90 research outputs found
Patients' Choices for Return of Exome Sequencing Results to Relatives in the Event of Their Death
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116009/1/jlme12290.pd
Temporal lobe (TL) damage following surgery and high-dose photon and proton irradiation in 96 patients affected by chordomas and chondrosarcomas of the base of the skull
Purpose: To determine the temporal lobe (TL) damage rate in 96 patients treated with high-dose proton and photon irradiation for chordomas and chondrosarcomas of the base of the skull. Methods and Materials: The records of 96 consecutive patients treated at Massachusetts General Hospital (MGH) and Harvard Cyclotron Laboratory (HCL) between June 1984 and 1993, for chordomas and chondrosarcomas of the base of the skull were reviewed. All the patients had undergone some degree of resection of the tumor prior to radiation therapy. Seventy-five patients were classified as 'primary tumors' and 21 as recurrent or regrowing tumors after one or more surgical procedures. All the patients were randomized to receive 66.6 or 72 cobalt Gray equivalent (CGE) on a prospective dose-searching study by proton and photon irradiation (Radiation Therapy Oncology Group No.85-26) with conventional fractionation (1.8 CGE/day, 5 fractions/week). All treatments were planned using the three-dimensional (3D) planning system developed at the Massachusetts General Hospital, and the dose was delivered using opposed lateral fields for the photon component and a noncoplanar isocentric technique for the proton component. Clinical symptoms of TL damage were classified into 4 grades. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated for white matter changes. Abnormalities associated with persistent or recurrent tumor were distinguished from radiation-induced changes. TLs were delineated on the original scans of the 10 patients with damage and those of a group of 33 patients with no clinical or MRI evidence of injury. Dose distributions were calculated and dose- volume histograms were obtained for these patients. Results: Of the patients, 10 developed TL damage, with bilateral injury in 2 and unilateral injury in 8. The cumulative TL damage incidence at 2 and 5 years was 7.6 and 13.2%, respectively. The MRI areas suggestive of TL damage were always separated from the tumor bed. Symptoms were severe to moderate in 8 patients. Several baseline factors, tumor- or host-related, were analyzed to evaluate their predictivity for TL damage: age, gender, tumor site, histology, type of presentation, type and number of surgical procedures, primary tumor volume, prescribed dose, normal tissue involvement, and volume of TL receiving doses ranging between 10 and 50 CGE or more. Only gender, in a univariate analysis (log rank) was a significant predictor of damage (0.0155), with male patients being at significantly higher risk of TL injury. In a stepwise Cox regression that included gender as a variable, no other baseline variable improved the prediction of damage. Conclusions: The 2- and 5-year cumulative TL damage rates were 7.6 and 13.2%, respectively. Despite the different TL damage rates related to age, tumor volume, number of surgical procedures prior to radiation therapy, and prescribed doses to the tumor, only gender was a significant predictor of damage (p = 0.0155) using a univariate (log rank) test. Chordomas and chondrosarcomas of the base of the skull may represent an interesting model to evaluate the TL damage rates because of their extradural origin, displacing the white matter instead of infiltrating it as gliomas do, because of their longer local recurrence-free survival other than gliomas and other brain tumors and because of the high doses of irradiation delivered to the target volume to obtain local control
Direct measurement of antiferromagnetic domain fluctuations
Measurements of magnetic noise emanating from ferromagnets due to domain
motion were first carried out nearly 100 years ago and have underpinned much
science and technology. Antiferromagnets, which carry no net external magnetic
dipole moment, yet have a periodic arrangement of the electron spins extending
over macroscopic distances, should also display magnetic noise, but this must
be sampled at spatial wavelengths of order several interatomic spacings, rather
than the macroscopic scales characteristic of ferromagnets. Here we present the
first direct measurement of the fluctuations in the nanometre-scale spin-
(charge-) density wave superstructure associated with antiferromagnetism in
elemental Chromium. The technique used is X-ray Photon Correlation
Spectroscopy, where coherent x-ray diffraction produces a speckle pattern that
serves as a "fingerprint" of a particular magnetic domain configuration. The
temporal evolution of the patterns corresponds to domain walls advancing and
retreating over micron distances. While the domain wall motion is thermally
activated at temperatures above 100K, it is not so at lower temperatures, and
indeed has a rate which saturates at a finite value - consistent with quantum
fluctuations - on cooling below 40K. Our work is important because it provides
an important new measurement tool for antiferromagnetic domain engineering as
well as revealing a fundamental new fact about spin dynamics in the simplest
antiferromagnet.Comment: 19 pages, 4 figure
Index Construction for Multiple Objective Analysis of Land and Water Use in a High Mountain Watershed
