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Plasma facing components are usually qualified to a given heat load density applied at the top face of the armour tiles with normal incidence angle. When employed in tokamak fusion machines, heat loading on the tile sides is possible due to optimised shaping, that doesn't provide edge shadowing for all design situations. An edge heat load may occur both at the tile and component scales. The edge load needs to be controlled and quantified. The adequate control of edge heat loads is especially critical for water cooled components that uses armour tiles which are bonded to the heat sink, for ensuring the long-term integrity of the tile bonding. An edge heat load allowance criterion of 10% of the top heat load is proposed. The 10% criterion is supported by experimental heat flux tests.

Background: The combination of oral pentoxifylline (Ptx) and vitamin E (VitE) has been used to treat radiation-induced fibrosis and soft tissue injury. Here, we review outcomes and perform a radiomic analysis of treatment effects in patients prescribed Ptx + VitE at our institution for the treatment of radiation necrosis (RN). Methods: A total of 48 patients treated with stereotactic radiosurgery (SRS) had evidence of RN and had MRI before and after starting Ptx + VitE. The radiation oncologist’s impression of the imaging in the electronic medical record was used to score response to treatment. Support Vector Machine (SVM) was used to train a model of radiomics features derived from radiation necrosis on pre- and 1st post-treatment T1 post-contrast MRIs that can classify the ultimate response to treatment with Ptx + VitE. Results: A total of 43.8% of patients showed evidence of improvement, 18.8% showed no change, and 25% showed worsening RN upon imaging after starting Ptx + VitE. The median time-to-response assessment was 3.17 months. Nine patients progressed significantly and required Bevacizumab, hyperbaric oxygen therapy, or surgery. Patients who had multiple lesions treated with SRS were less likely to show improvement (p = 0.037). A total of 34 patients were also prescribed dexamethasone, either before (7), with (16), or after starting (11) treatment. The use of dexamethasone was not associated with an improved response to Ptx + VitE (p = 0.471). Three patients stopped treatment due to side effects. Finally, we were able to develop a machine learning (SVM) model of radiomic features derived from pre- and 1st post-treatment MRIs that was able to predict the ultimate treatment response to Ptx + VitE with receiver operating characteristic (ROC) area under curve (AUC) of 0.69. Conclusions: Ptx + VitE appears safe for the treatment of RN, but randomized data are needed to assess efficacy and validate radiomic models, which may assist with prognostication.

The COVID-19 pandemic has negatively impacted numerous people?s mental health and created new barriers to services. To address the unknown effects of the pandemic on accessibility and equality issues in mental health care, this study aimed to investigate gender and racial/ethnic disparities in mental health and treatment use in undergraduate and graduate students amid the COVID-19 pandemic. The study was conducted based on a largescale online survey (N = 1,415) administered during the weeks following a pandemic-related university-wide campus closure in March 2020. We focused on the gender and racial disparities in current internalizing symptomatology and treatment use. Our results showed that in the initial period of the pandemic, students identified as cis women (p < 0.001), non-binary/genderqueer (p < .001), or Hispanic/Latinx (p = 0.002) reported higher internalizing problem severity (aggregated from depression, generalized anxiety, intolerance of uncertainty, and COVID-19-related stress symptoms) compared to their privileged counterparts. Additionally, Asian (p < 0.001) and multiracial students (p = 0.002) reported less treatment use than White students while controlling for internalizing problem severity. Further, internalizing problem severity was associated with increased treatment use only in cisgender, non-Hispanic/Latinx White students (pcis man = 0.040, pcis woman < 0.001). However, this relationship was negative in cis-gender Asian students (pcis man = 0.025, pcis woman = 0.016) and nonsignificant in other marginalized demographic groups. The findings revealed unique mental health challenges faced by different demographic groups and served as a call that specific actions to enhance mental health equity, such as continued mental health support for students with marginalized gender identities, additional COVID-related mental and practical support for Hispanic/Latinx students and promotion of mental health awareness, access, and trust in non-White, especially Asian, students are desperately needed.

