Genetic variability and ontogeny predict microbiome structure in a disease-challenged montane amphibian

Amphibian populations worldwide are at risk of extinction from infectious diseases, including chytridiomycosis caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Amphibian cutaneous microbiomes interact with Bd and can confer protective benefits to the host. The composition of the microbiome itself is influenced by many environment- and host-related factors. However, little is known about the interacting effects of host population structure, genetic variation and developmental stage on microbiome composition and Bd prevalence across multiple sites. Here we explore these questions in Amietia hymenopus, a disease-affected frog in southern Africa. We use microsatellite genotyping and 16S amplicon sequencing to show that the microbiome associated with tadpole mouthparts is structured spatially, and is influenced by host genotype and developmental stage. We observed strong genetic structure in host populations based on rivers and geographic distances, but this did not correspond to spatial patterns in microbiome composition. These results indicate that demographic and host genetic factors affect microbiome composition within sites, but different factors are responsible for host population structure and microbiome structure at the between-site level. Our results help to elucidate complex within- and among- population drivers of microbiome structure in amphibian populations. That there is a genetic basis to microbiome composition in amphibians could help to inform amphibian conservation efforts against infectious diseases

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

The Trichoptera barcode initiative: a strategy for generating a species-level Tree of Life

DNA barcoding was intended as a means to provide species-level identifications through associating DNA sequences from unknown specimens to those from curated reference specimens. Although barcodes were not designed for phylogenetics, they can be beneficial to the completion of the Tree of Life. The barcode database for Trichoptera is relatively comprehensive, with data from every family, approximately two-thirds of the genera, and one-third of the described species. Most Trichoptera, as with most of life’s species, have never been subjected to any formal phylogenetic analysis. Here, we present a phylogeny with over 16 000 unique haplotypes as a working hypothesis that can be updated as our estimates improve. We suggest a strategy of implementing constrained tree searches, which allow larger datasets to dictate the backbone phylogeny, while the barcode data fill out the tips of the tree. We also discuss how this phylogeny could be used to focus taxonomic attention on ambiguous species boundaries and hidden biodiversity. We suggest that systematists continue to differentiate between ‘Barcode Index Numbers’ (BINs) and ‘species’ that have been formally described. Each has utility, but they are not synonyms. We highlight examples of integrative taxonomy, using both barcodes and morphology for species description. This article is part of the themed issue ‘From DNA barcodes to biomes’

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Effect of Provider Experience on Clinician-Performed Ultrasonography for Hydronephrosis in Patients With Suspected Renal Colic

Study objectiveHydronephrosis is readily visible on ultrasonography and is a strong predictor of ureteral stones, but ultrasonography is a user-dependent technology and the test characteristics of clinician-performed ultrasonography for hydronephrosis are incompletely characterized, as is the effect of ultrasound fellowship training on predictive accuracy. We seek to determine the test characteristics of ultrasonography for detecting hydronephrosis when performed by clinicians with a wide range of experience under conditions of direct patient care.MethodsThis was a prospective study of patients presenting to an academic medical center emergency department with suspected renal colic. Before computed tomography (CT) results, an emergency clinician performed bedside ultrasonography, recording the presence and degree of hydronephrosis. CT data were abstracted from the dictated radiology report by an investigator blinded to the bedside ultrasonographic results. Test characteristics of bedside ultrasonography for hydronephrosis were calculated with the CT scan as the reference standard, with test characteristics compared by clinician experience stratified into 4 levels: attending physicians with emergency ultrasound fellowship training, attending physicians without emergency ultrasound fellowship training, ultrasound experienced non-attending physician clinicians (at least 2 weeks of ultrasound training), and ultrasound inexperienced non-attending physician clinicians (physician assistants, nurse practitioners, off-service rotators, and first-year emergency medicine residents with fewer than 2 weeks of ultrasound training).ResultsThere were 670 interpretable bedside ultrasonographic tests performed by 144 unique clinicians, 80.9% of which were performed by clinicians directly involved in the care of the patient. On CT, 47.5% of all subjects had hydronephrosis and 47.0% had a ureteral stone. Among all clinicians, ultrasonography had a sensitivity of 72.6% (95% confidence interval [CI] 65.4% to 78.9%), specificity of 73.3% (95% CI 66.1% to 79.4%), positive likelihood ratio of 2.72 (95% CI 2.25 to 3.27), and negative likelihood ratio of 0.37 (95% CI 0.31 to 0.44) for hydronephrosis, using hydronephrosis on CT as the criterion standard. Among attending physicians with fellowship training, ultrasonography had sensitivity of 92.7% (95% CI 83.8% to 96.9%), positive likelihood ratio of 4.97 (95% CI 2.90 to 8.51), and negative likelihood ratio of 0.08 (95% CI 0.03 to 0.23).ConclusionOverall, ultrasonography performed by emergency clinicians was moderately sensitive and specific for detection of hydronephrosis as seen on CT in patients with suspected renal colic. However, presence or absence of hydronephrosis as determined by emergency physicians with fellowship training in ultrasonography yielded more definitive test results. For clinicians without fellowship training, there was no significant difference between groups in the predictive accuracy of the application according to experience level

