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Background: The National Accreditation Program for Rectal Cancer (NAPRC) was developed to enhance the quality of rectal cancer care in the United States. This project compared NAPRC compliance at a single tertiary care academic hospital before and after the institution adopted these standards in 2019. Methods: Rectal cancer patients from 2016 to 2023 who met NAPRC eligibility criteria were retrospectively reviewed for compliance with pre-selected patient care standards. Patients diagnosed prior to August 1, 2019 (pre-NAPRC) were compared with those diagnosed afterward (post-NAPRC) to determine whether compliance with these standards differed following the institution's adoption of new guidelines. Results: This study included 353 patients, 146 pre-NAPRC and 207 post-NAPRC. The post-NAPRC group demonstrated significantly higher compliance with pretreatment standards compared to the pre-NAPRC group, including attaining magnetic resonance imaging (MRI) ( P = .015), computed tomography (CT) ( P < .001), and a carcinoembryonic antigen (CEA) level ( P < .001). Postoperative standards were more frequently met in the post-NAPRC group regarding the photographing of surgical specimens ( P < .001). No significant differences were observed in confirming a tissue diagnosis, starting treatment within a 60-day timeframe, or completing surgical pathology reports. Prior to initiation of the NAPRC process, the institution had achieved accreditation-level compliance in 2 of the 7 standards. Within 2 years of adopting NAPRC standards, complete compliance was met in 6 of the 7 measures. Conclusions: A single institution's adoption of NAPRC standards improved compliance with multiple rectal cancer care standards, achieving near-complete accreditation level compliance within 2 years., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In this work we seek to enhance the frameworks practitioners in asset management and wealth management may adopt to asses how different screening rules may influence the diversification benefits of portfolios. The problem arises naturally in the area of Environmental, Social, and Governance (ESG) based investing practices as practitioners often need to select subsets of the total available assets based on some ESG screening rule. Once a screening rule is identified, one constructs a dynamic portfolio which is usually compared with another dynamic portfolio to check if it satisfies or outperforms the risk and return profile set by the company. Our study proposes a novel method that tackles the problem of comparing diversification benefits of portfolios constructed under different screening rules. Each screening rule produces a sequence of graphs, where the nodes are assets and edges are partial correlations. To compare the diversification benefits of screening rules, we propose to compare the obtained graph sequences. The method proposed is based on a machine learning hypothesis testing framework called the kernel two-sample test whose objective is to determine whether the graphs come from the same distribution. If they come from the same distribution, then the risk and return profiles should be the same. The fact that the sample data points are graphs means that one needs to use graph testing frameworks. The problem is natural for kernel two-sample testing as one can use so-called graph kernels to work with samples of graphs. The null hypothesis of the two-sample graph kernel test is that the graph sequences were generated from the same distribution, while the alternative is that the distributions are different. A failure to reject the null hypothesis would indicate that ESG screening does not affect diversification while rejection would indicate that ESG screening does have an effect. The article describes the graph kernel two-sample testing framework, and further provides a brief overview of different graph kernels. We then demonstrate the power of the graph two-sample testing framework under different realistic scenarios. Finally, the proposed methodology is applied to data within the SnP500 to demonstrate the workflow one can use in asset management to test for structural differences in diversification of portfolios under different ESG screening rules., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gudmundarson, Peters. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: We investigated whether pulmonary metastases from historically considered radioresistant primaries would have inferior local control after radiation therapy than those from nonradioresistant nonlung primaries, and whether higher biologically effective dose assuming alpha/beta=10 (BED10) would be associated with superior local control., Methods and Materials: We identified patients treated with radiation therapy for oligometastatic or oligoprogressive pulmonary disease to 1 to 5 lung metastases from nonlung primaries in 2013 to 2020 at a single health care system. Radioresistant primary cancers included colorectal carcinoma, endometrial carcinoma, renal cell carcinoma, melanoma, and sarcoma. Nonradioresistant primary cancers included breast, bladder, esophageal, pancreas, and head and neck carcinomas. The Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazards regression were used to compare local recurrence-free survival (LRFS), new metastasis-free survival, progression-free survival, and overall survival., Results: Among 114 patients, 73 had radioresistant primary cancers. The median total dose was 50 Gy (IQR, 50-54 Gy) and the median number of fractions was 5 (IQR, 3-5). Median follow-up time was 59.6 months. One of 41 (2.4%) patients with a nonradioresistant metastasis experienced local failure compared with 18 of 73 (24.7%) patients with radioresistant metastasis (log-rank P = .004). Among radioresistant metastases, 12 of 41 (29.2%) patients with colorectal carcinoma experienced local failure compared with 6 of 32 (18.8%) with other primaries (log-rank P = .018). BED10 ≥100 Gy was associated with decreased risk of local recurrence. On univariable analysis, BED10 ≥100 Gy (hazard ratio [HR], 0.263; 95% CI, 0.105-0.656; P = .004) was associated with higher LRFS, and colorectal primary (HR, 3.060; 95% CI, 1.204-7.777; P = .019) was associated with lower LRFS, though these were not statistically significant on multivariable analysis. Among colorectal primary patients, BED10 ≥100 Gy was associated with higher LRFS (HR, 0.266; 95% CI, 0.072-0.985; P = .047) on multivariable analysis., Conclusions: Local control after radiation therapy was encouraging for pulmonary metastases from most nonlung primaries, even for many of those classically considered to be radioresistant. Those from colorectal primaries may benefit from testing additional strategies, such as resection or systemic treatment concurrent with radiation., Competing Interests: Henry S. Park reports consulting, personal honoraria, and being on an advisory board of AstraZeneca; personal honoraria from Bristol Myers Squibb, Daichii Sankyo, and G1 Therapeutics; being on the advisory board of Galera and Regeneron; institutional research funding from Merck; consulting and institutional research funding from RefleXion., (© 2024 The Author(s).)

