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Rami A El Shafie,1,2 Karina Böhm,1,2 Dorothea Weber,3 Kristin Lang,1,2 Fabian Schlaich,1,2 Sebastian Adeberg,1,2 Angela Paul,1,2,4 Matthias F Haefner,1,2 Sonja Katayama,1,2 Florian Sterzing,1,2,5 Juliane Hörner-Rieber,1,2 Sarah Löw,6 Klaus Herfarth,1,2,4 Jürgen Debus,1,2,4,7 Stefan Rieken,1,2,4 Denise Bernhardt1,2 1Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany; 2National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany; 3Institute of Medical Biometry and Informatics (IMBI), Heidelberg University Hospital, Heidelberg 69120, Germany; 4Heavy Ion Therapy Center (HIT), Heidelberg University Hospital, Heidelberg 69120, Germany; 5Department of Radiation Oncology, Klinikum Kempten, Kempten 87439, Germany; 6Department of Neurology, University Hospital of Heidelberg, Heidelberg 69120, Germany; 7German Cancer Research Center (DKFZ), Heidelberg 69120, Germany Background: Leptomeningeal carcinomatosis (LC) is a severe complication of metastatic tumor spread to the central nervous system. Prognosis is dismal with a median overall survival (OS) of ~10–15 weeks. Treatment options include radiotherapy (RT) to involved sites, systemic chemo- or targeted therapy, intrathecal chemotherapy and best supportive care with dexamethasone. Craniospinal irradiation (CSI) is a more aggressive radiotherapeutic approach, for which very limited data exists. Here, we report on our 10-year experience with palliative CSI of selected patients with LC. Patients and methods: Twenty-five patients received CSI for the treatment of LC at our institution between 2008 and 2018. Patients were selected individually for CSI based on clinical performance, presenting symptoms and estimated benefit. Median patient age was 53 years (IQR: 45–59), and breast cancer was the most common primary. Additional brain metastases were found in 18 patients (72.0%). RT was delivered at a TomoTherapy machine, using helical intensity-modulated radiotherapy (IMRT). The most commonly prescribed dose was 36 Gy in 20 fractions, corresponding to a median biologically equivalent dose of 40.8 Gy (IQR: 39.0– 2.5). Clinical performance and neurologic function were assessed before and in response to therapy, and deficits were retrospectively quantified on the 5-point neurologic function scale (NFS). A Cox proportional hazards model with univariate and multivariate analyses was fitted for survival.Results: Twenty-one patients died and four were alive at the time of analysis. Median OS from LC diagnosis was 19.3 weeks (IQR: 9.3–34.0, 95% CI: 11.0–32.0). In univariate analysis, a Karnofsky performance scale index (KPI) ≥70% (P=0.001), age ≤55 years at LC diagnosis (P=0.022), cerebrospinal fluid (CSF) protein

Background: Distortion arises during machining of metallic parts from two main mechanisms: 1) release of bulk residual stress (BRS) in the pre-form, and 2) permanent deformation induced by cut tools. Interaction between these mechanisms is unexplored. Objective: Assess this interaction using aluminum samples that have a flat surface with variations of BRS, where that surface is subsequently milled, and we observe milling-induced residual stress (MIRS) and distortion. Methods: Plate samples are cut from two kinds of large blocks, one kind stress-relieved by stretching and a second kind solution heat treated, quenched and aged. The BRS field in the plates is known from a recent series of measurements, being small in the stress relieved plates (within ±20 MPa) and large (±100 MPa) in the quenched plates, varying from tension to compression over the surface that is milled. MIRS is measured following milling using hole-drilling. Distortions of thin wafers cut at the milled surfaces are used to elucidate BRS/MIRS interactions. A finite element (FE) model and a strength of materials model are each used to assess consistency between wafer distortion and measured MIRS. Results: Milling in samples with high BRS magnitude changes the directions of MIRS and distortion relative to the milling direction, with the direction of maximum curvature rotating toward or away from the milling direction depending on the sign and direction of BRS. High magnitude BRS was also found to increase the wafer peak arc height, nearly doubling the amount found in low BRS samples. Conclusion: Measured residual stress and observed wafer distortion both show interactions between MIRS and BRS. Stress analysis models show that the differences in measured MIRS are consistent with the differences in observed distortion.

Background: While near surface residual stress (NSRS) from milling is a driver for distortion in aluminum parts there are few studies that directly compare available techniques for NSRS measurement. Objective: We report application and assessment of four different techniques for evaluating residual stress versus depth in milled aluminum parts. Methods: The four techniques are: hole-drilling, slotting, cos(α) x-ray diffraction (XRD), and sin2(ψ) XRD, all including incremental material removal to produce a stress versus depth profile. The milled aluminum parts are cut from stress-relieved plate, AA7050-T7451, with a range of table and tool speeds used to mill a large flat surface in several samples. NSRS measurements are made at specified locations on each sample. Results: Resulting data show that NSRS from three techniques are in general agreement: hole-drilling, slotting, and sin2(ψ) XRD. At shallow depths (< 0.03 mm), sin2(ψ) XRD data have the best repeatability (< 15 MPa), but at larger depths (> 0.04 mm) hole-drilling and slotting have the best repeatability (< 10 MPa). NSRS data from cos(α) XRD differ from data provided by other techniques and the data are less repeatable. NSRS data for different milling parameters show that the depth of NSRS increases with feed per tooth and is unaffected by cutting speed. Conclusion: Hole-drilling, slotting, and sin2(ψ) XRD provided comparable results when assessing milling-induced near surface residual stress in aluminum. Combining a simple distortion test, comprising removal of a 1 mm thick wafer at the milled surface, with a companion stress analysis showed that NSRS data from hole-drilling are most consistent with milling-induced distortion.

