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Previous research has demonstrated the positive impact of early remission on disease trajectory for patients with major depressive disorder. However, there is a paucity of literature assessing the response trajectory for patients with treatment resistant depression (TRD). These analyses investigated patient outcome trajectories to Week 32, including the relationship between short- and long-term outcomes with esketamine nasal spray (ESK-NS) treatment and symptom resolution.
Methods
ESCAPE-TRD (NCT04338321), a randomized, open-label, phase IIIb study, evaluated the efficacy and safety of ESK-NS versus quetiapine extended release (QTP-XR) in patients with TRD. Rater-blinded Montgomery-Åsberg Depression Rating Scale (MADRS) total score was used to assess depressive symptoms and the trajectory of patient responses to Week 32. For ESK-NS versus QTP-XR, time to symptom resolution across MADRS items was evaluated using Kaplan–Meier analyses.
Results
Of 676 patients, 336 and 340 were randomized to ESK-NS and QTP-XR, respectively. Most ESK-NS-treated patients achieved continuously improved outcomes to Week 32; early response was associated with better long-term outcomes. Among patients who achieved Week 4 response, 89.6% achieved remission at any point from Week 4 to 32; 78.3% of Week 8 responders achieved remission at any point from Week 8 to 32. Greater and earlier symptom resolution was observed with ESK-NS versus QTP-XR across most MADRS items.
Conclusions
Most ESK-NS-treated patients with TRD showed continuous improvements over time, with short-term response associated with better long-term outcomes. Long-term improvements were observed even among partial/minimal early responders, reinforcing the value of longer treatment. ESK-NS had a positive impact across the full spectrum of MADRS-assessed symptoms.
There is growing focus on community-engaged research (CEnR) in the clinical and translational sciences, supportive policies, environments, and processes within academic medical centers. The purpose of this evaluation was to gather academic and community member perspectives on key actionable strategies for supporting CEnR in an academic medical center.
Materials and Methods:
We used a sequential mixed method design by first conducting qualitative in-depth interviews with academic leaders, investigators, and staff (total, n = 54) and focus group discussions with community members (n = 33). Themes from these qualitative data informed the adaptation of an institutional survey that gathered perspectives from a broader group of academic and community members affiliated with the institution (n = 85). Both qualitative and quantitative data were integrated to inform actionable strategies.
Results:
Survey findings revealed that the institution was perceived as committed to health equity and CEnR, but institutional respondents expressed more concerns than community members about instrumental support of the work. Interviews and focus groups highlighted the opportunity to better align research efforts with community needs through more robust CEnR infrastructure and through interface with the clinical practice to promote patient access. Academic and community members emphasized the need for authentic, sustained engagement beyond federal mandates, including financial investment, capacity-building, and fostering trust. Leaders acknowledged structural challenges, siloed efforts, and the necessity for stronger coordination to increase integration of community engagement into the institutional mission.
Conclusion:
Findings suggest that aligning academic leaders, researchers, staff perspectives, and community members is essential to support and promote CEnR at an institutional level.
This study aims to investigate the key characteristics of a device to support patients with hearing impairments in utilising deep inspiration breath-hold (DIBH) radiation therapy (RT).
Method:
A qualitative approach was adopted. Semi-structured interviews were conducted both online and in person with 11 participants, including key stakeholders from a range of backgrounds: radiation oncologists, radiation therapists, medical physicists, RT service managers, industry vendors, and deaf service users. Data were analysed using thematic analysis, following the six-step approach outlined by Braun and Clarke.
Results:
Participants’ attitudes towards a device were explored across four key themes:
• Device characteristics
• Shape and size
• Interference with treatment
• Associated challenges
Thematic analysis identified several unifying themes, including the importance of co-designing a device incorporating both vibrational and visual elements. Overall, participants expressed a preference for a small and wireless device.
Conclusion:
This study identified potential characteristics for a device to support patients with hearing impairments in accessing DIBH during their radiation therapy treatment. A device incorporating both visual and vibrational elements may be optimal for addressing the diverse needs of patients in this cohort.