Purpose: Hypofractionated radiation therapy (HFRT) is a common treatment for thoracic tumors, typically delivered as 60 Gy in 15 fractions. We aimed to identify dosimetric risk factors associated with radiation pneumonitis in patients receiving HFRT at 4 Gy per fraction, focusing on lung V20, mean lung dose (MLD), and lung V5 as potential predictors of grade ≥2 pneumonitis., Methods and Materials: All patients were treated with thoracic HFRT to 60 Gy in 15 fractions or 72 Gy in 18 fractions at a single health care system from 2013 to 2020. Tumors near critical structures (trachea, proximal tracheobronchial tree, esophagus, spinal cord, or heart) were considered central (within 2 cm), and those closer were classified as ultracentral (within 1 cm). The primary endpoint was grade ≥2 pneumonitis. Logistic regression analyses, adjusting for target size and dosimetric variables, were used to establish a dose threshold associated with <20% risk of grade ≥2 pneumonitis., Results: During a median 24.3-month follow-up, 18 patients (16.8%) developed grade ≥2 radiation pneumonitis, with no significant difference between the 2 dose regimens (17.3% vs 16.3%, P = .88). Four patients (3.7%) experienced grade ≥3 pneumonitis, including 2 grade 5 cases. Patients with grade ≥2 pneumonitis had significantly higher lung V20 (mean 23.4% vs 14.5%, P < .001), MLD (mean 13.0 Gy vs 9.5 Gy, P < .001), and lung V5 (mean 49.6% vs 40.6%, P = .01). Dose thresholds for a 20% risk of grade ≥2 pneumonitis were lung V20 <17.7%, MLD <10.6 Gy, and V5 <41.3%. Multivariable analysis revealed a significant association between lung V20 and grade ≥2 pneumonitis (adjusted odds ratio, 1.48, P = .03)., Conclusions: To minimize the risk of grade ≥2 radiation pneumonitis when delivering 4 Gy per fraction at either 60 Gy or 72 Gy, it is advisable to maintain lung V20<17.7%. MLD <10.6 Gy and V5<41.3% can also be considered as lower-priority constraints. However, additional validation is necessary before incorporating these constraints into clinical practice or trial planning guidelines., Competing Interests: Disclosures Dr Park discloses the following relationships: AstraZeneca (consulting, advisory board), Bristol Myers Squibb (speaking fees/honoraria), Curio Sciences (consulting), G1 Therapeutics (speaking fees/honoraria), Galera Medical (advisory board), Merck (research funding), and RefleXion Medical (research funding, consulting). All other authors have no relevant disclosures., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

We develop a new model for spatio-temporal data. More specifically, a graph penalty function is incorporated in the cost function in order to estimate the unknown parameters of a spatio-temporal mixed-effect model based on a generalized linear model. This model allows for more flexible and general regression relationships than classical linear ones through the use of generalized linear models (GLMs) and also captures the inherent structural dependencies or relationships of the data through this regularization based on the graph Laplacian. We use a publicly available dataset from the National Centers for Environmental Information (NCEI) in the United States of America and perform statistical inferences of future CO2 emissions in 59 counties. We empirically show how the proposed method outperforms widely used methods, such as the ordinary least squares (OLS) and ridge regression for this challenging problem.

Purpose: Current guidelines recommend surgery as standard of care for primary lung neuroendocrine tumor (LNET). Given that LNET is a rare clinical entity, there is a lack of literature regarding treatment of LNET with stereotactic body radiation therapy (SBRT). We hypothesized that SBRT could lead to effective locoregional tumor control and long-term outcomes., Methods and Materials: We retrospectively reviewed 48 tumors in 46 patients from 11 institutions with a histologically confirmed diagnosis of LNET, treated with primary radiation therapy. Data were collected for patients treated nonoperatively with primary radiation therapy between 2006 and 2020. Patient records were reviewed for lesion characteristics and clinical risk factors. Kaplan-Meier analysis, log-rank tests, and Cox multivariate models were used to compare outcomes., Results: Median age at treatment was 71 years and mean tumor size was 2 cm. Thirty-two lesions were typical carcinoid histology, 7 were atypical, and 9 were indeterminate. The most common SBRT fractionation schedule was 50 to 60 Gy in 5 daily fractions. Overall survival at 3, 6, and 9 years was 64%, 43%, and 26%, respectively. Progression-free survival at 3, 6, and 9 years was 88%, 78%, and 78%, respectively. Local control at 3, 6, and 9 years was 97%, 91%, and 91%, respectively. There was 1 regional recurrence in a paraesophageal lymph node. No grade 3 or higher toxicity was identified., Conclusions: This is the largest series evaluating outcomes in patients with LNET treated with SBRT. This treatment is well tolerated, provides excellent locoregional control, and should be offered as an alternative to surgical resection for patients with early-stage LNET, particularly those who may not be ideal surgical candidates., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Radiation oncology is uniquely poised to benefit from the development of remote learning tools, given the need for mastery of often challenging basic science topics, as well as the interprogram heterogeneity of resident educational quality. Our team successfully created and disseminated 4 high-yield animated physics educational videos through the collaboration of radiation oncologists, medical physicists, and a graphic design specialist. This is a unique process requiring significant intellectual, monetary, and time capital. In this article, we describe important lessons learned throughout this process, in hopes that others will learn from our experience, applying the following concepts to their own digital content creation. These lessons include (1) playing to your teammates' strengths and personalizing tasks, rather than equally dividing work; (2) anticipating animations before and during script writing; (3) developing multiple routes of communication and being open to which one works best for your team; and (4) discussing funding up front and collaborating within an affiliated institution or company for graphic design to alleviate the financial stress of such endeavors., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: For patients with operable locally advanced esophageal carcinoma (LA-EC), we hypothesized that pre-operative induction chemotherapy followed by chemoradiotherapy (IC-CRT) would improve progression-free survival (PFS) and overall survival (OS) when compared to chemoradiotherapy (CRT)., Methods: This was a single institution retrospective cohort study including patients with LA-EC who received preoperative-intent IC-CRT vs. CRT between 2013-2019. The Kaplan-Meier method was used to estimate OS and PFS. Cox proportional hazards regression was used to assess for variables associated with survival. The impact of treatment group on pathologic response was assessed by chi-square., Results: Ninty-five patients were included for analysis (IC-CRT n=59; CRT n=36) and the median follow-up was 37.7 months (IQR: 16.8-56.1). There was no difference in median PFS or OS for IC-CRT or CRT, 22 months (95% CI: 12-59) vs. 32 months (95% CI: 10-57) (P=0.64) and 39 months (95% CI: 23-not reached) vs. 56.5 months (95% CI: 38-not reached) (P=0.36), respectively. Amongst the subset of patients with adenocarcinoma histology, there was no difference in median PFS or OS, nor was there when analyses were further restricted to those who received ≥3 cycles of induction 5-fluorouracil and platinum, or for those who underwent esophagectomy. Pathologic complete response occurred in 45% vs. 29% (P=0.24) and N-stage regression occurred in 72% vs. 58% (P=0.28) of patients in the IC-CRT and CRT cohorts, respectively. Distant metastasis occurred in 44% of patients in each treatment cohort., Conclusions: For patients with LA-EC, preoperative-intent IC-CRT was not associated with improved PFS or OS when compared with CRT., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-1005/coif). GWP reports RSNA/AUR/APDR/SCARD Radiology Education Research Development Grant for medical education. JL serves as an Consultant for Merck, AstraZeneca, Novartis, Deciphera, Opsen Pharma, and Celgene. MC reports Grant funding from the National Cancer Institute, and personal fees from Agios Pharmaceuticals, Eisai Inc, and AstraZeneca. SS serves as an Consultant for Genentech, QED Therapeutics, Exelixis, Astrazeneca, and Merck. KJ serves as an Editor for Radoncquestions.com, LLC. None of the above disclosures directly pertain to this work. The other authors have no conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Purpose: The quality of medical physics education is heterogenous across training programs, despite its importance in radiation oncology (RO) residency training. We present the results of a pilot series of free high-yield physics educational videos covering 4 topics chosen from the American Society for Radiation Oncology core curriculum., Methods and Materials: Scripting and storyboarding of videos were iterative processes performed by 2 ROs and 6 medical physicists, with animations created by a university broadcasting specialist. Current RO residents and those who had graduated after 2018 were recruited through social media and e-mail with an aim of 60 participants. Two validated surveys were adapted for use and were completed after each video as well as a final overall assessment. Content was released sequentially after completion of the survey instruments for each prior video. All videos were created and released within 1 year of project initiation with a duration of 9 to 11 minutes., Results: There were 169 enrollees for the pilot from across the world, 211% of the targeted cohort size. Of these, 154 met eligibility criteria and received the first video. One hundred eight enrollees initiated the series and 85 completed the pilot, resulting in a 78% completion rate. Participants reported improved understanding and confidence applying the knowledge learned in the videos (median score 4 out of 5). All participants reported that the use of graphic animation improved understanding across all videos. Ninety-three percent agreed with a need for additional resources geared specifically toward RO residents and 100% would recommend these videos to other residents. Use metrics revealed the average watch time was 7 minutes (range, 6:17-7:15)., Conclusions: The high-yield educational physics video pilot series was successful in developing videos that were effective in teaching RO physics concepts., (© 2023 The Authors.)

