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Motor functional neurological disorder (FND) is a common illness associated with significant functional impairment. There are no effective pharmacotherapies, and despite the early promise of physiotherapy studies, many suffer disabling symptoms in the long term. There is a theoretical rationale for combining psychedelics with physiotherapy; however, the potential benefit of this approach and optimal treatment model remains unexplored. Here, we present the protocol for the first study investigating the tolerability, feasibility, and potential efficacy of two distinct treatment regimens of psilocybin-assisted physiotherapy for refractory motor FND: a moderate dose that incorporates movement tasks during the acute drug effects versus a standard dose alone.
Methods:
Twenty-four participants with refractory motor FND will be randomised in a 1:1 ratio to either (1) psilocybin 15mg, with movement tasks conducted during the acute drug effects; or (2) psilocybin 25mg alone. All participants will receive two sessions of FND-specific physiotherapy pre-dosing, six sessions of physiotherapy post-dosing, and undergo follow-up visits one week and four weeks following their final physiotherapy session. A battery of outcome measures will be completed as scheduled, assessing tolerability, feasibility, motor FND symptom severity, psychiatric and physical symptoms, quality of life, treatment expectations, intensity of the acute drug effects, personality, motor function, force-matching performance, resting-state and task-based brain imaging, and subjective experiences of the study treatment.
Discussion:
These findings will assist the design of an adequately powered randomised controlled trial in this cohort. The findings may also inform the feasibility of psychedelic treatment in related functional and neuropsychiatric disorders.
Plants and animals are, unquestionably, important geomorphic agents. Nonetheless, their key roles in the geomorphic system have only recently been properly appreciated and studied. In fact, the term biogeomorphology was only introduced in 1988, by Professor Heather Viles, as an approach to geomorphology that explicitly considers the role of organisms.
Biogeomorphology focuses on the influence of plants, animals, and microorganisms on landforms and geomorphic processes, and vice versa. This chapter examines how the field of biogeomorphology has expanded since its formal definition in 1988. We will discuss the role of plants in geomorphology, usually simply referred to as phytogeomorphology, as well as the role of animals, whose role in landscape evolution is captured by the term zoogeomorphology. Despite the emphasis that researchers have placed on the role of macroorganisms in geomorphology, some more recent, pioneering work has also shown that microorganisms are also important.
Tetflupyrolimet is a novel herbicide that inhibits dihydroorotate dehydrogenase (DHODH), interfering with de novo pyrimidine biosynthesis in susceptible plants. While tetflupyrolimet efficacy for preemergence grassy weed control in rice (Oryza sativa L.) and managed turfgrass systems has been explored, there is minimal information regarding effects that edaphic factors may have on activity, particularly those pertaining to soil hydraulics. Dose–response experiments revealed 6- to 8-fold differences in tetflupyrolimet activity on annual bluegrass (Poa annua L.) due to soil texture, with higher activity reported following applications to sand compared with clay loam. Higher tetflupyrolimet activity in sand could be related to matric potential, as activity following applications to plants growing in sand exceeded that observed on clay loam across a wide range of volumetric water contents (15% to 60%). Once volumetric water content increased to ≥ 80%, no differences in tetflupyrolimet activity were detected between soils, suggesting that post-application irrigation could mitigate potential reductions in efficacy on finer-textured soils when moisture is limited. These findings underscore that soil texture and, consequently, moisture retention affect tetflupyrolimet activity to the extent that application rates could vary based on soil texture in turfgrass systems. Further research exploring a broader range of soil types and field conditions is warranted to refine tetflupyrolimet rate recommendations based on soil type.
Many experiments investigating different decision theories have relied heavily on pairwise choices between lotteries. These are easy to incentivise, but often yield only limited dichotomous information. This paper considers whether respondents’ judgments about their strength of preference (SoP) for one alternative over another can usefully supplement standard choice data. We report extensive evidence that such judgments show sensitivity to variations in question format and parameter values in the directions we should expect, not only within-subject but also between-sample. We illustrate how such judgments can usefully supplement standard pairwise choice data and enrich our understanding of observed behaviour.
