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Sativex (nabiximols) for the treatment of Agitation & Aggression in Alzheimer’s dementia in UK nursing homes: a randomised, double-blind, placebo-controlled feasibility trial
No full textBackground
Alzheimer’s Disease (ad) patients often experience clinically significant agitation, leading to distress, increased healthcare costs and earlier institutionalisation. Current treatments have limited efficacy and significant side effects. Cannabinoid-based therapies, such as the nabiximols oral spray (Sativex®; 1:1 delta-9-tetrahydrocannabinol and cannabidiol), offer potential alternatives. We aimed to explore the feasibility and safety of nabiximols as a potential treatment for agitation in ad.
Methods
The ‘Sativex® for Agitation & Aggression in Alzheimer’s Dementia’ (STAND) trial was a randomised, double-blind, placebo-controlled, feasibility study conducted in UK care homes. Participants with probable ad and predefined clinically significant agitation were randomised to receive placebo or nabiximols for 4 weeks on an up-titrated schedule, followed by a 4-week observation period. To be considered feasible, we prespecified the following thresholds that needed to be met: randomising 60 participants within 12 months, achieving a ≥ 75% follow-up rate at 4 weeks, maintaining ≥80% adherence to allocation and estimating a minimum effect size (Cohen’s d ≥ 0.3) on the Cohen–Mansfield Agitation Inventory. This trial is registered with ISRCTN 7163562.
Findings
Between October 2021 and June 2022, 53 candidates were assessed; 29 met eligibility criteria and were randomised. No participants withdrew, and adherence was high (100%) and was generally feasible to deliver. The intervention was well tolerated (0 adverse reactions), with no safety concerns reported.
Interpretation
Despite significant COVID-19 pandemic related challenges, administering nabiximols through oral mucosa to advanced ad patients with agitation demonstrated feasibility and safety. These findings support a larger confirmatory efficacy trial to evaluate the potential therapeutic efficacy of nabiximols for agitation in ad
Why the growth of arboviral diseases necessitates a new generation of global risk maps and future projections
No full textGlobal risk maps are an important tool for assessing the global threat of mosquito and tick-transmitted arboviral diseases. Public health officials increasingly rely on risk maps to understand the drivers of transmission, forecast spread, identify gaps in surveillance, estimate disease burden, and target and evaluate the impact of interventions. Here, we describe how current approaches to mapping arboviral diseases have become unnecessarily siloed, ignoring the strengths and weaknesses of different data types and methods. This places limits on data and model output comparability, uncertainty estimation and generalisation that limit the answers they can provide to some of the most pressing questions in arbovirus control. We argue for a new generation of risk mapping models that jointly infer risk from multiple data types. We outline how this can be achieved conceptually and show how this new framework creates opportunities to better integrate epidemiological understanding and uncertainty quantification. We advocate for more co-development of risk maps among modellers and end-users to better enable risk maps to inform public health decisions. Prospective validation of risk maps for specific applications can inform further targeted data collection and subsequent model refinement in an iterative manner. If the expanding use of arbovirus risk maps for control is to continue, methods must develop and adapt to changing questions, interventions and data availability
Overlooked influence of phosphate on the performance of a dual membrane process with coagulation pretreatment
No full textThe coagulation-ultrafiltration-nanofiltration (CUF-NF) treatment system is a promising approach for water treatment. However, the effects of phosphate on this system remain inadequately understood. In this study bench scale tests were conducted with both aluminium and iron salts using jar testing and membrane filtration, and a range of phosphate doses. Results in this study reveal that, in the CUF treatment stages, phosphate inhibits floc formation and reduces organic matter removal efficiency by competing for “active sites” and increasing the negative surface charge of flocs. Specifically, the flocculation index values decreased by 56 % for Fe³⁺ and 37 % for Al³⁺ as phosphate concentrations increased from 0 to 0.2 mM, leading to a reduction in dissolved organic carbon (DOC) removal from 34.4 % to 14 % due to phosphate interference. In contrast, the quality of NF effluent improved substantially as phosphate concentrations increased, with the NF reaching a maximum of 20.2 % DOC removal efficiency. At low phosphate concentrations (<0.05 mM), NF flux showed minimal change; however, at higher concentrations, a notable decline in NF flux was observed. Additionally, phosphate presence significantly reduced the formation potentials of trihalomethanes (THMFP) and haloacetic acids (HAAFP) in the NF effluent by over 80 % at 0.2 mM phosphate. This reduction may be attributed to the enhanced ability of the NF membrane to intercept low molecular weight organics, mainly due to the presence of macromolecules that CUF failed to remove. Furthermore, the presence of phosphate is thought to increase the electronegativity and hydrophilicity of the fouling layer on the NF surface, which in turn further enhances the rejection of negatively charged dissolved organic matter (DOM).This study provides a mechanistic understanding of how phosphate influences coagulation, floc formation, DOM removal, and membrane fouling within the CUF-NF treatment system. The findings offer valuable insights for optimizing the treatment of phosphate-containing raw waters using dual membrane processes with coagulation pretreatment in practical applications
Developing an inclusivity audit for higher education
