A Simple Model of Global Aerosol Indirect Effects

Most estimates of the global mean indirect effect of anthropogenic aerosol on the Earth's energy balance are from simulations by global models of the aerosol lifecycle coupled with global models of clouds and the hydrologic cycle. Extremely simple models have been developed for integrated assessment models, but lack the flexibility to distinguish between primary and secondary sources of aerosol. Here a simple but more physically based model expresses the aerosol indirect effect (AIE) using analytic representations of cloud and aerosol distributions and processes. Although the simple model is able to produce estimates of AIEs that are comparable to those from some global aerosol models using the same global mean aerosol properties, the estimates by the simple model are sensitive to preindustrial cloud condensation nuclei concentration, preindustrial accumulation mode radius, width of the accumulation mode, size of primary particles, cloud thickness, primary and secondary anthropogenic emissions, the fraction of the secondary anthropogenic emissions that accumulates on the coarse mode, the fraction of the secondary mass that forms new particles, and the sensitivity of liquid water path to droplet number concentration. Estimates of present-day AIEs as low as 5 W/sq m and as high as 0.3 W/sq m are obtained for plausible sets of parameter values. Estimates are surprisingly linear in emissions. The estimates depend on parameter values in ways that are consistent with results from detailed global aerosol-climate simulation models, which adds to understanding of the dependence on AIE uncertainty on uncertainty in parameter values

The genetic structure of Aedes aegypti populations is driven by boat traffic in the Peruvian Amazon.

In the Americas, as in much of the rest of the world, the dengue virus vector Aedes aegypti is found in close association with human habitations, often leading to high population densities of mosquitoes in urban settings. In the Peruvian Amazon, this vector has been expanding to rural communities over the last 10-15 years, but to date, the population genetic structure of Ae. aegypti in this region has not been characterized. To investigate the relationship between Ae. aegypti gene flow and human transportation networks, we characterized mosquito population structure using a panel of 8 microsatellite markers and linked results to various potential mechanisms for long-distance dispersal. Adult and immature Ae. aegypti (>20 individuals per site) were collected from Iquitos city and from six neighboring riverine communities, i.e., Nauta, Indiana, Mazan, Barrio Florida, Tamshiaco, and Aucayo. FST statistics indicate significant, but low to moderate differentiation for the majority of study site pairs. Population structure of Ae. aegypti is not correlated with the geographic distance between towns, suggesting that human transportation networks provide a reasonable explanation for the high levels of population mixing. Our results indicate that Ae. aegypti gene flow among sub-populations is greatest between locations with heavy boat traffic, such as Iquitos-Tamshiaco and Iquitos-Indiana-Mazan, and lowest between locations with little or no boat/road traffic between them such as Barrio Florida-Iquitos. Bayesian clustering analysis showed ancestral admixture among three genetic clusters; no single cluster was exclusive to any site. Our results are consistent with the hypothesis that human transportation networks, particularly riverways, are responsible for the geographic spread of Ae. aegypti in the Peruvian Amazon. Our findings are applicable to other regions of the world characterized by networks of urban islands connected by fluvial transport routes

Comparing the Psychometric Properties of Two Physical Activity Self-Efficacy Instruments in Urban, Adolescent Girls: Validity, Measurement Invariance, and Reliability

Aims: This study compared the psychometric properties of two self-efficacy instruments related to physical activity. Factorial validity, cross-group and longitudinal invariance, and composite reliability were examined.Methods: Secondary analysis was conducted on data from a group randomized controlled trial investigating the effect of a 17-week intervention on increasing moderate to vigorous physical activity among 5th–8th grade girls (N = 1,012). Participants completed a 6-item Physical Activity Self-Efficacy Scale (PASE) and a 7-item Self-Efficacy for Exercise Behaviors Scale (SEEB) at baseline and post-intervention. Confirmatory factor analyses for intervention and control groups were conducted with Mplus Version 7.4 using robust weighted least squares estimation. Model fit was evaluated with the chi-square index, comparative fit index, and root mean square error of approximation. Composite reliability for latent factors with ordinal indicators was computed from Mplus output using SAS 9.3.Results: Mean age of the girls was 12.2 years (SD = 0.96). One-third of the girls were obese. Girls represented a diverse sample with over 50% indicating black race and an additional 19% identifying as mixed or other race. Both instruments demonstrated configural invariance for simultaneous analysis of cross-group and longitudinal invariance based on alternative fit indices. However, simultaneous metric invariance was not met for the PASE or the SEEB instruments. Partial metric invariance for the simultaneous analysis was achieved for the PASE with one factor loading identified as non-invariant. Partial metric invariance was not met for the SEEB. Longitudinal scalar invariance was achieved for both instruments in the control group but not the intervention group. Composite reliability for the PASE ranged from 0.772 to 0.842. Reliability for the SEEB ranged from 0.719 to 0.800 indicating higher reliability for the PASE. Reliability was more stable over time in the control group for both instruments.Conclusions: Results suggest that the intervention influenced how girls responded to indicator items. Neither of the instruments achieved simultaneous metric invariance making it difficult to assess mean differences in PA self-efficacy between groups

