Antimicrobial Photodynamic Therapy – a promising alternative to treatment of prosthetic joint infections?

Periprosthetic joint infection (PJI) is associated with high patient morbidity and a large financial cost. This study investigated Photodynamic Therapy (PDT) as a means of eradicating bacteria that cause PJI, using a laser with a 665-nm wavelength and methylene blue (MB) as the photosensitizer. The effectiveness of MB concentration on the growth inhibition of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Pseudomonas aeruginosa and Acinetobacter baumannii was investigated. The effect of laser dose was also investigated and the optimized PDT method was used to investigate its bactericidal effect on species within planktonic culture and following the formation of a biofilm on polished titanium and hydroxyapatite coated titanium discs. Results showed that Staphylococci were eradicated at the lowest concentration of 0.1 mM methylene blue (MB). With P. aeruginosa and A. baumannii, increasing the MB concentration improved the bactericidal effect. When the laser dose was increased, results showed that the higher the power of the laser the more bacteria were eradicated with a laser power ≥ 35 J/cm2 and an irradiance of 35 mW/cm2, eradicating all S. epidermidis. The optimized PDT method had a significant bactericidal effect against planktonic MRSA and S. epidermidis compared to MB alone, laser alone, or control (no treatment). When biofilms were formed, PDT treatment had a significantly higher bactericidal effect than MB alone and laser alone for all species of bacteria investigated on the polished disc surfaces. P. aeruginosa grown in a biofilm was shown to be less sensitive to PDT when compared to Staphylococci, and a HA-coated surface reduced the effectiveness of PDT. This study demonstrated that PDT is effective for killing bacteria that cause PJI

Chondromyxoid fibroma management: a single institution experience of 22 cases

Background: Several different strategies have been reported for the treatment of chondromyxoid fibromas, all with variable outcomes and high recurrence rates. Methods: We report on 22 consecutive cases of chondromyxoid fibromas treated by intralesional curettage, four of which had adjuvant cementation at our institution between 2003 and 2010. We assessed the functional outcome using the Musculoskeletal Tumour Society (MSTS) scoring system. Results: Nine males and 16 females with a mean age of 36.5 years (range 11 to 73) and a mean follow-up of 60.7 months were included in the study. Local recurrence occurred in two patients (9%) within the first 2 years following the index procedure. This was treated by re-curettage only of the residual defect. Two postoperative complications occurred: a superficial wound infection in one patient and a transient deep peroneal nerve neurapraxia in the other. The mean postoperative MSTS score was 96.7%. Conclusions: Intralesional curettage and cementation is as an effective treatment strategy for chondromyxoid fibromas, providing satisfactory functional results with a low recurrence rate. Careful case selection with stringent clinical and radiographic follow-up is recommended

The Getting It right First Time (GIRFT) programme in urology; rationale and methodology

This is the final version. Available on open access from Wiley via the DOI in this recordThe Getting It Right First Time (GIRFT) programme is a quality improvement initiative covering the National Health Service in England. The programme aims to standardise clinical practices and improve patient and system level outcomes by utilising data-driven insights and clinically-led recommendations. There are GIRFT workstreams for every medical and surgical specialty, including urology. Defining features of the GIRFT methodology are that it is clinically led by experienced clinicians, data-driven, and specialty specific. Each specialty workstream conducts deep-dive visits to every hospital, analysing performance data and engaging with clinicians and management to identify and share improvement priorities. For urology, GIRFT has completed deep-dive visits and published reports outlining priority areas for development. Reports include recommendations pertaining to streamlining care pathways, reducing the acuity of care environments, enhancing emergency services, optimising utilisation of outpatient services, and workforce training and utilisation. The GIRFT academy provides guides for implementing best practices specific to priority areas of care. These include important disease pathways, and GIRFT-advocated innovations such as urology investigation units and urology area networks. GIRFT offers clinical transformation, cost reduction, equity in access to care, and leaner models of care that are often more environmentally sustainable. Evaluation efforts of the programme have focussed on assessing the adoption of GIRFT recommendations, understanding barriers to change, and modelling the climate impact of advocated practices

Untangling the environmental drivers of gross primary productivity in African rangelands

