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In the fungal pathogen Aspergillus fumigatus, resistance to azole antifungals is often linked to mutations in CYP51A, a gene that encodes the azole antifungal drug target lanosterol 14α-demethylase. The aim of this study was to investigate whether similar changes could be associated with azole resistance in a Malaysian Fusarium solani species complex (FSSC) isolate collection. Most (11 of 15) clinical FSSC isolates were Neocosmospora keratoplastica and the majority (6 of 10) of environmental isolates were Neocosmospora suttoniana strains. All 25 FSSC isolates had high minimum inhibitory concentrations (MICs) for itraconazole and posaconazole, low MICs for amphotericin B, and various (1 to >32 mg/l) voriconazole susceptibilities. There was a tight association between a 23 bp CYP51A promoter deletion and high (>32 mg/l) voriconazole MICs; of 19 FSSC strains sequenced, nine isolates had voriconazole MICs > 32 mg/l, and they all contained the 23 bp CYP51A promoter deletion, although it was absent in the ten remaining isolates with low (≤12 mg/l) voriconazole MICs. Surprisingly, this association between voriconazole resistance and the 23 bp CYP51A promoter deletion held true across species boundaries. It was randomly distributed within and across species boundaries and both types of FSSC isolates were found among environmental and clinical isolates. Three randomly selected N. keratoplastica isolates with low (≤8 mg/l) voriconazole MICs had significantly lower (1.3–7.5 times) CYP51A mRNA expression levels than three randomly selected N. keratoplastica isolates with high (>32 mg/l) voriconazole MICs. CYP51A expression levels, however, were equally strongly induced (~6,500-fold) by voriconazole in two representative strains reaching levels, after 80 min of induction, that were comparable to those of CYP51B. Our results suggest that FSSC isolates with high voriconazole MICs have a 23 bp CYP51A promoter deletion that provides a potentially useful marker for voriconazole resistance in FSSC isolates. Early detection of possible voriconazole resistance is critical for choosing the correct treatment option for patients with invasive fusariosis.

Abstract Background Since early antimicrobial therapy is mandatory in septic patients, immediate diagnosis and distinction from non-infectious SIRS is essential but hampered by the similarity of symptoms between both entities. We aimed to develop a diagnostic model for differentiation of sepsis and non-infectious SIRS in critically ill children based on routinely available parameters (baseline characteristics, clinical/laboratory parameters, technical/medical support). Methods This is a secondary analysis of a randomized controlled trial conducted at a German tertiary-care pediatric intensive care unit (PICU). Two hundred thirty-eight cases of non-infectious SIRS and 58 cases of sepsis (as defined by IPSCC criteria) were included. We applied a Random Forest approach to identify the best set of predictors out of 44 variables measured at the day of onset of the disease. The developed diagnostic model was validated in a temporal split-sample approach. Results A model including four clinical (length of PICU stay until onset of non-infectious SIRS/sepsis, central line, core temperature, number of non-infectious SIRS/sepsis episodes prior to diagnosis) and four laboratory parameters (interleukin-6, platelet count, procalcitonin, CRP) was identified in the training dataset. Validation in the test dataset revealed an AUC of 0.78 (95% CI: 0.70–0.87). Our model was superior to previously proposed biomarkers such as CRP, interleukin-6, procalcitonin or a combination of CRP and procalcitonin (maximum AUC = 0.63; 95% CI: 0.52–0.74). When aiming at a complete identification of sepsis cases (100%; 95% CI: 87–100%), 28% (95% CI: 20–38%) of non-infectious SIRS cases were assorted correctly. Conclusions Our approach allows early recognition of sepsis with an accuracy superior to previously described biomarkers, and could potentially reduce antibiotic use by 30% in non-infectious SIRS cases. External validation studies are necessary to confirm the generalizability of our approach across populations and treatment practices. Trial registration ClinicalTrials.gov number: NCT00209768; registration date: September 21, 2005.

