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In the midst of growing research and societal discourse on psychedelic substances, a consistent finding is reported: A majority of users report profound personal meaning from their experiences. This pioneering study in Sweden, a nation renowned for its strict drug policies, sought to quantify the extent of reported meaningfulness among Swedish psychedelic users. Results revealed that a majority of the sample, 58%, ranked their psychedelic experience among the top 5 most meaningful events in their lives, while 85% among the top 10. These findings align well with previous research from other types of studies and other countries. Participants acknowledged challenging and mystical aspects as part of their psychedelic experiences, and a large majority, 94%, reported positive life improvements. Factors such as a personal growth motive and supportive social networks were associated with improved well-being. Despite many study limitations, including the self-selected sample, self-reported measures, and cross-sectional design, the findings underscore the impact psychedelic experiences potentially can have on individuals' lives.

Pancreatic cancer is one of the most challenging tumor sites to treat safely and effectively with radiotherapy due to the anatomical location and aggressiveness of the disease. One modality that has shown promising results, which our institution has been employing, is online adaptive stereotactic radiotherapy using a magnetic resonance-guided linear accelerator (MR-linac). However, due to unforeseen circumstances regarding our MR-linac, it was necessary for our institution to use an alternative treatment technique. In this case report, we describe our experience using our ring-gantry linac equipped with an advanced cone-beam computed tomography (CBCT) system to treat a 61-year-old patient with advanced pancreatic cancer with CBCT-guided online adaptive stereotactic radiotherapy. In a short time period of four weeks, we prepared for this case by training with the surface scanning motion management system and developing procedures for planning and adaptation. The patient was prescribed 24 Gy in three fractions, with a risk-adapted approach using strict organ-at-risk (OAR) constraints. Daily CBCT was used for online adaptation of the plan, and the superior plan (non-adapted or adapted) was selected for treatment. For this patient, the adapted plan was chosen for all three fractions, due to OAR constraints being violated in the non-adapted plan. In summary, we found that for this patient, high-quality CBCT guidance for daily re-contouring, in combination with motion management, enabled the use of daily adaptive radiotherapy to safely deliver stereotactic radiotherapy. The results from this case report are promising, and CBCT-guided online adaptive stereotactic radiotherapy for pancreatic cancer warrants further investigation in more patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Den Videnskabsetiske Komité issued approval H-19075387. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Laura Rechner declare(s) a grant from Varian, a Siemens Healthineers Company. Laura Rechner is partially funded through a grant from Varian for work unrelated to this case report. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rechner et al.)

Evidence is lacking on how to understand the reasons for variations, both in prevalence of ADHD and ADHD medication prescribing patterns in children and adolescents, within Region Skåne. These variations are not in line with current national clinical guidelines and seem to have increased over time. This qualitative interview study illuminates pediatric psychiatrists' attitudes toward ADHD and their experiences of prescribing ADHD medication. Eleven pediatric psychiatrists described the complex interplay of variables that they experienced while assessing a child, which had influence on their decision to prescribe medication. Being part of a local unit's culture influenced how ADHD medications were prescribed. They wished that the assessment of the child's symptoms was consistent with guidelines in every unit but noted that such alignment was not implemented. They pointed out that an ADHD diagnosis is dependent on the surrounding's motivation and capacity to adapt to the present state of the child. The participants described how they balanced clinical guidelines with demands from the family, as well as from society at large. Their personal attitudes and clinical experiences towards diagnosing and prescribing medications to children with ADHD influenced their decisions. The study adds information about how attitudes may lead to variation in diagnostics and therapy.