Medical diagnostic methods that utilise modalities of patient symptoms such as speech are increasingly being used for initial diagnostic purposes and monitoring disease state progression. Speech disorders are particularly prevalent in neurological degenerative diseases such as Parkinson's disease, the focus of the study undertaken in this work. We will demonstrate state-of-the-art statistical time-series methods that combine elements of statistical time series modelling and signal processing with modern machine learning methods based on Gaussian process models to develop methods to accurately detect a core symptom of speech disorder in individuals who have Parkinson's disease. We will show that the proposed methods out-perform standard best practices of speech diagnostics in detecting ataxic speech disorders, and we will focus the study, particularly on a detailed analysis of a well regarded Parkinson's data speech study publicly available making all our results reproducible. The methodology developed is based on a specialised technique not widely adopted in medical statistics that found great success in other domains such as signal processing, seismology, speech analysis and ecology. In this work, we will present this method from a statistical perspective and generalise it to a stochastic model, which will be used to design a test for speech disorders when applied to speech time series signals. As such, this work is making contributions both of a practical and statistical methodological nature., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Campi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to understand baseline knowledge of basic principles of radiation therapy for lung cancer among medical oncology, thoracic surgery, and pulmonology trainees and practicing physicians and also assess whether a didactic lecture will improve objective knowledge and perceived comfort level in making appropriate referrals to radiation oncology (RO). Radiation oncologists at 8 academic institutions offered a presentation covering indications, logistics, efficacy, and toxicity of thoracic radiation. Participants completed a survey to assess their prior exposures to RO and perceived value of the lecture, and objective knowledge gained based on pre/post-lecture questions. Among 121 attendees, 76 completed the pre-test, and 25 the post-test (response rates 62.8% and 20.7%, respectively). Fifty-seven (75.0%) had never previously experienced a RO didactic about lung cancer, 62 (81.6%) had never seen a linear accelerator, and 65 (85.5%) had never rotated in a RO department. The mean pre-test score was 53.5% (SD 17.6%), with a trend (p = 0.066) towards thoracic surgeons (61.5%) performing better than medical oncologists (55.5%) or pulmonologists (48.3%). Level of training (p = 0.130), and prior RO exposures (p = 0.240), did not significantly impact pre-test scores. The mean post-test score of 75.1% (SD 3.6%) was significantly higher than mean pre-test score (p < 0.001). After the lecture, 25 participants (100%) felt more knowledgeable about RO, and 24 (96%) felt more comfortable making appropriate referrals to RO. A didactic lecture about RO for trainees and physicians who treat lung cancer at 8 academic institutions was feasible, filled a gap in exposure, and improved knowledge., (© 2022. The Author(s) under exclusive licence to American Association for Cancer Education.)

Purpose: To establish a simulation-based workshop for teaching hybrid intracavitary/interstitial (IC/IS) brachytherapy skills using a new, commercially available US/CT/MRI-compatible gynecologic phantom prototype., Methods and Materials: The VIOMERSE gynecological trainer phantom consisted of tissue-like colloid material and was US, CT, and MRI-compatible. We designed a hands-on workshop incorporating the phantom prototype to teach skills for hybrid IC/IS brachytherapy including pre-implant planning, procedural steps of implant placement, and post-implant evaluation. The workshop impact was evaluated with pre- and post-workshop surveys and responses were analyzed with Wilcoxon matched-pairs signed-rank test., Results: Thirteen residents, divided into small groups, attended one of three separate 1-h workshop sessions held during the gynecologic education block. Workshop steps included IC applicator placement, tumor mapping and pre-planning desired location and depth of needles for hybrid IC/IS application, IS needle labelling and insertion, image review of needle placements, comparison of IC-alone versus IC/IS brachytherapy plans. Responses to questions ascertaining knowledge, confidence, and ability in planning and executing hybrid IC/IS procedures all demonstrated significant improvement from pre- to post-workshop. In response to whether the session was an effective learning experience, all residents rated the workshop with a score of 9 (n = 1) or 10 (n = 12) out of 10, with a score of 10 indicating "strongly agree.", Conclusions: Implementation of a hybrid IC/IS brachytherapy workshop utilizing a new, commercially-available phantom prototype was successful, with clear, subjective benefit for the residents in our program. This experience may inform continued efforts towards standardizing brachytherapy curricula across programs and increasing trainee exposure to interstitial procedures., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

In this paper we focus on model risk and risk sensitivity when addressing the insurability of cyber risk. The standard statistical approaches to assessment of insurability and potential mispricing are enhanced in several aspects involving consideration of model risk. Model risk can arise from model uncertainty and parameter uncertainty. We demonstrate how to quantify the effect of model risk in this analysis by incorporating various robust estimators for key model parameters that apply in both marginal and joint cyber risk loss process modelling. Through this analysis we are able to address the question that, to the best of our knowledge, no other study has investigated in the context of cyber risk: is model risk present in cyber risk data, and how does is it translate into premium mispricing? We believe our findings should complement existing studies seeking to explore the insurability of cyber losses., Competing Interests: Competing interestsThe authors declared that they have no conflict of interest., (© The Author(s) 2023.)

