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Ketamine exerts potent but transient antidepressant effects in treatment-resistant depression (TRD). Combinations of ketamine and psychotherapy have attracted interest, but no trial has investigated a psychedelic model of ketamine–psychotherapy for TRD to our knowledge.
Aims
This secondary analysis of a randomised clinical trial (RCT) explores the therapeutic effects and experiential mechanisms of the Montreal Model of ketamine–psychotherapy for TRD, with or without music.
Method
A two-centre, single-blinded, RCT conducted in Montreal, Canada, between January 2021 and August 2022 (NCT04701866). Participants received ketamine–psychotherapy for TRD – six subanaesthetic infusions over 4 weeks and psychological support – with either music or matched non-music support during ketamine doses, as per random group assignments. The primary therapeutic outcome was the Montgomery–Åsberg Depression Rating Scale, assessed by blinded raters. Psychedelic-like experiences, evaluated by the Mystical Experience Questionnaire and Emotional Breakthrough Inventory, and their session-by-session relationships with depression were explored with multilevel, time-lagged covariate models with autoregressive residuals.
Results
Thirty-two participants with severe and highly comorbid TRD, including high rates of personality disorder and suicidality, received 181 ketamine infusions. Therapeutic outcomes and psychedelic experiences did not differ between music (n = 15) and non-music (n = 17) interventions. Both groups experienced significant reductions in clinician-rated and self-reported depression (d = 1.2 and d = 0.87, respectively; p < 0.001), anxiety (d = 0.8, p < 0.001) and suicidality (d = 0.4, p < 0.05) at 4 weeks, fully maintained at 8-week follow-up. Ketamine experiences were highly emotional and mystical. Converging analyses supported mystical-like ketamine experiences as mechanisms of its antidepressant effects.
Conclusions
This trial found large and notably sustained benefits of ketamine–psychotherapy for severe TRD, with or without music, and psychedelic experiences of comparable intensity to those observed with psilocybin. Mystical-like experiences may particularly contribute to ketamine’s immediate and persistent psychiatric benefits.
Submarine melting is one of the major mechanisms of ice loss from marine-terminating glaciers and ice shelves, but its contribution is yet to be fully understood. Here, we demonstrate the feasibility of monitoring melting using passive underwater acoustics, by sensing the loud crackling sound produced during melting due to the release of pressurised ice-trapped bubbles. We profile the acoustic field in glacial bays in Svalbard using a hydrophone array and show that the sound level in the bay contains clues on the melt activity. The sound level’s interpretation is hindered by its spatial variability, which we suppress using a model of melt-induced acoustic activity. Thereby, we show that the sound generated at the glacier terminus is correlated with the ablation rate at the calving glacier front and the water temperature and thus linked to the melt rate. This marks a step forward in using passive acoustics to monitor submarine melt, paving the way for an autonomous, long-term, large-scale monitoring tool providing data that can inform assessments and simulations of ice sheet loss and sea level rise.
In Nairobi, water rights emerge not through legal recognition alone but through relationships with infrastructurally powerful actors. Residents must engage with specific individuals across institutional levels who control urban water distribution. This explains neighborhood disparities in water access and why some residents secure better supplies than others. The fragmentation of water control challenges traditional legal and normative frameworks of water rights. Understanding how rights are embedded in everyday socio-material relationships is crucial for comprehending how people establish water access and thereby concretize their right to water in practice.
In survey experiments, should all covariates be administered before the experimental treatment? Some scholars argue that post-treatment items should never be used as covariates because the treatment could bias the measurement of those items and disrupt experimental randomization. Other scholars argue certain items—specifically sensitive questions measuring prejudice—should not be administered pre-treatment. They argue if asked pre-treatment, these items may prime respondents in ways that will influence how they engage with the experiment treatment, thereby affecting the overall outcome of the experiment. Using evidence from four studies (two original collections) that vary the placement of sensitive items—pre-treatment, post-treatment, or in a separate wave—we find little evidence that the placement of sensitive items influences the measurement of those items, the experimental outcomes, nor heterogeneously affects the outcome conditional on the treatment. However, we find the placement of sensitive items inconsistently affects the experimental outcome by interacting with both the measurement of the items and the experimental treatment condition. Overall, we find these measures to be robust to where they are administered. It may be best to place items pre-treatment to preserve randomization. If researchers have reason to include sensitive moderators post-treatment, they should transparently discuss this choice and the anticipated trade-offs.
The literature on user trust in social welfare systems appropriately highlights the quality of relationships with frontline workers and the perception of their skills and human qualities, which develop and evolve over time. However, it tends to place less emphasis on users’ perceptions of and experiences with the formal procedures within which these relational processes unfold. With this paper, we aim to contribute to knowledge on user (dis)trust-building by focusing on the microdynamics of its development, which equally considers citizens’ interactions with frontline workers and institutional procedures at various organisational levels. Drawing on empirical research conducted among disadvantaged families seeking support from social services and assistance institutions in the Czech Republic and Serbia, we analyse the narrated experiences and perception-based mechanisms that shape users’ (dis)trust within the dual context of institutional procedures governing access to services, and the relationship with frontline workers.
