidobacterium longum 04 (DSM23233)) or placebo was taken daily for 12 weeks. Data were collected at baseline, 6 and 12 weeks including psychological symptom severity (Beck Depression Inventory, BDI; Patient Health Questionnaire, PHQ; Hospital Anxiety Depression Scale, HADS; and Depression Anxiety and Stress Scale, DASS). Biomarkers of glycaemia, inflammation (high-sensitivity C-reactive protein, hs-CRP), antioxidant status (total glutathione (GSH)) and stress (cortisol awakening response, CAR) were also measured. Thirty-nine participants (nineteen probiotic; twenty placebo) were enrolled. There were no significant between-group differences in the examined psychological symptom severity scores, despite certain significant within-group changes observed in both groups from baseline to 6 and/or 12 weeks of follow-up. Regarding biomarkers, the probiotic group showed reduced hs-CRP (–1520; 95 % CI –273·7, −2766·2 ng/dl) and CAR (–0·28; 95 % CI −0·05, −0·51 μg/dl) at 12 weeks, but increased total GSH (3·9; 95 % CI 0·1, 7·5 ng/dl) at 6 weeks, compared with the placebo. The current study reported favourable decreases in depressive symptoms in both groups. Although the within-group changes observed in the probiotic group were supported by favourable inflammatory, antioxidant status and stress biomarker changes compared with the placebo, further research is required to shed more light on the role of gut microbiota modulation on emotional regulation.

Tuberculosis infection (TBI) has been associated with increased cardiovascular risks. We aimed to characterize abnormal blood pressure (BP) readings in individuals with TBI. We conducted a retrospective study of adults with TBI presenting for their initial medical visit at a large midwestern U.S. public health clinic between 2019 and 2020. Abnormal BP was defined as having a systolic BP ≥ 130 mmHg and/or a diastolic BP ≥ 80 mmHg. Of 310 individuals with TBI, median age was 36 years (interquartile range 27–48), 34% were male, 64% non-US-born; 58 (18.7%) were previously diagnosed with hypertension. The prevalence of any hypertension (i.e., had a history of hypertension and/or an abnormal BP reading) was 64.2% (95% confidence interval 58.7–69.4). Any hypertension was independently associated with older age, male sex, higher body mass index, and individuals of Black race. In conclusion, any hypertension was present in over half of the adults evaluated for TBI in our clinic. Established hypertension risk factors were also common among this group, suggesting that individuals with TBI could benefit from clinical and public health interventions aiming to reduce the risk of future cardiovascular events.

Our qualitative analysis of interviews with remote Australian healthcare professionals found that they require reliable, local antimicrobial resistance (AMR) data reflecting the geographical diversity of the population they serve. The optimal use of AMR data must consider challenges within this setting, including high staff turnover, limited diagnostic capacity, and antibiotic shortages.

OBJECTIVES/GOALS: To develop an untargeted metabolomics assay that can holistically characterize the small molecule signatures of different inborn errors of metabolism (IEM) for biomarker discovery and identification of novel IEMs, with the goal of implementing the assay into the clinical laboratory to improve testing efficiency. METHODS/STUDY POPULATION: A hydrophilic interaction liquid chromatography (HILIC) column and reverse phase (RP) column were assembled in tandem on a SCIEX X500B quadrupole time-of-flight (QTOF) system to create a dual liquid chromatography (LC), tandem mass spectrometry method. The X500B was operated in data-independent acquisition mode with both positive and negative ionization. A mixture of 165 reference standards from eleven compound classes common to IEMs were used to evaluate the capability of the assay to resolve small molecules. Chromatographic resolution for each standard was determined qualitatively by comparison to a reference spectral database. External validation of the assay will be performed by analyzing a commercial library of reference metabolites. RESULTS/ANTICIPATED RESULTS: A total of 88% (146/165) of the standards were detected by the assay. The RP column alone resolved 71% (117/165) of the standards, the HILIC column resolved 33% (55/165), while 17% (29/165) of the standards were resolved by both columns. The HILIC column resolved standards that were more polar, while the RP column resolved more non-polar compounds. To evaluate matrix effects, the reference standard mixture was spiked into pooled plasma. In the presence of plasma 6/146 (4%) of the standards were suppressed to levels below the limit of detection. We expect external validation with the commercial metabolite library will corroborate these results, and that the high-quality spectral data attained from this reference library can be used to improve identification of unknown metabolites in patient samples. DISCUSSION/SIGNIFICANCE: We have shown our untargeted metabolomics assay can detect known biomarkers for IEMs. Clinical implementation of this method could streamline diagnosis of IEMs while simultaneously improving patient outcomes by leveraging the metabolome for biomarker discovery, and improved understanding of IEM mechanisms to inform novel treatment strategies.

