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Efflux resistance breakers: a new technology to overcome efflux-mediated resistance in multidrug resistant bacteria
Get PDFWe have developed a novel approach to reduce efflux liability in different antibiotic classes, based on advanced structural modelling, identification of “efflux-resistance breaker” (ERB) pharmacophores, and detailed understanding of efflux liability in multidrug resistant (MDR) pathogens. This technology allows development of antimicrobials that are less susceptible to efflux and do not require the use of additional efflux pump inhibitors. These ERB-modified antibiotics maintain high intracellular concentrations resulting in bacterial death, even in the presence of multiple target mutations associated with resistance. The ERB-fluoroquinolones show notably better activity compared to parent fluoroquinolones in a variety of MDR bacteria with up to a 512-fold reduction in MIC (MIC90 0.03 to 2 µg/mL). The lead compounds, KSN-L22 and BL-7 showed MICs of 0.03 to 0.5 µg/mL against MRSA, 0.03 to 2 µg/mL against Acinetobacter baumannii, 0.03 to 2 µg/mL against Escherichia coli and 0.25 to 4 µg/mL against Klebsiella pneumoniae strains. The ERB-fluoroquinolones work by inhibiting both wild type and mutant (GyrA S84L) DNA gyrases (IC50 ~3.8 µg/mL). Both BL-7 and KSN-L22 showed in vivo efficacy in a thigh infection model with 5-log reduction of bacterial load at both 20 and 50 mg/kg oral dose levels and excellent oral and IV PK/PD profiles. The compounds did not show any toxicity at 1200 mg/kg/day in mice. The off-target toxicity screen did not reveal any issues, including the hERG channel, and the compounds do not induce or inhibit cytochrome p450 enzymes. Use of efflux resistance breaker technology to make the compounds less susceptible to efflux has the potential to revive the use of several classes of current antibiotics.
The European Court of Human Rights in 2025 and beyond: Philip Leach [Panel discussion]
No full textProposals as to reforms of the ECHR system
Constructing academic identity through positive performativity in teaching and research
No full textBusiness School legitimacy is subject to ongoing debate and stakeholder pressures resulting from evolving socio-economic and political conditions. Increasing societal demands for sustainability and inclusion – joined by technological developments such as digitisation and generative AI – have led to calls for more meaningful teaching and research that creates value at the intersection of personal, institutional and societal interests and generates positive impact for the common good. However, socio-material confines imposed by Business Schools’ corporatist legitimacy continue to shape academic behaviour, as most academics avoid challenging existing institutional structures. To resolve this tension between societal and institutional demands, we propose that academics can foster meaningfulness in their work by embracing the concept of positive performativity, enabling them to proactively construct more desirable identities in teaching and research. We create a Positive Performative Identity Construction Model, highlighting the dynamic relationship between identity work and positive performativity within the socio-material confines of Business Schools, joined by practical templates prompting academics to reflect on their teaching and research, evaluate their practices, and explore strategies for meaningful work. We call on all academics to move from passive compliance to proactive engagement, claiming new ground through meaningful work and fostering positive institutional and societal change
Contingency management interventions for substance use and addictive behaviours: review of the United Kingdom evidence base
Get PDFBackground and aims
Substance use and other addictive behaviours including gambling remain major public health concerns in the UK. Despite the effectiveness of substance use treatment approaches, treatment adherence and success rates remain low. Contingency Management (CM), a behavioural intervention using positive reinforcement, is a promising approach to enhance clinical outcomes; however, its implementation in UK settings remains limited. This scoping review aimed to explore how CM has been adopted to improve outcomes for substance use and addictive behaviours in the UK, addressing the gap between international evidence and UK-specific healthcare needs.