No full textThe delivery of inclusive education and the provision of content that is representative of a diverse student body is a key strategic aim of many higher education institutions. However, while there may be many checklists, design support documents, and benchmarking statements that suggest inclusive outputs for education practical options for updating existing content are rarely discussed. This paper offers an approach, based on the theories of inclusive education and learning design, to audit existing materials. This framework was developed as a collaboration between staff partners from a range of backgrounds and student interns to produce an output that is both pedagogically sound but relevant to, and informed by, student needs. This project does not seek to provide a score or make judgements, but to share good practice and find areas where targeted intervention could be made without the need for full scale curriculum review or a full redesign of teaching
Coherent domains and improved lower bounds for the maximum size of Condorcet domains
No full textIn this paper, we study Condorcet domains, sets of linear orders from which majority ranking produces a linear order. We introduce a new class of Condorcet domains, called coherent domains, which is natural from both a voting theoretic and combinatorial perspective. After studying the properties of these domains we introduce set-alternating schemes. This is a method for constructing well-behaved coherent domains. Using this we show that, for sufficiently large numbers of alternatives n, there are coherent domains of size more than 2.1973n. This improves the best existing asymptotic lower bounds for the size of the largest general Condorcet domains
Evaluating the effects of thermal processing on nucleosynthetic zinc isotope variations: insights from carbonaceous chondrites leachates
No full textVariations in the nucleosynthetic isotope compositions of meteorites have been suggested to result from variable destruction of some presolar grains through thermal processing. This mechanism has furthermore been linked to volatile depletion in chondritic meteorites. As a moderately volatile element with variable nucleosynthetic isotope compositions, Zn potentially records both processes. Here, we present the nucleosynthetic Zn isotope compositions of leachates that target distinct mineral phases from four carbonaceous chondrites (CCs). The isotopic similarities between some leaching steps imply that different phases were partially homogenized, obscuring the original hosts of the neutron-rich (NR) Zn component that characterizes CCs. However, some leachates of the most primitive sample, Murchison CM2, display distinct Zn isotope compositions. The results reveal that the NR Zn was possibly hosted in silicate or oxide grains, which are similar or identical to the carriers of the bulk of the Zn. Multiple scenarios that simulate preferential Zn loss from such phases were modelled and compared to estimated compositions of thermally processed components in chondrites. The modelling suggests that variable extents of Zn depletion cannot account for the observed variations in nucleosynthetic Zn isotope compositions, implying that these characteristics are decoupled. Instead, distinct isotope compositions are required for the different Zn carriers depending on the chondrite group. The results thus suggest that thermal processing alone is not responsible for the observed nucleosynthetic Zn isotope variations. Rather, they most likely reflect temporal or spatial changes in the composition of the molecular cloud as the protoplanetary disk evolved, in line with other studies
Tetramethylrhodamine self-quenching is a probe of conformational change on the scale of 15–25 Å
No full textTetramethylrhodamine (TMR) is a fluorescent dye whose self-quenching has been used as a probe of multiple biological phenomena. We determine the distance-dependence of self-quenching and place bounds on the timescale of TMR dissociation. Our results validate fluorescence self-quenching as an alternative to FRET and enable future assays to be designed with confidence
Efficient and inefficient hydrodynamic escape of exo-satellite atmospheres driven by irradiation from their young giant planets
No full textThe bolometric radiation from a central body is potentially a powerful driver of atmospheric escape from planets or satellites. When heated above their equilibrium temperatures those satellites, due to their low surface gravity, are be prone to significant atmospheric erosion. Such high temperatures can be reached through a known mechanism: a large ratio of the irradiation to re-radiation opacities of the atmospheric species. We investigate this mechanism for irradiating black-bodies of sub-stellar temperatures and find that specific molecules exist, such as and , which develop temperature inversions under the irradiation of young post-formation giant planets. These non-isothermal temperature profiles lead to escape rates that can significantly exceed isothermal Parker-model escape rates evaluated at the satellite’s equilibrium temperature. Our results indicate that exo-satellites can lose most of their atmospheric mass through this mechanism if the cooling of the exo-satellite’s interior is not too rapid. In all scenarios, we find a hierarchical ordering of escape rates of atmospheric species due to thermal decoupling in the upper atmosphere. This thermal decoupling leads to a natural depletion of and retention of in our models. We find that giant planets with masses above 2, for cold starts and above 1 in hot start scenarios are able to remove the majority of a Titan analogue’s atmosphere. Hence, finding and characterizing exomoon atmospheres in hypothetical future surveys can constrain the post-formation cooling behaviour of giant planets
Context-contingent privacy concerns and exploration of the privacy paradox in the age of ai, augmented reality, big data, and the internet of things: systematic review
No full textBackground: Despite extensive research into technology users’ privacy concerns, a critical gap remains in understanding why individuals adopt different standards for data protection across contexts. The rise of advanced technologies such as the Internet of Things (IoT), artificial intelligence (AI), augmented reality (AR), and big data has created rapidly evolving and complex privacy landscapes. However, privacy is often treated as a static construct, failing to reflect the fluid, context-dependent nature of user concerns. This oversimplification has led to fragmented research, inconsistent findings, and limited capacity to address the nuanced challenges posed by these technologies. Understanding these dynamics is especially crucial in fields such as digital health and informatics, where sensitive data and user trust are central to adoption and ethical innovation.