Background and Purpose: Online adaptive radiotherapy (oART) potentially reduces the dose to organs at risk (OARs) as the planning target volume (PTV) margins are reduced compared to a non-adaptive approach (non-ART). This study evaluates the feasibility and dosimetric impact of cone-beam computed tomography (CBCT)-guided oART of urinary bladder cancer for the first patients treated, using patient-specific margins., Materials and Methods: Sixteen consecutive patients with muscle-invasive bladder cancer received two or more (median = 23) fractions as oART, and remaining fractions as non-ART. The non-ART fractions were delivered with standard population-based margins, while reduced patient-specific margins based on intra-fractional variations extracted from 2-4 fractions were applied to the primary PTV (PTV-T) during the oART fractions. Target volume and coverage, and dose to OARs were compared between non-ART and oART plans, and the oART procedure time was recorded., Results: In total, 297/512 fractions were delivered as oART with full re-optimization to the anatomy of the day. The median (interquartile range, IQR) oART procedure time, measured from the end of CBCT generation to completion of plan review, and quality assurance was 13.9 (11.9;16.6) min. The median (IQR) volume reduction in PTV-T volume was 33.9 (24.2;45.0)%, comparing oART and non-ART plans, resulting in median (IQR) reductions in bowel bag V 45 Gy of 18.8 (12.7;27.9)% and rectum V 50 Gy of 70.7 (35.9;94.8)%. By re-optimizing the plan to the daily anatomy, full target coverage was achieved at all oART fractions., Conclusions: oART resulted in large reductions in treatment volumes and doses to OARs, compared to non-ART, while ensuring target coverage. This indicates potential reductions in gastrointestinal toxicity., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to evaluate our 2 years' experience with single-isocenter, non-coplanar, volumetric modulated arc therapy (VMAT) for brain metastasis (BM) stereotactic radiosurgery (SRS)., Methods: A total of 202 patients treated with the VMAT SRS solution were analyzed retrospectively. Plan quality was assessed for 5 mm (120) and 2.5 mm (high-definition, HD) central leaf width multileaf collimators (MLCs). For BMs at varying distances from the plan isocenter, the geometric offset from the ideal position for two image-guided radiotherapy workflows was calculated. In the workflow with ExacTrac (BrainLAB, München, Germany; W‑ET), patient positioning errors were corrected at each couch rotation. In the workflow without ExacTrac (W-noET), only the initial patient setup correction was considered. The dose variation due to rotational errors was simulated for multiple-BM plans with the HD-MLC., Results: Plan conformity and quality assurance were equivalent for plans delivered with the two MLCs while the HD-MLC plans provided better healthy brain tissue (BmP) sparing. 95% of the BMs had residual intrafractional setup errors ≤ 2 mm for W‑ET and 68% for W‑noET. For small BM (≤1 cc) situated >3 cm from the plan isocenter, the dose received by 95% of the BM decreased in median (interquartile range) by 6.3% (2.8-8.8%) for a 1-degree rotational error., Conclusion: This study indicates that the HD-MLC is advantageous compared to the 120-MLC for sparing healthy brain tissue. When a 2-mm margin is applied, W‑noET is sufficient to ensure coverage of BM situated ≤ 3 cm of the plan isocenter, while for BM further away, W‑ET is recommended., (© 2021. The Author(s).)

Background and Purpose: The Ethos system has enabled online adaptive radiotherapy (oART) by implementing an automated treatment planning system (aTPS) for both intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (VMAT) plan creation. The purpose of this study is to evaluate the quality of aTPS plans in the pelvic region., Material and Methods: Sixty patients with anal (n = 20), rectal (n = 20) or prostate (n = 20) cancer were retrospectively re-planned with the aTPS. Three IMRT (7-, 9- and 12-field) and two VMAT (2 and 3 arc) automatically generated plans (APs) were created per patient. The duration of the automated plan generation was registered. The best IMRT-AP and VMAT-AP for each patient were selected based on target coverage and dose to organs at risk (OARs). The AP quality was analyzed and compared to corresponding clinically accepted and manually generated VMAT plans (MPs) using several clinically relevant dose metrics. Calculation-based pre-treatment plan quality assurance (QA) was performed for all plans., Results: The median total duration to generate the five APs with the aTPS was 55 min, 39 min and 35 min for anal, prostate and rectal plans, respectively. The target coverage and the OAR sparing were equivalent for IMRT-APs and VMAT-MPs, while VMAT-Aps.demonstrated lower target dose homogeneity and higher dose to some OARs. Both conformity and homogeneity index were equivalent (rectal) or better (anal and prostate) for IMRT-APs compared to VMAT-MPs. All plans passed the patient-specific QA tolerance limit., Conclusions: The aTPS generates plans comparable to MPs within a short time-frame which is highly relevant for oART treatments., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background and Purpose: Studies have demonstrated the potential of online adaptive radiotherapy (oART). However, routine use has been limited due to resource demanding solutions. This study reports on experiences with oART in the pelvic region using a novel cone-beam computed tomography (CBCT)-based, artificial intelligence (AI)-driven solution., Material and Methods: Automated pre-treatment planning for thirty-nine pelvic cases (bladder, rectum, anal, and prostate), and one hundred oART simulations were conducted in a pre-clinical release of Ethos (Varian Medical Systems, Palo Alto, CA). Plan quality, AI-segmentation accuracy, oART feasibility and an integrated calculation-based quality assurance solution were evaluated. Experiences from the first five clinical oART patients (three bladder, one rectum and one sarcoma) are reported., Results: Auto-generated pre-treatment plans demonstrated similar planning target volume (PTV) coverage and organs at risk doses, compared to institution reference. More than 75% of AI-segmentations during simulated oART required none or minor editing and the adapted plan was superior in 88% of cases. Limitations in AI-segmentation correlated to cases where AI model training was lacking. The five first treated patients complied well with the median adaptive procedure duration of 17.6 min (from CBCT acceptance to treatment delivery start). The treated bladder patients demonstrated a 42% median primary PTV reduction, indicating a 24%-30% reduction in V 45Gy to the bowel cavity, compared to non-ART., Conclusions: A novel commercial oART solution was demonstrated feasible for various pelvic sites. Clinically acceptable AI-segmentation and auto-planning enabled adaptation within reasonable timeslots. Possibilities for reduced PTVs observed for bladder cancer indicated potential for toxicity reductions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Using a two-bottle choice test of short duration, we determined taste preference thresholds for sucrose, fructose, glucose, lactose, and maltose in three Western chimpanzees (Pan troglodytes verus). Further, we assessed relative preferences for these five saccharides when presented at equimolar concentrations and determined taste preference difference thresholds for sucrose, that is, the smallest concentration difference at which the chimpanzees display a preference for one of the two options. We found that the chimpanzees significantly preferred concentrations as low as 20 mM sucrose, 40 mM fructose, and 80 mM glucose, lactose, and maltose over tap water. When given a choice between all binary combinations of these five saccharides presented at equimolar concentrations of 100, 200, and 400 mM, respectively, the animals displayed significant preferences for individual saccharides in the following order: sucrose > fructose > glucose = maltose = lactose. The taste difference threshold for sucrose, expressed as Weber ratio (ΔI/I), was 0.3 and 0.4, respectively, at reference concentrations of 100 and 200 mM. The taste sensitivity of the chimpanzees to the five saccharides falls into the same range found in other primate species. Remarkably, their taste preference thresholds are similar, and with two saccharides even identical, to human taste detection thresholds. The pattern of relative taste preferences displayed by the chimpanzees was similar to that found in platyrrhine primates and to the pattern of relative sweetness as reported by humans. Taken together, the results of the present study are in line with the notion that taste sensitivity for food-associated carbohydrates may correlate positively with phylogenetic relatedness. Further, they support the notion that relative preferences for food-associated carbohydrates, but not taste difference thresholds, may correlate with dietary specialization in primates.

