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Everything is everywhere but Escherichia coli adapts to different niches
Get PDFPathogens that are harmless in one environment can cause a serious disease in another. Among host-associated bacteria, transition between hosts can have serious consequences for animal and human health. However, much remains unknown about how adaptation shapes bacterial distribution in the wild. Here, investigating the ecological genomics of Escherichia coli from diverse hosts and environments, we address the idea that bacteria disperse freely, and challenge the “everything is everywhere” paradigm. Using comparative genomics and parallelised high throughout pangenome-wide association studies (900 experiments) we investigate lineage distribution and identify adaptive genomic signatures associated with host species, physiology and ecology. Our findings provide insights into bacterial niche adaptation, emphasize the impact of agriculture on microbial evolution, and inform One Health frameworks by linking genomics, host ecology, and the emergence of antimicrobial resistance
Methicillin-resistant Staphylococcus aureus is raising global concern as it overcomes immune challenges through various virulence mechanisms
Get PDFMethicillin-resistant Staphylococcus aureus (MRSA) in the 21st century remains a global concern with increasing rates of morbidity and mortality in healthcare settings. Hospital-associated MRSA strains have developed multidrug resistance (MDR), limiting the effectiveness of several commonly used antibiotics. First-line treatment for MRSA depends on the type of infection caused. Antibiotics such as vancomycin, linezolid, and daptomycin remain central to managing serious MRSA infections. However, the rise of MDR and the need to prevent further antibiotic resistance have led to the use of combinational antibiotic regimens to manage serious infections. Furthermore, MRSA can acquire virulence determinants and resistance plasmids via mobile genetic elements (MGEs) and stably inherit diverse resistance mechanisms, fostering hypervirulent MDR lineages that complicate clinical management. Together, these factors enable MRSA to evade host immune defences and cause serious infections with poor clinical outcomes. Collectively, this review highlights the epidemiological burden of MRSA with a better understanding of its resistance and virulence mechanisms and reinforces the need for optimized approaches to prevent, manage, and control infections
The Patient-Doctor Relationship Questionnaire (PDRQ-9). An overview of 20 years of research and a proposal for normalisation of scores. Systematic review.
No full textAn advanced Petri-Net Modelling Approach for Risk Asset Management of Reinforced Concrete Ageing Transportation Infrastructure Under Climate Change Effects
No full textThis paper presents an advanced Petri Net (PN) modelling framework for the risk-based management of ageing reinforced concrete (RC) transportation infrastructure under climate change. The proposed framework introduces a modular PN architecture that decomposes infrastructure systems into interconnected submodules encompassing deterioration mechanisms, inspection policies, and maintenance strategies. These submodules are integrated into component, system and network-level PN modules, enabling holistic simulation and optimisation of asset-level decisions. A probabilistic degradation process is embedded within each submodule, incorporating climate-dependent parameters and allowing seamless integration of regional/national climate projections. Additionally, a multivariate statistical formulation is employed to capture interdependencies between component deterioration rates, enabling system-level reliability assessment.
To demonstrate the framework’s application, the model is implemented for a case-study RC bridge using the UKCP18 climate projection dataset, which includes 28 distinct climate scenarios. Monte Carlo simulations are conducted for three environmental trajectories: baseline ageing, expected and pessimistic climate change. Results indicate that climate change accelerates corrosion-induced deterioration, highlighting the need for adaptive inspection and maintenance strategies.
The proposed PN framework provides a generalised, data-driven tool for long-term infrastructure durability and life-cycle risk management under uncertainty
Effects of modified release hydrocortisone on restoration of early morning cortisol, quality of life, and fatigue in adrenal insufficiency (The CHAMPAIN study): a randomised, double-blind, double-dummy, cross-over study comparing Chronocort and Plenadren
Get PDFBackground
Cortisol has a circadian rhythm with an early morning rise, loss of this rhythm is associated with poor health. Our objective was to test the hypothesis that restoring the early morning cortisol rise will improve fatigue and quality of life (QoL) by comparing twice daily Chronocort with once daily Plenadren in patients with adrenal insufficiency.
Methods
A randomised, double-blind, double-dummy, cross-over study with no washout in 58 patients (29 in each arm) with primary adrenal insufficiency comparing four weeks' Chronocort, 15 mg at night and 10 mg in the morning, a formulation that restores early morning cortisol levels, with four weeks’ once daily Plenadren 25 mg, which only restores daytime cortisol levels. The primary endpoint was the 07:00 h serum cortisol level and secondary endpoints measures of fatigue and QoL. The trial was registered on ClinicalTrials.gov and EU Clinical Trials Register (NCT NCT05222152; Eudract 2021-000144-21), initiated on 11th January 2022 and completed on 18th October 2023.
