The hospital discharge game : A game theory-inspired workshop to encourage cooperation between health and social care organisations

Traditionally, health and social care organisations have operated independently, with minimal interaction and poor integration of the various services with which a patient comes into contact. In some cases, 'perverse' systemic incentives have discouraged cooperation and led to a 'silo mentality'. In this paper, we present an interactive workshop game that can be played with those working in and around health and social care. The game places teams in the roles of community and acute hospitals, and asks them to make discharge decisions about patients. However, a 'perverse' incentive is present in the system, and opposing teams are not allowed to communicate, which leads to increasingly 'selfish' decision making. We outline the details of this game, and show how it can be used as a tool to facilitate understanding of the benefits of cross-organisational communication and cooperation. We also present data from an initial pilot of this workshop.National Institute for Health Research (NIHR

Which factors most influence demand for ambulances in South West England?

This is the author accepted manuscript. The final version is available from Mark Allen Healthcare via the DOI in this record Ambulance demand in South West England is increasing year-on-year, but the driving forces behind such increases are poorly understood. We developed a system dynamics model to simulate the factors that influence a call being made for an ambulance. We used data from the South West Ambulance Service NHS Foundation Trust (SWAST), the Office of National Statistics (ONS) and quantitative relationship data in both national and international literature to parameterise the model. We compared predicted ambulance demand over 12 months in the base case model with scenarios in which each influencing factor was removed in turn. The model predicts that the prevalence of regular falls among older people most influences the level of demand for ambulances. The model also predicts that the number of users of adult mental health services could be a significant contributor to ambulance demand. Additional focus on, and investment in, falls prevention strategies could help to significantly alleviate increasing levels of demand for ambulance services in South West England. Additionally, efforts to understand why those with mental health needs tend to use ambulances more than those without such needs could also be beneficial.National Institute for Health Research (NIHR

Nitrogen and carbon isotope composition of organic Fertilizers.

Synthetic (e.g. urea) and organic fertilizers (e.g. compost) differed markedly in N isotope composition and the greater the difference between organic and synthetic fertilizer the more robust will be the differentiation of crops and vegetable grown under different farming systems. The objective of this study was to compare nitrogen and carbon isotope composition of organic fertilizers and manures available for conventional and organic farming in Brazil. Seven samples of organic fertilizer, two of organo-mineral fertilizers and two of different animal manures were analyzed for nitrogen and carbon isotope composition (15N, 13C). Organic fertilizers and manure samples were enriched in 15N as expected. Using synthetic fertilizers as the primary material of organo-mineral fertilizer can imprint a low 15N value to the final product. Organic fertilizers, organo-mineral fertilizers and manures can have their organic feedstock differentiated using 13C. These are preliminary data of the isotopic composition of organic fertilizer in Brazil. Therefore, a wider survey of fertilizers and an experimental approach for organic- and organo-mineral fertilizer production is needed to elucidate the natural isotope variation of the array of available products

Reducing delays in the diagnosis and treatment of muscle-invasive bladder cancer using simulation modelling

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record Objective: To develop a simulation model to identify key bottlenecks in the bladder cancer pathway at Royal Cornwall Hospital and predict the impact of potential changes to reduce these delays. Materials and methods: The diagnosis and treatment of muscle-invasive bladder cancer can suffer numerous delays, which can significantly affect patient outcomes. We developed a discrete event computer simulation model of the flow of patients through the bladder cancer pathway at the hospital, using anonymised patient records from 2014 and 2015. The changes tested in the model were for patients suspected to have muscle-invasive disease on flexible cystoscopy. Those patients were ‘fast-tracked’ to receive their transurethral resection of bladder tumour (TURBT) treatment using operating slots kept free for these patients. A staging computed tomography scan was booked in the haematuria clinic. Pathology requests were marked as 48 hour turnaround. The nurse specialist would then speak to the patient whilst they were on the ward following their TURBT to give information about their ongoing treatment and provide support. Results: The model predicted that if the changes were implemented, delays in the system could be reduced by around 5 weeks. The changes were implemented, and analysis of 3 months of the data post-implementation shows that the average time in the system was reduced by 5 weeks. The environment created by the changes in the pathway improved referral to treatment times in both muscle-invasive and non-muscle-invasive groups. Conclusion: The simulation model proved an invaluable tool for facilitating the implementation of changes. Simple changes to the pathway led to significant reductions in delays for bladder cancer patients at Royal Cornwall Hospital. Level of evidence: Not applicable for this cohort study.National Institute for Health Research (NIHR

