172 research outputs found

    Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control

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    <p>Abstract</p> <p>Background</p> <p>Melanoma and renal cell carcinoma (RCC) are traditionally considered less radioresponsive than other histologies. Whereas stereotactic body radiation therapy (SBRT) involves radiation dose intensification via escalation, we hypothesize SBRT might result in similar high local control rates as previously published on metastases of varying histologies.</p> <p>Methods</p> <p>The records of patients with metastatic melanoma (n = 17 patients, 28 lesions) or RCC (n = 13 patients, 25 lesions) treated with SBRT were reviewed. Local control (LC) was defined pathologically by negative biopsy or radiographically by lack of tumor enlargement on CT or stable/declining standardized uptake value (SUV) on PET scan. The SBRT dose regimen was converted to the single fraction equivalent dose (SFED) to characterize the dose-control relationship using a logistic tumor control probability (TCP) model. Additionally, the kinetics of decline in maximum SUV (SUV<sub>max</sub>) were analyzed.</p> <p>Results</p> <p>The SBRT regimen was 40-50 Gy/5 fractions (n = 23) or 42-60 Gy/3 fractions (n = 30) delivered to lung (n = 39), liver (n = 11) and bone (n = 3) metastases. Median follow-up for patients alive at the time of analysis was 28.0 months (range, 4-68). The actuarial LC was 88% at 18 months. On univariate analysis, higher dose per fraction (p < 0.01) and higher SFED (p = 0.06) were correlated with better LC, as was the biologic effective dose (BED, p < 0.05). The actuarial rate of LC at 24 months was 100% for SFED ≥45 Gy v 54% for SFED <45 Gy. TCP modeling indicated that to achieve ≥90% 2 yr LC in a 3 fraction regimen, a prescription dose of at least 48 Gy is required. In 9 patients followed with PET scans, the mean pre-SBRT SUV<sub>max </sub>was 7.9 and declined with an estimated half-life of 3.8 months to a post-treatment plateau of approximately 3.</p> <p>Conclusions</p> <p>An aggressive SBRT regimen with SFED ≥ 45 Gy is effective for controlling metastatic melanoma and RCC. The SFED metric appeared to be as robust as the BED in characterizing dose-response, though additional studies are needed. The LC rates achieved are comparable to those obtained with SBRT for other histologies, suggesting a dominant mechanism of in vivo tumor ablation that overrides intrinsic differences in cellular radiosensitivity between histologic subtypes.</p

    The scientific impact of the Structural Genomics Consortium: a protein family and ligand-centered approach to medically-relevant human proteins

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    As many of the structural genomics centers have ended their first phase of operation, it is a good point to evaluate the scientific impact of this endeavour. The Structural Genomics Consortium (SGC), operating from three centers across the Atlantic, investigates human proteins involved in disease processes and proteins from Plasmodium falciparum and related organisms. We present here some of the scientific output of the Oxford node of the SGC, where the target areas include protein kinases, phosphatases, oxidoreductases and other metabolic enzymes, as well as signal transduction proteins. The SGC has aimed to achieve extensive coverage of human gene families with a focus on protein–ligand interactions. The methods employed for effective protein expression, crystallization and structure determination by X-ray crystallography are summarized. In addition to the cumulative impact of accelerated delivery of protein structures, we demonstrate how family coverage, generic screening methodology, and the availability of abundant purified protein samples, allow a level of discovery that is difficult to achieve otherwise. The contribution of NMR to structure determination and protein characterization is discussed. To make this information available to a wide scientific audience, a new tool for disseminating annotated structural information was created that also represents an interactive platform allowing for a continuous update of the annotation by the scientific community

    HABITAT: A longitudinal multilevel study of physical activity change in mid-aged adults

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    Purpose. To explore the role of the neighborhood environment in supporting walking Design. Cross sectional study of 10,286 residents of 200 neighborhoods. Participants were selected using a stratified two-stage cluster design. Data were collected by mail survey (68.5% response rate). Setting. The Brisbane City Local Government Area, Australia, 2007. Subjects. Brisbane residents aged 40 to 65 years. Measures. Environmental: street connectivity, residential density, hilliness, tree coverage, bikeways, and street lights within a one kilometer circular buffer from each resident’s home; and network distance to nearest river or coast, public transport, shop, and park. Walking: minutes in the previous week categorized as < 30 minutes, ≥ 30 < 90 minutes, ≥ 90 < 150 minutes, ≥ 150 < 300 minutes, and ≥ 300 minutes. Analysis. The association between each neighborhood characteristic and walking was examined using multilevel multinomial logistic regression and the model parameters were estimated using Markov chain Monte Carlo simulation. Results. After adjustment for individual factors, the likelihood of walking for more than 300 minutes (relative to <30 minutes) was highest in areas with the most connectivity (OR=1.93, 99% CI 1.32-2.80), the greatest residential density (OR=1.47, 99% CI 1.02-2.12), the least tree coverage (OR=1.69, 99% CI 1.13-2.51), the most bikeways (OR=1.60, 99% CI 1.16-2.21), and the most street lights (OR=1.50, 99% CI 1.07-2.11). The likelihood of walking for more than 300 minutes was also higher among those who lived closest to a river or the coast (OR=2.06, 99% CI 1.41-3.02). Conclusion. The likelihood of meeting (and exceeding) physical activity recommendations on the basis of walking was higher in neighborhoods with greater street connectivity and residential density, more street lights and bikeways, closer proximity to waterways, and less tree coverage. Interventions targeting these neighborhood characteristics may lead to improved environmental quality as well as lower rates of overweight and obesity and associated chromic disease

    Prolonged Mechanical Ventilation Induces Cell Cycle Arrest in Newborn Rat Lung

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    Rationale: The molecular mechanism(s) by which mechanical ventilation disrupts alveolar development, a hallmark of bronchopulmonary dysplasia, is unknown. Objective: To determine the effect of 24 h of mechanical ventilation on lung cell cycle regulators, cell proliferation and alveolar formation in newborn rats. Methods: Seven-day old rats were ventilated with room air for 8, 12 and 24 h using relatively moderate tidal volumes (8.5 mL.kg-1). Measurement and Main Results: Ventilation for 24 h (h) decreased the number of elastin-positive secondary crests and increased the mean linear intercept, indicating arrest of alveolar development. Proliferation (assessed by BrdU incorporation) was halved after 12 h of ventilation and completely arrested after 24 h. Cyclin D1 and E1 mRNA and protein levels were decreased after 8-24 h of ventilation, while that of p27Kip1 was significantly increased. Mechanical ventilation for 24 h also increased levels of p57Kip2, decreased that of p16INK4a, while the levels of p21Waf/Cip1 and p15INK4b were unchanged. Increased p27Ki

    The Mid-infrared Instrument for JWST and Its In-flight Performance

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    The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI
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