Purpose: The COVID-19 pandemic largely suspended in-person scientific meetings because of risk of disease spread. In the era of vaccination and social distancing practices, meetings have begun returning to in-person formats. We surveyed attendees and potential attendees of 2 oncology meetings in the United States to identify rates of mixing behavior and the subsequent rate of self-reported COVID-19 infection., Methods and Materials: We collected via survey reported social mixing behavior and COVID-19 positivity (within 21 days of meeting conclusion) of actual and potential in-person attendees of the American Society of Clinical Oncology (ASCO) Quality Care Symposium held September 24 to 25, 2021, and the American Society for Radiation Oncology (ASTRO) Annual Meeting held October 24 to 27, 2021. Conference speakers and other participants were identified through publicly available meeting materials and targeted via e-mail when possible. Recruitment of additional attendees and potential attendees was also conducted through a sharable link promoted via oncology newsletters and social media. Descriptive statistics alone were performed owing to low COVID-19 event rates., Results: Response rates from targeted conference participants with publicly available e-mails were 27.4% for the ASCO and 14.3% for the ASTRO meetings. The ASCO survey produced 94 responses (48 in-person attendees). The ASTRO survey produced 370 responses (267 in-person attendees). Across both meetings, 3 of 308 (1.0%) in-person attendees versus 2 of 141 (1.4%) nonattendees tested positive for COVID-19. Low COVID-19 positivity rates were reported among in-person attendees spending more (>20) versus fewer (≤20) hours attending live sessions (2.2% vs 0%) and among indoor social event participants versus nonparticipants (0.8% vs 1.9%). Attendees largely felt comfortable attending additional in-person meetings after experiencing ASCO (87.5%) or ASTRO (91.9%) and felt mask compliance was good or excellent at ASCO (100%) and ASTRO (94.6%) meetings., Conclusions: In-person meetings do not seem to be contributing to high rates of new COVID-19 infections in the setting of vaccine and social distancing mandates, supporting paths forward for at least partially in-person conferences as COVID-19 becomes endemic., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Stereotactic body radiation therapy (SBRT) has increasingly been used to treat early-stage primary lung cancers, but its effectiveness and safety in patients with multiple synchronous primary lung tumors is not as well established. Our aim was to evaluate clinical outcomes, patterns of recurrence, and toxicities for these patients., Methods and Materials: We queried an institutional database of patients treated with SBRT for primary lung tumors from 2007 to 2019. Patients with known metastatic disease were excluded. Recurrences were described as new primaries (NP) if they occurred as an isolated pulmonary mass outside the previous planning target volume., Results: We analyzed 126 lesions from 60 consecutive patients who received SBRT synchronously to ≥2 lesions for nonmetastatic lung cancers. Median total dose per lesion was 50 Gy (range, 30-60 Gy) delivered over 3 to 5 fractions. All but 4 lesions were treated to a biologically effective dose ≥100 Gy. The median follow-up time was 47.3 months (interquartile range, 34.1-65.6). Median overall survival was 46.2 months. Two and 5-year overall survival for all patients was 70% and 48%, respectively. Median progression-free survival was 26 months (interquartile range, 7.6-32.6), and at the time of data collection 25 patients (42%) had experienced any disease progression. Median time to progression was 36 months: 9 (15%) patients experienced local failure, with 1- and 2-year local failure rates of 8% and 13%, respectively. Four patients (7%) experienced regional failure, at 3, 10, 30, and 50 months. Eleven patients (18%) experienced distant failure, with 2-year distant failure rate of 13%. Thirteen patients (21%) developed NPs, with 2-year NP rate of 15.1%. Fourteen patients (23%) experienced Common Terminology Criteria for Adverse Events grade ≥2 toxicity, and 2 patients (3%) experienced Common Terminology Criteria for Adverse Events grade ≥3 toxicity (pneumonitis and hemoptysis)., Conclusions: Synchronous SBRT to biologically effective dose ≥100 Gy appears safe and effective for selected patients with synchronous primary lung tumors., (Copyright © 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Although deep inspiratory breath-hold (DIBH) is routinely used for left-sided breast cancers, its benefits for right-sided breast cancer (rBC) have yet to be established. We compared free-breathing (FB) and DIBH treatment plans for a cohort of rBC undergoing regional nodal irradiation (RNI) to determine its potential benefits., Methods and Materials: rBC patients considered for RNI (internal mammary nodal chains, supraclavicular field, with or without axilla) from October 2017 to May 2020 were included in this analysis. For each patient, FB versus DIBH plans were generated and dose volume histograms evaluated the following parameters: mean lung dose, ipsilateral lung V 20 /V 5 (volumes of lung receiving 20 Gy and 5 Gy, respectively); mean heart dose and heart V 5 (volumes of heart receiving 5 Gy); liver V 20 absolute /V 30 absolute (absolute volume of liver receiving 20 Gy and 30 Gy, respectively), liver D max , and total liver volume irradiated (TVI liver ). The dosimetric parameters were compared using Wilcoxon signed-rank testing., Results: Fifty-four patients were eligible for analysis, comparing 108 FB and DIBH plans. DIBH significantly decreased all lung and liver parameters: mean lung dose (19.7 Gy-16.2 Gy, P < .001), lung V 20 (40.7%-31.7%, P < .001), lung V 5 (61.2%-54.5%, P < .001), TVI liver (1446 cc vs 1264 cc; P = .006) liver D max (50.2 Gy vs 48.9 Gy; P = .023), liver V 20 (78.8-23.9 cc, P < .001), and liver V 30 (58.1-14.6 cc, P < .001) compared with FB. DIBH use did not significantly improve heart parameters, although the V 5Heart trended on significance (1.25-0.6, P = .067)., Conclusions: This is the largest cohort to date analyzing DIBH for RNI-rBC. Our findings demonstrate significant improvement in all lung and liver parameters with DIBH, supporting its routine consideration for rBC patients undergoing comprehensive RNI., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To provide a comprehensive analysis of radiation oncology (RO) fellowship growth from 2010 to 2020., Methods and Materials: A collated database of RO fellowship programs and matriculants was created using (1) RO residency program (n = 92) and graduate (n = 2082) web searches, (2) prospective American Society for Radiation Oncology (ASTRO) Career Center postings database, (3) Association of Residents in Radiation Oncology Fellowship Directory, (4) RO fellowship survey data, (5) ASTRO Membership Directory, and (6) direct e-mail contact with fellowship program directors. Linear regression was used to assess the statistical significance of RO fellowship program, position, and matriculant growth over time., Results: From 2010 to 2020, the number of RO fellowship programs and annual positions significantly increased from 20 to 37 (1.60 increase per year; 95% confidence interval, 1.32-1.89; P < .001) and 20 to 39 (1.81 increase per year; 95% confidence interval, 1.52-2.10; P < .001), respectively. The most commonly offered fellowship disciplines were proton therapy (n = 10), brachytherapy (n = 7), stereotactic radiosurgery/stereotactic body radiation therapy (n = 6), general RO (n = 5), and customizable to trainees' interests (n = 3). Only 10 (27%) fellowships had a formal curriculum. All fellowships were unaccredited. Four (10.8%) programs were offered at institutions without an Accreditation Council for Graduate Medical Education-accredited RO residency training program, all established within the past 2 years. In addition, 54.8% (171 of 312) of available fellowship positions were filled between 2010 to 2020. Of these, 94 (55.0%) were graduates of US RO residency programs. The mean number of total fellows and US-residency trained fellows per year was 15 (range, 5-23) and 8 (range, 2-20), respectively. There was no significant increase in the number of annual matriculated fellows over time (P = .077). Among US-residency trained fellows, 27 (28.7%), 37 (39.4%), and 29 (30.9%) were from small (≤6), medium (7-12), and large (>12) residency programs, respectively. Twenty-eight (29.8%), 13 (13.8%), 25 (26.6%), and 27 (28.7%) trained in the Northeast, Midwest, South, and West, respectively., Conclusions: There has been significant growth in unaccredited RO fellowship programs and annual positions during the past decade, although the number of matriculants has remained stable. We report for the first time the recent establishment of fellowships at institutions without an Accreditation Council for Graduate Medical Education-accredited RO residency program. The impact of fellowship programs on the training of RO residents should be studied., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A class of models for non-Gaussian spatial random fields is explored for spatial field reconstruction in environmental and sensor network monitoring. The family of models explored utilises a class of transformation functions known as Tukey g-and-h transformations to create a family of warped spatial Gaussian process models which can support various desirable features such as flexible marginal distributions, which can be skewed, leptokurtic and/or heavy-tailed. The resulting model is widely applicable in a range of spatial field reconstruction applications. To utilise the model in applications in practice, it is important to carefully characterise the statistical properties of the Tukey g-and-h random fields. In this work, we study both the properties of the resulting warped Gaussian processes as well as using the characterising statistical properties of the warped processes to obtain flexible spatial field reconstructions. In this regard we derive five different estimators for various important quantities often considered in spatial field reconstruction problems. These include the multi-point Minimum Mean Squared Error (MMSE) estimators, the multi-point Maximum A-Posteriori (MAP) estimators, an efficient class of multi-point linear estimators based on the Spatial-Best Linear Unbiased (S-BLUE) estimators, and two multi-point threshold exceedance based estimators, namely the Spatial Regional and Level Exceedance estimators. Simulation results and real data examples show the benefits of using the Tukey g-and-h transformation as opposed to standard Gaussian spatial random fields in a real data application for environmental monitoring.

