We explore whether international disputes harm commerce by galvanizing consumer boycotts of foreign products. Boycotts increase the social penalty of owning goods associated with a foreign adversary, offsetting individual incentives to free ride or discount the utility of participation. By harming international commerce, boycotts can help reveal information about resolve and avoid more costly forms of conflict. Using administrative data on the universe of new passenger vehicle registration records in China from 2009 to 2015, we demonstrate that consumer boycotts that arose amid tensions between China and Japan over a territorial dispute in 2012 had significant and persistent effects on vehicle sales, especially in cities that witnessed anti-Japanese street demonstrations. The market share of Japanese brands dropped substantially during and after the boycott with long lasting effects. Our analysis provides concrete evidence of the short- and long-term impacts of international tensions on economic activities.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

Background: Over the past decade, the CLSI has updated susceptibility break points for several antimicrobial agents. The purpose of this study was to evaluate the impact of these changes against gram-negative bacteria at our academic medical center. Methods: In this retrospective, IRB-approved study, we collected consecutive, nonduplicate clinical isolates of Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, and Pseudomonas aeruginosa for the past decade (2010–2019) at our academic medical center and 3 adult ICUs. Susceptibility testing was performed using the BD Phoenix automated system. For these isolates, susceptibilities for 7 β-lactams (aztreonam, ceftriaxone, ceftazidime, cefepime, piperacillin/tazobactam, ertapenem, and meropenem) and 2 fluoroquinolones (levofloxacin, ciprofloxacin) were calculated based upon CLSI break points in 2010 and current CLSI break points in 2020. Any change >5% in susceptibility was deemed significant for this analysis. Results: In 17.5% of Enterobacteriales isolates tested, at least 1 antimicrobial demonstrated significant decline. Ertapenem was the most commonly affected antimicrobial (45% of the isolates) followed by ceftriaxone (35%) and cefepime (25%). Susceptibilities of aztreonam, ceftazidime, and meropenem were not affected for any of the Enterobacteriales. The most common organism demonstrating a significant impact on change in susceptibility among the Enterobacteriales was E. cloacae (41.7% of the time) followed by E. aerogenes (20.8%), K. oxytoca (12.5%), K. pneumoniae (8.3%) and E. coli (4.2%). Most of the impact was observed hospital-wide (33.3%), followed closely by the MICU (28.6%), the NSICU (23.8%) and the CVICU (14.3%). For P. aeruginosa, the impact of the antimicrobial break-point changes on susceptibility was more pronounced than the Enterobacteriales. Overall, 93.8% of the time there was a significant decline in antimicrobial susceptibility. Each antimicrobial (ciprofloxacin, levofloxacin, meropenem, and piperacillin/tazobactam) demonstrated a significant decline in susceptibility hospital-wide and in each ICU except for the susceptibility of meropenem in the NSICU. Conclusions: Changes in break points had a significant impact on the susceptibility of all antimicrobials for P. aeruginosa at our institution, both hospital-wide and in the adult ICUs. Although the impact was less for the Enterobacteriales, ertapenem, ceftriaxone, and cefepime demonstrated significant susceptibility changes, especially with E. cloacae. Understanding and evaluating the impact of the break-point changes may lead to changes in empiric therapy in other institutions.

Funding: No

Disclosures: None

Governments rely more and more on experts to manage the increasingly complex problems posed by a growing, diversifying, globalizing world. Surplus technocracy, however, usually comes with deficits of democracy. While especially true in liberal regimes, authoritarian states often face parallel dynamics. Recent trends illustrate how technocratic encroachment on civil society’s prerogatives can provoke populist backlash. Such cycles can build toward crises by eroding the legitimacy citizens invest in regimes. Surprisingly, by throwing both the need for and limits of expertise into sharp relief, the politics of COVID-19 create a novel opportunity to disrupt these trends. We assess how this opportunity may be unfolding in two crucial cases, the United States and China, and, more briefly, South Korea. We conclude by sketching some theoretical considerations to guide a geographically expanded and temporally extended research agenda on this important opportunity to slow or reverse a trend plaguing modern governance.