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All data used in this study are freely available and can be accessed in online repositories. The latest PML_V2 product39 is available through Google Earth Engine from https://github.com/gee-hydro/gee_PML. CHIRPS daily precipitation data38 is available at https://www.chc.ucsb.edu/data/chirps. ERA5-Land reanalysis data95 are available from the European Centre for Medium-Range Weather Forecasts at https://cds.climate.copernicus.eu/cdsapp#!/dataset/reanalysis-era5-land-monthly-means. The following MODIS datasets are available from the Land Processes Distributed Active Archive Center (LP DAAC): land cover classes90 (https://lpdaac.usgs.gov/products/mcd12q1v006/) and burned area96 (https://lpdaac.usgs.gov/products/mcd64a1v006/). The iSDAsoil dataset60 can be accessed at https://isda-africa.com/isdasoil. All datasets are also available through Google Earth Engine (Google account required) and are linked to in the Google Earth Engine repository detailed below. Processed data used for fitting the annual and multi-annual GAMs, as well as model output data used to generate Figs. 1–4, are available at https://doi.org/10.5281/zenodo.13294238.Code availability: Data preparation and analysis code is available at https://doi.org/10.5281/zenodo.7024961. The Google Earth Engine repository for data pre-processing can be accessed by registered Earth Engine users at https://code.earthengine.google.com/?accept_repo=users/guylomax01/africa_rangeland_ppt_gpp_analysis. Intermediate data pre-processing Earth Engine assets can also be accessed at https://code.earthengine.google.com/?asset=projects/ee-guylomax01/assets/africa_rangeland_precipitation_gpp.Precipitation variability is forecast to increase under climate change but its impacts on vegetation productivity are complex. Here, we use generalised additive models and remote sensing-derived datasets to quantify the effect of precipitation amount, distribution, and intensity on the gross primary productivity of dry rangelands across sub-Saharan Africa from 2000 to 2019 and differentiate these effects from other variables. We find that total precipitation is the primary driver of productivity, but that more variable rainfall has a small negative effect across vegetation types and rainfall regimes. Temperature and soil nitrogen also have strong effects, especially in drier rangelands. Shrublands and grasslands are more sensitive to environmental variability than savannas. Our findings support a model in which the main constraints on productivity are maintenance of soil moisture and minimisation of plant water stress. This highlights the risks of climate warming and increasing variability for productivity in water-limited grass and shrublands but suggests savannas may have greater resilience in Africa.Oppenheimer Programme in African Landscape Systems (OPALS)University of ExeterSarah TurvillOppenheimer Generations Research and ConservationEngineering and Physical Sciences Research Council (EPSRC)A. G. Leventis FoundationLeverhulme TrustAlan Turing InstituteEuropean Union Horizon 2020Cyprus Governmen

Trends in day-case bladder outflow obstruction surgery: a study using Hospital Episode Statistics

This is the final version. Available from Wiley via the DOI in this record. Data Availability Statement. This report does not contain patient identifiable data. Data in this report are anonymized. The underlying HES data cannot be made available directly by the authors as the data were obtained under licence/data-sharing agreement from NHS Digital. HES data are available from NHS Digital upon application.OBJECTIVES: To describe the contemporary evolution of day-case bladder outflow obstruction (BOO) surgery in England and to profile day-case BOO surgery practices across England in terms of the types of operation performed and their safety profiles. MATERIALS AND METHODS: This was a retrospective observational analysis of Hospital Episode Statistics and UK Office for National Statistics data. All 111 043 recorded operations across 117 hospital trusts over 66 months, from 1 January 2017 to 30 June 2022, were obtained. Operations were identified as one of: transurethral resection of prostate (TURP); laser ablation or enucleation; vapour therapy; prostatic urethral lift (PUL); or bladder neck incision. Monthly day-case rate trends were plotted across the study period. Descriptive data, day-case rates and 30-day hospital readmissions were analysed for each operation type. Multilevel regression modelling with mixed effects was performed to determine whether day-case surgery was associated with higher 30-day hospital readmissions. RESULTS: Day-case patients were younger, with fewer comorbidities. Time series analysis showed a linear day-case rate increase from 8.3% (January 2017) to 21.0% (June 2022). Day-case rates improved for 92/117 trusts in 2021/2022 compared with 2017. Three of the six trusts with the highest day-case rates performed predominantly day-case TURP, and the other three laser surgery. Nationally, PUL and vapour surgery had the highest day-case rates (80.9% and 38.1%). Most inpatient operations were TURP. Multilevel regression modelling found reduced odds of 30-day readmission after day-case BOO surgery (all operations pooled), no difference for day-case vs inpatient TURP, and reduced odds following day-case LASER operations. CONCLUSIONS: The day-case rates for BOO surgery have linearly increased. Minimally invasive surgical technologies are commonly performed as day cases, whereas high day-case rates for TURP and for laser ablation operations are seen in a minority of hospitals. Day-case pathways to treat BOO can be safely developed irrespective of operative modality

Estimating Nosocomial Infection and its Outcomes in Hospital Patients in England with a Diagnosis of COVID-19 Using Machine Learning