Background: Randomized controlled trials (RCTs) are the gold standard for evidence-based practice, but their development and implementation is resource intensive. We aimed to describe modern RCTs in gastrointestinal (GI) cancer and identify predictors of successful accrual and publication., Materials and Methods: ClinicalTrials.gov was queried for phase III GI cancer RCTs opened between 2010 and 2019 and divided into two cohorts: past and recruiting. Past trials were analyzed for predictors of successful accrual and the subset with ≥3 years follow-up were analyzed for predictors of publication. Univariate and multivariable (MVA) logistic regression were used to identify covariates associated with complete accrual and publication status., Results: A total of 533 GI RCTs were opened from 2010 to 2019, 244 of which are still recruiting. In the "past" trials cohort (235/533) MVA, Asian continent of enrollment was a predictor for successful accrual, whereas trials with prolonged enrollment (duration longer than median of 960 days) trended to failed accrual. Predictors for publication on MVA included international enrollment and accrual completion. Sponsorship was not associated with accrual or publication. Notably, 33% of past trials remain unpublished, and 60% of trials that were closed early remain unpublished., Conclusion: Accrual rate and the primary continent of enrollment drive both trial completion and publication in GI oncology. Accrual must be streamlined to enhance the impact of RCTs on clinical management. A large portion of trials remain unpublished, underscoring the need to encourage dissemination of all trials to, at a minimum, inform future trial design., Implications for Practice: Two-thirds of gastrointestinal (GI) oncology phase III randomized controlled trials successfully accrue; however, one third of these trials are unpublished and more than half of trials that close early are unpublished. The strongest predictors for publication are successful accrual and international collaborations. Initiatives to optimize the trial enrollment process need to be explored to maximize the potential for trials to engender progress in clinical practice. Moreover, this study identified a significant publication bias in the realm of GI oncology, and the field should promote reporting of all trials in order to better inform future trial questions and design., (© 2021 AlphaMed Press.)

During the COVID-19 pandemic, governments globally had to impose severe contact restriction measures and social mobility limitations in order to limit the exposure of the population to COVID-19. These public health policy decisions were informed by statistical models for infection rates in national populations. In this work, we are interested in modelling the temporal evolution of national-level infection counts for the United Kingdom (UK-Wales, England, Scotland), Germany (GM), Italy (IT), Spain (SP), Japan (JP), Australia (AU) and the United States (US). We model the national-level infection counts for the period January 2020 to January 2021, thus covering both the pre- and post-vaccine roll-out periods, in order to better understand the most reliable model structure for the COVID-19 epidemic growth curve. We achieve this by exploring a variety of stochastic population growth models and comparing their calibration, with respect to in-sample fitting and out-of-sample forecasting, both with and without exposure adjustment, to the most widely used and reported growth model, the Gompertz population model, often referred to in the public health policy discourse during the COVID-19 pandemic. Model risk as we explore it in this work manifests in the inability to adequately capture the behaviour of the disease progression growth rate curve. Therefore, our concept of model risk is formed relative to the standard reference Gompertz model used by decision-makers, and then we can characterise model risk mathematically as having two components: the dispersion of the observation distribution, and the structure of the intensity function over time for cumulative counts of new infections daily (i.e. the force of infection) attributed directly to the COVID-19 pandemic. We also explore how to incorporate in these population models the effect that governmental interventions have had on the number of infected cases. This is achieved through the development of an exposure adjustment to the force of infection comprised of a purpose-built sentiment index, which we construct from various authoritative public health news reporting. The news reporting media we employed were the New York Times, the Guardian, the Telegraph, Reuters global blog, as well as national and international health authorities: the European Centre for Disease Prevention and Control, the United Nations Economic Commission for Europe, the United States Centres for Disease Control and Prevention, and the World Health Organisation. We find that exposure adjustments that incorporate sentiment are better able to calibrate to early stages of infection spread in all countries under study., Competing Interests: The authors have declared that no competing interests exist.

