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Purpose: Cardiac substructure dose metrics are more strongly linked to late cardiac morbidities than to whole-heart metrics. Magnetic resonance (MR)-guided radiation therapy (MRgRT) enables substructure visualization during daily localization, allowing potential for enhanced cardiac sparing. We extend a publicly available state-of-the-art deep learning framework, "No New" U-Net, to incorporate self-distillation (nnU-Net.wSD) for substructure segmentation for MRgRT., Methods and Materials: Eighteen (institute A) patients who underwent thoracic or abdominal radiation therapy on a 0.35 T MR-guided linear accelerator were retrospectively evaluated. On each image, 1 of 2 radiation oncologists delineated reference contours of 12 cardiac substructures (chambers, great vessels, and coronary arteries) used to train (n = 10), validate (n = 3), and test (n = 5) nnU-Net.wSD by leveraging a teacher-student network and comparing it to standard 3-dimensional U-Net. The impact of using simulation data or including 3 to 4 daily images for augmentation during training was evaluated for nnU-Net.wSD. Geometric metrics (Dice similarity coefficient, mean distance to agreement, and 95% Hausdorff distance), visual inspection, and clinical dose-volume histograms were evaluated. To determine generalizability, institute A's model was tested on an unlabeled data set from institute B (n = 22) and evaluated via consensus scoring and volume comparisons., Results: nnU-Net.wSD yielded a Dice similarity coefficient (reported mean ± SD) of 0.65 ± 0.25 across the 12 substructures (chambers, 0.85 ± 0.05; great vessels, 0.67 ± 0.19; and coronary arteries, 0.33 ± 0.16; mean distance to agreement, <3 mm; mean 95% Hausdorff distance, <9 mm) while outperforming the 3-dimensional U-Net (0.583 ± 0.28; P <.01). Leveraging fractionated data for augmentation improved over a single MR simulation time point (0.579 ± 0.29; P <.01). Predicted contours yielded dose-volume histograms that closely matched those of the clinical treatment plans where mean and maximum (ie, dose to 0.03 cc) doses deviated by 0.32 ± 0.5 Gy and 1.42 ± 2.6 Gy, respectively. There were no statistically significant differences between institute A and B volumes (P >.05) for 11 of 12 substructures, with larger volumes requiring minor changes and coronary arteries exhibiting more variability., Conclusions: This work is a critical step toward rapid and reliable cardiac substructure segmentation to improve cardiac sparing in low-field MRgRT., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Personal recovery is a persisting concern for people with psychotic disorders. Accordingly, mental health services have adopted frameworks of personal recovery, prioritizing adaptation to psychosis alongside symptom remission. Group acceptance and commitment therapy (ACT) for psychosis aims to promote personal recovery alongside improved mood and quality of life., Aims: The objectives of this uncontrolled, prospective pilot study were to determine whether 'Recovery ACT' groups for adults are a feasible, acceptable and safe program within public mental health services, and assess effectiveness through measuring changes in personal recovery, wellbeing, and psychological flexibility., Method: Program feasibility, acceptability and safety indicators were collected from referred consumers ( n =105). Adults ( n =80) diagnosed with psychotic disorders participated in an evaluation of 'Recovery ACT' groups in Australian community public mental health services. Participants completed pre- and post-group measures assessing personal recovery, wellbeing, and psychological flexibility., Results: Of 101 group enrollees, 78.2% attended at least one group session ( n =79); 73.8% attended three or more, suggesting feasibility. Eighty of 91 first-time attendees participated in the evaluation. Based on completer analyses ( n =39), participants' personal recovery and wellbeing increased post-group. Outcome changes correlated with the linear combination of psychological flexibility measures., Conclusions: 'Recovery ACT' groups are feasible, acceptable and safe in Australian public mental health services. 'Recovery ACT' may improve personal recovery, wellbeing, and psychological flexibility. Uncontrolled study design, completer analyses, and program discontinuation rates limit conclusions.

Purpose: We aimed to demonstrate the clinical feasibility and safety of simulation-free hippocampal avoidance whole brain radiation therapy (HA-WBRT) in a pilot study (National Clinical Trial 05096286)., Methods and Materials: Ten HA-WBRT candidates were enrolled for treatment on a commercially available computed tomography (CT)-guided linear accelerator with online adaptive capabilities. Planning structures were contoured on patient-specific diagnostic magnetic resonance imaging (MRI), which were registered to a CT of similar head shape, obtained from an atlas-based database (AB-CT). These patient-specific diagnostic MRI and AB-CT data sets were used for preplan calculation, using NRG-CC001 constraints. At first fraction, AB-CTs were used as primary data sets and deformed to patient-specific cone beam CTs (CBCT) to give patient-matched density information. Brain, ventricle, and brain stem contours were matched through rigid translation and rotation to the corresponding anatomy on CBCT. Lens, optic nerve, and brain contours were manually edited based on CBCT visualization. Preplans were then reoptimized through online adaptation to create final, simulation-free plans, which were used if they met all objectives. Workflow tasks were timed. In addition, patients underwent CT-simulation to create immobilization devices and for prospective dosimetric comparison of simulation-free and simulation-based plans., Results: Median time from MRI importation to completion of "preplan" was 1 weekday (range, 1-4). Median on-table workflow duration was 41 minutes (range, 34-70). NRG-CC001 constraints were achieved by 90% of the simulation-free plans. One patient's simulation-free plan failed a planning target volume coverage objective (89% instead of 90% coverage); this was deemed acceptable for first-fraction delivery, with an offline replan used for subsequent fractions. Both simulation-free and simulation CT-based plans otherwise met constraints, without clinically meaningful differences., Conclusions: Simulation-free HA-WBRT using online adaptive radiation therapy is feasible, safe, and results in dosimetrically comparable treatment plans to simulation CT-based workflows while providing convenience and time savings for patients., (Copyright © 2024. Published by Elsevier Inc.)

Background: With efforts increasing worldwide to understand and treat paranoia, there is a pressing need for cross-culturally valid assessments of paranoid beliefs. The recently developed Revised Green et al., Paranoid Thoughts Scale (R-GPTS) constitutes an easy to administer self-report assessment of mild ideas of reference and more severe persecutory thoughts. Moreover, it comes with clinical cut-offs for increased usability in research and clinical practice. With multiple translations of the R-GPTS already available and in use, a formal test of its measurement invariance is now needed., Methods: Using data from a multinational cross-sectional online survey in the UK, USA, Australia, Germany, and Hong Kong ( N = 2510), we performed confirmatory factory analyses on the R-GPTS and tested for measurement invariance across sites., Results: We found sufficient fit for the two-factor structure (ideas of reference, persecutory thoughts) of the R-GPTS across cultures. Measurement invariance was found for the persecutory thoughts subscale, indicating that it does measure the same construct across the tested samples in the same way. For ideas of reference, we found no scalar invariance, which was traced back to (mostly higher) item intercepts in the Hong Kong sample., Conclusion: We found sufficient invariance for the persecutory thoughts scale, which is of substantial practical importance, as it is used for the screening of clinical paranoia. A direct comparison of the ideas of reference sum-scores between cultures, however, may lead to an over-estimation of these milder forms of paranoia in some (non-western) cultures.

Effective interventions that facilitate adjustment following acquired brain injury (ABI) are needed to improve long-term outcomes and meaningful reengagement in life. VaLiANT is an 8-week group intervention that combines cognitive rehabilitation with Acceptance and Commitment therapy to improve valued living, wellbeing, and adjustment. This study explored participant experiences of VaLiANT to optimize its ongoing development. This included characterization of individually meaningful treatment outcomes, mechanisms of action, and intervention acceptability. Qualitative interviews and quantitative ratings were collected from 39 ABI survivors ( M age  = 52, SD  = 15; 54% stroke) following their participation in VaLiANT. Participants reported diverse outcomes which resulted in three themes being generated following reflexive thematic analysis. "A fuller toolkit for life with brain injury" indicated increased strategy usage and better daily functioning; "The value of connection and belonging" captured the importance of social experiences in shaping recovery; and "Finding the me I can be" represented cognitive, behavioural, and emotional aspects of identity reconstruction post-ABI. The content and delivery of the intervention were rated highly but participants desired greater follow-up and tailoring of the intervention. Overall, VaLiANT appears to facilitate adjustment through several mechanisms, but greater intervention individualization and dosage may be required to enhance the treatment impact.

Background: Psychological interventions, along with antipsychotic medications, are recommended for adults diagnosed with a psychotic disorder. While initially designed to mitigate positive symptoms, psychological interventions targeting personal recovery were developed and aligned with the recovery framework that many mental health services have adopted. Acceptance and Commitment Therapy (ACT) for psychosis is one such intervention that shows promise when delivered in an individual format. There is preliminary evidence that ACT for psychosis in a group format improves recovery., Objective: This trial aims to evaluate the effectiveness of the "Recovery ACT" group program on personal recovery among adults living with a psychotic disorder., Methods: Our unfunded study is a multiagency, prospective, nonrandomized, waitlist control, single-group trial of the Recovery ACT group program. The program involves 7 weekly group sessions of 90 minutes duration and a 90-minute booster session held 1 month later. We intend to recruit 160 adults living with a psychotic disorder who enroll in a group that is offered as a routine clinical service at participating public mental health services in Melbourne, Victoria, Australia. The 4 assessment time points are 4-6 weeks before the start of the group program, at the start of the group program, at the end of the group program, and at the booster session. There is an optional midgroup assessment and follow-up study. The primary outcome is personal recovery. Secondary outcomes include participants' well-being and psychological flexibility processes. Qualitative data are also collected from participants and facilitators., Results: Recruitment began in September 2019 and is ongoing until 2024, subsequent to a 24-month disruption due to the COVID-19 pandemic. As of the submission of this paper, 93 participants consented to the evaluation, 65 completed T1 measures, and 40 had a complete data set for the proposed analyses., Conclusions: This is the first trial evaluating the effectiveness of the Recovery ACT group program on personal recovery for adults living with a psychotic disorder. Findings will contribute to knowledge about psychosocial interventions for adults living with psychosis. This trial may also serve as an example of a partnership between clinicians and academics that can facilitate the translation of research into practice., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12620000223932; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000223932., International Registered Report Identifier (irrid): DERR1-10.2196/49849., (©Marilyn L Cugnetto, Eric M J Morris, Siobain F Bonfield, Jesse Gates, Ilona Morrison, Ellie R Newman, Julia D Nicholls, Lisa M Soares, Megan T Antonucci, Jacinta R Clemente, Claire L M Garratt, Eliot Goldstone, David A Pavone, John Farhall. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 18.03.2024.)