Findings
Patients met the primary endpoint and achieved a physiological early morning serum cortisol, median 417 nmol/L on Chronocort versus 6 nmol/L on Plenadren (P < 0.0001). For secondary outcomes the majority of QoL and fatigue measures showed significant benefits for Chronocort including the disease-specific questionnaire AddiQol (P = 0.02), the fatigue questionnaire PROMIS 7b (P = 0.02), SF-36 physical component score (P = 0.01), and EQ-5D-5L (P = 0.02). The Multidimensional Assessment of Fatigue (MAF) was not significantly different between treatments; however, a pre-specified sensitivity analysis showed that in the first treatment period, Chronocort reduced the MAF Score (P = 0.008), suggesting a carry-over effect from period 1 to 2. A post hoc analysis of immune profile in a subset of 19 patients showed that those on Chronocort had an increase in circulating number or frequency of neutrophils, natural killer and natural killer T cells compared to both baseline glucocorticoid treatment and Plenadren treatment.
Interpretation
Restoring the early morning cortisol levels with twice daily Chronocort 15 mg at night 10 mg in the morning improved health-related quality of life, fatigue and the immune profile compared with 25 mg daily Plenadren. Funding Neurocrine UK Ltd
Modelling cognitive load using drift-diffusion models in pedestrian street-crossing: a method supported by neural evidence
Get PDFWhen pedestrians are cognitively loaded, this influences their street-crossing behaviour, leading to negative impact on overall road safety. However, the mechanisms underpinning this impact remain debated, and this study seeks to further investigate them through modelling and electroencephalography. We conducted a computer-based pedestrian crossing experiment, and employed drift-diffusion models to quantitatively analyse how cognitive load impacts pedestrian decision-making. To further test the models' validity, we analysed centro-parietal positive potential (CPP), a neural signal associated with evidence accumulation, to investigate whether this neural evidence aligned with the evidence accumulation predicted by the models. In our experiment, participants encountered a simulated scenario with a car approaching under four different time-to-arrival (TTA) conditions. In half the trials, participants performed cognitive tasks while deciding when to cross the street. Results showed that cognitive load weakened the effect of TTA on the probability of crossing before the car, increased response times, raised the probability of collision, and attenuated CPP amplitude. The best-performing model, which captured all of these effects, accumulated evidence based on utility estimates, but with a lower responsiveness to these utilities during cognitive load. This model also showed the strongest correlation between its evidence traces and the CPP amplitude, both with and without cognitive load. These findings support the hypothesis that cognitive load reduces responsiveness to perceptual evidence (at least in non-automatised tasks), making it a strong candidate for explaining both our results and existing research on the effects of cognitive load in other tasks
Perceived usefulness of cycling safety countermeasures in Australia and New Zealand: do stigma, stress and self-reported behaviours play a role?
Get PDFIncreasing modal share for cycling has many potential benefits for individuals and communities, especially in regions dominated by motor vehicle use and affected by issues such as extreme congestion. However, research suggests that cycling is not always a safe and positive experience, especially in car-centric communities that could benefit most from increasing cycling rates. Effective countermeasures can mitigate many issues that deter cycling, but their impact also depends on how useful they are perceived to be by riders. Therefore, the aim of this study was to understand the experiences of cyclists in terms of whether these are positive or negative and what factors underly these experiences (i.e. frequency of conflict with other road users, perceived stigma, cyclist behaviour) as well as to explore the perceived usefulness associated with a range of countermeasures considering safer behaviour, safer infrastructure, smarter cycles and more enforcement. Participants were 2135 cyclists living in Australia (n = 1239; average age 53.6; SD = 13.0; men = 74 %) and New Zealand (n = 896; average age = 46.8; SD = 14.6; men = 59 %) who completed an online questionnaire. Riders had mostly positive experiences with cycling, however 87 % felt there was a stigma towards cyclists and almost all riders (99 %) had experienced conflict with car drivers. These factors were associated with less positive perceptions of cycling. Understandably, almost all cyclists held positive views towards separated infrastructure countermeasures. Education campaigns for drivers were also seen as useful. Moreover, binary logistic regression analyses showed that across a range of countermeasures, cyclists who reported more positive experiences and more protective behaviours, yet also reported more conflict with other road users, tended to endorse infrastructure countermeasures. These cyclists may be more aware of safety concerns, adapt accordingly, and want to keep cycling. Riders perceiving stigma towards cyclists tended to support broader system-level changes; such as education and enforcement for drivers. Thus, a systems-level approach may be required to improve safety and positive riding experiences across a range of cyclists
Implementation of dementia communication skills training in acute hospitals:a longitudinal, mixed-methods case study evaluation
Get PDFObjectives Acute hospital staff identify that supporting patients with dementia is challenging. This study implemented a communication skills training programme for preventing and responding to distress in patients with dementia in acute hospitals and assessed its impact. Method A mixed-methods, multiple case study in six wards across three English acute hospitals. Observational, interview, and staff survey data was collected immediately pre, post and 1–3 months post training. The 7-h training programme consisted of two half-days separated by a reflective period of 2–4 wk. It was delivered face-to-face by local clinical educators, and comprised interactive content and discussion-based learning including multi-media PowerPoint presentations, video resources, a reflective diary and skills practice. Results 145 staff attended the training. Delivery was feasible, however challenges with training organisation and releasing staff occurred. Staff reported the training as engaging, relevant to their role, and valued opportunities for reflection and skills implementation between sessions. A statistically significant improvement was found immediate post-training on staff communication knowledge (CI 0.01–1.2) and confidence in caring for people with dementia (CI 4.9–7.3). Staff reported a range of learning which most planned to implement in practice. Some reported challenges applying specific communication principles to wider practice situations. Evidence of impacts on observed patient agitation and staff communication practices was challenging to provide. Conclusion Although challenging, it is feasible to deliver dementia communication skills training in acute hospital settings Communication training can lead to perceived increases in staff knowledge and confidence to support distress in this population
Models of perinatal care for women using drugs and their infants: synopsis of The Stepping Stones Study
Get PDFBackground
Women who use drugs during the perinatal period often have complex health and social care needs. Their infants can experience developmental and health problems. Despite United Kingdom’s guidelines and policies on the care of pregnant women and mothers who use drugs, there is little evidence of the services that are available in the United Kingdom and whether they meet the needs of women and their infants.