In another article in this issue, Black et al. discuss their preferred approach to estimating Supreme Court justices’ Big Five personality traits from written text and provide several critiques of the approach of Hall et al. In this rejoinder, we show that Black et al.’s critiques are substantially without merit, their preferred approach suffers from many of the same drawbacks that they project onto our approach, their specific method of implementing their preferred approach runs afoul of many contemporary social scientific norms, our use of concurrences to estimate personality traits is far more justifiable than they suggest (especially in contrast to their use of lower court opinions), and their substantive critiques reflect a potential misunderstanding of the nature of conscientiousness. Nonetheless, we also acknowledge their broader point regarding the state-of-the-art textual analysis methodology vis-à-vis the estimation of personality traits, and we provide some constructive suggestions for the path forward.

High courts are widely believed to influence the criminal justice system, yet judicial impact varies widely across political and institutional contexts. Here, we seek to identify the factors that constrain judicial influence on state incarceration rates. We find that the preferences of justices on state courts of last resort and the US Supreme Court influence incarceration; however, high-court impact is conditional on two factors. Judicial influence is stronger in states with divided partisan governments and occurs more quickly in states that lack intermediate appellate courts. Our findings suggest that legislative gridlock and institutional thickness significantly constrain judicial impact.

The legal brief is a primary vehicle by which lawyers seek to persuade appellate judges. Despite wide acceptance that briefs are important, empirical scholarship has yet to establish their influence on the Supreme Court or fully explore justices’ preferences regarding them. We argue that emotional language conveys a lack of credibility to justices and thereby diminishes the party’s likelihood of garnering justices’ votes. The data concur. Using an automated textual analysis program, we find that parties who employ less emotional language in their briefs are more likely to win a justice’s vote, a result that holds even after controlling for other features correlated with success, such as case quality. These findings suggest that advocates seeking to influence judges can enhance their credibility and attract justices’ votes by employing measured, objective language.

Models of behavior on the US Supreme Court almost universally assume that justices’ behavior depends, at least in part, on the characteristics of individual justices. However, few prior studies have attempted to assess these characteristics beyond ideological preferences. In contrast, we apply recent advances in machine learning to develop and validate measures of the Big Five personality traits for Supreme Court justices serving during the 1946 through 2015 terms based on the language in their written opinions. We then conduct an empirical application to demonstrate the importance of these Supreme Court Individual Personality Estimates and discuss their proper use.

There are numerous examples of translational science innovations addressing challenges in the translational process, accelerating progress along the translational spectrum, and generating solutions relevant to a wide range of human health needs. Examining these successes through an education lens can identify core principles and effective practices that lead to successful translational outcomes. The National Center for Advancing Translational Sciences (NCATS) is identifying and teaching these core principles and practices to a broad audience via online courses in translational science which teach from case studies of NCATS-led or supported research initiatives. In this paper, we share our approach to the design of these courses and offer a detailed description of our initial course, which focused on a preclinical drug discovery and development project spanning academic and government settings. Course participants were from a variety of career stages and institutions. Participants rated the course high in overall value to them and in providing a unique window into the translational science process. We share our model for course development as well as initial findings from the course evaluation with the goal of continuing to stimulate development of novel education activities teaching foundational principles in translational science to a broad audience.