Accounts of prosody in understudied languages are often impressionistic, potentially leading to conflicting accounts due to different researchers being drawn to different acoustic cues. The debate surrounding the location of primary stress in Plains Cree is such a case. One widely adopted claim states that stress is realized on the antepenult, whereas others argue for a penultimate accent. The present study investigates the phonetic properties of stress (duration, F0, intensity, vowel quality) in multisyllabic words and in phrases to understand the patterns that have led to the current debate. We find that there are cues supporting both previous claims: a high F0 on the antepenultimate syllable compatible with “antepenultimate stress” and a falling F0 on the penultimate syllable compatible with “penultimate accent.” Based on the acoustic evidence, we suggest that Plains Cree is a pitch-accent system, with a predictable penultimate HL word-level pitch-accent. Tonal patterns in other syllables are the result of prosodic boundaries, phonetic interpolation, or tonal spreading.
Global plastic production has more than doubled over the past two decades, fueling a parallel rise in transboundary plastic waste trade (PWT). Despite efforts to curb this through the Basel Convention and its 2021 Plastic Waste Amendments (BCPWA), loopholes and inconsistent implementation continue to allow large volumes of problematic and “hidden” plastic waste to bypass regulation. This flow of waste from high-income to lower-income countries has resulted in disproportionate environmental and social harms, often described as “waste colonialism.” Three years after the BCPWA entered into force, its limited impact highlights the urgent need for stronger, clearer, and universally enforceable rules. As the Global Plastics Treaty (GPT) nears conclusion at INC-5.2, negotiators have a critical opportunity to strengthen global controls. Expanding the Basel Prior Informed Consent (PIC) procedure to cover all plastic waste—including currently unregulated categories such as synthetic textiles and B3011 plastics—would close existing regulatory gaps, promote transparency, and ensure environmentally sound management. While a full ban on PWT may be politically unattainable in the near term, universal PIC represents a pragmatic step forward. Ultimately, meaningful progress demands upstream solutions: the GPT must prioritize reducing plastic production at its source, especially for the most harmful and unnecessary applications.
Identifying interactions between species is essential for understanding ecosystem dynamics. With their central position in trophic networks, anurans underscore the importance of studying their interactions with other organisms. Traditionally, collecting and describing anuran helminth parasites rely on lethal methods, posing challenges for studying threatened species. In this study, we tested the effectiveness of non-invasive fecal metabarcoding and compared its accuracy to traditional invasive methods for identifying parasites and dietary components. We collected anurans from 6 families in the Brazilian Atlantic Rainforest and analysed their feces using the 18S marker while performing necropsies for traditional identification. Traditional methods identified 12 parasite taxa and 3 dietary items at lower taxonomic resolution. Fecal metabarcoding, on the other hand, revealed greater diversity and fine taxonomic resolution for dietary items, although with lower accuracy for parasites due to database limitations. The metabarcoding approach demonstrated a high potential for non-lethal biodiversity assessments, offering a more comprehensive view of dietary diversity and a viable alternative for studying parasites in vulnerable populations. However, its effectiveness depends on improving reference databases, especially for parasite taxa. The advancement of non-invasive approaches that integrate parasitological data holds great potential to improve conservation strategies and enhance the ecological understanding of amphibian-parasite interactions.
Collective skill formation systems were central to sustaining a high-road to economic development while upholding social inclusion in industrial societies. But can they still deliver on both economic and social grounds in knowledge-based societies? The article argues that the transition to the knowledge economy may in fact strengthen the ‘traditional’ advantage of collective skill formation systems over other skill formation systems on both economic and social grounds while simultaneously, however, exerting pressure on them to recalibrate some of their underlying policy arrangements. It is argued that this dual relationship has to do with the institutional architecture of collective skill formation systems, in particular, their ‘shared governance’ between employers, unions and governments, and with the nature of technological change in the transition to the knowledge economy, in particular the bias toward complex cognitive skills that it produces. Quantitative and qualitative evidence lends overall support for the argument. Regression analysis shows that collective skill formation systems are still positively associated with a range of socio-economic outcomes also in the new knowledge economy, although conditional analyses suggest that they may be subject to ‘diminishing returns’ on social inclusion grounds, i.e., their ability to effectively perform a social policy function is confronted with greater challenges at high levels of technological intensity. Case studies of Austria, Germany, and Switzerland show how collective skill formation systems have adapted to the knowledge economy following country-specific patterns.
This introductory article challenges foundational assumptions that structure how international legal theory conceptualizes “the Global.” The prevailing approach remains anchored in a Eurocentric legacy that conflates the earth with a geometrically spherical, chronometrically linear, and cartographically fixed model of space and time. This triad has rendered “the Global” an ostensibly objective terrain—embodied by an iconic World Map of states that is presumably atheoretical and transhistorical. I argue this is a form of “misplaced concreteness,” which constrains international legal thought as it confronts increasingly fluid and non-contiguous patterns of global ordering that have become difficult to visualize via the reigning cartographic imaginary. Further, it ignores how “the Global” was constructed by multiple and intersecting types of power, which together manifested demarcations, borders, territories and states as proclaimed mimetic reflections of planetary reality. As contemporary challenges—ranging from e.g. climate change to cyber governance—create trans-territorial or planetary scales of consequence, time is ripe to unfold international legal theory beyond the legacy of a priori conceptualization. Accordingly, the special issue encourages bottom-up, practice-oriented approaches, inviting international lawyers to explore how global spatiality and temporality are actively (re)produced across diverse legal contexts—from mobility regimes and global value chains to counterterrorism forums and planetary systems. Rather than treating “the Global” as a fixed totality or singular map, this special issue reframes it as a historically engineered concept, shaped by ongoing practices of geo-political, geo-economic and legal world-making.
While geological and paleoanthropological studies at Laetoli have focused on the relatively fossiliferous Ndolanya and Laetolil beds, Laetoli’s younger Naibadad and Olpiro beds provide an important record of Pleistocene volcanism, tectonics, and landscape evolution in northern Tanzania. This study documents the mineralogical and geochemical compositions of their tephra using EPMA of glass and phenocrysts, and their ages using 40Ar/39Ar geochronology. Naibadad Beds tephra is rhyolitic or trachytic, compositionally distinct from the underlying Ndolanya and overlying Olpiro beds in their mineral assemblages and glass and phenocryst compositions. The Naibadad Beds can be divided into chronostratigraphic clusters as follows: Lower (2.189–2.154 Ma), Middle (2.115–2.104 Ma), and Upper (2.036–2.004 Ma). Most Naibadad Beds tephra could not be compositionally differentiated, although the basal Naibadad Beds tuff is unique in having both trachytic glass and andradite garnet. The uppermost Naibadad Beds tuff at Locality 23 has rhyolitic glass and aenigmatite like Olduvai Gorge’s Naabi ignimbrite and a similar age (2.033 Ma and 2.004 Ma, respectively), although they differ in feldspar and augite composition and are likely not from the same eruption. The lack of direct correlatives between Olduvai and Laetoli, which both derived tephra from Ngorongoro over the same time interval, is likely explained by paleotopography.
This paper examines Britain’s process of electrification following a disruptive stock market boom and bust in 1882. This is done by noting the companies that raise finance on British stock exchanges, the amounts raised, and the returns earned on that money. It also examines the impact of the Lighting Act of 1882, finding that the Act inhibited investment, but with important exceptions. We find the Act was not a barrier to entrepreneurs alert to the possibilities of electrification. However, the limited British electrical investment after the 1882 crash was more heavily and successfully concentrated on supplying electricity to end users than on developing electrical equipment. When electrification began in earnest after 1888, upon the amendment of the 1882 Lighting Act, there existed only a very weak engineering base to support it, leading to slow, expensive, and unimaginative electrification.
This theoretical pearl shows how a graphical, relational, point-free, and calculational approach to linear algebra, known as graphical linear algebra, can be used to reason not only about matrices (and matrix algebra, as can be found in the literature) but also vector spaces and more generally linear relations. Linear algebra is usually seen as the study of vector spaces and linear transformations. However, to reason effectively with subspaces in a point-free and calculational manner, both can be generalized to an unifying concept: linear relations, much like relational algebra. While the semantics is relational, the syntax is graphical and uses string diagrams, 2-dimensional formal diagrams, which represent the linear relations. Most importantly, in a number of cases, the relational semantics allows algorithms and properties to be derived calculationally instead of just verified. Our approach is to proceed primarily by examples which involve finding inverses, switching from an implicit basis to an explicit basis (solving a homogeneous linear system), exploring both the exchange lemma and the Zassenhaus’ algorithm.
This paper introduces a novel ray-tracing methodology for various gradient-index materials, particularly plasmas. The proposed approach utilizes adaptive-step Runge–Kutta integration to compute ray trajectories while incorporating an innovative rasterization step for ray energy deposition. By removing the requirement for rays to terminate at cell interfaces – a limitation inherent in earlier cell-confined approaches – the numerical formulation of ray motion becomes independent of specific domain geometries. This facilitates a unified and concise tracing method compatible with all commonly used curvilinear coordinate systems in laser–plasma simulations, which were previously unsupported or prohibitively complex under cell-confined frameworks. Numerical experiments demonstrate the algorithm’s stability and versatility in capturing diverse ray physics across reduced-dimensional planar, cylindrical and spherical coordinate systems. We anticipate that the rasterization-based approach will pave the way for the development of a generalized ray-tracing toolkit applicable to a broad range of fluid simulations and synthetic optical diagnostics.
