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Convergent evolution of antibiotic resistance mechanisms between pyrrolobenzodiazepines and albicidin in multidrug resistant Klebsiella pneumoniae
Get PDFPyrrolobenzodiazepines (PBDs) containing C8-linked aliphatic heterocycles have been developed as a new class of potent antibacterial compounds. They are active against multidrug resistant Gram-negative pathogens, including Klebsiella pneumoniae. When isolates were exposed to PBDs, they acquired resistance, with significant increases in inhibitory concentrations. Resistant strains showed mutations in genes associated with resistance to albicidin, specifically tsx and merR-family regulator albA. Heterologous expression of AlbA in E. coli and introducing the L120Q AlbA resistance-mediating modification into the genome of a sensitive K. pneumoniae strain conferred PBD and albicidin resistance. Proteomic analysis of the resistant strains showed elevated AlbA protein levels compared to isogenic wild-type strains. Crystallographic studies with the antibiotic binding domain of AlbA show binding of KMR-14-14 to the same groove shown to bind albicidin. Given the parallels between these two structurally unrelated compound classes, AlbA may offer resistance to further antibiotics and should be considered in future antibiotic discovery
Spillover in sustainable consumer behavior: a matter of commitment
Get PDFConsumers express their commitment to environmental protection by engaging in a variety of environmentally protective behaviors. We thus suggest that strengthening consumers' commitment to environmental protection will cause behavioral spillover, which is the joint change in multiple environmentally protective behaviors. This idea differs from other spillover notions that draw on psychological processes that follow a change in a specific behavior. By reanalyzing data from a pre-post treatment-control quasi-field experiment with customers of a retail company in which one group was exposed to a multiple-component intervention over the course of 8 months, whereas the other was not, we corroborated a significant commitment gain in the experimental group (n = 81) that did not occur in the control group (n = 152). This commitment gain manifested in the expected spillover effect that mirrored the Rasch-model-implied likelihood gains in increasingly favorable behavioral expressions of people's commitment to environmental protection. This research complements existing models of behavioral spillover by providing theoretical and empirical arguments that strengthening consumers' commitment to environmental protection can result in spillover. In practical terms, focusing on people's commitment to environmental protection could thus be a promising avenue for directly promoting sustainable lifestyles
Inhibiting metastatic potential: an analysis of migratory body formation in chondrosarcoma
No full textChondrosarcoma (CHS) is the 2nd most prevalent bone sarcoma. Approximately 27% of all bone cancer cases reported to the International Agency for Research on Cancer (IARC) database are CHS. CHS tends to primarily affect adults above the age of 30 with 70% of cases reported affecting patients of 40 years and above. While CHS has an optimistic 5-year survival rate of 75.2%, this can depend greatly on the accuracy and time of diagnosis, histological grade, and subtype. Metastasis which often leads to chemoresistance have been primary complications in this cancer which often leave minimal treatment options, prolong the treatment course, and cause severe damage to the patients’ quality of life.
In our research group, we have identified a potential route through which metastasis might occur. Our in vitro observations with CHS cell-line SW1353 have shown that spheroids which we call migratory bodies (MB) can detach from the monolayer in our cell culture plates and remain suspended in the media. These MBs have shown to be able to adhere and proliferate, forming new colonies once replated into a fresh cell culture plate. Different cell seeding densities were used in 6 well-plates to optimise the production of MBs. 5000 cells/cm2 was found to be the optimum seeding density to produce the maximum number of MBs in SW1353. EGF and FGF were used to further optimise the formation of these MBs. A combined dose of 10ng/ml EGF and 10ng/ml FGF was shown to maximise the production of MBs. Human osteoclasts were cultured from isolated PBMCs. When 20% media used for culturing osteoclast was introduced to SW1353 with optimum seeding density and optimum dose of growth factor, a significant downstream effect was observed in the production of MBs, suggesting the presence of factors in osteoclast conditioned media with the potential to inhibit metastasis in chondrosarcoma
Evaluating the reliability and seasonal sensitivity of a fitness-testing battery in elite youth soccer
Get PDFPurpose: To evaluate the reliability and seasonal sensitivity of a fitness testing battery in elite youth soccer players using two data treatment methods: (a) the best score of multiple trials, and (b) the mean of multiple trials. Methods: Countermovement jump (CMJ), single-leg CMJ (SLCMJ), isometric mid-thigh pull (IMTP), Nordic hamstring strength, 10-m sprint, 505 change of direction (COD), and the Bronco endurance test were assessed in twenty-four elite academy soccer players (age 17.6 ± 1.0 years, height 183.5 ± 8.5 cm, body mass 78.2 ± 8.5 kg) at preseason, midseason, and end of season. Results: The CMJ, Nordic hamstring strength, 10-m sprint, 505 COD, and Bronco tests demonstrated high sensitivity to change (SNR: 1.14 – 3.08), with over 60% of athletes displaying an individual SNR > 1.0. In contrast, SLCMJ and IMTP relative peak force exhibited the lowest reliability and sensitivity (SNR: 0.93 – 1.19), with less than 60% of athletes demonstrating an individual SNR > 1.0, suggesting limited utility for evaluating performance changes. While the mean of multiple trials generally yielded marginally better reliability and sensitivity, both data treatment methods were similar. Conclusions: The majority of the studied fitness tests were reliable and sensitive enough to detect meaningful changes over a season in elite youth soccer players. Practitioners can select either the best trial or mean of trials for data analysis, depending on their context. Overall, these findings illustrate the reliability and seasonal sensitivity of common fitness tests, enabling practitioners to prioritize tests that accurately monitor player performance changes
Exploring the relational impact of CSA in the female adult survivor population in therapy: an existential perspective and phenomenological enquiry
Get PDFThis doctoral research project explores the lived experience of social relationships for adult women who have experienced a single episode of non-familial childhood sexual abuse (CSA) and who are in therapy. The literature review demonstrates that CSA is a common problem with serious psychological, social, and physical consequences. While the relational consequences of CSA feature in the existing research for women in therapy, there is a lack of published evidence of the lived experience of these consequences, particularly from an existential perspective. This study conducted a phenomenological exploration of this from the existential perspective by asking the research question ‘How do adult female survivors of a single episode of non-familial CSA experience relatedness with others in their social world?’ The study was centred on a sensitive and reflective approach in which eight purposely sampled individuals who met the carefully chosen and ethically guided inclusion criteria were interviewed by the researcher using a semi-structured conversational interview. Van Manen’s (1997) hermeneutic phenomenology was used to provide a deep understanding of the participants’ experience using the hermeneutic circle. The meanings identified in each interview were distilled into three essential themes. These were:
• The primacy of seeking relational safety;
• Social isolation and solitude; and
• Intentional social moderation.
This paper provides an understanding of how their relational interactions in the external world and the meaning of these interactions are affected by their earlier life experience. It adds context to the existing studies and reinforces the value of the therapeutic relationship for survivors of CSA. Recognition of these potential issues may help aid the construction of understanding and meaning of relationships for individuals engaged in therapy. Given the limited generalisability and the deliberately narrow inclusion criteria further research should focus on the experience of broader groups of survivors
The experience of love in romantic relationships: an existential phenomenological exploration on the experience of love
Get PDFAlthough love is widely used in everyday language it’s depth and importance is often overlooked, especially in the consideration of the wellbeing of individuals. Love resides in the experience of being human in many different relationships, familial, friendships, religious, romantic as well as a general feeling of love towards humanity. This research looked at love as an experience between couples in committed romantic relationships. Previous research has explored love from an ontological perspective, i.e., what it means to love, I try to get closer to the experience through this research to try and understand and share my findings on what is the actual experience of people in loving relationships.
Semi structured interviews were conducted with eight participants who were all in romantic relationships of at least five years. The data gathered from these interviews was analysed using an existential phenomenological method – I used Structural Existential Analysis (SEA) in order to look at the experience of love from the physical, social, personal, and spiritual dimensions of our existence. In addition, I explore the presence of time in the narratives of each participant.
