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University systems maintain prohibitive closures that constitute a closed-loop system: opaque academic practices, control of what counts as knowledge, financial and social exclusion, and the perpetuation of privilege. Yet this closed-loop system is also governed by adherence to values around education as a public good, openness, and authenticity, and education as a vehicle for social mobility. The closures and openings created with such systems are in tension. Open education in universities is entwined in these tensions. In this paper, we differentiate between prohibitive closures and enabling closures. We define enabling closures as closed loops of activity that allow for openings both at the boundaries of the university and within. It is through these enabling closures that universities can adhere to open education as accepted policy and practice. As such, in this paper we explore how open education sits in tension with closed technological and increasingly commercialized educational infrastructures in higher education. [ABSTRACT FROM AUTHOR]

Line intensity mapping (LIM) is a new technique for tracing the global properties of galaxies over cosmic time. Detection of the very faint signals from redshifted carbon monoxide (CO), a tracer of star formation, pushes the limits of what is feasible with a total-power instrument. The CO Mapping Project Pathfinder is a first-generation instrument aiming to prove the concept and develop the technology for future experiments, as well as delivering early science products. With 19 receiver channels in a hexagonal focal plane arrangement on a 10.4 m antenna and an instantaneous 26â€"34 GHz frequency range with 2 MHz resolution, it is ideally suited to measuring CO (J = 1â€"0) from z ∼ 3. In this paper we discuss strategies for designing and building the Pathfinder and the challenges that were encountered. The design of the instrument prioritized LIM requirements over those of ancillary science. After a couple of years of operation, the instrument is well understood, and the first year of data is already yielding useful science results. Experience with this Pathfinder will guide the design of the next generations of experiments. [ABSTRACT FROM AUTHOR]

Diagnostic dinosaur fossils of the southeastern United States are rare discoveries, and even more precious are those fossils that preserve a large portion of a skeleton. Sixty years ago, the dinosaur Lophorhothon atopus was described from Upper Cretaceous sediments of Alabama. It then represented the oldest, most complete, dinosaur in the southeastern United States. Based on a reexamination of the holotype material and a new specimen collected from the same beds, we provide a new diagnosis of this taxon. In particular, the solid nasal crest has several autapomorphies including caudally projecting frontal processes that are oval in cross section, meaning that they did not coalesce at the midline. Other autapomorphies are found on the prefrontal and squamosal. Combining the two Lophorhothon specimens provides nearly the entire skeleton for phylogenetic analysis, which we find as a hadrosauromorph just outside of Hadrosauridae. The original diagnosis of this taxon included the frontonasal fontanelle as a distinguishing character, but comparing the many examples of frontonasal openings across hadrosauromorph taxa shows that in at least a few species, such as Lophorhothon, the structures should be considered a frontonasal fenestra instead of a fontanelle. Additionally, the notion that dinosaurs from the East Coast of the United States represent primitive relicts is an idea that originated before many of the European and Asian hadrosauromorphs known today had been discovered. With new dating and phylogenetic information, it appears that Appalachian dinosaurs are on par evolutionarily with most of the global community and the term "relict fauna" should be abandoned. [ABSTRACT FROM AUTHOR]

The dynamics of laser spot melting and metallic alloy solidification are investigated through synchrotron x-ray radiography, 3D electron backscatter diffraction data, and computational fluid dynamics (CFD) simulations on a model NiMoAl alloy. Solidification velocities are measured from in-situ images to validate a CFD model of the spot melt. TriBeam tomography is used to reconstruct the melt pool in 3D, characterize the microstructure, and validate the CFD model melt pool dimensions. 3D geometrically necessary dislocation (GND) density calculations reveal extensive deformation at the sample surface. GND calculations integrated with the CFD model reveal that the halo of small, equiaxed grains adjacent to the fusion line is a result of recrystallization that occurred in the heat affected zone. By combining in-situ and ex-situ data modalities across a variety of temporal and spatial length scales, the microstructure formation mechanisms and their relationship to melt pool solidification are quantified. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiotherapy (SBRT) is becoming increasingly used in treating localized prostate cancer (PCa), with evidence showing similar toxicity and efficacy profiles when compared with longer courses of definitive radiation. Magnetic resonance imaging (MRI)-guided radiotherapy has multiple potential advantages over standard computed tomography (CT)-guided radiotherapy, including enhanced prostate visualization (abrogating the need for fiducials and MRI fusion), enhanced identification of the urethra, the ability to track the prostate in real-time, and the capacity to perform online adaptive planning. However, it is unknown whether these potential advantages translate into improved outcomes. This phase III randomized superiority trial is designed to prospectively evaluate whether toxicity is lower after MRI-guided versus CT-guided SBRT.Methods: Three hundred men with localized PCa will be randomized in a 1:1 ratio to SBRT using CT or MRI guidance. Randomization will be stratified by baseline International Prostate Symptom Score (IPSS) (≤15 or > 15) and prostate gland volume (≤50 cc or > 50 cc). Five fractions of 8 Gy will be delivered to the prostate over the course of fourteen days, with or without hormonal therapy and elective nodal radiotherapy (to a dose of 5 Gy per fraction) as per the investigator's discretion. The primary endpoint is the incidence of physician-reported acute grade ≥ 2 genitourinary (GU) toxicity (during the first 90 days after SBRT), as assessed by the CTCAE version 4.03 scale. Secondary clinical endpoints include incidence of acute grade ≥ 2 gastrointestinal (GI) toxicity, 5-year cumulative incidences of physician-reported late grade ≥ 2 GU and GI toxicity, temporal changes in patient-reported quality of life (QOL) outcomes, 5-year biochemical recurrence-free survival and the proportion of fractions of MRI-guided SBRT in which online adaptive radiotherapy is used.Discussion: The MIRAGE trial is the first randomized trial comparing MRI-guided with standard CT-guided SBRT for localized PCa. The primary hypothesis is that MRI-guided SBRT will lead to an improvement in the cumulative incidence of acute grade ≥ 2 GU toxicity when compared to CT-guided SBRT. The pragmatic superiority design focused on an acute toxicity endpoint will allow an early comparison of the two technologies.Trial Registration: Clinicaltrials.gov identifier: NCT04384770. Date of registration: May 12, 2020. https://clinicaltrials.gov/ct2/show/NCT04384770 PROTOCOL VERSION: Version 2.1, Aug 28, 2020. [ABSTRACT FROM AUTHOR]

A newly developed CoNi-based superalloy is demonstrated to be tolerant of a wide range of laser powder bed fusion print conditions, with limited defect content and high relative densities. These promising traits motivated investigation of the structural uniformity in samples printed at the upper end of the scan velocity processing window (>▪). A new misorientation metric, starting reference orientation deviation (SROD), was calculated from ▪-scale 3D microstructure information to examine structure evolution during epitaxial growth of columnar grains. Misorientations of >20° were observed within the large columnar grains that grew through multiple build layers. The SROD observations highlight the CoNi superalloy's ability to plastically deform to high levels, as evidenced by misorientation gradients, across the range of temperatures experienced in laser additive manufacturing. Misorientation gradients within the columnar grain structure are high relative to Ni base superalloys, allowing for strengthening with high volume fractions of L 1 2 precipitates. [ABSTRACT FROM AUTHOR]

