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Objective: The purpose of this study was to validate our previous genetic association findings related to the endoglin (ENG) pathway from an American Caucasian preeclampsia cohort in independent preeclampsia cohorts. We also sought to explore the ENG pathway for new genetic associations in these independent cohorts.Study Design: We used a tagging single nucleotide (tSNP) approach to assess genetic variability across five ENG pathway genes (ENG, TGFβ1, TGFβR1, ALK1, and TGFβR2) in a Caucasian cohort from Norway (n = 77 preeclampsia cases & n = 63 normotensive controls) and a White Hispanic cohort from Southern California (n = 69 preeclampsia cases & n = 106 normotensive controls).Main Outcome Measures: Univariate analyses (Chi Square, Fisher's Exact) and multivariate logistic regression were conducted to evaluate the association between tSNP genotype distributions and pregnancy outcome in each cohort. Logistic regression models were adjusted for maternal age at delivery, infant sex, parity, smoking during pregnancy, and pre-pregnancy BMI.Results: Although we were unable to replicate our previous SNP-specific findings (ENG rs11792480, rs10121110; TGFβR2 rs6550005; p's > 0.05), we found that genetic variation in TGFβR1[ALK5] (rs6478974) and TGFβR2 (rs11129420, rs6802220, rs1155708, rs3773640, rs3773663) was significantly associated with preeclampsia in the Norwegian cohort and genetic variation in ALK1 (rs706819) and TGFβR2 (rs9843942) was significantly associated with preeclampsia in the Latina cohort.Conclusion: Overall, our results provide further support for the involvement and investigation of the endoglin pathway in preeclampsia. [ABSTRACT FROM AUTHOR]

An obstacle to the modeling of strategies to mitigate extreme urban temperatures is frequently the lack of on-site meteorological data. The current study thus reports on a method that used the Weather Research and Forecasting (WRF) model to generate inputs for the ENVI-met model to produce building-scale canyon temperatures within a 300 m square near downtown San Jose. A land use distribution was generated for WRF by a WUDAPT classification, and the days of interest were then the hottest day in California history and a typical summer day. The source of meteorological data for ENVI-met, run with a 1.5 m cubic grid, was either an urbanized version of WRF; its default version; or observations at the closest NWS site. All WRF simulations were run on a 1 km grid, and output at its grid closest to the study area provided ENVI-met with lateral boundary conditions. The mitigation strategy was comprised of three parts, which either increased vegetation, rooftop albedo, or architectural shade elements. Results showed all strategies with only negligible impacts on ENVI-met nighttime 1 m level street canyon temperatures. Increased vegetation, however, was the most effective daytime strategy on both days, as it affected the largest area. The maximum vegetative cooling on the extreme and average days was −3.5 and −3.3 °C, respectively. While increased rooftop albedos produced near negligible impacts, increased architectural shading produced corresponding values of −1.6 and −1.7 °C, respectively. • Urban WRF generally reproduced meteorological conditions better than default WRF. • WUDAPT Level-0 urban LCZ classification yielded an overall test accuracy of 62%. • Vegetation was the most effective urban canyon daytime thermal mitigation strategy. • Daytime canyon warming resulted from the increased albedo and shading strategies. [ABSTRACT FROM AUTHOR]

Cryptococcus gattii infections in southern California have been reported in patients with HIV/AIDS. In this study, we examined the molecular epidemiology, population structure, and virulence attributes of isolates collected from HIV/AIDS patients in Los Angeles County, California. We show that these isolates consist almost exclusively of VGIII molecular type, in contrast to the VGII molecular type isolates causing the North American Pacific Northwest outbreak. The global VGIII population structure can be divided into two molecular groups, VGIIIa and VGIIIb. Isolates from the Californian patients are virulent in murine and macrophage models of infection, with VGIIIa significantly more virulent than VGIIIb. Several VGIII isolates are highly fertile and produce abundant sexual spores that may serve as infectious propagules. The a and α VGIII MAT locus alleles are largely syntenic with limited rearrangements compared to the known VGI (a/α) and VGII (α) MAT loci, but each has unique characteristics including a distinct deletion flanking the 5' VGIII MATa alleles and the α allele is more heterogeneous than the a allele. Our studies indicate that C. gattii VGIII is endemic in southern California, with other isolates originating from the neighboring regions of Mexico, and in rarer cases from Oregon and Washington state. Given that >1,000,000 cases of cryptococcal infection and >620,000 attributable mortalities occur annually in the context of the global AIDS pandemic, our findings suggest a significant burden of C. gattii may be unrecognized, with potential prognostic and therapeutic implications. These results signify the need to classify pathogenic Cryptococcus cases and highlight possible host differences among the C. gattii molecular types influencing infection of immunocompetent (VGI/VGII) vs. immunocompromised (VGIII/VGIV) hosts.