My findings suggest that love is experienced in the physical, social psychological and spiritual realms of our lives, in addition time has a part to play in this experience. Each of these realms operate simultaneously within our day-to-day existence in and through time to create an experience which can bring immense comfort, security, and happiness and at other times shake the very foundations of our lives. Some of the key aspects of the experience of romantic love for my participants was that individuals chose to love romantically and were quite clear about the conditions which enabled this love to grow. In addition, love was expressed as an active and embodied aspect of my participants experiences, they showed and experienced love through their actions their words and through their bodies. Love was experienced as a way for them to feel connected to another person but also to become closer to their own sense of self and identity. Time played out in the way they experienced love through previous romantic relationships or parental love, it formulated their own perception of what they did or didn’t want in their present relationships.
Based on these findings, I propose that Counselling Psychologists/Psychotherapists and couples’ therapists could formulate the work around these four dimensions of existence, with a consideration on time as an important element to working with love in the therapeutic space
Unlocking the power of CNN models: enhancing training procedure with evolutionary based search for class-specific data augmentation
Get PDFData augmentation (DA) is a critical technique for improving the generalization capa-bilities of Convolutional Neural Networks (CNNs) in image classification tasks. This re-search introduces an automated data augmentation framework that leverages a genetic algorithm (GA) to optimize class-specific augmentation strategies, aiming to enhance CNN performance across diverse datasets and architectures. Our framework integrates a GA to search for optimal DA strategies and a CNN as a fitness function to evalu-ate the effectiveness of each strategy. By employing this fitness-driven, evolutionary approach, the framework iteratively refines augmentation strategies over generations, selecting individuals that yield improved model performance. The framework was rigor-ously evaluated on a diverse set of datasets spanning medical, agricultural, and general domains. Results demonstrated significant improvements in validation loss, with reduc-tions of up to 58.56% compared to a non-augmented baseline and 54.28% compared to a baseline augmented with traditional methods. Additionally, our approach was benchmarked against a similar state-of-the-art framework from the literature. In this comparison, our method achieved a relative improvement of 210%, underscoring its su-perior efficiency in optimizing DA strategies. These findings highlight the framework’s robustness and potential to serve as a universal solution for enhancing CNN classifi-cation performance. The framework provides a practical, adaptable tool that can be seamlessly integrated into existing workflows to improve model performance, particu-larly in domains with limited data and contributes to the growing field of automated data augmentation
AI governance: investigating a rights-based approach to explanation in AI
Get PDFThe hypothesis that Artificial Intelligence (AI) powered by Machine Learning (ML) algorithms will profoundly influence human cognition, interactions, and the exercise of power is gaining traction. AI is not only transforming how individuals perceive themselves but also revolutionising business practices. As admirable as the use of AI may be, its widespread adoption as a decision-making system in a variety of sectors, including the criminal justice system, healthcare, law enforcement, etc., merely because they are more effective and perform tasks better and faster than humans have created novel challenges that were previously unimaginable, such as algorithm bias, unfairness, trust, and opacity. Notably, these issues resonate with some ML algorithms that have exacerbated the relationship between humans and machines and have raised concerns about the effectiveness and sufficiency of prevalent data governance regimes as well as the legitimacy, ethics, and trustworthiness of AI. At the core of these concerns lies the "black box" nature of certain ML algorithms, particularly Deep Neural Networks (DNNs), which make it nearly impossible for individuals to understand the rationale behind automated decisions. These decisions, which can profoundly impact individuals’ lives—such as the denial of loans, parole, or medical treatments—are often made without sufficient transparency or opportunity for the affected individuals to challenge them. This lack of understanding of the decisions of AI algorithms contributes to a breakdown in trust, fairness, and accountability, all of which are essential for the ethical deployment of AI systems. Thus, a right to explanation, which requires that individuals are provided with comprehensible reasons for automated decisions that affect them, could address this issue by ensuring greater transparency and accountability in AI-driven decision-making processes.
