We know much about “how democracies die”: elites and masses become polarized, and norms of mutual toleration, forbearance, and institutional restraint erode. But why do elites feel free to undermine these guardrails of democracy? What are the sources of backsliding? Answers to these questions have focused on the impact of economic and cultural change, and on autocratic meddling. I consider another potential source of backsliding around the world: the impact of the reconfiguration of global politics after the Cold War and 9/11 on politics in the main prodemocratic actors that Samuel Huntington highlighted in his book The Third Wave: the United States, the European Union, and the Vatican. Today, the international context gives leaders in these global powers relatively weaker incentives to stand up for democracy, even in the face of aggressive meddling from Russia and China. Changes in international politics has left democracy with weaker ideational support in the global arena, potentially facilitating backsliding.

The 2022 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management, 7th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by an interdisciplinary team of healthcare providers and system planners caring for persons with an acute stroke or transient ischemic attack. These recommendations are a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, proven to reduce mortality and morbidity. The topics covered include prehospital care, emergency department care, intravenous thrombolysis and endovascular thrombectomy (EVT), prevention and management of inhospital complications, vascular risk factor reduction, early rehabilitation, and end-of-life care. These recommendations pertain primarily to an acute ischemic vascular event. Notable changes in the 7th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention, 1 the management of symptomatic intracerebral hemorrhage following thrombolysis, acute stroke imaging, care of patients undergoing EVT, medical assistance in dying, and virtual stroke care. An explicit effort was made to address sex and gender differences wherever possible. The theme of the 7th edition of the CSBPR is building connections to optimize individual outcomes, recognizing that many people who present with acute stroke often also have multiple comorbid conditions, are medically more complex, and require a coordinated interdisciplinary approach for optimal recovery. Additional materials to support timely implementation and quality monitoring of these recommendations are available at www.strokebestpractices.ca.

Conviction Narrative Theory (CNT) is a theory of choice under radical uncertainty—situations where outcomes cannot be enumerated and probabilities cannot be assigned. Whereas most theories of choice assume that people rely on (potentially biased) probabilistic judgments, such theories cannot account for adaptive decision-making when probabilities cannot be assigned. CNT proposes that people use narratives—structured representations of causal, temporal, analogical, and valence relationships—rather than probabilities, as the currency of thought that unifies our sense-making and decision-making faculties. According to CNT, narratives arise from the interplay between individual cognition and the social environment, with reasoners adopting a narrative that feels ‘right’ to explain the available data; using that narrative to imagine plausible futures; and affectively evaluating those imagined futures to make a choice. Evidence from many areas of the cognitive, behavioral, and social sciences supports this basic model, including lab experiments, interview studies, and econometric analyses. We propose 12 principles to explain how the mental representations (narratives) interact with four inter-related processes (explanation, simulation, affective evaluation, communication), examining the theoretical and empirical basis for each. We conclude by discussing how CNT can provide a common vocabulary for researchers studying everyday choices across areas of the decision sciences.

Background: Multidrug-resistant organisms (MDROs), such as carbapenem-resistant Enterobacterales (CRE), can spread rapidly in a region. Facilities that care for high-acuity patients with long average lengths of stay (eg, long-term acute-care hospitals or LTACHs and ventilator-capable skilled nursing facilities or vSNFs) may amplify this spread. We assessed the impact of interventions on CRE spread within a region individually, bundled, and implemented at different facility types. Methods: We developed a deterministic compartmental model, parametrized using CRE data reported to the NHSN and patient transfer data from the CMS specific to a US state. The model includes the community and the healthcare facilities within the state. Individuals may be either susceptible or infected and infectious. Infected patients determined to have CRE through admission screening or point-prevalence surveys at a facility are placed in a state of lower transmissibility if enhanced infection prevention and control (IPC) practices are in place. Results: Intervention bundles that included periodic point-prevalence surveys and enhanced IPC at high-acuity postacute-care facilities had the greatest impact on regional prevalence 10 years into an outbreak; the benefits of including admission screening and improved interfacility communication were more modest (Fig. 1A). Delaying interventions by 3 years is predicted to result in smaller reductions in prevalence (Fig. 1B). Increasing the frequency of point-prevalence surveys from biannually to quarterly resulted in a substantial relative reduction in prevalence (from 25% to 44%) if conducted from the start of an outbreak. IPC improvements in vSNFs resulted in greater relative reductions than in LTACHs. Admission screening at LTACHs and vSNFs was predicted to have a greater impact on prevalence if in place prior to CRE introduction (~20% reduction), and the impact decreased by approximately half if implementation was delayed until 3 years after CRE introduction. In contrast, the effect of admission screening in ACH was less (~10% reduction in prevalence) and did not change with implementation delays. Conclusions: Our model suggests that interventions that limit unrecognized MDRO introduction to, or dispersal from, LTACHs and vSNFs through screening are predicted to slow distribution regionally. Interventions to detect colonization and improve IPC practices within LTACHs and vSNFs may substantially reduce the regional burden. Prevention strategies are predicted to have the greatest impact when interventions are bundled and implemented before an MDRO is identified in a region, but reduction in overall prevalence is still possible if implemented after initial MDRO spread.

