node2vec2rank: Large Scale and Stable Graph Differential Analysis via Multi-Layer Node Embeddings and Ranking.

Computational methods in biology can infer large molecular interaction networks from multiple data sources and at different resolutions, creating unprecedented opportunities to explore the mechanisms driving complex biological phenomena. Networks can be built to represent distinct conditions and compared to uncover graph-level differences-such as when comparing patterns of gene-gene interactions that change between biological states. Given the importance of the graph comparison problem, there is a clear and growing need for robust and scalable methods that can identify meaningful differences. We introduce node2vec2rank (n2v2r), a method for graph differential analysis that ranks nodes according to the disparities of their representations in joint latent embedding spaces. Improving upon previous bag-of-features approaches, we take advantage of recent advances in machine learning and statistics to compare graphs in higher-order structures and in a data-driven manner. Formulated as a multi-layer spectral embedding algorithm, n2v2r is computationally efficient, incorporates stability as a key feature, and can provably identify the correct ranking of differences between graphs in an overall procedure that adheres to veridical data science principles. By better adapting to the data, node2vec2rank clearly outperformed the commonly used node degree in finding complex differences in simulated data. In the real-world applications of breast cancer subtype characterization, analysis of cell cycle in single-cell data, and searching for sex differences in lung adenocarcinoma, node2vec2rank found meaningful biological differences enabling the hypothesis generation for therapeutic candidates. Software and analysis pipelines implementing n2v2r and used for the analyses presented here are publicly available.

Improving reporting of meta-ethnography: the eMERGe reporting guidance.

AIMS: The aim of this study was to provide guidance to improve the completeness and clarity of meta-ethnography reporting. BACKGROUND: Evidence-based policy and practice require robust evidence syntheses which can further understanding of people's experiences and associated social processes. Meta-ethnography is a rigorous seven-phase qualitative evidence synthesis methodology, developed by Noblit and Hare. Meta-ethnography is used widely in health research, but reporting is often poor quality and this discourages trust in and use of its findings. Meta-ethnography reporting guidance is needed to improve reporting quality. DESIGN: The eMERGe study used a rigorous mixed-methods design and evidence-based methods to develop the novel reporting guidance and explanatory notes. METHODS: The study, conducted from 2015 to 2017, comprised of: (1) a methodological systematic review of guidance for meta-ethnography conduct and reporting; (2) a review and audit of published meta-ethnographies to identify good practice principles; (3) international, multidisciplinary consensus-building processes to agree guidance content; (4) innovative development of the guidance and explanatory notes. FINDINGS: Recommendations and good practice for all seven phases of meta-ethnography conduct and reporting were newly identified leading to 19 reporting criteria and accompanying detailed guidance. CONCLUSION: The bespoke eMERGe Reporting Guidance, which incorporates new methodological developments and advances the methodology, can help researchers to report the important aspects of meta-ethnography. Use of the guidance should raise reporting quality. Better reporting could make assessments of confidence in the findings more robust and increase use of meta-ethnography outputs to improve practice, policy, and service user outcomes in health and other fields. This is the first tailored reporting guideline for meta-ethnography. This article is being simultaneously published in the following journals: Journal of Advanced Nursing, Psycho-oncology, Review of Education, and BMC Medical Research Methodology.

Improving reporting of meta-ethnography: The eMERGe reporting guidance.

