Fabrication of a positional brain shift phantom through the utilization of the frozen intermediate hydrogel state

Synthetic models (phantoms) of the brain-skull system are useful tools for the study of surgical events that are otherwise difficult to study directly in humans. To date, very few studies can be found which replicate the full anatomical brain-skull system. Such models are required to study the more global mechanical events that can occur in neurosurgery, such as positional brain shift. Presented in this work is a novel workflow for the fabrication of a biofidelic brain-skull phantom which features a full hydrogel brain with fluid-filled ventricle/fissure spaces, elastomer dural septa and fluid-filled skull. Central to this workflow is the utilization of the frozen intermediate curing state of an established brain tissue surrogate, which allows for a novel moulding and skull installation approach that permits a much fuller recreation of the anatomy. The mechanical realism of the phantom was validated through indentation testing of the phantom's brain and simulation of the supine to prone brain shift event, while the geometric realism was validated through magnetic resonance imaging. The developed phantom captured a novel measurement of the supine to prone brain shift event with a magnitude that accurately reproduces that seen in the literature

An analysis of the relationship between microneedle spacing, needle force and skin strain during the indentation phase prior to skin penetration

Microneedle (MN) array patches present a promising new approach for the minimally invasive delivery of therapeutics and vaccines. However, ensuring reproducible insertion of MNs into the skin is challenging. The spacing and arrangement of MNs in an array are critical determinants of skin penetration and the mechanical integrity of the MNs. In this work, the finite element method was used to model the effect of MN spacing on needle reaction force and skin strain during the indentation phase prior to skin penetration. Spacings smaller than 2–3 mm (depending on variables, e.g., skin stretch) were found to significantly increase these parameters

Robust Single-view Cone-beam X-ray Pose Estimation with Neural Tuned Tomography (NeTT) and Masked Neural Radiance Fields (mNeRF)

Many tasks performed in image-guided, mini-invasive, medical procedures can be cast as pose estimation problems, where an X-ray projection is utilized to reach a target in 3D space. Expanding on recent advances in the differentiable rendering of optically reflective materials, we introduce new methods for pose estimation of radiolucent objects using X-ray projections, and we demonstrate the critical role of optimal view synthesis in performing this task. We first develop an algorithm (DiffDRR) that efficiently computes Digitally Reconstructed Radiographs (DRRs) and leverages automatic differentiation within TensorFlow. Pose estimation is performed by iterative gradient descent using a loss function that quantifies the similarity of the DRR synthesized from a randomly initialized pose and the true fluoroscopic image at the target pose. We propose two novel methods for high-fidelity view synthesis, Neural Tuned Tomography (NeTT) and masked Neural Radiance Fields (mNeRF). Both methods rely on classic Cone-Beam Computerized Tomography (CBCT); NeTT directly optimizes the CBCT densities, while the non-zero values of mNeRF are constrained by a 3D mask of the anatomic region segmented from CBCT. We demonstrate that both NeTT and mNeRF distinctly improve pose estimation within our framework. By defining a successful pose estimate to be a 3D angle error of less than 3 deg, we find that NeTT and mNeRF can achieve similar results, both with overall success rates more than 93%. However, the computational cost of NeTT is significantly lower than mNeRF in both training and pose estimation. Furthermore, we show that a NeTT trained for a single subject can generalize to synthesize high-fidelity DRRs and ensure robust pose estimations for all other subjects. Therefore, we suggest that NeTT is an attractive option for robust pose estimation using fluoroscopic projections

Full-field MRI measurements of in-vivo positional brain shift reveal the significance of intra-cranial geometry and head orientation for stereotactic surgery

Positional brain shift (PBS), the sagging of the brain under the effect of gravity, is comparable in magnitude to the margin of error for the success of stereotactic interventions (∼ 1 mm). This non-uniform shift due to slight differences in head orientation can lead to a significant discrepancy between the planned and the actual location of surgical targets. Accurate in-vivo measurements of this complex deformation are critical for the design and validation of an appropriate compensation to integrate into neuronavigational systems. PBS arising from prone-to-supine change of head orientation was measured with magnetic resonance imaging on 11 young adults. The full-field displacement was extracted on a voxel-basis via digital volume correlation and analysed in a standard reference space. Results showed the need for target-specific correction of surgical targets, as a significant displacement ranging from 0.52 to 0.77 mm was measured at surgically relevant structures. Strain analysis further revealed local variability in compressibility: anterior regions showed expansion (both volume and shape change), whereas posterior regions showed small compression, mostly dominated by shape change. Finally, analysis of correlation demonstrated the potential for further patient- and intervention-specific adjustments, as intra-cranial breadth and head tilt correlated with PBS reaching statistical significance