Methods
A systematic search of databases (Embase, MEDLINE, PsycArticles and PsycInfo) for UK-based CM studies published before March 2025 was undertaken. The review adhered to PRISMA-ScR guidelines, and the protocol was prospectively registered on the Open Science Framework. Eligible studies were peer-reviewed, full-text articles, reporting the exploration of CM interventions to improve outcomes for substance use and other addictive behaviours within UK settings. Screening and data extraction were independently conducted using Covidence. A narrative synthesis explored study outcomes including effectiveness, feasibility and acceptability. Using the Context and Implementation of Complex Interventions (CICI) framework, key contextual factors influencing CM implementation in the UK across setting, socio-cultural, political and ethical domains were explored.
Results
A total of 208 articles were identified, with 36 full texts reviewed and 29 eligible for inclusion. Nine studies assessed effectiveness, six included economic evaluations, six assessed feasibility and 14 assessed acceptability. Clinical effectiveness was supported in most studies, particularly for promoting abstinence and medication adherence. Feasibility concerns included resource limitations, training and recruitment challenges. CM was generally well-accepted by service users and professionals, and digital approaches showed promise with high adherence and accuracy. Barriers and facilitators to CM implementation operating at micro, meso and macro levels are presented.
Conclusion
This scoping review of studies implementing Contingency Management (CM) in UK addiction treatment highlights several barriers to CM adoption, including resource limitations, concerns about its impact on therapeutic relationships and ethical issues regarding manipulation and fairness. It also points to the need for adapting CM protocols to fit UK treatment philosophies, particularly aligning with harm reduction approaches. CM's success depends on multi-level support, including policy, training and integration with existing systems. Recommendations include strengthening research on CM's long-term impact, ensuring fidelity to core principles, and investing in digital tools to reduce administrative burden
CodeTutor: personalized programming learning through automated feedback and clustering
No full textFirst-year Computer Science students often struggle to learn Java programming, and this condition can have a negative impact on their academic progress. Recently, an online tutoring system has been developed to help students learn Java programming. It allows students to execute and check Java code, making the learning process easier. Although the use of this tool has led to improvements in learning, it has been observed that the system has some weaknesses that need to be improved. The gap consists in the lack of specific and personalised feedback for the students. Therefore, a specific software has been developed, with an innovative approach based on machine learning using auto-clustering and neural networks. The new online tutoring system offers a better personalisation thanks to a graph model tailored to the study plan based on individual performance, by optimising learning effectiveness through video tutorials and Java code evaluations. This system aims not only to increase the academic success of the students, but also to provide instructors with a more precise assessment tool
Early-stage nature positive innovation finance in the UK
No full textThe report focuses on he UK early-stage green innovation finance market, addressing two research questions: (i) how to measure and report green nature positive financial risk and mitigation impacts, and (ii) how to deliver an effective SME nature positive finance market
Flight for solo organ
No full textPrelude - Flight - Dance
Flight was inspired by a scene from F.W. Murnau’s silent film version of the Faust legend. In the scene, Mephisto conjures up for Faust a vision of the beautiful Duchess of Parma. Faust immediately wishes to go to her, and Mephisto invites him to step on his cloak for a magic carpet-like ride across the countryside, passing varied landscapes, to her castle. On arrival they find the Duchess’s wedding party in full flow, with dancing and elephants; Mephisto presents Faust to her.
Originally written to be performed with the film scene by a small instrumental ensemble at Dartington International Festival & Summer School in 2002, the music was reworked as an independent organ composition in 2025.
After a mysterious introductory prelude, toccata-like figuration and different registers depict motion through air in the central Flight. The final section features a ground bass underpinning a quasi-medieval dance.
Notwithstanding the initial inspiration, the work could also find a liturgical function in, for instance, depicting the rushing wind of Pentecost; and responding to Psalm 50’s exhortation to praise with cymbals and dancing.
