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3D full-field lacunar morphology and deformation of calcified fibrocartilage in the loaded Achilles enthesis of a mouse
Get PDFEnthesis calcified fibrocartilage (CFC) is a specialized structure anchoring tendon or ligament to bone and transmitting stresses from joint motion or muscle forces. Understanding the CFC 3D microstructure–mechanics relationship is key to explaining its mechanical behaviour, failure, and regeneration after injury. Such insights can guide biomaterial design and regenerative therapies. However, current methods cannot non-invasively measure localized mechanical behaviour within this anisotropic, heterogeneous insertion. In this research, full-field micromechanical structural analysis of a murine enthesis (n = 3) was conducted to understand the mechanics underlying its structural attributes using high-resolution in-situ micro-computed tomography with deep learning reconstruction and digital volume correlation. Our findings reveal that, depending on stress angle, the central region of the CFC lacunar morphology deforms more than other regions. We also identified that CFC microstructure organization and thickness strongly correlate with strain distribution at the interface, with regions of higher lacunar density experiencing greater deformation
Elevations of α-fetoprotein in patients undergoing chemotherapy for pure testicular seminoma: a retrospective cohort study
Get PDFBackground
α-Fetoprotein (AFP) is conventionally absent in testicular classical seminoma (TCS). However, moderate AFP elevations can occur in TCS patients, as observed at this and other centres, which can be challenging to diagnostic and management practices.
Methods
This retrospective cohort study considered AFP concentration in the context of germ-cell tumour diagnosis and characterisation at baseline (BL), disease status during chemotherapy, and long-term surveillance. The study considered patients with histologically diagnosed stage 1 TCS requiring chemotherapy over six years. For those with AFP above the reference interval at BL, histological imaging, case notes, and biochemical data were reviewed from BL to surveillance completion. Outcomes included AFP changes, diagnoses, therapy, disease progression, and death.
Results
Of the 175 patients included, eight (4.6%) had elevated AFP at BL. Of these, two showed statistically but not clinically significant AFP changes during therapy, while six had moderate, stable AFP elevations with no changes in diagnosis during follow-up. During therapy, one patient developed metastases, and one died of causes likely unrelated to their TCS.
Conclusions
Mild elevations of AFP in TCS may lead to diagnostic uncertainty or inappropriate management and investigation. However, AFP changes, alongside imaging, did not affect diagnosis, therapy, or follow-up at this centre for any of the patients examined. A subgroup of TCS patients has stable, moderate AFP elevations unrelated to tumour aetiology
Refining 3D Displacement Fields and Coseismic Slip Models of the 2023 Kahramanmaraş Earthquakes Using Subswath and Burst Overlap Interferometry (SBOI)
Get PDFThe 6 February 2023 Kahramanmaraş Earthquakes caused extensive deformation along the East Anatolian Fault Zone, producing significant north-south displacements. Standard Interferometric Synthetic Aperture Radar (InSAR) methods face significant challenges in resolving near-field deformation due to phase decorrelation caused by high displacement gradients. This study demonstrates the capability of Subswath and Burst Overlap Interferometry (SBOI), which leverages all possible overlap regions of Sentinel-1 TOPS mode to retrieve along-track deformation and improve the resolution of 3D displacement fields. We introduce an enhanced methodology that calculates pixel-based scaling factors for spectral separation, enabling accurate deformation measurements in both burst and subswath overlap regions. Although overlap regions are spatially discontinuous and cover only
of the frame, SBOI offers critical constraints that complement conventional SAR, enabling full spatial coverage. We combine SBOI with azimuth and range offsets to produce 3D displacement fields and perform unsmoothed Bayesian slip inversion. Results reveal significant improvements in constraining north-south deformation, reducing residuals, and decreasing uncertainties in the slip inversion model compared to solutions without SBOI. Linear regression analysis between solutions with and without SBOI demonstrates
reduction in RMS error for the north-south component of 3D displacement field. Near-field SBOI profiles also capture detailed deformation gradients along fault ruptures, offering insights into fault kinematics and rupture dynamics. This study highlights SBOI as a powerful tool for resolving high-gradient deformations and enhancing 3D displacement fields and geodetic slip models, particularly in regions experiencing large coseismic deformation with significant north-south components, where conventional InSAR and SAR measurements are insufficient
The ‘La Celle interglacial’:a key-record of MIS 11c palaeoenvironments and palaeoclimate in NW Europe