Purpose/objectives: Treatment planning systems (TPS) for Gamma Knife stereotactic radiosurgery (GK-SRS) include TMR10 algorithms, which assumes tissue homogeneity equivalent to water, and collapsed-cone convolutional (CCC) algorithms, which accounts for tissue inhomogeneity. This study investigated dosimetric differences between TMR10 and CCC TPS for acoustic neuromas (ANs) treated with GK-SRS., Materials/methods: A retrospective review of 56 AN treated with GK-SRS was performed. All patients underwent MRI and CT imaging during their initial treatment and were planned using TMR10. Each plan was recalculated with CCC using electron density extracted from CT. Parameters of interest included D max , D min , D 50% , cochlea D max , mean cochlea dose, target size, and laterality (>20 mm from central axis)., Results: Median target volume of patients was 1.5 cc (0.3 cc-2.8 cc) with median dose of 12 Gy prescribed to the 50% isodose line. Compared to CCC algorithms, the TMR10 calculated dose was higher: D max was higher by an average 6.2% (p < 0.001), D min was higher by an average 3.1% (p < 0.032), D 50% was higher by an average of 11.3%. For lateralized targets, calculated D max and D 50% were higher by 7.1% (p < 0.001) and 10.6% (p < 0.001), respectively. For targets <1 cc, D max and D 50% were higher by 8.9% (p ≤ 0.009) and 12.1% (p ≤ 0.001), respectively. Cochlea D max was higher, by an average of 20.1% (p < 0.001)., Conclusion: There was a statistically significant dosimetric differences observed between TMR10 and CCC algorithms for AN GK-SRS, particularly in small and lateralized ANs. It may be important to note these differences when relating GK-SRS with standard heterogeneity-corrected SRS regimens., Competing Interests: Authors’ disclosure of potential conflicts of interest Dr Aneja receives research support from the National Science Foundation, American Society for Clinical Oncology, National Cancer Institute, and Agency for Healthcare Research and Quality. Dr. Yu reports personal fees for consulting from Augment/Boston Scientific and is on the advisory board of Galera Pharmaceuticals, all of which are outside the submitted work. Dr. Chiang reports personal fees for consulting and speaking for Monteris Medical Inc, MRI Interventions, and Brainlab, all of which are outside the submitted work. Dr. Hansen reports stock options from Patrys Limited and has various patents outside of the submitted work. The remaining authors have nothing to disclose., (© 2021 Old City Publishing, Inc.)

Background: There are unique challenges to parenting in residency and there is limited data to guide policy regarding lactation facilities and support for female physicians-in-training. We aimed to assess issues surrounding breast-feeding during graduate medical training for current residents or recent graduates from United States (US) residency programs., Methods: A national cross-sectional survey was sent to current and recently graduated (2017 and later) female residents in June 2020. This questionnaire was administered using the Qualtrics Survey tool and was open to each participating woman's organization for 4 weeks. Summary statistics were used to describe characteristics of all respondents and free-text responses were reviewed to identify common themes regarding avenues for improvement., Results: Three hundred twelve women responded to the survey, representing a 15.6% response rate. The median duration of providing breastmilk was 9 months (IQR 6-12). 21% of residents reported access to usable lactation rooms within their training hospital, in which 12% reported a computer was present. 60% of lactating residents reported not having a place to store breast milk. 73% reported residency limited their ability to lactate, and 37% stopped prior to their desired goal. 40% reported their faculty and/or co-residents made them feel guilty for their decision to breastfeed, and 56% reported their difficulties with breastfeeding during residency impacted their mental health., Conclusion: Residents who become mothers during training face significant obstacles to meeting their breastfeeding/pumping needs and goals. With these barriers defined, informed policy change can be instituted to improve the lactation experience for physicians-in-training.

Purpose: Medical errors in radiation oncology sometimes involve tasks reliant on practitioners' grasp of numeracy. Numeracy has been shown to be suboptimal across various health care professionals. Herein, we assess health numeracy among American Society of Radiologic Technologists (ASRT) members., Methods and Materials: The Numeracy Understanding for Medicine instrument (NUMi), an instrument to measure numeracy in the general population, was adapted to oncology for this study and distributed to ASRT members (n = 14,228) in 2017. Per NUMi scoring, health numeracy scores were categorized as low (0-7), low average (8-12), high average (13-17), or high (18-20). The impact of cGy versus Gy on numeracy performance was investigated. Spearman's rho and a Wilcox-Mann-Whitney test were used for comparisons between the different groups., Results: A total of 662 eligible participants completed the instrument and identified as radiation oncology professionals. In the cGy and Gy NUMi scores, approximately 2% of respondents scored low-average, approximately 40% scored high-average, and approximately 58% scored high, with a median score of 18.0. Although the optimum NUMi score for ASRT members is unknown, one might expect our cohort to have numeracy skills at least as high as college freshmen. Roughly one-sixth of our study group scored at or below the average score of college freshmen (NUMi = 15). In the subset analysis of NUMi questions pertaining to radiation dose unit (cGy vs Gy), respondents performed better with cGy (mean score: 2.94; range, 2-3) versus Gy (mean: 2.91; range, 0-3; P = .011)., Conclusions: In this study of limited sample size, overall numeracy is quite good compared with the general population. However, the range of scores is wide, and some respondents have lower scores that may be concerning, suggesting that numeracy may be an issue that requires improvement for a subset of the studied cohort. Performance was superior with the unit cGy; thus, the adoption of cGy as the standard unit is reasonable.

