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Agreement testing of AMSTAR-PF, a tool for quality appraisal of systematic reviews of prognostic factor studies
Get PDFObjectives: To test the agreement and usability of a novel quality appraisal tool: A MeaSurement Tool to Assess systematic Reviews of Prognostic Factor studies (AMSTAR-PF). Design: Observational study. Participants: 14 appraisers of varied experience levels and backgrounds, including undergraduate, master’s and PhD students, postgraduate researchers, research fellows and clinicians. Study procedure: Eight systematic reviews were rated by all reviewers using AMSTAR-PF. Outcome measures: Planned measures included intrapair and inter-pair agreement using Cohen’s and Fleiss’ kappa, time of use and time to reach consensus. Interrater agreement was an added measure, and Gwet’s agreement coefficient was calculated and presented due to its greater stability across agreement levels. The percentage of intrapair agreements identical or one category apart was also presented. Results: Interrater agreement averaged 0.59 (range 0.21–0.90), inter-pair agreement 0.61 (range 0.24–0.91) and intrapair agreement 0.75 (range 0.45–0.95) across the domains, with agreement for the overall rating 0.46 (95% CI 0.30 to 0.62) for interrater agreement, 0.46 (95% CI 0.17 to 0.74) for inter-pair agreement and 0.68 (range of averages 0.22–1.00) for intrapair agreement. The majority (60.7%) of intrapair ratings were identical, with 94.6% of final ratings either identical or only one category different for the overall appraisal. The time taken to appraise a study with AMSTAR-PF improved with use and averaged around 34 min after the first two appraisals. Conclusions: Despite some variance in agreement for different domains and between different appraisers, the testing results suggest that AMSTAR-PF has clear utility for appraising the quality of systematic reviews of prognostic factor studies
Developing and validating a holistic welfare assessment tool for zoo-housed great apes:Integrating resource-based measures with behavioural ecology insights
Get PDFAssessing the welfare of zoo-housed great apes is essential to ensure high standards of care, maintain zoos’ ethical and educational credibility, and support their conservation roles. However, welfare assessment remains challenging due to the complex cognitive, social, and behavioural needs of great apes and the limitations of existing evaluation methods. Many zoos rely on resource-based measures, which are easy to collect but lack the specificity needed to assess welfare accurately. In this study, we developed and tested a new standardized, evidence-based approach that integrated resource-based data with ecological and behavioural insights. This Ape Welfare Assessment, Resources and Ecology (AWARE) Tool was developed through collaboration with the Great Ape Welfare group (GAWg) and aimed to: (1) collect a holistic suite of resource and husbandry data that measures the constraints on the apes opportunities to express key naturalistic behaviours, (2) contextualize results within species-specific research on wild and captive great ape behavioural ecology and welfare, and (3) extend beyond existing zoo accreditation standards to support zoos aspirations for higher levels of welfare. Using data from zoo-housed chimpanzees, we tested whether this approach enhanced the validity of resource-based welfare assessments. Results demonstrate that the approach strengthens welfare evaluations and provides a more nuanced understanding of captive great ape wellbeing. We also propose a new validation framework for holistic welfare assessment tools such as this, where validating all individual indicators is neither feasible nor informative. Ultimately, we aim for the AWARE Tool to serve as a web-based resource for independent zoo use and formal welfare assessments. Future research will expand its application to gorillas and orangutans. This study represents a major leap towards establishing robust, species-informed and validated welfare assessment methodologies for zoo-housed great apes
Characterization of the Extraction System of Supersonic Gas Curtain-Based Ionization Profile Monitor for FLASH Proton Therapy
Get PDFFLASH radiotherapy requires real-time, non-invasive beam monitoring systems capable of operating under ultra-high dose rate (UHDR) conditions without perturbing the therapeutic beam. In this work, we characterized the extraction system of Supersonic Gas Curtain-based Ionization Profile Monitor (SGC-IPM) for its capabilities as a transverse beam profile and position monitor for FLASH protons. The monitor utilizes a tilted gas curtain intersected by the incident beam, leading to the generation of ions that are extracted through a tailored electrostatic field, and detected using a two stage microchannel plate (MCP) coupled to a phosphor screen and CMOS camera. CST Studio Suite was employed to conduct electrostatic and particle tracking simulations evaluating the ability of the extraction system to measure both beam profile and position. The ion interface, at the interaction region of proton beam and gas curtain, was modeled with realistic proton beam parameters and uniform gas curtain density distributions. The ion trajectory was tracked to evaluate the performance across multiple beam sizes. The simulations suggest that the extraction system can reconstruct transverse beam profiles for different proton beam sizes. Simulations also supported the system’s capability as a beam position monitor within the boundary defined by the beam size, the dimensions of the extraction system, and the height of the gas curtain. Some simulation results were benchmarked against experimental data of 28 MeV proton beam with 70 nA average beam current. This study will further help to optimize the design of the extraction system to facilitate the integration of SGC-IPM in medical accelerators
Interoception in Female Adolescents with Inflammatory Bowel Diseases <i>Versus</i> Restrictive Eating Disorders
Get PDFBackground: Female individuals with inflammatory bowel diseases (IBDs) are more likely to develop restrictive eating disorders (REDs), with both conditions appearing to share common pathophysiological pathways. We conducted a case–control study exploring eating symptomatology and interoceptive profiles in female adolescents with IBDs compared with adolescents diagnosed with REDs, in order to test the hypothesis that the two clinical populations exhibit similar interoceptive characteristics. Methods: We recruited 33 female adolescents with IBDs and 54 controls with REDs matched for age and gender. All participants completed a validated psychometric battery assessing eating disorder features (EDI-3) and interoceptive awareness (MAIA-2). Results: Twenty-seven percent of patients with IBD scored above the cut-off (>70th percentile) on the EDI-3 Eating Disorder Risk Composite (EDRC), showing an eating and interoceptive profile comparable to that of patients with REDs. The two sub-cohorts within the IBD sample differed in the ‘Not-Worrying’ and ‘Trusting’ MAIA-2 subscales, with the IBD cohort at risk of developing an ED reporting lower scores. Conclusions: Our findings indicate comparable interoceptive profiles between adolescents with IBDs who are at risk of developing EDs and patients with a confirmed diagnosis of REDs. This similarity underscores the need to further investigate the shared pathogenic mechanisms underlying these conditions, particularly the role of the gut–brain axis (GBA)
