Large-scale meta-genome-wide association study reveals common genetic factors linked to radiation-induced acute toxicities across cancer types.

Background: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity across 4 cancer types (prostate, head and neck, breast, and lung).

Methods: A genome-wide association study meta-analysis was performed using 19 cohorts totaling 12 042 patients. Acute standardized total average toxicity (STATacute) was modelled using a generalized linear regression model for additive effect of genetic variants, adjusted for demographic and clinical covariates (rSTATacute).

Genome-wide association study of treatment-related toxicity two years following radiotherapy for breast cancer.

Background And Purpose: Up to a quarter of breast cancer patients treated by surgery and radiotherapy experience clinically significant toxicity. If patients at high risk of adverse effects could be identified at diagnosis, their treatment could be tailored accordingly. This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity two years following whole breast radiotherapy.

Penalized least-squares for imaging with hypertelescopes.

Practical considerations such as cost constrain the aperture size of conventional telescopes, which, combined with atmospheric turbulence effects, even in the presence of adaptive optics, limit achievable angular resolution. Sparse aperture telescopes represent a viable alternative for achieving improved angular resolution by combining light collected from small apertures distributed over a wide spatial area either using amplitude interferometry or a direct imaging approach to beam-combining. The so-called densified hypertelescope imaging concept in particular provides a methodology for direct image formation from large sparse aperture arrays.

Treatment time and circadian genotype interact to influence radiotherapy side-effects. A prospective European validation study using the REQUITE cohort.

Background: Circadian rhythm impacts broad biological processes, including response to cancer treatment. Evidence conflicts on whether treatment time affects risk of radiotherapy side-effects, likely because of differing time analyses and target tissues. We previously showed interactive effects of time and genotypes of circadian genes on late toxicity after breast radiotherapy and aimed to validate those results in a multi-centre cohort.

Atmospheric turbulence characterization through multiframe blind deconvolution.

Characterization of turbulence in the atmosphere and mitigation of its effects in optical systems are important capabilities in both commercial and military applications. We present an image processing approach that jointly characterizes the magnitude of turbulence in the atmosphere and mitigates the adverse effects imposed on optical imaging systems. The magnitude of turbulence is measured indirectly through a series of image frames in terms of the atmospheric coherence length.

External Validation of a Predictive Model for Acute Skin Radiation Toxicity in the REQUITE Breast Cohort.

Acute skin toxicity is a common and usually transient side-effect of breast radiotherapy although, if sufficiently severe, it can affect breast cosmesis, aftercare costs and the patient's quality-of-life. The aim of this study was to develop predictive models for acute skin toxicity using published risk factors and externally validate the models in patients recruited into the prospective multi-center REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve QUalITy of lifE in cancer survivors) study. Patient and treatment-related risk factors significantly associated with acute breast radiation toxicity on multivariate analysis were identified in the literature.

The sputum microbiome is distinct between COPD and health, independent of smoking history.

Background: Airway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD). However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD.

Methods: We compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium.

Target Localization and Tracking by Fusing Doppler Differentials from Cellular Emanations with a Multi-Spectral Video Tracker.

We present an algorithm for fusing data from a constellation of RF sensors detecting cellular emanations with the output of a multi-spectral video tracker to localize and track a target with a specific cell phone. The RF sensors measure the Doppler shift caused by the moving cellular emanation and then Doppler differentials between all sensor pairs are calculated. The multi-spectral video tracker uses a Gaussian mixture model to detect foreground targets and SIFT features to track targets through the video sequence.

Sputum microbiome temporal variability and dysbiosis in chronic obstructive pulmonary disease exacerbations: an analysis of the COPDMAP study.

Background: Recent studies suggest that lung microbiome dysbiosis, the disease associated disruption of the lung microbial community, might play a key role in chronic obstructive pulmonary disease (COPD) exacerbations. However, characterising temporal variability of the microbiome from large longitudinal COPD cohorts is needed to better understand this phenomenon.

Methods: We performed a 16S ribosomal RNA survey of microbiome on 716 sputum samples collected longitudinally at baseline and exacerbations from 281 subjects with COPD at three UK clinical centres as part of the COPDMAP consortium.

Blood and sputum eosinophils in COPD; relationship with bacterial load.

Background: Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients. Bacterial infection causes increased airway neutrophilic inflammation. The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain.

An informatics project and online "Knowledge Centre" supporting modern genotype-to-phenotype research.

Explosive growth in the generation of genotype-to-phenotype (G2P) data necessitates a concerted effort to tackle the logistical and informatics challenges this presents. The GEN2PHEN Project represents one such effort, with a broad strategy of uniting disparate G2P resources into a hybrid centralized-federated network. This is achieved through a holistic strategy focussed on three overlapping areas: data input standards and pipelines through which to submit and collect data (data in); federated, independent, extendable, yet interoperable database platforms on which to store and curate widely diverse datasets (data storage); and data formats and mechanisms with which to exchange, combine, and extract data (data exchange and output).

Locus-specific database domain and data content analysis: evolution and content maturation toward clinical use.

Genetic variation databases have become indispensable in many areas of health care. In addition, more and more experts are depositing published and unpublished disease-causing variants of particular genes into locus-specific databases (LSDBs). Some of these databases contain such extensive information that they have become known as knowledge bases.

Sperm cross-over activity in regions of the human genome showing extreme breakdown of marker association.

Population diversity data have recently provided profound, albeit inferential, insights into meiotic recombination across the human genome, revealing a landscape dominated by thousands of cross-over hotspots. However, very few of these putative hotspots have been directly analyzed for cross-over activity. We now describe a search for very active hotspots, by using extreme breakdown of marker association as a guide for high-resolution sperm cross-over analysis.

Meiotic recombination hot spots and human DNA diversity.

Meiotic recombination plays a key role in the maintenance of sequence diversity in the human genome. However, little is known about the fine-scale distribution and processes of recombination in human chromosomes, or how these impact on patterns of human diversity. We have therefore developed sperm typing systems that allow human recombination to be analysed at very high resolution.