A Spatially Resolved and Environmentally Informed Forecast Model of West Nile Virus in Coachella Valley, California.

West Nile virus (WNV) is the most significant arbovirus in the United States in terms of both morbidity and mortality. West Nile exists in a complex transmission cycle between avian hosts and the arthropod vector, Culex spp. mosquitoes. Human spillover events occur when humans are bitten by an infected mosquito and predicting these rates of infection and therefore the risk to humans may be associated with fluctuations in environmental conditions. In this study, we evaluate the hydrological and meteorological drivers associated with mosquito biology and viral development to determine if these associations can be used to forecast seasonal mosquito infection rates with WNV in the Coachella Valley of California. We developed and tested a spatially resolved ensemble forecast model of the WNV mosquito infection rate in the Coachella Valley using 17 years of mosquito surveillance data and North American Land Data Assimilation System-2 environmental data. Our multi-model inference system indicated that the combination of a cooler and dryer winter, followed by a wetter and warmer spring, and a cooler than normal summer was most predictive of the prevalence of West Nile positive mosquitoes in the Coachella Valley. The ability to make accurate early season predictions of West Nile risk has the potential to allow local abatement districts and public health entities to implement early season interventions such as targeted adulticiding and public health messaging before human transmission occurs. Such early and targeted interventions could better mitigate the risk of WNV to humans.

Aedes aegypti and Aedes albopictus (Diptera: Culicidae) Oviposition Activity and the Associated Socio-environmental Factors in the New Orleans Area.

The transmission of Aedes-borne viruses is on the rise globally. Their mosquito vectors, Aedes aegypti (Linnaeus, Diptera: Culicidae) and Ae. albopictus (Skuse, Diptera: Culicidae), are focally abundant in the Southern United States. Mosquito surveillance is an important component of a mosquito control program. However, there is a lack of long-term surveillance data and an incomplete understanding of the factors influencing vector populations in the Southern United States. Our surveillance program monitored Ae. aegypti and Ae. albopictus oviposition intensity in the New Orleans area using ovicups in a total of 75 sites from 2009 to 2016. We found both Aedes spp. throughout the study period and sites. The average number of Ae. aegypti and Ae. albopictus hatched from collected eggs per site per week was 34.1 (SD = 57.7) and 29.0 (SD = 46.5), respectively. Based on current literature, we formed multiple hypotheses on how environmental variables influence Aedes oviposition intensity, and constructed Generalized Linear Mixed Effect models with a negative binomial distribution and an autocorrelation structure to test these hypotheses. We found significant associations between housing unit density and Ae. aegypti and Ae. albopictus oviposition intensity, and between median household income and Ae. albopictus oviposition intensity. Temperature, relative humidity, and accumulated rainfall had either a lagged or an immediate significant association with oviposition. This study provides the first long-term record of Aedes spp. distribution in the New Orleans area, and sheds light on factors associated with their oviposition activity. This information is vital for the control of potential Aedes-borne virus transmission in this area.

Statistical Tools for West Nile Virus Disease Analysis.

West Nile virus (WNV) is the most widespread arbovirus in the world and endemic to much of the United States. Its range continues to expand as land use patterns change, creating more habitable environments for the mosquito vector. Though WNV is endemic, the year-to-year risk is highly variable, thus making it difficult to understand the risk for human spillover events. Abatement districts monitor for infected mosquitoes to help understand these potential risks and to help guide our understanding of the risk posed by these observed infected mosquitoes. Creating optimal monitoring networks will provide more informed decision-making tools for abatement districts and policy makers. Investment in these monitoring networks that capture robust observations on mosquito infection rates will allow for environmentally informed inference systems to help guide decision-making and WNV risk. In turn, enhanced decision-making tools allow for faster response times of more targeted and economical surveillance and mosquito population reduction efforts and the overall reduction of WNV transmission. Here we discuss the data streams, their processing, and specifically three ways to calculate WNV infection rates in mosquitoes.

A proposed framework for the development and qualitative evaluation of West Nile virus models and their application to local public health decision-making.

West Nile virus (WNV) is a globally distributed mosquito-borne virus of great public health concern. The number of WNV human cases and mosquito infection patterns vary in space and time. Many statistical models have been developed to understand and predict WNV geographic and temporal dynamics. However, these modeling efforts have been disjointed with little model comparison and inconsistent validation. In this paper, we describe a framework to unify and standardize WNV modeling efforts nationwide. WNV risk, detection, or warning models for this review were solicited from active research groups working in different regions of the United States. A total of 13 models were selected and described. The spatial and temporal scales of each model were compared to guide the timing and the locations for mosquito and virus surveillance, to support mosquito vector control decisions, and to assist in conducting public health outreach campaigns at multiple scales of decision-making. Our overarching goal is to bridge the existing gap between model development, which is usually conducted as an academic exercise, and practical model applications, which occur at state, tribal, local, or territorial public health and mosquito control agency levels. The proposed model assessment and comparison framework helps clarify the value of individual models for decision-making and identifies the appropriate temporal and spatial scope of each model. This qualitative evaluation clearly identifies gaps in linking models to applied decisions and sets the stage for a quantitative comparison of models. Specifically, whereas many coarse-grained models (county resolution or greater) have been developed, the greatest need is for fine-grained, short-term planning models (m-km, days-weeks) that remain scarce. We further recommend quantifying the value of information for each decision to identify decisions that would benefit most from model input.

Hürthle Cells on Fine-Needle Aspiration Cytology Are Important for Risk Assessment of Focally PET/CT FDG Avid Thyroid Nodules.