Machining-induced residual stresses (MIRS) are a main driver for distortion of thin-walled monolithic aluminum workpieces. Before one can develop compensation techniques to minimize distortion, the effect of machining on the MIRS has to be fully understood. This means that not only an investigation of the effect of different process parameters on the MIRS is important. In addition, the repeatability of the MIRS resulting from the same machining condition has to be considered. In past research, statistical confidence of MIRS of machined samples was not focused on. In this paper, the repeatability of the MIRS for different machining modes, consisting of a variation in feed per tooth and cutting speed, is investigated. Multiple hole-drilling measurements within one sample and on different samples, machined with the same parameter set, were part of the investigations. Besides, the effect of two different clamping strategies on the MIRS was investigated. The results show that an overall repeatability for MIRS is given for stable machining (between 16 and 34% repeatability standard deviation of maximum normal MIRS), whereas instable machining, detected by vibrations in the force signal, has worse repeatability (54%) independent of the used clamping strategy. Further experiments, where a 1-mm-thick wafer was removed at the milled surface, show the connection between MIRS and their distortion. A numerical stress analysis reveals that the measured stress data is consistent with machining-induced distortion across and within different machining modes. It was found that more and/or deeper MIRS cause more distortion.

Cutting-edge DNA methylation-based epigenetic aging techniques were applied to Gulf of Mexico northern red snapper (Lutjanus campechanus; n = 10; 1-26 years old) and red grouper (Epinephelus morio; n = 10; 2-14 years old). Bisulfiteconverted restriction site-associated DNA sequencing was used to identify CpG sites (cytosines followed by guanines) that exhibit age-correlated DNA methylation, and species-specific epigenetic clocks developed from hundreds of CpG sites in each species showed strong agreement between predicted and otolith-derived age [r.sup.2] > 0.99 for both species). Results suggest epigenetic age estimation could provide an accurate and efficient approach to mass-aging fishes in a non-invasive manner. Des methodes epigenetiques de pointe de determination de l'age reposant sur la methylation de l'ADN ont ete appliquees au vivaneau campeche (Lutjanus campechanus; n = 10; 1-26 ans) et au merou rouge (Epinephelus morio; n = 10; 2-14 ans). Le sequencage avec conversion au bisulfite d'ADN associe a des sites de restriction a ete utilise pour cerner des sites CpG (cytosines suivies de guanines) qui presentent une methylation de l'ADN correlee a l'age, et des horloges epigenetiques propres a l'espece developpees a partir de centaines de sites CpG de chaque espece ont revele de fortes concordances entre les ages predits et les ages obtenus par analyse d'otolites [r.sup.2] > 0,99 pour les deux especes). Les resultats donnent a penser que l'estimation epigenetique de l'age pourrait constituer une approche non invasive exacte et efficiente de determination des ages de quantites massives de poissons., Introduction Age data are fundamental to determining life history parameters (e.g., age-at-length, age-at-maturity, age-related fecundity) and are thus critical for fisheries assessment and management, particularly when age-structured stock assessment models [...]

Objective. Online adaptive radiation therapy requires fast and automated contouring of daily scans for treatment plan re-optimization. However, automated contouring is imperfect and introduces contour uncertainties. This work aims at developing and comparing robust optimization strategies accounting for such uncertainties. Approach. A deep-learning method was used to predict the uncertainty of deformable image registration, and to generate a finite set of daily contour samples. Ten optimization strategies were compared: two baseline methods, five methods that convert contour samples into voxel-wise probabilities, and three methods accounting explicitly for contour samples as scenarios in robust optimization. Target coverage and organ-at-risk (OAR) sparing were evaluated robustly for simplified proton therapy plans for five head-and-neck cancer patients. Results. We found that explicitly including target contour uncertainty in robust optimization provides robust target coverage with better OAR sparing than the baseline methods, without increasing the optimization time. Although OAR doses first increased when increasing target robustness, this effect could be prevented by additionally including robustness to OAR contour uncertainty. Compared to the probability-based methods, the scenario-based methods spared the OARs more, but increased integral dose and required more computation time. Significance. This work proposed efficient and beneficial strategies to mitigate contour uncertainty in treatment plan optimization. This facilitates the adoption of automatic contouring in online adaptive radiation therapy and, more generally, enables mitigation also of other sources of contour uncertainty in treatment planning. [ABSTRACT FROM AUTHOR]

In the late 1900s, shark populations in the western North Atlantic Ocean declined drastically in size (Musick et al., 1993), because of overexploitation and sharks being captured as bycatch in [...]