Understanding the complexity of living with, and managing, secretions in motor neuron disease/amyotrophic lateral sclerosis (MND/ALS/ALS): protocol for a complex intervention systematic review

Introduction Motor neuron disease/amyotrophic lateral sclerosis (MND/ALS/ALS) is an incurable disease which leads to muscle weakness that worsens over time. MND/ALS is highly heterogeneous in its presentation, with many people experiencing a rapidly progressive trajectory of symptoms. Many people living with MND/ALS (plwMND/ALS) experience a combination of flaccidity and spasticity of the muscles involved in speech, swallowing, breathing and coughing. This makes it challenging to deal with the saliva and mucous (‘secretions”) produced by the body. Failure to manage these problems effectively can lead to accumulation and aspiration of secretions, which may cause pneumonia and respiratory insufficiency. Knowing the best way to treat this problem is a challenge. Systematic reviews report substantive ongoing uncertainty regarding secretions management (SM). Little is known about the comparative effectiveness of secretion management interventions, their impact on quality of life and acceptability for plwMND/ALS and their unpaid/family. Methods and analysis A complex intervention systematic review of SM for plwMND/ALS and/or their carers will be conducted using an iterative logic model approach, designed in accordance with the principles and guidance laid out in a series of articles published by the Agency for Healthcare Research and Quality on complex intervention reviews . Eight electronic databases will be searched for publications between 1996 and present: Ovid Embase, EBSCO CINAHL, EBSCO Academic Search Ultimate, Scopus, EBSCO PsycInfo, Ovid MEDLINE and the Social Sciences Citation Index. This will be supplemented by hand searching of reference lists of included studies. Two reviewers will independently screen the results for potentially eligible studies using AS Review Lab (a semi-automated machine learning tool). Study selection, data extraction and risk of bias assessment, using Gough’s Weight of Evidence Framework, will be independently performed by two reviewers. A framework thematic synthesis approach will be employed to analyse and report quantitative and qualitative data. The reporting will be conducted in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Complex Intervention Extension Statement and Checklist

In vivo sonic hedgehog pathway antagonism temporarily results in ancestral proto-feather-like structures in the chicken

The morphological intricacies of avian feathers make them an ideal model for investigating embryonic patterning and morphogenesis. In particular, the sonic hedgehog (Shh) pathway is an important mediator of feather outgrowth and branching. However, functional in vivo evidence regarding its role during feather development remains limited. Here, we demonstrate that an intravenous injection of sonidegib, a potent Shh pathway inhibitor, at embryonic day 9 (E9) temporarily produces striped domains (instead of spots) of Shh expression in the skin, arrests morphogenesis, and results in unbranched and non-invaginated feather buds—akin to proto-feathers—in embryos until E14. Although feather morphogenesis partially recovers, hatched treated chickens exhibit naked skin regions with perturbed follicles. Remarkably, these follicles are subsequently reactivated by seven weeks post-hatching. Our RNA-sequencing data and rescue experiment using Shh-agonism confirm that sonidegib specifically down-regulates Shh pathway activity. Overall, we provide functional evidence for the role of the Shh pathway in mediating feather morphogenesis and confirm its role in the evolutionary emergence and diversification of feathers

What are the experiences of people with heart failure regarding participation in physical activity? A systematic review, meta-aggregation and development of a logic model

Objectives To (1) synthesise the experiences of people with heart failure and those who care for them concerning participation in physical activity (2) develop a logic model for a future intervention which will support people with heart failure to feel confident and safe in being physically active. Design A systematic review and meta-aggregation using Joanna Briggs Institute (JBI) methodology. Data sources MEDLINE, Emcare and PsycINFO databases were searched through until June 2024 inclusively. Eligibility criteria Studies with a qualitative design, including qualitative components of mixed-methods studies, which describe experiences of participation in physical activity by adults with chronic heart failure. Data extraction and synthesis Two independent reviewers used standardised methods to search and screen studies. Data extraction included the PROGRESS-Plus items. The JBI checklist for qualitative studies was applied. Meta-aggregation guided by JBI methods was used to synthesise the data. This evidence, along with input from a patient and public involvement group, healthcare professionals and charity organisations, was used to develop a logic model. Results We included 28 papers (25 studies) comprising 14 qualitative studies and 11 mixed-method studies describing the perspectives of 483 people with heart failure, 64 carers and 12 healthcare professionals. The meta-aggregation produced seven synthesised findings describing the impact of physical symptoms, emotional factors, extrinsic factors, access to knowledge, self-motivation and peer/professional motivation and the positive impact of physical activity. The PROGRESS-PLUS tool identified significant inclusivity issues within the studies. The meta-aggregation with relevant contributor input informed behavioural determinants and potential intervention components of a logic model. Conclusions This study identifies behavioural determinants that underlie the actions of people with heart failure in their relationship with physical activity and potential intervention components for a novel intervention design to support this population. There is a lack of studies exploring health professionals’ and carers’ perspectives on this topic. PROSPERO registration number CRD42022342883

Self-sealing of argillaceous media in the context of geological disposal of radioactive waste – a perspective from past and ongoing studies