The Dystrophin Complex Controls BK Channel Localization and Muscle Activity in Caenorhabditis elegans

Genetic defects in the dystrophin-associated protein complex (DAPC) are responsible for a variety of pathological conditions including muscular dystrophy, cardiomyopathy, and vasospasm. Conserved DAPC components from humans to Caenorhabditis elegans suggest a similar molecular function. C. elegans DAPC mutants exhibit a unique locomotory deficit resulting from prolonged muscle excitation and contraction. Here we show that the C. elegans DAPC is essential for proper localization of SLO-1, the large conductance, voltage-, and calcium-dependent potassium (BK) channel, which conducts a major outward rectifying current in muscle under the normal physiological condition. Through analysis of mutants with the same phenotype as the DAPC mutants, we identified the novel islo-1 gene that encodes a protein with two predicted transmembrane domains. We demonstrate that ISLO-1 acts as a novel adapter molecule that links the DAPC to SLO-1 in muscle. We show that a defect in either the DAPC or ISLO-1 disrupts normal SLO-1 localization in muscle. Consistent with observations that SLO-1 requires a high calcium concentration for full activation, we find that SLO-1 is localized near L-type calcium channels in muscle, thereby providing a mechanism coupling calcium influx with the outward rectifying current. Our results indicate that the DAPC modulates muscle excitability by localizing the SLO-1 channel to calcium-rich regions of C. elegans muscle

952-30 Left Ventricular Ejection Performance Improves Late After Aortic Valve Replacement in Patients with Aortic Stenosis and Reduced Ejection Fraction

To assess the time course and magnitude of change in left ventricular (LV) wall stress and ejection performance indices, 24 patients undergoing aortic valve replacement (AVR) for aortic stenosis were prospectively evaluated. Each patient underwent resting radionuclide angiography (RNA), echocardiography, and cardiac catheterization (high fidelity pressure) before AVR, then RNA and echocardiogram at one week and six months after AVR. Patients were stratified by preoperative ejection fraction (EF) into reduced EF (<50%) and normal EF (≥50%) groups.Pre-operatively, peak positive dp/dt was lower in the reduced EF group (1300 vs 1700mmHg/sec, p=0.035), and wall stress was elevated similarly in both groups (p=NS).Temporal Relationships of EF and Wall StressPre-op1 Week6 MosNormal EF (n=14)Mean Ejection Fraction (%)666468Mean Wall Stress (dyne/cm2×103)623444Reduced EF (n=10)Mean Ejection Fraction (%)383757Mean Wall Stress (dyne/cm2×103)785261Wall stress was reduced at one week post-operatively (p<0.005) in both groups. Ejection fraction remained depressed in the reduced EF group. By six months, however, EF had dramatically improved in the reduced EF group (p=0.002).ConclusionIn patients with LV dysfunction, EF remains low one week after AVR despite rectification of afterload mismatch. At six months, however, ejection performance improves. Therefore, when measured by ejection phase indices, the surgical benefit from AVR is not evident until late post-operatively

Applicant Reactions to the AAMC Standardized Video Interview During the 2018 Application Cycle