Lessons learned from allergen adsorption on engineered nanomaterials:bridging experimental insights and computational technologies
Get PDFAllergic disease has increased over past decades, coinciding with the use of nanomaterials in medicine, industry, and environmental applications. This trend introduces new opportunities for human exposure to allergen–nanomaterial complexes through different routes like inhalation, ingestion, and dermal exposure. Such interactions have emerged as a determinant influencing immune response. Recent studies reveal that allergen adsorption onto nanomaterial surfaces varies with shape, particle size, surface chemistry, morphology, and agglomeration state. These surface interactions can modify allergen structure, epitope accessibility, and proteolytic stability, thereby reshaping the immune outcomes. Key considerations including dose, exposure route, and kinetics play an important role in determining physiological effects and pathological consequences. This special report provides a comprehensive overview of current research on allergen-nanomaterial interactions, summarizing known mechanisms, structural and immunological consequences, and critically assessing the challenges, gaps, and controversies. Understanding the impact of allergen-nanomaterial interactions on the human immune response demands a cross-disciplinary approach that integrates the complexities in nanotechnology and immunology. Advances in molecular toxicology employing new approach methodologies provide mechanistic insight which can support regulatory science and improve the acceptance of innovative therapeutic strategies in the field of nanomedicine. Allergen-nanomaterial interactions may serve as a model for best practice in this context
Optimising anti-seizure medication timing using a dynamic network model of seizure rhythms
Get PDFEpileptic seizures and interictal discharges exhibit robust circadian and multidien rhythms, yet the interaction between these biological cycles and anti-seizure medication (ASM) pharmacology remains poorly understood. Here, we present a dynamical network model that integrates rhythmic fluctuations in cortical excitability with pharmacokinetic properties of common ASMs to explore how treatment timing influences efficacy. The framework embeds a slow, rhythm-generating process directly within the governing equations, allowing seizure-like dynamics to emerge endogenously. We simulated ASMs with a range of distinct half-lives under single-daily and twice-daily dosing schedules. For the short half-life ASM, efficacy depended strongly on the phase of administration, with doses delivered approximately 6 h before the peak in seizure likelihood achieving up to 20% greater reduction in epileptiform discharges than suboptimal phases. In contrast, phase dependence was minimal for slower half-life drugs due to their slower elimination and flatter concentration profiles. These findings suggest that short half-life ASMs could benefit most from chronotherapeutic timing. Our framework unifies seizure dynamics, biological rhythms, and ASM pharmacology within a single model, offering a mechanistic tool to explore patient-specific optimization of treatment timing. This work establishes a foundation for translating chronotherapy into epilepsy care and provides a conceptual bridge between computational neuroscience and clinical pharmacology
Framework for Developing Resistivity Models to Identify Potential Safety Threats in Embankment Dams and Assessing the use of Bentonite in Repairing Deep Cracks in the Embankments
Get PDFThe structural integrity of embankments is critical for sustainable water resource management, particularly in seismic-prone regions. This study presents a comprehensive framework integrating field inspections, geophysical assessments, and geotechnical interventions to identify and rehabilitate subsurface anomalies in earthfill embankment dams. The Mangla Dam in Pakistan was selected to demonstrate the framework’s practicality. Following the 24 September 2019 earthquake, Sukian Dyke, a major embankment section, was severely damaged with transverse and longitudinal cracks. To address this, a four-phase methodology was developed. First, physical inspections and Ground Penetrating Radar (GPR) surveys determined the extent and geometry of cracks. Second, a bentonite mixture was formulated and used to seal cavities. Third, a post-repair GPR survey confirmed the efficacy of sealing. Finally, an Electrical Resistivity Tomography (ERT) survey evaluated the hydraulic performance of treated zones. Results showed higher electrical resistivity (100–150 Ω·m) in repaired areas, confirming the bentonite’s effectiveness. This research represents Pakistan’s first integrated geophysical–geotechnical investigation of earthfill dams, setting a precedent for safety monitoring and resilience enhancement in seismic regions
Pre-attention
No full textIn the preceding chapters, we have discussed a wide range of attention-related functions and how they may change with age, mild cognitive impairment, and various aetiologies of dementia. Within some of these chapters, automatic processing has been discussed, e.g., the automatic capture of attention by a salient object or sound within the environment, i.e., visual search, or response to a visual or auditory warning or cue. Here we take a more detailed look at the concept of automatic attention, commonly termed ‘pre-attentive processing’ in the research literature.</p
Simulations all the way up! An atheist’s response to the Fine-tuning Argument
Get PDFSo the Fine-tuning Argument goes, because it is so unlikely for the physical constants of the laws of nature to have taken the values that they in fact take, we should significantly raise our credence that God exists. Simulation Arguments argue that our world might be (or, in stronger versions, that it probably is) a mere computer simulation. This paper argues that, in light of a Simulation Argument with a particularly weak conclusion, fine-tuning reasoning instead motivates atheists to believe that we live in a computer simulation
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