Abstract: The present invention discloses a method for determining improved radiation gene expression profiles by sequential application of sensitive and specific gene signatures. The method involves evaluating a sample of target cells from a patient against a highly sensitive, first radiation gene signature, to determine the radiation exposed gene signature. If the signature does not completely distinguish radiation exposures from other conditions or phenotypes, the sample may be evaluated against a second radiation gene signature, which is a radiation gene signature with high specificity. On sequential application of sensitive and specific gene signatures, any misclassified unirradiated samples remaining in the determined gene signatures are identified and removed. Thus, the method enables rejection of radiation signatures with high false positive radiation diagnosis in conditions that confound the results with the first signature.

Abstract: Automation of microscopic pathological diagnosis relies on digital image quality, which, in turn, affects the rates of false positive and negative cellular objects designated as abnormalities. Cytogenetic biodosimetry is a genotoxic assay that detects dicentric chromosomes (DCs) arising from exposure to ionizing radiation. The frequency of DCs is related to radiation dose received, so the inferred radiation dose depends on the accuracy of DC detection. To improve this accuracy, image segmentation methods are used to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data in a sample based on novel quality measures. When sufficient numbers of high quality images are found, the microscope system is directed to terminate metaphase image collection for a sample. The International Atomic Energy Agency recommends at least 500 images be used to estimate radiation dose, however often many more images are collected in order to select the metaphase cells with good morphology for analysis.

Abstract: Automation of microscopic pathological diagnosis relies on digital image quality, which, in turn, affects the rates of false positive and negative cellular objects designated as abnormalities. Cytogenetic biodosimetry is a genotoxic assay that detects dicentric chromosomes (DCs) arising from exposure to ionizing radiation. The frequency of DCs is related to radiation dose received, so the inferred radiation dose depends on the accuracy of DC detection. To improve this accuracy, image segmentation methods are used to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data in a sample based on novel quality measures. When sufficient numbers of high quality images are found, the microscope system is directed to terminate metaphase image collection for a sample. The International Atomic Energy Agency recommends at least 500 images be used to estimate radiation dose, however often many more images are collected in order to select the metaphase cells with good morphology for analysis.

Abstract: The present invention discloses a method for identifying and quantifying populations exposed to environmental hazards across a geographic region. The environmental hazards include radiation, pollution and communicable infectious agent hotspots, such as locations of COVID-19 hotspots. The method of the present invention uses geographic distributions of infected individuals over time to develop robust methods that pinpoint locations of emerging COVID-19 hotspots. The method assays a fraction of infected individuals of a local population and adjacent locations of the infected individuals and detects spatial asymmetries and clustered distributions of infected individuals. The spatial resolution of the assay is increased by assigning infected cases in each county to subdivisions weighted by population census and performing spatial interpolation to pinpoint potential local clusters of infected individuals.

Abstract: An automated microscope system is described that detects dicentric chromosomes (DCs) in metaphase cells arising from exposure to ionizing radiation. The radiation dose depends on the accuracy of DC detection. Accuracy is increased using image segmentation methods are used to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data in a sample based on novel quality measures. When a sufficient number of high quality images are detected, the microscope system is directed to terminate metaphase image collection for a sample. The microscope system integrates image selection procedures that control an automated digitally controlled microscope with the analysis of acquired metaphase cell images to accurately determine radiation dose. Early termination of image acquisition reduces sample processing time without compromising accuracy. This approach constitutes a reliable and scalable solution that will be essential for analysis of large numbers of potentially exposed individuals.

Abstract: An automated microscope system is described that detects dicentric chromosomes (DCs) in metaphase cells arising from exposure to ionizing radiation. The radiation dose depends on the accuracy of DC detection. Accuracy is increased using image segmentation methods are used to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data in a sample based on novel quality measures. When a sufficient number of high quality images are detected, the microscope system is directed to terminate metaphase image collection for a sample. The microscope system integrates image selection procedures that control an automated digitally controlled microscope with the analysis of acquired metaphase cell images to accurately determine radiation dose. Early termination of image acquisition reduces sample processing time without compromising accuracy. This approach constitutes a reliable and scalable solution that will be essential for analysis of large numbers of potentially exposed individuals.