Early life arsenic exposure and acute and long-term responses to influenza A infection in mice

Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood

Effect of Provider Experience on Clinician-Performed Ultrasonography for Hydronephrosis in Patients With Suspected Renal Colic

STUDY OBJECTIVE: Hydronephrosis is readily visible on ultrasonography and is a strong predictor of ureteral stones, but ultrasonography is a user-dependent technology and the test characteristics of clinician-performed ultrasonography for hydronephrosis are incompletely characterized, as is the effect of ultrasound fellowship training on predictive accuracy. We seek to determine the test characteristics of ultrasonography for detecting hydronephrosis when performed by clinicians with a wide range of experience under conditions of direct patient care. METHODS: This was a prospective study of patients presenting to an academic medical center emergency department with suspected renal colic. Before computed tomography (CT) results, an emergency clinician performed bedside ultrasonography, recording the presence and degree of hydronephrosis. CT data were abstracted from the dictated radiology report by an investigator blinded to the bedside ultrasonographic results. Test characteristics of bedside ultrasonography for hydronephrosis were calculated with the CT scan as the reference standard, with test characteristics compared by clinician experience stratified into 4 levels: attending physicians with emergency ultrasound fellowship training, attending physicians without emergency ultrasound fellowship training, ultrasound experienced non–attending physician clinicians (at least 2 weeks of ultrasound training), and ultrasound inexperienced non–attending physician clinicians (physician assistants, nurse practitioners, off-service rotators, and first-year emergency medicine residents with fewer than 2 weeks of ultrasound training). RESULTS: There were 670 interpretable bedside ultrasonographic tests performed by 144 unique clinicians, 80.9% of which were performed by clinicians directly involved in the care of the patient. On CT, 47.5% of all subjects had hydronephrosis and 47.0% had a ureteral stone. Among all clinicians, ultrasonography had a sensitivity of 72.6% (95% confidence interval [CI] 65.4% to 78.9%), specificity of 73.3% (95% CI 66.1% to 79.4%), positive likelihood ratio of 2.72 (95% CI 2.25 to 3.27), and negative likelihood ratio of 0.37 (95% CI 0.31 to 0.44) for hydronephrosis, using hydronephrosis on CT as the criterion standard. Among attending physicians with fellowship training, ultrasonography had sensitivity of 92.7% (95% CI 83.8% to 96.9%), positive likelihood ratio of 4.97 (95% CI 2.90 to 8.51), and negative likelihood ratio of 0.08 (95% CI 0.03 to 0.23). CONCLUSION: Overall, ultrasonography performed by emergency clinicians was moderately sensitive and specific for detection of hydronephrosis as seen on CT in patients with suspected renal colic. However, presence or absence of hydronephrosis as determined by emergency physicians with fellowship training in ultrasonography yielded more definitive test results. For clinicians without fellowship training, there was no significant difference between groups in the predictive accuracy of the application according to experience level