A review of discontinuity self-sealing mechanisms in argillaceous media is presented. Argillaceous rocks cover a range of siliceous materials generally defined by their particle size (<0.063 mm), composition, and the quantity and type of the clay minerals present. These properties have a strong influence on their material, rock mass and hydrogeological behaviour. In the context of geological disposal of radioactive waste in England and Wales currently (2024), the Mercia Mudstone Group and Ancholme Group are being considered as potential host rocks. These rocks are potentially suitable for the isolation and containment of radioactive waste due to their low primary permeability and potential for discontinuities to self-seal, thereby reducing secondary permeability. The ability of discontinuities to self-seal is a function of lithology, mineralogy, strength, stiffness, groundwater, groundwater chemistry and the in situ state of stress. These properties are strongly affected by depositional provenance, geological history and depth of burial. The processes and mechanisms that lead to self-sealing include swelling, creep, shear, slaking and precipitation of minerals. Self-sealing, therefore, is an important factor influencing the suitability of argillaceous media as a potential host rock for geological disposal of radioactive waste as part of the multi-barrier system

The influence of obstacle geometric fidelity on blast wave propagation: a reduced-scale case study examining the role of the grain siloes in the 2020 Beirut explosion

In the field of blast protection engineering, it remains challenging to validate large, complex numerical models and the implications of modelling assumptions relating to how structures are represented (e.g., geometric fidelity) are not well understood. This paper presents experimental work addressing these two issues, in the context of the 2020 Beirut explosion, which remains an important case study for understanding urban blast effects. A series of reduced-scale (1:250) blast tests examined shielding effects caused by the Beirut grain siloes and investigated the influence of the siloes’ geometric fidelity on blast loading. Rigid obstacles were constructed at two geometric fidelities: “rectangular” (i.e., cuboid) and “accurate”, with closer resemblance to the siloes. Pressure gauges were mounted at multiple locations but at fixed blast scaled distances to examine blast–obstacle interaction behaviour. Additionally, Viper::Blast was used to perform computational fluid dynamics analyses of the tests. Experimental findings confirmed significant shielding (reduced pressure and specific impulse) locally behind the siloes (Z 5 m/kg1/3). Overall, blast wave parameters did not exhibit significant differences between the rectangular and accurate representation of the siloes geometry, except for minor differences (10%) in peak overpressures in localised zones. Numerical models confirmed that these discrepancies were caused by differing blast wave scattering, diffraction, and superposition behaviour attributed to the siloes outer geometry. The results suggest that city-scale blast loading analyses can yield reliable results through idealising structures as simplified cuboidal obstacles. These findings will be of direct relevance to blast protection practitioners and researchers concerned with modelling urban blast scenarios

Critical intervention points for European adaptation to cascading climate change impacts

In an interconnected world, climate change impacts can cascade across sectors and regions, creating systemic risks. Here we analyse cascading climate change impacts on the EU, originating from outside the region, and identify critical intervention points for adaptation. Using network analysis, we integrate stakeholder-co-produced impact chains with quantitative data for 102 countries across foreign policy, human security, trade and finance. Our archetypal impact cascade model reveals critical intervention points related to water, livelihoods, agriculture, infrastructure and economy, and violent conflict. Livelihood instability, with violence exacerbating conditions in conflict-prone regions, tends to amplify risks of cascading impacts emerging from low-income countries. High-income countries can trigger cascading impacts through, for example, reduced crop exports. Our findings highlight the importance of policy coherence in addressing interconnected vulnerabilities rather than isolated risks. Thus, agricultural intensification without integrated water management may exacerbate scarcity, whereas safeguarding livelihoods alleviates cascading risks related to forced migration, violent conflict and instability

Lead-Free (1 – x)Ba(Zr0.2Ti0.8)O3 – x(Ba0.7Ca0.3)TiO3-based ferroelectrics with diffuse phase transitions for sustainable electrocaloric applications

The electrocaloric effect of a ferroelectric material is an effective technique for solid-state refrigeration. Although the peak value of the adiabatic temperature change (ΔT) due to the electrocaloric effect in normal ferroelectrics is found near the Curie point (Tc), ferroelectrics with a diffuse phase transition are always desirable due to their wide temperature span of ΔT. In this work, the electrocaloric effect in sustainable Pb-free weak relaxor ferroelectrics, (1 – x)Ba(Zr0.2Ti0.8)O3 – x(Ba0.7Ca0.3)TiO3 (x = 0.19 and 0.21), with diffuse phase transition is reported. The diffuseness of each composition is determined based on the fitting of the temperature-dependent dielectric permittivity data to the Lorenz-type quadratic law. Interestingly, the maxima of ΔT of the compositions are observed at much higher temperatures than the temperature at maximum dielectric permittivity (Tm) and freezing temperature (Tf), which work as the effective Tc of a relaxor ferroelectric. The wide temperature span (40 K) and high ΔT (0.8 K) of the x = 0.19 composition show the potential of this material for solid-state refrigeration applications. Moreover, the effects of diffuse phase transition on ΔT and its temperature span are discussed in (1 – x)Ba(Zr0.2Ti0.8)O3 – x(Ba0.7Ca0.3)TiO3-based ferroelectrics, which will help to design Pb-free electrocaloric materials with a diffuse phase transition for a wide working temperature range