Primary meningeal melanomatosis is an extremely rare tumor with very few documented responses to treatment. A 3-year-old male with a complex past medical history, including prematurity and shunted hydrocephalus, was diagnosed with primary meningeal melanomatosis with peritoneal implants. Molecular testing revealed an NRAS Q61R mutation. The patient received proton craniospinal radiation followed by immunotherapy with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) IV every 3 weeks and, upon progression, he was switched to a higher dose of nivolumab (3 mg/kg IV every 2 weeks) and binimetinib (24 mg/m2/dose, twice a day). The patient had significant improvement of CNS disease with radiation therapy and initial immunotherapy but progression of extracranial metastatic peritoneal and abdominal disease. Radiation was not administered to the whole abdomen. After two cycles of nivolumab and treatment with the MEK inhibitor binimetinib, he had radiographic and clinical improvement in abdominal metastasis and ascitis. He ultimately died from RSV infection, Klebsiella sepsis, and subdural hemorrhage without evidence of tumor progression. This is the first report of a child with primary meningeal melanomatosis with extracranial metastatic disease with response to a combination of radiation, immunotherapy and MEK inhibitor therapy.

Radiation therapy (RT) is a critical part of definitive therapy for pediatric high-grade glioma (pHGG). RT is designed to treat residual tumor defined on conventional MRI (cMRI), though pHGG lesions may be ill-characterized on standard imaging. Spectroscopic MRI (sMRI) measures endogenous metabolite concentrations in the brain, and Choline (Cho)/N-acetylaspartate (NAA) ratio is a highly sensitive biomarker for metabolically active tumor. We provide a preliminary report of our study introducing a novel treatment approach of whole brain sMRI-guided proton therapy for pHGG. An observational cohort (c1 = 10 patients) receives standard of care RT; a therapeutic cohort (c2 = 15 patients) receives sMRI-guided proton RT. All patients undergo cMRI and sMRI, a high-resolution 3D whole-brain echo-planar spectroscopic imaging (EPSI) sequence (interpolated resolution of 12 µL) prior to RT and at several follow-up timepoints integrated into diagnostic scans. Treatment volumes are defined by cMRI for c1 and by cMRI and Cho/NAA ≥ 2x for c2. A longitudinal imaging database is used to quantify changes in lesion and metabolite volumes. Four subjects have been enrolled (c1 = 1/c2 = 3) with sMRI imaging follow-up of 4–18 months. Preliminary data suggest sMRI improves identification of pHGG infiltration based on abnormal metabolic activity, and using proton therapy to target sMRI-defined high-risk regions is safe and feasible.

Abstract Stony coral tissue loss disease (SCTLD) has been causing significant whole colony mortality on reefs in Florida and the Caribbean. The cause of SCTLD remains unknown, with the limited concurrence of SCTLD-associated bacteria among studies. We conducted a meta-analysis of 16S ribosomal RNA gene datasets generated by 16 field and laboratory SCTLD studies to find consistent bacteria associated with SCTLD across disease zones (vulnerable, endemic, and epidemic), coral species, coral compartments (mucus, tissue, and skeleton), and colony health states (apparently healthy colony tissue (AH), and unaffected (DU) and lesion (DL) tissue from diseased colonies). We also evaluated bacteria in seawater and sediment, which may be sources of SCTLD transmission. Although AH colonies in endemic and epidemic zones harbor bacteria associated with SCTLD lesions, and aquaria and field samples had distinct microbial compositions, there were still clear differences in the microbial composition among AH, DU, and DL in the combined dataset. Alpha-diversity between AH and DL was not different; however, DU showed increased alpha-diversity compared to AH, indicating that, prior to lesion formation, corals may undergo a disturbance to the microbiome. This disturbance may be driven by Flavobacteriales, which were especially enriched in DU. In DL, Rhodobacterales and Peptostreptococcales–Tissierellales were prominent in structuring microbial interactions. We also predict an enrichment of an alpha-toxin in DL samples which is typically found in Clostridia. We provide a consensus of SCTLD-associated bacteria prior to and during lesion formation and identify how these taxa vary across studies, coral species, coral compartments, seawater, and sediment.