We successfully implemented an APRT specializing in CBCT-guided online adaptive contouring. These data show statistical improvements in contouring time with APRT-led vs non-APRT led ART contouring, suggesting that an APRT specifically trained to manage the ART process may reduce physician workload and patient treatment time., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purpose: Acceptance and Commitment Therapy for psychosis (ACTp) is a contextual behavioural intervention that promotes psychological flexibility by fostering active acceptance, cognitive defusion, values construction and committed action to enhance well-being and recovery. Multiple studies have shown that ACTp is acceptable and efficacious, but questions remain as to its distinction from similar approaches and the conditions under which it would be implemented most effectively., Methods: We present the current evidence for processes and outcomes of ACTp and summarise the qualitative findings of experiences of service users in ACT programmes. We compare ACTp with other cognitive behavioural therapies and mindfulness-informed interventions for psychosis., Results: Acceptance and commitment therapy for psychosis is promising as a pragmatic, process-driven intervention model. Further efforts are needed to investigate psychological flexibility in the context of psychosis with observational, experimental and intervention studies that will inform model scope and treatment refinement. Additionally, implementation research is the necessary next step, including how support persons can be trained in ACTp. Lower intensity and technology-assisted approaches have the potential to reduce barriers to accessing ACTp and extend impact., Conclusions: Over the last 20 years, ACTp has demonstrated meaningful effects in individual and group formats in a range of settings, targeting outcomes such as rehospitalisation, depression, psychotic symptom distress and impact. Future work should focus on how best to integrate ACTp with other current evidence-based interventions for psychosis., (© 2023 The Authors. Psychology and Psychotherapy: Theory, Research and Practice published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Although mostly considered distinct, conspiracy mentality and paranoia share conceptual similarities (e.g., persecutory content, resistance to disconfirming evidence). Using self-report data from a large and multinational online sample (N = 2510; from the UK, the US, Hong Kong, Germany, and Australia), we examined whether paranoia and conspiracy mentality represent distinct latent constructs in exploratory and confirmatory factor analyses. Utilising network analysis, we then explored common and unique correlates of paranoia and conspiracy mentality while accounting for their shared variance. Across sites, paranoia and conspiracy mentality presented distinct, yet weakly correlated (r = 0.26), constructs. Both were associated with past traumatic experiences, holding negative beliefs about the self and other people, sleep problems, and a tendency to worry. However, paranoia was related to increased negative affect (i.e., anxiety) and decreased social support, whereas the opposite pattern was observed for conspiracy mentality (i.e., decreased anxiety and depression, increased social support). Paranoia and conspiracy mentality are related but not the same constructs. Their similar and distinct correlates point to common and unique risk factors and underlying mechanisms., (© 2023. The Author(s).)

Background: The public's adherence to recommended COVID-19 preventative behaviors, including vaccinations and social distancing, has been low in certain groups and has contributed to many preventable deaths worldwide. An examination of general and pandemic-specific aspects of nonclinical paranoid ideation may aid in the understanding of the public's response to the pandemic, given that it is a global threat event., Methods: A representative international sample of general adults (N = 2,510) from five international sites were recruited with stratified quota sampling. Structural equation modeling (SEM) was used to examine the relationships among general paranoid ideation, pandemic paranoid ideation (interpersonal mistrust, conspiratorial thinking, and persecutory threat), general distress (depression, anxiety), vaccine willingness, and other preventative behaviors (masking, social distancing, hygiene)., Results: Although general distress and paranoid ideation were associated with vaccination willingness and preventative behaviors, their effects were inconsistent or weak. Pandemic paranoid ideation showed robust direct and indirect effects that differentially predicted COVID-19 preventative behaviors, with higher interpersonal mistrust associated with higher adherence to all behaviors, higher conspiratorial thinking related to lower adherence to all behaviors, and higher persecutory threat related to higher vaccine willingness, but lower adherence to other preventative behaviors., Conclusions: Examination of pandemic-specific paranoid ideation leads to more precise prediction of the public's adherence to recommended health behaviors during the COVID-19 outbreak. This information could be used to inform intervention strategies for micro-targeting different subgroups with nonclinical paranoid thinking, as well as for improving responses to future pandemics and vaccination efforts for other common illnesses., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Deep neural nets have revolutionized the science of auto-segmentation and present great promise for treatment planning automation. However, little data exists regarding clinical implementation and human factors. We evaluated the performance and clinical implementation of a novel deep learning-based auto-contouring workflow for 0.35T magnetic resonance imaging (MRI)-guided pelvic radiotherapy, focusing on automation bias and objective measures of workflow savings., Methods: An auto-contouring model was developed using a UNet-derived architecture for the femoral heads, bladder, and rectum in 0.35T MR images. Training data was taken from 75 patients treated with MRI-guided radiotherapy at our institution. The model was tested against 20 retrospective cases outside the training set, and subsequently was clinically implemented. Usability was evaluated on the first 30 clinical cases by computing Dice coefficient (DSC), Hausdorff distance (HD), and the fraction of slices that were used un-modified by planners. Final contours were retrospectively reviewed by an experienced planner and clinical significance of deviations was graded as negligible, low, moderate, and high probability of leading to actionable dosimetric variations. In order to assess whether the use of auto-contouring led to final contours more or less in agreement with an objective standard, 10 pre-treatment and 10 post-treatment blinded cases were re-contoured from scratch by three expert planners to get expert consensus contours (EC). EC was compared to clinically used (CU) contours using DSC. Student's t-test and Levene's statistic were used to test statistical significance of differences in mean and standard deviation, respectively. Finally, the dosimetric significance of the contour differences were assessed by comparing the difference in bladder and rectum maximum point doses between EC and CU before and after the introduction of automation., Results: Median (interquartile range) DSC for the retrospective test data were 0.92(0.02), 0.92(0.06), 0.93(0.06), 0.87(0.04) for the post-processed contours for the right and left femoral heads, bladder, and rectum, respectively. Post-implementation median DSC were 1.0(0.0), 1.0(0.0), 0.98(0.04), and 0.98(0.06), respectively. For each organ, 96.2, 95.4, 59.5, and 68.21 percent of slices were used unmodified by the planner. DSC between EC and pre-implementation CU contours were 0.91(0.05*), 0.91*(0.05*), 0.95(0.04), and 0.88(0.04) for right and left femoral heads, bladder, and rectum, respectively. The corresponding DSC for post-implementation CU contours were 0.93(0.02*), 0.93*(0.01*), 0.96(0.01), and 0.85(0.02) (asterisks indicate statistically significant difference). In a retrospective review of contours used for planning, a total of four deviating slices in two patients were graded as low potential clinical significance. No deviations were graded as moderate or high. Mean differences between EC and CU rectum max-doses were 0.1 ± 2.6 Gy and -0.9 ± 2.5 Gy for pre- and post-implementation, respectively. Mean differences between EC and CU bladder/bladder wall max-doses were -0.9 ± 4.1 Gy and 0.0 ± 0.6 Gy for pre- and post-implementation, respectively. These differences were not statistically significant according to Student's t-test., Conclusion: We have presented an analysis of the clinical implementation of a novel auto-contouring workflow. Substantial workflow savings were obtained. The introduction of auto-contouring into the clinical workflow changed the contouring behavior of planners. Automation bias was observed, but it had little deleterious effect on treatment planning., (© 2023 American Association of Physicists in Medicine.)

Background: The term 'pandemic paranoia' has been coined to refer to heightened levels of mistrust and suspicion towards other people specifically due to the COVID-19 pandemic. In this study, we examine the international prevalence of pandemic paranoia in the general population and its associated sociodemographic profile., Methods: A representative international sample of general population adults ( N = 2510) from five sites (USA N = 535, Germany N = 516, UK N = 512, Australia N = 502 and Hong Kong N = 445) were recruited using stratified quota sampling (for age, sex, educational attainment) and completed the Pandemic Paranoia Scale (PPS)., Results: The overall prevalence rate of pandemic paranoia was 19%, and was highest in Australia and lowest in Germany. On the subscales of the PPS, prevalence was 11% for persecutory threat, 29% for paranoid conspiracy and 37% for interpersonal mistrust. Site and general paranoia significantly predicted pandemic paranoia. Sociodemographic variables (lower age, higher population size and income, being male, employed and no migrant status) explained additional variance and significantly improved prediction of pandemic paranoia., Conclusions: Pandemic paranoia was relatively common in a representative sample of the general population across five international sites. Sociodemographic variables explained a small but significant amount of the variance in pandemic paranoia.

There has been a recent effort to treat high-risk ventricular tachycardia (VT) patients through radio-ablation. However, manual segmentation of the VT target is complex and time-consuming. This work introduces ASSET, or Auto-segmentation of the Seventeen SEgments for Tachycardia ablation, to aid in radiation therapy (RT) planning. ASSET was retrospectively applied to CTs for 26 thoracic RT patients (13 undergoing VT ablation). The physician-defined parasternal long-axis of the left ventricle (LV) and the axes generated from principal component analysis (PCA) were compared using mean distance to agreement (MDA) and angle of separation. The manually selected right ventricle insertion point and LVs were used to apply the ASSET model to automatically generate the 17 segments of the LV myocardium (LVM). Physician-defined parasternal long-axis differed from PCA by 1.2 ± 0.3 mm MDA and 6.9 ± 0.7 degrees. Segments differed by 0.69 ± 0.29 mm MDA and 0.89 ± 0.03 Dice similarity coefficient. Running ASSET takes <5 min where manual segmentation took >2 h/patient. Agreement between ASSET and expert contours was comparable to inter-observer variability. Qualitative scoring conducted by three experts revealed automatically generated segmentations were clinically useable as-is. ASSET offers efficient and reliable automatic segmentations for the 17 segments of the LVM for target generation in RT planning.