Science-based forest management requires quantitative estimation of forest attributes traditionally collected via sampled field plots in a forest inventory program. Three-dimensional (3D) remotely sensed data such as Light Detection and Ranging (lidar), are increasingly utilized to supplement and even replace field-based forest inventories. However, lidar remains cost prohibitive for smaller areas and repeat measurements, often limiting its use to single acquisitions of large contiguous areas. Recent advancements in unpiloted aerial systems (UAS), digital aerial photogrammetry (DAP) and high precision global positioning systems (HPGPS) have the potential to provide low-cost time and place flexible 3D data to support forest inventory and monitoring. The primary objective of this study was to assess the ability of low-cost commercial off the shelf UAS DAP and HPGPS to create accurate 3D data and predictions of key forest attributes, as compared to both lidar and field observations, in a wide range of forest conditions in California, USA. A secondary objective was to assess the accuracy of nadir vs. off-nadir UAS DAP, to determine if oblique imagery provides more accurate 3D data and forest attribute predictions. UAS DAP digital terrain models (DTMs) were comparable to lidar DTMS across most sites and nadir vs. off-nadir imagery collection (R2 = 0.74–0.99), although model accuracy using off-nadir imagery was very low in mature Douglas-fir forest (R2 = 0.17) due to high canopy density occluding the ground from the image sensor. Surface and canopy height models were shown to have less agreement to lidar (R2 = 0.17–0.69), with off-nadir imagery surface models at high canopy density sites having the lowest agreement with lidar. UAS DAP models predicted key forest metrics with varying accuracy compared to field data (R2 = 0.53–0.85), and were comparable to predictions made using lidar. Although lidar provided more accurate estimates of forest attributes across a range of forest conditions, this study shows that UAS DAP models, when combined with low-cost HPGPS, can accurately predict key forest attributes across a range of forest types, canopies densities, and structural conditions.

This article is part of a larger ethnographic study on teaching and learning in one of Australia's only stand-alone adolescent New Arrival Programs (NAPs) for students learning English. These multilingual adolescents represent four world regions: the Middle East, Africa, South Asia, and East Asia. Eventually, they will enter mainstream high schools. Instead of grade levels, the school uses initial language and literacy assessments to assign students Pathways, which determine their lengths of stay in the NAP. The school focuses on intensive English language instruction and social/emotional well-being through subject-area lessons, electives, excursions, community partnerships, personal wellness, and clubs. Through all of these efforts, the collective goal is to prompt students to use literacy and language as tools for living with the past and interpreting new experiences in Australia. According to the author, Mary and Roger teach in the school's Pathway A program, where students typically come from refugee backgrounds. Pathway A students have had unreliable access to formalized schooling due to displacement, poverty, and simple or complex health issues. While new to English, the students are all experienced language learners. In this particular state, students in Pathway A attend the NAP for up to two years before transitioning into mainstream high schools. Previous or current trauma affects these students' progress in written literacy; sometimes, they appear afraid, resistant, or anxious about new experiences. Most of the time, however, they smile and laugh, play soccer at recess, sing, dance, use social media, misbehave, and engage in a range of typical adolescent behaviors. Students' trauma does not define them. Some might see these students as leagues behind their native English speaking counterparts, but Mary and Roger know they are substantially ahead in their linguistic, cultural, and life experiences.

Sphingolipids, modified by dietary fatty acids, are integral components of plasma membrane and caveolae that are also vasoactive compounds. We hypothesized that dietary fatty acid saturation affects vasoconstriction to sphingosine-1-phosphate (S1P) through caveolar regulation of rho kinase. Wild type (WT) and caveolin-1-deficient (cav-1 KO) mice which lack vascular caveolae were fed a low-fat diet (LF), 60% high-saturated fat diet (lard, HF), or 60% fat diet with equal amounts of lard and n-3 polyunsaturated menhaden oil (MO). Weight gain of WT on HF and MO diets was similar while markedly blunted in cav-1 KO. Neither high-fat diet affected the expression of cav-1, rho, or rho kinase in arteries from WT. In cav-1 KO, MO increased the vascular expression of rho but had no effect on rho kinase. HF had no effect on rho or rho kinase expression in cav-1 KO. S1P produced a concentration-dependent constriction of gracilis arteries from WT on LF that was reduced with HF and restored to normal with MO. Constriction to S1P was reduced in cav-1 KO and no longer affected by a high-saturated fat diet. Inhibition of rho kinase which reduced constriction to PE independent of diet in arteries from WT and cav-1 KO only reduced constriction to S1P in arteries from WT fed MO. The data suggest that dietary fatty acids modify vascular responses to S1P by a caveolar-dependent mechanism which is enhanced by dietary n-3 polyunsaturated fats.