The mechanism and control of DNA transfer by the conjugative relaxase of resistance plasmid pCU1

Bacteria expand their genetic diversity, spread antibiotic resistance genes, and obtain virulence factors through the highly coordinated process of conjugative plasmid transfer (CPT). A plasmid-encoded relaxase enzyme initiates and terminates CPT by nicking and religating the transferred plasmid in a sequence-specific manner. We solved the 2.3 Å crystal structure of the relaxase responsible for the spread of the resistance plasmid pCU1 and determined its DNA binding and nicking capabilities. The overall fold of the pCU1 relaxase is similar to that of the F plasmid and plasmid R388 relaxases. However, in the pCU1 structure, the conserved tyrosine residues (Y18,19,26,27) that are required for DNA nicking and religation were displaced up to 14 Å out of the relaxase active site, revealing a high degree of mobility in this region of the enzyme. In spite of this flexibility, the tyrosines still cleaved the nic site of the plasmid’s origin of transfer, and did so in a sequence-specific, metal-dependent manner. Unexpectedly, the pCU1 relaxase lacked the sequence-specific DNA binding previously reported for the homologous F and R388 relaxase enzymes, despite its high sequence and structural similarity with both proteins. In summary, our work outlines novel structural and functional aspects of the relaxase-mediated conjugative transfer of plasmid pCU1

Embodied viewing and Degas’s Little Dancer Aged Fourteen: a multi-disciplinary experiment in eye-tracking and motion capture

This paper presents a cross-disciplinary project based on an experiment in eye-tracking and motion capture (Sainsbury’s Centre for Visual Arts), which aimed to study viewers’ movements around an iconic sculpture: Edgar Degas’s Little Dancer Aged Fourteen. The experiment studies how viewers respond to this three-dimensional artwork not only by looking at it but also through their own bodily reactions to it, such as by unconsciously mimicking a represented attitude or gesture. We compared two groups of viewers: classically trained dancers and non-dancers. Our hypothesis was that the skills and embodied experiences of the dancers would alter the ways in which they engage bodily with the work compared to the non-dancers. Our underlying research question was: how are vision and the body interlinked in esthetic and kinesthetic experience? This paper does not give results, which are forthcoming. It focuses on methodology and provides a commentary on the design and development of the interdisciplinary collaboration behind the project. It explores an interdisciplinary collaboration that bridges the humanities and experimental sciences and asks how being confronted with unfamiliar methodologies forces researchers in a given field to critically self-examine the limits and presuppositions of their practices

Galaxy zoo DESI: large-scale bars as a secular mechanism for triggering AGN

Despite the evidence that supermassive black holes (SMBHs) co-evolve with their host galaxy, and that most of the growth of these SMBHs occurs via merger-free processes, the underlying mechanisms which drive this secular co-evolution are poorly understood. We investigate the role that both strong and weak large-scale galactic bars play in mediating this relationship. Using 72,940 disc galaxies in a volume-limited sample from Galaxy Zoo DESI, we analyse the active galactic nucleus (AGN) fraction in strongly barred, weakly barred, and unbarred galaxies up to z = 0.1 over a range of stellar masses and colours. After controlling for stellar mass and colour, we find that the optically selected AGN fraction is 31.6 ± 0.9 per cent in strongly barred galaxies, 23.3 ± 0.8 per cent in weakly barred galaxies, and 14.2 ± 0.6 per cent in unbarred disc galaxies. These are highly statistically robust results, strengthening the tantalising results in earlier works. Strongly barred galaxies have a higher fraction of AGNs than weakly barred galaxies, which in turn have a higher fraction than unbarred galaxies. Thus, while bars are not required in order to grow a SMBH in a disc galaxy, large-scale galactic bars appear to facilitate AGN fuelling, and the presence of a strong bar makes a disc galaxy more than twice as likely to host an AGN than an unbarred galaxy at all galaxy stellar masses and colours

Socio-ecological factors shape the distribution of a cultural keystone species in Malaysian Borneo