Purpose: The physical properties of protons lower doses to surrounding normal tissues compared with photons, potentially reducing acute and long-term adverse effects, including subsequent cancers. The magnitude of benefit is uncertain, however, and currently based largely on modeling studies. Despite the paucity of directly comparative data, the number of proton centers and patients are expanding exponentially. Direct studies of the potential risks and benefits are needed in children, who have the highest risk of radiation-related subsequent cancers. The Pediatric Proton and Photon Therapy Comparison Cohort aims to meet this need. Methods and Materials: We are developing a record-linkage cohort of 10,000 proton and 10,000 photon therapy patients treated from 2007 to 2022 in the United States and Canada for pediatric central nervous system tumors, sarcomas, Hodgkin lymphoma, or neuroblastoma, the pediatric tumors most frequently treated with protons. Exposure assessment will be based on state-of-the-art dosimetry facilitated by collection of electronic radiation records for all eligible patients. Subsequent cancers and mortality will be ascertained by linkage to state and provincial cancer registries in the United States and Canada, respectively. The primary analysis will examine subsequent cancer risk after proton therapy compared with photon therapy, adjusting for potential confounders and accounting for competing risks. Results: For the primary aim comparing overall subsequent cancer rates between proton and photon therapy, we estimated that with 10,000 patients in each treatment group there would be 80% power to detect a relative risk of 0.8 assuming a cumulative incidence of subsequent cancers of 2.5% by 15 years after diagnosis. To date, 9 institutions have joined the cohort and initiated data collection; additional centers will be added in the coming year(s). Conclusions: Our findings will affect clinical practice for pediatric patients with cancer by providing the first large-scale systematic comparison of the risk of subsequent cancers from proton compared with photon therapy.

Abstract An experiment evaluated the ability of 30 younger and older adults to visually judge object size under three conditions: (1) full cue, (2) in the dark, with linear perspective, and (3) in complete darkness. Each observer made repeated judgments for the same square stimuli (the task was to adjust a separation until it matched the perceived size of the squares), enabling an evaluation of precision as well as accuracy. The judgments were just as accurate in the dark with linear perspective condition as in the full cue condition, indicating that linear perspective serves as an important source of optical information to support the perception of object size). In contrast, in complete darkness (where linear perspective information was unavailable), the accuracy of the observers’ judgments was poor. Finally, there was no difference in either the accuracy or the precision of the observers’ judgments between the two age groups, despite the fact that the older adults were more than 50 years older than the younger adults (mean age of the younger and older adults was 22.3 and 74.1 years, respectively). The ability to visually perceive object size is well maintained with increasing age, unlike a number of other important visual abilities.

Purpose: Proton vertebral body sparing craniospinal irradiation (CSI) treats the thecal sac while avoiding the anterior vertebral bodies in an effort to reduce myelosuppression and growth inhibition. However, robust treatment planning needs to compensate for proton range uncertainty, which contributes unwanted doses within the vertebral bodies. This work aimed to develop an early in vivo radiation damage quantification method using longitudinal magnetic resonance (MR) scans to quantify the dose effect during fractionated CSI. Methods and Materials: Ten pediatric patients were enrolled in a prospective clinical trial of proton vertebral body sparing CSI, in which they received 23.4 to 36 Gy. Monte Carlo robust planning was used, with spinal clinical target volumes defined as the thecal sac and neural foramina. T1/T2-weighted MR scans were acquired before, during, and after treatments to detect a transition from hematopoietic to less metabolically active fatty marrow. MR signal intensity histograms at each time point were analyzed and fitted by multi-Gaussian models to quantify radiation damage. Results: Fatty marrow filtration was observed in MR images as early as the fifth fraction of treatment. Maximum radiation-induced marrow damage occurred 40 to 50 days from the treatment start, followed by marrow regeneration. The mean damage ratios were 0.23, 0.41, 0.59, and 0.54, corresponding to 10, 20, 40, and 60 days from the treatment start. Conclusions: We demonstrated a noninvasive method for identifying early vertebral marrow damage based on radiation-induced fatty marrow replacement. The proposed method can be potentially used to quantify the quality of CSI vertebral sparing and preserve metabolically active hematopoietic bone marrow.