Background: Presently, educational programming is not standardized across radiation oncology (RO) training programs. Specifically, there are limited materials through national organizations or structured practice exams for residents preparing for the American Board of Radiology (ABR) oral board examination. We present our 2019 experience implementing a formalized program of early mock oral board examinations (MOBE) for residents in post-graduate years (PGY) 3-5., Methods: A mixed-methods survey regarding MOBE perception and self-reported comfort across five clinical domains were administered to PGY2-5 residents. MOBEs and a post-intervention survey were implemented for the PGY3-5. The pre and post-intervention score across clinical domains were compared using t-tests. Faculty and residents were asked for post-intervention comments., Results: A total of 14 PGY2-5 residents completed the pre-intervention survey; 9 residents participated in the MOBE (5/14 residents were PGY2s) and post-intervention survey. This was the first mock oral radiation oncology examination experience for 65% of residents. 100% of residents felt the MOBE increased their clinical knowledge and comfort with clinical reasoning. Overall, there was a trend towards improved resident confidence giving planning dose parameters and (p = 0.08). There was also unanimous request for more MOBE experiences from residents and faculty, but time was identified as a significant barrier., Conclusions: Future directions for this MOBE program are inclusion of more disease sites, better emulation of the exam, the creation of a more rigorous consolidated format testing all sites at once, and consideration for grading of these sessions for future correlation with certifying oral board examination (OBE) performance.

Longitudinal human gut microbiome datasets generated using community-level, sequence-based approaches often report a sub-set of long-lived "resident" taxa that rarely, if ever, are lost. This result contrasts with population-level turnover of resident clones on the order of months to years. We hypothesized that the disconnect between these results is due to a relative lack of simultaneous discrimination of the human gut microbiome at both the community and population-levels. Here, we present results of a small, longitudinal cohort study (n = 8 participants) of healthy human adults that identifies static and dynamic members of the gut microbiome at the clone level based on cultivation/genetic discrimination and at the operational taxonomic unit/amplified sequence variant levels based on 16S rRNA sequencing. We provide evidence that there is little "stability" within resident clonal populations of the common gut microbiome bacterial family, Enterobacteriaceae. Given that clones can vary substantially in genome content and that evolutionary processes operate on the population level, these results question the biological relevance of apparent stability at higher taxonomic levels.

We derive explicit solutions to the problem of completing a partially specified correlation matrix. Our results apply to several block structures for the unspecified entries that arise in insurance and risk management, where an insurance company with many lines of business is required to satisfy certain capital requirements but may have incomplete knowledge of the underlying correlation matrix. Among the many possible completions, we focus on the one with maximal determinant. This has attractive properties and we argue that it is suitable for use in the insurance application. Our explicit formulae enable easy solution of practical problems and are useful for testing more general algorithms for the maximal determinant correlation matrix completion problem., Competing Interests: The authors have no competing interests.

Quantifying the effects of environmental factors over the duration of the growing process on Agaricus Bisporus (button mushroom) yields has been difficult, as common functional data analysis approaches require fixed length functional data. The data available from commercial growers, however, is of variable duration, due to commercial considerations. We employ a recently proposed regression technique termed Variable-Domain Functional Regression in order to be able to accommodate these irregular-length datasets. In this way, we are able to quantify the contribution of covariates such as temperature, humidity and water spraying volumes across the growing process, and for different lengths of growing processes. Our results indicate that optimal oxygen and temperature levels vary across the growing cycle and we propose environmental schedules for these covariates to optimise overall yields.

The mechanical properties determine to a large extent the functioning of a blood clot. These properties depend on the composition of the clot and have been related to many diseases. However, the various involved components and their complex interactions make it difficult at this stage to fully understand and predict properties as a function of the components. Therefore, in this study, a constitutive model is developed that describes the viscoelastic behavior of blood clots with various compositions. Hereto, clots are formed from whole blood, platelet-rich plasma and platelet-poor plasma to study the influence of red blood cells, platelets and fibrin, respectively. Rheological experiments are performed to probe the mechanical behavior of the clots during their formation. The nonlinear viscoelastic behavior of the mature clots is characterized using a large amplitude oscillatory shear deformation. The model is based on a generalized Maxwell model that accurately describes the results for the different rheological experiments by making the moduli and viscosities a function of time and the past and current deformation. Using the same model with different parameter values enables a description of clots with different compositions. A sensitivity analysis is applied to study the influence of parameter variations on the model output. The relative simplicity and flexibility make the model suitable for numerical simulations of blood clots and other materials showing similar behavior.

Blood clot formation is important to prevent blood loss in case of a vascular injury but disastrous when it occludes the vessel. As the mechanical properties of the clot are reported to be related to many diseases, it is important to have a good understanding of their characteristics. In this study, a constitutive model is presented that describes the nonlinear viscoelastic properties of the fibrin network, the main structural component of blood clots. The model is developed using results of experiments in which the fibrin network is subjected to a large amplitude oscillatory shear (LAOS) deformation. The results show three dominating nonlinear features: softening over multiple deformation cycles, strain stiffening and increasing viscous dissipation during a deformation cycle. These features are incorporated in a constitutive model based on the Kelvin-Voigt model. A network state parameter is introduced that takes into account the influence of the deformation history of the network. Furthermore, in the period following the LAOS deformation, the stiffness of the networks increases which is also incorporated in the model. The influence of cross-links created by factor XIII is investigated by comparing fibrin networks that have polymerized for 1 and 2 h. A sensitivity analysis provides insights into the influence of the eight fit parameters. The model developed is able to describe the rich, time-dependent, nonlinear behavior of the fibrin network. The model is relatively simple which makes it suitable for computational simulations of blood clot formation and is general enough to be used for other materials showing similar behavior.

