An observational time-series study on the behavioral effects of adjunctive artisanal cannabidiol use by adults with treatment resistant epilepsies.

BACKGROUND: For approximately 30% of people with epilepsy, seizures are not well-controlled by anti-seizure medication (ASM). This condition, called treatment resistant epilepsy (TRE), is associated with increased morbidity and mortality, and substantially impacts the quality of life of both the individual and their family. Non-responsiveness to ASMs leads many people with TRE to seek alternative therapies, such as cannabinoid-based medication, particularly cannabidiol (CBD), with or without medical or professional advice. This is due in part to widespread reporting in the media about the benefits of CBD for seizures in some forms of epilepsy. METHODS: Adults with TRE, opting to add CBD to their existing treatment regime, completed this prospective, observational, longitudinal, quasi-experimental, time-series study. We hypothesized that adjunctive CBD use would positively impact participants' quality of life and psychological well-being in comparison to a baseline period without CBD use. Participants were followed for a period of approximately six months - for approximately one month of baseline prior to the initiation of CBD use and approximately five months after the initiation of CBD use. Participants provided urine samples and completed behavioral questionnaires that assessed quality of life, anxiety/depression, and adverse events during baseline and at two times during CBD use. RESULTS: Complete case analyses (n = 10) showed a statistically significant improvement in quality of life, a statistically significant decrease in anxiety symptoms, and a statistically significant decrease in the experience of adverse events over time (p < 0.05). Improvements noted in the experience of depression symptoms did not reach statistical significance. Urinalysis revealed the majority of participants had no CBD/metabolites in their system at the beginning of the study, and confirmed the presence of CBD/metabolites in participants' urine after CBD was added to their treatment regime. Analysis of missing data using multiple imputation supported the findings of the complete case analysis. INTERPRETATION: For a small group of individuals with TRE of varying etiologies, adjunctive use of artisanal CBD was associated with improvements in the behavioral and psychological symptoms of TRE, as well as improved medication tolerability.

Cochlea to categories: The spatiotemporal dynamics of semantic auditory representations.

How does the auditory system categorize natural sounds? Here we apply multimodal neuroimaging to illustrate the progression from acoustic to semantically dominated representations. Combining magnetoencephalographic (MEG) and functional magnetic resonance imaging (fMRI) scans of observers listening to naturalistic sounds, we found superior temporal responses beginning ∼55 ms post-stimulus onset, spreading to extratemporal cortices by ∼100 ms. Early regions were distinguished less by onset/peak latency than by functional properties and overall temporal response profiles. Early acoustically-dominated representations trended systematically toward category dominance over time (after ∼200 ms) and space (beyond primary cortex). Semantic category representation was spatially specific: Vocalizations were preferentially distinguished in frontotemporal voice-selective regions and the fusiform; scenes and objects were distinguished in parahippocampal and medial place areas. Our results are consistent with real-world events coded via an extended auditory processing hierarchy, in which acoustic representations rapidly enter multiple streams specialized by category, including areas typically considered visual cortex.

Shared cognitive mechanisms involved in the processing of scene texture and scene shape.

Recent research has demonstrated that the parahippocampal place area represents both the shape and texture features of scenes, with the importance of each feature varying according to perceived scene category. Namely, shape features are predominately more diagnostic to the processing of artificial human-made scenes, while shape and texture are equally diagnostic in natural scene processing. However, to date little is known regarding the degree of interactivity or independence observed in the processing of these scene features. Furthermore, manipulating the scope of visual attention (i.e., globally vs. locally) when processing ensembles of multiple objects-stimuli that share a functional neuroanatomical link with scenes-has been shown to affect their cognitive visual representation. It remains unknown whether manipulating the scope of attention impacts scene processing in a similar manner. Using the well-established Garner speeded-classification behavioral paradigm, we investigated the influence of both feature diagnosticity and the scope of visual attention on potential interactivity or independence in the shape and texture processing of artificial human-made scenes. The results revealed asymmetric interference between scene shape and texture processing, with the more diagnostic feature (i.e., shape) interfering with the less diagnostic feature (i.e., texture), but not vice versa. Furthermore, this interference was attenuated and enhanced with more local and global visual processing strategies, respectively. These findings suggest that the scene shape and texture processing are mediated by shared cognitive mechanisms and that, although these representations are governed primarily via feature diagnosticity, they can nevertheless be influenced by the scope of visual attention.

Patient survival following renal transplantation in Indigenous populations: A systematic review.

BACKGROUND: Inequities in health care predispose Indigenous populations to poor health outcomes. The objective of this study was to examine patient survival and other post-transplant outcomes of kidney transplantation among Indigenous patients compared with non-Indigenous populations. METHODS: A systematic review of MEDLINE, EMBASE, and Google Scholar was undertaken from inception to September 30, 2019, using a computerized search. Publication descriptors and methodological and statistical details were extracted. Articles were assessed using the methodological index for non-randomized studies (MINORS) scale. RESULTS: Twelve studies were included. All studies were retrospective and published between 2004 and 2018. Mean Indigenous patient age was 40 (range: 8-76), while non-Indigenous was 41 (range: 6-74). Mean sample size for Indigenous populations was 398 (range: 24-1459), while for non-Indigenous patients was 1102 (range: 53-7555). Eight studies examined indigenous populations in Australia, two in Canada, one in the United States, and one in New Zealand. All studies were considered of high methodological quality and clinically homogenous. Results indicated that patient survival, graft survival, and delayed graft function were significantly reduced among Indigenous populations compared with non-Indigenous populations. CONCLUSIONS: Post-transplant outcomes among various Indigenous populations are significantly worse compared with non-Indigenous populations. The reasons for poor outcomes are likely multifactorial. Improved standardized reporting of transplant outcomes of Indigenous patients is necessary to better inform healthcare services and improve clinical outcomes.

How do cognitive and functional impairment relate to the use of anticholinergic medications in hospitalised patients aged 65 years and over?

BACKGROUND: Anticholinergic medications are commonly prescribed to older adults despite their unfavourable pharmacological profile. There are no specific systems in place to alert prescribers about the wide range of medications with anticholinergic properties and their cumulative potential. AIMS: To examine associations between medications with anticholinergic properties and cognitive and functional impairment in hospitalised patients aged 65 years and older. METHODS: This descriptive, cross-sectional study included 94 patients admitted to a rehabilitation ward and a geriatric evaluation and management unit. Anticholinergic burden was calculated using the Anticholinergic Risk Scale. The Addenbrooke's Cognitive Examination and the Elderly Symptom Assessment Scale tools were utilised to assess cognitive function and burden of anticholinergic symptoms, respectively. RESULTS: Medications with anticholinergic properties were taken by 72.3% of patients with level 1 being the most commonly consumed (median 1, IQR = 0-2) medications. There was no association between anticholinergic medication use and cognitive function or anticholinergic symptoms. Increasing age and the hospital length of stay were associated with fewer anticholinergic symptoms (p < 0.001 and p = 0.021, respectively), whereas the total number of medications consumed was linked to a greater burden of anticholinergic symptoms (p < 0.001). CONCLUSION: A lack of association between anticholinergic medications and cognitive function could be related to duration of exposure to this group of medications and the age sensitivity. Additionally, the total number of medications consumed by patients was linked to a greater burden of anticholinergic symptoms. These findings highlight the need for improved knowledge and attentiveness when prescribing medications in general in this vulnerable population.

The Impact of Bed Traffic Control and Improved Flow Process on Throughput Measures in a Metropolitan Emergency Department.

INTRODUCTION: ED crowding is a complex phenomenon that presents many challenges to patients, hospitals, and staff. Using Lewin's change model, we implemented an ED improvement plan, including an innovative bed traffic control and improved flow system. We hypothesized that this plan would reduce door-to-provider time and emergency medical service-offloading time, decrease the length of stay and number of patients leaving without being seen by a physician, and increase overall patient satisfaction. METHODS: We examined the ED improvement plan's impact on institutional throughput metrics over a 4-year period (2015-2019). Data on door-to-provider time, door-to-discharge time, patient volume, leaving without being seen by a physician, and patient satisfaction by Press Ganey were analyzed. RESULTS: Between 2015 and 2018, the median door-to-provider time decreased 56.9% and the median door-to-discharge time decreased 29.6%. Percentage of patients who left without being seen by a physician decreased 73.8%. In 2018, the patient satisfaction rank increased by 16 points (84.2% increase). Emergency medical services-offloading time decreased significantly, prompting a change of the 30-minute cutoff to 20 minutes. In 2018, 0.84% of patients had an offloading time of more than 20 minutes. Preliminary 2019 data show maintenance of this trend for all hospital metrics. DISCUSSION: Implementing a pod system, with flow and bed placement managed by bed traffic control, reduced door-to-provider time, door-to-discharge time, leaving without being seen by a physician, emergency medical service-offload time, and increased patient satisfaction. Our results may provide a model for other emergency departments to effectively manage the challenges of crowding.

Testing Darwin's Hypothesis about the Wonderful Venus Flytrap: Marginal Spikes Form a "Horrid Prison" for Moderate-Sized Insect Prey.

Botanical carnivory is a novel feeding strategy associated with numerous physiological and morphological adaptations. However, the benefits of these novel carnivorous traits are rarely tested. We used field observations, lab experiments, and a seminatural experiment to test prey capture function of the marginal spikes on snap traps of the Venus flytrap (Dionaea muscipula). Our field and laboratory results suggested inefficient capture success: fewer than one in four prey encounters led to prey capture. Removing the marginal spikes decreased the rate of prey capture success for moderate-sized cricket prey by 90%, but this effect disappeared for larger prey. The nonlinear benefit of spikes suggests that they provide a better cage for capturing more abundant insects of moderate and small sizes, but they may also provide a foothold for rare large prey to escape. Our observations support Darwin's hypothesis that the marginal spikes form a "horrid prison" that increases prey capture success for moderate-sized prey, but the decreasing benefit for larger prey is unexpected and previously undocumented. Thus, we find surprising complexity in the adaptive landscape for one of the most wonderful evolutionary innovations among all plants. These findings enrich understanding of the evolution and diversification of novel trap morphology in carnivorous plants.

Neural representation of geometry and surface properties in object and scene perception.

Multiple cortical regions are crucial for perceiving the visual world, yet the processes shaping representations in these regions are unclear. To address this issue, we must elucidate how perceptual features shape representations of the environment. Here, we explore how the weighting of different visual features affects neural representations of objects and scenes, focusing on the scene-selective parahippocampal place area (PPA), but additionally including the retrosplenial complex (RSC), occipital place area (OPA), lateral occipital (LO) area, fusiform face area (FFA) and occipital face area (OFA). Across three experiments, we examined functional magnetic resonance imaging (fMRI) activity while human observers viewed scenes and objects that varied in geometry (shape/layout) and surface properties (texture/material). Interestingly, we found equal sensitivity in the PPA for these properties within a scene, revealing that spatial-selectivity alone does not drive activation within this cortical region. We also observed sensitivity to object texture in PPA, but not to the same degree as scene texture, and representations in PPA varied when objects were placed within scenes. We conclude that PPA may process surface properties in a domain-specific manner, and that the processing of scene texture and geometry is equally-weighted in PPA and may be mediated by similar underlying neuronal mechanisms.

Germline competency of human embryonic stem cells depends on eomesodermin.

In humans, germline competency and the specification of primordial germ cells (PGCs) are thought to occur in a restricted developmental window during early embryogenesis. Despite the importance of specifying the appropriate number of PGCs for human reproduction, the molecular mechanisms governing PGC formation remain largely unexplored. Here, we compared PGC-like cell (PGCLC) differentiation from 18 independently derived human embryonic stem cell (hESC) lines, and discovered that the expression of primitive streak genes were positively associated with hESC germline competency. Furthermore, we show that chemical inhibition of TGFß and WNT signaling, which are required for primitive streak formation and CRISPR/Cas9 deletion of Eomesodermin (EOMES), significantly impacts PGCLC differentiation from hESCs. Taken together, our results suggest that human PGC formation involves signaling and transcriptional programs associated with somatic germ layer induction and expression of EOMES.

Feature diagnosticity and task context shape activity in human scene-selective cortex.

Scenes are constructed from multiple visual features, yet previous research investigating scene processing has often focused on the contributions of single features in isolation. In the real world, features rarely exist independently of one another and likely converge to inform scene identity in unique ways. Here, we utilize fMRI and pattern classification techniques to examine the interactions between task context (i.e., attend to diagnostic global scene features; texture or layout) and high-level scene attributes (content and spatial boundary) to test the novel hypothesis that scene-selective cortex represents multiple visual features, the importance of which varies according to their diagnostic relevance across scene categories and task demands. Our results show for the first time that scene representations are driven by interactions between multiple visual features and high-level scene attributes. Specifically, univariate analysis of scene-selective cortex revealed that task context and feature diagnosticity shape activity differentially across scene categories. Examination using multivariate decoding methods revealed results consistent with univariate findings, but also evidence for an interaction between high-level scene attributes and diagnostic visual features within scene categories. Critically, these findings suggest visual feature representations are not distributed uniformly across scene categories but are shaped by task context and feature diagnosticity. Thus, we propose that scene-selective cortex constructs a flexible representation of the environment by integrating multiple diagnostically relevant visual features, the nature of which varies according to the particular scene being perceived and the goals of the observer.

AutoLock: a semiautomated system for radiotherapy treatment plan quality control.

A semiautomated system for radiotherapy treatment plan quality control (QC), named AutoLock, is presented. AutoLock is designed to augment treatment plan QC by automatically checking aspects of treatment plans that are well suited to computational evaluation, whilst summarizing more subjective aspects in the form of a checklist. The treatment plan must pass all automated checks and all checklist items must be acknowledged by the planner as correct before the plan is finalized. Thus AutoLock uniquely integrates automated treatment plan QC, an electronic checklist, and plan finalization. In addition to reducing the potential for the propagation of errors, the integration of AutoLock into the plan finalization workflow has improved efficiency at our center. Detailed audit data are presented, demonstrating that the treatment plan QC rejection rate fell by around a third following the clinical introduction of AutoLock.

De novo assembly of red clover transcriptome based on RNA-Seq data provides insight into drought response, gene discovery and marker identification.

BACKGROUND: Red clover (Trifolium pratense L.) is a versatile forage crop legume, which can tolerate a variety of soils and is suitable for silage production for winter feed and for grazing. It is one of the most important forage legumes in temperate livestock agriculture. Its beneficial attributes include ability to fix nitrogen, improve soil and provide protein rich animal feed. It is however, a short-lived perennial providing good biomass yield for two or three years. Improved persistency is thus a major breeding target. Better water-stress tolerance is one of the key factors influencing persistency, but little is known about how red clover tolerates water stress. RESULTS: Plants from a full sib mapping family were used in a drought experiment, in which the growth rate and relative water content (RWC) identified two pools of ten plants contrasting in their tolerance to drought. Key metabolites were measured and RNA-Seq analysis was carried out on four bulked samples: the two pools sampled before and after drought. Massively parallel sequencing was used to analyse the bulked RNA samples. A de novo transcriptome reconstruction based on the RNA-Seq data was made, resulting in 45181 contigs, representing 'transcript tags'. These transcript tags were annotated with gene ontology (GO) terms. One of the most striking results from the expression analysis was that the drought sensitive plants were characterised by having approximately twice the number of differentially expressed transcript tags than the tolerant plants after drought. This difference was evident in most of the major GO terms. Before onset of drought the sensitive plants overexpressed a number of genes annotated as senescence-related. Furthermore, the concentration of three metabolites, particularly pinitol, but also proline and malate increased in leaves after drought stress. CONCLUSIONS: This de novo assembly of a red clover transcriptome from leaf material of droughted and non-droughted plants provides a rich source for gene identification, single nucleotide polymorphisms (SNP) and short sequence repeats (SSR). Comparison of gene expression levels between pools and treatments identified candidate genes for further analysis of the genetic basis of drought tolerance in red clover.

Long-term benefits to psychological health and well-being after ceremonial use of Ayahuasca in Middle Eastern and North African immigrants and refugees.

Background: Refugees and immigrants can experience complex stressors from the process of immigration that can have lasting and severe long-term mental health consequences. Experiences after ayahuasca ingestion are shown to produce positive effects on psychological wellbeing and mental health, including anecdotal reports of improved symptoms of trauma and related disorders. However, data on the longitudinal health impact of naturalistic ayahuasca use in Middle Eastern and North African (MENA) immigrant and refugee populations is limited. Aims: The current longitudinal online survey study was conducted to gather prospective data on ceremonial ayahuasca use in a group (N = 15) of primarily female MENA immigrants and refugees and to provide further insight into the patterns and outcomes surrounding that use. The study sought to assess self-reported changes in physical and mental health, well-being, and psychological functioning, examine relationships between aspects of individual mindset (e.g., psychedelic preparedness) prior to ayahuasca use and observed outcomes during (e.g., subjective drug effects) and afterwards (i.e., persisting effects), characterize risks and negative experiences, and describe trauma exposure and personal history. Results/Outcomes: Our findings revealed ceremonial use of ayahuasca is associated with significant improvements in mental health, well-being, and psychological functioning, including reductions in depression, anxiety, and shame, and increases in cognitive reappraisal and self-compassion. Most participants reported no lasting adverse effects and experienced notable positive behavioral changes persisting months after ingestion. Conclusion/Interpretation: While preliminary, results suggest naturalistic ayahuasca use might hold therapeutic potential for MENA populations exposed to trauma prior to and during the process of migration.

Psychedelic Experiences Increase Mind Perception but do not Change Atheist-Believer Status: A Prospective Longitudinal Study.

Recent studies suggest psychedelic use may be associated with changes in a variety of beliefs or belief-like states, including increased 1) mind perception, 2) non-naturalistic beliefs, and 3) Atheist-Believer status (e.g. believer, agnostic, or nonbeliever). We conducted a prospective longitudinal study among participants (N = 657) who planned to have a psilocybin experience outside a laboratory setting. We asked participants about their beliefs concerning mind perception of various entities, specific metaphysical positions, and Atheist-Believer status both before (and after their experience. Replicating previous findings, we observed increases in mind perception across a variety of living and non-living targets (e.g. plants, rocks). However, we found little to no change in metaphysical beliefs (e.g. dualism) or Atheist-Believer status. Taken together, these findings contrast with those from cross-sectional studies that psilocybin experiences result in changes to Atheist-Believer status and non-naturalistic beliefs but support the relevance of mind perception and mentalization.

Multi-institutional consensus on machine QA for isochronous cyclotron-based systems delivering ultra-high dose rate (FLASH) pencil beam scanning proton therapy in transmission mode.

BACKGROUND: The first clinical trials to assess the feasibility of FLASH radiotherapy in humans have started (FAST-01, FAST-02) and more trials are foreseen. To increase comparability between trials it is important to assure treatment quality and therefore establish a standard for machine quality assurance (QA). Currently, the AAPM TG-224 report is considered as the standard on machine QA for proton therapy, however, it was not intended to be used for ultra-high dose rate (UHDR) proton beams, which have gained interest due to the observation of the FLASH effect. PURPOSE: The aim of this study is to find consensus on practical guidelines on machine QA for UHDR proton beams in transmission mode in terms of which QA is required, how they should be done, which detectors are suitable for UHDR machine QA, and what tolerance limits should be applied. METHODS: A risk assessment to determine the gaps in the current standard for machine QA was performed by an international group of medical physicists. Based on that, practical guidelines on how to perform machine QA for UHDR proton beams were proposed. RESULTS: The risk assessment clearly identified the need for additional guidance on temporal dosimetry, addressing dose rate (constancy), dose spillage, and scanning speed. In addition, several minor changes from AAPM TG-224 were identified; define required dose rate levels, the use of clinically relevant dose levels, and the use of adapted beam settings to minimize activation of detector and phantom materials or to avoid saturation effects of specific detectors. The final report was created based on discussions and consensus. CONCLUSIONS: Consensus was reached on what QA is required for UHDR scanning proton beams in transmission mode for isochronous cyclotron-based systems and how they should be performed. However, the group discussions also showed that there is a lack of high temporal resolution detectors and sufficient QA data to set appropriate limits for some of the proposed QA procedures.

"Why am I still suffering?": Experience of long-term fatigue and neurocognitive changes in oropharyngeal cancer survivors following (chemo)radiotherapy.

Background: Late effects of cancer treatment, such as neurocognitive deficits and fatigue, can be debilitating. Other than head and neck-specific functional deficits such as impairments in swallowing and speech, little is known about survivorship after oropharyngeal cancer. This study examines the lived experience of fatigue and neurocognitive deficits in survivors of oropharyngeal squamous cell cancer and impact on their daily lives. Methods: This work is part of the multicentre mixed method ROC-oN study (Radiotherapy for Oropharyngeal Cancer and impact on Neurocognition), evaluating fatigue and neurocognitive function in patients following radiotherapy +/- chemotherapy for oropharyngeal cancer and impact on quality of life. Semi-structured interviews were conducted in adults treated with radiotherapy (+/-chemotherapy) for oropharyngeal squamous cell carcinoma >/=24 months from completing treatment. Reflexive thematic analysis performed. Results: 21 interviews (11 men and 10 women; median age 58 years and median time post-treatment 5 years) were conducted and analysed, yielding six themes: (1) unexpected burden of fatigue, (2) noticing changes in neurocognitive function, (3) the new normal, (4) navigating changes, (5)insufficient awareness and (6)required support. Participants described fatigue that persisted beyond the acute post-treatment period and changes in neurocognitive abilities across several domains. Paid and unpaid work, emotions and mood were impacted. Participants described navigating the new normal by adopting self-management strategies and accepting external support. They reported lack of recognition of these late effects, being poorly informed and being unprepared. Follow-up services were thought to be inadequate. Conclusions: Fatigue and neurocognitive impairment were frequently experienced by survivors of oropharyngeal cancer, at least two years after treatment. Patients felt ill-prepared for these late sequelae, highlighting opportunities for improvement of patient information and support services.

Neurocognitive function following (chemo)radiotherapy for nasopharyngeal cancer and other head and neck cancers: A systematic review.

When radiotherapy is used in the treatment of head and neck cancers, the brain commonly receives incidental doses of radiotherapy with potential for neurocognitive changes and subsequent impact on quality of life. This has not been widely investigated to date. A systematic search of MEDLINE, EMBASE, Psycinfo Info and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases was conducted. Of 2077 records screened, 20 were eligible comprising 1308 patients. There were no randomised studies and 73.3% of included patients were from single center studies. IMRT was delivered in 72.6% of patients, and chemotherapy used in 61%. There was considerable heterogeneity in methods. Narrative synthesis was therefore carried out. Most studies demonstrated inferior neurocognitive outcomes when compared to control groups at 12 months and beyond radiotherapy. Commonly affected neurocognitive domains were memory and language which appeared related to radiation dose to hippocampus, temporal lobe, and cerebellum. Magnetic Resonance Imaging could be valuable in the detection of early microstructural and functional changes, which could be indicative of future neurocognitive changes. In studies investigating quality of life, the presence of neurocognitive impairment was associated with inferior quality of life outcomes. (Chemo)radiotherapy for head and neck cancer appears to be associated with a risk of long-term neurocognitive impairment. Few studies were identified, with substantial variation in methodology, thus limiting conclusions. High quality large prospective head and neck cancer studies using standardised, sensitive, and reliable neurocognitive tests are needed.

Reconstituted ovaries self-assemble without an ovarian surface epithelium.

Three-dimensional (3D) stem cell models of the ovary have the potential to benefit women's reproductive health research. One such model, the reconstituted ovary (rOvary) self-assembles with pluripotent stem cell-derived germ cells creating a 3D ovarian mimic competent to support the differentiation of functional oocytes inside follicles. In this study, we evaluated the cellular composition of the rOvary revealing the capacity to generate multiple follicles surrounded by NR2F2+ stroma cells. However, the rOvary does not develop a surface epithelium, the source of second-wave pre-granulosa cells, or steroidogenic theca. Therefore, the rOvary models represent the self-assembly of activated follicles in a pre-pubertal ovary poised but not yet competent for hormone production.

Naturalistic psilocybin use is associated with persisting improvements in mental health and wellbeing: results from a prospective, longitudinal survey.

Introduction: The classic psychedelic psilocybin, found in some mushroom species, has received renewed interest in clinical research, showing potential mental health benefits in preliminary trials. Naturalistic use of psilocybin outside of research settings has increased in recent years, though data on the public health impact of such use remain limited. Methods: This prospective, longitudinal study comprised six sequential automated web-based surveys that collected data from adults planning to take psilocybin outside clinical research: at time of consent, 2 weeks before, the day before, 1-3 days after, 2-4 weeks after, and 2-3 months after psilocybin use. Results: A sample of 2,833 respondents completed all baseline assessments approximately 2 weeks before psilocybin use, 1,182 completed the 2-4 week post-use survey, and 657 completed the final follow-up survey 2-3 months after psilocybin use. Participants were primarily college-educated White men residing in the United States with a prior history of psychedelic use; mean age = 40 years. Participants primarily used dried psilocybin mushrooms (mean dose = 3.1 grams) for "self-exploration" purposes. Prospective longitudinal data collected before and after a planned psilocybin experience on average showed persisting reductions in anxiety, depression, and alcohol misuse, increased cognitive flexibility, emotion regulation, spiritual wellbeing, and extraversion, and reduced neuroticism and burnout after psilocybin use. However, a minority of participants (11% at 2-4 weeks and 7% at 2-3 months) reported persisting negative effects after psilocybin use (e.g., mood fluctuations, depressive symptoms). Discussion: Results from this study, the largest prospective survey of naturalistic psilocybin use to date, support the potential for psilocybin to produce lasting improvements in mental health symptoms and general wellbeing.

TORPEdO: A phase III trial of intensity-modulated proton beam therapy versus intensity-modulated radiotherapy for multi-toxicity reduction in oropharyngeal cancer.

•There is a lack of prospective level I evidence for the use of PBT for most adult cancers including oropharyngeal squamous cell carcinoma (OPSCC).•TORPEdO is the UK's first PBT clinical trial and aims to determine the benefits of PBT for OPSCC.•Training and support has been provided before and during the trial to reduce variations of contouring and radiotherapy planning.•There is a strong translational component within TORPEdO. Imaging and physics data along with blood, tissue collection will inform future studies in refining patient selection for IMPT.