Prevalence of Antibodies against Hantaviruses in Serum and Saliva of Adults Living or Working on Farms in Yorkshire, United Kingdom

We acknowledge Clement and colleagues for their comments [1] on our paper [2]. We agree that many controversies are being discussed by the hantavirus community, particularly surrounding the interpretation of serological results and the designation of new species and strains. Within this setting, we are grateful for the opportunity to respond to the key factual and methodological points raised by Clements et al. [...

Do topical repellents divert mosquitoes within a community? Health equity implications of topical repellents as a mosquito bite prevention tool.

OBJECTIVES: Repellents do not kill mosquitoes--they simply reduce human-vector contact. Thus it is possible that individuals who do not use repellents but dwell close to repellent users experience more bites than otherwise. The objective of this study was to measure if diversion occurs from households that use repellents to those that do not use repellents. METHODS: The study was performed in three Tanzanian villages using 15%-DEET and placebo lotions. All households were given LLINs. Three coverage scenarios were investigated: complete coverage (all households were given 15%-DEET), incomplete coverage (80% of households were given 15%-DEET and 20% placebo) and no coverage (all households were given placebo). A crossover study design was used and coverage scenarios were rotated weekly over a period of ten weeks. The placebo lotion was randomly allocated to households in the incomplete coverage scenario. The level of compliance was reported to be close to 100%. Mosquito densities were measured through aspiration of resting mosquitoes. Data were analysed using negative binomial regression models. FINDINGS: Repellent-users had consistently fewer mosquitoes in their dwellings. In villages where everybody had been given 15%-DEET, resting mosquito densities were fewer than half that of households in the no coverage scenario (Incidence Rate Ratio [IRR]=0.39 (95% confidence interval [CI]: 0.25-0.60); p<0.001). Placebo-users living in a village where 80% of the households used 15%-DEET were likely to have over four-times more mosquitoes (IRR=4.17; 95% CI: 3.08-5.65; p<0.001) resting in their dwellings in comparison to households in a village where nobody uses repellent. CONCLUSIONS: There is evidence that high coverage of repellent use could significantly reduce man-vector contact but with incomplete coverage evidence suggests that mosquitoes are diverted from households that use repellent to those that do not. Therefore, if repellents are to be considered for vector control, strategies to maximise coverage are required

Eye movements during scene inspection: A test of the saliency map hypothesis

What attracts attention when we inspect a scene? Two experiments recorded eye movements while viewers inspected pictures of natural office scenes in which two objects of interest were placed. One object had low contour density and uniform colouring (a piece of fruit), relative to another that was visually complex (for example, coffee mugs and commercial packages). In each picture the visually complex object had the highest visual saliency according to the Itti and Koch algorithm. Two experiments modified the task while the pictures were inspected, to determine whether visual saliency is invariably dominant in determining the pattern of fixations, or whether the purpose of inspection can provide a cognitive override that renders saliency secondary. In the first experiment viewers inspected the scene in preparation for a memory task, and the more complex objects were potent in attracting early fixations, in support of a saliency map model of scene inspection. In the second experiment viewers were set the task of detecting the presence of a low saliency target, and the effect of a high saliency distractor was negligible, supporting a model in which the saliency map can be built with cognitive influences that override low-level visual features

Exogenous double-stranded RNA inhibits the infection physiology of rust fungi to reduce symptoms in planta

Rust fungi (Pucciniales) are a diverse group of plant pathogens in natural and agricultural systems. They pose ongoing threats to the diversity of native flora and cause annual crop yield losses. Agricultural rusts are predominantly managed with fungicides and breeding for resistance, but new control strategies are needed on non-agricultural plants and in fragile ecosystems. RNA interference (RNAi) induced by exogenous double-stranded RNA (dsRNA) has promise as a sustainable approach for managing plant-pathogenic fungi, including rust fungi. We investigated the mechanisms and impact of exogenous dsRNA on rust fungi through in vitro and whole-plant assays using two species as models, Austropuccinia psidii (the cause of myrtle rust) and Coleosporium plumeriae (the cause of frangipani rust). In vitro, dsRNA either associates externally or is internalized by urediniospores during the early stages of germination. The impact of dsRNA on rust infection architecture was examined on artificial leaf surfaces. dsRNA targeting predicted essential genes significantly reduced germination and inhibited development of infection structures, namely appressoria and penetration pegs. Exogenous dsRNA sprayed onto 1-year-old trees significantly reduced myrtle rust symptoms. Furthermore, we used comparative genomics to assess the wide-scale amenability of dsRNA to control rust fungi. We sequenced genomes of six species of rust fungi, including three new families (Araucariomyceaceae, Phragmidiaceae, and Skierkaceae) and identified key genes of the RNAi pathway across 15 species in eight families of Pucciniales. Together, these findings indicate that dsRNA targeting essential genes has potential for broad-use management of rust fungi across natural and agricultural systems

A Randomized Placebo-Controlled Trial of \u3cem\u3eN\u3c/em\u3e-Acetylcysteine for Cannabis Use Disorder in Adults