Funding: None

Disclosures: None

Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

OBJECTIVES/GOALS: Identification of COVID-19 patients at risk for deterioration following discharge from the emergency department (ED) remains a clinical challenge. Our objective was to develop a prediction model that identifies COVID-19 patients at risk for return and hospital admission within 30 days of ED discharge. METHODS/STUDY POPULATION: We performed a retrospective cohort study of discharged adult ED patients (n = 7,529) with SARS-CoV-2 infection from 116 unique hospitals contributing to the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER). The primary outcome was return hospital admission within 30 days. Models were developed using Classification and Regression Tree (CART), Gradient Boosted Machine (GBM), Random Forest (RF), and least absolute shrinkage and selection (LASSO) approaches. RESULTS/ANTICIPATED RESULTS: Among COVID-19 patients discharged from the ED on their index encounter, 571 (7.6%) returned for hospital admission within 30 days. The machine learning (ML) models (GBM, RF,: and LASSO) performed similarly. The RF model yielded a test AUC of 0.74 (95% confidence interval [CI] 0.71–0.78) with a sensitivity of 0.46 (0.39-0.54) and specificity of 0.84 (0.82-0.85). Predictive variables including: lowest oxygen saturation, temperature; or history of hypertension,: diabetes, hyperlipidemia, or obesity, were common to all ML models. DISCUSSION/SIGNIFICANCE: A predictive model identifying adult ED patients with COVID-19 at risk for return hospital admission within 30 days is feasible. Ensemble/boot-strapped classification methods outperform the single tree CART method. Future efforts may focus on the application of ML models in the hospital setting to optimize allocation of follow up resources.

Despite extensive paleoenvironmental research on the postglacial history of the Kenai Peninsula, Alaska, uncertainties remain regarding the region's deglaciation, vegetation development, and past hydroclimate. To elucidate this complex environmental history, we present new proxy datasets from Hidden and Kelly lakes, located in the eastern Kenai lowlands at the foot of the Kenai Mountains, including sedimentological properties (magnetic susceptibility, organic matter, grain size, and biogenic silica), pollen and macrofossils, diatom assemblages, and diatom oxygen isotopes. We use a simple hydrologic and isotope mass balance model to constrain interpretations of the diatom oxygen isotope data. Results reveal that glacier ice retreated from Hidden Lake's headwaters by ca. 13.1 cal ka BP, and that groundwater was an important component of Kelly Lake's hydrologic budget in the Early Holocene. As the forest developed and the climate became wetter in the Middle to Late Holocene, Kelly Lake reached or exceeded its modern level. In the last ca. 75 years, rising temperature caused rapid changes in biogenic silica content and diatom oxygen isotope values. Our findings demonstrate the utility of mass balance modeling to constrain interpretations of paleolimnologic oxygen isotope data, and that groundwater can exert a strong influence on lake water isotopes, potentially confounding interpretations of regional climate.