New occurrences of flask-shaped and envelope-bearing microfossils, including the predominantly Cambrian taxon Granomarginata, are reported from new localities, as well as from earlier in time (Ediacaran) than previously known. The stratigraphic range of Granomarginata extends into the Cambrian System, where it had a cosmopolitan distribution. This newly reported Ediacaran record includes areas from Norway (Baltica), Newfoundland (Avalonia) and Namibia (adjacent to the Kalahari Craton), and puts the oldest global occurrence of Granomarginata in the Indreelva Member (< 563 Ma) of the Stáhpogieddi Formation on the Digermulen Peninsula, Arctic Norway. Although Granomarginata is rare within the assemblage, these new occurrences together with previously reported occurrences from India and Poland, suggest a potentially widespread palaeogeographic distribution of Granomarginata through the middle–late Ediacaran interval. A new flask-shaped microfossil Lagoenaforma collaris gen. et sp. nov. is also reported in horizons containing Granomarginata from the Stáhpogieddi Formation in Norway and the Dabis Formation in Namibia, and flask-shaped fossils are also found in the Gibbett Hill Formation in Newfoundland. The Granomarginata–Lagoenaforma association, in addition to a low-diversity organic-walled microfossil assemblage, occurs in the strata postdating the Shuram carbon isotope excursion, and may eventually be of use in terminal Ediacaran biostratigraphy. These older occurrences of Granomarginata add to a growing record of body fossil taxa spanning the Ediacaran–Cambrian boundary.

We present a new methodology that uses professional forecasts to estimate the effects of fiscal policy. We use short-term forecasts to better identify exogenous shocks to government spending by controlling for anticipatory information already in the public domain. We use longer-term forecasts to net out expectations from the future path of other variables, which improves accuracy and efficiency by focusing on more precise measures of the impact of shocks. We show that this improves the statistical fit relative to both local projection methods and vector autoregression-based analyses that do not control for the entire future path of expectations.

Large translational research initiatives can strengthen efficiencies and support science with enhanced impact when practical conceptual models guide their design, implementation, and evaluation. The National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) program brings together data from 72 ongoing maternal–child cohort studies – involving more than 50,000 children and over 1200 investigators – to conduct transdisciplinary solution-oriented research that addresses how early environmental exposures influence child health. ECHO uses a multi-team system approach to consortium-wide data collection and analysis to generate original research that informs programs, policies, and practices to enhance children’s health. Here, we share two conceptual models informed by ECHO’s experiences and the Science of Team Science. The first conceptual model illuminates a system of teams and associated tasks that support collaboration toward shared scientific goals. The second conceptual model provides a framework for designing evaluations for continuous quality improvement of manuscript writing teams. Together, the two conceptual models offer guidance for the design, implementation, and evaluation of translational and transdisciplinary multi-team research initiatives.

Psychological attachment to political parties can bias people’s attitudes, beliefs, and group evaluations. Studies from psychology suggest that self-affirmation theory may ameliorate this problem in the domain of politics on a variety of outcome measures. We report a series of studies conducted by separate research teams that examine whether a self-affirmation intervention affects a variety of outcomes, including political or policy attitudes, factual beliefs, conspiracy beliefs, affective polarization, and evaluations of news sources. The different research teams use a variety of self-affirmation interventions, research designs, and outcomes. Despite these differences, the research teams consistently find that self-affirmation treatments have little effect. These findings suggest considerable caution is warranted for researchers who wish to apply the self-affirmation framework to studies that investigate political attitudes and beliefs. By presenting the “null results” of separate research teams, we hope to spark a discussion about whether and how the self-affirmation paradigm should be applied to political topics.

