75079 research outputs found
Sort by
Alzheimer's disease pathophysiology in the retina
No full textThe retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer’s disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid β-protein (Aβ) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aβ deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT angiography, confocal scanning laser ophthalmoscopy, and hyper-spectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD’s impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring
Sex differences in the serum proteomic profile during acute low back pain : a preliminary study of the relationship to future low back pain
No full textThe molecular processes driving the transition from acute to chronic low back pain (LBP) remain poorly understood and are likely to be sexually dimorphic. This study aimed to explore sex differences in the serum proteomic profile of people experiencing an acute LBP episode and determine if serum protein concentrations were associated with three-month outcome. Serum samples were collected through venepuncture from 30 female and 29 male participants experiencing an acute LBP episode. Serum samples underwent trypsin digestion and fractionation using hydrophobic interaction chromatography and were then analysed using mass-spectrometry. Mass-spectrometry spectra were searched in the Swissprot database for protein identification. Sex differences in protein abundance changes were evident upon inspection of fold changes. Multivariable data analysis identified 21 serum proteins during the acute episode that correctly classified 93% of males and 23 serum proteins that correctly classified 90% of females with ongoing LBP at 3 months. Pathway analysis suggested the differentially expressed proteins during acute LBP were frequently involved in immune, inflammatory, complement, or coagulation responses. This data provides preliminary evidence that biological pro- cesses during an acute LBP episode may contribute to the resolution, or persistence, of LBP symptoms at 3 months, however, these processes differ between males and females. Perspective: Differential expression of serum proteins was observed between male and female participants during an acute LBP episode. This preliminary work provides a foundation for future research targeting distinct immune system processes in males and females that may interfere with the transition from acute to chronic LBP
Arterial and venous peripheral vascular assessment using wearable electro-resistive morphic sensors
No full textPeripheral vascular diseases (PVDs) represent a significant burden on global human health and healthcare systems. With continued growth in obesity and diabetes, it is likely that the incidence of these conditions will increase. As many PVDs remain undiagnosed, low-cost and easy to use diagnostic methods are required. This work uses newly developed wearable electro-resistive morphic sensors to assess venous and arterial competence in the lower limbs of 36 healthy subjects. Comparison of this HeMo device was made to currently available benchtop light reflection rheography and photoplethymography devices. Results indicate that HeMo can detect the physiological signals of interest for both chronic venous insufficiency and peripheral arterial disease and all subjects were interpreted as healthy by each system. However, measurement repeatability of HeMo was highlighted as an issue that requires further system development. Furthermore, as HeMo captures changes in a section of limb circumference due to changes in underlying blood movement, rather than at a single point, the recorded signal is typically damped by comparison. This factor should be considered in any future developments
Corporate governance, home country governance, and MNE CSR : evidence from Ghana
No full textThis study examines how the corporate social responsibility (CSR) of multinational enterprises (MNEs) operating in Ghana is affected by home country governance and corporate governance. Using data manually collected from a sample of MNEs from 2010 to 2018, we find that (1) MNE CSR is positively affected by home country governance; and (2) the positive effect of home country governance is strengthened by the subsidiary's board independence but not by board gender diversity. Our additional analyses show that MNEs from better governed home countries are more likely to establish CSR foundations and that CSR foundations have positive impact on MNE CSR. This study contributes to the literature on MNE CSR by providing empirical evidence from Ghana, where MNEs play an increasingly important role but scholars have paid little attention to what drives corporate giants to help address the country's social issues
Evaluating recalibrating AI models for breast cancer diagnosis in a new context : insights from transfer learning, image enhancement and high-quality training data integration
No full textThis paper investigates the adaptability of four state-of-the-art artificial intelligence (AI) models to the Australian mammographic context through transfer learning, explores the impact of image enhancement on model performance and analyses the relationship between AI outputs and histopathological features for clinical relevance and accuracy assessment. A total of 1712 screening mammograms (n = 856 cancer cases and n = 856 matched normal cases) were used in this study. The 856 cases with cancer lesions were annotated by two expert radiologists and the level of concordance between their annotations was used to establish two sets: a ‘high-concordances subset’ with 99% agreement of cancer location and an ‘entire dataset’ with all cases included. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of Globally aware Multiple Instance Classifier (GMIC), Global-Local Activation Maps (GLAM), I&H and End2End AI models, both in the pretrained and transfer learning modes, with and without applying the Contrast Limited Adaptive Histogram Equalization (CLAHE) algorithm. The four AI models with and without transfer learning in the high-concordance subset outperformed those in the entire dataset. Applying the CLAHE algorithm to mammograms improved the performance of the AI models. In the high-concordance subset with the transfer learning and CLAHE algorithm applied, the AUC of the GMIC model was highest (0.912), followed by the GLAM model (0.909), I&H (0.893) and End2End (0.875). There were significant differences (p < 0.05) in the performances of the four AI models between the high-concordance subset and the entire dataset. The AI models demonstrated significant differences in malignancy probability concerning different tumour size categories in mammograms. The performance of AI models was affected by several factors such as concordance classification, image enhancement and transfer learning. Mammograms with a strong concordance with radiologists’ annotations, applying image enhancement and transfer learning could enhance the accuracy of AI models
Robustness of corner-supported modular steel buildings with core walls
No full textThis paper studies the dynamic response of corner-supported modular steel buildings with a core wall system, under progressive collapse scenarios, associated with corner module removals. Since using secondary systems such as concrete core in mid- to high-rise buildings is currently unavoidable, understanding their impact on load transfer between modules during collapse scenarios becomes essential. The designated four-, eight-, and twelve-story buildings were modelled using the macro-model-based finite element method in Abaqus. In addition, three different locations are considered for the concrete shear core within the building plan, leading to nine various case scenarios. Each vertical and horizontal inter-module connection was modelled by one axial and two shear springs with predefined nonlinear force-displacement behavior. The local and global buckling, which plays an essential role in the building’s stability, was considered to obtain accurate results. Finally, parametric studies on the building response were carried out, including the intra-module connection rigidity and inter-module connection stiffness. The results demonstrated that the core wall could maintain the robustness of a modular steel building through two mechanisms dependent on its location within the plan. In addition, preventing plastic hinges from forming in beams could be introduced as an anti-collapse mechanism in the corner module removal scenarios
[In Press] Viewing life as a 'timeline' : digital visual research to retrace people's journeys
No full textThis research note introduces the experience of using ‘timelines’ as a visual research method during online interviewing. It does so through a series of questions and answers that guide the reader through an exploration, understanding of and reflection on the method. This qualitative approach was used while conducting research on the influence that participation in a Reality TV show had on its finalists, and on the opportunities and life choices that were afforded to participants after the end of the show. The reader is encouraged to draw links between their own work as a qualitative researcher and the possibilities that this method can offer either in filling gaps or in expanding their current endeavour. Ultimately, the ‘quality’ of the answers we find in our qualitative work is illustrative of the way we choose to ask our questions
Pyrogeography in flux : reorganization of Australian fire regimes in a hotter world
No full textChanges to the spatiotemporal patterns of wildfire are having profound implications for ecosystems and society globally, but we have limited understanding of the extent to which fire regimes will reorganize in a warming world. While predicting regime shifts remains challenging because of complex climate–vegetation–fire feedbacks, understanding the climate niches of fire regimes provides a simple way to identify locations most at risk of regime change. Using globally available satellite datasets, we constructed 14 metrics describing the spatiotemporal dimensions of fire and then delineated Australia's pyroregions—the geographic area encapsulating a broad fire regime. Cluster analysis revealed 18 pyroregions, notably including the (1) high-intensity, infrequent fires of the temperate forests, (2) high-frequency, smaller fires of the tropical savanna, and (3) low-intensity, diurnal, human-engineered fires of the agricultural zones. To inform the risk of regime shifts, we identified locations where the climate under three CMIP6 scenarios is projected to shift (i) beyond each pyroregion's historical climate niche, and (ii) into climate space that is novel to the Australian continent. Under middle-of-the-road climate projections (SSP2-4.5), an average of 65% of the extent of the pyroregions occurred beyond their historical climate niches by 2081–2100. Further, 52% of pyroregion extents, on average, were projected to occur in climate space without present-day analogues on the Australian continent, implying high risk of shifting to states that also lack present-day counterparts. Pyroregions in tropical and hot-arid climates were most at risk of shifting into both locally and continentally novel climate space because (i) their niches are narrower than southern temperate pyroregions, and (ii) their already-hot climates lead to earlier departure from present-day climate space. Such a shift implies widespread risk of regime shifts and the emergence of no-analogue fire regimes. Our approach can be applied to other regions to assess vulnerability to rapid fire regime change
Goal-directed therapeutic exercise for paediatric posterior fossa brain tumour survivors : a qualitative analysis of experiences
No full textPurpose: To explore child and parent experiences of a 12-week goal-directed therapeutic exercise intervention in paediatric posterior fossa brain tumours survivors and to identify features of the program that influenced program adherence and acceptability. Methods: Eleven interviews were conducted; five parent-child dyads (mothers = 83%) and one parent only (mean child age = 10.6 ± 3.0 years; 83% male). Posterior fossa brain tumour survivors, who participated in a weekly goal-directed exercise program for 12 weeks, completed semi-structured interviews to discuss their experience of the program. An inductive content analysis was undertaken. Interviews were transcribed, imported into NVivo and independently coded by two reviewers. Code and content categories were iteratively discussed and refined. Results: Five content categories were generated: (1) perceived improvements, (2) program logistics, (3) activity selection, (4) connection with the therapist and (5) options for technology. All participants valued the tailored exercise program and described improvements in movement competence. Children and their parents discussed preferring home- and community-based locations and favoured face-to-face delivery. Occasionally, parents reported difficulty completing the home program due to low child motivation or family time restrictions. Multiple families suggested an interactive digital application would be an effective delivery channel for the supplemental home-based program. Conclusion: A goal-directed exercise program delivered at home and in community-based locations was considered valuable and helpful for improving movement competence in paediatric survivors of posterior fossa brain tumour
[In Press] Follow the allosteric transitions to predict variant pathogenicity : a channel-specific approach
No full textWe were intrigued to read a recent article by Brünger et al. outlining an innovative method to predict pathogenicity for variants in ion channel-encoding genes by determining the 2D distance of amino acids from the central axis of the ion channel pore using published high-resolution protein structures. The resulting dataset was combined with amino acid properties and then machine learning algorithms to describe the potential pathogenicity of genetic variants. A major advance of this approach is the clear distinction in the distance to the pore axis for pathogenic versus benign population variants: the closer to the pore axis, the greater the likelihood of pathogenicity. This enabled correlation with clinical representations whereby more severe phenotypes were observed for variants closest to the pore. We find this an elegant approach to a complex problem. However, the universal approach ultimately limits precision in predicting pathogenicity, which may be overcome with a protein-specific approach