In this article we describe and critique a methodological exercise that brings together multimodality, ethnography and walking in order to investigate the city. Drawing on the experience of enacting our methodology in central London, we describe how an openness to the full range of meaning-making phenomena encountered during an unscripted excursion through the city provided ways of thinking critically about our relationship with the city. This research is undertaken against a backdrop of a growing critical interest in the complex and shifting nature of the urban environment, reflected in the range of approaches that investigate how we understand and experience our surroundings. Central to this methodological approach is the intersection of ethnography and multimodality which, when brought together within the device of an unscripted walk, provides valuable opportunities for thinking critically about our surroundings. [ABSTRACT FROM AUTHOR]

Focuses on a study that examined semiconductor-metal graded-index composite thin films for infrared applications. Uniqueness of composite thin films; Analysis of the reflectance spectra of different germanium:silver composite films deposited on silver mirrors; Application of the thin films to tunnel infrared detectors.

Purpose To determine whether image guidance with rigid registration (RR) to intraprostatic markers (IPMs) yields acceptable coverage of the pelvic lymph nodes in the context of a stereotactic body radiation therapy (SBRT) regimen. Methods and Materials Four to seven kilovoltage cone-beam CTs (CBCTs) from 12 patients with high-risk prostate cancer were analyzed, allowing approximation of an SBRT regimen. The nodal clinical target volume (CTV N ) and bladder were contoured on all kilovoltage CBCTs. The V 100 CTV N , expressed as a ratio to the same parameter on the initial plan, and the magnitude of translational shift between RR to the IPMs versus RR to the pelvic bones, were computed. The ability of a multimodality bladder filling protocol to minimize bladder height variation was assessed in a separate cohort of 4 patients. Results Sixty-five CBCTs were assessed. The average V 100 CTV N was 92.6%, but for a subset of 3 patients the average was 80.0%, compared with 97.8% for the others ( P <.0001). The average overall and superior–inferior axis magnitudes of the bony-to-fiducial translations were significantly larger in the subgroup with suboptimal nodal coverage (8.1 vs 3.9 mm and 5.8 vs 2.4 mm, respectively; P <.0001). Relative bladder height changes were also significantly larger in the subgroup with suboptimal nodal coverage (42.9% vs 18.5%; P <.05). Use of a multimodality bladder-filling protocol minimized bladder height variation ( P <.001). Conclusion A majority of patients had acceptable nodal coverage after RR to IPMs, even when approximating SBRT. However, a subset of patients had suboptimal nodal coverage. These patients had large bony-to-fiducial translations and large variations in bladder height. Nodal coverage should be excellent if the superior–inferior axis bony-to-fiducial translation and the relative bladder height change (both easily measured on CBCT) are kept to a minimum. Implementation of a strict bladder filling protocol may achieve this goal. [ABSTRACT FROM AUTHOR]

Highlights: [•] We critically review the WHO-UNEP 2012 report on endocrine disruptors. [•] WHO-UNEP report is not an update of the WHO-IPCS 2002 state-of-the-science review. [•] WHO-UNEP report should not guide evidence-based decisions on endocrine disruption. [•] A balanced and objective review of all available literature is needed. [•] An update must note controversies, data gaps, and provide supported conclusions. [Copyright &y& Elsevier]

Purpose: To develop a novel 4-dimensional computed tomography (4D-CT) technique that exploits standard fast helical acquisition, a simultaneous breathing surrogate measurement, deformable image registration, and a breathing motion model to remove sorting artifacts. Methods and Materials: Ten patients were imaged under free-breathing conditions 25 successive times in alternating directions with a 64-slice CT scanner using a low-dose fast helical protocol. An abdominal bellows was used as a breathing surrogate. Deformable registration was used to register the first image (defined as the reference image) to the subsequent 24 segmented images. Voxel-specific motion model parameters were determined using a breathing motion model. The tissue locations predicted by the motion model in the 25 images were compared against the deformably registered tissue locations, allowing a model prediction error to be evaluated. A low-noise image was created by averaging the 25 images deformed to the first image geometry, reducing statistical image noise by a factor of 5. The motion model was used to deform the low-noise reference image to any user-selected breathing phase. A voxel-specific correction was applied to correct the Hounsfield units for lung parenchyma density as a function of lung air filling. Results: Images produced using the model at user-selected breathing phases did not suffer from sorting artifacts common to conventional 4D-CT protocols. The mean prediction error across all patients between the breathing motion model predictions and the measured lung tissue positions was determined to be 1.19 ± 0.37 mm. Conclusions: The proposed technique can be used as a clinical 4D-CT technique. It is robust in the presence of irregular breathing and allows the entire imaging dose to contribute to the resulting image quality, providing sorting artifact–free images at a patient dose similar to or less than current 4D-CT techniques. [ABSTRACT FROM AUTHOR]

Highlights: [•] We have tested a variety of passive electronic components at cryogenic temperatures. [•] A suitable subset has been identified for low-voltage cryogenic device protection. [•] A protection circuit for millimeterwave HEMT amplifiers has been demonstrated. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether kilovoltage x-ray projection radiation therapy setup images could be used to perform patient identification and detect gross errors in patient setup using a computer algorithm. Methods and Materials: Three patient cohorts treated using a commercially available image guided radiation therapy (IGRT) system that uses 2-dimensional to 3-dimensional (2D-3D) image registration were retrospectively analyzed: a group of 100 cranial radiation therapy patients, a group of 100 prostate cancer patients, and a group of 83 patients treated for spinal lesions. The setup images were acquired using fixed in-room kilovoltage imaging systems. In the prostate and cranial patient groups, localizations using image registration were performed between computed tomography (CT) simulation images from radiation therapy planning and setup x-ray images corresponding both to the same patient and to different patients. For the spinal patients, localizations were performed to the correct vertebral body, and to an adjacent vertebral body, using planning CTs and setup x-ray images from the same patient. An image similarity measure used by the IGRT system image registration algorithm was extracted from the IGRT system log files and evaluated as a discriminant for error detection. Results: A threshold value of the similarity measure could be chosen to separate correct and incorrect patient matches and correct and incorrect vertebral body localizations with excellent accuracy for these patient cohorts. A 10-fold cross-validation using linear discriminant analysis yielded misclassification probabilities of 0.000, 0.0045, and 0.014 for the cranial, prostate, and spinal cases, respectively. Conclusions: An automated measure of the image similarity between x-ray setup images and corresponding planning CT images could be used to perform automated patient identification and detection of localization errors in radiation therapy treatments. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To quantify the benefit of motion-specific internal target volumes for FDG-avid mediastinal and hilar lymph nodes generated using 4D-PET, vs. conventional internal target volumes generated using non-respiratory gated PET and 4D-CT scans. Materials and methods: Five patients with FDG-avid tumors metastatic to 11 hilar or mediastinal lymph nodes were imaged with respiratory-correlated FDG-PET (4D-PET) and 4D-CT. FDG-avid nodes were contoured by a radiation oncologist in two ways. Standard-of-care volumes were contoured using conventional un-gated PET, 4D-CT, and breath-hold CT. A second, motion-specific, set of volumes were contoured using 4D-PET.Contours based on 4D-PET corresponded directly to an internal target volume (ITV4D), whereas contours based on un-gated PET were expanded by a series of exploratory isotropic margins (from 5 to 13mm) based on literature recommendations on lymph node motion to form internal target volumes (ITV3D). Results: A 13mm expansion of the un-gated PET nodal volume was needed to cover the ITV4D for 10 of 11 nodes studied. The ITV3D based on a 13mm expansion included on average 45cm3 of tissue that was not included in the ITV4D. Conclusions: Motion-specific lymph-node internal target volumes generated from 4D-PET imaging could be used to improve accuracy and/or reduce normal-tissue irradiation compared to the standard-of-care un-gated PET based internal target volumes. [Copyright &y& Elsevier]

