Understanding the Essex Junto: Fear, Dissent, and Propaganda in the Early Republic

Historians have never formed a consensus over the Essex Junto. In fact, though often associated with New England Federalists, propagandists evoked the Junto long after the Federalist Party’s demise in 1824. This article chronicles uses of the term Essex Junto and its significance as it evolved from the early republic through the 1840s

Investigation of the correlation between odd oxygen and secondary organic aerosol in Mexico City and Houston

Many recent models underpredict secondary organic aerosol (SOA) particulate matter (PM) concentrations in polluted regions, indicating serious deficiencies in the models' chemical mechanisms and/or missing SOA precursors. Since tropospheric photochemical ozone production is much better understood, we investigate the correlation of odd-oxygen ([Ox]≡[O3]+[NO2]) [([O subscript x] ≡ [O subscript 3] + [NO subscript 2])] and the oxygenated component of organic aerosol (OOA), which is interpreted as a surrogate for SOA. OOA and Ox [O subscript x] measured in Mexico City in 2006 and Houston in 2000 were well correlated in air masses where both species were formed on similar timescales (less than 8 h) and not well correlated when their formation timescales or location differed greatly. When correlated, the ratio of these two species ranged from 30 μg [mu g] m−3/ppm [m superscript -3 / ppm] (STP) in Houston during time periods affected by large petrochemical plant emissions to as high as 160 μg [mu g] m−3/ppm [m superscript -3 / ppm] in Mexico City, where typical values were near 120 μg [mu g] m−3/ppm [m superscript -3 / ppm]. On several days in Mexico City, the [OOA]/[Ox] [[OOA] / O subscript x]] ratio decreased by a factor of ~2 between 08:00 and 13:00 local time. This decrease is only partially attributable to evaporation of the least oxidized and most volatile components of OOA; differences in the diurnal emission trends and timescales for photochemical processing of SOA precursors compared to ozone precursors also likely contribute to the observed decrease. The extent of OOA oxidation increased with photochemical aging. Calculations of the ratio of the SOA formation rate to the Ox [O subscript x] production rate using ambient VOC measurements and traditional laboratory SOA yields are lower than the observed [OOA]/[Ox] [[OOA] / O subscript x]] ratios by factors of 5 to 15, consistent with several other models' underestimates of SOA. Calculations of this ratio using emission factors for organic compounds from gasoline and diesel exhaust do not reproduce the observed ratio. Although not successful in reproducing the atmospheric observations presented, modeling P(SOA)/P(Ox) [P (SOA) / P (O subscript x)] can serve as a useful test of photochemical models using improved formulation mechanisms for SOA.National Science Foundation (U.S.) (Grant ATM-528227)National Science Foundation (U.S.) (Grant ATM-0528170)National Science Foundation (U.S.) (Grant ATM-0513116)National Science Foundation (U.S.) (Grant ATM-0449815)United States. Dept. of Energy. Office of Biological and Environmental Research. Atmospheric Science Program (Grant DE-FGO2-05ER63982)United States. Dept. of Energy. Office of Biological and Environmental Research. Atmospheric Science Program (Grant DEFGO2- 05ER63980)United States. Dept. of Energy. Office of Biological and Environmental Research. Atmospheric Science Program (Grant DE-FG02-08ER64627)United States. National Oceanic and Atmospheric Administration (Grant NA08OAR4310656

Technical Aspects of Flow Cytometry-based Measurable Residual Disease Quantification in Acute Myeloid Leukemia: Experience of the European LeukemiaNet MRD Working Party

Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll. The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories. The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment and are a next step toward further harmonization

The Sloan Digital Sky Survey Reverberation Mapping project : photometric g and i light curves

Funding: P.H. acknowledges the support of the Natural Sciences and Engineering Research Council of Canada (NSERC), funding reference number 2017-05983. C.J.G., W.N.B., and D.P.S. acknowledge support from NSF grant AST-1517113. Y.S. acknowledges support from an Alfred P. Sloan Research Fellowship and NSF grant AST-1715579. L.C.H. acknowledges the National Key R&D Program of China (2016YFA0400702) and the National Science Foundation of China (11721303, 11991052). J.V.H.S. and K.H. acknowledge support from a STFC grant ST/R000824/1. C.S.K. is supported by NSF grants AST-1814440 and AST-1908570.The Sloan Digital Sky Survey (SDSS) Reverberation Mapping program monitors 849 active galactic nuclei (AGNs) both spectroscopically and photometrically. The photometric observations used in this work span over 4 yr and provide an excellent baseline for variability studies of these objects. We present the photometric light curves from 2014 to 2017 obtained by the Steward Observatory's Bok telescope and the Canada-France-Hawaii telescope with MegaCam. We provide details on the data acquisition and processing of the data from each telescope, the difference imaging photometry used to produce the light curves, and the calculation of a variability index to quantify each AGN's variability. We find that the Welch-Stetson J index provides a useful characterization of AGN variability and can be used to select AGNs for further study.PostprintPeer reviewe

