Cerebrospinal fluid (CSF) flow is crucial for clearing metabolic waste from the brain, a process whose dysregulation is linked to neurodegenerative diseases like Alzheimer's. Traditional approaches like particle tracking velocimetry (PTV) are limited by their reliance on single-plane two-dimensional measurements, which fail to capture the complex dynamics of CSF flow fully. To overcome these limitations, we employ artificial intelligence velocimetry (AIV) to reconstruct three-dimensional velocities, infer pressure and wall shear stress and quantify flow rates. Given the experimental nature of the data and inherent variability in biological systems, robust uncertainty quantification (UQ) is essential. Towards this end, we have modified the baseline AIV architecture to address aleatoric uncertainty caused by noisy experimental data, enhancing our measurement refinement capabilities. We also implement UQ for the model and epistemic uncertainties arising from the governing equations and network representation. Towards this end, we test multiple governing laws, representation models and initializations. Our approach not only advances the accuracy of CSF flow quantification but also can be adapted to other applications that use physics-informed machine learning to reconstruct fields from experimental data, providing a versatile tool for inverse problems.

This article documents the early development of the first transcranial Doppler (TCD)-based ultrasound system for continuous monitoring of brain tissue pulsations (BTPs). Transcranial tissue Doppler (TCTD) uses a lightweight, wearable single-element ultrasound probe to track tissue motion perpendicular to the skin's surface, providing tissue displacement estimates along a single beam line. Feasibility tests using an adapted TCD system confirmed that brain tissue motion data can be obtained from existing TCD hardware. Brain Tissue Velocimetry (Brain TV), a TCTD data acquisition system, was then developed to provide a lightweight and portable means of continuously recording TCTD data in real-time. Brain TV measurements are synchronized to a 3-lead electrocardiogram and can be recorded alongside other physiological measurements, such as blood pressure, heart rate and end-tidal carbon dioxide. We have shown that Brain TV is able to record BTPs from sample depths ranging from 22 to 80 mm below the probe's surface and from multiple positions on the head. Studies in healthy volunteers, stroke patients and ultrasound phantom brain models demonstrate how TCTD might provide insights into the relationships between physiological measurements and brain tissue motion and show promise for rapid clinical assessment and continuous monitoring of BTPs.

Excessive brain tissue pulsations (BTP), measured by ultrasound, have been associated with depression and are hypothesized to contribute to brain damage in this population at risk for cerebrovascular lesions. However, previous research has been limited by small sample sizes. To address this issue, our study pooled data from three separate investigations, resulting in the largest cohort of depressed participants with BTP measurements to date. We analysed 123 participants (74 individuals with depression and 49 healthy controls) using ultrasound tissue pulsatility imaging (TPI) to assess resting BTP. Results showed that both MeanBTP and MaxBTP were significantly associated with depression, as determined by multiple linear regression models that included age, sex and blood pressure as covariates. Additionally, we found that age, sex and diastolic blood pressure were significant predictors of BTP. Specifically, BTP decreased with age, was higher in men, and was more strongly predicted by diastolic blood pressure than by systolic blood pressure. In this large cohort, we replicated the association between depression and increased BTP, supporting the notion that elevated BTP may be a potential mechanism underlying brain damage over time. Our findings suggest that TPI could serve as a valuable surrogate marker for brain health in clinical practice.

Intracerebral blood volume changes along the cardiac cycle cause volumetric strain in brain tissue, measurable with displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging. Individual volumetric strain maps show compressing and expanding voxels, raising the question whether systolic compressions reflect a physiological phenomenon. In DENSE data from nine healthy volunteers, voxels were grouped into three clusters according to volumetric strain in a tissue mask excluding extracerebral blood vessels and cerebrospinal fluid using a two-stage clustering approach. To confirm the physiological source of the compressions, data from a patient with a cranial opening was analysed. Spatial patterns of compressing and expanding clusters were matched to high-resolution anatomical scans, acquired in one additional individual. All healthy subjects consistently showed a cluster with compressive volumetric strain during systole, covering 10.2% [7.3-13.1%] (mean [95% confidence interval]) of the tissue mask, besides two expansion clusters. In the patient, no compression was observed. Although the compression cluster did not consistently co-localize with intracerebral veins or perivascular spaces on the anatomical scans, the first-stage clustering results suggested that the distinction between the clusters has a (peri)vascular source. In conclusion, brain tissue shows heartbeat-induced volumetric compressions, possibly indicating compression of porous structures such as intracerebral veins or perivascular spaces.

