A novel method for the quantitative morphometric characterization of soluble salts on volcanic ash

<jats:title>Abstract</jats:title><jats:p>Formation of soluble sulfate and halide salts on volcanic ash particles via syn-eruptive interactions between ash surfaces and magmatic gases is a ubiquitous phenomenon in explosive eruptions. Surficial salts may be rapidly mobilized into their depositional environment undermining the quality of drinking water, harming aquatic life, and damaging soil and vegetation. Assessment of the potential for salt formation on ash and related environmental impacts have been based almost exclusively on bulk mineralogical or chemical analyses of ash; similarly, quantification of surficial salts has been made via leachate analysis only. However, it is the ash surface state and salt crystal properties that exert the predominant control on its reactivity, thus in determining their immediate environmental impact. Here, using scanning electron microscope (SEM) images, we present a novel image analysis protocol for the quantitative characterization of surficial salts, together with chemical analyses of resulting leachates. As volcanic ash proxies, we used synthetic rhyolitic glass particles (with systematic variations in FeO<jats:sub>T</jats:sub> and CaO content) and a crushed obsidian. Using an ash-gas reactor, we artificially surface-loaded samples with CaSO<jats:sub>4</jats:sub> and NaCl crystals, the most common crystal phases found on volcanic ash surfaces. Analogous variations were found using both methods: for CaSO<jats:sub>4</jats:sub> crystals, higher temperature treatments or increasing FeO<jats:sub>T</jats:sub> content at the same temperature led to higher concentrations of salt leachate and higher salt volumes; unexpectedly, increasing the CaO content caused only a minor increase in salt formation. In addition to bulk salt formation, morphometric results provided insight into formation processes, nucleation and growth rates, and limiting factors for salt formation. Higher temperatures increased CaSO<jats:sub>4</jats:sub> crystal size and surface coverage which we infer to result from higher element mobility in the glasses driving crystal growth. Increasing FeO<jats:sub>T</jats:sub> content of the glasses yielded increased salt surface coverage and leachate concentrations, but decreased crystal size (i.e., the salt number density increased). This latter effect likely relates to the role of iron as an electron-donor to charge balance salt-forming cation migration to the ash surface, indicating the importance of iron in determining surface reaction site density and, consequently, environmental reactivity. The controlling roles of ash composition and temperature on salt formation observed here can improve estimations for surface salt formation, volatile scavenging, and environmental impact for eruptions producing glass-rich ash. Our characterization protocol can therefore become a useful tool for the investigation of solid–gas reactions for terrestrial and planetary processes, and it also appears to be a powerful complement to research into atmospheric processes mediated by ash surfaces, such as ash aggregation and nucleation of water or ice on ash.</jats:p&gt

Use of multivariate analysis to evaluate antigenic relationships between US BVDV vaccine strains and non-US genetically divergent isolates.

Bovine viral diarrhea virus (BVDV) comprises two species, BVDV-1 and BVDV-2. But given the genetic diversity among pestiviruses, at least 22 subgenotypes are described for BVDV-1 and 3-4 for BVDV-2. Genetic characterization is generally accomplished through complete or partial sequencing and phylogeny, but it is not a reliable method to define antigenic relationships. The traditional method for evaluating antigenic relationships between pestivirus isolates is the virus neutralization (VN) assay, but interpretation of the data to define antigenic relatedness can be difficult to discern for BVDV isolates within the same BVDV species. Data from this study utilized a multivariate analysis for visualization of VN results to analyze the antigenic relationships between US vaccine strains and field isolates from Switzerland, Italy, Brazil, and the UK. Polyclonal sera were generated against six BVDV strains currently contained in vaccine formulations, and each serum was used in VNs to measure the titers against seven vaccine strains (including the six homologous strains) and 23 BVDV field isolates. Principal component analysis (PCA) was performed using VN titers, and results were interpreted from PCA clustering within the PCA dendrogram and scatter plot. The results demonstrated clustering patterns among various isolates suggesting antigenic relatedness. As expected, the BVDV-1 and BVDV-2 isolates did not cluster together and had the greatest spatial distribution. Notably, a number of clusters representing antigenically related BVDV-1 subgroups contain isolates of different subgenotypes. The multivariate analysis may be a method to better characterize antigenic relationships among BVDV isolates that belong to the same BVDV species and do not have distinct antigenic differences. This might be an invaluable tool to ameliorate the composition of current vaccines, which might well be important for the success of any BVDV control program that includes vaccination in its scheme

Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile

Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid boxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular c-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH

Genomic profiling of uterine aspirates and cfDNA as an integrative liquid biopsy strategy in endometrial cancer

The incidence and mortality of endometrial cancer (EC) have risen in recent years, hence more precise management is needed. Therefore, wecombined di erent types of liquid biopsies to better characterize the genetic landscape of EC in a non-invasive and dynamic manner. Uterine aspirates (UAs) from 60 patients with EC were obtained during surgery and analyzed by next-generation sequencing (NGS). Blood samples, collected at surgery, were used for cell-free DNA (cfDNA) and circulating tumor cell (CTC) analyses. Finally, personalized therapies were tested in patient-derived xenografts (PDXs) generated from the UAs. NGS analyses revealed the presence of genetic alterations in 93% of the tumors. Circulating tumor DNA (ctDNA) was present in 41.2% of cases, mainly in patients with high-risk tumors, thus indicating a clear association with a more aggressive disease. Accordingly, the results obtained during the post-surgery follow-up indicated the presence of ctDNA in three patients with progressive disease. Moreover, 38.9% of patients were positive for CTCs at surgery. Finally, the e cacy of targeted therapies based on the UA-specific mutational landscape was demonstrated in PDX models. Our study indicates the potential clinical applicability of a personalized strategy based on a combination of different liquid biopsies to characterize and monitor tumor evolution, and to identify targeted therapiesThis work was supported by grants and support from the Instituto de Salud Carlos III (ISCIII) and FEDER (PI17/01919, PI17/02071), CIBERONC (CB16/12/00328), and the AECC (Grupos Estables de Investigacion 2018-AECC) to A.G.-M. and M.A.; Instituto de Salud Carlos III (ISCIII) and FEDER (PI16/00134), CIBERONC (CB16/12/00295), and the AECC (Grupos Estables de Investigacion 2018-AECC) to G.M.-B.; and the AECC to L.M.-R

Genomic and serologic characterization of enterovirus A71 brainstem encephalitis

OBJECTIVE: In 2016, Catalonia experienced a pediatric brainstem encephalitis outbreak caused by enterovirus A71 (EV-A71). Conventional testing identified EV in the periphery but rarely in CSF. Metagenomic next-generation sequencing (mNGS) and CSF pan-viral serology (VirScan) were deployed to enhance viral detection and characterization. METHODS: RNA was extracted from the CSF (n = 20), plasma (n = 9), stool (n = 15), and nasopharyngeal samples (n = 16) from 10 children with brainstem encephalitis and 10 children with meningitis or encephalitis. Pathogens were identified using mNGS. Available CSF from cases (n = 12) and pediatric other neurologic disease controls (n = 54) were analyzed with VirScan with a subset (n = 9 and n = 50) validated by ELISA. RESULTS: mNGS detected EV in all samples positive by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 25). In qRT-PCR-negative samples (n = 35), mNGS found virus in 23% (n = 8, 3 CSF samples). Overall, mNGS enhanced EV detection from 42% (25/60) to 57% (33/60) (p-value = 0.013). VirScan and ELISA increased detection to 92% (11/12) compared with 46% (4/12) for CSF mNGS and qRT-PCR (p-value = 0.023). Phylogenetic analysis confirmed the EV-A71 strain clustered with a neurovirulent German EV-A71. A single amino acid substitution (S241P) in the EVA71 VP1 protein was exclusive to the CNS in one subject. CONCLUSION: mNGS with VirScan significantly increased the CNS detection of EVs relative to qRT-PCR, and the latter generated an antigenic profile of the acute EV-A71 immune response. Genomic analysis confirmed the close relation of the outbreak EV-A71 and neuroinvasive German EV-A71. A S241P substitution in VP1 was found exclusively in the CSF.Grants supporting this project include the National Multiple Sclerosis Society and the American Academy of Neurology award FAN-1608-25607 (R.D.S.), Clinical Research Training Scholarship P0534134 (P.S.R.), Sandler and William K. Bowes Jr Foundations (M.R.W., J.L.D., L.M.K., H.A.S., K.C.Z.), Rachleff Family Foundation (M.R.W.), and NINDS of the NIH under award K08NS096117 (M.R.W.) and F31NS113432 (K.E.L.). This study was partially supported by a grant from the Spanish National Health Institute [grant number PI15CIII-00020] and the European Regional Development Fund (FEDER funds). UCSF Biomedical Sciences Program (I.A.H., K.E.L.), UCSF Medical Scientist Training Program (K.E.L.), and the Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., J.L.D., E.D.C.) also supported this project.S

PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical–pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-013-2416-2) contains supplementary material, which is available to authorized users

Risks of dengue secondary infective biting associated with aedes aegypti in home environments in Monterrey, Mexico

Abstract. Secondary dengue virus infections are a major risk for developing dengue hemorrhagic fever. Recent exposure to infectious bites of Aedes aegypti (L.) females in previously diagnosed dengue cases fulfills the epidemiological model of dengue hemorrhagic fever. A study was comprised of 357 (89.2%) dengue and 43 (10.8%) dengue hemorrhagic fever cases confirmed by laboratory tests and clinical manifestations. An entomological survey was done in homes and backyards. Concurrently, a questionnaire was used to assess the impact of healthpromotion campaigns through knowledge of the vector and its epidemiological role. Seventy-six (28.4%) of the 268 (67.0%) total wet or dry oviposition sites were positive for the presence of larvae or pupae, while adult Ae. aegypti were found in 32 (8.0%). One hundred thirty-two (33%) householders who formerly had dengue fever or dengue hemorrhagic fever had knowledge of either larval or adult dengue vector stages. According to gender distribution, 145 (36.2%) and 14 (3.5%) of the males confirmed with cases of dengue and dengue hemorrhagic fever lived in houses with 17.9 and 2% of the Ae. aegypti larval and pupal habitats. Houses with females who had dengue and dengue hemorrhagic fever were 212 (53%) and 29 (7.3%), with containers with immature Ae. aegypti in 19.4 and 7%, respectively. Lack of sustainability of government-targeted health education campaigns is the major problem for involving communities in prevention and control of dengu

ADHD symptomatology in eating disorders : a secondary psychopathological measure of severity?

Background: Attention-deficit/hyperactivity disorder (ADHD) has commonly been described in psychiatric disorders. Although several studies have found positive associations between abnormal eating patterns during childhood and ADHD, there is a lack of studies on ADHD and Eating Disorders (ED). The aims of this exploratory study were 1) to assess the ADHD symptoms level in ED and to ascertain whether there are differences among ED subtypes; 2) to analyze whether the presence of ADHD symptoms is associated with more severe eating disorder symptoms and greater general psychopathology; and 3) to assess whether the ADHD symptoms level is associated with specific temperament and character traits. Methods: 191 female ED patients were included. Assessment was carried out with the EDI-2, ASRS-v1.1, the SCL-90-R and the TCI-R. Results: The ADHD symptoms level was similar in bulimia, eating disorder not otherwise specified and binge eating subtypes, and lower in anorexic patients. Obsessiveness and Hostility were significantly positively associated with ADHD symptoms. A path model showed that ADHD was associated with high Novelty Seeking and low Self-Directedness, whereas ED severity was influenced by ADHD severity and low Self-Directedness. Conclusions: Bingeing/purging ED subtypes have a high ADHD symptoms level, also related with more severe eating, general and personality psychopathology