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Mediator and cohesin connect gene expression and chromatin architecture

Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect two DNA segments. The cohesin-loading factor Nipbl is associated with mediator–cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell.National Institutes of Health (U.S.) (Fellowship)Canadian Institutes of Health Research (Research Fellowship)National Institutes of Health (U.S.) (Grant R01 HG002668

Coordinated Activity of Ventral Tegmental Neurons Adapts to Appetitive and Aversive Learning

Our understanding of how value-related information is encoded in the ventral tegmental area (VTA) is based mainly on the responses of individual putative dopamine neurons. In contrast to cortical areas, the nature of coordinated interactions between groups of VTA neurons during motivated behavior is largely unknown. These interactions can strongly affect information processing, highlighting the importance of investigating network level activity. We recorded the activity of multiple single units and local field potentials (LFP) in the VTA during a task in which rats learned to associate novel stimuli with different outcomes. We found that coordinated activity of VTA units with either putative dopamine or GABA waveforms was influenced differently by rewarding versus aversive outcomes. Specifically, after learning, stimuli paired with a rewarding outcome increased the correlation in activity levels between unit pairs whereas stimuli paired with an aversive outcome decreased the correlation. Paired single unit responses also became more redundant after learning. These response patterns flexibly tracked the reversal of contingencies, suggesting that learning is associated with changing correlations and enhanced functional connectivity between VTA neurons. Analysis of LFP recorded simultaneously with unit activity showed an increase in the power of theta oscillations when stimuli predicted reward but not an aversive outcome. With learning, a higher proportion of putative GABA units were phase locked to the theta oscillations than putative dopamine units. These patterns also adapted when task contingencies were changed. Taken together, these data demonstrate that VTA neurons organize flexibly as functional networks to support appetitive and aversive learning

Has the DOTS Strategy Improved Case Finding or Treatment Success? An Empirical Assessment

Background: Nearly fifteen years after the start of WHO's DOTS strategy, tuberculosis remains a major global health problem. Given the lack of empirical evidence that DOTS reduces tuberculosis burden, considerable debate has arisen about its place in the future of global tuberculosis control efforts. An independent evaluation of DOTS, one of the most widely-implemented and longest-running interventions in global health, is a prerequisite for meaningful improvements to tuberculosis control efforts, including WHO's new Stop TB Strategy. We investigate the impact of the expansion of the DOTS strategy on tuberculosis case finding and treatment success, using only empirical data. Methods and Findings: We study the effect of DOTS using time-series cross-sectional methods. We first estimate the impact of DOTS expansion on case detection, using reported case notification data and controlling for other determinants of change in notifications, including HIV prevalence, GDP, and country-specific effects. We then estimate the effect of DOTS expansion on treatment success. DOTS programme variables had no statistically significant impact on case detection in a wide range of models and specifications. DOTS population coverage had a significant effect on overall treatment success rates, such that countries with full DOTS coverage benefit from at least an 18% increase in treatment success (95% CI: 5–31%). Conclusions: The DOTS technical package improved overall treatment success. By contrast, DOTS expansion had no effect on case detection. This finding is less optimistic than previous analyses. Better epidemiological and programme data would facilitate future monitoring and evaluation efforts

Global Regulation of Nucleotide Biosynthetic Genes by c-Myc

The c-Myc transcription factor is a master regulator and integrates cell proliferation, cell growth and metabolism through activating thousands of target genes. Our identification of direct c-Myc target genes by chromatin immunoprecipitation (ChIP) coupled with pair-end ditag sequencing analysis (ChIP-PET) revealed that nucleotide metabolic genes are enriched among c-Myc targets, but the role of Myc in regulating nucleotide metabolic genes has not been comprehensively delineated.Here, we report that the majority of genes in human purine and pyrimidine biosynthesis pathway were induced and directly bound by c-Myc in the P493-6 human Burkitt's lymphoma model cell line. The majority of these genes were also responsive to the ligand-activated Myc-estrogen receptor fusion protein, Myc-ER, in a Myc null rat fibroblast cell line, HO.15 MYC-ER. Furthermore, these targets are also responsive to Myc activation in transgenic mouse livers in vivo. To determine the functional significance of c-Myc regulation of nucleotide metabolism, we sought to determine the effect of loss of function of direct Myc targets inosine monophosphate dehydrogenases (IMPDH1 and IMPDH2) on c-Myc-induced cell growth and proliferation. In this regard, we used a specific IMPDH inhibitor mycophenolic acid (MPA) and found that MPA dramatically inhibits c-Myc-induced P493-6 cell proliferation through S-phase arrest and apoptosis.Taken together, these results demonstrate the direct induction of nucleotide metabolic genes by c-Myc in multiple systems. Our finding of an S-phase arrest in cells with diminished IMPDH activity suggests that nucleotide pool balance is essential for c-Myc's orchestration of DNA replication, such that uncoupling of these two processes create DNA replication stress and apoptosis