Cardiac arrest (CA) is associated with high incidence and mortality rates. Among patients who survive the acute phase, brain injury stands out as a primary cause of death or disability. Effective intensive care management, including targeted temperature management, seizure treatment and maintenance of normal physiological parameters, plays a crucial role in improving survival and neurological outcomes. Current guidelines advocate for neuroprotective strategies to mitigate secondary brain injury following CA, although certain treatments remain subjects of debate. Clinical examination and neuroimaging studies, both invasive and non-invasive neuromonitoring methods and serum biomarkers are valuable tools for predicting outcomes in comatose resuscitated patients. Neuromonitoring, in particular, provides vital insights for identifying complications, personalizing treatment approaches and forecasting prognosis in patients with brain injury post-CA. In this review, we offer an overview of advanced strategies and best practices aimed at optimizing brain protection after CA.

Intracranial pressure (ICP) monitoring is crucial in the management of traumatic brain injury (TBI) and other neurological conditions. Elevated ICP or too low intracranial compliance (ICC) can compromise brain perfusion. Simultaneous monitoring of ICP and ICC is needed to optimize patient-specific brain perfusion in pathological conditions. Surrogate ICC changes can be extracted by analysis of ICP pulse wave morphology. Non-invasive, fully passive sensor and ICC changes monitoring are needed. This study introduces Archimedes, a novel, fully passive, non-invasive ICP wave monitor that utilizes mechanical pulsatile movement of the eyeball to assess ICP pulse waveforms. Preliminary findings indicate a high correlation = [0.919; 0.96] between non-invasive and invasive ICP pulse wave morphologies, demonstrating the device's potential for accurate ICP pulse waveform monitoring. Additionally, the monitor can discern ICC changes, providing valuable insights for TBI and normal tension glaucoma patients according to the shape of non-invasive measured ICP pulse wave. The k-nearest neighbours algorithm used in preliminary glaucoma studies yielded promising diagnostic performance, with an accuracy of 0.89, sensitivity of 0.82, specificity of 1.0 and area under curve 0.91. Ethical approvals for ongoing studies have been secured. Initial results indicate that Archimedes real-time ICC non-invasive monitor is safe, cost-effective alternative to conventional monitoring techniques.

Functional magnetic resonance imaging (fMRI) captures rich physiological and neuronal information, offering insight into neurofluid dynamics, vascular health and waste clearance. Accurate cerebral vessel segmentation could greatly facilitate fluid dynamics research in fMRI. However, existing vessel identification methods, such as magnetic resonance angiography or deep-learning-based segmentation on structural MRI, cannot reliably locate cerebral vessels in fMRI space due to misregistration from inherent fMRI distortions. To address this challenge, we developed a data-driven, automatic segmentation of cerebral vessels directly within fMRI space. This approach identified large cerebral arteries and the superior sagittal sinus (SSS) by leveraging these vessels' distinct pulsatile signal patterns during the cardiac cycle. The method was validated in a local dataset by comparing it to ground truth cerebral artery and SSS segmentations. Using the Human Connectome Project (HCP) ageing dataset, the method's reproducibility was tested on 422 participants aged 36-90, each with four repeated fMRI scans. The method demonstrated high reproducibility, with an intraclass correlation coefficient > 0.7 in both cerebral artery and SSS segmentation volumes. This study demonstrates that large cerebral arteries and SSS can be reproducibly and automatically segmented in fMRI datasets, facilitating reliable fluid dynamics investigation in these regions.

The brain is arguably the most complex human organ and modelling its mechanical behaviour has challenged researchers for decades. There is still a lack of understanding on how this multiphase tissue responds to mechanical loading and how material parameters can be reliably calibrated. While previous viscoelastic models with two relaxation times have successfully captured the response of brain tissue, the Theory of Porous Media provides a continuum mechanical framework to explore the underlying physical mechanisms, including interactions between solid matrix and free-flowing interstitial fluid. Following our previously published experimental testing protocol, here we perform finite element simulations of cyclic compression-tension loading and compression-relaxation experiments on human brain white and gray matter specimens. The solid volumetric stress proves to be a crucial factor for the overall biphasic tissue behaviour as it strongly interferes with porous effects controlled by the permeability. An inverse parameter identification reveals that poroelasticity alone is insufficient to capture the time-dependent material behaviour, but a poro-viscoelastic formulation captures the response of brain tissue well. We provide valuable insights into the individual contributions of viscous and porous effects. However, due to the strong coupling between porous, viscous, and volumetric effects, additional experiments are required to reliably determine all material parameters.

