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Impact of counterion and salt form on the properties of long-acting injectable peptide hydrogels for drug delivery
Full text linkModifying the salt form of active pharmaceutical ingredients is a common method to enhance their physicochemical and biological properties, whilst improving their ability to be formulated into medicines that can be effectively delivered to patients. Salts and counterions are especially relevant to peptide therapies, given that the majority of low molecular weight peptides synthesised by solid-phase protocols form a trifluoroacetate (TFA) salt due to the use of trifluoroacetic acid in resin cleaving and follow-on purification methods. TFA salts are not viewed as favourably by medicine regulators and can be defined as a new chemical entity entirely due to their different biological and physicochemical properties. Despite some exceptions, the vast majority of therapeutic peptides are marketed as hydrochloride (HCl) or acetate salts, even though most early research and development is centred on TFA salts. The aim of the study was to compare the impact of salt form (TFA vs. HCl) on the biostability, cell cytotoxicity, drug release and rheological properties of a Napffky(p)G-OH peptide hydrogel platform that demonstrates promise as a long-acting drug delivery system. This study demonstrated no significant difference between the salt forms for properties important to its intended use. This paper also raises important points for discussion relating to the environmental and regulatory status of peptide salts and their use as pharmaceuticals
The healthcare needs of children with Down syndrome in the first year of life: an analysis of the EUROlinkCAT data linkage study
Full text linkABSTRACTBackgroundGlobally, Down syndrome is the most common chromosomal anomaly, often co‐occurring with cardiac or gastrointestinal anomalies. There is a lack of robust data on specific healthcare needs of children with Down syndrome compared to children with other major congenital anomalies.ObjectivesTo quantify the healthcare needs of children with Down syndrome in the first year of life compared to children with major congenital anomalies in a large population‐based cohort across Europe.MethodsThe EUROlinkCAT study was a multicentre data linkage study between congenital anomaly registries in Europe and hospital and mortality databases. Children born between 1st January 1997 and 31st December 2014 were included. Summary statistics were used to compare differences between children (those with Down syndrome compared to all major anomalies) and regions. Random‐effects meta‐analysis was used to pool results related to survival, need for intensive care and ventilation support.ResultsA total of 3554 children were born with Down syndrome out of 89,081 children with major congenital anomalies. The pooled 1‐year survival was 95.4%. In every region, > 80% of children with Down syndrome had a hospital admission excluding the birth admission. Hospital length of stay in the first year was higher for children with Down syndrome compared to those with all anomalies (median: 14 versus 7 days). Despite having similar need for ventilation support (9.7% vs. 8.4%), children with Down syndrome had higher rates of intensive care admission than all children with anomalies (24.8% vs. 13.0%).ConclusionsThere is a high need for hospital care for children born with Down syndrome in the first year of life. Future work should continue to explore the long‐term prognosis for children with Down syndrome to ensure their care needs are met
(Out there in the perimeter) Loud Quiet Loud
Full text linkThe research, undertaken as the introductory text to the work of Photographer and Irish Artist Rich Gilligan's monograph The First Draft, examines the cultural shifts that emerged as a consequence of the establishing of satellite towns and suburban spaces adjacent to the M50 circular motorway that surrounds Dublin. Since the 1960's. communities of working class and lower middle class families have relocated to the periphery of the city with, as a consequence, a generation of youth initiating cultural practices remote to the more central Dublin City that had been common amongst their predecessors. Taking Rich Gilligan's adolescence and professional career as a conduit, Grant's essay affirms the qualities that young people on the edge of the major city drew upon -their preoccupations, cultural practices and influences. The essay explores Gilligan's innovative early work and follows its maturing through themes of migration and eventual return. The essay was commissioned by leading Irish curator Linda Shevlin and the book was published to coincide with Gilligan's exhibition at Draoicht, Dublin, and a book launch, hosted by Photo Museum Ireland. Since the early 1990's, Ken grant has taught photographers in Ireland and wider Europe. Many have progressed to sit at the heart of a new wave of contemporary practice. This essay, serving as the foreword for Rich Gilligan's first retrospective, examines the photographer's early practices and the influence of music, street culture and a suburban adolescence lived on the outskirts of Dublin. The book was published to accompany an exhibition to be held at Draoicht, Blanchardstown, in February 2025
An ontological approach to investigate the impact of deep convolutional neural networks in anomaly detection of left ventricular hypertrophy using echocardiography images
Full text linkLeft Ventricular Hypertrophy (LVH) is a critical predictor of cardiovascular disease, making it essential to incorporate it as a fundamental parameter in both diagnostic screening and clinical management. Addressing the need for efficient, accurate, and scalable medical image analysis, we introduce a state-of-the-art preprocessing pipeline coupled with a novel Deep Convolutional Neural Network (DCNN) architecture. This paper details our choice of the HMC-QU dataset, selected for its robustness and its proven efficacy in enhancing model generalization. We also describe innovative preprocessing techniques aimed at improving the quality of input data, thereby boosting the model's feature extraction capabilities. Our multi-disciplinary approach includes deploying a DCNN for automated LVH diagnosis using echocardiography A4C and A2C images. We evaluated the model using architectures based on VGG16, ResNet50, and InceptionV3, where our proposed DCNN exhibited enhanced performance. In our study, 93 out of 162 A4C recordings and 68 out of 130 A2C recordings confirmed the presence of LVH. The novel DCNN model achieved an impressive 99.8% accuracy on the training set and 98.0% on the test set. Comparatively, ResNet50 and InceptionV3 models showed lower accuracy and higher loss values both in training and testing phases. Our results underscore the potential of our DCNN architecture in enhancing the precision of MRI echocardiograms in diagnosing LVH, thereby providing critical support in the screening and treatment of cardiovascular conditions. The high accuracy and minimal losses observed with the novel DCNN model indicate its utility in clinical settings, making it a valuable tool for improving patient outcomes in cardiovascular care
Extreme heat risk and the potential implications for the scheduling of football matches at the 2026 FIFA World Cup
Full text linkClimate change is making extreme heat events more frequent and intense. This negatively impacts many aspects of society, including organised sport. As the world’s most watched sporting event, the FIFA World Cup commands particular attention around the threat of extreme heat. The 2022 tournament in Qatar was moved from summer to winter in response to this threat, and now attention turns to the 2026 tournament in North America with extreme heat risk across many of the 16 host locations. We examine this risk by modelling wet bulb globe temperature (WBGT) – a widely used measure of heat stress – for the host locations using hourly meteorological data for the period 2003–2022. Our results show that 14 out of 16 host locations exceed WBGTs of 28 °C, with four (nine) exceeding this threshold more than half the time during afternoons across the mean (hottest year) of the 20 year record. This threshold is important as the level beyond which some football governing bodies recommend match delay or postponement. A climatically sound argument is therefore presented to reschedule kick-off times outside the hottest afternoon hours for the host locations with highest heat risk at which no indoor air conditioned environment exists – primarily Miami and Monterrey, but also Philadelphia, Kansas City, Boston and New York. This study highlights the need to carefully assess heat risk ahead of major sporting events to help inform any potential interventions needed in the scheduling of matches and competitions in a warming climate
Naming, Stimulus Equivalence and Relational Frame Theory: Stronger Together than Apart
Full text linkResearch on human language started to change when Murray Sidman and colleagues demonstrated that a participant was able to derive unreinforced stimulus relations after conditional discrimination training. This work provided the basis for a novel approach to research on symbolic behavior and fostered the development of three main theoretical accounts: stimulus equivalence (SE), relational frame theory (RFT), and naming theory (NT). These accounts unfolded in the last decades of the twentieth century, promoting intense debate and discussion within behavior analysis. Although experimental research emerging from these three accounts is still highly active today, the theoretical discussions have, to a large extent, faded. Considering the importance of rekindling a dialogue, this article aims to describe the differences among the three accounts, but focus on their common points. We conclude by arguing that developing a more complete behavior-analytic account of human language would be served best by considering both research and theoretical analyses of SE, RFT and NT. Finally, we provide examples of two successful research groups that adopted this approach and in doing so have advanced our understanding of language within behavior analysis.</p
Understanding Individual Differences in Happiness Sources and Implications for Health Technology Design:Exploratory Analysis of an Open Dataset
Full text linkBackground:Psychologists have developed frameworks to understand many constructs, which have subsequently informed the design of digital mental health interventions (DMHIs) aimed at improving mental health outcomes. The science of happiness is one such domain that holds significant applied importance due to its links to well-being and evidence that happiness can be cultivated through interventions. However, as with many constructs, the unique ways in which individuals experience happiness present major challenges for designing personalized DMHIs.Objective:This paper aims to (1) present an analysis of how sex may interact with age, marital status, and parental status to predict individual differences in sources of happiness, and (2) to present a preliminary discussion of how open datasets may contribute to the process of designing health-related technology innovations.Methods:The HappyDB is an open database of 100,535 statements of what people consider to have made them happy, with some people asking to consider the past 24 hours (49,831 statements) and some considering the last 3 months (50,704 statements). Demographic information is also provided. Binary logistic regression analyses are used to determine whether various groups differed in their likelihood of selecting or not selecting a category as a source of their happiness.Results:Sex and age interacted to influence what was selected as sources of happiness, with patterns being less consistent among female individuals in comparison with male individuals. For marital status, differences in sources of happiness were predominantly between married individuals and those who are divorced or separated, but these were the same for both sexes. Married, single, and widowed individuals were all largely similar in their likelihood of selecting each of the categories as a source of their happiness. However, there were some anomalies, and sex appeared to be important in these anomalies. Sex and parental status also interacted to influence what was selected as sources of happiness.Conclusions:Sex interacts with age, marital status, and parental status in the likelihood of reporting affection, bonding, leisure, achievement, or enjoying the moment as sources of happiness. The contribution of an open dataset to understanding individual differences in sources of happiness is discussed in terms of its potential role in addressing the challenges of designing DMHIs that are ethical, responsible, evidence based, acceptable, engaging, inclusive, and effective for users. The discussion considers how the content design of DMHIs in general may benefit from exploring new methods informed by diverse data sources. It is proposed that examining the extent to which insights from nondigital settings can inform requirements gathering for DMHIs is warranted
Artificial Intelligence user interface preferences in radiology: a scoping review
Full text linkIntroduction/BackgroundModern forms of Artificial intelligence (AI) have developed in radiology over the past few years. With the current workforce shortages, in both radiology and radiography professions, AI continues to prove its place in supporting clinical radiology processes. The aim of the scoping review was to investigate the existing literature on the topic of preference of use of artificial intelligence interfaces within a radiology context.MethodsUsing a systematic approach, papers were chosen against an inclusion criterion of addressing radiological AI user interface preferences to be included in the scoping review. Arksey O'Malley's and Levac's framework were used to inform the procedural steps for the scoping review. Four databases were searched including MEDLINE Ovid, Scopus, Web of Science and Engineering Village. Reliability was improved through the involvement of three researchers to select the papers against the inclusion criteria.ResultsSix papers were identified to fit the inclusion criteria of radiological AI user interface preferences. These varied methodologically including two observational studies, two simulated user testing studies, a diagnostic accuracy study and a multi-case study. AI user interfaces were evaluated in two studies. Mixed responses were obtained with some alignment in preference for heatmap image overlays and highly detailed user interfaces are linked to higher preference amongst users. Limited literature exists on AI user interfaces and a lack of research evaluating current AI interface preference, either in post or pre-deployment.DiscussionThe mix of methods used within studies indicated that there is not yet a standardised method for assessing AI tool design and preference within radiology, with common use of a System Usability Scale survey tool in conjunction with another method. There was also a varied response when considering the preferred user interface in radiology, though simple, non-complicated designs were suggested to be ideal by participants.ConclusionMedical imaging AI user interface research is essential for the acceptability of AI technology into radiology departments. This scoping review identified the current landscape of AI user interface research within a radiology setting. There is a requirement for more radiology AI research focussing on end user or imaging professional involvement and their preferences. There is an explicit need for further research in the field, due to the lack of standardised outcome measures, lack clear findings regarding ideal user interfaces and lack of inclusion of radiographers. The dearth of studies including radiographers and small sample sizes of participants within these studies identifies the mindset shift required for radiology, and AI vendors alike
Food portion sizes: trends and drivers in an obesogenic environment
Full text linkThe prevalence of overweight and obesity in children and adults has increased worldwide. A strong environmental factor contributing to the obesity epidemic is food portion size (PS). This review evaluates the current evidence linking food PS to obesity, examines the effects of PS on energy intake (EI), and discusses the drivers of food PS selection. The leading causes of the rise in PS include globalisation, intensive farming methods, the impact of World War II, due to shortage of staple foods, and the notion of waste not, want not. Large PS of energy-dense foods may stimulate overconsumption, leading to high EI levels. However, the studies have not shown a cause-and-effect relationship, due to confounding factors. Important mechanisms explaining the attractiveness of larger PS leading to higher EI levels are value for money, portion distortion, labels on food packaging, and tableware. Consumers depend on external rather than internal PS cues to guide consumption, irrespective of satiety levels. Further research is recommended on food consumption patterns to inform policymakers and provide information and insights about changes in diet. </p
Countdown VR: a Serious Game in Virtual Reality to Develop Mental Computation Skills
Full text linkVirtual reality (VR) can be utilized to create video games exploring novel ways to control and interact with the environment. VR can be employed to revisit, extend, and enhance old video games to give them a new lease of life. In this paper, we describe the game Countdown VR in which players must use mental computation to reach a target number. Mental computation is used in everyday life, it is used for quick calculations and estimations. Countdown VR is a serious game designed and implemented using the Learning Mechanics-Game Mechanics framework. We provide an analysis of different approaches for determining the difficulty level of the game based on a number and target to attain and a selection of numbers combined to reach the target. We assess the user's performance and user's experience in the game, with questionnaires to quantify the related workload, usability, flow, motivation, and potential symptoms of users playing the game. The results provide key information related to the relationships between the subjective and objective evaluations of the proposed VR game by players, with a high correlation between VR sickness questionnaires, and moderate correlations between usability and motivation, flow and motivation