P-value functions are modern statistical tools that unify effect estimation and hypothesis testing and can provide alternative point and interval estimates compared to standard meta-analysis methods, using any of the many p-value combination procedures available (Xie et al., 2011, JASA). We provide a systematic comparison of different combination procedures, both from a theoretical perspective and through simulation. We show that many prominent p-value combination methods (e.g. Fisher’s method) are not invariant to the orientation of the underlying one-sided p-values. Only Edgington’s method, a lesser-known combination method based on the sum of p-values, is orientation-invariant and still provides confidence intervals not restricted to be symmetric around the point estimate. Adjustments for heterogeneity can also be made and results from a simulation study indicate that Edgington’s method can compete with more standard meta-analytic methods.
There is considerable data suggesting that the gut microbiota (GM) contributes to health and regulates host immunity and influences brain function, findings with implications for neurodegenerative diseases, such as Alzheimer’s Disease (AD).
In the present study, using three non-fat diets with different ratios of unsaturated ω-6/ω-3 fatty acids (FAs)(high or low), we analyzed how minor differences in diet can affect the microbiota of amyloid precursor protein/Presenilin 1 transgenic (APP/PS1 [TG]) mice, a mice model of AD, next, we studied how the levels of sex hormones may affect the GM. The data obtained show that sex hormones in males fed our standard diet (S) modified alpha and beta diversity, whereas no differences were observed in TG mice compared with wild-type mice. Moreover, there were significant differences in both alpha or beta diversity in mice fed with an H or L diet compared with an S diet.
In conclusion, our data indicate that the levels of sex hormones or differences in the ω-6/ω-3 FA ratio alter the GM more than expected. Thus, it is tantalizing to propose that low levels of ω-3 FAs in APP/PS1 mice fed an “H” diet may be responsible for modifying some bacterial genera, exacerbating the basal neuropathology in this AD model.
We evaluated the physiological condition of the Pygoscelis penguins at Isla 25 de Mayo/King George Island (Antarctica Peninsula). Samples were collected from adults and chicks of Adélie (Pygoscelis adeliae, n = 20 each), gentoo (Pygoscelis papua, n = 20 chicks and n = 24 adults) and chinstrap penguins (Pygoscelis antarcticus, n = 18 each). We analysed haematological and biochemical parameters as indicators of health, immune response and nutrition. Gentoo penguin chicks exhibited higher haematocrits, indicating development linked to erythropoiesis and reticulocyte release from bone marrow or signalling dehydration related to fasting periods in chicks. Adélie penguins had increased total leukocyte counts, basophils and eosinophils, whereas gentoo penguins showed elevated heterophils and decreased lymphocytes, resulting in a higher heterophil/lymphocyte ratio stress index, possibly due to the impact of human activities. Chinstrap penguins from a remote area exhibited the lowest heterophil/lymphocyte ratio values. Adélie penguins showed more erythrocytic nuclear abnormalities, indicating sensitivity to environmental deterioration due to human impacts. The biochemical results were less consistent; Adélie penguins had higher cholesterol, whereas gentoo penguins had elevated triglycerides. Gentoo penguins showed dietary adaptability based on prey availability in this area. Our findings highlight the vulnerability of Adélie penguins and contribute to a 20 year physiological monitoring dataset for Antarctic penguins, which will aid future comparative studies.
The numerous ephemeral glacial meltwater streams that flow during the summer in the McMurdo Dry Valleys of South Victoria Land, Antarctica, provide habitats for microbial mats. One of the common mat types is composed of Chlorophyta (colloquially known as a ‘green mat’ due to its colour). While the presence of these mats is regularly monitored, their taxonomic makeup is still under investigation. Using 18S rRNA gene sequencing, the composition of the chlorophyte-dense mats from between rocks and in the main channel from several streams across two valleys was examined. Samples were maintained in native stream water, and select samples from representative locations were transferred to Bristol Medium. The appearance of other eukaryotic species - diatoms and tardigrades - in these green mats completed this integrated study. The results show that the relative abundance of Chlorophyta was significantly increased with the introduction of inorganic nitrogen from Bristol Medium. Chlorophyte taxa in the Hazenia and Pleurastrum genera dominated the samples across both sample types (rock or exposed) and treatments (Antarctic water or Bristol Medium). Furthermore, a reduction in overall sample diversity was observed in samples in Bristol Medium, suggesting preferential nitrogen utilization by these chlorophytes.