It has been argued that the historical nature of evolution makes it a highly path-dependent process. Under this view, the outcome of evolutionary dynamics could have resulted in organisms with different forms and functions. At the same time, there is ample evidence that convergence and constraints strongly limit the domain of the potential design principles that evolution can achieve. Are these limitations relevant in shaping the fabric of the possible? Here, we argue that fundamental constraints are associated with the logic of living matter. We illustrate this idea by considering the thermodynamic properties of living systems, the linear nature of molecular information, the cellular nature of the building blocks of life, multicellularity and development, the threshold nature of computations in cognitive systems and the discrete nature of the architecture of ecosystems. In all these examples, we present available evidence and suggest potential avenues towards a well-defined theoretical formulation.

Organoids and stem-cell-based embryo models (SEMs) are imperfect organ or embryo representations that explore a much larger space of possible forms, or morphospace, compared to their counterparts. Here, we discuss SEM biology in light of seminal work by Pere Alberch, a leading figure in early evo-devo, interpreting SEMs as developmental 'monstrosities' in the Alberchian sense. Alberch suggested that ordered patterns in aberrant development-i.e. 'the logic of monsters'-reveal developmental constraints on possible morphologies. In the same vein, we detail how SEMs have begun to shed light on structural features of normal development, such as developmental variability, the relative importance of internal versus external constraints, boundary conditions and design principles governing robustness and canalization. We argue that SEMs represent a powerful experimental tool to explore and expand developmental morphospace and propose that the 'monstrosity' of SEMs can be leveraged to uncover the 'hidden' rules and developmental constraints that robustly shape and pattern the embryo.

Pere Alberch played a pivotal role in shaping the field of evolutionary developmental biology during the 1980s and 1990s. Whereas initially his contributions were sidelined by the empirical advancements of the molecular revolution in developmental and evolutionary biology, his theoretical insights have left a lasting impact on the discipline. This article provides a comprehensive review of the legacy and evolvability of Alberch's ideas in contemporary evo-devo, which included the study of morphogenesis as the proper level of developmental causation, the interplay between developmental constraints and natural selection, the epistemic role of teratologies, the origin of evolutionary novelties and the concept of evolvability.

The project aimed to develop porous materials for sustainable energy applications, namely, hydrogen storage, and valorization of biomass to renewable fuels. At the core of the project was a training programme for Africa-based researchers in (i) the exploitation of renewable locally available raw materials; (ii) the use of advanced state-of-the-art techniques for the design and synthesis of porous materials (zeolites and metal-organic frameworks (MOFs)) for energy storage; and (iii) the valorization of sustainable low-value feedstock to renewable fuels. We found that compaction of the UiO-66 MOF at high pressure improves volumetric hydrogen storage capacity without any loss in gravimetric uptake, and experimentally demonstrated the temperature-dependent dynamic behaviour of UiO-66, which allowed us to propose an activation temperature of ≤ 150°C for UiO-66. Co-pelletization was used to fabricate UiO-66/nanofibre monoliths as hierarchical porous materials with enhanced usable (i.e. deliverable) hydrogen storage capacity. We clarified the use of naturally occurring kaolin as a source of silica and alumina species for zeolite synthesis. The kaolin-derived zeolite X was successfully used as a catalyst for the transesterification of oil (from non-edible biomass) to biodiesel. We also prepared porous composites (i.e. carbon/UiO-66, organoclay/UiO-66 and zeolite/carbon) that were successfully applied in electrochemical sensing.