Abstract: Effects of trichloroethylene (TCE) on male reproduction and fertility have been studied in mice and rats, and assessed in workers exposed to TCE. Only limited evidence exists for any male reproductive effects in rats or humans. The human studies of TCE male reproductive effects failed to provide much useful information for risk assessment. First, the TCE-specific studies are limited in group size, scope, and typically provide no data on dose, so dose–response assessment is impossible. In other studies, TCE is only one of many solvents identified in the workplace, such that the confounding exposures or lack of evidence of specific exposures make the exposure assessment useless. For TCE risk assessment, one currently must rely upon animal studies as more reliable and useful. The rat studies were generally negative, showing systemic toxicity but little or no male reproductive toxicity. The mouse studies showed various organ effects in the male reproductive system and were typically associated with increased liver weight and kidney toxicity. Enzyme induction and oxidative metabolism appear to be important in the systemic toxicity and may likewise play a role in the reproductive toxicity of TCE. Oxidative metabolites of TCE are formed in the mouse epididymis resulting in epididymal damage, and at systemically toxic high doses, TCE may adversely affect the maturation of sperm and decreasing sperm motility. Protection against systemic toxicity should also protect against adverse effects including male reproductive toxicity. [Copyright &y& Elsevier]

The Atacama Large Millimeter Array (ALMA) will be a powerful new interferometer for millimeter and submillimeter astronomy on an excellent site in Chile. The design of the receiver optics plays a crucial role in the ultimate sensitivity of the ALMA instrument. We present the design concepts used in the development of the optical layout of the receivers. Properties of optical elements are reviewed, and the suitability of various types of optical components is discussed. Particular emphasis is placed on principles of high efficiency optical train designs. It is shown that the optical systems should be a simple as possible and that truncation losses have to be minimized. The areas which have the greatest uncertainty are the windows and IR filters where the tradeoffs between the radio frequency losses, IR blocking, pressure resistance and gas permeability have to be carefully evaluated. A sample design for the ALMA Band 3 (84-116 GHz) is given. [ABSTRACT FROM AUTHOR]

Discusses issues concerning environmental health. Herbicide effects on embryo implantation and litter size; Incidence of asthma among Gulf War veterans; Emergency communication.

Present knowledge of patient setup and alignment errors in image guided radiation therapy (IGRT) relies on voluntary reporting, which is thought to underestimate error frequencies. A manual retrospective patient-setup misalignment error search is infeasible owing to the bulk of cases to be reviewed. We applied a deep learning–based misalignment error detection algorithm (EDA) to perform a fully automated retrospective error search of clinical IGRT databases and determine an absolute gross patient misalignment error rate. The EDA was developed to analyze the registration between planning scans and pretreatment cone beam computed tomography scans, outputting a misalignment score ranging from 0 (most unlikely) to 1 (most likely). The algorithm was trained using simulated translational errors on a data set obtained from 680 patients treated at 2 radiation therapy clinics between 2017 and 2022. A receiver operating characteristic analysis was performed to obtain target thresholds. DICOM Query and Retrieval software was integrated with the EDA to interact with the clinical database and fully automate data retrieval and analysis during a retrospective error search from 2016 to 2017 and from 2021 to 2022 for the 2 institutions, respectively. Registrations were flagged for human review using both a hard-thresholding method and a prediction trending analysis over each individual patient's treatment course. Flagged registrations were manually reviewed and categorized as errors (>1 cm misalignment at the target) or nonerrors. A total of 17,612 registrations were analyzed by the EDA, resulting in 7.7% flagged events. Three previously reported errors were successfully flagged by the EDA, and 4 previously unreported vertebral body misalignment errors were discovered during case reviews. False positive cases often displayed substantial image artifacts, patient rotation, and soft tissue anatomy changes. Our results validated the clinical utility of the EDA for bulk image reviews and highlighted the reliability and safety of IGRT, with an absolute gross patient misalignment error rate of 0.04% ± 0.02% per delivered fraction. [ABSTRACT FROM AUTHOR]

Argues against the theory of evaluative compatibilism, which states that arguments for the incompatibility of free will and determinism are irrelevant to moral responsibility for an action. Principle of alternate possibilities; Strong, moderate and weak as variations to the principle; Counterexamples to the principle.

Proton radiotherapy has clear dosimetric advantages over photon radiotherapy. In contrast to photons, which are absorbed exponentially, protons have a finite range dependent on the initial proton energy. Protons therefore do not deposit dose beyond the tumor, resulting in great conformality, and offers the promise of dose escalation to increase tumor control while minimizing toxicity. In this review, we discuss the rationale for using proton radiotherapy in the treatment of upper abdominal tumors—hepatocellular carcinomas, cholangiocarcinomas and pancreatic cancers. We also review the clinical outcomes and technical challenges of using proton radiotherapy for the treatment of these malignancies. Finally, we discuss the ongoing clinical trials implementing proton radiotherapy for the treatment of primary liver and pancreatic tumors. [ABSTRACT FROM AUTHOR]

Describes contact planarization (CP), an alternative to chemical mechanical planarization. Steps of CP; Application of the process to a dielectric topography substrate from SKW; Topography scans and film thickness measurements; Types of isolated and dense features; Role of CP to enhance planarization under two difficult conditions; Benefits of the process.