This research addresses the gap in current legal frameworks surrounding AI decision-making by investigating the existence of a universal right to explanation. It explores whether such a right exists within legal instruments, such as the European Convention on Human Rights (ECHR), the Universal Declaration of Human Rights (UDHR), the General Data Protection Regulation (GDPR), the Artificial Intelligence Act (AIA), and various other human rights and AI governance frameworks. The findings reveal that while some legal provisions hint at a right to explanation, they are either region-specific or lack enforceability, rendering them ineffective in providing meaningful protections for individuals impacted by algorithmic decisions. In response, this research proposes the establishment of a universal right to explanation, embedded in the human rights framework and legal jurisprudence. This right is formalised through the development of the REMLA (Right to Explanation of Machine Learning Algorithms) Protocol, a proposed addition to the Council of Europe’s Convention on AI. Along with the protocol, this work provides an accompanying set of compliance guidelines (Appendix A to the Protocol) for AI providers and designers, aimed at ensuring the responsible development and deployment of AI systems in alignment with this new right. The research further evaluates the proposed right through a legal analysis using Hohfeldian legal theory, specifically assessing whether the right to explanation qualifies as a claim-right, thus imposing an obligation on duty on deployers and providers to provide clear and understandable explanations for automated decisions. The results confirm that the right to explanation satisfies the criteria of a claim-right. To validate the practical applicability of the REMLA Protocol and its compliance guidelines, two expert surveys were conducted. The feedback from AI experts and legal scholars was overwhelmingly positive, with respondents acknowledging the potential of the protocol to enhance AI transparency and accountability. Experts recommended several refinements to improve the protocol's clarity and implementation, leading to further updates.
Thus, this research makes a significant contribution to the field of AI governance by proposing a robust, actionable framework for ensuring transparency and accountability in algorithmic decision-making. The REMLA Protocol, alongside its compliance guidelines, represents a pioneering step towards integrating a universal, enforceable right to explanation into global AI regulation, ultimately safeguarding human rights and promoting ethical AI development
Effects of exercise on inflammation in female survivors of nonmetastatic breast cancer: a systematic review and meta-analysis
Get PDFDespite advances in breast cancer treatment, recurrence remains common and contributes to higher mortality risk. Among the potential mechanisms, inflammation plays a key role in recurrence by promoting tumor progression. Exercise provides a wide array of health benefits and may reduce inflammation, potentially reducing mortality risk. However, the effects of exercise, including mode (ie, resistance training [RT], aerobic training [AT], and combined RT and AT) and program duration, on inflammatory biomarkers in breast cancer survivors remain to be elucidated. A systematic search was undertaken in PubMed, CINAHL, Embase, SPORTDiscus and CENTRAL in August 2024. Randomized controlled trials examining the effects of exercise on IL-1β, IL-6, IL-8, IL-10, TNF-α, and CRP were included. A random-effects meta-analysis was undertaken to quantify the magnitude of change. Twenty-two studies were included (n = 968). Exercise induced small to large significant reductions in IL-6 (SMD = -0.85; 95% CI = -1.68 to -0.02; p = .05) and TNF-α (SMD = -0.40; 95% CI = -0.81 to 0.01; p = .05) and a trend for a decrease in CRP. When stratifying by exercise mode, trends toward reduction in IL-6 and TNF-α were observed for combined exercise, whilst changes were not generally affected by exercise program duration. Exercise, especially combined RT and AT, can reduce pro-inflammatory biomarkers, and may be a suitable strategy to reduce inflammation in breast cancer survivors. However, further research is needed to investigate the effects of exercise mode and program duration on markers of inflammation in this survivor group. [Abstract copyright: © The Author(s) 2025. Published by Oxford University Press.
Enabling community maintenance for local flood risk management: risk management authorities' guide to supporting community maintenance (C821b)
No full textGuidance produced for UK risk management authorities. It describes the benefits of a positive collaboration with local groups to sustain flood risk assets