This study sought evidence of (1) best practice models for care that have the potential to interrupt the transmission of adversity across generations and (2) the views and experiences of women and staff on different models of care and how services could be improved. The study involved systematic reviews, longitudinal qualitative research and coproduction. There were three phases.
In phase 1, an Expert Advisory and CoProduction Group was established to guide the research and to develop a theory of change for improved service models. The group comprised multidisciplinary stakeholders from health and social care and peer advisers.
Two reviews were undertaken:
1. A scoping review of UK guidance for perinatal care for women who use drugs included 111 documents, recommending integrated multidisciplinary working.
2. A mixed-methods systematic review of evidence of integrated models of perinatal care for women who use drugs and their babies reviewed 197 studies. Qualitative findings suggest that women appreciate collocated services that are easy to access. Quantitative findings found evidence that integrated programmes at the point of delivery decrease substance use during the perinatal period.
Phase 2 involved a qualitative longitudinal study in four sites, two in England and two in Scotland, that aimed to explore perinatal care pathways. Up to five interviews were conducted with 36 women, from early pregnancy up to 18 months post natal (131 interviews). Many women experienced stigma and were anxious about social services’ involvement. Access to residential treatment and mental health support was uneven. Support for women who had lost care of their babies was poor.
Focus group interviews (79 staff) and individual interviews (21 staff) were conducted with health and social care practitioners. Staff reported that high caseloads, staff turnover and training gaps contributed to difficulties in providing care to this challenging group.
In phase 3, the Expert Advisory and CoProduction Group worked with the research team to develop a theory of change for recommendations for an optimised service model. The theory of change identified eight key recommendations and emphasised that a whole-system approach is required to meet the complex needs of this population.
Limitations
For the quantitative findings of the mixed-methods systematic review, the diversity of study types made it difficult to draw firm conclusions on the effectiveness of different approaches. Not all women recruited to the qualitative longitudinal study took part in all the anticipated interviews.
Future research
There is a need for high-quality research studies into effective interventions for pregnant women who use drugs. Implementation research is required to test and implement the theory of change for optimum services for women who use drugs in the perinatal period.
Funding
This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR130619
Prevalence of self-harm across urgent and emergency care settings among young people and factors associated with reattendance: protocol for a prospective cohort study
Get PDFIntroduction: Self-harm represents a significant public health concern and is a common reason for contact with urgent and emergency care (UEC) services among young people. Although young people frequently interact with multiple components of the urgent care system following self-harm, there is limited system-level evidence describing patterns of service use, transitions between services and repeat emergency department (ED) attendance. An improved understanding of how young people use UEC services after self-harm is needed to inform the design of more effective and appropriate care pathways.
Methods and analysis: This protocol describes a prospective cohort study using an extract from the Centre for URgent and Emergency care research database (CUREd+) research database, which comprises routinely collected, linked healthcare data from the National Health Service 111 (NHS 111), ambulance services, urgent care centres, walk-in centres and EDs across Yorkshire and the Humber, England. The study population will include young people aged ≤25 years presenting to UEC services between April 2019 and March 2022 with self-harm coded as the reason for attendance. Analyses will describe the prevalence of self-harm presentations across UEC settings, quantify the proportion of NHS 111 and ambulance contacts resulting in ED attendance within 24 hours and examine factors associated with ED reattendance at 3 and 12 months. Mixed-effects logistic regression models will be used to account for repeated attendances, confounding variables and temporal variation, including changes related to the COVID-19 pandemic. Anticipated analysis period: January 2026–January 2027.
Ethics and dissemination: Ethical approval has been granted by the University of Leeds (MREC 22-079 Amd1) and the University of Sheffield (Ref 068194). The CUREd+ research database operates under Research Ethics Committee approval (23/YH/0079) and Confidentiality Advisory Group approval (18/CAG/0126). Individual consent is not required as all data are pseudonymised at source. Findings will be disseminated through peer-reviewed publications, conference presentations and public-facing outputs coproduced with patient and public involvement groups
Data sources:
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