We performed two surveys to uncover the status of philanthropic endowments in general internal medicine divisions. The initial survey of U.S. medical school departments of medicine found that only 14.1% of general internal medicine divisions hold endowments versus 21.9% of all other divisions, and that endowment sources for general medicine are atypical. The second survey of successfully endowed divisions found that sympathetic administrators and active pursuit of endowments were associated with endowment success. Aggressive pursuit of endowments, publicizing successes of general medicine, and consideration of endowment sources noted in this study are recommended to improve philanthropic contributions to general internal medicine. [ABSTRACT FROM AUTHOR]

Real-time intrafraction tracking/gating is an integral component of magnetic resonance imaging-guided radiation therapy (MRgRT) and may have contributed to the acute toxicity reduction during prostate stereotactic body radiation therapy observed on the MRgRT-arm of the MIRAGE (M AGNET I C R ESONANCE IM A GING- G UID E D Stereotactic Body Radiotherapy for Prostate Cancer) randomized trial (NCT04384770). Herein we characterized intrafraction prostate motion and assessed gating effectiveness. Seventy-nine patients were treated on an MR-LINAC. Real-time cine imaging was acquired at 4Hz in a sagittal plane. If >10% of the prostate area moved outside of a 3-mm gating boundary, an automatic beam hold was initiated. An in-house tool was developed to retrospectively extract gating signal for all patients and identify the tracked prostate in each cine frame for a subgroup of 40 patients. The fraction of time the prostate was within the gating window was defined as the gating duty cycle (GDC). A total of 391 treatments from 79 patients were analyzed. Median GDC was 0.974 (IQR, 0.916-0.983). Fifty (63.2%) and 24 (30.4%) patients had at least 1 fraction with GDC ≤0.9 and GDC ≤0.8, respectively. Incidence of low GDC fractions among patients appeared stochastic. Patients with minimum GDC <0.8 trended toward more frequent grade 2 genitourinary toxicity compared with those with minimum GDC >0.8 (38% vs 18%, P =.065). Prostate intrafraction motion was mostly along the bladder-rectum axis and predominantly in the superior-anterior direction. Motion in the inferior-posterior direction was associated with significantly higher rate of acute grade 2 genitourinary toxicity (66.7% vs 13.9%, P =.001). Gating limited mean prostate motion during treatment delivery in fractions with a GDC <0.9 (<0.8) to 2.9 mm (2.9 mm) versus 4.1 mm (4.7 mm) for ungated motion. Fractions with large intrafraction motion were associated with increased toxicity and their occurrence among patients appears stochastic. Real-time tracking/gating effectively mitigated this motion and is likely a major contributing factor of acute toxicity reduction associated with MRgRT. [ABSTRACT FROM AUTHOR]

Emerging data suggest that trigone dosimetry may be more associated with poststereotactic body radiation therapy (SBRT) urinary toxicity than whole bladder dosimetry. We quantify the dosimetric effect of interfractional displacement and deformation of the whole bladder and trigone during prostate SBRT using on-board, pretreatment 0.35T magnetic resonance images (MRI). Seventy-seven patients treated with MRI-guided prostate SBRT (40 Gy/5 fractions) on the MRI arm of a phase 3 single-center randomized trial were included. Bladder and trigone structures were contoured on images obtained from a 0.35T simulation MRI and 5 on-board pretreatment MRIs. Dice similarity coefficient (DSC) scores and changes in volume between simulation and daily treatments were calculated. Dosimetric parameters including D max , D 0.03 cc , D mean , V 40 Gy , V 39 Gy , V 38 Gy , and V 20 Gy for the bladder and trigone for the simulation and daily treatments were collected. Both physician-scored (Common Terminology Criteria for Adverse Events, version 4.03 scale) as well as patient-reported (International Prostate Symptom Scores and the Expanded Prostate Cancer Index Composite-26 scores) acute genitourinary (GU) toxicity outcomes were collected and analyzed. The average treatment bladder volume was about 30% smaller than the simulation bladder volume; however, the trigone volume remained fairly consistent despite being positively correlated with total bladder volume. Overall, the trigone accounted for <2% of the bladder volume. Median DSC for the bladder was 0.79, whereas the median DSC of the trigone was only 0.33. No statistically significant associations between our selected bladder and trigonal dosimetric parameters and grade ≥2 GU toxicity were identified, although numerically, patients with GU toxicity (grade ≥2) had higher intermediate doses to the bladder (V 20 Gy and D mean) and larger volumes exposed to higher doses in the trigone (V 40 Gy , V 39 Gy , and V 38 Gy). The trigone exhibits little volume change, but considerable interfractional displacement/deformation. As a result, the relative volume of the trigone receiving high doses during prostate SBRT varies substantially between fractions, which could influence GU toxicity and may not be predicted by radiation planning dosimetry. [ABSTRACT FROM AUTHOR]

Purpose: Motion prediction can compensate for latency in image‐guided radiotherapy and has been an active area of research. However, motion predictions are subject to error and variations. We have developed and evaluated a novel motion prediction confidence estimation framework to improve the efficacy and robustness of prediction‐based radiotherapy gating decision‐making. The specific scenario of adaptive gating in magnetic resonance imaging (MRI)‐guided radiotherapy is studied as an example, but the method generalizes to other modalities and motion management setups. Methods: The proposed prediction confidence estimator is based on a generic training/testing paradigm and consists of a weighted combination of three components: the prediction model's goodness of fit, variation in the prediction using a leave‐one‐out process and the velocity of the tracked target. Roughly, these terms quantify respectively the consistency between prediction and the training data, the robustness of model inference, and the stability due to target speed. The weight parameters and the action level in triggering beam‐off decision are optimized. The method is assessed and validated in 8 healthy volunteer and 13 patient studies using a 0.35T MRI‐guided radiotherapy system predicting 0.25–0.33 s ahead. The effect of the action level on the predicted gating decision accuracy, beam‐on positive predictive value (PPV) and median distance between the predicted and ground‐truth target centroids were evaluated. Statistical significance was evaluated using a paired t‐test. The tradeoff between these performance metrics and gating duty cycle was assessed. Results: Use of the confidence estimator threshold increased gating accuracy by up to 2.42%, increased PPV by up to 3.00%, and reduced the median centroid distance up to 0.28 mm. The confidence estimator threshold on average increased gating accuracy to 96.5% (P = 2.08 × 10−4), increased PPV to 96.7% (P = 1.46 × 10−5), reduced the median centroid distance to 0.54 mm (P = 1.71 × 10−5) at the cost of reducing the gating duty cycle by 14.3% to 48.5%. Hyperparameter tuning revealed that contrary to intuition, the velocity term offered only minimal performance improvement in some cases but also introduced potential stability issues. The combination of goodness of fit and leave‐one‐out prediction variation provided the most effective confidence estimator, yielding universally better performance in gating decisions. Conclusion: Confidence estimation utilizing prediction model fitness criterion and validation principles can complement prediction methods to guide MRI‐guided radiotherapy gating. Results from both volunteer and patient studies showed improved gating quality. [ABSTRACT FROM AUTHOR]

Refractory alloys can be difficult to fabricate by laser-based manufacturing methods due to their high melting temperatures, high interstitial solubility, and propensity for low temperature brittleness. Laser-based processes, such as welding and additive manufacturing (AM), yield similar populations of defects, including microsegregation and solidification and solid-state cracking. Given the extreme challenges and cost associated with the production of refractory powders, this research aimed to develop a rapid screening methodology that combines predictive defect formation metrics with single track melting experiments. A flexible single laser track melting platform was designed to perform screening experiments on conventional and multi-principal element refractory alloys across a wide range of laser energy inputs. The platform was employed to investigate laser melting on solid substrates, or on a substrate with a single layer of powder feedstock, and is demonstrated with the highly fabricable Nb-base alloy C103. Preliminary investigations are performed on refractory multi-principal element alloys in the Hf-Mo-Nb-Ta-Ti family, and significant differences in cracking resistance and solidification morphology are observed. Implications for future alloy design and processing strategies for defect-resistant refractory alloys for AM are discussed. • A single track laser set-up was developed for rapid screening of refractory multi-principal element alloys. • Similarities in solidification morphology and defects observed in laser melted C103 wrought and powder feedstock substrates. • Significant changes in crack resistance, solidification morphology observed with Ta substitution in the Hf-Nb-Mo-Ti family. • Predictive ductility and cracking criteria in tandem with single track experiments can assist refractory alloy design for AM. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer treatment with radiation therapy has advanced significantly over the years. Leveraging the proposed low α / β ratio of prostate cancer, radiation therapy for the definitive treatment of upfront prostate cancer has moved from conventionally fractioned approaches to ultrahypofractionated fractionation schemes that require increased precision in both treatment planning and treatment delivery. MRI-guided radiation therapy (MRIgRT) enables this precision-based approach by improving visualization of the prostate and the surrounding structures, enabling safer dose escalation with reduced toxicity profiles relative to CT-guided radiation therapy. Real-time gating and on-table adaptive treatment further reduce dose to normal structures. Treatment efficacy and reduced toxicity must be balanced with ongoing challenges pertaining to MRIgRT workflow and training. In this review, we focus on the utility of MRIgRT in the treatment of prostate cancer and highlight ongoing trials using ultrafractionated MRIgRT. Technological advances in MRI-guided radiation therapy (MRIgRT) have improved real-time visualization of the prostate and its surrounding structures over CT-guided radiation therapy. Seminal studies have demonstrated safe dose escalation achieved through ultrahypofractionation with MRIgRT due to planning target volume (PTV) margin reduction and treatment gating. On-table adaptation with MRI-based technologies can also incorporate real-time changes in target shape and volume and can reduce high doses of radiation to sensitive surrounding structures that may move into the treatment field. Ongoing clinical trials seek to refine ultrahypofractionated radiotherapy treatments for prostate cancer using MRIgRT. Though these studies have the potential to demonstrate improved biochemical control and reduced side effects, limitations concerning patient treatment times and operational workflows may preclude wide adoption of this technology outside of centers of excellence. In this review, we discuss the advantages and limitations of MRIgRT for prostate cancer, as well as clinical trials testing the efficacy and toxicity of ultrafractionation in patients with localized or post-prostatectomy recurrent prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Misalignment to the incorrect vertebral body remains a rare but serious patient safety risk in image‐guided radiotherapy (IGRT). Purpose: Our group has proposed that an automated image‐review algorithm be inserted into the IGRT process as an interlock to detect off‐by‐one vertebral body errors. This study presents the development and multi‐institutional validation of a convolutional neural network (CNN)‐based approach for such an algorithm using patient image data from a planar stereoscopic x‐ray IGRT system. Methods: X‐rays and digitally reconstructed radiographs (DRRs) were collected from 429 spine radiotherapy patients (1592 treatment fractions) treated at six institutions using a stereoscopic x‐ray image guidance system. Clinically‐applied, physician approved, alignments were used for true‐negative, "no‐error" cases. "Off‐by‐one vertebral body" errors were simulated by translating DRRs along the spinal column using a semi‐automated method. A leave‐one‐institution‐out approach was used to estimate model accuracy on data from unseen institutions as follows: All of the images from five of the institutions were used to train a CNN model from scratch using a fixed network architecture and hyper‐parameters. The size of this training set ranged from 5700 to 9372 images, depending on exactly which five institutions were contributing data. The training set was randomized and split using a 75/25 split into the final training/ validation sets. X‐ray/ DRR image pairs and the associated binary labels of "no‐error" or "shift" were used as the model input. Model accuracy was evaluated using images from the sixth institution, which were left out of the training phase entirely. This test set ranged from 180 to 3852 images, again depending on which institution had been left out of the training phase. The trained model was used to classify the images from the test set as either "no‐error" or "shifted", and the model predictions were compared to the ground truth labels to assess the model accuracy. This process was repeated until each institution's images had been used as the testing dataset. Results: When the six models were used to classify unseen image pairs from the institution left out during training, the resulting receiver operating characteristic area under the curve values ranged from 0.976 to 0.998. With the specificity fixed at 99%, the corresponding sensitivities ranged from 61.9% to 99.2% (mean: 77.6%). With the specificity fixed at 95%, sensitivities ranged from 85.5% to 99.8% (mean: 92.9%). Conclusion: This study demonstrated the CNN‐based vertebral body misalignment model is robust when applied to previously unseen test data from an outside institution, indicating that this proposed additional safeguard against misalignment is feasible. [ABSTRACT FROM AUTHOR]

Growth of intact axons of noninjured neurons, often termed collateral sprouting, contributes to both adaptive and pathological plasticity in the adult nervous system, but the intracellular factors controlling this growth are largely unknown. An automated functional assay of genes regulated in sensory neurons from the rat in vivo spared dermatome model of collateral sprouting identified the adaptor protein CD2-associated protein (CD2AP; human CMS) as a positive regulator of axon growth. In non-neuronal cells, CD2AP, like other adaptor proteins, functions to selectively control the spatial/temporal assembly of multiprotein complexes that transmit intracellular signals. Although CD2AP polymorphisms are associated with increased risk of late-onset Alzheimer's disease, its role in axon growth is unknown. Assessments of neurite arbor structure in vitro revealed CD2A Pover expression, and siRNA-mediated knockdown, modulated (1) neurite length, (2) neurite complexity, and (3) growth cone filopodia number, in accordance with CD2AP expression levels.Weshow, for the first time, that CD2AP forms a novel multiprotein complex with the NGF receptor TrkA and the PI3K regulatory subunit p85, with the degree of TrkA:p85 association positively regulated by CD2AP levels. CD2AP also regulates NGF signaling through AKT, but not ERK, and regulates long-range signaling though TrkA+/RAB5+ signaling endosomes. CD2AP mRNA and protein levels were increased in neurons during collateral sprouting but decreased following injury, suggesting that, although typically considered together, these two adult axonal growth processes are fundamentally different. These data position CD2AP as a major intracellular signaling molecule coordinating NGF signaling to regulate collateral sprouting and structural plasticity of intact adult axons. [ABSTRACT FROM AUTHOR]

Background: In cone‐beam computed tomography (CBCT)‐guided radiotherapy, off‐by‐one vertebral‐body misalignments are rare but serious errors that lead to wrong‐site treatments. Purpose: An automatic error detection algorithm was developed that uses a three‐branch convolutional neural network error detection model (EDM) to detect off‐by‐one vertebral‐body misalignments using planning computed tomography (CT) images and setup CBCT images. Methods: Algorithm training and test data consisted of planning CTs and CBCTs from 480 patients undergoing radiotherapy treatment in the thoracic and abdominal regions at two radiotherapy clinics. The clinically applied registration was used to derive true‐negative (no error) data. The setup and planning images were then misaligned by one vertebral‐body in both the superior and inferior directions, simulating the most likely misalignment scenarios. For each of the aligned and misaligned 3D image pairs, 2D slice pairs were automatically extracted in each anatomical plane about a point within the vertebral column. The three slice pairs obtained were then inputted to the EDM that returned a probability of vertebral misalignment. One model (EDM1) was trained solely on data from institution 1. EDM1 was further trained using a lower learning rate on a dataset from institution 2 to produce a fine‐tuned model, EDM2. Another model, EDM3, was trained from scratch using a training dataset composed of data from both institutions. These three models were validated on a randomly selected and unseen dataset composed of images from both institutions, for a total of 303 image pairs. The model performances were quantified using a receiver operating characteristic analysis. Due to the rarity of vertebral‐body misalignments in the clinic, a minimum threshold value yielding a specificity of at least 99% was selected. Using this threshold, the sensitivity was calculated for each model, on each institution's test set separately. Results: When applied to the combined test set, EDM1, EDM2, and EDM3 resulted in an area under curve of 99.5%, 99.4%, and 99.5%, respectively. EDM1 achieved a sensitivity of 96% and 88% on Institution 1 and Institution 2 test set, respectively. EDM2 obtained a sensitivity of 95% on each institution's test set. EDM3 achieved a sensitivity of 95% and 88% on Institution 1 and Institution 2 test set, respectively. Conclusion: The proposed algorithm demonstrated accuracy in identifying off‐by‐one vertebral‐body misalignments in CBCT‐guided radiotherapy that was sufficiently high to allow for practical implementation. It was found that fine‐tuning the model on a multi‐facility dataset can further enhance the generalizability of the algorithm. [ABSTRACT FROM AUTHOR]

Chronic exposure to toxaphene resulted in an increase in liver tumors in B6C3F1 mice. This study was performed to investigate the mode of action of toxaphene induced mouse liver tumors. Following an initial 14 day dietary dose range-finding study in male mice, a mechanistic study (0, 3, 32, and 320ppm toxaphene in diet for 7, 14, and 28 days of treatment) was performed to examine the potential mechanisms of toxaphene induced mouse liver tumors. Toxaphene induced a significant increase in expression of constitutive androstane receptor (CAR) target genes (Cyp2b10, Cyp3a11) at 32 and 320ppm toxaphene. aryl hydrocarbon receptor (AhR) target genes (Cyp1a1 and Cyp1a2) were slightly increased in expression at the highest toxaphene dose (320 ppm). No increase in peroxisome proliferator-activated receptor alpha activity or related genes was seen following toxaphene treatment. Lipid peroxidation was seen following treatment with 320ppm toxaphene. These changes correlated with increases in hepatic DNA synthesis. To confirm the role of CAR in this mode of action, CAR knockout mice (CAR-/-) treated with toxaphene confirmed that the induction of CAR responsive genes seen in wild-type mice was abolished following treatment with toxaphene for 14 days. These findings, taken together with previously reported studies, support the mode of action of toxaphene induced mouse liver tumors is through a nongenotoxic mechanism involving primarily a CAR-mediated processes that results in an increase in cell proliferation in the liver, promotes the clonal expansion of preneoplastic lesions leading to adenoma formation. [ABSTRACT FROM AUTHOR]

The CO Mapping Array Project (COMAP) aims to use line-intensity mapping of carbon monoxide (CO) to trace the distribution and global properties of galaxies over cosmic time, back to the Epoch of Reionization (EoR). To validate the technologies and techniques needed for this goal, a Pathfinder instrument has been constructed and fielded. Sensitive to CO(1â€"0) emission from z = 2.4â€"3.4 and a fainter contribution from CO(2â€"1) at z = 6â€"8, the Pathfinder is surveying 12 deg2 in a 5 yr observing campaign to detect the CO signal from z ∼ 3. Using data from the first 13 months of observing, we estimate P CO(k) = âˆ'2.7 ± 1.7 Ă— 104 ÎĽ K2 Mpc3 on scales k = 0.051 âˆ'0.62 Mpcâˆ'1, the first direct three-dimensional constraint on the clustering component of the CO(1â€"0) power spectrum. Based on these observations alone, we obtain a constraint on the amplitude of the clustering component (the squared mean CO line temperature bias product) of Tb 2 < 49 ÎĽ K2, nearly an order-of-magnitude improvement on the previous best measurement. These constraints allow us to rule out two models from the literature. We forecast a detection of the power spectrum after 5 yr with signal-to-noise ratio (S/N) 9â€"17. Cross-correlation with an overlapping galaxy survey will yield a detection of the COâ€"galaxy power spectrum with S/N of 19. We are also conducting a 30 GHz survey of the Galactic plane and present a preliminary map. Looking to the future of COMAP, we examine the prospects for future phases of the experiment to detect and characterize the CO signal from the EoR. [ABSTRACT FROM AUTHOR]

We describe the first-season CO Mapping Array Project (COMAP) analysis pipeline that converts raw detector readouts to calibrated sky maps. This pipeline implements four main steps: gain calibration, filtering, data selection, and mapmaking. Absolute gain calibration relies on a combination of instrumental and astrophysical sources, while relative gain calibration exploits real-time total-power variations. High-efficiency filtering is achieved through spectroscopic common-mode rejection within and across receivers, resulting in nearly uncorrelated white noise within single-frequency channels. Consequently, near-optimal but biased maps are produced by binning the filtered time stream into pixelized maps; the corresponding signal bias transfer function is estimated through simulations. Data selection is performed automatically through a series of goodness-of-fit statistics, including χ 2 and multiscale correlation tests. Applying this pipeline to the first-season COMAP data, we produce a data set with very low levels of correlated noise. We find that one of our two scanning strategies (the Lissajous type) is sensitive to residual instrumental systematics. As a result, we no longer use this type of scan and exclude data taken this way from our Season 1 power spectrum estimates. We perform a careful analysis of our data processing and observing efficiencies and take account of planned improvements to estimate our future performance. Power spectrum results derived from the first-season COMAP maps are presented and discussed in companion papers. [ABSTRACT FROM AUTHOR]

We introduce COMAP- EoR, the next generation of the Carbon Monoxide Mapping Array Project aimed at extending CO intensity mapping to the Epoch of Reionization. COMAP- EoR supplements the existing 30 GHz COMAP Pathfinder with two additional 30 GHz instruments and a new 16 GHz receiver. This combination of frequencies will be able to simultaneously map CO(1â€"0) and CO(2â€"1) at reionization redshifts (z ∼ 5â€"8) in addition to providing a significant boost to the z ∼ 3 sensitivity of the Pathfinder. We examine a set of existing models of the EoR CO signal, and find power spectra spanning several orders of magnitude, highlighting our extreme ignorance about this period of cosmic history and the value of the COMAP- EoR measurement. We carry out the most detailed forecast to date of an intensity mapping cross correlation, and find that five out of the six models we consider yield signal to noise ratios (S/Ns) ≳ 20 for COMAP- EoR, with the brightest reaching a S/N above 400. We show that, for these models, COMAP- EoR can make a detailed measurement of the cosmic molecular gas history from z ∼ 2â€"8, as well as probe the population of faint, star-forming galaxies predicted by these models to be undetectable by traditional surveys. We show that, for the single model that does not predict numerous faint emitters, a COMAP- EoR -type measurement is required to rule out their existence. We briefly explore prospects for a third-generation Expanded Reionization Array (COMAP- ERA) capable of detecting the faintest models and characterizing the brightest signals in extreme detail. [ABSTRACT FROM AUTHOR]