With the future of liberal internationalism in question, how will China's growing power and influence reshape world politics? We argue that views of the Liberal International Order (LIO) as integrative and resilient have been too optimistic for two reasons. First, China's ability to profit from within the system has shaken the domestic consensus in the United States on preserving the existing LIO. Second, features of Chinese Communist Party rule chafe against many of the fundamental principles of the LIO, but could coexist with a return to Westphalian principles and markets that are embedded in domestic systems of control. How, then, do authoritarian states like China pick and choose how to engage with key institutions and norms within the LIO? We propose a framework that highlights two domestic variables—centrality and heterogeneity—and their implications for China's international behavior. We illustrate the framework with examples from China's approach to climate change, trade and exchange rates, Internet governance, territorial sovereignty, arms control, and humanitarian intervention. Finally, we conclude by considering what alternative versions of international order might emerge as China's influence grows.

Background: Urinary tract infections (UTIs) are often misdiagnosed and mismanaged. Disease state stewardship initiatives targeting UTIs through the development of institutional guidelines and real-time prospective audit and feedback (PAAF) on provider management may have a significant impact on the overuse of antimicrobials. Objective: Our study evaluated the effectiveness of a UTI focused disease state stewardship intervention by assessing institutional guideline adherence before and after implementation. Methods: This retrospective quasi-experimental study was conducted at a tertiary-care academic medical center. Patients >18 years of age receiving antimicrobials for a UTI were included. A previously performed retrospective review of UTI management from September-November 2017 was used as the baseline. The UTI management guideline was implemented in July 2018, and service lines were educated. A PAAF initiative began in June 2019, whereby the antimicrobial stewardship team performed daily reviews of patients receiving antimicrobials for UTIs. Data was collected on their management, and providers were contacted in real time with recommendations based on the institutional guideline. Patients reviewed June–October 2019 were included in the postimplementation analysis. Patients were excluded if they were pregnant, underwent a urological procedure with risk of mucosal bleeding, or were an outside hospital transfer already on UTI therapy. The primary outcome of this study was to evaluate guideline adherence before and after the implementation of PAAF for the management of UTIs. Results: In total, 198 patients in the preintervention group and 246 in the PAAF group were included. The emergency department was the primary ordering service of urinalyses (60.1% vs 66.1%; P = .2287) in both periods and altered mental status as the main indication for testing (35.2% vs 31.3%; P = .5465). Treatment of asymptomatic bacteriuria and pyuria decreased significantly between the 2 periods: 74.8% versus 36.2% (P = .0001). Appropriate ordering of urinalyses (33.8% vs 68.3%; P = .0001) and urine cultures (29.3% vs 61.0%; P = .0001) also improved in the PAAF group. Recommendations made during PAAF included therapy discontinuation (66.7%), antimicrobial therapy change (15.5%), or duration modification (15.5%), and 59.5% of first interventions were accepted. Overall guideline compliance significantly improved from 13.1% in the preintervention period to 26.1% in the PAAF period (P = .0011). Conclusions: A UTI disease state intervention was associated with significant reductions in the treatment of asymptomatic presentations as well as an improvement in overall guideline adherence. We believe that this approach represents a powerful stewardship strategy for decreasing unnecessary antimicrobial usage.

Funding: None

Disclosures: None

What are the consequences of nationalist unrest? This paper utilizes two original datasets, which cover 377 city-level anti-Japanese protests during the 2012 Senkaku/Diaoyu Island crisis and the careers of municipal leaders, to analyse the downstream effects of nationalist unrest at the subnational level. We find both political and economic consequences of China's 2012 protest demonstrations against Japan. Specifically, top Party leaders in cities that saw relatively spontaneous, early protests were less likely to be promoted to higher office, a finding that is consistent with the widely held but rarely tested expectation that social instability is punished in the Chinese Communist Party's cadre evaluation system. We also see a negative effect of nationalist protest on foreign direct investment (FDI) growth at the city level. However, the lower promotion rates associated with relatively spontaneous protests appear to arise through political rather than economic channels. By taking into account data on social unrest in addition to economic performance, these results add to existing evidence that systematic evaluation of leaders’ performance plays a major role in the Chinese political system. These findings also illuminate the dilemma that local leaders face in managing popular nationalism amid shifting national priorities.