Nitrogen loss (NH3, N2O) patterns in bench-scale composting.

Nitrogen (N) losses during composting reduce the value of the end product as a fertilizer. Nitrogen is lost during composting mainly by ammonia (NH3) volatilization in the thermophilic phase. We used three bench-scale aerobic bioreactors with a controlled temperature difference (CDT) system as an experimental approach to investigate the pattern of N losses during composting. N2O peak emission occurred much earlier (7h) than NH3 volatilization (48-60h) during the thermophilic phase (~55°C) of bench-scale composting. The NH3 volatilization peak rate occurred following the greater biological activity (O2 consumed/CO2 evolved) at 40°C which could coincide with greater ammonification, but immobilization of NH4+/NH3 also occurs at this point affecting NH3 volatilization. Differences in temperature curves and accumulated NH3-N were related to the biological activity in each vessel. Therefore, O2 consumed/CO2 evolved measurements must be part of the evaluation of composting in further studies for comparisons of techniques to reduce NH3 volatilizatio

Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance

Mutations in the P53 pathway are a hallmark of human cancer. The identification of pathways upon which p53-deficient cells depend could reveal therapeutic targets that may spare normal cells with intact p53. In contrast to P53 point mutations in other cancer, complete loss of P53 is a frequent event in osteosarcoma (OS), the most common cancer of bone. The consequences of p53 loss for osteoblastic cells and OS development are poorly understood. Here we use murine OS models to demonstrate that elevated Pthlh (Pthrp), cAMP levels and signalling via CREB1 are characteristic of both p53-deficient osteoblasts and OS. Normal osteoblasts survive depletion of both PTHrP and CREB1. In contrast, p53-deficient osteoblasts and OS depend upon continuous activation of this pathway and undergo proliferation arrest and apoptosis in the absence of PTHrP or CREB1. Our results identify the PTHrP-cAMP-CREB1 axis as an attractive pathway for therapeutic inhibition in OS.Mannu K Walia, Patricia MW Ho, Scott Taylor, Alvin JM Ng, Ankita Gupte, Alistair M Chalk, Andrew CW Zannettino, T John Martin, Carl R Walkle

Disease-specific, neurosphere-derived cells as models for brain disorders

There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery

Structural Insights into Notum Covalent Inhibition

The carboxylesterase Notum hydrolyzes a palmitoleate moiety from Wingless/Integrated(Wnt) ligands and deactivates Wnt signaling. Notum inhibitors can restore Wnt signaling which may be of therapeutic benefit for pathologies such as osteoporosis and Alzheimer’s disease. We report the identification of a novel class of covalent Notum inhibitors, 4-(indolin-1-yl)-4-oxobutanoate esters. High-resolution crystal structures of the Notum inhibitor complexes reveal a common covalent adduct formed between the nucleophile serine-232 and hydrolyzed butyric esters. The covalent interaction in solution was confirmed by mass spectrometry analysis. Inhibitory potencies vary depending on the warheads used. Mechanistically, the resulting acyl-enzyme intermediate carbonyl atom is positioned at an unfavorable angle for the approach of the active site water, which, combined with strong hydrophobic interactions with the enzyme pocket residues, hinders the intermediate from being further processed and results in covalent inhibition. These insights into Notum catalytic inhibition may guide development of more potent Notum inhibitors