This paper considers how online, distance students enact the space of 'the university', in the context of the rise of distance education within a traditional, 'elite' institution. Aiming to provide insight into how students translate into distance the space of a university which has traditionally had its basis in conventional on-campus education, it locates itself within the 'new mobilities' paradigm (Urry in Mobilities. Polity Press, Cambridge, ), drawing on four different kinds of social space delineated by Mol and Law (Soc Stud Sci 24(4):641-741, ) and Law and Mol (Environ Plan D 19:609-621, ) in order to analyse narrative and visual data generated with distance students at the University of Edinburgh. The paper shows that the material campus continues to be symbolically and materially significant for a group of students who may never physically attend that campus. Distance students, we find, need their own version of the 'spatial certainties' of bounded, campus space. Yet, in exploring the 'new proximities' of online distance education, we also argue that to define institutional and academic authenticity solely in terms of this bounded, 'regional' space is inadequate in the face of the other topologies which also come into play throughout distance students' accounts of what it means to be 'at' university. [ABSTRACT FROM AUTHOR]

• SBRT using MR-Co is a safe and feasible option for treatment of liver tumors with ablative doses. • 2-year LC with MRgRT is comparable to prior series using a conventional CT-guided linear accelerator. • A difference in LC between number of lesions (single vs. multiple) and BED (< or ≥100 Gy) was observed. • MR-guided SBRT is very well tolerated without any acute grade 3 toxicities. • V35Gy < 0.35 cc to individual loops of small bowel should be recognized as a dose constraint for 3-fx SBRT. To prospectively determine the feasibility, safety, and efficacy of stereotactic body radiation therapy (SBRT) to primary and secondary liver tumors with MR-guided radiation therapy (MRgRT). Treatment plans with a conventional CT-guided linear accelerator and a MRI-guided tri-60Co teletherapy unit (MR-Co) were generated and compared for patients undergoing liver-directed SBRT from 2015 to 2017. If dosimetric parameters were met on MR-Co, patients were treated with MRgRT. The highest priority constraint was >1000 cc or >800 cc of normal liver receiving <15 Gy for single- or multiple-lesion treatments, respectively. Treatment was delivered every other day. Of 23 patients screened, 20 patients (8 primary, 12 secondary) and 25 liver tumors underwent MR-guided SBRT to a median dose of 54 Gy (range 11.5–60) in a median of 3 fractions (range 1–5). With a median follow up of 18.9 months, the 1- and 2-year estimate of local control were 94.7% and 79.6%, respectively. A difference in local control between single and multiple lesions or BED ≥ 100 Gy 10 and BED < 100 Gy 10 , respectively, was observed. The 2-year estimate of overall survival (OS) was 50.7% with a median OS of 29 months. There were no acute grade ≥ 3 toxicities and one late grade 3/4 toxicity from a single patient whose plan exceeded an unrecognized dose constraint at the time. MR-guided SBRT is a viable and safe option in the delivery of ultrahypofractionated ablative radiation treatment to primary and secondary liver tumors resulting in high rates of local control and very favorable toxicity profiles. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to develop a methodology to quantitatively measure the thorax-to-abdomen breathing ratio from a 4DCT dataset for breathing motion modeling and breathing motion studies. Methods: The thorax-to-abdomen breathing ratio was quantified by measuring the rate of cross-sectional volume increase throughout the thorax and abdomen as a function of tidal volume. Twenty-six 16-slice 4DCT patient datasets were acquired during quiet respiration using a protocol that acquired 25 ciné scans at each couch position. Fifteen datasets included data from the neck through the pelvis. Tidal volume, measured using a spirometer and abdominal pneumatic bellows, was used as breathing-cycle surrogates. The cross-sectional volume encompassed by the skin contour when compared for each CT slice against the tidal volume exhibited a nearly linear relationship. A robust iteratively reweighted least squares regression analysis was used to determine η(i), defined as the amount of cross-sectional volume expansion at each slice i per unit tidal volume. The sum Ση(i) throughout all slices was predicted to be the ratio of the geometric expansion of the lung and the tidal volume; 1.11. The Xiphoid process was selected as the boundary between the thorax and abdomen. The Xiphoid process slice was identified in a scan acquired at mid-inhalation. The imaging protocol had not originally been designed for purposes of measuring the thorax-to-abdomen breathing ratio so the scans did not extend to the anatomy with η(i) = 0. Extrapolation of η(i)-η(i) = 0 was used to include the entire breathing volume. The thorax and abdomen regions were individually analyzed to determine the thorax-to-abdomen breathing ratios. There were 11 image datasets that had been scanned only through the thorax. For these cases, the abdomen breathing component was equal to 1.11 - Ση(i) where the sum was taken throughout the thorax. Results: The average Ση(i) for thorax and abdomen image datasets was found to be 1.20 ± 0.17, close to the expected value of 1.11. The thorax-to-abdomen breathing ratio was 0.32 ± 0.24. The average Ση(i) was 0.26 ± 0.14 in the thorax and 0.93 ± 0.22 in the abdomen. In the scan datasets that encompassed only the thorax, the average Ση(i) was 0.21 ± 0.11. Conclusions: A method to quantify the relationship between abdomen and thoracic breathing was developed and characterized. [ABSTRACT FROM AUTHOR]

Abstract: This paper evaluates new data for cholinesterase inhibition with chlorpyrifos (CPF). recently conducted a CPF cholinesterase inhibition study in rats that included testing of males and females, dosing by gavage or diet, administration in corn oil or milk, and with pups and adults. Additionally, the study included cholinesterase inhibition testing for CPF-oxon, the active moiety that inhibits cholinesterase. The study included 5–6 dose groups with eight animals/sex/group for most of the tests. This paper provides a benchmark dose (BMD) analysis of the data from , including a BMD meta-analysis that includes CPF cholinesterase inhibition data from different assays within the study and, in one case, from another study. From the meta-analysis, the recommended BMD10s, based on brain acetylcholinesterase inhibition, are 1.7mg/kg/day (BMDL10 =1.3mg/kg/day) for acute doses to children and adults, and 0.67mg/kg/day (BMDL10 =0.53mg/kg/day) for repeat doses to children and adults. At the dose levels considered in this analysis, there was no evidence of a difference in responses between males and females, corn oil versus milk administration, or pups versus adults. The data on pups versus adults show that an extra safety factor to protect the young is not needed for CPF. CPF data from the literature suggest that brain cholinesterase inhibition is the most appropriate metric for cholinesterase inhibition risk assessment. [Copyright &y& Elsevier]

The article discusses the characteristics of the temporary bonding/debonding system designed for ultrathin wafer processing. The author also presented the critical parameters to be identified in manufacturing thin wafers and through-silicon via (TSV) technology. The system enables flexible, fast bonding scheme that uses carrier substrates and provides efficient, low-cost solution for providing the support essential to the creation of TSVs on ultrathin wafers.