Primates have been found to differ widely in their taste perception and studies suggest that a co-evolution between plant species bearing a certain taste substance and primate species feeding on these plants may contribute to such between-species differences. Considering that only platyrrhine primates, but not catarrhine or prosimian primates, share an evolutionary history with the neotropical plant Stevia rebaudiana , we assessed whether members of these three primate taxa differ in their ability to perceive and/or in their sensitivity to its two quantitatively predominant sweet-tasting substances. We found that not only neotropical black-handed spider monkeys, but also paleotropical black-and-white ruffed lemurs and Western chimpanzees are clearly able to perceive stevioside and rebaudioside A. Using a two-bottle preference test of short duration, we found that Ateles geoffroyi preferred concentrations as low as 0.05 mM stevioside and 0.01 mM rebaudioside A over tap water. Taste preference thresholds of Pan troglodytes were similar to those of the spider monkeys, with 0.05 mM for stevioside and 0.03 mM for rebaudioside A, whereas Varecia variegata was slightly less sensitive with a threshold value of 0.1 mM for both substances. Thus, all three primate species are, similar to human subjects, clearly more sensitive to both steviol glycosides compared to sucrose. Only the spider monkeys displayed concentration-response curves with both stevioside and rebaudioside A which can best be described as an inverted U-shaped function suggesting that Ateles geoffroyi , similar to human subjects, may perceive a bitter side taste at higher concentrations of these substances. Taken together, the results of the present study do not support the notion that a co-evolution between plant and primate species may account for between-species differences in taste perception of steviol glycosides.

It has been recognized for a long time that the secretory granules of mast cells are acidic, but the functional importance of maintaining an acidic pH in the mast cell granules is not fully understood. Here we addressed this issue by examining the effects of raising the pH of the mast cell secretory granules. Mast cells were incubated with bafilomycin A1, an inhibitor of the vacuolar-type ATPase proton pump. Supporting a role of vacuolar-type ATPase in mast cell granule acidification, bafilomycin A1 treatment caused a robust increase in granule pH. This was accompanied by marked effects on mast cell granules, including swelling and acquisition of vacuole-like morphology. Moreover, bafilomycin A1 caused extensive, yet selective effects on the granule content. These included aberrant processing of pro-carboxypeptidase A3 and a reduction in the level of intracellular histamine, the latter being accompanied by an increase in extracellular histamine. In contrast, the storage of β-hexosaminidase, a prototype lysosomal hydrolase known to be stored in mast cell granules, was not affected by abrogation of granule acidification. Moreover, bafilomycin A1 caused a reduction of tryptase enzymatic activity and appearance of tryptase degradation products. Tryptase inhibition prevented the formation of such degradation products, suggesting that the pH elevation causes tryptase to undergo autoproteolysis. Taken together, our findings reveal that mast cell secretory granule homeostasis is critically dependent on an acidic milieu.