Praziquantel (PZQ) remains the only drug of choice for the treatment of schistosomiasis, caused by parasitic flatworms. The widespread use of PZQ in schistosomiasis endemic areas for about four decades raises concerns about the emergence of resistance of Schistosoma spp. to PZQ under drug selection pressure. This reinforces the urgency in finding alternative therapeutic options that could replace or complement PZQ. We explored the potential of medicinal plants commonly used by indigenes in Kenya for the treatment of various ailments including malaria, pneumonia, and diarrhoea for their antischistosomal properties. Employing the Soxhlet extraction method with different solvents, seven medicinal plants Artemisia annua, Ajuga remota, Bredilia micranta, Cordia africana, Physalis peruviana, Prunus africana and Senna didymobotrya were extracted. Qualitative phytochemical screening was performed to determine the presence of various phytochemicals in the plant extracts. Extracts were tested against Schistosoma mansoni newly transformed schistosomula (NTS) and adult worms and the schistosomicidal activity was determined by using the adenosine triphosphate quantitation assay. Phytochemical analysis of the extracts showed different classes of compounds such as alkaloids, tannins, terpenes, etc., in plant extracts active against S. mansoni worms. Seven extracts out of 22 resulted in <20% viability against NTS in 24 h at 100 μg/ml. Five of the extracts with inhibitory activity against NTS showed >69.7% and ≥72.4% reduction in viability against adult worms after exposure for 24 and 48 h, respectively. This study provides encouraging preliminary evidence that extracts of Kenyan medicinal plants deserve further study as potential alternative therapeutics that may form the basis for the development of the new treatments for schistosomiasis.

Yarkoni's analysis clearly articulates a number of concerns limiting the generalizability and explanatory power of psychological findings, many of which are compounded in infancy research. ManyBabies addresses these concerns via a radically collaborative, large-scale and open approach to research that is grounded in theory-building, committed to diversification, and focused on understanding sources of variation.

There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63–2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06–1.56), guanfacine (OR = 1.43, 95% CI = 1.12–1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09–1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.

We compute a presentation of the fundamental group of a higher-rank graph using a coloured graph description of higher-rank graphs developed by the third author. We compute the fundamental groups of several examples from the literature. Our results fit naturally into the suite of known geometrical results about higher-rank graphs when we show that the abelianization of the fundamental group is the homology group. We end with a calculation which gives a non-standard presentation of the fundamental group of the Klein bottle to the one normally found in the literature.

Storytelling is increasingly recognized as a culturally relevant, human-centered strategy and has been linked to improvements in health knowledge, behavior, and outcomes. The Community Engagement Program of the Johns Hopkins Institute for Clinical and Translational Research designed and implemented a storytelling training program as a potentially versatile approach to promote stakeholder engagement. Data collected from multiple sources, including participant ratings, responses to open-ended questions, and field notes, consistently pointed to high-level satisfaction and acceptability of the program. As a next step, the storytelling training process and its impact need to be further investigated.

To mimic the unsteady vortex–wall interaction of animal propulsion in a canonical test case, a vorticity-annihilating boundary layer was examined through the spin-down of a vortex from solid-body rotation. A cylindrical, water-filled tank was rapidly stopped, and the decay of the vortex from solid-body rotation was observed by means of planar and stereo particle image velocimetry. High Reynolds-number ($Re$) measurements were achieved by combining a large-scale facility (diameter, $D=13\ \textrm {m}$) with a novel approach to reduce end-wall effects. The influence of the boundary-layer formation at the tank's bottom wall was minimised by introducing a saturated salt-water layer. The experimental efforts have allowed us to assess the $Re$ dependency of the laminar–turbulent transition of the vorticity-annihilating side-wall boundary layer at scales similar to large cetaceans. The scaling of the transition mechanism and its onset time were found to agree with predictions from linear stability analysis. Furthermore, the growth rate of the curved turbulent boundary layer was also in good agreement with an empirical scaling formulated in the literature for much smaller $Re$. Eventually, the scaling of vorticity annihilation was addressed. The earlier onset of transition at high $Re$ compensates for the reduced effects of viscosity, leading to similar vorticity annihilation rates during the early stages of the spin-down for a wide $Re$ range.

A Melody valve was successfully placed across a very stenotic right-sided component of a common atrioventricular valve because of ongoing troublesome arrhythmias in a young woman with an unbalanced atrioventricular septal defect, a very dilated right atrium and a hypoplastic right ventricle. Four years later, she remains well.