Comprehensive planning is an elusive ideal. The practical planner must sort the relevant information from the vast amounts of data that modern technology can collect. The objective of this study was to use the Upper Blackfoot watershed in the mountains of Southeastern Idaho as an arena for developing methods for construction, refinement, and application of indices needed to design land and water management schemes, compare alternatives, and influence the public in their uses of the area. A total of 21 uses were examined on 242 land units of a 160 square-mile area ranging in elevation from 6300 to 9000 feet and where the principal activities of grazing, lumbering, mining, and recreation can only be undertaken in the summer after the snow has melted. The indices considered were a reasonability index for screening out unreasonable uses at the start of the planning process, an index of use intensity for estimating an amount for reasonable uses, and an index for estimating the utility of the amount of use made from the public viewpoint. Data were collected on 42 attributes for the 343 land units and used in a linear programming model to maximize 1) economic benefits from use of the area and 2) minimize environmental disturbance. The resolution in the available use data limited the model solution to allocating uses among 18 larger land units. The primary factor limiting the modeling, however, was the lack of information for defining the interactions among the uses. The analysis provides a framework for classifying and identifying interactions beginning with the simplest case of simultaneous use by two uses in near proximity. The contribution of the study was a framework for analysis and the identification of the needs for research on the physical interactions among simultaneous uses, the perceived interactions of simultaneous users, and characterization of attributes for defining the quality of an area for a use
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Clinical Genetics Lacks Standard Definitions and Protocols for the Collection and Use of Diversity Measures
Genetics researchers and clinical professionals rely on diversity measures such as race, ethnicity, and ancestry (REA) to stratify study participants and patients for a variety of applications in research and precision medicine. However, there are no comprehensive, widely accepted standards or guidelines for collecting and using such data in clinical genetics practice. Two NIH-funded research consortia, the Clinical Genome Resource (ClinGen) and Clinical Sequencing Evidence-generating Research (CSER), have partnered to address this issue and report how REA are currently collected, conceptualized, and used. Surveying clinical genetics professionals and researchers (n = 448), we found heterogeneity in the way REA are perceived, defined, and measured, with variation in the perceived importance of REA in both clinical and research settings. The majority of respondents (>55%) felt that REA are at least somewhat important for clinical variant interpretation, ordering genetic tests, and communicating results to patients. However, there was no consensus on the relevance of REA, including how each of these measures should be used in different scenarios and what information they can convey in the context of human genetics. A lack of common definitions and applications of REA across the precision medicine pipeline may contribute to inconsistencies in data collection, missing or inaccurate classifications, and misleading or inconclusive results. Thus, our findings support the need for standardization and harmonization of REA data collection and use in clinical genetics and precision health research
Signal Transmission in the Auditory System
Contains table of contents for Section 3, an introduction and reports on six research projects.Health Sciences FundNational Institutes of Health Grant 5 R01 DC00194National Institutes of Health Grant 8 P01 DC00119National Institutes of Health Grant 5 R01 DC00473National Institutes of Health Grant 5 R01 DC00238National Institutes of Health Grant 5 T32 DC00006National Institutes of Health Grant 5 P01 DC00361National Institutes of Health Grant 5 R01 DC00235Peoples Republic of China FellowshipUnisys Corporation Doctoral FellowshipWhitaker Health Sciences Fellowshi
Signal Transmission in the Auditory System
Contains table of contents for Section 3, an introduction and reports on nine research projects.National Institutes of Health Grant 5 T32 NS07047National Institutes of Health Grant 5 P01 NS13126National Institutes of Health Grant 8 R01 DC00194National Institutes of Health Grant 5 R01 NS25995National Institutes of Health Grant 8 R01 DC00238National Institutes of Health Grant 5 R01 NS20322National Institutes of Health Grant 5 R01 DC00235National Institutes of Health Grant 5 R01 NS20269National Institutes of Health Grant 1 P01 NS23734Johnson and Johnson FoundationUnisys Corporation Doctoral Fellowshi
Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study
Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = −0.14; 95% confidence interval [CI]: −0.24 to −0.03; p value = 0.010) and MDD (β = −0.16; 95% CI: −0.27 to −0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34–1.93; p value = 2e−7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD
Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine
Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine
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