Glioblastoma is a highly invasive brain tumor, whose cells infiltrate surrounding normal brain tissue beyond the lesion outlines visible in the current medical scans. These infiltrative cells are treated mainly by radiotherapy. Existing radiotherapy plans for brain tumors derive from population studies and scarcely account for patient-specific conditions. Here we provide a Bayesian machine learning framework for the rational design of improved, personalized radiotherapy plans using mathematical modeling and patient multimodal medical scans. Our method, for the first time, integrates complementary information from high resolution MRI scans and highly specific FET-PET metabolic maps to infer tumor cell density in glioblastoma patients. The Bayesian framework quantifies imaging and modeling uncertainties and predicts patient-specific tumor cell density with credible intervals. The proposed methodology relies only on data acquired at a single time point and thus is applicable to standard clinical settings. An initial clinical population study shows that the radiotherapy plans generated from the inferred tumor cell infiltration maps spare more healthy tissue thereby reducing radiation toxicity while yielding comparable accuracy with standard radiotherapy protocols. Moreover, the inferred regions of high tumor cell densities coincide with the tumor radioresistant areas, providing guidance for personalized doseescalation. The proposed integration of multimodal scans and mathematical modeling provides a robust, non-invasive tool to assist personalized radiotherapy design.

Objective To demonstrate that TNFα, via sphingosine-1-phosphate (S1P) signaling, has the potential to alter cochlear blood flow and thus, cause ischemic hearing loss. Methods and Results TNFα induced a pro-constrictive state throughout the cochlear microvasculature, which reduced capillary diameter and cochlear blood flow in vivo. In vitro isolated preparations of the spiral modiolar artery and spiral ligament capillaries confirmed these observations. Antagonizing S1P receptor 2 subtype signaling (1µmol/L JTE013) attenuated the effects of TNFα in all models. TNFα activated Sk1 and induced its translocation to the smooth muscle cell membrane. Expression of a dominant-negative Sk1 mutant (Sk1G82D) eliminated both baseline spiral modiolar artery calcium sensitivity and TNFα effects, while a non-phosphorylatable Sk1 mutant (Sk1S225A) only blocked the effects of TNFα. A small group of etanercept-treated hearing loss patients recovered with a one-phase exponential decay (t½=1.56±0.20 weeks), which matched a kinetic predicted for a vascular origin. Conclusions TNFα indeed reduces cochlear blood flow via the activation of vascular S1P signaling. This integrates hearing loss into the family of ischemic microvascular pathologies, with implications for risk stratification, diagnosis and treatment.

Few studies have described objective methods to evaluate repigmentation among vitiligo patients. Digital morphometry provides an objective assessment of repigmentation in vitiligo. Objective vitiligo repigmentation with topical C/DSO at 10 months is similar to topical 0.05% betamethasone. Although a mild adverse effect was related to the use of C/DSO, such finding was not severe enough to discontinue treatment.

Corticosteroid therapy and hyperglycemia were strongly associated with impaired survival rates and serves as negative prognostic factors. Diabetes did not influence survival. Interestingly, our findings showed an association of metformin therapy and prolonged progression-free survival in glioblastoma patients with diabetes and therefore serve as a foundation for further preclinical and clinical investigations.

We present time-series photometric observations of thirteen transits in the planetary systems WASP-24, WASP-25 and WASP-26. All three systems have orbital obliquity measurements, WASP-24 and WASP-26 have been observed with Spitzer, and WASP-25 was previously comparatively neglected. Our light curves were obtained using the telescope-defocussing method and have scatters of 0.5 to 1.2 mmag relative to their best-fitting geometric models. We used these data to measure the physical properties and orbital ephemerides of the systems to high precision, finding that our improved measurements are in good agreement with previous studies. High-resolution Lucky Imaging observations of all three targets show no evidence for faint stars close enough to contaminate our photometry. We confirm the eclipsing nature of the star closest to WASP-24 and present the detection of a detached eclipsing binary within 4.25 arcmin of WASP-26.

Two previously unknown variable stars in the crowded central region of the globular cluster NGC 6981 are presented. The observations were made using the electron multiplying CCD (EMCCD) camera at the Danish 1.54 m Telescope at La Silla, Chile. The two variables were not previously detected by conventional CCD imaging because of their proximity to a bright star. This discovery demonstrates that EMCCDs are a powerful tool for performing high-precision time-series photometry in crowded fields and near bright stars, especially when combined with difference image analysis.

Brain metastases show a recurrence rate of about 50% after surgical resection. Adjuvant radiotherapy can prevent progression; however, whole‐brain radiotherapy (WBRT) can be associated with significant side effects. Local hypofractionated stereotactic radiotherapy (HFSRT) is a good alternative to provide local control with minimal toxicity. In this multicenter analysis, we evaluated the treatment outcome of local HFSRT after resection brain metastases in 181 patients. Patient's characteristics, treatment data as well as follow‐up data were collected and analyzed with special focus on local control, locoregional control and survival. After a median follow‐up of 12.6 months (range 0.3–80.2 months), the crude rate for local control was 80.5%; 1‐ and 2‐year local recurrence‐free survival rates were 75% and 70% (median not reached). Resection cavity size was a significant predictor for local recurrence (P = 0.033). The median overall survival was 16.0 months. Both graded prognostic assessment score and recursive partitioning analysis were accurate predictors of survival. HFSRT leads to excellent local control and has a high potential to consolidate results after surgery; acute and late toxicity is low. Distant intracerebral metastases occur frequently during follow‐up, and therefore, a close patient monitoring needs to be warranted if whole‐brain radiotherapy is omitted.

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