Get PDFThe La Celle calcareous tufa formation, located in the Seine valley (Paris Basin, France) provides an exceptional stratigraphic record (9 m thick), yielding a wide variety of palaeontological remains (molluscs, leaf prints, ostracods, mammals) as well as geochemical data allowing a detailed reconstruction of the environmental and climatic dynamics during the Marine Isotope Stage (MIS) 11c interglacial. The chronological assignment of the site is particularly well constrained by a number of methods (U-series, electron spin resonance, thermoluminescence). This review synthesises previously published data as well as new research on the formation of the deposit (stratigraphy, micromorphology), amino-acid geochronology, palaeobotany, and compares these results with those of European palynological references. Several important markers of the continental environments during MIS 11c are identified. The malacological succession is of particular importance for reconstructing the vegetation dynamics, reflecting the expansion of forest biotopes and their subsequent degradation and is closely linked to geochemical analyses, providing a reliable framework for the associated climatic conditions. The La Celle sequence yields the only complete record for the development of the “ Lyrodiscus fauna”, a characteristic biostratigraphic signature of MIS 11c in NW Europe. The long molluscan succession of La Celle is the relevant reference for the integration of shorter regional malacological series into the environmental dynamics of the interglacial. The occurrence of several Mediterranean trees, and mammal remains of Hippopotamus and Macaca are registered during the climatic optimum revealed by geochemistry. Together with isotopic data this set of thermophilic bioproxies indicates the warmest and wettest conditions ever recorded for late Middle Pleistocene interglacials in the region. Comparison of the reconstructed palaeoenvironmental and climatic succession with the nearest long pollen series demonstrates that the La Celle tufa deposit records almost the entire interglacial. Therefore, the “La Celle Interglacial” is proposed as a major reference for understanding the evolution of the MIS 11c continental landscapes and biodiversity in northwestern Europe
The use of enhanced analytical pipelines for the characterization of poly(A) and poly(A)-LNP formulation critical quality attributes
Get PDFThe number of nucleic acid therapeutics is set to grow within the pharmaceutical industry sector, deploying nanocarrier-based delivery systems as drug products. Poly(A) is a widely used model sequence used in lipid nanoparticle (LNP) formulations for which there are no reported critical quality attributes (CQAs) such as molecular weight, chain length, and impurity profile. In this study, we analyze Poly(A) from three different vendors to measure any existing differences in their CQAs. Poly(A) from these brands was encapsulated in SM102 LNPs using microfluidics to produce three branded Poly(A)-based LNPs. We utilized an orthogonal analytical pipeline approach for both Poly(A) drug substance and LNP drug product CQA evaluation, which included a combination of dynamic light scattering and flow field flow fractionation multiplexed with inline UV, dynamic, and multiangle light-scattering detectors. Similar purity (260/280) values of >3 were obtained across all three brands of Poly(A); however, distinct differences in molecular weight and chain length distributions were identified across Poly(A) brands, with this study representing the first to apply EAF4 methodology for in-depth characterization of model RNA drug substances. Brand A produced a smaller and broader molecular weight distribution, followed by Brand B, and then Brand C produced the largest molecular weight species and the most uniform molecular weight distribution. On encapsulation in LNPs, differences seen in Poly(A) CQAs did not translate to CQA differences in resultant LNPs. We show that a deeper understanding of drug substance CQAs and their subsequent impact on resultant overall drug product characteristics is needed on a case-by-case basis. We show correlations between analytical pipelines, with future work investigating the impact of RNA molecular weight in LNP formulations with different lipid compositions and using these correlations in AI or machine learning to further enhance our knowledge of the correlation between drug substance and resultant drug product CQAs
Diophantine approximations with restrained denominators. Balance condition on decay and growth rates
Get PDFWe strengthen known results on Diophantine approximation with restricted denominators by presenting a new quantitative Schmidt-type theorem that applies to denominators growing much more slowly than in previous works. In particular, we can handle sequences of denominators with polynomial growth and Rajchmann measures exhibiting arbitrary slow decay, allowing several applications. For instance, our results yield non-trivial lower bounds on the Hausdorff dimensions of intersections of two sets of inhomogeneously well-approximable numbers (each with restricted denominators) and enable the construction of Salem subsets of well-approximable numbers of arbitrary Hausdorff dimension
Synergistic interaction between the γ-Al2O3 washcoat and Cu-SSZ-13 for enhancing NH3-SCR performance