Background: Acute respiratory infections (ARIs) are a key target to improve antibiotic use in the outpatient setting. The Core Elements of Outpatient Antibiotic Stewardship provide a framework for improving antibiotic use, but data on safety and effectiveness of interventions to improve antibiotic use are limited. We report the impact of Core Elements implementation within Veterans’ Healthcare Administration clinics on antibiotic prescribing and patient outcomes. Methods: The intervention targeting treatment of uncomplicated ARIs (sinusitis, pharyngitis, bronchitis, and viral upper respiratory infections [URIs]) in emergency department and primary care settings was initiated within 10 sites between September 2017 and January 2018. The intervention was developed using the Core Elements and included local site champions, audit-and-feedback with peer comparison, and academic detailing. We evaluated the following outcomes: per-visit antibiotic prescribing rates overall and by diagnosis; appropriateness of treatment; 30-day ARI revisits; 30-day infectious complications (eg,, pneumonia,); 30-day adverse medication effects; 90-day Clostridium difficile infection (CDI); and 30-day hospitalizations. Multilevel logistic regression was used to calculate rate ratios (RR) with 95% CI for each outcome in the postintervention period (12 months) compared to the preintervention period (39–42 months). Results: There were 14,020 uncomplicated ARI visits before the intervention and 4,866 uncomplicated ARI visits after the intervention. The proportions of uncomplicated ARI visits with antibiotics prescribed were 59.17% before the intervention versus 44.34% after the intervention. A trend in reduced antibiotic prescribing for ARIs throughout the entire (before and after) observation period was evident (0.92; 95% CI, 0.90–0.94); however, a significant reduction in antibiotic prescribing after the intervention was identified (0.74; 95% CI, 0.59–0.93). Per-visit antibiotic prescribing rates decreased significantly for bronchitis and URI (0.54; 95% CI, 0.44–0.65), pharyngitis (0.76; 95% CI, 0.67–0.86), and sinusitis (0.92; 95% CI, 0.85–1.0). Appropriate therapy for pharyngitis increased (1.43; 95% CI, 1.21–1.68), but appropriate therapy for sinusitis remained unchanged (0.92; 95% CI, 0.85–1.0) after the intervention. Complications associated with antibiotic undertreatment were not different after the intervention: ARI-related revisit rates (1.01; 95% CI, 0.98–1.05) and infectious complications (1.01; 95% CI, 0.79–1.28). A potential benefit of improved antibiotic use included a reduction in visits for adverse medication effects (0.82; 95% CI, 0.72–0.94). Furthermore, 90-day CDI events were too sparse to model: preintervention incidence was 0.08% and postintervention incidence was 0.06%. Additionally, 30-day hospitalizations were significantly lower in the postintervention period (0.79; 95% CI, 0.72–0.87). Conclusions: Implementation of the Core Elements was safe and effective and was associated with reduced antibiotic prescribing rates for uncomplicated ARIs, improvements in diagnosis-specific appropriate therapy, visits for adverse antibiotic effects, and 30-day hospitalization rates. No adverse events were noted in ARI-related revisit rates or infectious complications. CDI rates were low and unchanged.

Funding: None

Disclosures: None

Drawing on a 2010 analysis of the reform and costs of adult social care commissioned by Downing Street and the UK Department of Health, this paper sets out projected future costs under different reform scenarios, reviews what happened in practice from 2010-19, explores the impact of the growing gap between need and funding, and explores the relationship between future spending and economic growth. In the process, it identifies a ‘lost decade’ in which policy makers failed to act on the warnings which they received in 2010, draws attention to the disproportionate impact of cuts on older people (compared to services for people of working age) and calls for urgent action before the current system becomes unsustainable.

A Nutrition Society member-led meeting was held on 9 January 2020 at The University of Surrey, UK. Sixty people registered for the event, and all were invited to participate, either through chairing a session, presenting a ‘3 min lightning talk’ or by presenting a poster. The meeting consisted of an introduction to the topic by Dr Barbara Fielding, with presentations from eight invited speakers. There were also eight lightning talks and a poster session. The meeting aimed to highlight recent research that has used stable isotope tracer techniques to understand human metabolism. Such studies have irrefutably shaped our current understanding of metabolism and yet remain a mystery to many. The meeting aimed to de-mystify their use in nutrition research.