The recent decline of coral health and substantial loss of coral cover along Florida’s Coral Reef (FCR) results from local stressors such as degraded water quality and disease outbreaks in addition to anthropogenically driven global stressors including ocean warming and acidification. Intervention strategies intended for the restoration of degraded reef habitats need a better understanding of the influence of ocean warming and acidification on coral health to target coral species and individual genotypes that may be more resistant or resilient to such stressors. Here, we examined a suite of physiological traits (coral host and algal symbiont) in response to experimentally elevated water temperatures and pCO2 levels, both separately and in concert, using threatened reef-building corals Pseudodiploria clivosa and Orbicella faveolata reared within a land-based coral nursery. After two months of exposure, responses differed by coral species, where P. clivosa showed declined physiology in response to combined ocean warming and acidification stress and ocean warming alone, whereas O. faveolata showed a positive response under ocean acidification. Responses to temperature could be associated with the algal symbionts harbored, as P. clivosa was dominated by the thermally sensitive Breviolum, and O. faveolata was dominated by the thermally tolerant Durusdinium. Additionally, corals were raised in well-sourced seawater that was naturally high in pCO2, which could have led to corals acclimating to acidified conditions. Of the three P. clivosa genets tested, we determined a top-performing genotype under the combined warming and acidification treatment. O. faveolata, however, displayed high genet variation by treatment and phenotypic trait, making genotype performance rankings challenging to discern. The evidence provided in this study demonstrates that high phenotypic variation in nursery-reared corals contributes to variable warming-acidification responses, suggesting that high-standing genetic variation in nursery-reared corals could support diverse coral restoration population outcomes along FCR.

Abstract Premise The degree of gametophyte dependence on the sporophyte life stage is a major feature that differentiates the life cycles of land plants, yet the evolutionary consequences of this difference remain poorly understood. Most evolutionary models assume organisms are either haploid or diploid for their entire lifespan, which is not appropriate for simulating plant life cycles. Here, we introduce shadie (Simulating Haploid–Diploid Evolution), a new, simple Python program for implementing simulations with biphasic life cycles and analyzing their results, using SLiM 3 as a simulation back end. Methods We implemented evolutionary simulations under three realistic plant life cycle models supported in shadie, using either standardized or biologically realistic parameter settings to test how variation in plant life cycles and sexual systems affects patterns of genome diversity. Results The dynamics of single beneficial mutation fixation did not vary dramatically between different models, but the patterns of spatial variation did differ, demonstrating that different life histories and model parameters affect both genetic diversity and linkage disequilibrium. The rate of linkage disequilibrium decay away from selected sites varied depending on model parameters such as cloning and selfing rates, through their impact on effective population sizes. Discussion Evolutionary simulations are an exciting, underutilized approach in evolutionary research and education. shadie can aid plant researchers in developing null hypotheses, examining theory, and designing empirical studies, in order to investigate the role of the gametophyte life stage, and the effects of variation in plant life cycles, on plant genome evolution.