The COVID-19 pandemic resulted in many supply chain issues, including crippling of essential personal protective equipment (PPE) needed for high-risk occupations such as those in healthcare. As a result of these supply chain issues, unprecedented crisis capacity strategies were implemented to divert PPE items such as filtering facepiece respirators (FFRs, namely N95s) to those who needed them most for protection. Large-scale methods for decontamination were used throughout the world to preserve these items and provided for their extended use. The general public also adopted the use of non-specialized protective equipment such as face coverings. So, the need for cleaning, decontamination, or disinfection of these items in addition to normal clothing items became a necessary reality. Some items could be laundered, but other items were not appropriate for washing/drying. To fill research gaps in small-scale, non-commercial cleaning and disinfection, this bench-scale research was conducted using small coupons (swatches) of multiple PPE/barrier protection materials inoculated with virus (non-pathogenic bacteriophages Phi6 and MS2) and tested against a range of decontamination methods including bleach-, alcohol- and quaternary ammonium compound (QAC)-based liquid sprays, as well as low concentration hydrogen peroxide vapor (LCHPV) and bench-scale laundering. In general, non-porous items were easier to disinfect than porous items, and the enveloped virus Phi6 was overall easier to inactivate than MS2. Multiple disinfection methods were shown to be effective in reducing viral loads from PPE coupons, though only laundering and LCHPV were effective for all materials tested that were inoculated with Phi6. Applications of this and follow-on full-scale research are to provide simple effective cleaning/disinfection methods for use during the current and future pandemics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Introduction: Our institution was the first in the world to clinically implement MR-guided adaptive radiotherapy (MRgART) in 2014. In 2021, we installed a CT-guided adaptive radiotherapy (CTgART) unit, becoming one of the first clinics in the world to build a dual-modality ART clinic. Herein we review factors that lead to the development of a high-volume dual-modality ART program and treatment census over an initial, one-year period., Materials and Methods: The clinical adaptive service at our institution is enabled with both MRgART (MRIdian, ViewRay, Inc, Mountain View, CA) and CTgART (ETHOS, Varian Medical Systems, Palo Alto, CA) platforms. We analyzed patient and treatment information including disease sites treated, radiation dose and fractionation, and treatment times for patients on these two platforms. Additionally, we reviewed our institutional workflow for creating, verifying, and implementing a new adaptive workflow on either platform., Results: From October 2021 to September 2022, 256 patients were treated with adaptive intent at our institution, 186 with MRgART and 70 with CTgART. The majority (106/186) of patients treated with MRgART had pancreatic cancer, and the most common sites treated with CTgART were pelvis (23/70) and abdomen (20/70). 93.0% of treatments on the MRgART platform were stereotactic body radiotherapy (SBRT), whereas only 72.9% of treatments on the CTgART platform were SBRT. Abdominal gated cases were allotted a longer time on the CTgART platform compared to the MRgART platform, whereas pelvic cases were allotted a shorter time on the CTgART platform when compared to the MRgART platform. Our adaptive implementation technique has led to six open clinical trials using MRgART and seven using CTgART., Conclusions: We demonstrate the successful development of a dual platform ART program in our clinic. Ongoing efforts are needed to continue the development and integration of ART across platforms and disease sites to maximize access and evidence for this technique worldwide., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alex Price receives grants from Varian Medical Systems and support for travel from ViewRay Inc and Sun Nuclear Corporation. Joshua Schiff receives grants from Varian Medical Systems. Eric Laugeman has no disclosures. Borna Maraghechi has no disclosures. Matthew Schmidt receives consulting fees, support for travel, and honoraria from Varian Medical Systems and Siemens Healthineers. Tong Zhu has no disclosures. Francisco Reynoso has no conflicts of interest. Yao Hao has no conflicts of interest. Taeho Kim has no conflicts of interest. Eric Morris has no conflicts of interest. Xiandong Zhao has no disclosures. Geoffrey Hugo receives grants from Varian Medical Systems, Siemens Healthineers, ViewRay, and Mevion, and royalties and consulting fees from Varian Medical Systems. Gregory Vlacich has no conflicts of interest. Carl DeSelm has no disclosures. Pamela Samson receives grants from Varian Medical Systems. Brian Baumann receives grants from Varian Medical Systems, consulting fees from Varian Medical Systems, Boston Scientific, Galera, and Myovant, and leadership for the National Association of Proton Therapy. Shahed Badiyan receives honoraria from Mevion. Clifford Robinson receives research funding from Varian Medical Systems and Merck, leadership for Radialogica, stock for Radialogica, consulting for Varian Medical Systems, Astrazeneca, EMD Serono, Quantaras, and has US patent No. 62/598 and WO 2017078757. Hyun Kim receives grants from Varian Medical Systems and honoraria from ViewRay and Varian Medical Systems. Lauren Henke receives grants from Varian Medical Systems, consulting fees from Varian Medical Systems and Radialogica, honoraria from ViewRay, Varian Medical Systems, and LusoPalex, and participates on a safety board for ViewRay., (© 2023 The Authors.)

Field-level exercises with the purpose to assess remediation following the deliberate release of a highly toxic chemical in an indoor environment can be conducted using low(er) toxicity simulants if they are closely linked to the behavior of the toxic chemical itself. Chemical warfare agent (CWA) simulants have been identified on their suitability based on chemical structural similarities and associated physical and chemical properties. However, there are no reported studies that combine measurement of simulant parameters like persistence on surfaces, ability to sample for, and capability to degrade during the decontamination phase such that the level of success of a field-level exercise can be quantified. Experimental research was conducted to assess these gaps using a select number of CWA simulants. The organophosphate pesticide malathion was found to be a suitable simulant for use in field-level exercises that simulate the release of the highly persistent nerve agent VX based on its high persistence, effective surface sampling and analysis using standard analytical equipment, and the in situ degradation in the presence of different oxidizing decontaminants., Competing Interests: The authors declare no competing financial interest.

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster (HZ). We evaluated the incidence of HZ in ulcerative colitis (UC) and Crohn's disease (CD) patients and compared this with HZ incidence in a non-IBD population., Methods: We conducted a retrospective cohort study (GSK study identifier: VEO-000043) of adults aged ≥18 years with UC and CD and without IBD who were identified from claims recorded in a US healthcare database between October 2015 and February 2020. Crude HZ incidence rates/1,000 person-years (PY) were calculated, and comparisons of HZ incidence rates between UC or CD and non-IBD cohorts were made using adjusted generalized linear models., Results: The study population comprised a total of 29,928 UC, 25,959 CD, and 11,839,329 non-IBD patients. Crude overall HZ incidence rates were 13.64/1,000 PY (UC), 15.94/1,000 PY (CD), and 7.95/1,000 PY (non-IBD). UC and CD patients had increased HZ incidence rates, with adjusted incidence rate ratios of 1.35 (95% confidence interval [CI], 1.26-1.44) and 1.66 (95% CI, 1.56-1.77), respectively, compared with non-IBD patients. Stratified analysis indicated increased relative rates of HZ in progressively younger age strata in the UC and CD patients compared with non-IBD patients. HZ incidence rates were higher in UC and CD patients who had previously received thiopurines or methotrexate, TNF-inhibitors, or corticosteroids than in UC and CD patients who did not take those medicines., Conclusion: UC and CD patients had increased HZ incidence rates compared with patients without IBD, demonstrating the importance of HZ prevention in IBD patients., Competing Interests: D.S., S.P., and J.E.P. are employed by and hold shares in GSK. P.T.-L., D.G., W.Y.C., and M.S.D. are employees of Analysis Group, Inc., a consulting firm that has received funding from GSK for the conduct of this study. E.D.M. and F.D. were employees of Analysis Group, Inc., at the time of the study. S.M. was a Post-Doctoral Research Fellow affiliated to both Tufts Medical Center and GSK at the time of the study and declares to have received grant support for vaccine studies from GSK. F.A.F. declares royalties or licenses from Jones and Bartlett; consulting fees from BMS, Braintree Labs, GI Reviewers, GSK, IBD Educational Group, Iterative Scopes, Janssen, Pfizer, and Sebela; participation on data safety monitoring boards or advisory boards for Adiso Therapeutics and Lilly; and stock or stock options in Innovation Pharmaceuticals. The authors declare no other financial and non-financial relationships and activities., (© The Author(s) 2023. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Depression and poor sleep quality commonly co-occur with autism, and depression has been associated with loneliness and reduced social support. In non-autistic samples, poor sleep quality and daytime fatigue also contribute to depression. However, the contribution of sleep quality and fatigue to depressive symptoms, and how they interact with social factors to influence depression in autism remain unexplored. Our aim was to examine these relationships in 114 young autistic adults aged 15-25 years (57% male) from the SASLA online, longitudinal study (baseline and 2-year follow-up). Hierarchical multiple regression models examined the association between social well-being (social integration and social contribution; T1), sleep quality (T1, T2), and fatigue (T1, T2) on depression (T1, T2). Two mediation models were conducted on T1 data predicting depression from sleep quality though fatigue and sleep quality through social well-being. Depression and fatigue scores did not change over 2 years, but sleep quality worsened. The T1 regression model was significant (R 2 = 36%) with fatigue and social contribution individually predicting depression symptomatology. The longitudinal regression model was also significant (adjusted R 2 = 57%) with social contribution (T1) as the only significant predictor of depression (T2). Fatigue trended towards mediating the sleep quality-depression relationship, while social well-being was a significant partial mediator of this relationship. Results highlight that sleep quality, fatigue, and social well-being contribute to depression among young autistic adults. Interestingly, fatigue and social well-being were independently associated with depression. Thus, addressing sleep quality and associated fatigue, and social well-being is important when treating depression in autistic individuals., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Background: Insomnia and disturbed sleep are more common in autistic adults compared with non-autistic adults, contributing to significant social, psychological and health burdens. However, sleep intervention research for autistic adults is lacking., Aims: The aim of the study was to implement an acceptance and commitment therapy group insomnia intervention (ACT-i) tailored for autistic adults to examine its impact on insomnia and co-occurring mental health symptoms., Method: Eight individuals (6 male, 2 female) aged between 18 and 70 years, with a clinical diagnosis of autism spectrum disorder, and scores ranging from 9 to 26 on the Insomnia Severity Index (ISI) participated in the trial. Participants were assigned to one of two intervention groups (4 per group) within a multiple baseline over time design for group. Participants completed questionnaires pre-intervention, post-intervention, and at 2-month follow-up, actigraphy 1 week prior to intervention and 1 week post-intervention, and a daily sleep diary from baseline to 1 week post-intervention, and 1 week at follow-up., Results: At a group level there were significant improvements in ISI (λ 2 =10.17, p =.006) and HADS-A (anxiety) (λ 2 =8.40, p =.015) scores across the three time points. Clinically reliable improvement occurred for ISI scores ( n= 5) and HADS-A scores ( n= 4) following intervention. Client satisfaction indicated that ACT-i was an acceptable intervention to the participants (median 4 out of 5)., Conclusions: This pilot study with eight autistic adults indicates that ACT-i is both an efficacious and acceptable intervention for reducing self-reported insomnia and anxiety symptoms in autistic adults.

