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OBJECTIVES/GOALS: Recent research has attempted to identify diagnostic, prognostic, and predictive biomarkers, however, currently, no biomarkers can accurately diagnose GBC and predict patients prognosis. Using machine learning, we can utilize high-throughput RNA sequencing with clinicopathologic data to develop a predictive tool for GBC prognosis. METHODS/STUDY POPULATION: Current predictive models for GBC outcomes often utilize clinical data only. We aim to build a superior algorithm to predict overall survival in GBC patients with advanced disease, using machine learning approaches to prioritize biomarkers for GBC prognosis. We have identified over 80 fresh frozen GBC tissue samples from Rochester, Minnesota, Daegu, Korea, Vilnius, Lithuania, and Calgary, Canada. We will perform next-generation RNA sequencing on these tissue samples. The patients clinical, pathologic and survival data will be abstracted from the medical record. Random forests, support vector machines, and gradient boosting machines will be applied to train the data. Standard 5-fold cross validation will be used to assess performance of each ML algorithm. RESULTS/ANTICIPATED RESULTS: Our preliminary analysis of next generation RNA sequencing from 18 GBC tissue samples identified recurrent mutations in genes enriched in pathways in cytoskeletal signaling, cell organization, cell movement, extracellular matrix interaction, growth, and proliferation. The top three most significantly altered pathways, actin cytoskeleton signaling, hepatic fibrosis/hepatic stellate cell activation, and epithelial adherens junction signaling, emphasized a molecular metastatic and invasive fingerprint in our patient cohort. This molecular fingerprint is consistent with the previous knowledge of the highly metastatic nature of gallbladder tumors and is also manifested physiologically in the patient cohort. DISCUSSION/SIGNIFICANCE: Integrative analysis of molecular and clinical characterization of GBC has not been fully established, and minimal improvement has been made to the survival of these patients. If overall survival can be better predicted, we can gain a greater understanding of key biomarkers driving the tumor phenotype.
When and why do legislatures impeach presidents? We analyse six cases of attempted impeachment in Paraguay, Brazil and Peru to argue that intra-coalitional politics is central to impeachment outcomes. Presidents in Latin America often govern with multiparty, ideologically heterogeneous coalitions sustained by tenuous pacts. Coalitions are tested when crises, scandals or mass protests emerge, but presidents can withstand these threats if they tend to allies’ interests and maintain coalitions intact. Conversely, in the absence of major threats, presidents can be impeached if they fail to serve partners’ interests, inducing allies to support impeachment as acts of opportunism or self-preservation.
Recent patterns of democratic “backsliding” around the world have followed in the wake of a generalized weakening of organized labor under the modern, globalized variant of capitalism. Scholars have long debated whether and how labor contributes to the construction of democratic regimes and the expansion of social citizenship rights, but the current period makes it abundantly clear that democratic advances are always subject to reversal. As such, it is imperative to interrogate labor’s role in the defense of democratic rights and liberties, and not merely the introduction or expansion of those rights. These questions call for a multi-dimensional approach to the study of labor’s relationship to democracy, one that explores labor’s role in (1) constructing democratic regimes, (2) “deepening” democracy by expanding social citizenship rights, and (3) defending democracy against its adversaries and authoritarian currents in society.
Politics in the United States has become more polarized in recent decades as both political elites and everyday citizens have been divided into rival and mutually antagonistic partisan camps. Increasingly, these rival camps question the political legitimacy and democratic commitments of the other side. Such polarization or “teamsmanship” can have a number of important political consequences: it can drive actors further apart, intensify political conflict, impede negotiation and compromise, and block the construction of bipartisan legislative and policymaking coalitions. Since polarization makes it difficult, if not impossible, to find common political ground, it can prevent democratic institutions from making important policy choices and responding to the critical issues of the day. Polarization, in short, can easily lead to democratic gridlock, paralysis, the decay of rights, and, in the extreme, violent conflict, as the Trump administration’s waning weeks so vividly demonstrated.
Politics in the United States has become increasingly polarized in recent decades. Both political elites and everyday citizens are divided into rival and mutually antagonistic partisan camps, with each camp questioning the political legitimacy and democratic commitments of the other side. Does this polarization pose threats to democracy itself? What can make some democratic institutions resilient in the face of such challenges? Democratic Resilience brings together a distinguished group of specialists to examine how polarization affects the performance of institutional checks and balances as well as the political behavior of voters, civil society actors, and political elites. The volume bridges the conventional divide between institutional and behavioral approaches to the study of American politics and incorporates historical and comparative insights to explain the nature of contemporary challenges to democracy. It also breaks new ground to identify the institutional and societal sources of democratic resilience.
Background: Urine cultures are the most common microbiological tests in the outpatient setting and heavily influence treatment of suspected urinary tract infections (UTIs). Antibiotics for UTI are usually prescribed on an empiric basis in primary care before the urine culture results are available. However, culture results may be needed to confirm a UTI diagnosis and to verify that the correct antibiotic was prescribed. Although urine cultures are considered as the gold standard for diagnosis of UTI, cultures can easily become contaminated during collection. We determined the prevalence, predictors, and antibiotic use associated with contaminated urine cultures in 2 adult safety net primary care clinics. Methods: We conducted a retrospective chart review of visits with provider-suspected UTI in which a urine culture was ordered (November 2018–March 2020). Patient demographics, culture results, and prescription orders were captured for each visit. Culture results were defined as no culture growth, contaminated (ie, mixed flora, non-uropathogens, or ≥3 bacteria isolated on culture), low-count positive (growth between 100 and 100,000 CFU/mL), and high-count positive (>100,000 CFU/mL). A multivariable multinomial logistic regression model was used to identify factors associated with contaminated culture results. Results: There were 1,265 visits with urine cultures: 264 (20.9%) had no growth, 694 (54.9%) were contaminated, 159 (12.6%) were low counts, and 148 (11.7%) were high counts. Encounter-level factors are presented in Table 1. Female gender (adjusted odds ratio [aOR], 15.8; 95% confidence interval [CI], 10.21–23.46; P < .001), pregnancy (aOR, 13.98; 95% CI, 7.93–4.67; P < .001), and obesity (aOR, 1.9; 95% CI 1.31–2.77; P < .001) were independently associated with contaminated cultures. Of 264 patients whose urine cultures showed no growth, 36 (14%) were prescribed an antibiotic. Of 694 patients with contaminated cultures, 153 (22%) were prescribed an antibiotic (Figure 1). Conclusions: More than half of urine cultures were contaminated, and 1 in 5 patients were treated with antibiotics. Reduction of contamination should improve patient care by providing a more accurate record of the organism in the urine (if any) and its susceptibilities, which are relevant to managing future episodes of UTI in that patient. Optimizing urine collection represents a diagnostic stewardship opportunity in primary care.
Funding: This study was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (grant no. UM1AI104681). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.