136986 research outputs found
Sort by
What we mean when we say semantic: Toward a multidisciplinary semantic glossary
No full textTulving characterized semantic memory as a vast repository of meaning that underlies language and many other cognitive processes. This perspective on lexical and conceptual knowledge galvanized a new era of research undertaken by numerous fields, each with their own idiosyncratic methods and terminology. For example, "concept" has different meanings in philosophy, linguistics, and psychology. As such, many fundamental constructs used to delineate semantic theories remain underspecified and/or opaque. Weak construct specificity is among the leading causes of the replication crisis now facing psychology and related fields. Term ambiguity hinders cross-disciplinary communication, falsifiability, and incremental theory-building. Numerous cognitive subdisciplines (e.g., vision, affective neuroscience) have recently addressed these limitations via the development of consensus-based guidelines and definitions. The project to follow represents our effort to produce a multidisciplinary semantic glossary consisting of succinct definitions, background, principled dissenting views, ratings of agreement, and subjective confidence for 17 target constructs (e.g., abstractness, abstraction, concreteness, concept, embodied cognition, event semantics, lexical-semantic, modality, representation, semantic control, semantic feature, simulation, semantic distance, semantic dimension). We discuss potential benefits and pitfalls (e.g., implicit bias, prescriptiveness) of these efforts to specify a common nomenclature that other researchers might index in specifying their own theoretical perspectives (e.g., They said X, but I mean Y)
An evaluation of in vitro culture conditions for Haemonchus contortus for compound screening
No full text© 2025 Sandani Sachintha Thilakarathne AthukoralageParasitic nematodes, such as Haemonchus contortus, pose significant global health and
economic challenges, causing extensive production losses in livestock animals. The
control of H. contortus has relied heavily on the use of anthelmintic drugs, but widespread resistance needs novel interventions. In this project, the supplementation of
the culture medium lysogeny broth (LB*) with sheep serum was evaluated to improve in vitro development, motility and survival of H. contortus larvae.
Supplementation with 7.5% sheep serum (designated LBS*) significantly enhanced larval development compared to LB*, achieving early sexual differentiation at 7 days. Larvae in LBS* exhibited increased motility and survival at 14 days relative to LB*. Proteomic analysis revealed elevated expression of structural proteins, metabolic enzymes and genetic information processing pathways in LBS* cultured larvae, reflecting improved physiological adaptation in vitro. Specifically, zona pellucida domain and Mago nashi proteins were markedly upregulated, suggesting roles in cuticle integrity and sexual differentiation. The utility of LBS* was further tested in compound screening. While the screening results in LB* and LBS* differed due to potential serum compound interactions, LBS* enabled the identification of moderate activity compounds when the motility reduction threshold was adjusted. This highlights the importance of optimising in vitro assay conditions for anthelmintic discovery.
Overall, this study demonstrated that serum-enriched culture conditions improve larval physiological relevance, supporting development, motility and resilience in vitro. These findings provide a platform for improved screening of anthelmintic compounds and emphasise the importance of mimicking the host environment to facilitate discovery
efforts against drug resistant nematodes
The relationship between ON–OFF function and OCT structural and angiographic parameters in early diabetic retinal disease
No full textPURPOSE: This study measured associations between ON and OFF functional indicators and structural optical coherence tomography (OCT) and OCT angiography (OCTA) markers in diabetic retinal disease. METHODS: Fifty-four participants with type 1 or type 2 diabetes (mean age = 34.1 years; range 18-60) and 48 age-matched controls (mean age = 35.4 years, range 18-59) underwent visual psychophysical testing, OCT and OCTA retinal imaging. Psychophysical tasks measuring (A) contrast increment and decrement sensitivity and (B) response times to increment and decrement targets were assessed as surrogate measures of ON and OFF retinal ganglion cell function. RESULTS: The group with diabetes had worse foveal contrast increment and decrement thresholds (p = 0.04) and were slower to search for increment and decrement targets relative to controls (p = 0.009). Individuals with diabetes had a less circular foveal avascular zone (FAZ) (p < 0.001) but did not differ from controls in foveal vessel density and FAZ area. Functional and structural outcome measures related to the peripheral retina were also comparable between those with and without diabetes. Functional responses to increments and decrements were not significantly correlated with FAZ circularity or vessel density in individuals with diabetes. CONCLUSIONS: Diabetic retinal disease results in impaired performance on measures of inferred ON and OFF pathway function in addition to vascular deficits measurable with OCTA. Future longitudinal studies may determine the temporal relationship between these deficits, and whether they predict future diabetic retinopathy
Quorum sensing and DNA methylation play active roles in clinical Burkholderia phase variation
No full textPhenotypic diversity in bacteria often results from adaptation to changing environmental conditions, exemplified by variable colony morphotypes. In Burkholderia pseudomallei, discrete genomic alterations and modulation of gene expression facilitate adaptation. Adapted variants of species within the Burkholderia cepacia complex (Bcc) often lose the pC3 virulence megaplasmid, impacting their colony morphology and their production of virulence factors. In this study, we characterize variants arising in Burkholderia ambifaria clinical isolates using proteomics and phenotypic tests and show that some of them have retained the pC3, indicating a distinct phase variation mechanism at play in this Bcc species. Interestingly, variants of B. ambifaria strains CEP0996 (pC3-null) and HSJ1 (pC3-positive) still share similarities in phenotypes controlled by the Cep quorum-sensing (QS) system. We further investigated the role of QS in B. ambifaria HSJ1 phase variation and confirmed that the Cep QS system is important for the emergence of variants. Given that DNA methylation is a key epigenetic factor regulating virulence factors in Burkholderia cenocepacia, we hypothesized that adenosine DNA methylation also governs phase variation in B. ambifaria HSJ1. By deleting the genes encoding putative adenosine DNA methyltransferases, we discovered that an orphan type II DNA methyltransferase inhibits the emergence of phase variants. This study is the first to demonstrate that quorum sensing and adenosine DNA methylation are two antagonistic systems independently controlling phase variation in B. ambifaria
Patient perspectives on surgical handover quality: a mixed-methods survey
No full textBackground: In-hospital handover of patient care is an essential but high-risk professional activity that often lacks transparency for patients. The purpose of this survey was to gain insight into surgical patients’ perceptions of handover communications between doctors, incorporating patient and public involvement to enhance accessibility and understanding. Methods: A cross-sectional, mixed-methods survey was developed with patient and public involvement and distributed to general surgery patients in two University Teaching Hospitals between 24 October 2023 and 21 July 2024. Comparative analyses of quantitative data were performed using McNemar’s test for paired nominal data and Wilcoxon rank-sum test for continuous data. Free-text responses underwent thematic analysis to validate and expand on quantitative findings. Patient and public involvement partners contributed to study design, methodology, and the final manuscript. Results: In total, 208 responses were received (52.3%). Significantly more patients reported having prior knowledge of nursing handovers (73.1%) compared to doctors' handovers (63.9%; x2 = 14.53, p = 0.0002). Patient perceptions of the handover process were generally positive; although satisfaction declined significantly with weekend handovers (p < 0.05). Thematic analysis identified four themes: (1) the impact of poor inter-professional communication, (2) the importance of teamwork, (3) external factors influencing handover effectiveness, and (4) patient nonchalance about their care. The use of patient and public involvement in this study improved survey accessibility and understanding of the concept and importance of handover. Conclusions: This study shows limited prior awareness of handover between doctors among surgical patients, especially the potential hazards that can arise if performed poorly. Patient and public involvement improved accessibility and understanding of the topic; however, challenges such as adequate training for meaningful engagement remain
Reduced Red Blood Cell Deformability in Vivax Malaria
No full textReduced deformability of both infected and uninfected red blood cells (RBCs) contributes to pathogenesis in Plasmodium falciparum malaria. Whole-blood RBC deformability (RBC-D) is not well characterized in Plasmodium vivax malaria. We used a laser-assisted optical rotational cell analyzer to measure the RBC-D in fresh whole-blood samples from Malaysian patients with vivax malaria (n = 25). Deformability of whole-blood RBCs, the vast majority of which were uninfected, was reduced in vivax malaria compared with controls (n = 15), though not to the same degree as in falciparum malaria (n = 90). Reduced RBC-D may contribute to the pathogenesis of vivax malaria, including splenic retention of uninfected RBCs
A systematic review of how endocrine-disrupting contaminants are sampled in environmental compartments: wildlife impacts are overshadowed by environmental surveillance
No full textEndocrine-disrupting contaminants (EDCs) are frequently monitored in environments because of their biological impacts on wildlife and humans. We conducted a systematic review using Web of Science to identify global research trends for EDC environmental sampling. Specifically, we aim to better understand geographic variation in (1) the compartment that EDCs were sampled in the environment; (2) the types of EDC sampled; and (3) the taxa that are sampled. A total of 9140 papers were found, of which 2554 were included in our review. The number of studies sampling EDCs varied between continents, with majority of research occurring in Europe, Asia, and North America. Although economy and access to technology will contribute to the number of articles published, we found the current output of research showed distinct disparities in sampling methods. Across all continents, water was the most frequently sampled compartment to determine EDC concentrations (sampled in 50-75% of studies). Wildlife was sampled far less often in studies across all continents, comprising 30% of studies at most. Pharmaceuticals were the most commonly studied chemical group, and fish were the most commonly sampled taxonomic group. Although far fewer studies sampled for EDCs in wildlife compared with abiotic compartments, these studies provide valuable information on the potential consequences of environmental EDC exposure and link environmental surveillance of EDCs with lab-measured organism-level effects. Studies that sampled only the water matrix for EDCs may be doing so as a proxy despite the large knowledge gaps on how environmental EDCs affect wildlife at varying concentrations
Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial
No full textBACKGROUND AND PURPOSE: In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. METHODS: ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0-2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. RESULTS: Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0-2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8-10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. CONCLUSION: Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles
Understanding experiences of optimal survivorship care: findings from a population-based study of cancer survivors
No full textBackground: Multiple frameworks describing optimal cancer survivorship care recommend the development of systems to monitor delivery of quality care. This study reports the experiences of cancer survivorship care in Australia and examines associations with patient-level sociodemographic and clinical characteristics. Methods: People aged ≥ 16 years, with any cancer receiving cancer care in a Victorian public hospital in 2018, were invited to complete a survey assessing care experiences. Seven items assessed follow-up care experiences with optimal care indicated by the response: ‘Yes, definitely received’, and sub-optimal care by responses ‘Yes, I think so’, ‘No’, and ‘Not sure’. A composite score was derived with optimal care defined as positive experiences on the majority of items. Sociodemographic and clinical factors associated with optimal care were examined using multivariable logistic regression. Results: Of the 4998 (47% response rate) respondents, 3555 were receiving follow-up care. The item most respondents indicated receiving optimal care was ‘receiving information about schedule of tests/check-ups’ (73%), with optimal care least likely to be reported for the item ‘receiving information about new symptoms needing investigation’ (44%). Based on our composite measure, only 40% had optimal survivorship care overall. Those more likely to report optimal survivorship care were male, from lower socioeconomic advantage areas, reported excellent health, diagnosed with breast, prostate, lung or a haematological cancer, and diagnosed less recently. Conclusions: Large numbers of Australian cancer survivors report sub-optimal survivorship care, with experiences varying by some sociodemographic and clinical characteristics. Understanding reasons for differences can provide insight into strategies to ameliorate variations
Rapid, reference-free identification of bacterial pathogen transmission using optimized split k-mer analysis
No full textInfections caused by multidrug-resistant organisms (MDROs) are difficult to treat and often life threatening and place a burden on the healthcare system. Minimizing the transmission of MDROs in hospitals is a global priority with genomics proving to be a powerful tool for identifying the transmission of MDROs. To optimize the utility of genomics for prospective infection control surveillance, results must be available in real time, reproducible and simple to communicate to clinicians. Traditional reference-based approaches suffer from several limitations for prospective genomic surveillance. Whilst reference-free or pairwise genome comparisons avoid some of these limitations, they can be computationally intensive and time consuming. Split k-mer analysis (SKA) offers a viable alternative facilitating rapid reference-free pairwise comparisons of genomic data, but the optimum SKA parameters for the detection of transmission have not been determined. Additionally, the accuracy of SKA-based inferences has not been measured, nor whether modified quality control parameters are required. Here, we explore the performance of 60 SKA parameter combinations across 50 simulations to quantify the false negative and positive SNP proportions for Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae and Staphylococcus aureus. Using the optimum parameter combination, we explore concordance between SKA, multilocus sequence typing (MLST), core genome MLST (cgMLST) and Snippy in a real-world dataset. Lastly, we investigate whether simulated plasmid gain or loss could impact SNP detection with SKA. This work identifies that the use of SKA with sequencing reads, a k-mer length of 19 and a minor allele frequency filter of 0.01 is optimal for MDRO transmission detection. Whilst SNP detection with SKA (when used with sequencing reads) undercalls SNPs compared to Snippy, it is significantly faster, especially with larger datasets. SKA has excellent concordance with MLST and cgMLST and is not impacted by simulated plasmid movement. We propose that the use of SKA for the detection of bacterial pathogen transmission is superior to traditional methodologies, capable of providing results in a much shorter timeframe