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Nonlinear effects in a high-power laser amplification system based on thin-rod active elements are experimentally investigated. It is shown that the most important nonlinear effect is the Kerr effect leading to self-focusing and self-phase modulation of laser radiation. The observed luminescence in Yb : YAG crystals in the visible region of the spectrum is caused by the charge transfer luminescence effect, which, in turn, is due to multiphoton absorption of laser radiation. Second-order nonlinearity in the crystal is used to effectively convert femtosecond pulses to second harmonic and sum-frequency waves which exhibit radiations of green and UV spectra.

Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. Patients and methods: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death. Results: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90). Conclusions: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2-mutated patients with PSROC compared to patients not previously receiving poly (ADP-ribose) polymerase inhibitors (PARPi). The optimal strategy for patients who relapse after PARPi is an area of ongoing research.

Background Idiopathic pulmonary fibrosis is a progressive disease and antifibrotic therapies do not reverse existing fibrosis. There has been emerging evidence of potential role for statins in idiopathic pulmonary fibrosis. The aim of this review is to synthesise the evidence on the efficacy of statins in idiopathic pulmonary fibrosis, focusing on associations with all-cause mortality, disease-specific mortality and change in pulmonary function. Methods Medline and Embase were reviewed to identify relevant publications. Studies were selected if they examined disease-related outcomes including mortality, pulmonary function and adverse events in people with idiopathic pulmonary fibrosis receiving statin therapy. Results Five studies with a total of 3407 people with IPF were selected and analysed. The overall risk of bias of five included studies was moderate to serious. In the fixed effect meta-analysis, statin use was associated with a reduction in mortality (RR 0.8; 95% CI 0.72–0.99). However, in the random effects model, there was no longer any significant association between statin use and all-cause mortality (RR 0.87; 95% CI 0.68–1.12). There was no statistically significant association between statin use and decline in FVC % predicted. Conclusion There is currently insufficient evidence to conclude the effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis. Considering the limitations of available literature, we would recommend a prospective cohort study with capture of dosage and preparation of statin, statin adherence and use of concurrent antifibrotic treatment. PROSPERO registration number CRD42019122745.

PURPOSE/OBJECTIVE(S) To evaluate the performance and clinical acceptability of the highest objective performing 3D convolutional neural network models developed to contour regions of interest (ROIs) in medical images. MATERIALS/METHODS Radiation treatment planning data from 582 HNC patients treated at a large tertiary cancer center were used for this study. Eleven open-source 3D segmentation models (6 UNETs, 3 DenseNets, 1 3D pyramid abstraction network, and 1 3D recurrent slice-wise attention network), originally engineered for medical image segmentation, were trained to segment 19 OARs. The same 80/10/10 split was used for training, validating and testing corresponding to 479, 44 and 59 scans. A model's performance was ranked by volumetric Dice similarity coefficient (DSC) and Hausdorff distance (HD). The best performing model was selected and re-trained on full-resolution patient scans and validated using sliding-window inference. With the best model, two radiation oncologists assessed clinical acceptability, using 5-scale ratings of 5 for "anatomically perfect, not requiring editing" and score 1 for "anatomically incorrect, unusable for planning purpose." At least 10 cases were randomly selected and deep learning-based (DLCs) and manual contours (MCs), for the entire range of the OAR, were presented to the blinded observers. The mean ratings between DLC and MC were compared using Wilcoxon signed rank test and Student's T-test for the groups where significant differences between the groups represented the ability to distinguish between the MC and DLC contours by the observers. RESULTS A simple 3D Unet performed the best among the 11 models when comparing average DSC (0.75 ± 0.12) and HD (mean HD 0.44 ± 0.09) for every OAR. Mandible (0.90 ± 0.03), brainstem (0.89 ± 0.04), and spinal cord (0.85 ± 0.05) received the highest mean DSC, and chiasm (0.38 ± 0.19), optic nerves (0.65 ± 0.15), and lips (0.70 ± 0.09) the lowest mean DSC. Lens (0.052 ± 0.019), optic nerve (0.069 ± 0.026), and chiasm (0.075 ± 0.02) received the lowest mean HD, and spinal cord (1.15 ± 0.15), mandible (1.11 ± 0.18), and brachial plexus (0.90 ± 0.12) the highest mean HD. For clinical acceptability, MC received a significantly higher rating than DLC (3.75 ± 0.77 vs. 3.23 ± 0.86) when all OARs were considered (P < 0.01). When evaluating OARs individually, MC showed significantly higher ratings for brainstem, esophagus, larynx, eyes, optic nerves, while lips, whereas parotids, acoustics, and lenses were indistinguishable. CONCLUSION Simple 3D architectures consistently outcompete more complex networks by quantitative measures. Qualitative assessment for clinical acceptability may not agree with quantitative performance, especially when the entire range of OARs is evaluated.

Purpose/Objective(s) To evaluate the association of contralateral nodal involvement (CNI) with automatically defined midline proximity in patients (pts) with head and neck cancer based on treatment planning (TP) real world data (RWD). Materials/Methods All available TPs for head and neck cancer pts between 2010 and 2017 were analyzed in an automated data analysis pipeline where the pt's midline was determined objectively using their external contour and discounting distortion due to neck lymphadenopathy via linear modeling. Primary gross tumor volumes (GTVp) and nodal volumes (GTVn) were contoured by treating radiation oncologists. Objective tumor laterality (OTL) was calculated as the difference between the GTVp center of mass and the midline in the R/L direction. OTL accuracy compared to the clinically assigned laterality (when available) was assessed. Midline proximity (MP) was the difference between the medial edge of the GTVp bounding box to the patient midline with positive values representing progressively lateralized tumors and negative values representing tumors crossing midline. Nodal involvement (ipsilateral and contralateral levels 1-5 and retropharyngeal) was determined using the TP nodal target contours labeled by neck level as is standard practice at our institution during treatment planning. The primary endpoint, CNI, was defined based on these TP contours. Volumes of GTVp were calculated from the TP. Clinical variables including HPV status, age, smoking, disease site and subsite were used for model development. The factors predictive of CNI were assessed using logistic regression (LR). Results Of 2458 pts available for analysis, 2031 had a clinically assigned laterality. The accuracy of automatically assigned laterality was 0.91 when compared with the clinically assigned laterality. Using the automatically assigned laterality (n = 2458), the overall rate of CNI was 45% and varied by disease site and nodal level involved: oropharynx (55.1%, n = 629/1142), larynx (17.6%, n = 124/703), nasopharynx (79.7%, n = 231/290). Multivariable logistic regression (LR) including subsite, HPV status, GTVp, GTVp center of mass relative to midline, GTVp midline proximity, and ipsilateral nodal involvement was performed. In the oropharynx, multivariable LR demonstrated GTVp volume (P Conclusion Automated TP analysis can be used to generate RWD-based predictions of CNI. CNI risk remains a critical radiotherapy endpoint and RWD may help determine CLI risk using combinations of anatomic and clinical features.