The concept of interaction classes (iClasses) for multi-environment trial data was introduced to address the problem of summarising variety performance across environments in the presence of variety by environment interaction (VEI). The approach involves the fitting of a factor analytic linear mixed model (FALMM), with the resultant estimates of factor loadings being used to form groups of environments (iClasses) that discriminate varieties with different patterns of VEI. It is then meaningful to summarise variety performance across environments within iClasses. The iClass methodology was developed with respect to a FALMM in which the genetic effects for different varieties were assumed independent. This was done for pedagogical reasons but it was pointed out that the accuracy of variety selection is greatly enhanced by considering the genetic relatedness of varieties, either via ancestral or genomic information. The focus of the current paper is therefore to extend the iClass approach for FALMMs which incorporate such information. In addition, a measure of stability of variety performance across iClasses is defined. The utility of the approach for variety selection is illustrated using a multi-environment trial dataset from the lentil breeding programme operated by Agriculture Victoria.
To explore the potential of incorporating personally meaningful rituals as a spiritual resource for Western secular palliative care settings. Spiritual care is recognized as critical to palliative care; however, comprehensive interventions are lacking. In postmodern societies, the decline of organized religion has left many people identifying as “no religion” or “spiritual but not religious.” To assess if ritual could provide appropriate and ethical spiritual care for this growing demographic requires comprehensive understanding of the spiritual state and needs of the secular individual in postmodern society, as well as a theoretical understanding of the elements and mechanisms of ritual. The aim of this paper is to provide a comprehensive and theoretically informed exploration of these elements through a critical engagement with heterogeneous literatures.
Methods
A hermeneutic narrative review, inspired by complexity theory, underpinned by a view of understanding of spiritual needs as a complex mind–body phenomenon embedded in sociohistorical context.
Results
This narrative review highlights a fundamental spiritual need in postmodern post-Christian secularism as need for embodied spiritual experience. The historical attrition of ritual in Western culture parallels loss of embodied spiritual experience. Ritual as a mind–body practice can provide an embodied spiritual resource. The origin of ritual is identified as evolutionary adaptive ritualized behaviors universally observed in animals and humans which develop emotional regulation and conceptual cognition. Innate human behaviors of creativity, play, and communication develop ritual. Mechanisms of ritual allow for connection to others as well as to the sacred and transcendent.
Significance of results
Natural and innate behaviors of humans can be used to create rituals for personally meaningful spiritual resources. Understanding the physical properties and mechanisms of ritual making allows anyone to build their own spiritual resources without need of relying on experts or institutionalized programs. This can provide a self-empowering, client-centered intervention for spiritual care.
OBJECTIVES/GOALS: To introduce the new Team Science Community Toolkit, co-created by community and academic partners, and showcase its potential to empower Community Organizations (COs) in achieving equity in community-engaged research (CER). METHODS/STUDY POPULATION: In response to the challenges faced by COs in CER collaborations, qualitative interviews were conducted with CO staff from historically marginalized communities. These interviews informed the development of the Team Science Community Toolkit, a collaborative effort involving a Community Advisory Board (CAB) and Team Science experts from Northwestern University. The toolkit, designed using a community-based participatory research approach, incorporates the Science of Team Science and User-Centered Design principles. Integrated into the NIH-sponsored COALESCE website, it includes templates, checklists, and interactive tools, along with a real-world simulation, to support COs in all stages of the research process. RESULTS/ANTICIPATED RESULTS: Focus groups and usability testing involving external community experts validated the toolkit’s content and usability. Participants expressed enthusiasm and a sense of empowerment, indicating that the toolkit allows them to actively shape research processes and infuse their specific voices and needs into their partnerships. The toolkit is designed to support breaking down barriers like jargon and cultural adaptability to improve accessibility and open conversation. The impact of this Team Science focused toolkit is under evaluation. This presentation will showcase the toolkit, detail its collaborative development, and explore potential applications, ultimately offering a path to more equitable and valuable community-based research. DISCUSSION/SIGNIFICANCE: By providing COs with the resources and knowledge to participate as equal partners in research collaborations, it enhances self-advocacy, transparency, and equity. The toolkit has the potential to utilize Team Science to foster productive communication in community-academic research partnerships.
The potential of artificial intelligence (AI) in water management is widely recognised by research and practice communities alike, with an increasing number of applications showed tackling water supply, stormwater and wastewater management challenges. However, there is a critical knowledge gap in understanding the fundamental role of AI in the development of urban water infrastructure (UWI). This review aimed to provide an analysis of how AI could be aligned to support the future development of UWI systems. Four types of AI analytics – descriptive, diagnostic, predictive and prescriptive – are discussed and linked to the improvement in the performance of UWI systems from three categories: reliability, resilience and sustainability. It is envisioned that AI technology will play a pivotal role in UWI transitioning to the future through underpinning the five development pathways: decentralisation, circular economy, greening, decarbonisation and automation. The barriers in improving AI adoption in the real world are also highlighted from four dimensions: cyber-physical infrastructure, institutional governance, social-economic systems and technological development in wider society. Embedding AI in the development pathways and tackling the barriers can ensure that AI-empowered systems are deployed in an equitable and responsible way to improve the resilience and sustainability of future UWI systems.
Birnbaum (2020) reanalyses the data from Butler and Pogrebna (2018) using his ‘true and error’ test of choice patterns. His results generally support the evidence we presented in that paper. Here we reiterate the reasons for our agnosticism as to the direction any cycles might take, even though the paradox that motivated our study takes a ‘probable winner’ direction. We conclude by returning to the potential significance of predictably intransitive preferences for decision theory generally.
The transitivity axiom is common to nearly all descriptive and normative utility theories of choice under risk. Contrary to both intuition and common assumption, the little-known ’Steinhaus-Trybula paradox’ shows the relation ’stochastically greater than’ will not always be transitive, in contradiction of Weak Stochastic Transitivity. We bespoke-design pairs of lotteries inspired by the paradox, over which individual preferences might cycle. We run an experiment to look for evidence of cycles, and violations of expansion/contraction consistency between choice sets. Even after considering possible stochastic but transitive explanations, we show that cycles can be the modal preference pattern over these simple lotteries, and we find systematic violations of expansion/contraction consistency.
Data from neurocognitive assessments may not be accurate in the context of factors impacting validity, such as disengagement, unmotivated responding, or intentional underperformance. Performance validity tests (PVTs) were developed to address these phenomena and assess underperformance on neurocognitive tests. However, PVTs can be burdensome, rely on cutoff scores that reduce information, do not examine potential variations in task engagement across a battery, and are typically not well-suited to acquisition of large cognitive datasets. Here we describe the development of novel performance validity measures that could address some of these limitations by leveraging psychometric concepts using data embedded within the Penn Computerized Neurocognitive Battery (PennCNB).
Methods:
We first developed these validity measures using simulations of invalid response patterns with parameters drawn from real data. Next, we examined their application in two large, independent samples: 1) children and adolescents from the Philadelphia Neurodevelopmental Cohort (n = 9498); and 2) adult servicemembers from the Marine Resiliency Study-II (n = 1444).
Results:
Our performance validity metrics detected patterns of invalid responding in simulated data, even at subtle levels. Furthermore, a combination of these metrics significantly predicted previously established validity rules for these tests in both developmental and adult datasets. Moreover, most clinical diagnostic groups did not show reduced validity estimates.
Conclusions:
These results provide proof-of-concept evidence for multivariate, data-driven performance validity metrics. These metrics offer a novel method for determining the performance validity for individual neurocognitive tests that is scalable, applicable across different tests, less burdensome, and dimensional. However, more research is needed into their application.
B-type supergiants show enormous potential as resourceful tools to address a wide range of astrophysical questions concerning stellar atmospheres, stellar and galactic evolution and the cosmic distance scale. For the purposes of a comprehensive analysis of these objects we test a hybrid non-LTE approach – line-blanketed model atmospheres computed under the assumptions of local thermodynamic equilibrium (LTE) in combination with non-LTE line-formation calculations. An observational sample of 14 Galactic B-type supergiants with masses below about 30 Mȯ is investigated on the basis of high-resolution Echelle spectra. The results of this analysis – atmospheric and fundamental stellar parameters, the characterisation of the interstellar sightlines to the objects, as well as derived spectroscopic distances and multi-species abundances – are subjected to multiple tests of consistency.
Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.
Aims
The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.
Method
This was a naturalistic study of community patients recommended for clozapine treatment.
Results
Of 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).
Conclusions
These findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.
OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 μg/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 μm thick sagittal sections from each joint, 50 μm apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.
Although baseball can lay claim to be the home of sports economics in North America, association football (soccer) is the subject's primary focus in Europe. Fifteen years after Rottenberg's paper (1956), the first football paper was published on the labour market of the professional game in England (Sloane 1969). Sloane's contribution paved the way for investigations into many aspects of football from an economic perspective. This chapter purposefully aims to address three topics that are important to the economics of association football: (a) competitive balance; (b) empirical studies of attendance demand (spectator turnout); and (c) labour mobility. Notwithstanding that these are stand-alone issues addressed in detail elsewhere, we aim to provide a concise and accessible introduction to these research areas. Our intention is to offer an overview for those unfamiliar with these areas. From the outset it is important to note that the reach of the economics of football far exceeds the topics covered in this chapter. That said, the three branches we focus on here are all part of a developed literature in their own right and have a strong historical basis with solid theoretical and empirical foundations. They are also of universal interest and remain central to the economics of football today. As outlined in Chapter 1
, the need for competitive balance within sport goes to the very heart of sport economics, from where Rottenberg's (1956) examination began. We focus on the “big five” European leagues of England, France, Germany, Italy and Spain. Second, we survey studies that examine the demand for football, focusing on the traditional form of consuming the sport, namely ticket demand (stadium attendance). We collate literature on this topic for studies published over a 45-year period and offer a brief synopsis (biased toward studies published in English), which can serve as a companion to those exploring the literature for the first time. The third and final part of the chapter examines the labour market for footballers since the early 1990s. We consider the internationalization of this market, again in the context of the “big five” leagues (England, France, Germany, Italy and Spain) from 1992 to 2015, and describe a new dataset on the topic.
This chapter reviews five decades of research on reactions to mirrors and self-recognition in nonhuman primates, starting with Gallup’s (1970) pioneering experimental demonstration of self-recognition in chimpanzees and its apparent absence in monkeys. Taking a decade-by-decade approach, developments in the field are presented separately for great apes on the one hand, and all other primates on the other (prosimians, monkeys, and so-called lesser apes), considering both empirical studies and theoretical issues. The literature clearly shows that among nonhuman primates the most compelling evidence for something approaching human-like visual self-recognition is seen only in great apes, despite an impressive range of sometimes highly original procedures employed to study many monkey species. In the past decade, research has been shifting from simple questions about whether great apes can self-recognize (now considered beyond doubt), to addressing possible biological bases for individual and species differences in the strength of self-recognition, analysis of possible adaptive functions of the capacity for self-visualization, and searching for evidence of self-recognition in a range of nonprimate species.
This paper explores the interaction of informal constraints on human behaviour by examining the evolution of English football jerseys. The jersey provides an excellent setting to demonstrate how informal constraints emerge from formal rules and shape human behaviour. Customs, approved norms and habits are all observed in this setting. The commercialisation of football in recent decades has resulted in these informal constraints, in many cases dating back over a century, co-existing with branding, goodwill and identity effects. Combined, these motivate clubs to maintain the status quo. As a result, club colours have remained remarkably resilient within a frequently changing landscape.
An early economic evaluation to inform the translation into clinical practice of a spectroscopic liquid biopsy for the detection of brain cancer. Two specific aims are (1) to update an existing economic model with results from a prospective study of diagnostic accuracy and (2) to explore the potential of brain tumor-type predictions to affect patient outcomes and healthcare costs.
Methods
A cost-effectiveness analysis from a UK NHS perspective of the use of spectroscopic liquid biopsy in primary and secondary care settings, as well as a cost–consequence analysis of the addition of tumor-type predictions was conducted. Decision tree models were constructed to represent simplified diagnostic pathways. Test diagnostic accuracy parameters were based on a prospective validation study. Four price points (GBP 50-200, EUR 57-228) for the test were considered.