Objective: This study synthesized existing research on privacy behaviors in emerging technologies, focusing on IoT, AI, AR, and big data. Its primary objectives were to identify the psychological antecedents, outcomes, and theoretical frameworks explaining privacy behavior, and to assess whether insights from traditional online privacy literature, such as e-commerce and social networking, apply to these advanced technologies. It also advocates a context-dependent approach to understanding privacy.
Methods: A systematic review of 179 studies synthesized psychological antecedents, outcomes, and theoretical frameworks related to privacy behaviors in emerging technologies. Following established guidelines and using leading research databases such as ScienceDirect (Elsevier), SAGE, and EBSCO, studies were screened for relevance to privacy behaviors, focus on emerging technologies, and empirical grounding. Methodological details were analyzed to assess the applicability of traditional privacy findings from e-commerce and social networking to today’s advanced technologies.
Results: The systematic review revealed key gaps in the privacy literature on emerging technologies, such as IoT, AI, AR, and big data. Contextual factors, such as data sensitivity, recipient transparency, and transmission principles, were often overlooked, despite their critical role in shaping privacy concerns and behaviors. The findings also showed that theories developed for traditional technologies often fall short in addressing the complexities of modern contexts. By synthesizing psychological antecedents, behavioral outcomes, and theoretical frameworks, this study underscores the need for a context-contingent approach to privacy research.
Conclusions: This study advances understanding of user privacy by emphasizing the critical role of context in data sharing, particularly amid ubiquitous and emerging health technologies. The findings challenge static views of privacy and highlight the need for tailored frameworks that reflect dynamic, context-dependent behaviors. Practical implications include guiding health care providers, policy makers, and technology developers toward context-sensitive strategies that build trust, enhance data protection, and support ethical digital health innovation.
Trial Registration: PROSPERO CRD420251037954; https://www.crd.york.ac.uk/PROSPERO/view/CRD42025103795
Self‐perceptions of aging predict recovery after a fall: prospective analysis from the english longitudinal study of aging
No full textObjective
To investigate how mindsets around aging at baseline affect physical recovery following a subsequent fall.
Design
Longitudinal observational study.
Setting
English Longitudinal Study of Aging (ELSA).
Participants
We analyzed data for 694 individuals who had not fallen in the 2 years prior to baseline (Wave 4) but experienced a fall during follow-up (between Waves 4 and 5).
Measurements
Self-perceptions of aging at baseline (Wave 4) and gait speed, activities of daily living (ADL) dependence, and physical (in)activity after a fall at a 2-year follow-up (Wave 5). Multivariable logistic regression analyses were used to determine to what extent aging-related mindset variables as measured at baseline predicted outcome measures at follow-up.
Results
In a fully-adjusted model controlling for confounding baseline factors (including baseline gait speed, ADL dependence and physical inactivity), individuals with positive self-perceptions of aging at baseline had significantly lower odds of slow gait speed (OR = 0.729; 95% CI = 0.627–0.849), ADL dependence (OR = 0.667; 95% CI = 0.561–0.792) and physical inactivity (OR = 0.795; 95% CI = 0.700–0.904) following a fall at a 2-year follow-up.
Conclusions
These findings identify self-perceptions of aging as a strong predictor of physical recovery and disability following a fall, independent of other important factors such as age, gender, and pre-fall physical function. These novel observations advance our understanding of the psychological factors impacting physical recovery from a fall. Future work should explore if targeting such perceptions can directly improve physical recovery and outcomes following a fall