This study assesses the role of [18F] FDG PET/CT, fine needle aspiration (FNA) cytology and ultrasound in the 1-2% of patients with focally positive thyroid nodules on FDG PET/CT. All FDG PET/CT scans with focally increased thyroid FDG PET/CT uptake performed over 37 months in one institution were matched to patients undergoing thyroid FNA. Diffuse FDG PET/CT uptake patients were excluded. A total of 47 patients showed focally increased thyroid uptake. Consistent with previous studies, 18 (38.2%) patients had malignancy-12 primary thyroid carcinoma, 1 parathyroid carcinoma, 3 metastatic carcinoma to the thyroid and 2 lymphoma. A total of 15 (31.9%) lesions categorized as non-malignant contained Hürthle cells/oncocytes. A total of 14 lesions (29.8%) had focally increased FDG PET/CT uptake with no specific cytological or histopathological cause identified. No focally PET avid Hürthle cell/oncocytic lesions were found to be malignant. Exclusion of oncocytic lesions increased the calculated risk of malignancy (ROM) of focally PET avid nodules from 38% to 68%. It may be useful to exclude focally FDG PET/CT avid Hürthle cell/oncocytic lesions, typically reported as follicular neoplasm or suspicious for a follicular neoplasm, Hürthle cell type (Oncocytic) type, RCPath Thy 3F: Bethesda IV or sometimes Thy 3a: Bethesda III FNAs) from ROM calculations. Oncocytic focally PET/CT FDG avid lesions appear of comparatively lower risk of malignancy and require investigation or operation but these lesions should be readily identified by FNA cytology on diagnostic work up of focally PET avid thyroid nodules.

Immune outcomes of Zika virus infection in nonhuman primates.

Although the Zika virus (ZIKV) epidemic is subsiding, immune responses that are important for controlling acute infection have not been definitively characterized. Nonhuman primate (NHP) models were rapidly developed to understand the disease and to test vaccines, and these models have since provided an understanding of the immune responses that correlate with protection during natural infection and vaccination. Here, we infected a small group of male rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques with a minimally passaged Brazilian ZIKV isolate and used multicolor flow cytometry and transcriptional profiling to describe early immune patterns following infection. We found evidence of strong innate antiviral responses together with induction of neutralizing antibodies and T cell responses. We also assessed the relative importance of CD8 T cells in controlling infection by carrying out CD8 T cell depletion in an additional two animals of each species. CD8 depletion appeared to dysregulate early antiviral responses and possibly increase viral persistence, but the absence of CD8 T cells ultimately did not impair control of the virus. Together, these data describe immunological trends in two NHP species during acute ZIKV infection, providing an account of early responses that may be important in controlling infection.

Short Report: Asymptomatic Zika virus infections with low viral loads not likely to establish transmission in New Orleans Aedes populations.

Aedes aegypti and Aedes albopictus are both vectors of Zika virus and both are endemic to the New Orleans Metropolitan area. Fortunately, to date there has been no known autochthonous transmission of Zika virus in New Orleans. No studies of the vector competence of local populations of Ae. aegypti and Ae. albopictus for Zika virus transmission have been conducted. To determine if New Orleans Ae. aegypti and Ae. albopictus mosquitoes are competent for Zika virus, mosquitoes were reared to generation F3 from eggs collected in New Orleans during the 2018 mosquito season. Adults were fed an infectious blood meal and kept for 15 days in an environmental chamber. Transmission assays were conducted at 4, 10, and 15 days post exposure and RT-PCR was run on bodies and saliva to detect the presence of Zika virus RNA. We observed remarkably low susceptibility of both Ae. aegypti and Ae. albopictus from New Orleans to a Zika strain from Panama after oral challenge. These results suggest a limited risk of Zika virus transmission should it be introduced to the New Orleans area, and may partially explain why no transmission was detected in Louisiana during the 2016 epidemic in the Americas, despite multiple known travel associated introductions to New Orleans. Despite these results these mosquito populations are known to be competent vectors for some other mosquito-borne viruses and control measures should not be relaxed.

Author Correction: Pan-cancer deconvolution of tumour composition using DNA methylation.

The original version of this Article contained an error in Figure 4. In panel a, the colour code for hot and cold clusters was inadvertently inverted. In the correct version of panel a, the hot clusters are blue and the cold clusters are yellow. This error has now been corrected in both the PDF and HTML versions of the Article.

X-ray emission spectroscopy: an effective route to extract site occupation of cations.

Cation site occupation is an important determinant of materials properties, especially in a complex system with multiple cations such as in ternary spinels. Many methods for extracting the cation site information have been explored in the past, including analysis of spectra obtained through K-edge X-ray absorption spectroscopy (XAS). In this work, we measure the effectiveness of X-ray emission spectroscopy (XES) for determining the cation site occupation. As a test system we use spinel phase CoxMn3-xO4 nanoparticles contaminated with CoO phases because Co and Mn can occupy all cation sites and the impurity simulates typical products of oxide syntheses. We take advantage of the spin and oxidation state sensitive Kß1,3 peak obtained using XES and demonstrate that XES is a powerful and reliable technique for determining site occupation in ternary spinel systems. Comparison between the extended X-ray absorption fine structure (EXAFS) and XES techniques reveals that XES provides not only the site occupation information as EXAFS, but also additional information on the oxidation states of the cations at each site. We show that the error for EXAFS can be as high as 35% which makes the results obtained ambiguous for certain stoichiometries, whereas for XES, the error determined is consistently smaller than 10%. Thus, we conclude that XES is a superior and a far more accurate method than XAS in extracting cation site occupation in spinel crystal structures.