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Does RSClin provide additional information over classic clinico-pathologic scores (PREDICT 2.1, INFLUENCE 2.0, CTS5)?
Get PDFPurposeFew studies have compared the performance of gene-expression profiling tests (e.g. Oncotype-Dx) to clinico-pathologic risk calculators (e.g. PREDICT 2.1, INFLUENCE 2.0, and CTS5) or tools that combine both (e.g. RSClin) in patients with early breast cancer (EBC). A large trial dataset was used to evaluate the prognostic performance of different tests based on patient outcomes.MethodsThe TEAM pathology cohort accrued samples from 4736 postmenopausal hormone positive women with EBC, treated with either exemestane or tamoxifen followed by exemestane. Oncotype-Dx-trained risk scores were previously generated by gene-expression profiling. Patient data was used to calculate various recurrence scores. Analysis was restricted to the N0/N1 population and prognostic ability of selected risk tools was assessed using Cox regression analysis and Harrell's C-statistic.ResultsResults were available for 2065 patients. There was low correlation between PREDICT 2.1 (r = -0.12), INFLUENCE 2.0 (r = 0.20), CTS5 (r = 0.16) with Oncotype-Dx-trained results. In N0 patients, RSClin had improved prognostic ability (C-statistic = 0.66) on DMFS compared to PREDICT 2.1 (0.60), INFLUENCE 2.0 (0.57), CTS-5 (0.62), and Oncotype-Dx (0.63).ConclusionCombining molecular and clinico-pathologic factors enhances prognostic information. However, the impact of this on actual patient management requires further prospective validation.The trial is registered with clinicaltrials.gov NCT00279448 and NCT00032136; with Netherlands Trial Register, number NTR 267; and the Ethics Commission Trial, number 27/2001
Thermal Marangoni natural convection enables directional transport across immiscible liquids
Get PDFThe ability to control molecular transport across immiscible liquid interfaces is critical for applications in manufacturing, biotechnology, and space research. Such transport mechanisms have garnered attention for their intriguing behavior and transformative potential in technology and science for a long time. Here, we demonstrate that unsteady temperature fields drive directional transport of water molecules across the oil-water interface, where weakened hydrogen bonding orients hydroxyl groups toward the oil phase. Through the Marangoni natural convection, water molecules migrate into the oil phase, forming stable nanoscale dispersions. We provide evidence that this transport is tunable via temperature gradients, offering a controllable pathway for mass transfer. This approach offers a potential, scalable, surfactant-free method for nanoemulsions production, with applications in drug delivery and advanced manufacturing. With surface tension as one of the driving forces, this phenomenon is equally valid in microgravity or zero-gravity environments. These findings advance the understanding of Marangoni natural convection and provide new insights into microscale fluid dynamics and spontaneous molecular migration at the oil-water interface
Global diversity of soil-transmitted helminths reveals population-biased genetic variation that impacts diagnostic targets
Get PDFSoil-transmitted helminths (STHs) are intestinal parasites that affect over a billion people worldwide. STH control relies on microscopy-based diagnostics to monitor parasite prevalence and enable post-treatment surveillance; however, molecular diagnostics are rapidly being developed due to increased sensitivity, particularly in low-STH-prevalence settings. The genetic diversity of helminths and its potential impact on molecular diagnostics remain unclear. Using low-coverage genome sequencing, we assess the genetics of STHs within worm, faecal, and purified egg samples from 27 countries, identifying differences in the genetic connectivity and diversity of STH-positive samples across regions and cryptic diversity between closely related human- and pig-infective species. We define substantial copy number and sequence variants in current diagnostic target regions and validate the impact of genetic variation on qPCR diagnostics using in vitro assays. Our study provides insights into the diversity and genomic epidemiology of STHs, highlighting both the challenges and opportunities for developing molecular diagnostics needed to support STH control efforts.</p
Preoperative chronic opiate use associated with a worse joint-specific function and quality of life before and after total hip and knee arthroplasty
Get PDFAims: The aim of this study was to assess whether chronic pre-arthroplasty use of strong opiates impacted the pre- and postoperative joint-specific function, quality of life (QoL), pain scores, and satisfaction in those undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Methods: This prospective study assessed 1,487 patients (THA n = 729; TKA n = 758). Preoperative opiate use of more than a month was used to define the opioid group. Patient demographics, comorbidities, Oxford Hip Score (OHS), Oxford Knee Score (OKS), and EuroQol five-dimension questionnaire (EQ-5D) scores were collected preoperatively and at six months postoperatively. Patient satisfaction with their joint was assessed at six months. Results: The opioid groups consisted of 95 patients in both the THA (13.0%) and TKA (12.5%) cohorts. Pre- and postoperative OHS, OKS, and EQ-5D were clinically (greater than the minimal clinically important difference) and statistically (p < 0.001) significantly worse for the opioid groups undergoing THA and TKA. The opioid group was independently associated with a significantly worse improvement in OHS (-3.0, 95% CI -4.8 to -1.2; p = 0.001) and EQ-5D (-0.089, 95% CI -0.132 to -0.041; p < 0.001) for those undergoing THA, but no significant (OKS, p = 0.650 and EQ-5D, p = 0.485) association was demonstrated in the TKA cohort. There was no difference in satisfaction with their arthroplasty between opioid and opiate-naive groups undergoing THA (p = 0.133) or TKA (p = 0.797). Conclusion: Preoperative opiate use was associated with clinically significantly worse pre- and postoperative joint-specific function and QoL. Those undergoing THA had a clinically worse improvement in their joint-specific function, but this was not observed in those undergoing TKA. However, patients were equally satisfied with outcomes.</p
Norwegian sheep farmers’ perception of the advantages and disadvantages of Precision Livestock Farming (PLF) technologies
Get PDFDespite enthusiastic industry and policy developments around Precision Livestock Farming (PLF) technology, it is unclear how often the development of new tools is centred around farmers' needs and means. This study aimed to identify the perceived benefits and disadvantages of PLF technology on Norwegian sheep farms. Semi-structured interviews were conducted with 24 Norwegian sheep farmers who use one or more PLF tool. Participants were between 35 and 70 years old, were from three Norwegian regions and farmed between 20 and 400 ewes. The most used technologies were GPS collars monitoring sheep location and registration software. Interview transcripts were analysed using reflexive thematic analysis and six themes were identified: Resources and Savings, Gaining Control, The User Experience, The Human-Animal Relationship, Trust in Technology and Stewards of the Land. The identified advantages of technology use were time, energy and economic savings that lightened farmers' cognitive burden, offered an increased sense of control gained through access to new data, an improved relationship between the farmers and their sheep, and an increased ability to preserve their farming lifestyle and the land they farm on. However, these benefits were not unanimously agreed upon, with many participants suggesting that the economic costs outweighed the time and energy savings, that farmers’ cognitive burden actually increased, that sellers and digital information could be untrustworthy and that technology posed a risk to the quality of the human-animal relationship. These findings could inform the future development and applications of user-centric PLF products to support the resilience of farming communities
Stain-free artificial intelligence-assisted light microscopy for the identification of blood cells in microfluidic flow.
Get PDFThe identification and classification of blood cells are essential for diagnosing and managing various haematological conditions. Haematology analysers typically perform full blood counts but often require follow-up tests such as blood smears. Traditional methods like stained blood smears are laborious and subjective. This study explores the application of artificial neural networks for rapid, automated, and objective classification of major blood cell types from unstained brightfield images. The YOLO v4 object detection architecture was trained on datasets comprising erythrocytes, echinocytes, lymphocytes, monocytes, neutrophils, and platelets imaged using a microfluidic flow system. Binary classification between erythrocytes and echinocytes achieved a network F1 score of 86%. Expanding to four classes (erythrocytes, echinocytes, leukocytes, platelets) yielded a network F1 score of 85%, with some misclassified leukocytes. Further separating leukocytes into lymphocytes, monocytes, and neutrophils, while also increasing the dataset and tweaking model parameters resulted in a network F1 score of 84.1%. Most importantly, the neural network's performance was comparable to that of flow cytometry and haematology analysers when tested on donor samples. These findings demonstrate the potential of artificial intelligence for high-throughput morphological analysis of unstained blood cells, enabling rapid screening and diagnosis. Integrating this approach with microfluidics could streamline conventional techniques and provide a fast automated full blood count with morphological assessment without the requirement for sample handling. Further refinements by training on abnormal cells could facilitate early disease detection and treatment monitoring
Alexithymia in schizophrenia and psychosis vulnerability:A systematic review and meta‐analysis
Get PDFAimsDisturbances involving impairments in experience and expression of affect are frequently identified in schizophrenia samples. Alexithymia underlies cognitive impairments in identification and expression of affect, further implicated in affect dysregulation. The current review aimed to systematically review the literature and estimate the strength of associations between alexithymia and schizophrenia phenomenology.MethodA systematic review and meta-analysis identified 67 studies involving measures of alexithymia in psychosis. All studies were assessed for quality and publication bias. Overall, data from 47 studies were suitable for meta-analysis.ResultsAlexithymia and schizophrenia were consistently positively associated with a large effect size (k = 11). Compared to control groups, a schizophrenia diagnosis was positively associated with large magnitude effects for difficulties in identifying feelings (k = 18) and moderate effect sizes for difficulties in describing feelings (k = 17) and externally oriented thinking (k = 11). Data from community samples indicated moderate associations between subclinical negative symptoms and difficulties in identifying and describing feelings (k = 4) and a small association between positive symptoms and difficulties in identifying feelings (k = 5).ConclusionsAlexithymia and schizophrenia are strongly associated. However, methodological issues limit the establishment of directionality in these associations. The majority of studies use cross-sectional designs reliant on self-report assessments which may result in over-estimation of the reported effect sizes. Future research could conceptualize alexithymia as a stress-reactive multidimensional construct, and modeling dynamic relationships between alexithymia, psychological distress, and schizophrenia phenomenology should incorporate confounders such as gender, age, and neurocognition
Evaluating archaeological field survey with tephrochronology - a case study from southern Iceland
Get PDFA scoping review of sense of coherence and salutogenesis among LGBTQ+ populations
Get PDFSalutogenesis and sense of coherence can buffer the effects of external threats such as stigma, discrimination, and emergencies. Lesbian, gay, bisexual, trans, and queer (LGBTQ+) communities globally face discrimination, prejudice, and victimization. Understanding salutogenesis and sense of coherence among LGBTQ+ people could improve policy and health promotion responses and reduce the impact of these stressors on LGBTQ+ people’s health. This scoping review addressed the following question: To what extent has salutogenesis, either qualitatively or through measurement of sense of coherence, been explored among LGBTQ+ populations globally? Systematic searches of five databases identified 448 unique sources: 413 were excluded through title and abstract screening, and 18 by full-text screening. Of the 17 included studies, 14 were quantitative, two qualitative, and one mixed methods. Studies recruited participants from 11 high-income countries. Two-thirds (11) recruited participants only from within the LGBTQ+ community and six had more broadly based samples. The studies sampled a diverse range of subpopulations and subgroups from a variety of contexts limiting generalizability. The quantitative measure of sense of coherence most often used was the SoC-13 (n = 7), however, heterogeneity in the results reporting prevented quantitative synthesis. The limited evidence suggests that sense of coherence may be lower in LGBTQ+ populations than in comparison groups of cisgender heterosexuals, at least in some contexts, and is related to measures of wellbeing and discrimination. Further research is needed to understand how sense of coherence and its dimensions influence, and is influenced by, LGBTQ + people’s life experiences and resources and their responses to external stressors
Association between maternal mental health, the COVID-19 pandemic, and children's developmental outcomes in Scotland
Get PDFBackground: The number of reported maternal mental health (MH) difficulties during the COVID-19 pandemic was higher than during the pre-pandemic period. Findings on the link between the COVID-19 pandemic and children's developmental outcomes suggest lower scores on the Ages and Stages Questionnaire (ASQ-3) among children born during the COVID-19 pandemic compared to pre-pandemic cohorts. The present study explored the interaction between maternal MH and being born during the COVID-19 pandemic on children's developmental outcomes. Furthermore, it examined the combined effect of maternal MH and birth during the pandemic on children's developmental outcomes.Study designThis study used a linked administrative dataset from Scotland. Children born between 1st March 2020 and 30th June 2021, inclusive (n=32,683), and a comparative historical cohort that included those born between 1st April 2017 and 31st October 2018 in Scotland (n=50,257) were included. Regression models were used to adjust for covariates, with outcomes such as ASQ-3 scores and developmental concerns and predictors such as maternal MH and birth during the COVID-19 pandemic. Results A history of MH hospital admission was associated with increased odds of developmental concerns: OR= 1.038, 95% CI [1.012, 1.064], p=0.004** and reduced ASQ-3 scores (effect size=0.130, 95% CI [-0.204, -0.056], p<0.001***). There were mixed findings on the association between being born during the COVID-19 pandemic (developmental concerns: OR= 1.024, 95% CI [1.019, 1.029], p<0.001***) and ASQ-3 scores (ES= 0.012, 95% CI [-0.002, 0.025], p=0.08) but no interaction between a history of MH hospital admission and birth during the COVID-19 pandemic. However, there was an interaction effect on mental health assessed by psychiatric outpatient attendance records association and birth during the COVID-19 pandemic on the ASQ-3 scores SD; -0.07 (ES =-0.066, 95% CI [-0.106, -0.027], p<0.001***). ConclusionsOur findings suggest that being born during the COVID-19 pandemic and maternal MH influenced child development with relatively small effects, with mixed findings on their combined presence. Our study only examined developmental outcomes up to age 13 – 15 months. Future studies should explore the potential long-term effects of being born during the pandemic and MH.<br/
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