Pesticide misuse incidents are reported worldwide each year. The potential exposure to pesticides creates a concern for occupants in affected homes, apartments, and other occupied buildings. Pesticides that are improperly applied within these locations may require remediation prior to reoccupation. Incident response personnel rely heavily on data from sampling results to identify residue levels and determine when site remediation is complete. Surface wipe samples are often collected for this purpose. Therefore, it is important to ensure sampling and analysis procedures are well established for the contaminants of concern, particularly for wipe sampling variables that can affect analysis results. This investigation evaluated the effects of surface wipe media, wipe wetting solvents, pesticide concentrations effects, composite sampling, surface types, and pesticide formulation effects on analysis results for fipronil, permethrin, and deltamethrin. Tested surface types included galvanized steel, vinyl tile, and plywood. Wipe media included pre-packaged, sterile cotton gauze, pre-cleaned cotton twill, and a pre-packaged, pre-wetted wipes. Surface recovery results are reported for commercially available fipronil formulations and compared to technical grade fipronil solutions. Fipronil recoveries were 92-107 % for twill wipes, 81-98 % for cotton gauze wipes, and 79 % for pre-packaged, pre-wetted wipes on a galvanized steel surface. Permethrin recoveries were 83-116 % for twill wipes, 66-94 % for cotton gauze wipes, and 73 % for pre-packaged, pre-wetted wipes on a galvanized steel surface. Deltamethrin recoveries were 67-88 % for twill wipes, 55-71 % for cotton gauze wipes, and 63 % for pre-packaged, pre-wetted wipes on a galvanized steel surface. The data collected in this study can inform surface wipe sampling methods and potentially assist in obtaining more accurate sampling data associated with pesticide misuse incidents involving the target analytes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Adjustment to life with acquired brain injury (ABI) requires self-identity and behaviour to be updated, incorporating injury-related changes. Identifying and enabling new values-consistent behaviours could facilitate this process. We evaluated the feasibility, acceptability, and preliminary efficacy of VaLiANT, a new group intervention that aims to enhance "valued living" following ABI. We used a non-concurrent multiple baseline single-case experimental design (SCED) with an 8-week follow-up phase and randomization to multiple baseline lengths (5-7 weeks). Eight participants (50% women, aged 26-65; 4 Stroke, 3 Traumatic Brain Injury, 1 Epilepsy) attended eight group sessions with assessments before, during, and after the group. Target behaviour was valued living, assessed weekly by the Valued Living Questionnaire. Secondary outcomes included measures of wellbeing, mood, psychological acceptance, self-efficacy regarding ABI consequences, cognitive complaints, and intervention acceptability. Target behaviour was analysed through visual and statistical analysis while secondary outcome data were analysed via reliable change indices and descriptive statistics. Target behaviour data displayed no convincing patterns of improvement. Reliable improvements were found for most participants on secondary outcomes, particularly subjective wellbeing and anxiety. Intervention delivery was feasible with high acceptability ratings. Further investigation of VaLiANT is warranted, based on the feasibility and acceptability of intervention delivery and signals of efficacy identified across adjustment-related secondary outcomes.

This protocol provides an example of a laboratory process for conducting laundering studies that generate data on viral disinfection. While the protocol was developed for research during the coronavirus disease 2019 (COVID-19) pandemic, it is intended to be a framework, adaptable to other virus disinfection studies; it demonstrates the steps for preparing the test virus, inoculating the test material, assessing visual and integrity changes to the washed items due to the laundering process, and quantifying the reduction in viral load. Additionally, the protocol outlines the necessary quality control samples for ensuring the experiments are not biased by contamination and measurements/observations that should be recorded to track the material integrity of the personal protective equipment (PPE) items after multiple laundering cycles. The representative results presented with the protocol use the Phi6 bacteriophage inoculated onto cotton scrub, denim, and cotton face-covering materials and indicate that the hot water laundering and drying process achieved over a 3-log (99.9%) reduction in viral load for all samples (a 3-log reduction is the disinfectant performance metric in U.S. Environmental Protection Agency's Product Performance Test Guideline 810.2200). The reduction in viral load was uniform across different locations on the PPE items. The results of this viral disinfection efficacy testing protocol should help the scientific community explore the effectiveness of home laundering for other types of test viruses and laundering procedures.

Background: During the COVID-19 pandemic, an increase in paranoid thinking has been reported internationally. The development of the Pandemic Paranoia Scale (PPS) has provided a reliable assessment of various facets of pandemic paranoia. This study aimed to (i) identify classes of individuals with varying levels of general paranoia and pandemic paranoia, and (ii) examine associations between classification and worry, core beliefs, and pro-health behaviours., Methods: An international sample of adults (N = 2510) across five sites completed the Revised-Green Paranoid Thoughts Scale and the PPS. Latent class analysis (LCA) was conducted using these two paranoia variables. Classes were compared on trait worry (Penn State Worry Questionnaire), beliefs about self/others (Brief Core Schema Scales), and pro-health behaviour., Results: Three latent classes emerged: Class 1 with low R-GPTS and PPS scores, Class 2 with a high R-GPTS score and a moderate PPS score, and Class 3 with high R-GPTS and PPS scores. Compared to Class 1, Classes 2-3 were associated with more worry and negative self- and other-beliefs. Class 3 was further characterised by greater positive-self beliefs and less engagement in pro-health behaviours. Engagement in pro-health behaviours was positively correlated with interpersonal mistrust and negatively correlated with paranoid conspiracy and persecutory threat., Conclusions: Individuals with a general paranoia tendency were more likely to respond to the global health threats in a suspicious and distrusting way. Our findings suggested that worry and negative self/other beliefs may contribute to not just general paranoia but also pandemic paranoia. The preliminary finding of a link between pro-health behaviours and interpersonal mistrust warrants further examination., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study reports the initial results for the first 15 patients on a prospective phase II clinical trial exploring the safety, feasibility, and efficacy of the HyperArc technique for recurrent head and neck cancer treatment. Eligible patients were simulated and planned with both conventional VMAT and HyperArc techniques and the plan with superior dosimetry was selected for treatment. Dosimetry, delivery feasibility and safety, treatment-related toxicity, and patient-reported quality of life (QOL) were all evaluated. HyperArc was chosen over conventional VMAT for all 15 patients and enabled statistically significant increases in dose conformity (R50% reduced by 1.2 ± 2.1, p < 0.05) and mean PTV and GTV doses (by 15.7 ± 4.9 Gy, p < 0.01 and 17.1 ± 6.0 Gy, p < 0.01, respectively). The average HyperArc delivery was 2.8 min longer than conventional VMAT ( p < 0.01), and the mean intrafraction motion was ≤ 0.5 ± 0.4 mm and ≤0.3 ± 0.1°. With a median follow-up of 12 months, treatment-related toxicity was minimal (only one grade 3 acute toxicity above baseline) and patient-reported QOL metrics were favorable. HyperArc enabled superior dosimetry and significant target dose escalation compared to conventional VMAT planning, and treatment delivery was feasible, safe, and well-tolerated by patients.

Understanding factors driving vaccine hesitancy is crucial to vaccination success. We surveyed adults (N = 2510) from February to March 2021 across five sites (Australia = 502, Germany = 516, Hong Kong = 445, UK = 512, USA = 535) using a cross-sectional design and stratified quota sampling for age, sex, and education. We assessed willingness to take a vaccine and a comprehensive set of putative predictors. Predictive power was analysed with a machine learning algorithm. Only 57.4% of the participants indicated that they would definitely or probably get vaccinated. A parsimonious machine learning model could identify vaccine hesitancy with high accuracy (i.e. 82% sensitivity and 79-82% specificity) using 12 variables only. The most relevant predictors were vaccination conspiracy beliefs, various paranoid concerns related to the pandemic, a general conspiracy mentality, COVID anxiety, high perceived risk of infection, low perceived social rank, lower age, lower income, and higher population density. Campaigns seeking to increase vaccine uptake need to take mistrust as the main driver of vaccine hesitancy into account., (© 2022. The Author(s).)

Artificial intelligence (AI) has great potential to transform the clinical workflow of radiotherapy. Since the introduction of deep neural networks, many AI-based methods have been proposed to address challenges in different aspects of radiotherapy. Commercial vendors have started to release AI-based tools that can be readily integrated to the established clinical workflow. To show the recent progress in AI-aided radiotherapy, we have reviewed AI-based studies in five major aspects of radiotherapy including image reconstruction, image registration, image segmentation, image synthesis, and automatic treatment planning. In each section, we summarized and categorized the recently published methods, followed by a discussion of the challenges, concerns, and future development. Given the rapid development of AI-aided radiotherapy, the efficiency and effectiveness of radiotherapy in the future could be substantially improved through intelligent automation of various aspects of radiotherapy.

Subcutaneous (SC) administration of rituximab provides an opportunity for reduced patient treatment burden and increased healthcare efficiencies as an alternative to intravenous (IV) rituximab. There is minimal evidence comparing costs associated with SC and IV rituximab in a US setting. This research assessed the impact of transitioning patients from IV to SC rituximab for treatment of non-Hodgkin's lymphoma (NHL) from the US payer, provider, and patient perspective. We developed a model to estimate cost differences for transitioning 20% of a patient cohort from IV to SC rituximab. We included patients with incident diffuse large B-cell lymphoma, incident and recurrent follicular lymphoma, and incident and recurrent chronic lymphocytic leukemia. In the model, each patient received the same number of doses and that there was no difference in discontinuation between cohorts due to non-inferior efficacy and a similar safety profile. Model inputs were collected from published literature and publicly available data. Scenario analyses tested the impact of availability of low-cost biosimilars. In the base case (1,000,000 covered lives), we estimated a total of 157 patients, with 769 total drug administrations. A transition of 20% of patients from IV to SC was projected to generate $153,000 in payer savings, increase provider capacity by 270 hours, and free 470 hours of patient time. Scenario analyses suggest SC administration will be cost saving for payers even with a market where biosimilars approach 50% market share. A 20% transition to SC rituximab in a single cohort of patients has the potential to generate significant US health system value in the form of payer savings, increased practice capacity, and patient time., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: Cognitive and emotional changes affect the majority of individuals with acquired brain injury (ABI) and are associated with poorer outcomes. The evidence for "siloed" rehabilitation approaches targeting cognition and mood separately remains mixed. Valued living (i.e., acting consistently with personal values) is associated with better psychological functioning and participation in work and other productive activities. Rehabilitation interventions that concurrently address cognitive and emotional barriers to valued living may therefore result in improved outcomes. VaLiANT (Valued Living After Neurological Trauma) is an 8-week group intervention developed by our team, which uniquely combines cognitive rehabilitation and psychological therapy to improve wellbeing and meaningful participation (i.e., valued living) following ABI., Method: This protocol describes the design and implementation of a Phase II parallel-group randomized controlled trial with blinded outcome assessors, to evaluate the potential efficacy of VaLiANT and the feasibility of a Phase III trial. Participants are adults with a history of ABI at least 3 months prior to study entry, who experience cognitive and/or emotional difficulties and associated reduced participation in valued activities. Random allocation to the treatment condition (8-week VaLiANT group program) or a usual care waitlist control condition occurs at a 2:1 treatment: control ratio. The primary outcome is wellbeing, measured by the Warwick-Edinburgh Mental Wellbeing Scale. Secondary outcomes include measures of valued living, mood, cognitive complaints, quality of life, community participation, post-traumatic growth, and self-efficacy. All measures are collected across three time points by blinded assessors (baseline, 8-week follow-up, 16-week follow-up). Trial feasibility will be evaluated against recruitment rates, drop-out rates, intervention acceptability, and treatment fidelity (manual adherence and therapist competence)., Discussion: This trial will extend current knowledge on how to improve long-term outcomes following ABI by evaluating an innovative integrated, multi-domain approach to rehabilitation concurrently addressing cognitive and emotional barriers to participation in meaningful life roles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sathananthan, Morris, Gillanders, Knox, Dimech-Betancourt, Wright, das Nair and Wong.)