Biophysical and socio-cultural factors have jointly shaped the distribution of global biodiversity, yet relatively few studies have quantitatively assessed the influence of social and ecological landscapes on wildlife distributions. We sought to determine whether social and ecological covariates shape the distribution of a cultural keystone species, the bearded pig (Sus barbatus). Drawing on a dataset of 295 total camera trap locations and 25,755 trap days across 18 field sites and three years in Sabah and Sarawak, Malaysian Borneo, we fitted occupancy models that incorporated socio-cultural covariates and ecological covariates hypothesized to influence bearded pig occupancy. We found that all competitive occupancy models included both socio-cultural and ecological covariates. Moreover, we found quantitative evidence supporting Indigenous pig hunting rights: predicted pig occupancy was positively associated with predicted high levels of Indigenous pig-hunting groups in low-accessibility areas, and predicted pig occupancy was positively associated with predicted medium and low levels of Indigenous pig-hunting groups in high-accessibility areas. These results suggest that bearded pig populations in Malaysian Borneo should be managed with context-specific strategies, promoting Indigenous pig hunting rights. We also provide important baseline information on bearded pig occupancy levels prior to the 2020–2021 outbreak of African Swine Fever (ASF), which caused social and ecological concerns after mass dieoffs of bearded pigs in Borneo. The abstract provided in Malay is in the Supplementary file

Socio-ecological factors shape the distribution of a cultural keystone species in Malaysian Borneo

Biophysical and socio-cultural factors have jointly shaped the distribution of global biodiversity, yet relatively few studies have quantitatively assessed the influence of social and ecological landscapes on wildlife distributions. We sought to determine whether social and ecological covariates shape the distribution of a cultural keystone species, the bearded pig (Sus barbatus). Drawing on a dataset of 295 total camera trap locations and 25,755 trap days across 18 field sites and three years in Sabah and Sarawak, Malaysian Borneo, we fitted occupancy models that incorporated socio-cultural covariates and ecological covariates hypothesized to influence bearded pig occupancy. We found that all competitive occupancy models included both socio-cultural and ecological covariates. Moreover, we found quantitative evidence supporting Indigenous pig hunting rights: predicted pig occupancy was positively associated with predicted high levels of Indigenous pig-hunting groups in low-accessibility areas, and predicted pig occupancy was positively associated with predicted medium and low levels of Indigenous pig-hunting groups in high-accessibility areas. These results suggest that bearded pig populations in Malaysian Borneo should be managed with context-specific strategies, promoting Indigenous pig hunting rights. We also provide important baseline information on bearded pig occupancy levels prior to the 2020–2021 outbreak of African Swine Fever (ASF), which caused social and ecological concerns after mass dieoffs of bearded pigs in Borneo. The abstract provided in Malay is in the Supplementary file

Rad21-Cohesin Haploinsufficiency Impedes DNA Repair and Enhances Gastrointestinal Radiosensitivity in Mice

Approximately half of cancer-affected patients receive radiotherapy (RT). The doses delivered have been determined upon empirical experience based upon average radiation responses. Ideally higher curative radiation doses might be employed in patients with genuinely normal radiation responses and importantly radiation hypersensitive patients would be spared the consequences of excessive tissue damage if they were indentified before treatment. Rad21 is an integral subunit of the cohesin complex, which regulates chromosome segregation and DNA damage responses in eukaryotes. We show here, by targeted inactivation of this key cohesin component in mice, that Rad21 is a DNA-damage response gene that markedly affects animal and cell survival. Biallelic deletion of Rad21 results in early embryonic death. Rad21 heterozygous mutant cells are defective in homologous recombination (HR)-mediated gene targeting and sister chromatid exchanges. Rad21+/− animals exhibited sensitivity considerably greater than control littermates when challenged with whole body irradiation (WBI). Importantly, Rad21+/− animals are significantly more sensitive to WBI than Atm heterozygous mutant mice. Since supralethal WBI of mammals most typically leads to death via damage to the gastrointestinal tract (GIT) or the haematopoietic system, we determined the functional status of these organs in the irradiated animals. We found evidence for GIT hypersensitivity of the Rad21 mutants and impaired bone marrow stem cell clonogenic regeneration. These data indicate that Rad21 gene dosage is critical for the ionising radiation (IR) response. Rad21 mutant mice thus represent a new mammalian model for understanding the molecular basis of irradiation effects on normal tissues and have important implications in the understanding of acute radiation toxicity in normal tissues