PURPOSE: This study examined applicant reactions to the Association of American Medical Colleges (AAMC) Standardized Video Interview (SVI) during its first year of operational use in emergency medicine (EM) residency program selection in order to identify strategies to improve applicants\u27 SVI experience and attitudes. METHOD: Individuals who self-classified as EM applicants applying in the Electronic Residency Application Service 2018 cycle and completed the SVI in summer 2017 were invited to participate in two surveys. Survey 1, which focused on procedural issues, was administered immediately after SVI completion. Survey 2, which focused on applicants\u27 SVI experience, was administered in fall 2017, after SVI scores were released. RESULTS: The response rates for surveys 1 and 2 were 82.3% (2,906/3,532) and 58.7% (2,074/3,532), respectively. Applicant reactions varied by aspect of the SVI studied and their SVI total scores. Most applicants were satisfied with most procedural aspects of the SVI, but most applicants were not satisfied with the SVI overall or with their total SVI scores. About 20-30% of applicants had neutral opinions about most aspects of the SVI. Negative reactions to the SVI were stronger for applicants who scored lower on the SVI. CONCLUSIONS: Applicants had generally negative reactions to the SVI. Most were skeptical of its ability to assess the target competencies and its potential to add value to the selection process. Applicant acceptance and appreciation of the SVI will be critical to the SVI\u27s acceptance by the graduate medical education community

The AAMC Standardized Video Interview: Reactions and Use by Residency Programs During the 2018 Application Cycle

PURPOSE: To evaluate how emergency medicine (EM) residency programs perceived and used Association of American Medical Colleges (AAMC) SVI total scores and videos during the Electronic Residency Application Service (ERAS) 2018 cycle. METHOD: Study 1 (November 2017) used a program director survey to evaluate user reactions to the SVI following the first year of operational use. Study 2 (January 2018) analyzed program usage of SVI video responses using data collected through the AAMC Program Director\u27s Workstation. RESULTS: Results from the survey (125/175 programs, 71% response rate) and video usage analysis suggested programs viewed videos out of curiosity and to understand the range of SVI total scores. Programs were more likely to view videos for attendees of U.S. MD-granting medical schools and applicants with higher United States Medical Licensing Examination Step 1 scores, but there were no differences by gender or race/ethnicity. More than half of programs that did not use SVI total scores in their selection processes were unsure of how to incorporate them (36/58, 62%) and wanted additional research on utility (33/58, 57%). More than half of programs indicated being at least somewhat likely to use SVI total scores (55/97; 57%) and videos (52/99; 53%) in the future. CONCLUSIONS: Program reactions on the utility and ease of use of SVI total scores were mixed. Survey results indicate programs used the SVI cautiously in their selection processes, consistent with AAMC recommendations. Future surveys of SVI users will help the AAMC gauge improvements in user acceptance and familiarity with the SVI

Radiative effect of clouds on tropospheric chemistry in a global three‐dimensional chemical transport model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94988/1/jgrd12465.pd

Climate and Landscape Factors Associated with Buruli Ulcer Incidence in Victoria, Australia

Background Buruli ulcer (BU), caused by Mycobacterium ulcerans (M. ulcerans), is a necrotizing skin disease found in more than 30 countries worldwide. BU incidence is highest in West Africa; however, cases have substantially increased in coastal regions of southern Australia over the past 30 years. Although the mode of transmission remains uncertain, the spatial pattern of BU emergence in recent years seems to suggest that there is an environmental niche for M. ulcerans and BU prevalence. Methodology/Principal Findings Network analysis was applied to BU cases in Victoria, Australia, from 1981–2008. Results revealed a non-random spatio-temporal pattern at the regional scale as well as a stable and efficient BU disease network, indicating that deterministic factors influence the occurrence of this disease. Monthly BU incidence reported by locality was analyzed with landscape and climate data using a multilevel Poisson regression approach. The results suggest the highest BU risk areas occur at low elevations with forested land cover, similar to previous studies of BU risk in West Africa. Additionally, climate conditions as far as 1.5 years in advance appear to impact disease incidence. Warmer and wetter conditions 18–19 months prior to case emergence, followed by a dry period approximately 5 months prior to case emergence seem to favor the occurrence of BU. Conclusions/Significance The BU network structure in Victoria, Australia, suggests external environmental factors favor M. ulcerans transmission and, therefore, BU incidence. A unique combination of environmental conditions, including land cover type, temperature and a wet-dry sequence, may produce habitat characteristics that support M. ulcerans transmission and BU prevalence. These findings imply that future BU research efforts on transmission mechanisms should focus on potential vectors/reservoirs found in those environmental niches. Further, this study is the first to quantitatively estimate environmental lag times associated with BU outbreaks, providing insights for future transmission investigations.This project was supported by the World Health Organization and the National Institutes of Health and Fogarty International Center (NIH - R01TW007550). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Fogarty International Center or the National Institutes of Health. R.W. Merritt is gratefully acknowledged for supporting this research as part of NIH grant R01TW007550

The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression.

Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM-AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer