A bioinformatics workflow for detecting signatures of selection in genomic data

The detection of “signatures of selection” is now possible on a genome-wide scale in many plant and animal species, and can be performed in a population-specific manner due to the wealth of per-population genome-wide genotype data that is available. With genomic regions that exhibit evidence of having been under selection shown to also be enriched for genes associated with biologically important traits, detection of evidence of selective pressure is emerging as an additional approach for identifying novel gene-trait associations. While high-density genotype data is now relatively easy to obtain, for many researchers it is not immediately obvious how to go about identifying signatures of selection in these data sets. Here we describe a basic workflow, constructed from open source tools, for detecting and examining evidence of selection in genomic data. Code to install and implement the pipeline components, and instructions to run a basic analysis using the workflow described here, can be downloaded from our public GitHub repository: http://www.github.com/smilefreak/selectionTools

Commensal microbiota modulates larval foraging behaviour, development rate and pupal production in Bactrocera tryoni

Project Raising Q-fly Sterile Insect Technique to World Standard (HG14033) is funded by the Hort Frontiers Fruit Fly Fund, part of the Hort Frontiers strategic partnership initiative developed by Hort Innovation, with co-investment from Macquarie University and contributions from the Australian Government. BN is supported by an international Research Training Program (iRTP) scholarship from Macquarie University (NSW, Australia).Peer reviewedPublisher PD

X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy and Photodynamic Therapy

Conventional photodynamic therapy (PDT)'s clinical application is limited by depth of penetration by light. To address the issue, we have recently developed X-ray induced photodynamic therapy (X-PDT) which utilizes X-ray as an energy source to activate a PDT process. In addition to breaking the shallow tissue penetration dogma, our studies found more efficient tumor cell killing with X-PDT than with radiotherapy (RT) alone. The mechanisms behind the cytotoxicity, however, have not been elucidated. In the present study, we investigate the mechanisms of action of X-PDT on cancer cells. Our results demonstrate that X-PDT is more than just a PDT derivative but is essentially a PDT and RT combination. The two modalities target different cellular components (cell membrane and DNA, respectively), leading to enhanced therapy effects. As a result, X-PDT not only reduces short-term viability of cancer cells but also their clonogenecity in the long-run. From this perspective, X-PDT can also be viewed as a unique radiosensitizing method, and as such it affords clear advantages over RT in tumor therapy, especially for radioresistant cells. This is demonstrated not only in vitro but also in vivo with H1299 tumors that were either subcutaneously inoculated or implanted into the lung of mice. These findings and advances are of great importance to the developments of X-PDT as a novel treatment modality against cancer

Spatial and Temporal Stability of Airglow Measured in the Meinel Band Window at 1191.3 nm

We report on the temporal and spatial fluctuations in the atmospheric brightness in the narrow band between Meinel emission lines at 1191.3 nm using a λ/Δλ = 320 near-infrared instrument. We present the instrument design and implementation, followed by a detailed analysis of data taken over the course of a night from Table Mountain Observatory. At low airmasses, the absolute sky brightness at this wavelength is found to be 5330 ± 30 nW m^(−2) sr^(−1), consistent with previous measurements of the inter-band airglow at these wavelengths. This amplitude is larger than simple models of the continuum component of the airglow emission at these wavelengths, confirming that an extra emissive or scattering component is required to explain the observations. We perform a detailed investigation of the noise properties of the data and find no evidence for a noise component associated with temporal instability in the inter-line continuum. This result demonstrates that in several hours of ~100 s integrations the noise performance of the instrument does not appear to significantly degrade from expectations, giving a proof of concept that near-infrared line intensity mapping may be feasible from ground-based sites

Longitudinal population analysis of dual infection with recombination in two strains of HIV type 1 subtype B in an individual from a phase 3 HIV vaccine efficacy trial

This study documents a case of coinfection (simultaneous infection of an individual with two or more strains) of two HIV-1 subtype B strains in an individual from a Phase 3 HIV-1 vaccine efficacy trial, conducted in North American and the Netherlands. We examined 86 full-length gp120 (env) gene sequences from this individual collected from nine different time points over a 20-month period. We estimated evolutionary relationships using maximum likelihood and Bayesian methods and inferred recombination breakpoints and recombinant sequences using phylogenetic and substitutional methods. These analyses identified two strongly supported monophyletic clades (clades A and B) of 14 and 69 sequences each and a small paraphyletic recombinant clade of three sequences. We then studied the genetic characteristics of these lineages by comparing estimates of genetic diversity generated by mutation and recombination and adaptive selection within a coalescent and maximum likelihood framework. Our results suggest significant differences on the evolutionary dynamics of these strains. We then discuss the implications of these results for vaccine development

Making 'chemical cocktails' - evolution of urban geochemical processes across the periodic table of elements.

Urbanization contributes to the formation of novel elemental combinations and signatures in terrestrial and aquatic watersheds, also known as 'chemical cocktails.' The composition of chemical cocktails evolves across space and time due to: (1) elevated concentrations from anthropogenic sources, (2) accelerated weathering and corrosion of the built environment, (3) increased drainage density and intensification of urban water conveyance systems, and (4) enhanced rates of geochemical transformations due to changes in temperature, ionic strength, pH, and redox potentials. Characterizing chemical cocktails and underlying geochemical processes is necessary for: (1) tracking pollution sources using complex chemical mixtures instead of individual elements or compounds; (2) developing new strategies for co-managing groups of contaminants; (3) identifying proxies for predicting transport of chemical mixtures using continuous sensor data; and (4) determining whether interactive effects of chemical cocktails produce ecosystem-scale impacts greater than the sum of individual chemical stressors. First, we discuss some unique urban geochemical processes which form chemical cocktails, such as urban soil formation, human-accelerated weathering, urban acidification-alkalinization, and freshwater salinization syndrome. Second, we review and synthesize global patterns in concentrations of major ions, carbon and nutrients, and trace elements in urban streams across different world regions and make comparisons with reference conditions. In addition to our global analysis, we highlight examples from some watersheds in the Baltimore-Washington DC region, which show increased transport of major ions, trace metals, and nutrients across streams draining a well-defined land-use gradient. Urbanization increased the concentrations of multiple major and trace elements in streams draining human-dominated watersheds compared to reference conditions. Chemical cocktails of major and trace elements were formed over diurnal cycles coinciding with changes in streamflow, dissolved oxygen, pH, and other variables measured by high-frequency sensors. Some chemical cocktails of major and trace elements were also significantly related to specific conductance (p<0.05), which can be measured by sensors. Concentrations of major and trace elements increased, peaked, or decreased longitudinally along streams as watershed urbanization increased, which is consistent with distinct shifts in chemical mixtures upstream and downstream of other major cities in the world. Our global analysis of urban streams shows that concentrations of multiple elements along the Periodic Table significantly increase when compared with reference conditions. Furthermore, similar biogeochemical patterns and processes can be grouped among distinct mixtures of elements of major ions, dissolved organic matter, nutrients, and trace elements as chemical cocktails. Chemical cocktails form in urban waters over diurnal cycles, decades, and throughout drainage basins. We conclude our global review and synthesis by proposing strategies for monitoring and managing chemical cocktails using source control, ecosystem restoration, and green infrastructure. We discuss future research directions applying the watershed chemical cocktail approach to diagnose and manage environmental problems. Ultimately, a chemical cocktail approach targeting sources, transport, and transformations of different and distinct elemental combinations is necessary to more holistically monitor and manage the emerging impacts of chemical mixtures in the world's fresh waters

The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis

Objective: The Surviving Sepsis Campaign (SSC or “the Campaign”) developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations on process improvement and patient outcomes. Design and setting: A multifaceted intervention to facilitate compliance with selected guideline recommendations in the ICU, ED, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the US, Europe, and South America. Elements of the guidelines were “bundled” into two sets of targets to be completed within 6 h and within 24 h. An analysis was conducted on data submitted from January 2005 through March 2008. Main results: Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 years (P < 0.0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 years (P = 0.008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37 to 30.8% over 2 years (P = 0.001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 years (95% CI, 2.5–8.4%). Conclusions: The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts.Electronic supplementary material The online version of this article (doi:10.1007/s00134-009-1738-3) contains supplementary material, which is available to authorized users

Clinical Trial Protocol for PRIMARY2: A Multicentre, Phase 3, Randomised Controlled Trial Investigating the Additive Diagnostic Value of [68Ga]Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Negative or Equivocal Multiparametric Magnetic Resonance Imaging for the Diagnosis of Clinically Significant Prostate Cancer

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa). The PRIMARY trial demonstrated that [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) was associated with a significant improvement in sensitivity and negative predictive value for sPCa detection. OBJECTIVE: To demonstrate that addition of prostate-specific membrane antigen (PSMA) radioligand PET/CT will enable some men to avoid transperineal prostate biopsy without missing sPCa, and will facilitate biopsy targeting of PSMA-avid sites. DESIGN, SETTING, AND PARTICIPANTS: This multicentre, two-arm, phase 3, randomised controlled trial will recruit 660 participants scheduled to undergo biopsy. Eligible participants will have clinical suspicion of sPCa with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2 and red flags, or a PI-RADS score of 3 on mpMRI (PI-RADS v2). Participants will be randomised at a 1:1 ratio in permuted blocks stratified by centre. The trial is registered on ClinicalTrials.gov as NCT05154162. INTERVENTION: In the experimental arm, participants will undergo pelvic PSMA PET/CT. Local and central reviewers will interpret scans independently using the PRIMARY score. Participants with a positive result will undergo targeted transperineal prostate biopsies, whereas those with a negative result will undergo prostate-specific antigen monitoring alone. In the control arm, all participants undergo template transperineal prostate biopsies. Participants will be followed for subsequent clinical care for up to 2 yr after randomisation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: sPCa is defined as Gleason score 3 + 4 (≥10%) = 7 disease (grade group 2) or higher on transperineal prostate biopsy. Avoidance of transperineal prostate biopsy will be measured at 6 mo from randomisation. The primary endpoints will be analysed on an intention-to-treat basis. CONCLUSIONS: Patient enrolment began in March 2022, with recruitment expected to take 36 mo. PATIENT SUMMARY: For patients with suspected prostate cancer who have nonsuspicious or unclear MRI (magnetic resonance imaging) scan findings, a different type of scan (called PSMA PET/CT; prostate-specific membrane antigen positron emission tomography/computed tomography) may identify men who could avoid an invasive prostate biopsy. This type of scan could also help urologists in better targeting of samples from suspicious lesions during prostate biopsies

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment