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Major depressive disorder (MDD) is the leading cause of disability worldwide, affecting roughly 322 million people. Recently, doses of psilocybin have shown promise in treating mood disorders, sparking interest in other dosing practices. According to anecdotal reports and observational studies, microdosing psilocybin yields benefits to mental health; however, rigorously controlled trials have failed to produce compelling evidence for this.
Aims
To conduct a phase II, double-blind, placebo-controlled, randomised partial crossover trial to compare microdosing psilocybin to placebo for MDD, evaluating its safety, tolerability and preliminary antidepressant effects.
Method
Forty adults with MDD will be randomised to four doses of psilocybin (2 mg) or placebo (maltodextrin) once weekly over 4 weeks, then four doses of psilocybin (2 mg) once weekly for an additional 4 weeks. The primary efficacy end-point will be change in depression symptoms, as measured at baseline (0 weeks), after the experimental phase (4 weeks), and after the open-label phase (8 weeks). A battery of mood, well-being, attention, creativity, mindfulness and pro-sociality measures will be administered at each time point. Follow-ups will occur every 6 months for up to 2 years after the trial start date, as part of a long-term extension study.
Results
The results of the primary outcome of this trial will be published as a manuscript in a peer-reviewed science or medical journal regardless of the magnitude or direction of effect.
Conclusions
Findings will inform future research on microdosing psilocybin for MDD, regarding dose regimens, effect sizes and expectancy bias. Findings will also facilitate discussions on the comparable benefits of sub- versus threshold doses of psilocybin and the therapeutic value of radically altered perception.
A combined experimental and numerical investigation of equilibrium states arising from quasi-two-dimensional turbulent flows in a rotating quadrangular basin with a central flat region and steep slopes adjacent to the sidewalls is presented. The study examines freely decaying and continuously forced regimes. Laboratory experiments show that decaying turbulence consistently evolves into a robust equilibrium state characterised by: (i) a boundary current around the basin along the topographic contours, and (ii) a central anticyclone – features accurately reproduced by shallow-water numerical simulations at laboratory scale. Additional simulations using a mesoscale basin suggest the relevance of these findings to oceanic regimes for different initial conditions and topographic parameters. In the case of continuously forced flows, time-averaged fields reveal qualitatively similar structures, despite the randomness of the applied forcing and the consequent absence of a strict equilibrium. These results demonstrate the emergence of robust flow patterns with implications for the modelling and understanding of semi-permanent flows that are often found in statistical theories of geophysical turbulence.
This paper studies the transition to high inflation during the COVID-19 pandemic, using a behavioral version of the New Keynesian model, which replaces the conventional assumption of rational expectations with subjective and heterogeneous expectations. Different shares of agents in the economy form expectations based on alternative views regarding future economic variables: (1) a share of agents forecasts that inflation and output will rapidly revert to steady state; (2) another share forms forecasts based on a model resembling the MSV solution under rational expectations; (3) a third share of agents uses an under-specified model that captures trend-following, adaptive, or extrapolative behavior. Agents learn over time the parameters of their perceived model and they can also shift across different views based on past forecasting performance. The macroeconomic model is estimated using Bayesian methods to fit realized macroeconomic variables and data on expectations from surveys. The results document an additional channel that operates through switches in agents’ perceptions and amplifies the impact of the original inflationary shocks. In response to rising inflation after COVID, agents begin shifting from the mean reversion model to the trend-following specification (with a belief about perceived inflation persistence that is simultaneously revised upward). Consequently, the impact of inflationary shocks is magnified and the effects of monetary policy attenuated.
The fossil record of medusozoan cnidarians is relatively sparse and, in some cases, contentious. Here, we describe a new genus and species of a well-preserved, soft-bodied, tubicolous polyp, Paleocanna tentaculum n. gen. n. sp., from the Upper Ordovician (Katian) Neuville Formation in Québec. These fossils, preserved as carbonaceous compressions, were found in association with typical shelly assemblages. Fifteen slabs of shaly limestone containing ~ 135 specimens of Paleocanna tentaculum n. gen. n. sp. were examined. Individual polyps occupied upright tubes, which occur either solitarily or in clusters. Some tubes exhibit a striated periderm near their base. The polyp is elongated, with a rounded aboral end and a consistent ring of tentacles protruding distally from the tube. A phylogenetic analysis of 69 taxa and 236 discrete morphological characters indicated that the species is more closely related to the extant crown group than it is to the other stem-group medusozoans, e.g., conulariids and carinachitids. The uniform orientation of specimens on single slabs suggests rapid burial. Paleocanna tentaculum n. gen. n. sp. represents an exceptionally preserved member of an Ordovician deposit exhibiting Burgess Shale-type soft-tissue preservation.
Vitamin A deficiency (VAD) is common among pregnant women (PW) and has been associated with anaemia and adverse birth outcomes. However, in the Free State Province of South Africa, evidence regarding this is limited. Hence, this cross-sectional study investigated the vitA intake and status of PW in Bloemfontein and its association with anaemia, iron status and birth outcomes. Blood was taken from 427 PW to assess status of vitA (retinol-binding protein 4 (RBP4)), iron (ferritin, soluble transferrin receptor), and anaemia (haemoglobin (Hb)). Sociodemographic, HIV, birth outcomes (birth weight and gestational age), and dietary vitA intake data were obtained using a questionnaire in an interview and medical records. Descriptive statistics and linear regression were used to describe variables and association between vitA and iron status and birth outcomes. Median vitA intake was 1007µgRAE/d, with 19% of participants’ intake below the EAR of 550µg/d. Median (IQR) RBP4 concentration was 1.51 (0.78) µmol/L. Insufficient vitA and VAD prevalence was 12.2% and 1.2%, respectively. VitA intake was positively associated with RBP4 (β=0.068; 95%CI: 0.020, 0.116; p=0.006). RBP4 was positively associated with Hb (β=0.363; 95%CI: 0.186, 0.539; p <0.001) and ferritin (β=0.359; 95%CI: 0.139, 0.579; p=0.001) but negatively with sTfR (β=-0.125; 95%CI: -0.246, -0.005, p=0.041). No significant association between plasma RBP4 and birth weight, as well as preterm birth was observed. There was a low prevalence of VAD in the study population. Nonetheless, the positive association between RBP4 and Hb, and ferritin highlights the importance of optimal vitA status in preventing maternal anaemia in pregnancy.
Research teams studying bilingualism often focus on a specific population of bilinguals, which can limit the generalizability of their findings. This study explored how U.S. adolescents who speak a non-English language vary in their language experiences and cognition using data from the Adolescent Brain Cognitive Development (ABCD) study. The sample included 6683 English monolinguals, 1138 heritage bilinguals, 592 dual language education (DLE) bilinguals and 1751 other bilinguals. SES varied across groups: sequential bilinguals (i.e., DLE and other bilinguals) had higher parental education and income than monolinguals, while heritage bilinguals had the lowest SES. Sequential bilinguals reported higher English proficiency and greater English use with family and friends than heritage bilinguals. Sequential bilinguals initially outperformed monolinguals on cognitive tasks, who in turn outperformed heritage bilinguals. However, these differences disappeared once SES was controlled. Findings highlight the importance of considering SES and language experiences when studying bilingualism’s cognitive effects and help explain inconsistencies in prior research.
We compute the Galois groups of the reductions modulo a prime number p of the generating series of Apéry numbers, Domb numbers and Almkvist–Zudilin numbers. We observe in particular that their behaviour is governed by congruence conditions on p.
This article examines anti-colonialism and Third World solidarities in Britain during the 1970s and 1980s. It does so through a study of the Black Liberation Front (BLF), a Black Power group formed in London in 1971. The BLF saw themselves as part of a global Third World solidarity, and, as activists in Britain, identified their location as ‘inside the belly of the monster’. They understood racism and colonialism as global phenomena, and offered material support to anti-colonial movements across the world, especially in Africa. The prevailing historiography of Black activism in post-war Britain foregrounds domestic anti-racism. Based on a reading of the BLF’s publications, alongside subsequent memoirs by and interviews with former BLF members, this article argues for Black activism in Britain to be viewed through a more global lens. Moreover, it shows how a deeper understanding of transnational anti-colonialism reconfigures our understanding of the domestic politics of race. Historians of decolonization must attend to how twentieth-century geographies of race and migration created the conditions for solidarities that do not fit within a metropole–colony binary.
The notion of $\theta $-congruent numbers generalises the classical congruent number problem. A positive integer n is $\theta $-congruent if it is the area of a rational triangle with an angle $\theta $ whose cosine is rational. Das and Saikia [‘On $\theta $-congruent numbers over real number fields’, Bull. Aust. Math. Soc.103(2) (2021), 218–229] established criteria for numbers to be $\theta $-congruent over certain real number fields and concluded their work by posing four open questions regarding the relationship between $\theta $-congruent and properly $\theta $-congruent numbers. In this work, we provide complete answers to those questions. Indeed, we remove a technical assumption from their result on fields with degrees coprime to six, provide a definitive answer for real cubic fields without congruence restrictions, extend the analysis to fields of degree six and examine the exceptional cases $n=1, 2, 3$ and $6$.
Ibogaine is a psychedelic alkaloid without an approved indication. Observational clinical research shows linkages between single administration of ibogaine and relief of symptoms of neuropsychiatric conditions including substance use disorder, multiple sclerosis, and traumatic brain injury. Ibogaine has multi-receptor actions, but the neurobiological mechanisms underlying such putative effects is unknown. Here we review and discuss the relevant literature, focusing on remyelination and metabolic restoration. We provide evidence that ibogaine upregulates markers of myelination following opioid administration; that conditions such as opioid use disorder, multiple sclerosis and traumatic brain injury are characterized by white matter pathology; that decreased myelination is related to dysregulated metabolic homeostasis, ischemia and hypoxia which may also play a role in these disorders. We conclude that multi-receptor actions of ibogaine, especially its affinities for the NMDA, kappa opioid and sigma receptors, in turn account for reduction in excitotoxicity, metabolic regulation, lasting neuroplasticity and immunomodulation that facilitates neuronal repair and remyelination providing a rationale for future investigation of its use as a therapeutic agent for these common central nervous system disorders.
The set of sums of two squares plays a significant role in number theory. We establish the existence of several rich monochromatic configurations in the natural numbers by exploiting algebraic structures induced by the set of sums of two squares. The proofs rely on algebraic properties arising from the induced structures on the Stone–Čech compactification of the natural numbers.
The widespread use of atrazine in corn since the 1960s has raised environmental concerns, such as ground and surface water contamination. The U.S. Environmental Protection Agency has proposed label restrictions on atrazine to address these concerns and requires applicators to achieve herbicide mitigation points before applying herbicides. One way to achieve mitigation points is to reduce the proportion of the field that is treated. Therefore, research was conducted in 2023 in Arkansas, Mississippi, Tennessee, North Carolina, Indiana, and Virginia, and in 2024 in Arkansas, Tennessee, and Indiana, to determine whether targeted applications can mitigate atrazine use in corn while maintaining weed control levels comparable to those achieved with broadcast applications. All plots, except the nontreated control, received paraquat and S-metolachlor immediately after planting in 2023, with amicarbazone and metribuzin added in 2024. Combinations of atrazine, glyphosate, and mesotrione were applied postemergence either broadcast, target-applied to emerged weeds, or a combination of broadcast and target-applied. Targeted applications of herbicides did not differ in weed control, including Palmer amaranth and morningglory species, compared to broadcast applications of the same active ingredients. No injury or differences in corn grain yield were observed. Targeted applications in 2023 covered 86% of the area, on average, while 52% of the area was sprayed on average in 2024. Differences in the area sprayed during the targeted application between years can be attributed to the reduced area of weed emergence from a more robust residual herbicide combination in 2024. Based on this research, targeted spray technology can reduce atrazine use in corn while providing weed control comparable to that achieved with broadcast applications.
The integration of phenotypic, genomic and pedigree data into a single-step model for predicting genomically enhanced estimated breeding values (GEBVs) has become crucial for the accurate genetic evaluation of dairy cattle. This study compared two widely used software implementations, MiXBLUP and BLUPF90IOD3, for the prediction of breeding values using the single-step G-BLUP model based on data from the Polish national evaluation for stature. Four core animal sets were tested, which differed in the selection of bulls and cows. The GEBVs were predicted and validated using different subsets of the population. Both software packages resulted in high correlations (0.89 and 0.97) between full and truncated dataset predictions and similar validation performance, with MiXBLUP exhibiting slightly greater consistency across different sets of core animals. The ranking of the top 50 bulls remained stable across the implementations. This study concludes that both software implementations provide comparable GEBV predictions, suggesting that software choice should consider computational efficiency, cost and modeling flexibility, with MiXBLUP offering additional options for GEBV estimation.
We report a new species of stem ibis (Threskiornithidae) from the early Eocene Fossil Butte Member of the Green River Formation. Rhynchaeites mcfaddeni n. sp. is represented by an articulated partial skeleton and was a diminutive species, with an estimated body mass of under 300 g. The holotype specimen is preserved in an unusual manner, leaving the skull, presacral vertebral column, wings, and feet in approximate life position despite the loss of the trunk, pelvis, tail, and upper legs. This peculiar mode of preservation may represent a case of the “stick ‘n’ peel” model of preservation, by which a portion of a carcass becomes firmly adhered to the sediment by substances released during decay. Like other members of the stem ibis genus Rhynchaeites, Rhynchaeites mcfaddeni n. sp. lacks the dense pitting of the bill tip associated with abundant Herbst corpuscles, which is developed in extant ibises. However, the new species differs from all stem and crown ibises in possessing a sharply tapering beak tip, which suggests a unique mode of foraging, possibly including prying mollusks from their shells. Given that Rhynchaeites messelensis Wittich, 1898 is one of the most common birds in the prolific Messel deposits but Rhynchaeites mcfaddeni n. sp. is represented by a single specimen after more than 50 years of intense collecting in the Green River Formation, it is likely the two species had divergent foraging strategies, with the former perhaps feeding closer to the lake margin and the latter in streams.
Carers of people living with breathlessness face common challenges due to the chronic, distressing and unpredictable nature of the symptom. These include unmet information and support needs resulting in worsened health and psychosocial outcomes. This review aimed to (1) identify the relative volume of studies on supportive interventions for carers of people living with breathlessness due to different respiratory diseases, (2) characterize the nature of the interventions, and (3) explore their reported effectiveness on outcomes identified by carers as being important.
Methods
Medline and CINAHL were searched for studies reporting interventions targeting unpaid adult carers of people with breathlessness, lung cancer, chronic obstructive pulmonary disease (COPD), Interstitial Lung Diseases (ILD) published 2000-2025. Intervention characteristics and reported outcomes were extracted and compared across diagnoses and intervention categories. Our findings were shaped by consultation with unpaid carers in a series of patient and public involvement workshops.
Results
From 72 included interventions, three approaches were identified: Education, therapeutic support, and interventions for patient management. Interventions for lung cancer carers most frequently offered therapeutic support to the carer, while those for COPD carers most frequently focused on managing the patient. COPD and ILD carers have been underserved by research. We found few therapeutic support interventions for COPD carers. Reporting of carer demographics was poor, including among RCTs.
Significance of results
There was a dominance of research focusing on carers of people with lung cancer (56% of participants). In PPI consultations, carers identified stigma and poor communication with health providers as factors contributing to the disparity between lung cancer and other respiratory diseases. More research is needed to compare the efficacy of different intervention strategies to improve outcomes that matter most to carers. To improve equity, researchers must consistently report carer demographics and prioritize developing interventions for carers underserved by research.
We report an exceptionally early diagnosis of a Kommerell diverticulum on the first day of life, distinguished by unusual mid-ductal aneurysmal dilatation of the patent ductus arteriosus. Serial echocardiography documented the serial evolution of spontaneous ductal closure and thrombosis formation. CT confirmed a right aortic arch with a retroesophageal Kommerell diverticulum. The infant remains asymptomatic under close surveillance. This case represents one of the youngest reported cases with serial imaging documentation, providing unique insights into the early natural history and highlighting management challenges in asymptomatic neonatal patients.