Abstract: A method is described for the automatic validation of DNA sequencing variants that alter mRNA splicing from nucleic acids isolated from a patient or tissue sample. Evidence of a predicted splicing mutation is demonstrated by performing statistically valid comparisons between sequence read counts of abnormal RNA species in mutant versus non-mutant tissues. The method leverages large numbers of control samples to corroborate the consequences of predicted splicing variants in complete genomes and exomes for individuals carrying such mutations. Because the method examines all transcript evidence in a genome, it is not necessary a priori to know which gene or genes carry a splicing mutation.

Abstract: Mutations that affect mRNA splicing often produce multiple mRNA isoforms containing different exon structures. Definition of an exon and its inclusion in mature mRNA relies on joint recognition of both acceptor and donor splice sites. The instant methodology predicts cryptic and exon skipping isoforms in mRNA produced by splicing mutations from the combined information contents and the distribution of the splice sites and other regulatory binding sites defining these exons. In its simplest form, the total information content of an exon, Ri,total, is the sum of the information contents of its corresponding acceptor and donor splice sites, adjusted for the self-information of the exon length. Differences between Ri,total values of mutant versus normal exons that are concordant with gene expression data demonstrate alterations in the structures and relative abundance of the mRNA transcripts resulting from these mutations.

Abstract: The invention relates to a process and apparatus that treats waste water, in particular waste water containing surfactants and including grey water, for local reuse. According to the invention, the process comprises a) collecting waste water in a reservoir; b) injecting gas into waste water from the reservoir to form bubbles in the waste water; c) separating the bubbles, and any entrained contaminants, from the waste water; d) drying the separated bubbles and returning any water recovered from the dried bubbles to the waste water undergoing treatment; e) optionally repeating steps b) to d) to achieve the desired purification of the waste water; and f) collecting the purified waste water. The invention provides a robust process and a mechanically simple apparatus that does not require regular replacement of chemicals or filters, yet is capable of treating waste water locally, and in particular grey water for household reuse.

Abstract: A method for determining genes in breast cancer that are stable in copy number, expression and sequence in tumors from nearly all patients. Certain stable genes are targets of standard chemotherapy. The effectiveness of therapies that act upon these targets depends on maintaining the stability and integrity of these genes in tumors. Mutations in these targets result in poor response to therapies that target these gene products. In the instant invention, ordinarily stable gene targets are characterized as either normal or mutant for the purpose of determining whether to include or exclude particular drugs as potential treatments.

Abstract: The various aspects of the invention pertain to devices and related methods for treating heart conditions, including, for example, dilatation, valve incompetencies, including mitral valve leakage, and other similar heart failure conditions. The devices and related methods of the present invention operate to assist in the apposition of heart valve leaflets to improve valve function. According to one aspect of the invention, a method improves the function of a valve of a heart by placing an elongate member transverse a heart chamber so that each end of the elongate member extends through a wall of the heart, and placing first and second anchoring members external the chamber. The first and second anchoring members are attached to first and second ends of the elongate member to fix the elongate member in a position across the chamber so as to reposition papillary muscles within the chamber.

Abstract: Embodiments relate to implantable devices for the treatment of syndesmosis injuries. Embodiments include a first anchor attachable to a first bone, the first anchor being coupled to a flexible component, the flexible component in turn being coupled to a base component. The base component may be rigid, and may be externally threaded for engaging with a second anchor. Position of the second anchor may be adjusted by rotating the second anchor with respect to the base component, thereby adjusting relative position of the two bones. An assembly may be created in which an outer tube contains the flexible component and the base component inside the outer tube, and at its distal end the outer tube may engage the first anchor so as to allow transmission of torque. The outer tube may be withdrawn proximally after implantation of the first anchor. The bones may be a tibia and a fibula.