Purpose: Patient tolerability of magnetic resonance (MR)-guided radiation treatment delivery is limited by the need for repeated deep inspiratory breath holds (DIBHs). This volunteer study assessed the feasibility of continuous positive airway pressure (CPAP) with and without DIBH for respiratory motion management during radiation treatment with an MR-linear accelerator (MR-linac)., Methods and Materials: MR imaging safety was first addressed by placing the CPAP device in an MR-safe closet and configuring a tube circuit via waveguide to the magnet bore. Reproducibility and linearity of the final configuration were assessed. Six healthy volunteers underwent thoracic imaging in a 0.35T MR-linac, with one free breathing (FB) and 2 DIBH acquisitions being obtained at 5 pressures from 0 to 15 cm-H 2 O. Lung and heart volumes and positions were recorded; repeatability was assessed by comparing 2 consecutive DIBH scans. Blinded reviewers graded images for motion artifact using a 3-point grading scale. Participants completed comfort and perception surveys before and after imaging sessions., Results: Compared with FB alone, FB-10, FB-12, and FB-15 cm H 2 O significantly increased lung volumes (+23%, +34%, +44%; all P <.05) and inferiorly displaced the heart (0.86 cm, 0.96 cm, 1.18 cm; all P < . 05). Lung volumes were significantly greater with DIBH-0 cm H 2 O compared with FB-15 cm H 2 O (+105% vs +44%, P  = .01), and DIBH-15 cm H 2 O yielded additional volume increase (+131% vs +105%, P  = .01). Adding CPAP to DIBH decreased lung volume differences between consecutive breath holds (correlation coefficient 0.97 at 15 cm H 2 O vs 0.00 at 0 cm H 2 O). The addition of 15 cm H 2 O CPAP reduced artifact scores ( P  = .03) compared with FB; all DIBH images (0-15 cm H 2 O) had less artifact ( P < .01)., Conclusions: This work demonstrates the feasibility of integrating CPAP in an MR-linac environment in healthy volunteers. Extending this work to a larger patient cohort is warranted to further establish the role of CPAP as an alternative and concurrent approach to DIBH in MR-guided radiation therapy., (© 2022 The Authors.)

Aims: Use of comprehensive genomic profiling (CGP) in metastatic colorectal cancer (mCRC) is limited. We estimated impacts of expanded 1 L CGP, using the Tempus xT test, on detection of actionable alterations and testing budgets in a modeled US health plan over two-years., Materials and Methods: A decision analytic model was developed to estimate the impact of replacing 20% of usual testing (a mix of CGP and non-CGP) with Tempus xT CGP. Actionable alterations for matched treatments or clinical trial included KRAS , NRAS , RAF , BRAF , deficient mismatch repair (dMMR)/microsatellite instability (MSI), NTRK , RET , EGFR , HER2 , MET , PIK3CA and POLE1 . Costs included initial and repeat testing, physician-associated and administrative costs., Results: In a hypothetical five-million-member plan, 50% Medicare and 50% commercial, 1,112 new cases of mCRC were expected per year. Of these, 566 (51%) would undergo 1 L molecular testing, with 55 re-tested upon progression. Based on current testing rates, there were an expected 521 missed opportunities for genomically informed treatment (47% of new cases), with 442 missed due to lack of testing and 79 due to testing without CGP. Replacing 20% of usual testing with Tempus xT CGP was associated with up to a $0.003 per member per month testing cost increase (net total cost of $202,102 for the five-million-member plan) and 15.5 additional patients with an opportunity for genomically informed care (12.7 patients for treatment and 2.8 for clinical trial). The testing total cost (initial test, repeat test, biopsy and physician services, and administrative cost) to put one additional patient with mCRC on matched therapy or matched clinical trial was estimated to be $13,005. Number needed to test to identify one actionable alteration with Tempus xT CGP versus usual testing was 7.8 patients., Limitations: Conservative assumptions were made for inputs with limited evidence. Based on high concordance rates with dMMR/MSI status, tumor mutational burden (TMB) status was not calculated separately., Conclusions: Replacing 20% of usual testing with Tempus xT CGP was associated with a small incremental testing cost and can identify meaningfully more actionable alterations.

Purpose: Accurate and robust auto-segmentation of highly deformable organs (HDOs), for example, stomach or bowel, remains an outstanding problem due to these organs' frequent and large anatomical variations. Yet, time-consuming manual segmentation of these organs presents a particular challenge to time-limited modern radiotherapy techniques such as on-line adaptive radiotherapy and high-dose-rate brachytherapy. We propose a machine-assisted interpolation (MAI) that uses prior information in the form of sparse manual delineations to facilitate rapid, accurate segmentation of the stomach from low field magnetic resonance images (MRI) and the bowel from computed tomography (CT) images., Methods: Stomach MR images from 116 patients undergoing 0.35T MRI-guided abdominal radiotherapy and bowel CT images from 120 patients undergoing high dose rate pelvic brachytherapy treatment were collected. For each patient volume, the manual delineation of the HDO was extracted from every 8th slice. These manually drawn contours were first interpolated to obtain an initial estimate of the HDO contour. A two-channel 64 × 64 pixel patch-based convolutional neural network (CNN) was trained to localize the position of the organ's boundary on each slice within a five-pixel wide road using the image and interpolated contour estimate. This boundary prediction was then input, in conjunction with the image, to an organ closing CNN which output the final organ segmentation. A Dense-UNet architecture was used for both networks. The MAI algorithm was separately trained for the stomach segmentation and the bowel segmentation. Algorithm performance was compared against linear interpolation (LI) alone and against fully automated segmentation (FAS) using a Dense-UNet trained on the same datasets. The Dice Similarity Coefficient (DSC) and mean surface distance (MSD) metrics were used to compare the predictions from the three methods. Statistically significance was tested using Student's t test., Results: For the stomach segmentation, the mean DSC from MAI (0.91 ± 0.02) was 5.0% and 10.0% higher as compared to LI and FAS, respectively. The average MSD from MAI (0.77 ± 0.25 mm) was 0.54 and 3.19 mm lower compared to the two other methods. Only 7% of MAI stomach predictions resulted in a DSC < 0.8, as compared to 30% and 28% for LI and FAS, respectively. For the bowel segmentation, the mean DSC of MAI (0.90 ± 0.04) was 6% and 18% higher, and the average MSD of MAI (0.93 ± 0.48 mm) was 0.42 and 4.9 mm lower as compared to LI and FAS. Sixteen percent of the predicted contour from MAI resulted in a DSC < 0.8, as compared to 46% and 60% for FAS and LI, respectively. All comparisons between MAI and the baseline methods were found to be statistically significant (p-value < 0.001)., Conclusions: The proposed MAI algorithm significantly outperformed LI in terms of accuracy and robustness for both stomach segmentation from low-field MRIs and bowel segmentation from CT images. At this time, FAS methods for HDOs still require significant manual editing. Therefore, we believe that the MAI algorithm has the potential to expedite the process of HDO delineation within the radiation therapy workflow., (© 2021 American Association of Physicists in Medicine.)

Purpose: Whole-heart dose metrics are not as strongly linked to late cardiac morbidities as radiation doses to individual cardiac substructures. Our aim was to characterize the excursion and dosimetric variation throughout respiration of sensitive cardiac substructures for future robust safety margin design., Methods and Materials: Eleven patients with cancer treatments in the thorax underwent 4-phase noncontrast 4-dimensional computed tomography (4DCT) with T2-weighted magnetic resonance imaging in end-exhale. The end-exhale phase of the 4DCT was rigidly registered with the magnetic resonance imaging and refined with an assisted alignment surrounding the heart from which 13 substructures (chambers, great vessels, coronary arteries, etc) were contoured by a radiation oncologist on the 4DCT. Contours were deformed to the other respiratory phases via an intensity-based deformable registration for radiation oncologist verification. Measurements of centroid and volume were evaluated between phases. Mean and maximum dose to substructures were evaluated across respiratory phases for the breast (n = 8) and thoracic cancer (n = 3) cohorts., Results: Paired t tests revealed reasonable maintenance of geometric and anatomic properties ( P < .05 for 4/39 volume comparisons). Maximum displacements >5 mm were found for 24.8%, 8.5%, and 64.5% of the cases in the left-right, anterior-posterior, and superior-inferior axes, respectively. Vector displacements were largest for the inferior vena cava and the right coronary artery, with displacements up to 17.9 mm. In breast, the left anterior descending artery D mean varied 3.03 ± 1.75 Gy (range, 0.53-5.18 Gy) throughout respiration whereas lung showed patient-specific results. Across all patients, whole heart metrics were insensitive to breathing phase (mean and maximum dose variations <0.5 Gy)., Conclusions: This study characterized the intrafraction displacement of the cardiac substructures through the respiratory cycle and highlighted their increased dosimetric sensitivity to local dose changes not captured by whole heart metrics. Results suggest value of cardiac substructure margin generation to enable more robust cardiac sparing and to reduce the effect of respiration on overall treatment plan quality., (© 2021 The Authors.)

Background and Purpose: Sickle cell disease (SCD) is a collection of rare inherited blood disorders affecting approximately 100,000 people in the U.S. and 20-25 million people globally. Individuals with SCD experience recurrent episodes of severe and unpredictable pain that are caused by vaso-occlusive crises (VOCs), a hallmark of the disease. VOCs are the primary cause of hospitalization in SCD, result in missed workdays and school days, and decrease quality of life (QoL). Although VOCs cause significant burden in the lives of individuals with SCD, there is no synthesis on the frequency of VOCs in the real world. This systematic literature review sought to identify literature describing the frequency of VOCs experienced by individuals with SCD in real-world settings., Methods: MEDLINE and 6 congresses were searched (date range: January 1, 2000 to June 30, 2020). Studies were reviewed independently by two researchers. Studies assessing frequency or prevalence of VOCs or VOC-related outcomes were included., Results: Of 1438 studies identified in the search, 52 met pre-specified inclusion and exclusion criteria. Reported frequency of VOCs varied widely ranging from a mean or median of 0 VOCs/year to 18.2 VOCs/year. The proportion of patients experiencing ≥ 3 VOCs/year ranged from 4 to 67% and the proportion of patients experiencing ≥ 5 VOCs/year ranged from 18 to 59%. Measures of VOC severity were limited, with 13 studies considering frequency of complicated VOCs and only 1 study reporting duration of VOC episodes., Conclusions: This is the first study to systematically assess published evidence pertaining to VOCs in real-world settings. Reported VOC frequency in real-world settings varied widely, with a majority of studies only considering VOCs managed in an inpatient or outpatient setting. Studies that considered VOCs managed at home reported a higher frequency of VOCs, suggesting that many studies may underestimate the frequency of VOCs. This systematic literature review (SLR) highlights the need for consistent reporting of (1) self-reported VOCs, including those managed at home, (2) definitions of VOCs, (3) complicated VOCs, and (4) duration of VOC episodes in literature., (© 2021. The Author(s).)

Objective: To evaluate the effects of metreleptin in distinct subgroups of patients with generalized lipodystrophy (GL) and partial lipodystrophy (PL), using multivariate linear regression modeling to account for the role of patients' baseline usage of concomitant glucose and lipid-lowering medications and other covariates on their outcomes., Materials and Methods: A post-hoc statistical analysis of two published single-arm, interventional, phase 2 clinical trials at NIH was conducted. Concomitant medication use was assessed for the clinical trial population using prescription fill data, measured at baseline and the post-one year following metreleptin initiation. Pre-specified co-primary efficacy endpoints measured were change from baseline in HbA1c at month 12, and the percent change from baseline in fasting serum triglycerides (TG) at month 12. Descriptive and statistical analyses were conducted for the overall population, the separate populations with GL and PL, and additional PL subgroups defined by baseline metabolic markers of elevated HbA1c and elevated fasting TG., Results: As previously reported, improvement in HbA1c and fasting TG from baseline to 12 months on metreleptin were observed in the overall population (mean change -1.57 percentage points and median change -37.9%, respectively) and subgroups. For both HbA1c and TG, baseline levels were significant predictors of changes after metreleptin. After considering baseline characteristics such as disease type, age, sex, and baseline HbA1c, baseline insulin use was not found to be a significant predictor of HbA1c improvement following metreleptin initiation. Similar results were seen for TG levels, with the use of any lipid-lowering medications at baseline not found to be a significant predictor of reductions in fasting TG levels., Conclusions: Patients treated with metreleptin experienced statistically significant improvement in metabolic markers of glycemic and hypertriglyceridemic control-e.g. HbA1c and triglyceride levels-across various subgroups after controlling for baseline characteristics and concomitant medication usage.

Purpose: Emerging evidence suggests cardiac substructures are highly radiosensitive during radiation therapy for cancer treatment. However, variability in substructure position after tumor localization has not been well characterized. This study quantifies inter-fraction displacement and planning organ at risk volumes (PRVs) of substructures by leveraging the excellent soft tissue contrast of magnetic resonance imaging (MRI)., Methods: Eighteen retrospectively evaluated patients underwent radiotherapy for intrathoracic tumors with a 0.35 T MRI-guided linear accelerator. Imaging was acquired at a 17-25 s breath-hold (resolution 1.5 × 1.5 × 3 mm 3 ). Three to four daily MRIs per patient (n = 71) were rigidly registered to the planning MRI-simulation based on tumor matching. Deep learning or atlas-based segmentation propagated 13 substructures (e.g., chambers, coronary arteries, great vessels) to daily MRIs and were verified by two radiation oncologists. Daily centroid displacements from MRI-simulation were quantified and PRVs were calculated., Results: Across substructures, inter-fraction displacements for 14% in the left-right, 18% in the anterior-posterior, and 21% of fractions in the superior-inferior were > 5 mm. Due to lack of breath-hold compliance, ~4% of all structures shifted > 10 mm in any axis. For the chambers, median displacements were 1.8, 1.9, and 2.2 mm in the left-right, anterior-posterior, and superior-inferior axis, respectively. Great vessels demonstrated larger displacements (> 3 mm) in the superior-inferior axis (43% of shifts) and were only 25% (left-right) and 29% (anterior-posterior) elsewhere. PRVs from 3 to 5 mm were determined as anisotropic substructure-specific margins., Conclusions: This exploratory work derived substructure-specific safety margins to ensure highly effective cardiac sparing. Findings require validation in a larger cohort for robust margin derivation and for applications in prospective clinical trials., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The submitting author holds research agreements with Philips Healthcare. Research reported in this publication was partially supported by the National Cancer Institute of the National Institutes of Health under award Number R01 CA204189-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (© 2021 The Authors.)

Background: The Health Resources and Services Administration's Ryan White HIV/AIDS Program provides services to more than half of all people diagnosed with HIV in the United States. We present and validate a mathematical model that can be used to estimate the long-term public health and cost impact of the federal program., Methods: We developed a stochastic, agent-based model that reflects the current HIV epidemic in the United States. The model simulates everyone's progression along the HIV care continuum, using 2 network-based mechanisms for HIV transmission: injection drug use and sexual contact. To test the validity of the model, we calculated HIV incidence, mortality, life expectancy, and lifetime care costs and compared the results with external benchmarks., Results: The estimated HIV incidence rate for men who have sex with men (502 per 100,000 person years), mortality rate of all people diagnosed with HIV (1663 per 100,000 person years), average life expectancy for individuals with low CD4 counts not on antiretroviral therapy (1.52-3.78 years), and lifetime costs ($362,385) all met our validity criterion of within 15% of external benchmarks., Conclusions: The model represents a complex HIV care delivery system rather than a single intervention, which required developing solutions to several challenges, such as calculating need for and receipt of multiple services and estimating their impact on care retention and viral suppression. Our strategies to address these methodological challenges produced a valid model for assessing the cost-effectiveness of the Ryan White HIV/AIDS Program., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: With an annual budget of more than $2 billion, the Health Resources and Services Administration's Ryan White HIV/AIDS Program (RWHAP) is the third largest source of public funding for HIV care and treatment in the United States, yet little analysis has been done to quantify the long-term public health and economic impacts of the federal program., Methods: Using an agent-based, stochastic model, we estimated health care costs and outcomes over a 50-year period in the presence of the RWHAP relative to those expected to prevail if the comprehensive and integrated system of medical and support services funded by the RWHAP were not available. We made a conservative assumption that, in the absence of the RWHAP, only uninsured clients would lose access to these medical and support services., Results: The model predicts that the proportion of people with HIV who are virally suppressed would be 25.2 percentage points higher in the presence of the RWHAP (82.6 percent versus 57.4 percent without the RWHAP). The number of new HIV infections would be 18 percent (190,197) lower, the number of deaths among people with HIV would be 31 percent (267,886) lower, the number of quality-adjusted life years would be 2.7 percent (5.6 million) higher, and the cumulative health care costs would be 25 percent ($165 billion) higher in the presence of the RWHAP relative to the counterfactual. Based on these results, the RWHAP has an incremental cost-effectiveness ratio of $29,573 per quality-adjusted life year gained compared with the non-RWHAP scenario. Sensitivity analysis indicates that the probability of transmitting HIV via male-to-male sexual contact and the cost of antiretroviral medications have the largest effect on the cost-effectiveness of the program., Conclusions: The RWHAP would be considered very cost-effective when using standard guidelines of less than the per capita gross domestic product of the United States. The results suggest that the RWHAP plays a critical and cost-effective role in the United States' public health response to the HIV epidemic., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the dosimetric and image-guided radiation therapy (IGRT) performance of a novel generative adversarial network (GAN) generated synthetic CT (synCT) in the brain and compare its performance for clinical use including conventional brain radiotherapy, cranial stereotactic radiosurgery (SRS), planar, and volumetric IGRT., Methods and Materials: SynCT images for 12 brain cancer patients (6 SRS, 6 conventional) were generated from T1-weighted postgadolinium magnetic resonance (MR) images by applying a GAN model with a residual network (ResNet) generator and a convolutional neural network (CNN) with 5 convolutional layers as the discriminator that classified input images as real or synthetic. Following rigid registration, clinical structures and treatment plans derived from simulation CT (simCT) images were transferred to synCTs. Dose was recalculated for 15 simCT/synCT plan pairs using fixed monitor units. Two-dimensional (2D) gamma analysis (2%/2 mm, 1%/1 mm) was performed to compare dose distributions at isocenter. Dose-volume histogram (DVH) metrics (D 95% , D 99% , D 0.2cc, and D 0.035cc ) were assessed for the targets and organ at risks (OARs). IGRT performance was evaluated via volumetric registration between cone beam CT (CBCT) to synCT/simCT and planar registration between KV images to synCT/simCT digital reconstructed radiographs (DRRs)., Results: Average gamma passing rates at 1%/1mm and 2%/2mm were 99.0 ± 1.5% and 99.9 ± 0.2%, respectively. Excellent agreement in DVH metrics was observed (mean difference ≤0.10 ± 0.04 Gy for targets, 0.13 ± 0.04 Gy for OARs). The population averaged mean difference in CBCT-synCT registrations were <0.2 mm and 0.1 degree different from simCT-based registrations. The mean difference between kV-synCT DRR and kV-simCT DRR registrations was <0.5 mm with no statistically significant differences observed (P > 0.05). An outlier with a large resection cavity exhibited the worst-case scenario., Conclusion: Brain GAN synCTs demonstrated excellent performance for dosimetric and IGRT endpoints, offering potential use in high precision brain cancer therapy., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Rising evidence suggests that cardiac substructures are highly radiosensitive. However, they are not routinely considered in treatment planning as they are not readily visualized on treatment planning CTs (TPCTs). This work integrated the soft tissue contrast provided by low-field MRIs acquired on an MR-linac via image registration to further enable cardiac substructure sparing on TPCTs., Methods: Sixteen upper thoracic patients treated at various breathing states (7 end-exhalation, 7 end-inhalation, 2 free-breathing) on a 0.35T MR-linac were retrospectively evaluated. A hybrid MR/CT atlas and a deep learning three-dimensional (3D) U-Net propagated 13 substructures to TPCTs. Radiation oncologists revised contours using registered MRIs. Clinical treatment plans were re-optimized and evaluated for beam arrangement modifications to reduce substructure doses. Dosimetric assessment included mean and maximum (0.03cc) dose, left ventricular volume receiving 5Gy (LV-V5), and other clinical endpoints. As metrics of plan complexity, total MU and treatment time were evaluated between approaches., Results: Cardiac sparing plans reduced the mean heart dose (mean reduction 0.7 ± 0.6, range 0.1 to 2.5 Gy). Re-optimized plans reduced left anterior descending artery (LADA) mean and LADA 0.03cc (0.0-63.9% and 0.0 to 17.3 Gy, respectively). LV 0.03cc was reduced by >1.5 Gy for 10 patients while 6 cases had large reductions (>7%) in LV-V5. Left atrial mean dose was equivalent/reduced in all sparing plans (mean reduction 0.9 ± 1.2 Gy). The left main coronary artery was better spared in all cases for mean dose and D 0.03cc . One patient exhibited >10 Gy reduction in D 0.03cc to four substructures. There was no statistical difference in treatment time and MU, or clinical endpoints to the planning target volume, lung, esophagus, or spinal cord after re-optimization. Four patients benefited from new beam arrangements, leading to further dose reductions., Conclusions: By introducing 0.35T MRIs acquired on an MR-linac to verify cardiac substructure segmentations for CT-based treatment planning, an opportunity was presented for more effective sparing with limited increase in plan complexity. Validation in a larger cohort with appropriate margins offers potential to reduce radiation-related cardiotoxicities., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Objective: Psychological interventions reduce the impact of psychosis, but widescale implementation is problematic. We tested the feasibility of group acceptance and commitment therapy for Psychosis (G-ACTp), delivered by frontline staff, and co-facilitated by service-user experts-by-experience (SU-EbyE), for service-users and informal caregivers (ISRCTN: 68540929). We estimated recruitment/retention rates and outcome variability for future evaluation., Methods: Staff and SU-EbyE facilitators completed 1-day workshops, then delivered closely supervised G-ACTp, comprising four sessions (weeks 1-4) and two boosters (10 and 12 weeks). Participants recruited from adult community psychosis services were randomized to receive G-ACTp immediately or after 12 weeks, completing outcome assessments at 0, 4, and 12 weeks. Service-use/month was calculated for 1-year pre-randomization, weeks 0-12, and 5-year uncontrolled follow-up., Results: Of 41 facilitators trained (29 staff, 12 SU-EbyE), 29 (71%; 17 staff, 12 SU-EbyE) delivered 18 G-ACTp courses. Participant refusal rates were low (9% of service-users [10/112]; 5% of caregivers [4/79]); 60% of those invited to participate attended ≥1 G-ACTp session (64% of service-users [39/61]; 56% of caregivers [35/63]). Randomization of facilitators and participants proved problematic and participant follow-up was incomplete (78% [66/85]; 82% of service-users [36/44]; 73% of caregivers [30/41]). Effect sizes ranged from very small to large mostly favouring treatment. Service-use reductions require cautious interpretation, as very few participants incurred costs., Conclusions: Implementation appears feasible for service-users; for caregivers, retention needs improving. Outcome variability indicated n = 100-300/arm followed up (α = 0.05, 90% power). Methodological limitations' mean replication is needed: identified sources of potential bias may be reduced in a cluster randomized design with sessional outcome completion., Practitioner Points: Group acceptance and commitment therapy can be successfully adapted for people with psychosis and their caregivers. Implementation (training and delivery) is possible in routine community mental health care settings. Clinical and economic outcomes are promising, but replication is needed. Recommendations are made for future studies., (© 2020 British Psychological Society.)

Purpose: Radiation dose to cardiac substructures is related to radiation-induced heart disease. However, substructures are not considered in radiation therapy planning (RTP) due to poor visualization on CT. Therefore, we developed a novel deep learning (DL) pipeline leveraging MRI's soft tissue contrast coupled with CT for state-of-the-art cardiac substructure segmentation requiring a single, non-contrast CT input., Materials/methods: Thirty-two left-sided whole-breast cancer patients underwent cardiac T2 MRI and CT-simulation. A rigid cardiac-confined MR/CT registration enabled ground truth delineations of 12 substructures (chambers, great vessels (GVs), coronary arteries (CAs), etc.). Paired MRI/CT data (25 patients) were placed into separate image channels to train a three-dimensional (3D) neural network using the entire 3D image. Deep supervision and a Dice-weighted multi-class loss function were applied. Results were assessed pre/post augmentation and post-processing (3D conditional random field (CRF)). Results for 11 test CTs (seven unique patients) were compared to ground truth and a multi-atlas method (MA) via Dice similarity coefficient (DSC), mean distance to agreement (MDA), and Wilcoxon signed-ranks tests. Three physicians evaluated clinical acceptance via consensus scoring (5-point scale)., Results: The model stabilized in ~19 h (200 epochs, training error <0.001). Augmentation and CRF increased DSC 5.0 ± 7.9% and 1.2 ± 2.5%, across substructures, respectively. DL provided accurate segmentations for chambers (DSC = 0.88 ± 0.03), GVs (DSC = 0.85 ± 0.03), and pulmonary veins (DSC = 0.77 ± 0.04). Combined DSC for CAs was 0.50 ± 0.14. MDA across substructures was <2.0 mm (GV MDA = 1.24 ± 0.31 mm). No substructures had statistical volume differences (P > 0.05) to ground truth. In four cases, DL yielded left main CA contours, whereas MA segmentation failed, and provided improved consensus scores in 44/60 comparisons to MA. DL provided clinically acceptable segmentations for all graded patients for 3/4 chambers. DL contour generation took ~14 s per patient., Conclusions: These promising results suggest DL poses major efficiency and accuracy gains for cardiac substructure segmentation offering high potential for rapid implementation into RTP for improved cardiac sparing., (© 2019 American Association of Physicists in Medicine.)

Model-based iterative reconstruction (MBIR) reduces CT imaging dose while maintaining image quality. However, MBIR reduces noise while preserving edges which may impact intensity-based tasks such as auto-segmentation. This work evaluates the sensitivity of an auto-contouring prostate atlas across multiple MBIR reconstruction protocols and benchmarks the results against filtered back projection (FBP). Images were created from raw projection data for 11 prostate cancer cases using FBP and nine different MBIR reconstructions (3 protocols/3 noise reduction levels) yielding 10 reconstructions/patient. Five bony structures, bladder, rectum, prostate, and seminal vesicles (SVs) were segmented using an auto-segmentation pipeline that renders 3D binary masks for analysis. Performance was evaluated for volume percent difference (VPD) and Dice similarity coefficient (DSC), using FBP as the gold standard. Nonparametric Friedman tests plus post hoc all pairwise comparisons were employed to test for significant differences (P < 0.05) for soft tissue organs and protocol/level combinations. A physician performed qualitative grading of 396 MBIR contours across the prostate, bladder, SVs, and rectum in comparison to FBP using a six-point scale. MBIR contours agreed with FBP for bony anatomy (DSC ≥ 0.98), bladder (DSC ≥ 0.94, VPD < 8.5%), and prostate (DSC = 0.94 ± 0.03, VPD = 4.50 ± 4.77% (range: 0.07-26.39%). Increased variability was observed for rectum (VPD = 7.50 ± 7.56% and DSC = 0.90 ± 0.08) and SVs (VPD and DSC of 8.23 ± 9.86% range (0.00-35.80%) and 0.87 ± 0.11, respectively). Over the all protocol/level comparisons, a significant difference was observed for the prostate VPD between BSPL1 and BSTL2 (adjusted P-value = 0.039). Nevertheless, 300 of 396 (75.8%) of the four soft tissue structures using MBIR were graded as equivalent or better than FBP, suggesting that MBIR offered potential improvements in auto-segmentation performance when compared to FBP. Future work may involve tuning organ-specific MBIR parameters to further improve auto-segmentation performance. Running title: Impact of CT Reconstruction Algorithm on Auto-segmentation Performance., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: Radiation dose to the heart and cardiac substructures has been linked to cardiotoxicities. Because cardiac substructures are poorly visualized on treatment-planning computed tomography (CT) scans, we used the superior soft-tissue contrast of magnetic resonance (MR) imaging to optimize a hybrid MR/CT atlas for substructure dose assessment using CT., Methods and Materials: Thirty-one patients with left-sided breast cancer underwent a T2-weighted MR imaging scan and noncontrast simulation CT scans. A radiation oncologist delineated 13 substructures (chambers, great vessels, coronary arteries, etc) using MR/CT information via cardiac-confined rigid registration. Ground-truth contours for 20 patients were inputted into an intensity-based deformable registration atlas and applied to 11 validation patients. Automatic segmentations involved using majority vote and Simultaneous Truth and Performance Level Estimation (STAPLE) strategies with 1 to 15 atlas matches. Performance was evaluated via Dice similarity coefficient (DSC), mean distance to agreement, and centroid displacement. Three physicians evaluated segmentation performance via consensus scoring by using a 5-point scale. Dosimetric assessment included measurements of mean heart dose, left ventricular volume receiving 5 Gy, and left anterior descending artery mean and maximum doses., Results: Atlas approaches performed similarly well, with 7 of 13 substructures (heart, chambers, ascending aorta, and pulmonary artery) having DSC >0.75 when averaged over 11 validation patients. Coronary artery segmentations were not successful with the atlas-based approach (mean DSC <0.3). The STAPLE method with 10 matches yielded the highest DSC and the lowest mean distance to agreement for all high-performing substructures (omitting coronary arteries). For the STAPLE method with 10 matches, >50% of all validation contours had centroid displacements <3.0 mm, with the largest shifts in the coronary arteries. Atlas-generated contours had no statistical difference from ground truth for left anterior descending artery maximum dose, mean heart dose, and left ventricular volume receiving 5 Gy (P > .05). Qualitative contour grading showed that 8 substructures required minor modifications., Conclusions: The hybrid MR/CT atlas provided reliable segmentations of chambers, heart, and great vessels for patients undergoing noncontrast CT, suggesting potential widespread applicability for routine treatment planning., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pesticide misuse incidents in residential indoor areas are typically associated with misapplications that are inconsistent with the label directions of the product. Surface wipe sampling and analysis procedures are relied upon to evaluate the extent of indoor contamination and the remediation efforts successfully. In general, surface wipe sampling procedures are widely varied, which can complicate the comparison of the results and data interpretation. Wipe sampling parameters were studied for the insecticides malathion and carbaryl. The parameters evaluated include wipe media, wetting solvents, composite sampling, surface concentration, and the influence of differing product formulations. Porous and nonporous surfaces tested include vinyl tile, plywood and painted drywall (porous/permeable) and stainless steel and glass (nonporous/impermeable). Specific wipe materials included pre-packaged sterile-cotton gauze, pre-cleaned cotton twill, cotton balls, and a pre-packaged, pre-wetted wipe. Commercially available insecticide formulations were tested, and the results were compared to surfaces fortified with neat analytes to determine surface recovery results (efficiency). A sampling procedure to measure pesticide residues was developed, and variables associated with the sampling methods were evaluated to clarify how estimations of surface residues are impacted. Malathion recoveries were 73-86% for twill and pre-wetted, pre-packaged isopropanol wipes on nonporous materials. Malathion formulations ranged from 78 to 124% for pre-wetted, pre-packaged isopropanol wipes and cotton gauze wipes on nonporous materials. Carbaryl and carbaryl formulation recoveries were 82-115% and 77-110%, respectively, on nonporous surfaces for all tested wipe materials. While not every wipe sampling variable could be tested, the collected information from this study may be useful and applied to sampling plans for classes of chemicals with similar physicochemical properties., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Chronic active multiple sclerosis lesions, characterized by a hyperintense rim of iron-enriched, activated microglia and macrophages, have been linked to greater tissue damage. Post-mortem studies have determined that chronic active lesions are primarily related to the later stages of multiple sclerosis; however, the occurrence of these lesions, and their relationship to earlier disease stages may be greatly underestimated. Detection of chronic active lesions across the patient spectrum of multiple sclerosis requires a validated imaging tool to accurately identify lesions with persistent inflammation. Quantitative susceptibility mapping provides efficient in vivo quantification of susceptibility changes related to iron deposition and the potential to identify lesions harbouring iron-laden inflammatory cells. The PET tracer 11C-PK11195 targets the translocator protein expressed by activated microglia and infiltrating macrophages. Accordingly, this study aimed to validate that lesions with a hyperintense rim on quantitative susceptibility mapping from both relapsing and progressive patients demonstrate a higher level of innate immune activation as measured on 11C-PK11195 PET. Thirty patients were enrolled in this study, 24 patients had relapsing remitting multiple sclerosis, six had progressive multiple sclerosis, and all patients had concomitant MRI with a gradient echo sequence and PET with 11C-PK11195. A total of 406 chronic lesions were detected, and 43 chronic lesions with a hyperintense rim on quantitative susceptibility mapping were identified as rim+ lesions. Susceptibility (relative to CSF) was higher in rim+ (2.42 ± 17.45 ppb) compared to rim- lesions (-14.6 ± 19.3 ppb, P < 0.0001). Among rim+ lesions, susceptibility within the rim (20.04 ± 14.28 ppb) was significantly higher compared to the core (-5.49 ± 14.44 ppb, P < 0.0001), consistent with the presence of iron. In a mixed-effects model, 11C-PK11195 uptake, representing activated microglia/macrophages, was higher in rim+ lesions compared to rim- lesions (P = 0.015). Validating our in vivo imaging results, multiple sclerosis brain slabs were imaged with quantitative susceptibility mapping and processed for immunohistochemistry. These results showed a positive translocator protein signal throughout the expansive hyperintense border of rim+ lesions, which co-localized with iron containing CD68+ microglia and macrophages. In conclusion, this study provides evidence that suggests that a hyperintense rim on quantitative susceptibility measure within a chronic lesion is a correlate for persistent inflammatory activity and that these lesions can be identified in the relapsing patients. Utilizing quantitative susceptibility measure to differentiate chronic multiple sclerosis lesion subtypes, especially chronic active lesions, would provide a method to assess the impact of these lesions on disease progression.