The Royal Society and UK Department for International Development supported a consortium of three universities across sub-Saharan Africa and Imperial College London with the aim of developing new knowledge on direct-steam-generation concentrated solar power (CSP) plants and supporting relevant capacity building across the Universities of Lagos, Mauritius and Pretoria. Key research findings from the programme include an improved flow-classification scheme for two-phase, liquid-liquid flows; testing of advanced surfaces with much-improved steady-state heat transfer performance-the commercial nanoFLUX surface showed up to 200% higher heat-transfer coefficients (HTCs) in pool boiling compared with other surfaces with R-134a/R-245fa; first-of-a-kind measurements of transient flow boiling HTCs, which were up to 30% lower in step perturbations than quasi-steady-state expectations in horizontal pipes with R-245fa; error estimation and corrections for laser-induced fluorescence (LIF) measurements, leading to the development of an adapted planar LIF technique with uncertainty <10% for local, instantaneous film thickness measurements in annular flows, and the application of such diagnostic methods to pool, falling-film and flow boiling in pipes; and predictions of an ~80% increase in the net present value of a case-study CSP plant when integrated with solid storage media.

Africa's potential for scientific research is not yet being realized, for various reasons including a lack of researchers in many fields and insufficient funding. Strengthened research capacity through doctoral training programmes in higher education institutes (HEIs) in Africa, to include collaboration with national, regional and international research institutions, can facilitate self-reliant and sustainable research to support socio-economic development. In 2012, the Royal Society and the UK's Department for International Development (now the Foreign, Commonwealth and Development Office) launched the Africa Capacity Building Initiative (ACBI) Doctoral Training Network which aimed to strengthen research capacity and training across sub-Saharan Africa. The ACBI supported 30 core PhD scholarships, all registered/supervised within African HEIs with advisory support from the UK-based institutes. Our 'Soil geochemistry to inform agriculture and health policies' consortium project, which was part of the ACBI doctoral training programme network, was implemented in Malawi, Zambia and Zimbabwe between 2014 and 2020. The aims of our consortium were to explore linkages between soil geochemistry, agriculture and public health for increased crop productivity, nutrition and safety of food systems and support wider training and research activities in soil science. Highlights from our consortium included: (i) the generation of new scientific evidence on linkages between soils, crops and human nutrition; (ii) securing new projects to translate science into policy and practice; and (iii) maintaining sustainable collaborative learning across the consortium. Our consortium delivered high-quality science outputs and secured new research and doctoral training funding from a variety of sources to ensure the continuation of research and training activities. For example, follow-on Global Challenges Research Funded Translation Award provided a strong evidence base on the prevalence of deficiencies in children under 5 years of age and women of reproductive age in Zimbabwe. This new evidence will contribute towards the design and implementation of a nationally representative micronutrient survey as an integral part of the Zimbabwe Demographic and Health Surveys conducted by the Ministry of Health and Child Care. The award also generated new evidence and a road map for creating quality innovative doctorates through a doctoral training landscape activity led by the Zimbabwe Council for Higher Education. Although our project and the wider ACBI has contributed to increasing the self-reliance and sustainability of research within the region, many challenges remain and ongoing investment is required.

In this article, we examine the scientific and sustainable research capacity outcomes of the 'Congo River: user Hydraulics and Morphology' or CRuHM project, a six-year effort supported by the Royal Society's Africa Capacity Building Initiative. This project brought together a consortium of African and UK universities to undertake the first large-scale scientific expeditions to the Congo basin of the modern era in order to better understand the hydraulics and geomorphology of this understudied but globally important river. The river is essential for navigation, irrigation, drinking water and hydroelectric power generation for the 10 basin countries and is critically important for biodiversity and global nutrient, carbon and climatological cycles. This article summarizes the new scientific understanding contributed by the project and the steps taken to ensure a meaningful legacy that would continue long beyond the finite lifetime of available funding. Actions taken to achieve this include establishing a new hydrology research centre at the University of Kinshasa as well as steps to build a wider international community of Congo basin researchers. In this way, we hope to build momentum for future funding initiatives and collaboration.

This article provides insights into building research capacity in computational modelling of materials at the University of Limpopo (UL), formerly University of the North, in South Africa, through a collaboration with a consortium of universities in the United Kingdom (UK) through the support of the National Research Foundation (NRF), formerly the Foundation for Research and Development, and the Royal Society (RS). A background that led to the choice of building research capacity at historically disadvantaged universities in South Africa, including the UL, is given. The of the collaboration between the UL and several UK universities on computational modelling of materials is outlined, together with the scientific highlights that were achieved in themes of minerals, energy storage and alloy development. The capacity built in terms of human capital and institutions set up is shared, which is followed by a discussion of the continuing research activities after the formal NRF-RS collaboration ceased with more alignment to industrial applications with national and international support. We conclude by highlighting the success of the project in capacity-building and consolidating the Materials Modelling Centre with developments of high-performance computing in South Africa and the African continent. We comment on the lessons learned regarding successful capacity-building programmes.