While contemporary historiography has comprehensively surveyed the doctrinal and disciplinary dimensions of sacramental penance in early modern Catholicism, the material culture of confessionals has received comparatively little attention. Focusing on the administration and regulation of confessional booths in the diocese of Verona, Northeastern Italy, during the late eighteenth century, this article argues that the administration of confessionals constituted a crucial intersection between sacred materiality and ecclesiastical governance. Through close examination of synodal constitutions, reports of pastoral visitations, and episcopal correspondence concerning the relocation, renovation, and installation of confessionals, it reconstructs the composite yet hitherto understudied social and cultural networks surrounding these objects. Besides helping us to better understand the vital role of sacred materiality in the experience and practice of early modern Catholicism, the article shows how the administration of confessionals emerged as a site of negotiation among diocesan authorities, parish clergy, and lay communities, revealing how the management of religious infrastructure served as a decisive interface between local pastoral practice and the expanding bureaucratic structures of eighteenth-century Catholic governance.
This article examines the late colonial performances of Adolphe Kisimba, a Congolese producer and performer who toured his show Mu Kongo – Mu Belgique to Belgium in early 1959. Developed under the auspices of the Belgian colonial state, this multimedia spectacular featured sketches, songs, a magic lantern light show, and a satirical “reverse ethnography” film of Belgian culture as narrated by Kisimba. This article traces Kisimba’s trajectory through state-sponsored shows such as Changwe Yetu, Spectacles Populaires, and the idiosyncratic Mu Kongo – Mu Belgique and argues that staged performance, and the international mobility that this art form inherently enables, served as a contested space in which Central Africans sought to redefine colonial hierarchies and through which they envisioned new professional horizons. The overlooked histories of Kisimba and late colonial African artists like him, this article suggests, offer new insights into African cultural negotiations and global outlooks before independence.
The nonlinear dynamics of equatorial shallow-water waves is examined both theoretically and numerically. While unidirectional Kelvin waves are non-dispersive and can evolve into shocks, they also excite Poincaré waves which are dispersive. This dispersion significantly impacts the dynamics of the shock. A reduced model has been developed to describe the behaviours of the Kelvin wave and the first Poincaré wave, where the dispersive term appears in a form similar to that in the Ostrovsky equation. The findings indicate that a sharp spike forms in the profile of the first Poincaré wave, resulting in an overshoot of the shock. Theoretical predictions are validated through numerical simulations of the primitive equations.
Stable carbon and oxygen isotopes in carbonate nodules were controlled by the type of vegetation (C3 or C4) and soil temperature, respectively. These signatures can reflect the paleoclimatic conditions during the formation of the carbonate nodules. Carbonate nodules were sampled along a soil chronosequence in southwestern Taiwan, representing different ages of shoreline changes associated with phases of marine transgression and regression. The stable carbon and oxygen isotopes in carbonate nodules were analyzed. The ages of the carbonate nodules were determined by radiocarbon (14C) dating. The climofunctions of mean annual precipitation and temperature were calculated to interpret the climatic conditions. The carbonate nodules were relictic pedofeatures that formed episodically under favorable pedogenic conditions between 4063 and 690 years before present (years BP). The δ13C values indicated a mixed vegetation of C3 and C4 plants, with a predominance of C4 plants (68.0 to 98%). The mean annual temperature estimated by the climofunction of δ18O value (12.3 to 14 °C) was lower than the present (24.7 °C). The mean annual precipitation (1036 to 1342 mm yr–1) calculated by the geochemical climofunction was lower than the present (1829 mm yr–1). The climate was drier and cooler during this period, and this may be due to a weaker East Asian Summer Monsoon, which favored calcification in the soils. The climatic conditions, as interpreted by the stable carbon and oxygen isotopes of carbonate nodules, were consistent with the calcification process.
Patient transfers provide a critical mechanism for enhancing care capacity and distributing patient load across hospitals and communities. Yet, during disasters and surge events, decisions about where to send patients are often made by Medical Operations Coordination Centers and similar centralized regional coordination bodies, with limited visibility into how transfers are unfolding across the broader hospital system. This study proposes a spatial-network framework, informed by a typology of patient transfers, that represents interhospital transfers as patient flows across a geographic network of hospitals. The framework provides tools to identify and interpret transfer patterns that coordination bodies need to enhance situational awareness and make timely, informed decisions at the local, regional, and state levels. Using inpatient discharge data from a Florida health agency, this study further demonstrates the framework’s applicability during a disaster and shows how administrative health data can be transformed into spatial networks that support interhospital transfer coordination decision-making.