BACKGROUND: COVID-19 nosocomial infections (NIs) may have played a significant role in the dynamics of the pandemic in England, but analysis of their impact at the national scale has been lacking. Our aim was to provide a comprehensive account of NIs, identify their characteristics and outcomes in patients with a diagnosis of COVID-19 and use machine learning modelling to refine these estimates. METHODS: From the Hospital Episodes Statistics database all adult hospital patients in England with a diagnosis of COVID-19 and discharged between March 1st 2020 and March 31st 2021 were identified. A cohort of suspected COVID-19 NIs was identified using four empirical methods linked to hospital coding. A random forest classifier was designed to model the relationship between acquiring NIs and the covariates: patient characteristics, comorbidities, frailty, trust capacity strain and severity of COVID-19 infections. FINDINGS: In total, 374,244 adult patients with COVID-19 were discharged during the study period. The four empirical methods identified 29,896 (8.0%) patients with NIs. The random forest classifier estimated a mean NI rate of 10.5%, with a peak close to 18% during the first wave, but much lower rates thereafter and around 7% in early spring 2021. NIs were highly correlated with longer lengths of stay, high trust capacity strain, greater age and a higher degree of patient frailty. NIs were also found to be associated with higher mortality rates and more severe COVID-19 sequelae, including pneumonia, kidney disease and sepsis. INTERPRETATION: Identification of the characteristics of patients who acquire NIs should help trusts to identify those most at risk. The evolution of the NI rate over time may reflect the impact of changes in hospital management practices and vaccination efforts. Variations in NI rates across trusts may partly reflect different data recording and coding practice

Operationalising Positive Tipping Points towards Global Sustainability

This is the final version. Available from the Global Systems Institute, University of Exeter via the link in this recordGSI scientific working paper series number 2021/01Data Availability: The article contains no new data.Non-Technical Summary: Transforming towards global sustainability requires a dramatic acceleration of current progress. Hence there is growing interest in finding ‘positive tipping points’ at which small interventions can trigger self-reinforcing feedbacks that accelerate systemic change. Examples have recently been seen in power generation, personal transport, and lighting. But how to identify positive tipping points that have yet to occur? We synthesise theory and examples to provide initial guidelines for creating enabling conditions, sensing when a system can be positively tipped, who can trigger it, and how they can trigger it. All of us can play a part in triggering positive tipping points. Technical Summary: Recent work on positive tipping points towards sustainability has focused on social-technological systems and the agency of policymakers to tip change, whilst earlier work identified socialecological positive feedbacks triggered by diverse actors. We bring these together to consider positive tipping points across social-ecological-technological systems and the potential for multiple actors and interventions to trigger them. Established theory and examples provide several generic mechanisms for triggering tipping points. From these we identify specific enabling conditions, reinforcing feedbacks, actors, and interventions that can contribute to triggering positive tipping points in the adoption of sustainable behaviours and technologies. Actions that can create enabling conditions for positive tipping include targeting smaller populations, reducing price, improving performance, desirability and accessibility, coordinating complementary technologies, providing relevant information, and altering social network structure. Actions that can trigger positive tipping include social, ecological, and technological innovations, policy interventions, public investment, private investment, broadcasting public information, and behavioural nudges. Positive tipping points can help counter widespread feelings of disempowerment in the face of global challenges and help unlock ‘paralysis by complexity’. A key research agenda is to consider how different agents and interventions can most effectively work together to create system-wide positive tipping points whilst ensuring a just transformation.Leverhulme TrustAlan Turing Institut

Detection and quantitation of copy number variation in the voltage-gated sodium channel gene of the mosquito Culex quinquefasciatus

Insecticide resistance is typically associated with alterations to the insecticidal target-site or with gene expression variation at loci involved in insecticide detoxification. In some species copy number variation (CNV) of target site loci (e.g. the Ace-1 target site of carbamate insecticides) or detoxification genes has been implicated in the resistance phenotype. We show that field-collected Ugandan Culex quinquefasciatus display CNV for the voltage-gated sodium channel gene (Vgsc), target-site of pyrethroid and organochlorine insecticides. In order to develop field-applicable diagnostics for Vgsc CN, and as a prelude to investigating the possible association of CN with insecticide resistance, three assays were compared for their accuracy in CN estimation in this species. The gold standard method is droplet digital PCR (ddPCR), however, the hardware is prohibitively expensive for widespread utility. Here, ddPCR was compared to quantitative PCR (qPCR) and pyrosequencing. Across all platforms, CNV was detected in ≈10% of mosquitoes, corresponding to three or four copies (per diploid genome). ddPCR and qPCR-Std-curve yielded similar predictions for Vgsc CN, indicating that the qPCR protocol developed here can be applied as a diagnostic assay, facilitating monitoring of Vgsc CN in wild populations and the elucidation of association between the Vgsc CN and insecticide resistance