The CaGSUMI consortium was funded by the Royal Society-Department for International Development (later the Foreign, Commonwealth & Development Office) on the Africa Capacity Building Initiative programme between the years 2015 and 2022 and involved three Sub-Saharan African universities: Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, University of Yaoundé I, Cameroon, and the University of Zululand, South Africa; and the University of Manchester in the United Kingdom. The project was used to cement an emergent UK-Africa network in the areas of materials chemistry related to renewable energy generation with both thin films and nanomaterials. The consortium's outputs led to numerous publications of African science in international journals, a number of graduated PhDs who went on to permanent academic positions and prestigious fellowships, the establishment of a capacity-building plan relevant to the chemistry departments in each of the African countries, and the installation of a number of first-in-kind pieces of kit for African laboratories that will keep them on a competitive footing at an international level for the next decade and more.

Anthropogenic activities around local villages in mesic savanna landscapes of West Africa have resulted in soil improvement and forest establishment outside their climatic zones. Such unique 'forest islands' have been reported to provide ecosystem services including biodiversity conservation. However, the science underpinning their formations is limitedly studied. In 2015 and with funding support from the Royal Society-DFID (now FCDO), we set out to investigate the biogeochemistry of the forest islands in comparison with adjacent natural savanna and farmlands across 11 locations in Burkina Faso, Ghana and Nigeria. Our results showed that the forest islands do not differ significantly from the adjoining ecosystems in soil mineralogy implying that their formation was anthropogenically driven. We observed greater soil organic carbon and nutrient distributions in the forest islands, which also had more stable macro (>500 μm) and meso-aggregates (500-250 μm) than the adjoining agricultural lands. We found that soil micro-aggregate (250-53 μm) stability was climate (precipitation) driven in the West African ecosystems while meso- and macro-aggregate stability was land-use driven. In one of the unique forest islands we studied in the Mole National Park of Ghana, we found its mineral-associated organic carbon over 40% greater than the adjoining natural savanna with potential implications for the achievement of the global initiative of the '4p1000' in West Africa. We conclude that the North-South-South research collaboration has established clearly, the science underlying the age-long West African forest island phenomenon and has, among many successes, led to capacity building of young scientists driving cutting-edge research in climate change adaptation and food systems transformation in the sub-region.

This study presents a novel hierarchical nested honeycomb drawing inspiration from the hierarchical structures found in energy-absorbing citrus peels. Our investigation reveals that integrating secondary hierarchical units into primary honeycomb cells results in energy absorption profiles featuring two distinct plateaus. Notably, we found that these profiles can be finely tuned by adjusting the thickness of primary and secondary cell walls. Additionally, our study demonstrates a strategic removal of cell walls at key positions, reducing material consumption without compromising specific energy absorption. By establishing comprehensive structure-property relationships, we offer valuable insights into the design and optimization of hierarchical cellular materials. Compared with traditional honeycomb structures, the nested honeycomb structure shows a twofold increase in compressive strength and a fivefold increase in specific energy absorption, positioning them as promising candidates for applications requiring two-step impact protection and tunable performance, ranging from packaging to high-speed automobiles.

The asymptotic homogenization method is applied to characterize the effective behaviour of periodic multi-laminated micropolar elastic heterogeneous composites under perfect contact conditions. The local problem formulations and the analytical expressions for the effective stiffness and torque coefficients are derived for the centrosymmetric case. One of the main findings in this work is the analysis of the rotations effect of the layers' constitutive properties on the mechanical response of bi-laminated composites. The effects of microstructure and interfacial interactions on the composite's mechanical behaviour are captured through the independent effective moduli. Comparisons with the classical elastic case show the approach validation. Some numerical examples are shown. Furthermore, considering the micropolar media's prevalence in bio-inspired systems, the model's applicability is evaluated for reconstructing bone fractures using multi-laminated biocomposites. An important finding in this bio-inspired simulation is related to the analysis of a periodic bi-laminated micropolar composite whose isotropic constituents are a bioceramic material and a compact bone. This artificial bio-inspired material should integrate with host tissue to support cell growth and be stable and compatible. These characteristics are crucial in the enhancement of the fractured bone.