• Prostate volume consistently increased during the course of prostate SBRT. • Interfraction prostatic rotation was minimal. • Rotation of the proximal seminal vesicle (SV) was considerable. • Prostate dosimetry was favorable with 2 mm PTV margin with MRI-guided SBRT. • Online adaptive therapy may be indicated to account for proximal SV rotations. Interfraction volumetric changes/rotations in the prostate and proximal seminal vesicles (SVs) might compromise target coverage when tight margins are used for prostate stereotactic body radiotherapy (SBRT). We investigated on-board MRI images from MRI-guided SBRT to better understand this. Twenty consecutive patients treated with MRI-guided prostate SBRT (40 Gy/5 fractions) enrolled on the MRI arm of a phase III randomized trial were included. A 2 mm isotropic margin was used for prostate and proximal SVPTV. Target volume, prostate dimensions, angles of the proximal SV on axial (angle α) and sagittal view (angle θ) were measured on a 0.35 T simulation MRI and five on-board pre-treatment MRIs. Dice coefficient of the targets and target dosimetry were calculated. All patients experienced an isotropic increase in prostate volume during SBRT (p = 0.0016): 0.1%, 9.0%, 12.1%, 15.1%, and 14.2% (median) at fractions 1–5, respectively, regardless of baseline volume, which was significantly reduced with neoadjuvant ADT (p = 0.0042). There was minimal interfraction rotation of prostate, however, considerable variations in proximal SV angle α (median 21.5°) and angle θ (median 17.6°) were seen. Median V100% was 97.5% and 87.1% for prostate and proximal SV CTV, respectively. V95%≥95% was achieved in 94% of fractions for the prostate and in 59% for proximal SV. Prostate volume consistently increased during SBRT. Interfraction prostatic rotation was minimal while rotation of the proximal SV was considerable. Prostate dosimetry was favorable, but online adaptive therapy may be indicated occasionally to account for prostatic swelling and in particular proximal SV rotations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiotherapy (SBRT) delivers ablative doses with excellent local control. However, implementing SBRT for abdominal and pelvic tumors has been limited by the risk for treatment‐related gastrointestinal toxicity. MRI‐guided radiotherapy may ameliorate these risks and increase the therapeutic ratio. We report the clinical outcomes of stereotactic MRI‐guided adaptive radiotherapy (SMART) for primary and metastatic tumors in the abdomen and pelvis. Methods: From November 2014 to August 2017, the first 106 consecutive patients with 121 tumors in the abdomen and pelvis were treated with SMART at a single institution. Of the cohort, 41.5%, 15.1%, and 43.4% had primary, locally recurrent, and oligometastatic tumors, respectively. SMART was delivered using a tri‐cobalt‐60 gantry with on‐board 0.35 Tesla MRI with respiratory breath‐hold and daily adaptive re‐planning when anatomically necessary. A median of 40Gy in five fractions was prescribed. The Common Terminology Criteria for Adverse Events v.4.03 was used to score treatment‐related toxicities. Local control (LC), progression‐free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier method. Results: Of the 510 treatments, seventy‐one (13.9%) were adapted. Fatigue, nausea, and pain were the most common acute toxicities. 0.9 and 0% of patients experienced acute grade three and four toxicities, respectively. 5.2 and 2.1% of patients experienced late grade three and four toxicities, respectively. After a median follow‐up of 20.4 months, the 2‐year LC rate was 74% on a per‐lesion basis. Two‐year LC was 96% for lesions that were treated with BED10≥100 versus 69% for BED10<100 (p = 0.02). PFS was significantly different between patients with and without locally controlled tumors (2‐year PFS 21 vs. 8%, p = 0.03). Two‐year OS was 57% for the entire cohort. Conclusions: Favorable LC and PFS outcomes were observed with minimal morbidity for tumors in the abdomen and pelvis treated with SMART. Future prospective clinical trials to validate these findings are warranted. [ABSTRACT FROM AUTHOR]

Intermetallics with crystals derived from body-centered cubic structures are promising materials to enhance the performance and high temperature capability of high-strength alloys both as matrix materials and as strengthening precipitates. Given the ordered nature of these materials, the defect structures that ultimately mediate plasticity can be complex and strongly dependent on processing vis-à-vis the extent of disorder inherited from high temperature phases. Here, we elucidate the elementary characteristics of the defect structures in the Heusler (L 2 1) intermetallic MnCu 2 Al as investigated by the orientation-dependent strength and compressive plasticity measured from in situ micro-compression experiments and post-mortem transmission electron microscopy. Our experiments reveal single crystal compressive yield strengths as high as 1.2 GPa and a capacity for stable plastic deformation, accompanied by slip characteristics reminiscent of bcc-derived crystals. We study the equilibrium dissociation mechanisms and critical stresses of 〈 111 〉 {110}-type dislocations in the Heusler intermetallic using an ab initio informed phase field dislocation dynamics model. The calculations suggest that the dislocation dissociates into multiple distinct partials, which depend on the character of the dislocation, and are closely spaced to a degree that intervening faults are undetectable using conventional transmission electron microscopy. Critical stresses to initiate glide of these defect structures quantitatively agree with measured yield strengths. Our work details the interplay between the significant degree of elastic anisotropy, stacking fault energies, and glissile defect structures governing mechanical properties and motivates an increased awareness of the role that complex defect structures play for alloy design involving bcc-derived intermetallics. [Display omitted] • MnCu 2 Al deforms through stable compressive plasticity via 〈 111 〉 { 110 } slip • Dislocation cores are composed of partials, resulting in planar defect structures • Predicted critical stresses quantitatively agree with the experimental τ C R S S [ABSTRACT FROM AUTHOR]

The authors provide three personal perspectives on personality disorder, based on their involvement in writing, directing and acting in a Resurgence Theatre Company production, Differentia, which provided a dramatic representation of personality disorder. The production was shown at the First National Personality Disorder Congress. [ABSTRACT FROM AUTHOR]

• BEP prints United States currency using alkyd-based inks that dry oxidatively. • ASTM, Beck-Koller (BK) Dryer measures dry time using a stylus, in real time, and is sensitive to environmental conditions. • Differential Scanning Calorimetry (DSC) can measure dry time quickly (minutes to hours). • Dry times measured by DSC and BK Dryer correlate. • DSC offers increased accuracy and faster analysis time compared to the ASTM method. A new method for analyzing the drying characteristics of ink has been developed using Differential Scanning Calorimetry (DSC). DSC is able to determine the drying time of an ink in 30–45 min. In contrast, the ASTM method uses a Beck-Koller (BK) Dryer instrument to draw a stylus across an ink film to evaluate film drying, which can take hours or days depending on the film. This DSC method is comparative and does not reflect dry times under standard atmospheric conditions. A commercial offset ink was analyzed using DSC and BK Dryer methods. The two methods correlated highly (r = 0.976) with DSC offering comparable or smaller relative standard deviations and a significantly shorter analysis time. This method has the potential to analyze any oxygen-dependent coating. [ABSTRACT FROM AUTHOR]