High-resolution large eddy simulations are conducted of locally forced, shear-free turbulence in the presence of an initially sharp density interface. The simulations are reminiscent of oscillating grid turbulence experiments used to isolate the effect of turbulent diffusion and entrainment from background shear. By simulating such a flow we avoid common challenges of the experiments such as secondary-flow contamination due to sidewall effects and the inevitable interaction of the stratifying agent and forcing region. To address the latter concern, we add a heating term (potential energy sink) to the governing equations in the forcing layer, thereby preventing a heat flux through the source region. This modification sets up a continuous stratification in the mixed layer that is often assumed to be negligible in experiments. Despite this difference, we are able to make meaningful comparisons in terms of the overall entrainment rate, which varies as a power law with a turbulent Richardson number. Two exponents, $-2$ and $-1$, are measured depending on the definition of the Richardson number and entrainment rate used. The definition leading to $-1$ is consistent with most experiments, and we argue it is the superior choice if one is able to measure the relevant quantities. We also verify the self-similar scaling of turbulence velocity and length scales in the homogeneous fluid and propose ‘inner’ and ‘outer’ scalings for the stratified cases based on a local Froude number. The detailed scaling results are useful for turbulence model validation.
Entomopathogenic nematodes (EPNs) from the genera Steinernema and Heterorhabditis are potent biocontrol agents. They kill insects through a unique symbiosis with pathogenic bacteria (Xenorhabdus or Photorhabdus), making them ideal for integrated pest management due to their broad host range and environmental safety. Despite high species diversity, genomic resources for these nematodes remain limited. The aim of this study was to characterise the nuclear and mitochondrial genomes of a newly described species, S. tarimense, and a putative novel Heterorhabditis species (strain XJ-55), both obtained from Xinjiang, China. A comprehensive genomic annotation and analysis were conducted to investigate the evolutionary origins of insect parasitism and the molecular adaptation mechanisms involved in host–parasite interactions. Through Illumina sequencing and de novo assembly, we obtained fragmented yet biologically informative genomes for both species. The assembly of S. tarimense reached a BUSCO completeness of 84.06% with an estimated genome size of 84.27 Mb, while that of Heterorhabditis sp. XJ-55 achieved 92.28% completeness with an estimated size of 75.11 Mb. Functional annotation revealed conserved metabolic profiles between the two species, with the Metabolism category being the most abundant. Mitochondrial genomes were successfully reconstructed using MitoZ and NOVOPlasty, resulting in a complete mitogenome of S. tarimense (13,836 bp) and a partial mitogenome of Heterorhabditis sp. XJ-55 (16,865 bp). Comparative mitogenomic analysis highlighted characteristic features such as pronounced A+T bias and distinct codon usage patterns, providing new evolutionary insights into these genera. These genomic resources establish a foundation for future comparative studies and functional investigations, with promising implications for enhancing the biological control efficacy of EPNs in sustainable agricultural systems.
An estimated 5% of cases of first-episode psychosis are due to rare and sometimes reversible causes that can be identified through diagnostic investigations that are currently less common in psychiatry, e.g. lumbar puncture, specialised brain imaging and genetic testing. The current clinical practice of the use of such technologies, however, raises several challenging ethical questions. Drawing on our multidisciplinary perspective spanning psychiatry, neurology, philosophy, neuroscience, sociology and medical ethics from three countries, we identify emerging ethical issues in the diagnosis of rare causes of psychosis. We group challenges thus: (a) diagnostic justice, (b) moral responsibility and (c) unintended consequences of diagnostic work-up. Justice challenges surrounded the role of (a) ‘luck’, (b) social capital and (c) prior psychiatric diagnoses in determining access to work-up. Moral responsibility challenges surround the extent to which (a) clinicians are expected to know the red flags and work-up for rare or ultra-rare causes; and (b) those running health systems should enable knowledgeable clinicians to provide the requisite work-up. Challenges related to unintended consequences include the risk of pursuing work-up of rare causes to reinforce (a) psychiatric exceptionalism and (b) paternalistic decision-making that doesn’t allow space for patient preferences. Finally, we reflect on unresolved issues and future directions.