Background—Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. Methods—In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18–50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200 mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. Results—There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio = 1.00, 95% confidence interval 0.63 – 1.59; p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. Conclusions—In contrast with prior findings in adolescents, there is no evidence that NAC 1200 mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors

Organizational impact of evidence-informed decision making training initiatives : a case study comparison of two approaches

Background The impact of efforts by healthcare organizations to enhance the use of evidence to improve organizational processes through training programs has seldom been assessed. We therefore endeavored to assess whether and how the training of mid- and senior-level healthcare managers could lead to organizational change. Methods We conducted a theory-driven evaluation of the organizational impact of healthcare leaders’ participation in two training programs using a logic model based on Nonaka’s theory of knowledge conversion. We analyzed six case studies nested within the two programs using three embedded units of analysis (individual, group and organization). Interviews were conducted during intensive one-week data collection site visits. A total of 84 people were interviewed. Results We found that the impact of training could primarily be felt in trainees’ immediate work environments. The conversion of attitudes was found to be easier to achieve than the conversion of skills. Our results show that, although socialization and externalization were common in all cases, a lack of combination impeded the conversion of skills. We also identified several individual, organizational and program design factors that facilitated and/or impeded the dissemination of the attitudes and skills gained by trainees to other organizational members. Conclusions Our theory-driven evaluation showed that factors before, during and after training can influence the extent of skills and knowledge transfer. Our evaluation went further than previous research by revealing the influence—both positive and negative—of specific organizational factors on extending the impact of training programs

Surface complexation model for strontium sorption to amorphous silica and goethite

Strontium sorption to amorphous silica and goethite was measured as a function of pH and dissolved strontium and carbonate concentrations at 25°C. Strontium sorption gradually increases from 0 to 100% from pH 6 to 10 for both phases and requires multiple outer-sphere surface complexes to fit the data. All data are modeled using the triple layer model and the site-occupancy standard state; unless stated otherwise all strontium complexes are mononuclear. Strontium sorption to amorphous silica in the presence and absence of dissolved carbonate can be fit with tetradentate Sr2+ and SrOH+ complexes on the β-plane and a monodentate Sr2+complex on the diffuse plane to account for strontium sorption at low ionic strength. Strontium sorption to goethite in the absence of dissolved carbonate can be fit with monodentate and tetradentate SrOH+ complexes and a tetradentate binuclear Sr2+ species on the β-plane. The binuclear complex is needed to account for enhanced sorption at hgh strontium surface loadings. In the presence of dissolved carbonate additional monodentate Sr2+ and SrOH+ carbonate surface complexes on the β-plane are needed to fit strontium sorption to goethite. Modeling strontium sorption as outer-sphere complexes is consistent with quantitative analysis of extended X-ray absorption fine structure (EXAFS) on selected sorption samples that show a single first shell of oxygen atoms around strontium indicating hydrated surface complexes at the amorphous silica and goethite surfaces

Genetic diversity and connectivity of southern right whales (Eubalaena australis) found in the Brazil and Chile-Peru wintering grounds and the South Georgia (Islas Georgias del Sur) feeding ground

As species recover from exploitation, continued assessments of connectivity and population structure are warranted to provide information for conservation and management. This is particularly true in species with high dispersal capacity, such as migratory whales, where patterns of connectivity could change rapidly. Here we build on a previous long-term, large-scale collaboration on southern right whales (Eubalaena australis) to combine new (nnew) and published (npub) mitochondrial (mtDNA) and microsatellite genetic data from all major wintering grounds and, uniquely, the South Georgia (Islas Georgias del Sur: SG) feeding grounds. Specifically, we include data from Argentina (npub mtDNA/microsatellite=208/46), Brazil (nnew mtDNA/microsatellite=50/50), South Africa (nnew mtDNA/microsatellite=66/77, npub mtDNA/microsatellite=350/47), Chile-Peru (nnew mtDNA/microsatellite=1/1), the Indo-Pacific (npub mtDNA/microsatellite=769/126), and SG (npub mtDNA/microsatellite=8/0, nnew mtDNA/microsatellite=3/11) to investigate the position of previously unstudied habitats in the migratory network: Brazil, SG and Chile-Peru. These new genetic data show connectivity between Brazil and Argentina, exemplified by weak genetic differentiation and the movement of one genetically identified individual between the South American grounds. The single sample from Chile-Peru had a mtDNA haplotype previously only observed in the Indo-Pacific and had a nuclear genotype that appeared admixed between the Indo-Pacific and South Atlantic, based on genetic clustering and assignment algorithms. The SG samples were clearly South Atlantic, and were more similar to the South American than the South African wintering grounds. This study highlights how international collaborations are critical to provide context for emerging or recovering regions, like the SG feeding ground, as well as those that remain critically endangered, such as Chile-Peru

Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1.

The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities. The activation of Nrf2 is required for the anti-inflammatory action of itaconate. We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons