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Regenerative Therapeutics for Chronic Obstructive Pulmonary Disease
Get PDFChronic obstructive pulmonary disease (COPD) is one of the most common lung diseases worldwide, characterized by an accelerated loss of lung function. A key problem underlying COPD is increased tissue destruction in combination with defective lung tissue repair. As current therapies do not modify the progression of the disease, new therapies aimed at restoring lung tissue repair in COPD need to be developed. In an attempt to address this major unmet need, there has been a surge in both preclinical and clinical studies, aiming to identify key mechanisms underpinning defective lung repair and the ability to inhibit or even reverse this defect. This includes small molecules such as retinoids, as well as advanced therapy medicinal products such as cell therapies or therapies with cell-derived products such as extracellular vesicles, or secreted proteins. The results of these endeavors have been variable with failures as well as successful proof-of-concepts. In this review, we provide an overview of the current state of the field, including modes of action of the therapeutics that are or have been considered for lung regeneration, including a discussion on the reasons for failure where relevant. In addition, we discuss hurdles in the clinical development of regenerative therapeutics for COPD including clinical outcomes, route of administration and formulation as these are pivotal considerations moving forward
A Dirichlet Distribution-Based Trust-Adaptive Ensemble Approach for Pneumonia Classification from Chest X-Ray Images
No full textPneumonia diagnosis from chest radiographs is hindered by AI model variability and limited decision transparency.We present a deployment-ready, abstaining Dirichlet-evidence ensemble for paediatric CXR triage that elevates “Indeterminate”to a first-class outcome and implements dynamic, trust-adaptive weighting. Eight diverse pre-trained models each provide binary predictions, which are converted to three-way CXR supports,scaled by ongoing trust scores, and fused using a Dirichlet-evidence mechanism. Selective gates on class separation and pooled evidence allow the ensemble to defer, with auditable reasoning, when the decision is uncertain. On a 200-image paediatric hold-out, simple majority voting achieved 94.5% accuracy but dropped to 83.0%when two training models were intentionally inverted. At a fixed operating point, the proposed ensemble maintained zero errors(100% accuracy) on decided cases in both settings, abstaining on only 1–2% of studies instead of issuing incorrect labels. Unlike prior work, our system tightly integrates uncertainty, selective prediction, and per-case logging for clinical governance. This framework advances safe, interpretable automation for paediatric pneumonia assessment
Antimicrobial Resistance and Comparative Genome Analysis of High-Risk Escherichia coli Strains Isolated from Egyptian Children with Diarrhoea
Get PDFEscherichia coli is an important human pathogen that is able to cause a variety of infections, which can result in diarrhoea, urinary tract infections, sepsis, and even meningitis, depending on the pathotype of the infecting strain. Like many Gram-negative bacteria, E. coli is becoming increasingly resistant to many frontline antibiotics, including third-generation cephalosporins and carbapenems, which are often considered the antibiotics of last resort for these infections. This is particularly the case in Egypt, where multidrug-resistant (MDR) E. coli is highly prevalent. However, in spite of this, few Egyptian MDR E. coli strains have been fully characterised by genome sequencing. Here, we present the genome sequences of ten highly MDR E. coli strains, which were isolated from children who presented with diarrhoea at the Outpatients Clinic of Assiut University Children’s Hospital in Assiut, Egypt. We report that they carry multiple antimicrobial resistance genes, which includes extended spectrum β-lactamase genes, as well as blaNDM and blaOXA carbapenemase genes, likely encoded on IncX3 and IncF plasmids. Many of these strains were also found to be high-risk extra-intestinal pathogenic E. coli (ExPEC) clones belonging to sequence types ST167, ST410, and ST617. Thus, their presence in the Egyptian paediatric population is particularly worrying, and this highlights the need for increased surveillance of high-priority pathogens in this part of the world
Morpheme knowledge is shaped by information available through orthography
Get PDFA large portion of words in a language are formed by combining smaller meaningful units called morphemes (e.g., teach + -er → teacher). Understanding a language’s morphology is vital for skilled reading as it allows readers to interpret both familiar and unfamiliar words (e.g., tweeter). It is widely agreed that children rely on reading experience to acquire morpheme knowledge in English, and emerging research suggests that different aspects of this experience may impact affix learning in different ways. We contrasted three potential definitions of what constitutes readers’ affix experience using the morpheme interference paradigm with 120 adults. We found that skilled readers’ affix knowledge most closely aligns with a definition proposing that affix learning is primarily supported by experience with words in which affixes are identifiable without specialised linguistic knowledge. Due to the nature of morpheme presentation in English orthography, this excludes a significant number of genuinely complex words, while including affix-like patterns in non-meaningful contexts (e.g., -er in corner). This definition also posits that these morphological false alarms actively hinder learning. Our research represents a critical step towards a psychologically realistic theory of morpheme learning from text experience
The Longitudinal Impact of Psychosocial Factors on Cognition and Hearing in Younger and Older Adults During the COVID-19 Pandemic
Get PDFPurpose: In March 2020, a unique situation unfolded wherein the U.K. government announced social restriction measures to reduce the spread of the virus that causes COVID-19. Various measures remained in place until April 2021, with older adults, who were considered clinically vulnerable, being placed under stricter restrictions. This study aimed to determine the effect of psychosocial factors, including loneliness, depression, and engagement in various recreational lifestyle activities, on hearing and cognitive function in younger and older adults during the COVID-19 pandemic. Method: One hundred twelve older adults aged 60–82 ( M = 70.08, SD = 5.89) years and 121 younger adults aged 18–29 ( M = 20.52, SD = 2.63) years participated online between June 2020 and February 2022. Participants completed questionnaires assessing loneliness, depression, auditory and lifestyle engagement, and hearing ability, as well as behavioral tasks assessing auditory function and global cognition. All measures were completed 12 times at 4-week intervals. Results: Linear mixed-effects analyses found that, of the variables examined, increased loneliness was significantly associated with poorer auditory function. There were no main effects of time during the pandemic on auditory or cognitive outcomes. However, the interaction between time and age group significantly affected global cognition; in younger adults, global cognition decreased over time, whereas older adults displayed an unexpected positive change. Conclusions: These data show that there are associations between loneliness and auditory function but provide a lack of support for the impact of time experiencing auditory deprivation, or other psychosocial factors, on hearing and cognitive function. Such observations may be underpinned by motivational differences, learning effects, or sample biases. Future research may wish to investigate these factors further, to determine how psychological factors such as loneliness affect hearing and cognitive processes across diverse participant groups
National Hydrogen Strategies and Their Role on the Design of Clean Hydrogen Supply Chains
No full textThe transition to a sustainable energy system depends on the development of efficient hydrogen supply chains (HSCs) capable of meeting the rising demand for clean hydrogen. National hydrogen strategies play a pivotal role in shaping these supply chains by defining technological pathways, regulatory frameworks, and market incentives. This study analyses the strategies of seven leading countries – Australia, Germany, Spain, the United States, the Netherlands, the United Kingdom, and France – to identify the key elements influencing HSC design. A systematic literature review complements the policy analysis by linking these elements to academic perspectives in business and management research. The findings reveal that countries adopt distinct strategic positions based on their resource endowments, industrial capabilities, and geopolitical goals, resulting in varied configurations of hydrogen supply systems. The study also identifies common global drivers and barriers, including cost challenges, infrastructure gaps, and policy alignment. Based on these insights, we propose a conceptual framework that connects national strategic positioning to supply chain design and outline a typology of HSC configurations across country roles. This research contributes to the understanding of hydrogen strategy implementation and offers a research agenda to guide future studies in hydrogen supply chain management and policy design within the global energy transition
Assessing text experience in British primary school children: New validated title and author recognition tests
No full textBecoming a skilled reader requires that children accumulate extensive experience with text through independent reading. Research shows that greater text experience is associated with stronger reading skills, better comprehension, and improved spelling, and, consequently, higher reading motivation. Reliable objective measures of children’s reading experience are therefore essential; however, because such measures are typically highly sensitive to temporal and cultural contexts, none of the existing tests are suitable for capturing the reading experience of British children today. We address this gap by introducing a new Author Recognition Test (ART) and Title Recognition Test (TRT) designed specifically for primary school children in the United Kingdom and validated with a large cohort of British pupils. The battery also includes a new multiple-choice spelling test that can be easily administered online. We further demonstrate that single-word reading and sentence reading efficiency tests from the Rapid Online Assessment of Reading (ROAR) can be adapted for use with British children and provide valid measures of reading proficiency. Together, these tools offer a much-needed, freely available resource for both researchers and practitioners, enabling reliable measurement of children’s text experience and basic literacy skills. The test battery is openly available on https://osf.io/gmv72/
Breathing-Driven Modulation of Reticulospinal Tract Activity
Get PDFBreathing rhythms influence brain activity, but whether they modulate the excitability of the reticulospinal tract (RST; a key pathway for motor control and recovery after stroke) remains unknown. In this study, we used the StartReact paradigm to examine how respiratory rhythms modulate RST excitability during motor tasks, measuring reaction times across visual, visual–auditory and visual–auditory startling conditions in three arm muscles (first dorsal interosseous, flexor digitorum superficialis and biceps) of healthy adults (n = 13). Reaction times decreased significantly from visual to visual–auditory to visual–auditory startling conditions. Crucially, respiratory-phase transitions, particularly from inspiration to expiration, significantly enhanced RST excitability specifically during startle-evoked responses, with StartReact effects being significantly stronger during respiratory transitions compared with mid-phases (P ≤ 0.011). These findings suggest that respiratory rhythms modulate RST excitability dynamically in a phase- and condition-specific manner. The identification of respiratory transition phases as optimal periods for RST activation could inform new neurorehabilitation strategies, such as respiratory-phase-aligned stimulation, to enhance motor recovery following corticospinal lesions
Parental use of distraction and portioning to reduce snack intake by children with avid eating behaviour: An experimental laboratory study
Get PDFIntroduction Children's avid eating behaviour is characterised by frequent snacking and food responsiveness. Parents need evidence-based advice on specific feeding practices, such as distraction techniques and portioning, that can be used to reduce children's intake of high energy-dense snacks. This experimental laboratory study tested the effectiveness of these feeding practices. Methods Parents and children (3–5 years; N = 129) who were identified as having an avid or typical eating profile were recruited and randomly allocated to one of three conditions. Following a standardised meal, children's energy intake (kcal) in the absence of hunger was assessed. While children had access to a snack buffet, parents were asked to use one of the following feeding practices: (1) Distract – using distraction techniques to delay children's snack intake; (2) Portion – allowing children to have snacks from pre-portioned pots; or (3) Control – allowing children to eat the type and number of snacks that their child wanted to. Results Children in the distraction condition consumed significantly less energy from snacks (M = 54.44 kcal, SD = 73.30) compared to children in the portion (M = 103.89 kcal, SD = 91.33, p .05). Children with avid versus typical eating profiles did not differ significantly in energy intake (p > .05). Conclusion Parental use of distraction techniques may be effective for reducing children's intake of high energy-dense snacks and could be recommended for use to support the development of children's healthy eating. Research to examine the effectiveness of distraction in real-world settings is now needed
Online Graph Based Transforms for Intra-Predicted Imaging Data
Get PDFOrthogonal transforms are key components of several image and video compression systems and standards, as they provide a de-correlated representation of signals to enhance compressibility. However, the most commonly used transforms for compression, such as the Discrete Cosine transforms (DCT) and Discrete Sine transforms (DST), are fixed and non-adaptive, limiting their ability to capture complex or varying signal characteristics. Graph-based transforms (GBTs) have shown improved energy compaction and reconstruction performance, but face two major limitations: the need to signal graph information in the compressed bitstream, which increases overhead and may complicates decoder synchronization, and a dependency on offline training process, which is highly dependent on the quality and completeness of the training data. To address these issues, this paper introduces a novel framework, GBT-ONL, which learns GBTs online in the context of block-based predictive transform coding. The proposed GBT-ONL framework uses a shallow fully connected neural network to predict the graph Laplacian needed for both the forward and inverse GBT. By relying only on information available during encoding, GBT-ONL eliminates the need to signal additional information in the compressed bitstream, and removes the requirement for any prior offline training. Evaluations on several video sequences show that GBT-ONL outperforms both traditional (non-learnable) transforms and existing learnable transforms in terms of energy compaction, reconstruction error, and compression efficiency, as measured by BD-PSNR and BD-Rate metrics
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