Purpose: This work characterizes a novel exponential 4DCT reconstruction algorithm (EXPO), in phantom and patient, to determine its impact on image quality as compared to the standard cosine-squared weighted 4DCT reconstruction., Methods: A motion platform translated objects in the superior-inferior (S-I) direction at varied breathing rates (8-20 bpm) and couch pitches (0.06-0.1) to evaluate interplay between parameters. Ten-phase 4DCTs were acquired and data were reconstructed with cosine squared and EXPO weighting. To quantify the magnitude of image blur, objects were translated in the anterior-posterior (A-P) and S-I directions for full-width half maximum (FWHM) analysis between both 4DCT algorithms and a static case. 4DCT sinogram data for 10 patients were retrospectively reconstructed using both weighting factors. Image subtractions elucidated intensity and boundary differences. Subjective image quality grading (presence of image artifacts, noise, spatial resolution (i.e., lung/liver boundary sharpness), and overall image quality) was conducted yielding 200 evaluations., Results: After taking static object size into account, the FWHM of EXPO reconstructions in the A-P direction was 3.3 ± 1.7 mm (range: 0-4.9) as compared to cosine squared 9.8 ± 4.0 mm (range: 2.6-14.4). The FWHM of objects translated in the S-I direction reconstructed with EXPO agreed better with the static FWHM than the cosine-squared reconstructions. Slower breathing periods, faster couch pitches, and intermediate 4DCT phases had the largest reductions of blurring with EXPO. 18 of 60 comparisons of artifacts were improved with EXPO reconstruction, whereas no appreciable changes were observed in image quality scores. In 18 of 20 cases, EXPO provided sharper images although the reduced projections also increased baseline noise., Conclusion: Exponential weighted 4DCT offers potential for reducing image blur (i.e., improving image sharpness) in 4DCT with a tendency to reduce artifacts. Future work will involve evaluating the impact on treatment planning including delineation ability and dose calculation., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: Recent advancements in synthetic computed tomography (synCT) from magnetic resonance (MR) imaging data have made MRI-only treatment planning feasible in the brain, although synCT performance for image guided radiation therapy (IGRT) is not well understood. This work compares geometric equivalence of digitally reconstructed radiographs (DRRs) from CTs and synCTs for brain cancer patients and quantifies performance for partial brain IGRT., Methods and Materials: Ten brain cancer patients (12 lesions, 7 postsurgical) underwent MR-SIM and CT-SIM. SynCTs were generated by combining ultra-short echo time, T1, T2, and fluid attenuation inversion recovery datasets using voxel-based weighted summation. SynCT and CT DRRs were compared using patient-specific thresholding and assessed via overlap index, Dice similarity coefficient, and Jaccard index. Planar IGRT images for 22 fractions were evaluated to quantify differences between CT-generated DRRs and synCT-generated DRRs in 6 quadrants. Previously validated software was implemented to perform 2-dimensional (2D)-2D rigid registrations using normalized mutual information. Absolute (planar image/DRR registration) and relative (differences between synCT and CT DRR registrations) shifts were calculated for each axis and 3-dimensional vector difference. A total of 1490 rigid registrations were assessed., Results: DRR agreements in anteroposterior and lateral views for overlap index, Dice similarity coefficient, and Jaccard index were >0.95. Normalized mutual information results were equivalent in 75% of quadrants. Rotational registration results were negligible (<0.07°). Statistically significant differences between CT and synCT registrations were observed in 9/18 matched quadrants/axes (P < .05). The population average absolute shifts were 0.77 ± 0.58 and 0.76 ± 0.59 mm for CT and synCT, respectively, for all axes/quadrants. Three-dimensional vectors were <2 mm in 77.7 ± 10.8% and 76.5 ± 7.2% of CT and synCT registrations, respectively. SynCT DRRs were sensitive in postsurgical cases (vector displacements >2 mm in affected quadrants)., Conclusions: DRR synCT geometry was robust. Although statistically significant differences were observed between CT and synCT registrations, results were not clinically significant. Future work will address synCT generation in postsurgical settings., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Bipolar disorder is a chronic and disabling psychiatric condition, characterised by recurrent episodes of mania, hypomania and depression. It places a heavy burden on sufferers and families, with high societal and healthcare costs. Many service users with a diagnosis of bipolar disorder also experience prominent psychotic symptoms, with differential diagnoses of schizoaffective disorder, and relapses characterised by repeated manic psychotic episodes and grandiosity. Such presentations require specific adaptations to standard bipolar disorder interventions in order to address their psychosis, alongside mood regulation, with a particular emphasis on impulsivity, irritability, disinhibition and elation. The Balancing ACT study aims to evaluate an innovative group intervention combining Acceptance and Commitment Therapy and psychoeducation approaches (ACT/PE) with individuals experiencing bipolar disorder and/or symptoms within community psychosis services., Methods: The Balancing ACT study is a randomised controlled trial comparing Balancing ACT groups (ACT/PE) plus routine care to routine care alone. Balancing ACT (ACT/PE) comprises ten group sessions, each lasting 2 hours, delivered weekly. The primary outcome is psychological wellbeing; secondary outcomes are mental health relapses (measured by service use averages for the 12 months pre baseline and 3 months post baseline). We will also measure mood, distress, recovery and psychological change processes. Participants will be randomised in a 1:1 ratio, after baseline assessment. Outcomes will be assessed by trained assessors blind to treatment condition at 0, 10 and 14 weeks. Recruitment began in April 2017 and is on-going until the end of October 2017., Discussion: The Balancing ACT study will contribute to the currently limited evidence base for psychological interventions for people experiencing bipolar disorder and/or symptoms in the context of community psychosis services., Trial Registration: ISRCTN73327972 . Registered on 27 March 2017. Balancing ACT: evaluating the effectiveness of psychoeducation and Acceptance and Commitment Therapy (ACT) groups for people with bipolar disorder.

Lesbian, gay, bisexual, and transgender (LGBT) people seek psychotherapy at high rates, and the importance of providing culturally appropriate and LGBT-affirmative psychotherapy has been widely acknowledged. Despite this, remarkably little research has investigated the effects of therapist training in LGBT-affirmative psychotherapy. Here we examined the effectiveness of a training protocol for LGBT-affirmative psychotherapy with 96 mental health professionals, ranging in therapeutic experience from <1 year to 37 years (M = 6.54 years). Across all outcomes, therapists reported increased knowledge and skills related to working with LGBT clients following the training. Therapists also displayed reductions in homo-negativity and trans-negativity. Therapists' characteristics did not influence the extent to which they benefited from training. Specifically, years of clinical experience, therapist religiosity, and therapist psychological flexibility were unrelated to changes in attitudes, knowledge, and skills. The results of this study clearly suggest that providing training in LGBT-affirmative psychotherapy can enhance therapists' attitudes, knowledge, and skills. Of particular importance is that the benefits associated with such training appear to hold regardless of therapists' characteristics. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Objective: Over the past 50 years, the field of chronic pain has witnessed an evolution of psychological approaches with some notable success. Some of this evolution has included "mindfulness-based interventions" (MBIs), now regarded as having encouraging partial support for their effectiveness. However, several theoretical challenges remain that may inhibit the progress of MBIs. These challenges include a lack of clarity surrounding the mindfulness construct itself, the proliferation of purported underlying mechanisms arising from different theories, and limited evidence for the mechanisms through which MBIs work. The current conceptual review provides a critique of existing theoretical models of mindfulness that have been applied to understanding and treating chronic pain., Design: A conceptual narrative review was conducted., Setting: Treatment programs for people with chronic pain., Patients: Individuals with any type of chronic pain., Interventions: MBIs for chronic pain., Outcome Measures: Mindfulness-based mechanisms explored in relation to several domains of functioning., Results and Conclusions: Based on this assessment, a summary of available evidence for a particular contextual behavioral theory of "mindfulness"-psychological flexibility-is outlined. Findings show the need for further integration of existing mindfulness constructs to better guide development and evaluation of mindfulness-based treatment methods in the future., (© 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)