AIMS: The aim of this study was to provide guidance to improve the completeness and clarity of meta-ethnography reporting. BACKGROUND: Evidence-based policy and practice require robust evidence syntheses which can further understanding of people's experiences and associated social processes. Meta-ethnography is a rigorous seven-phase qualitative evidence synthesis methodology, developed by Noblit and Hare. Meta-ethnography is used widely in health research, but reporting is often poor quality and this discourages trust in and use of its findings. Meta-ethnography reporting guidance is needed to improve reporting quality. DESIGN: The eMERGe study used a rigorous mixed-methods design and evidence-based methods to develop the novel reporting guidance and explanatory notes. METHODS: The study, conducted from 2015 - 2017, comprised of: (1) a methodological systematic review of guidance for meta-ethnography conduct and reporting; (2) a review and audit of published meta-ethnographies to identify good practice principles; (3) international, multidisciplinary consensus-building processes to agree guidance content; (4) innovative development of the guidance and explanatory notes. FINDINGS: Recommendations and good practice for all seven phases of meta-ethnography conduct and reporting were newly identified leading to 19 reporting criteria and accompanying detailed guidance. CONCLUSION: The bespoke eMERGe Reporting Guidance, which incorporates new methodological developments and advances the methodology, can help researchers to report the important aspects of meta-ethnography. Use of the guidance should raise reporting quality. Better reporting could make assessments of confidence in the findings more robust and increase use of meta-ethnography outputs to improve practice, policy, and service user outcomes in health and other fields. This is the first tailored reporting guideline for meta-ethnography. This article is being simultaneously published in the following journals: Journal of Advanced Nursing, Psycho-oncology, Review of Education, and BMC Medical Research Methodology.

Improving reporting of meta-ethnography: The eMERGe reporting guidance.

AIMS: The aim of this study was to provide guidance to improve the completeness and clarity of meta-ethnography reporting. BACKGROUND: Evidence-based policy and practice require robust evidence syntheses which can further understanding of people's experiences and associated social processes. Meta-ethnography is a rigorous seven-phase qualitative evidence synthesis methodology, developed by Noblit and Hare. Meta-ethnography is used widely in health research, but reporting is often poor quality and this discourages trust in and use of its findings. Meta-ethnography reporting guidance is needed to improve reporting quality. DESIGN: The eMERGe study used a rigorous mixed-methods design and evidence-based methods to develop the novel reporting guidance and explanatory notes. METHODS: The study, conducted from 2015 to 2017, comprised of: (1) a methodological systematic review of guidance for meta-ethnography conduct and reporting; (2) a review and audit of published meta-ethnographies to identify good practice principles; (3) international, multidisciplinary consensus-building processes to agree guidance content; (4) innovative development of the guidance and explanatory notes. FINDINGS: Recommendations and good practice for all seven phases of meta-ethnography conduct and reporting were newly identified leading to 19 reporting criteria and accompanying detailed guidance. CONCLUSION: The bespoke eMERGe Reporting Guidance, which incorporates new methodological developments and advances the methodology, can help researchers to report the important aspects of meta-ethnography. Use of the guidance should raise reporting quality. Better reporting could make assessments of confidence in the findings more robust and increase use of meta-ethnography outputs to improve practice, policy, and service user outcomes in health and other fields. This is the first tailored reporting guideline for meta-ethnography. This article is being simultaneously published in the following journals: Journal of Advanced Nursing, Psycho-oncology, Review of Education, and BMC Medical Research Methodology.

Using a 2D detector array for meaningful and efficient linear accelerator beam property validations.

Following linear accelerator commissioning, the qualified medical physicist is responsible for monitoring the machine's ongoing performance, detecting and investigating any changes in beam properties, and assessing the impact of unscheduled repairs. In support of these responsibilities, the authors developed a method of using a 2D ionization chamber array to efficiently test and validate important linear accelerator photon beam properties. A team of three physicists identified critical properties of the accelerator and developed constancy tests that were sensitive to each of the properties. The result was a 14-field test plan. The test plan includes large and small fields at varying depths, a reduced SSD field at shallow depth for sensitivity to extra focal photon and electron components, and analysis of flatness, symmetry, dose, dose profiles, and dose ratios. Constancy tests were repeated five times over a period of six weeks and used to set upper and lower investigation levels at ± 3 SDs. Deliberate variations in output, penumbra, and energy were tested to determine the suitability of the proposed method. Measurements were also performed on a similar, but distinct, machine to assess test sensitivity. The results demonstrated upper and lower investigation levels significantly smaller than the comparable TG-142 annual recommendations, with the exception of the surrogate used for output calibration, which still fell within the TG-142 monthly recommendation. Subtle changes in output, beam energy, and penumbra were swiftly identified for further investigation. The test set identified the distinct nature of the second accelerator. The beam properties of two photon energies can be validated in approximately 1.5 hrs using this method. The test suite can be used to evaluate the impact of minor repairs, detect changes in machine performance over time, and supplement other machine quality assurance testing.

