53 research outputs found

    Topical rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model

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    <p>Abstract</p> <p>Background</p> <p>Skin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical rapamycin in a mouse model for TSC-related tumors.</p> <p>Methods</p> <p>0.4% and 0.8% rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts.</p> <p>Results</p> <p>Treatment with topical rapamycin improved survival and reduced tumor growth. Topical rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected rapamycin.</p> <p>Conclusion</p> <p>Topical rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.</p

    The Early Royal Society and Visual Culture

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    Recent studies have fruitfully examined the intersection between early modern science and visual culture by elucidating the functions of images in shaping and disseminating scientific knowledge. Given its rich archival sources, it is possible to extend this line of research in the case of the Royal Society to an examination of attitudes towards images as artefacts –manufactured objects worth commissioning, collecting and studying. Drawing on existing scholarship and material from the Royal Society Archives, I discuss Fellows’ interests in prints, drawings, varnishes, colorants, images made out of unusual materials, and methods of identifying the painter from a painting. Knowledge of production processes of images was important to members of the Royal Society, not only as connoisseurs and collectors, but also as those interested in a Baconian mastery of material processes, including a “history of trades”. Their antiquarian interests led to discussion of painters’ styles, and they gradually developed a visual memorial to an institution through portraits and other visual records.AH/M001938/1 (AHRC

    Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

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    The clinical significance of the tumor-immune interaction in breast cancer (BC) has been well established, and tumor-infiltrating lymphocytes (TILs) have emerged as a predictive and prognostic biomarker for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer (TNBC) and HER2-positive breast cancer. How computational assessment of TILs can complement manual TIL-assessment in trial- and daily practices is currently debated and still unclear. Recent efforts to use machine learning (ML) for the automated evaluation of TILs show promising results. We review state-of-the-art approaches and identify pitfalls and challenges by studying the root cause of ML discordances in comparison to manual TILs quantification. We categorize our findings into four main topics; (i) technical slide issues, (ii) ML and image analysis aspects, (iii) data challenges, and (iv) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns, or design choices in the computational implementation. To aid the adoption of ML in TILs assessment, we provide an in-depth discussion of ML and image analysis including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial- and routine clinical management of patients with TNBC

    Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

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    The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer

    Characterization of anthropogenic methane plumes with the Hyperspectral Thermal Emission Spectrometer (HyTES): A retrieval method and error analysis

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    We introduce a retrieval algorithm to estimate lower tropospheric methane (CH4) concentrations from the surface to 1 km with uncertainty estimates using Hyperspectral Thermal Emission Spectrometer (HyTES) airborne radiance measurements. After resampling, retrievals have a spatial resolution of 6 × 6 m2. The total error from a single retrieval is approximately 20 %, with the uncertainties determined primarily by noise and spectral interferences from air temperature, surface emissivity, and atmospheric water vapor. We demonstrate retrievals for a HyTES flight line over storage tanks near Kern River Oil Field (KROF), Kern County, California, and find an extended plume structure in the set of observations with elevated methane concentrations (3.0 ± 0.6 to 6.0 ± 1.2 ppm), well above mean concentrations (1.8 ± 0.4 ppm) observed for this scene. With typically a 20 % estimated uncertainty, plume enhancements with more than 1 ppm are distinguishable from the background values with its uncertainty. HyTES retrievals are consistent with simultaneous airborne and ground-based in situ CH4 mole fraction measurements within the reported accuracy of approximately 0.2 ppm (or ∌8 %), due to retrieval interferences related to air temperature, emissivity, and H2O
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