This article examines the conditions under which policy learning occurs, distinguishing between instrumental learning (evidence-based, problem-solving oriented) and political learning (strategic, shaped by institutional position and incentives). Drawing on three cases presented by Claudio Radaelli – examining bureaucrats, politicians, and experts – the paper shows that much of what occurs in policy practice is best understood as political learning: actors acquire and deploy knowledge strategically, filtered through professional hierarchies, electoral pressures, and reputational concerns. While the literature has long recognised these dynamics, the paper argues that existing accounts of political learning understate its relational and contextual character. Political learning emerges through positioned interactions within institutional and epistemic communities, rather than from individual strategic calculation alone, and from alignment with shifting background political conditions that determine what knowledge becomes actionable. Recognising this relational dimension has implications for institutional design aimed at fostering democratic accountability and integrating expertise more effectively into policy making.
Tropheryma whipplei was identified by plasma microbial cell-free DNA sequencing within 4 days in severe culture-negative endocarditis after antibiotics had already been started. The result supported earlier diagnostic clarification and antimicrobial de-escalation before valve pathology was available, illustrating a practical diagnostic-stewardship role for noninvasive sequencing in high-acuity endocarditis.
This Article explores future fact-finding as a distinct subject of legal research. Usually, legal decision makers, such as judges, decide cases based on past or present facts. However, sometimes, legal norms oblige them to engage in future assessments. The Article argues that future fact-finding is fundamentally different from past or present fact-finding and should be treated as a separate legal phenomenon. It conceptualizes this practice in a legal context and sketches an initial theoretical framework for thinking about and engaging in future fact-finding. To do this, the Article draws on philosophical (epistemological) insights and applies a classical doctrinal method by examining positive law, case law, and doctrine.
This article examines the influential yet contested legacy of Mohammad-Karim Pirnia (1920–97), arguably the most influential figure in the historiography of Iranian architecture over the past six decades. At a time when Western scholarship dominated the field, Pirnia proposed a novel stylistic framework as an alternative to dynastic periodization, identifying six culturally grounded architectural styles, including the Pārti and Esfahāni. He also formulated five principles, such as mardomvāri (human orientation) and darungarāi (inwardness), as the shared spirit of Iranian architecture throughout history. Rather than repeating familiar critiques of Pirnia’s nationalist and regionally selective narrative, this article examines his methodology, arguing that his principles often functioned as normative ideals shaped by modernist concerns rather than empirical historical analysis. Nonetheless, it acknowledges Pirnia’s contribution to the introduction of indigenous terminology and greater attention to craft and construction techniques in architectural historiography.
State legislative turnover is one of the most commonly included measures in state and legislative politics. Yet, few states count legislative turnover or maintain records of internal shifts and those that do often have differences in how these records are maintained. To help resolve these differences we introduce SEAT, State Exits & Annual Turnover, a new dataset tracking legislative turnover in all 50 states spanning 30 years. In brief, we review the importance of turnover as a measure and offer insight into state legislative resources. In doing so, we illustrate the breadth of the data, demonstrate its usefulness, and offer a brief replication-extension. Focusing on annual turnover rates, we find numerous discrepancies with existing measures and state records. This release offers a more up to date understanding of turnover and its variation, as well as an inadvertent call for better records and measurements.
We introduce a slice-based quaternionic analog of wavelet sets in the right- quaternionic Hilbert space $L^{2}(\mathbb {R}^{d},\mathbb {H})$. Using a slice-quaternionic Fourier transform, we characterize boundedness and Parseval tightness of affine systems generated by $\widehat {\psi }=(2\pi )^{-d/2}\chi _{E}q$ via translation and dilation multiplicity conditions on E. These results extend the classical frame wavelet-set theory of Dai et al. (2003, J. Comput. Appl. Math. 155, 69–82) to the quaternionic setting under a natural slice-phase restriction. Several dyadic, directional, and multiwavelet examples illustrate the framework and provide the first systematic construction of quaternionic wavelet sets.