179566 research outputs found
Sort by
Climate-driven shifts in Southern Ocean primary producers and biogeochemistry in CMIP6 models
Get PDFAs a net source of nutrients fuelling global primary production, changes in Southern Ocean productivity are expected to influence biological carbon storage across the global ocean. Following a high-emission, low-mitigation pathway (SSP5-8.5), we show that primary productivity in the Antarctic zone of the Southern Ocean is predicted to increase by up to 30 % over the 21st century. The ecophysiological response of marine phytoplankton experiencing climate change will be a key determinant in understanding the impact of Southern Ocean productivity shifts on the carbon cycle. Yet, phytoplankton ecophysiology is poorly represented in Coupled Model Intercomparison Project phase 6 (CMIP6) climate models, leading to substantial uncertainty in the representation of its role in carbon sequestration. Here we synthesise the existing spatial and temporal projections of Southern Ocean productivity from CMIP6 models, separated by phytoplankton functional type, and identify key processes where greater observational data coverage can help to improve future model performance. We find substantial variability between models in projections of light concentration (>15 000 (µE m−2 s−1)2) across much of the iron- and light-limited Antarctic zone. Projections of iron and light limitation of phytoplankton vary by up to 10 % across latitudinal zones, while the greatest increases in productivity occurs close to the coast. Temperature, pH and nutrients are less spatially variable – projections for 2090–2100 under SSP5-8.5 show zonally averaged changes of +1.6 °C and −0.45 pH units and Si* ([Si(OH)4]–[NO]) decreases by 8.5 µmol L−1. Diatoms and picophytoplankton and/or miscellaneous phytoplankton are equally responsible for driving productivity increases across the subantarctic and transitional zones, but picophytoplankton and miscellaneous phytoplankton increase at a greater rate than diatoms in the Antarctic zone. Despite the variability in productivity with different phytoplankton types, we show that the most complex models disagree on the ecological mechanisms behind these productivity changes. We propose that a sampling approach targeting the regions with the greatest rates of climate-driven change in ocean biogeochemistry and community assemblages would help to resolve the empirical principles underlying the phytoplankton community structure in the Southern Ocean
A precision image-guided murine model of stereotactic ablative radiotherapy for hepatocellular carcinoma
Get PDFLiver tumours, both primary and metastatic, are diseases of unmet clinical need. Hepatocellular carcinoma (HCC) the most common primary liver tumour, like many other cancers, may be treated by stereotactic ablative radiotherapy (SABR), reducing off-target effects of radiation on local anatomical structures. However, integrating all the necessary components for stereotactic irradiation of hepatocellular carcinoma in murine models has not yet been reported. Here we provide the development and detailed characterisation of a murine SABR model combining both MRI and CT image-guided delineation of the tumour, together with CT-guided liver tumour radiotherapy. The model enables accurate delivery of clinically relevant doses of radiotherapy with good tolerability and on-target tumour responses in models with otherwise universally progressive disease. The development of this preclinical modelling platform paves the way for its integration into multimodal therapeutic and mechanistic testing in preclinical murine models of both metastatic and primary liver tumours, including hepatocellular carcinoma.</p
Bindone-based polymer for colorimetric detection of volatile amines
Get PDFEffective detection and monitoring of volatile amines are crucial for protecting human health and the environment, particularly in areas such as disease diagnosis and food spoilage detection. Traditional gas sensors, including electrochemical, semiconductor, and photochemical types, often suffer from limited selectivity, sensitivity and require complex and expensive synthesis and detection equipment. Colorimetric sensors, which are easily interpreted through visible colour changes, have recently gained attention for their simplicity and real-time detection capabilities. In this study, we present a chemosensing system based on the bindone motif, both as a small molecule (Bin) and embedded in a polymer backbone (PBin), for the effective colorimetric detection of volatile amines. Our system exhibits high selectivity and sensitivity, with detection limits as low as 0.04 ppm for Bin and 1.57 ppm for PBin. The colour change, driven by amine-induced tautomerisation, was confirmed through UV-Vis spectroscopy, NMR spectroscopy, and TD-DFT calculations. pH dependent studies reveal the importance of basicity on the mechanism and selectivity. By incorporating the bindone moiety into the polymer backbone, its thermal stability was significantly enhanced. The versatility of the sensor was demonstrated in solution, and paper-based film formats, with successful application in detecting amines released during fish spoilage. This work highlights the potential of the bindone-based chemosensor as a cost-effective, portable, and efficient tool for monitoring food freshness and other applications requiring the detection of volatile amines.</p
Differential benefit of adjuvant everolimus according to endocrine therapy backbone in the randomized UNIRAD trial
Get PDFBackgroundThe randomized, double-blind UNIRAD trial evaluating the addition of 2 years of everolimus to endocrine therapy in patients with high-risk, early luminal breast cancer failed to demonstrate a benefit. We report the subgroup analyses.Patients and methodsWe randomly assigned 1278 patients in a 1 : 1 ratio to receive 2 years of placebo or everolimus, added to endocrine therapy for up to 4 years after initiation. Randomization was stratified by endocrine therapy agent, prior adjuvant versus neoadjuvant therapy, progesterone receptor expression, and lymph node involvement. Subgroup analyses by each stratification factor were pre-specified. Post hoc analyses were carried out according to menopausal status and age. Treatment adherence was also analyzed.ResultsWe observed a limited trend toward more favorable prognostic features in tamoxifen-treated patients, with more frequent estrogen receptor-positive/progesterone receptor-positive tumors (88.5% versus 84.1%, P = 0.026) and less frequent pN2-positive status (39.8% versus 46.0%, P = 0.032). In premenopausal women, we observed a numerical benefit of everolimus: 3-year disease-free survival was 86% in the placebo group and 90% in the everolimus group (hazard ratio 0.76, 95% confidence interval 0.43-1.34). In premenopausal patients treated with tamoxifen (n = 153; 12.3%), we observed an even stronger trend in favor of everolimus as 3-year DFS was 84% in the placebo group and 91% in the everolimus group (hazard ratio 0.54, 95% confidence interval 0.28-1.02). Early discontinuation of either everolimus or placebo was less frequent in the tamoxifen group than in the aromatase inhibitor group: 48.0% versus 56.9% (P = 0.028).ConclusionsThe present post hoc analyses generate hypotheses regarding the interaction between menopausal status, tamoxifen, and everolimus in patients with high-risk, ER-positive, human epidermal growth factor receptor type 2-negative early breast cancer. They suggest that tamoxifen alone is an underpowered endocrine treatment in high-risk premenopausal patients
COSMIN review of the PANSS Marder factor solution and other factor models in people with schizophrenia
Get PDFThe Positive and Negative Syndrome Scale (PANSS) is widely used to assess schizophrenia symptoms. Initially designed with three subscales, Marder et al.´s 5-factor-Model (M5M) first proposed in 1997 has been frequently used in treatment trials, but it has never been systematically reviewed for its measurement properties. We utilized the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for systematic reviews and meta-analytical procedures to assess the psychometric properties of the M5M-PANSS. COSMIN comprises several steps: literature search, risk-of-bias assessments, assessing the updated criteria for good measurement properties, feasibility aspects and grading the quality of the evidence. We further assessed the goodness of fit of other PANSS factor models. We included 95 publications. The M5M-PANSS showed good construct validity, but "insufficient" structural validity. Evidence of other COSMIN domains is largely lacking. Among the multiple (73) factor solutions examined with confirmatory methods, several other 5-factor solutions had better model fit. According to COSMIN rules the M5M should not be recommended for use. Other five-factor models such as the one proposed by Wallwork et al. 1 warrant further evaluation. Nevertheless, the factor composition of the M5M and these other models was relatively similar, so previously published results should not be disregarded. </p
Longitudinal associations between cultural engagement and mental and social well-being:A fixed-effects analysis of the English Longitudinal Study of Ageing
Get PDFObjectives Cultural engagement (e.g., going to museums, the theater, and concerts) has been evidenced to support older adults' well-being. However, whether cultural engagement is associated with multiple well-being domains and whether associations vary by sociodemographics and health warrants further investigation. Methods Using 14 years of data from the English Longitudinal Study of Ageing, we tested the longitudinal associations between cultural engagement and 7 well-being outcomes among 6,932-10,428 individuals aged 50-99 years. We used fixed-effects regression to explore the longitudinal associations between cultural engagement and the outcomes, generalized method of moments estimators to assess directionality, and interactions to test for moderation effects of sociodemographic and health conditions. Results We found that increases in cultural engagement were associated with increases in life satisfaction, quality of life, happiness, and having a worthwhile life and decreases in depressive symptoms, anxiety, and loneliness. After assessing directionality, cultural engagement increases predicted decreases in depressive symptoms. Interactions suggest that older adults with a long-standing health condition, living without a partner, and who are female may experience greater well-being benefits from being culturally engaged. Discussion Our findings underscore the potential of cultural engagement to enhance multiple well-being domains for older adults. This emphasizes the need to ensure equitable access to cultural engagement for all older adults, particularly those facing barriers to participation and those with poorer health, who may benefit the most from such initiatives.</p
Accountability and hyperaccountability in child protection scandals
Get PDFThe number of child abuse–related deaths has decreased significantly in the United Kingdom over the past 50 years, but there remains public and political concern about the actual and perceived risk of child deaths, with resultant processes enacted to supervise child protection practice. Drawing upon an analysis of the ways in which the deaths of two children, Victoria Climbié and Peter Connelly, became child protection scandals in England, we examine the gap between notions of accountability as an ideal, and enacted accountability, as the embodiments of supervisory mechanisms. We consider how these two sides of accountability are produced in child protection practice via three mechanisms: the inspectorate, the child death review process, and the oversight of individual social workers by their employers and professional regulator. We explore how these mechanisms can lead to the unbalanced apportioning of blame in child protection scandals, whereby social workers and managers are held individually responsible for a child abuse–related death beyond any reasonable conception of answerability—what we refer to as hyperaccountability. Through exploring these issues, we seek to contribute to debates as to how child protection services can be robust, while proportionate, in how they seek to support families and protect vulnerable children
BA and object state changes:Unspecific morphosyntactic cues shape Mandarin discourse comprehension
Get PDFUnderstanding object state changes as consequences of transitive events is an important part of event cognition. How do people do this? Previous research shows that comprehenders use verb-based morphosyntactic cues that have specific meanings to generate expectations about the state of the upcoming objects in discourse processing. Can they also do so using non–verb-based and unspecific morphosyntactic cues, such as the preposition “BA” in the Mandarin “BA” structure? In four forced-choice image selection experiments, we found a robust “BA” effect in shaping Mandarin comprehenders’ discourse expectations about object state changes. Moreover, this effect was amplified by the presence of classifiers and modulated by contexts with varying levels of constraint on the upcoming objects. These findings provide important insights into discourse expectations based on a previously unstudied type of unspecific morphosyntactic cue (i.e., a preposition) and shed new light on language-mediated visual attention and event segmentation in discourse processing
Decoding the genetic and environmental forces in propelling the surge of early-onset colorectal cancer
No full textEarly-onset colorectal cancer (EOCRC) shows a different epidemiological trend compared to later-onset colorectal cancer, with its incidence rising in most regions and countries worldwide. However, the reasons behind this trend remain unclear. The etiology of EOCRC is complex and could involve both genetic and environmental factors. Apart from Lynch syndrome and Familial Adenomatous Polyposis, sporadic EOCRC exhibits a broad spectrum of pathogenic germline mutations, genetic polymorphisms, methylation changes, and chromosomal instability. Early-life exposures and environmental risk factors, including lifestyle and dietary risk factors, have been found to be associated with EOCRC risk. Meanwhile, specific chronic diseases, such as inflammatory bowel disease, diabetes, and metabolic syndrome, have been associated with EOCRC. Interactions between genetic and environmental risk factors in EOCRC have also been explored. Here we present findings from a narrative review of epidemiological studies on the assessment of early-life exposures, of EOCRC-specific environmental factors, and their interactions with susceptible loci. We also present results from EOCRC-specific genome-wide association studies that could be used to perform Mendelian randomization analyses to ascertain potential causal links between environmental factors and EOCRC.</p
Poka: a necro-robot beetle with a measured payload ratio of 6847%
No full textThis paper is concerned with the design, manufacture and validation of 'Poka', a novel millimetre-scale necro-robot aimed at bridging the performance gap between miniature robots and insects. To create Poka, we use the exoskeleton of a deceased five-horned rhinoceros beetle (Eupatorus gracilicornis) as a mechanical chassis, which is mechatronically functionalised to enable ambulation. When comparing the payload ratio, PR, of Poka against reported values of the rhinoceros beetle Xyloryctes thestalus, we find that Poka's PR is more than 2-fold higher, reaching a measured maximum of 6847% (i.e. 68.47 times its own body weight). The specific power at maximum payload, Ps,t, is nevertheless of the same order of magnitude in both Xyloryctes thestalus (0.21 W/kg) and Poka (0.28 W/kg). Poka's highest average speed, v (1.55 mm/s) is achieved at a PR = 2739%, after which it progressively decreases with increasing payload ratio, reaching its minimum v = 1.3 mm/s at maximum payload ratio. When comparing Poka's maximum measured PR of 6847% against those of sixteen other ambulating robots, we find that Poka's PR far exceeds that of any other robot to date, the highest being otherwise from SuperBot who has a PR = 530%. Poka's payload ratio is therefore the highest robot payload ratio recorded to date and we attribute this to (a) the use of the beetle body as a natural composite chassis with high specific properties, and (b) the additive manufacture of bionic beetle parts using low density but stiff polylactic acid, designed with structurally stable geometries.<br/
Access Repository Dashboard
Do you manage Edinburgh Research Explorer? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!