Infectious disease outbreaks are a primary contributor to coral reef decline worldwide. A particularly lethal disease, black band disease (BBD), was one of the first coral diseases reported and has since been documented on reefs worldwide. BBD is described as a microbial consortium of photosynthetic cyanobacteria, sulfate-reducing and sulfide-oxidizing bacteria, and heterotrophic bacteria and archaea. The disease is visually identified by a characteristic dark band that moves across apparently healthy coral tissue leaving behind bare skeleton. Despite its virulence, attempts to effectively treat corals with BBD in the field have been limited. Here, we developed and tested several different therapeutic agents on Pseudodiploria spp. corals with signs of active BBD at Buck Island Reef National Monument in St. Croix, USVI. A variety of therapies were tested, including hydrogen peroxide-based treatments, ointment containing antibiotics, and antiviral/antimicrobial-based ointments (referred to as CoralCure). The CoralCure ointments, created by Ocean Alchemists LLC, focused on the dosing regimen and delivery mechanisms of the different active ingredients. Active ingredients included carbamide peroxide, Lugol's iodine solution, along with several proprietary essential oil and natural product blends. Additionally, the active ingredients had different release times based on treatment: CoralCure A-C had a release time of 24 hours, CoralCure D-F had a release time of 72 hours. The ointments were applied directly to the BBD lesion. Also, jute rope was saturated with a subset of these CoralCure ointment formulations to assist with adhesion. These ropes were then applied to the leading edge of the BBD lesion for one week to ensure sufficient exposure. Corals were revisited approximately three to five months after treatment application to assess disease progression rates and the presence/absence of lesions-the metrics used to quantify the efficacy of each treatment. Although most of the treatments were unsuccessful, two CoralCure rope formulations-CoralCure D rope and CoralCure E rope, eliminated the appearance of BBD in 100% of the corals treated. As such, these treatments significantly reduced the likelihood of BBD occurrence compared to the untreated controls. Additionally, lesions treated with these formulations lost significantly less tissue compared with controls. These results provide the mechanisms for an easily employable method to effectively treat a worldwide coral disease.

Hawaiian Melicope are one of the major adaptive radiations of the Hawaiian Islands comprising 54 endemic species. The lineage is monophyletic with an estimated crown age predating the rise of the current high islands. Phylogenetic inference based on Sanger sequencing has not been sufficient to resolve species or deeper level relationships. Here, we apply restriction site-associated DNA sequencing (RAD-seq) to the lineage to infer phylogenetic relationships. We employ Quartet Sampling to assess information content and statistical support, and to quantify discordance as well as partitioned ABBA-BABA tests to uncover evidence of introgression. Our new results drastically improved resolution of relationships within Hawaiian Melicope. The lineage is divided into five fully supported main clades, two of which correspond to morphologically circumscribed infrageneric groups. We provide evidence for both ancestral and current hybridization events. We confirm the necessity for a taxonomic revision of the Melicope section Pelea, as well as a re-evaluation of several species complexes by combining genomic and morphological data.

Species with large geographic distributions often exhibit complex patterns of diversity that can be further complicated by human activities. Cutthroat trout (Oncorhynchus clarkii) are one of the most widely distributed freshwater fish species in western North America exhibiting substantial phenotypic and genetic variability; however, fish stocking practices have translocated populations outside of their native range and may have obscured intraspecific boundaries. This study focuses on cutthroat trout populations representing three distinct evolutionary clades that are found intermixed within a contact zone between the Bonneville and upper Snake River watersheds in the western United States. We used mitochondrial and microsatellite genetic data, as well as historical stocking records, to evaluate whether populations of cutthroat trout in the contact zone are native or are introduced. We found significant genetic differentiation and fine-scale genetic population structure that was organized primarily by watershed boundaries. While we detected increased genetic diversity in some areas in close proximity to the greatest number of stocking events, the highly organized population structure both within and between areas of the contact zone indicates that the populations are native to the watersheds. Intermixing of distinct evolutionary lineages of cutthroat trout appears to be the result of historical connections between paleodrainages. Our analyses provide a context for understanding how genetic data can be used to assess the status of populations as native or introduced.