Abstract: A method is described for the automatic validation of DNA sequencing variants that alter mRNA splicing from nucleic acids isolated from a patient or tissue sample. Evidence the a predicted splicing mutation is demonstrated by performing statistically valid comparisons between sequence read counts of abnormal RNA species in mutant versus non-mutant tissues. The method leverages large numbers of control samples to corroborate the consequences of predicted splicing variants in complete genomes and exomes for individuals carrying such mutations. Because the method examines all transcript evidence in a genome, it is not necessary a priori to know which gene or genes carry a splicing mutation.

Abstract: A method for determining genes in breast cancer that are stable in copy number, expression and sequence in tumors from nearly all patients. Certain stable genes are targets of standard chemotherapy. The effectiveness of therapies that act upon these targets depends on maintaining the stability and integrity of these genes in tumors. Mutations in these targets result in poor response to therapies that target these gene products. In the instant invention, ordinarily stable gene targets are characterized as either normal or mutant for the purpose of determining whether to include or exclude particular drugs as potential treatments.

Abstract: Mutations that affect mRNA splicing often produce multiple mRNA isoforms containing different exon structures. Definition of an exon and its inclusion in mature mRNA relies on joint recognition of both acceptor and donor splice sites. The instant methodology predicts cryptic and exon skipping isoforms in mRNA produced by splicing mutations from the combined information contents and the distribution of the splice sites and other regulatory binding sites defining these exons. In its simplest form, the total information content of an exon, Ri,total, is the sum of the information contents of its corresponding acceptor and donor splice sites, adjusted for the self-information of the exon length. Differences between Ri,total values of mutant versus normal exons are consistent with the relative abundance of these exons in distinct processed mRNAs.

Abstract: Devices and methods that mitigate reperfusion injury (RI) in a clinically practical manner so as to avoid significantly increasing time to reperfusion. In general, these systems and methods involve an antegrade approach to deliver a fluid to the myocardium at risk of RI before, during and after reperfusion is established by a percutaneous coronary intervention such as aspiration and stenting.

Abstract: A method for determining radiation exposure from chromosome abnormalities present in a specimen by determining the location or locations of the centromere of each chromosome in a cell in an image of a metaphase cell by segmentation of an accurately drawn chromosome centerline followed by selection of a longitudinal cross-section with the minimum width or intensity or width and intensity; counting the number of centromeres in each chromosome in each cell; computing the frequency of dicentric chromosomes in a population of cells; and determining the radiation dose by comparing the computed frequency of dicentric chromosomes with a previously determined dose-response curve from a calibrated source.

Abstract: The invention relates to a process and apparatus that treats waste water, in particular waste water containing surfactants and including grey water, for local reuse. According to the invention, the process comprises a) collecting waste water in a reservoir; b) injecting gas into waste water from the reservoir to form bubbles in the waste water; c) separating the bubbles, and any entrained contaminants, from the waste water; d) drying the separated bubbles and returning any water recovered from the dried bubbles to the waste water undergoing treatment; e) optionally repeating steps b) to d) to achieve the desired purification of the waste water; and f) collecting the purified waste water.

Abstract: A method for determining radiation exposure from chromosome abnormalities present in a specimen by determining the location or locations of the centromere of each chromosome in a cell in an image of a metaphase cell by segmentation of an accurately drawn chromosome centerline followed by selection of a longitudinal cross-section with the minimum width or intensity or width and intensity; counting the number of centromeres in each chromosome in each cell; computing the frequency of dicentric chromosomes in a population of cells; and determining the radiation dose by comparing the computed frequency of dicentric chromosomes with a previously determined dose-response curve from a calibrated source.

Abstract: Baroreflex activation is achieved by providing suitable control signals to a baroreflex activation device. A method comprises establishing a therapy interval within the therapy interval, establishing a plurality of dose intervals, and generating an electrical output signal. The electrical output signal has a time dependence such that the average electrical power applied to the baroreflex activation device differs between first and second portions of at least some dose intervals. Another method comprises establishing a series of therapy interval portions, during at least some therapy intervals, establishing a plurality of burst intervals, and generating an electrical output signal. The electrical output signal has a time dependence such that the average electrical power applied to the baroreflex activation device differs between first and second portions of the therapy intervals and also differs between first and second portions of at least some burst intervals.