In 2006, Palmer amaranth with confirmed resistance to glyphosate (GLY-R) was not controlled effectively in cotton with pyrithiobac, an acetolactate synthase (ALS)-inhibiting herbicide. Glyphosate at 870 g ae ha−1 or pyrithiobac at 70 g ai ha−1 applied postemergence provided 5 to 28% control of a putative GLY/ALS-R Palmer amaranth biotype in the field. Glyphosate at 6,930 g ha−1 and pyrithiobac at 420 g ha−1 applied alone provided no more than 89 and 65% control 1 to 8 wk after treatment (WAT), respectively. When applied as a tank mixture, glyphosate plus pyrithiobac at 870 + 70 g ha−1 provided between 16 and 41% control; glyphosate plus pyrithiobac at 6,930 + 420 g ha−1 controlled the Palmer amaranth in the field 89 to 95%. Dose-response analyses developed from greenhouse data indicated that the estimated glyphosate rates required to produce 50% injury and reduce plant fresh weights by 50% relative to the nontreated control in a suspected GLY/ALS-R Palmer amaranth biotype were 12 and 14 times greater, respectively, than the estimated values for the susceptible (S) biotype. The predicted pyrithiobac rates required to produce the same responses in the putative resistant population were 151 (50% injury) and 563 times (50% fresh weight reduction) greater than the estimated rates for the S biotype. Field and greenhouse analyses confirm that the Palmer amaranth biotype evaluated in both studies is resistant to glyphosate and an ALS-inhibiting herbicide.

Why do some Chinese cities take part in waves of nationalist protest but not others? Nationalist protest remains an important but understudied topic within the study of contentious politics in China, particularly at the subnational level. Relative to other protests, nationalist mobilization is more clustered in time and geographically widespread, uniting citizens in different cities against a common target. Although the literature has debated the degree of state-led and grassroots influence on Chinese nationalism, we argue that it is important to consider both the propensity of citizens to mobilize and local government fears of instability. Analysing an original dataset of 377 anti-Japanese protests across 208 of 287 Chinese prefectural cities, we find that both state-led patriotism and the availability of collective action resources were positively associated with nationalist protest, particularly “biographically available” populations of students and migrants. In addition, the government's role was not monolithically facilitative. Fears of social unrest shaped the local political opportunity structure, with anti-Japanese protests less likely in cities with larger populations of unemployed college graduates and ethnic minorities and more likely in cities with established leaders.

Economic statistics inform citizens of general conditions, while central leaders use them to evaluate local officials. Are economic data systematically manipulated? After establishing discrepancies in economic data series cross-nationally, this article examines Chinese sub-national growth data. It leverages variation in the likelihood of manipulation over two dimensions, arguing that politically sensitive data are more likely to be manipulated at politically sensitive times. Gross domestic product (GDP) releases generate headlines, while highly correlated electricity production and consumption data are relatively unnoticed. In Chinese provinces, the difference between GDP and electricity growth increases in years with leadership turnover, which is consistent with juking the stats for political reasons. The analysis points to the political role of information and the limits of non-electoral accountability mechanisms in authoritarian regimes.

A series of editorials in this Journal have argued that psychiatry is in the midst of a crisis. The various solutions proposed would all involve a strengthening of psychiatry's identity as essentially ‘applied neuroscience’. Although not discounting the importance of the brain sciences and psychopharmacology, we argue that psychiatry needs to move beyond the dominance of the current, technological paradigm. This would be more in keeping with the evidence about how positive outcomes are achieved and could also serve to foster more meaningful collaboration with the growing service user movement.