Flow-induced structure formation is investigated with in situ wide-angle X-ray diffraction with high acquisition rate (30 Hz) using isotactic polypropylene in a piston-driven slit flow with high wall shear rates (up to ≈900 s(-1) ). We focus on crystallization within the shear layers that form in the high shear rate regions near the walls. Remarkably, the kinetics of the crystallization process show no dependence on either flow rate or flow time; the crystallization progresses identically regardless. Stronger or longer flows only increase the thickness of the layers. A conceptual model is proposed to explain the phenomenon. Above a certain threshold, the number of shish-kebabs formed affects the rheology such that further structure formation is halted. The critical amount is reached already within 0.1 s under the current flow conditions. The change in rheology is hypothesized to be a consequence of the "hairy" nature of shish. Our results have large implications for process modelling, since they suggest that for injection molding type flows, crystallization kinetics can be considered independent of deformation history., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A Bayesian statistical model and estimation methodology based on forward projection adaptive Markov chain Monte Carlo is developed in order to perform the calibration of a high-dimensional nonlinear system of ordinary differential equations representing an epidemic model for human papillomavirus types 6 and 11 (HPV-6, HPV-11). The model is compartmental and involves stratification by age, gender and sexual-activity group. Developing this model and a means to calibrate it efficiently is relevant because HPV is a very multi-typed and common sexually transmitted infection with more than 100 types currently known. The two types studied in this paper, types 6 and 11, are causing about 90% of anogenital warts. We extend the development of a sexual mixing matrix on the basis of a formulation first suggested by Garnett and Anderson, frequently used to model sexually transmitted infections. In particular, we consider a stochastic mixing matrix framework that allows us to jointly estimate unknown attributes and parameters of the mixing matrix along with the parameters involved in the calibration of the HPV epidemic model. This matrix describes the sexual interactions between members of the population under study and relies on several quantities that are a priori unknown. The Bayesian model developed allows one to estimate jointly the HPV-6 and HPV-11 epidemic model parameters as well as unknown sexual mixing matrix parameters related to assortativity. Finally, we explore the ability of an extension to the class of adaptive Markov chain Monte Carlo algorithms to incorporate a forward projection strategy for the ordinary differential equation state trajectories. Efficient exploration of the Bayesian posterior distribution developed for the ordinary differential equation parameters provides a challenge for any Markov chain sampling methodology, hence the interest in adaptive Markov chain methods. We conclude with simulation studies on synthetic and recent actual data., (Copyright © 2012 John Wiley & Sons, Ltd.)

Deterministic dynamic compartmental transmission models (DDCTMs) of human papillomavirus (HPV) transmission have been used in a number of studies to estimate the potential impact of HPV vaccination programs. In most cases, the models were built under the assumption that an individual who cleared HPV infection develops (life-long) natural immunity against re-infection with the same HPV type (this is known as SIR scenario). This assumption was also made by two Australian modelling studies evaluating the impact of the National HPV Vaccination Program to assist in the health-economic assessment of male vaccination. An alternative view denying natural immunity after clearance (SIS scenario) was only presented in one study, although neither scenario has been supported by strong evidence. Some recent findings, however, provide arguments in favour of SIS. We developed HPV transmission models implementing life-time (SIR), limited, and non-existent (SIS) natural immunity. For each model we estimated the herd immunity effect of the ongoing Australian HPV vaccination program and its extension to cover males. Given the Australian setting, we aimed to clarify the extent to which the choice of model structure would influence estimation of this effect. A statistically robust and efficient calibration methodology was applied to ensure credibility of our results. We observed that for non-SIR models the herd immunity effect measured in relative reductions in HPV prevalence in the unvaccinated population was much more pronounced than for the SIR model. For example, with vaccine efficacy of 95% for females and 90% for males, the reductions for HPV-16 were 3% in females and 28% in males for the SIR model, and at least 30% (females) and 60% (males) for non-SIR models. The magnitude of these differences implies that evaluations of the impact of vaccination programs using DDCTMs should incorporate several model structures until our understanding of natural immunity is improved., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Extreme risks in ecology are typified by circumstances in which data are sporadic or unavailable, understanding is poor, and decisions are urgently needed. Expert judgments are pervasive and disagreements among experts are commonplace. We outline approaches to evaluating extreme risks in ecology that rely on stochastic simulation, with a particular focus on methods to evaluate the likelihood of extinction and quasi-extinction of threatened species, and the likelihood of establishment and spread of invasive pests. We evaluate the importance of assumptions in these assessments and the potential of some new approaches to account for these uncertainties, including hierarchical estimation procedures and generalized extreme value distributions. We conclude by examining the treatment of consequences in extreme risk analysis in ecology and how expert judgment may better be harnessed to evaluate extreme risks., (© 2012 Society for Risk Analysis.)

Skin is a multilayer composite and exhibits highly non-linear, viscoelastic, anisotropic material properties. In many consumer product and medical applications (e.g. during shaving, needle insertion, patient re-positioning), large tissue displacements and deformations are involved; consequently large local strains in the skin tissue can occur. Here, we present a novel imaging-based method to study skin deformations and the mechanics of interacting skin layers of full-thickness skin. Shear experiments and real-time video recording were combined with digital image correlation and strain field analysis to visualise and quantify skin layer deformations during dynamic mechanical testing. A global shear strain of 10% was applied to airbrush-patterned porcine skin (thickness: 1.2-1.6mm) using a rotational rheometer. The recordings were analysed with ARAMIS image correlation software, and local skin displacement, strain and stiffness profiles through the skin layers determined. The results of this pilot study revealed inhomogeneous skin deformation, characterised by a gradual transition from a low (2.0-5.0%; epidermis) to high (10-22%; dermis) shear strain regime. Shear moduli ranged from 20 to 130kPa. The herein presented method will be used for more extended studies on viable human skin, and is considered a valuable foundation for further development of constitutive models which can be used in advanced finite element analyses of skin., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Nature uses mechanochemical transduction processes to achieve diverse and vital functions, such as hearing, cellular adhesion and gating of ion channels. One fascinating example of biological mechanotransduction is the emission of light on mechanical stimulation. However, molecular-level transduction of force into luminescence in a synthetic system remains a challenge. Here, we show that bis(adamantyl)-1,2-dioxetane emits visible light when force is applied to a polymer chain or network in which this unit is incorporated. Bright-blue luminescence was observed on sonication of solutions of dioxetane-containing linear polymers and on the straining of polymer networks with dioxetane crosslinkers. Light is emitted from the adamantanone-excited state that forms on opening of the four-membered dioxetane ring. Increased sensitivity and colour tuning were achieved by energy transfer to suitable acceptors. High spatial and temporal resolutions highlight the potential to study the failure of polymeric materials in unprecedented detail.

Although subcutaneous adipose tissue undergoes large deformations on a daily basis, there is no adequate mechanical model to describe the transfer of mechanical load from the skin throughout the tissue to deeper layers. In order to develop such a non-linear model, a set of experimental data is required. Accordingly, this study examines the long term behavior of adipose tissue under small strain and its response to various large strain profiles. The results show that the shear modulus dramatically increases to about an order of magnitude after a loading period between 250 and 1250 s, but returns to its initial value within 3 h of recovery from loading. In addition, it was observed that the stress-strain responses for various large strain history sequences are reproducible up to a strain of 0.15. For increasing strains, the stress decreases for subsequent loading cycles and, above 0.3 strain, tissue structure changes such that the stress becomes independent of the applied strain. From the results, it can be concluded that adipose tissue likely behaves as an (anti-) thixotropic material and that a Mooney-Rivlin model might be appropriate to simulate behavior at physiologically relevant high strains. However, before the model is developed more fully, further experimental research is needed to ratify that the material is (anti-)thixotropic., (Copyright 2009 Elsevier Ltd. All rights reserved.)