First performance: Simon Hogan, organ, St Bride's Church Fleet Street London 26 March 2026 (JAM Music Of Our Time concert
Swing speed training for golfers: an acute comparison of the stack system vs. driver in NCAA Division 1 players
No full textThe aim of the present study was to compare the acute effects of a maximal swing speed potentiation protocol using a speed sticks product vs. a driver, in high-level NCAA Division 1 male (n = 6; age = 19.7 ± 1.5 years; height = 186.8 ± 7.8 cm; body mass = 93.1 ± 25.8 kg) and female (n = 8; age = 20.7 ± 2.2 years; height = 168.2 ± 2.7 cm; body mass = 69.8 ± 11.3 kg) golfers. Each golfer performed baseline golf shot data using their own driver, where clubhead speed (CHS), ball speed and carry distance were recorded using a Trackman 4 launch monitor. For testing session one, a 3 x 3 maximal effort swing protocol (without hitting a ball) was employed using the Stack System product, with subsequent shot data recorded at 0-, 4-, 8- and 12 mins. For testing session two, the same protocol was repeated, but each player used their own driver to undertake the 3 x 3 potentiation protocol, without hitting a ball. The mass of the Stack system and each player’s driver were equated. Given the volume of data points, comparisons were made back to baseline, with trivial to small non-significant changes evident for either protocol, in any metric (males: g = -0.40 to 0.41; p > 0.05; females: g = 0.01 to 0.23; p > 0.05). Individual data analysis was also conducted comparing the change in golf shot data to the baseline measurement error, enabling an understanding of ‘true’ changes at the individual level. In male players, true changes were evident for CHS (Stack System: n = 11; driver: n = 18), ball speed (Stack System: n = 4; driver: n = 12) and carry distance (Stack System: n = 8; driver: n = 10). In female players, true changes were evident for CHS (Stack System: n = 8; driver: n = 16), ball speed (Stack System: n = 9; driver: n = 14) and carry distance (Stack System: n = 4; driver: n = 5). Despite the lack of meaningful group differences, individual differences were evident more frequently after the driver protocol. Although one aim of using speed sticks in golf is to manipulate the load to gain either an overload (when heavier) or overspeed (when lighter) effect; when mass is equated, some individual golfers who use their own driver may be able to elicit greater acute responses to maximal swing speed training
Digitale Geschäftsmodelle im Schweizer Gesundheitswesen: theoretische und empirische Analyse ihrer Wirkung auf integrierte Versorgung
Get PDFThis dissertation examines the acceptance of data-driven platform business models as enablers of regional, cross-sectoral healthcare provision in Switzerland. The focus is justified by the digital transformation and the role of inpatient providers within multi-sided markets subject to high levels of regulation. This constellation has so far received only limited scholarly attention.
A theory-based impact model was derived from the Technology Acceptance Model as well as diffusion and adoption research, and was extended through grounded theory based on nine expert interviews. Quantitative validation was conducted through a standardised online survey of 350 executives from Swiss inpatient providers, yielding 86 complete responses from 66 institutions. Reliabilities were tested using Cronbach’s alpha and Spearman–Brown. Multiple linear regression included 14 predictors, with N = 83 valid cases.
The average intention to participate was 63.3 %. Approximately 26 % of respondents envisaged themselves as data providers or recipients, while about 22 % intended to assume the role of platform operator, mainly university hospitals and national groups. The regression model explained 51 % of the variance in participation intention. Perceived usefulness, compatibility with existing processes, testability in pilot environments, and technological innovativeness showed significant positive effects. Environmental factors such as regulation, data law, and financing were not significant, although they were frequently mentioned in the interviews.
The findings support the transferability of established adoption logics to business model innovation in regulated healthcare markets and specify these further, since perceived ease of use showed no independent effect. Practical consequences include the prioritisation of value propositions, integration with primary systems, and protected pilot environments. Organisational readiness outweighed external framework conditions. Limitations concern the non-probabilistic sampling, sample size, and restricted reliability of individual environmental indices. Future research should systematically incorporate governance and ethics and provide for context-specific replications