A measurement technique to determine the calibration accuracy of an electromagnetic tracking system to radiation isocenter.

PURPOSE: To present and characterize a measurement technique to quantify the calibration accuracy of an electromagnetic tracking system to radiation isocenter. METHODS: This technique was developed as a quality assurance method for electromagnetic tracking systems used in a multi-institutional clinical hypofractionated prostate study. In this technique, the electromagnetic tracking system is calibrated to isocenter with the manufacturers recommended technique, using laser-based alignment. A test patient is created with a transponder at isocenter whose position is measured electromagnetically. Four portal images of the transponder are taken with collimator rotations of 45° 135°, 225°, and 315°, at each of four gantry angles (0°, 90°, 180°, 270°) using a 3×6 cm2 radiation field. In each image, the center of the copper-wrapped iron core of the transponder is determined. All measurements are made relative to this transponder position to remove gantry and imager sag effects. For each of the 16 images, the 50% collimation edges are identified and used to find a ray representing the rotational axis of each collimation edge. The 16 collimator rotation rays from four gantry angles pass through and bound the radiation isocenter volume. The center of the bounded region, relative to the transponder, is calculated and then transformed to tracking system coordinates using the transponder position, allowing the tracking system's calibration offset from radiation isocenter to be found. All image analysis and calculations are automated with inhouse software for user-independent accuracy. Three different tracking systems at two different sites were evaluated for this study. RESULTS: The magnitude of the calibration offset was always less than the manufacturer's stated accuracy of 0.2 cm using their standard clinical calibration procedure, and ranged from 0.014 to 0.175 cm. On three systems in clinical use, the magnitude of the offset was found to be 0.053±0.036, 0.121±0.023, and 0.093±0.013 cm. CONCLUSIONS: The method presented here provides an independent technique to verify the calibration of an electromagnetic tracking system to radiation isocenter. The calibration accuracy of the system was better than the 0.2 cm accuracy stated by the manufacturer. However, it should not be assumed to be zero, especially for stereotactic radiation therapy treatments where planning target volume margins are very small.

Dosimetric impact of density variations in Solid Water 457 water-equivalent slabs.

The purpose of this study was to determine the dosimetric impact of density variations observed in water-equivalent solid slabs. Measurements were performed using two 30 cm × 30 cm water-equivalent slabs, one being 4 cm think and the other 5 cm thick. The location and extent of density variations were determined by computed tomography (CT) scans. Additional imaging measurements were made with an amorphous silicon megavoltage portal imaging device and an ultrasound unit. Dosimetric measurements were conducted with a 2D ion chamber array, and a scanned diode in water. Additional measurements and calculations were made of small rectilinear void inhomogeneities formed with water-equivalent slabs, using a 2D ion chamber array and the convolution superposition algorithm. Two general types of density variation features were observed on CT images: 1) regions of many centimeters across, but typically only a few millimeters thick, with electron densities a few percent lower than the bulk material, and 2) cylindrical regions roughly 0.2 cm in diameter and up to 20 cm long with electron densities up to 5% lower than the surrounding material. The density variations were not visible on kilovoltage, megavoltage or ultrasound images. The dosimetric impact of the density variations were not detectable to within 0.1% using the 2D ion chamber array or the scanning photon diode at distances 0.4 cm to 2 cm beyond the features. High-resolution dosimetric calculations using the convolution-superposition algorithm with density corrections enabled on CT-based datasets showed no discernable dosimetric impact. Calculations and measurements on simulated voids place the upper limit on possible dosimetric variations from observed density variations at much less than 0.6%. CT imaging of water-equivalent slabs may reveal density variations which are otherwise unobserved with kV, MV, or ultrasound imaging. No dosimetric impact from these features was measureable with an ion chamber array or scanned photon diode. Consequently, they were determined to be acceptable for all clinical use.