Get PDFThe development of coated monolithic catalysts that combine high catalytic activity with high N2 selectivity remains a significant challenge for NOx abatement in diesel exhaust gas. The slurry with Cu-SSZ-13 (CS), silica sol and γ-Al2O3 derived from alumina sol calcination was deposited on honeycomb cordierite monolith (CC) to obtain coated monolithic catalysts. This study aims to unravel the synergistic interaction between the γ-Al2O3 washcoat and CS as an active component to enhance the catalytic performance of CS. The CS-SiAl-4/CC displays excellent NOx purification performance in the absence of water vapor as well as outstanding hydrothermal aging resistance. The results indicate that γ-Al2O3 exhibits excellent adhesion and uniform dispersion on the CS surface without disrupting CS's crystalline structure. The coordination environment, redox properties and amount of Cu species are not affected by γ-Al2O3. Furthermore, γ-Al2O3 features a substantial number of both Brønsted and Lewis acid sites, which play a crucial role in storing NH3 and providing NH4+. In situ DRIFTS results demonstrate that CS-SiAl-4/CC can adsorb more NOx species (free ionic nitrates and monodentate nitrates), which react with NH3 adsorbed on the Lewis acid sites through the Langmuir-Hinshelwood (L-H) mechanism. NH4+ plays a more important role as the main active intermediates, and its reaction with gaseous NO suggests the Eley-Rideal (E-R) mechanism. More importantly, bidentate nitrates can convert to monodentate nitrites, which serve as the active species for the SCR reaction. This phenomenon is likely the main reason for the superior SCR performance of CS-SiAl-4/CC compared to CS-Si/CC
A survey of multimodal fusion for Alzheimer’s disease prediction: a new taxonomy and trends
Get PDFAlzheimer’s disease (AD) is a neurodegenerative disease, well-known for its incurability, and is common among the elderly population worldwide. Previous studies have demonstrated that early intervention positively influences disease progression, leading to increased research into pathological analysis and disease trajectory prediction through machine learning (ML) methods. Given the similarities across different neurodegenerative disorders, a diagnosis relying solely upon a single modality of data is inadequate. Consequently, current research predominantly focuses on multimodal analysis, integrating medical imaging and clinical patient information, with continuous identification of new data types potentially aiding AD diagnosis. Multimodal approaches have been explored extensively over the past two decades, with significant advances observed following the introduction of Deep Learning (DL) techniques. Deep neural networks can adaptively extract and fuse features directly from input data, significantly broadening the scope of multimodal analysis. However, earlier classification studies have primarily concentrated on traditional ML, often neglecting the rapid advancements in DL networks. This article provides a comprehensive description of the acquisition pathways based on modalities, discusses the modalities currently used for research in neuroimaging, human body fluids, and other relevant sources. Additionally, it classifies fusion methodologies utilised in both DL and traditional ML contexts, highlights existing challenges, and outlines potential directions for future research
‘I just go headbutt a tree or something’: Children’s contextualised digital play drivers and subjective well-being in the United Kingdom, South Africa, Australia and Cyprus
Get PDFThe relationship between children’s digital play and well-being remains under-researched, with debates often polarised and limited by a lack of holistic studies in diverse global contexts. This article draws on empirical data from an ecoculturally informed study of children’s (6–12) digital play in the United Kingdom, South Africa, Australia and Cyprus to examine how individual and contextual circumstances influence children’s self-led digital play choices and practices. To do so, we theorise ‘contextualised digital play drivers’, understood as children’s own accounts, or adults’ interpretations, of the deep interests, needs and desires their play appears to fulfil. This approach moves beyond dominant lenses focused on individual autonomy, offering a more situated reading acknowledging the individual and contextual circumstances shaping digital play. Eleven contextualised digital play drivers are identified and discussed in relation to children’s well-being. The article concludes with implications for game designers, educators, families, policy and research methodology
Cutting through the noise: the legitimacy of the European convention on human rights in the British press
Get PDFThis article presents the first systematic analysis of British press coverage regarding the legitimacy of the European Convention on Human Rights and European Court of Human Rights over 25 years (1997–2022). It finds that coverage undermining legitimacy falls into three main areas: limiting or eroding national sovereignty, inadequate performance or effectiveness and disrupting the ‘natural order’. Coverage supporting or defending legitimacy is about providing a safety net, maintaining the international human rights system, and protecting freedoms and liberties. These are distributed unevenly across the six newspapers included in the sample. Critical coverage maps closely to legal scholarship on challenges for legitimacy associated with the identity of the United Kingdom as a political constitutionalist state. Supportive coverage, however, does not fully reflect the broad range of arguments in favour of the legitimacy of the European Convention on Human Rights as identified by human rights campaigners; it is also less abundant, narrower and more tactically defensive
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