Results
In both settings, the use of liquid biopsy produced QALY gains. In primary care, at test costs below GBP 100 (EUR 114), testing was cost saving. At GBP 100 (EUR 114) per test, the ICER was GBP 13,279 (EUR 15,145), whereas at GBP 200 (EUR 228), the ICER was GBP 78,300 (EUR 89,301). In secondary care, the ICER ranged from GBP 11,360 (EUR 12,956) to GBP 43,870 (EUR 50,034) across the range of test costs.
Conclusions
The results demonstrate the potential for the technology to be cost-effective in both primary and secondary care settings. Additional studies of test use in routine primary care practice are needed to resolve the remaining issues of uncertainty—prevalence in this patient population and referral behavior.
The Late Triassic fauna of the Lossiemouth Sandstone Formation (LSF) from the Elgin area, Scotland, has been pivotal in expanding our understanding of Triassic terrestrial tetrapods. Frustratingly, due to their odd preservation, interpretations of the Elgin Triassic specimens have relied on destructive moulding techniques, which only provide incomplete, and potentially distorted, information. Here, we show that micro-computed tomography (μCT) could revitalise the study of this important assemblage. We describe a long-neglected specimen that was originally identified as a pseudosuchian archosaur, Ornithosuchus woodwardi. μCT scans revealed dozens of bones belonging to at least two taxa: a small-bodied pseudosuchian and a specimen of the procolophonid Leptopleuron lacertinum. The pseudosuchian skeleton possesses a combination of characters that are unique to the clade Erpetosuchidae. As a basis for investigating the phylogenetic relationships of this new specimen, we reviewed the anatomy, taxonomy and systematics of other erpetosuchid specimens from the LSF (all previously referred to Erpetosuchus). Unfortunately, due to the differing representation of the skeleton in the available Erpetosuchus specimens, we cannot determine whether the erpetosuchid specimen we describe here belongs to Erpetosuchus granti (to which we show it is closely related) or if it represents a distinct new taxon. Nevertheless, our results shed light on rarely preserved details of erpetosuchid anatomy. Finally, the unanticipated new information extracted from both previously studied and neglected specimens suggests that fossil remains may be much more widely distributed in the Elgin quarries than previously recognised, and that the richness of the LSF might have been underestimated.
To develop a regional antibiogram within the Chicagoland metropolitan area and to compare regional susceptibilities against individual hospitals within the area and national surveillance data.
Design:
Multicenter retrospective analysis of antimicrobial susceptibility data from 2017 and comparison to local institutions and national surveillance data.
Setting and participants:
The analysis included 51 hospitals from the Chicago–Naperville–Elgin Metropolitan Statistical Area within the state of Illinois. Overall, 18 individual collaborator hospitals provided antibiograms for analysis, and data from 33 hospitals were provided in aggregate by the Becton Dickinson Insights Research Database.
Methods:
All available antibiogram data from calendar year 2017 were combined to generate the regional antibiogram. The final Chicagoland antibiogram was then compared internally to collaborators and externally to national surveillance data to assess its applicability and utility.
Results:
In total, 167,394 gram-positive, gram-negative, fungal, and mycobacterial isolates were collated to create a composite regional antibiogram. The regional data represented the local institutions well, with 96% of the collaborating institutions falling within ±2 standard deviations of the regional mean. The regional antibiogram was able to include 4–5-fold more gram-positive and -negative species with ≥30 isolates than the median reported by local institutions. Against national surveillance data, 18.6% of assessed pathogen–antibiotic combinations crossed prespecified clinical thresholds for disparity in susceptibility rates, with notable trends for resistant gram-positive and gram-negative bacteria.
Conclusions:
Developing an accurate, reliable regional antibiogram is feasible, even in one of the largest metropolitan areas in the United States. The biogram is useful in assessing susceptibilities to less commonly encountered organisms and providing clinicians a more accurate representation of local antimicrobial resistance rates compared to national surveillance databases.