A healthcare space planning simulation model for Accident and Emergency (A&E)

The National Health Service (NHS) in the United Kingdom provides a range service for its population including primary care and hospital services. The impact of the 2008 economic and financial crises prompted a tightening of public budgets including health. Over the next few years, and most likely beyond, the NHS is planning for unprecedented levels of efficiency saving in the order of £ billions. With little doubt, the NHS will need to review its way of working will need to do more with less. Simulation is an established technique with applications in many industries including healthcare. Potentially, there are huge opportunities for simulation use to make further inroads in the field of healthcare. Despite the potential, arguably, simulation has failed to make a significant impact in health. Some evidence has tended to suggest that within health there has been poor adaption along with poor linkage to real-world problems, as perceived by healthcare stakeholders. The aim of this thesis is to develop a model to help address real-world healthcare issues as recognised by healthcare stakeholders. In doing so, this thesis will focus on a couple of real-world problems, namely: What space is needed to meet service demand, when is it needed and what will it cost? What space do we have, how can it be used to meet service demand and at what cost? The developed simulation space demand model will demonstrate its value modelling dynamic systems over static models. The developed models will also show its value highlighting space demand issues by groups of patients, by time of day. Real, readily available data (arrival and length of stay, by patient group) would drive the model inputs, supporting ease of use and clarity for healthcare stakeholders. The model was modular by design to support rapid reconfiguration. Dynamically modelled space information allows service managers and Healthcare Planners to better manage and organise their space in a flexible way to meet service requirements. This work will also describe how space demand can linked with building notes to determine Schedules of Accommodation which can be used to cost floor space and consequent building or refurbishment costs. Furthermore, this information could be used to drive business plans and to develop operational cost pertaining to the floor area. This body of work debates using function-to-space ratios and attaching facilities management cost. Our findings suggest great variance in function-to-space ratios. Our findings also suggest that moving to median or lower quartile function-to-space ratios could potentially save hospitals £ millions in facilities management costs. This thesis will reflect on the level of modelling taking place in the healthcare industry by non-academic healthcare modellers, sometimes collectively known as Healthcare Planners, the Healthcare Planning role in space planning and their links with healthcare stakeholders. This reflection will also consider whether healthcare stakeholders perceive a great need for academic healthcare modelling, if they believe their modelling needs are met by Healthcare Planners. A central theme of this thesis is that academic modelling and Healthcare Planning have great synergy and that bringing together Healthcare Planners’ industry knowledge and stakeholder relationships with academic know-how, can make a significant contribution to the healthcare simulation modelling arena

A system for patient management based discrete-event simulation and hierarchical clustering

Hospital Accident and Emergency (A&E) departments in England have a 4 hour target to treat 98% of patients from arrival to discharge, admission or transfer. Managing resources to meet the target and deliver care across the range of A&E services is a huge challenge for A&E managers. This paper develops an intelligent patient management tool to help managers and clinicians better understand patient length of stay and resources within an A&E area. The developed discrete-event simulation model gives a highlevel representation of ambulance arrivals into A&E. The model facilitates analysis in the following ways: visually interactive software showing patient length of stay in the A&E area; patient activity broken down into sub-groups so that intelligence might be gathered on how sub-groups affect the overall length of stay; understanding the number of patient treatment places and nurse resources required. To support ease of inputs for scenario and sensitivity testing, data is entered into the simulation model (Simul8) via Excel spreadsheets. The model discussed in this paper used patient length of stay grouped by A&E diagnosis codes and was limited to ambulance arrivals. The analysis was derived from A&E attendance in 2004 from an English hospital

Evaluating the Impact of an Interprofessional Practice Experience Involving Pharmacy and Dental Students on Medication Histories within an Urban Academic Dental Admissions Clinic

Primary Objective: To compare interprofessional (IP) care versus standard care on medication history clarifications in dental patients. Secondary Objectives: To assess the clinical significance of these clarifications with regards to the potential impact on dental treatment plans. To describe the interventions provided by IP care to clarify discrepancies and/or resolve medication-related problems

Calcium Channel CaV2.3 Subunits Regulate Hepatic Glucose Production by Modulating Leptin-Induced Excitation of Arcuate Pro-opiomelanocortin Neurons.

Leptin acts on hypothalamic pro-opiomelanocortin (POMC) neurons to regulate glucose homeostasis, but the precise mechanisms remain unclear. Here, we demonstrate that leptin-induced depolarization of POMC neurons is associated with the augmentation of a voltage-gated calcium (CaV) conductance with the properties of the "R-type" channel. Knockdown of the pore-forming subunit of the R-type (CaV2.3 or Cacna1e) conductance in hypothalamic POMC neurons prevented sustained leptin-induced depolarization. In vivo POMC-specific Cacna1e knockdown increased hepatic glucose production and insulin resistance, while body weight, feeding, or leptin-induced suppression of food intake were not changed. These findings link Cacna1e function to leptin-mediated POMC neuron excitability and glucose homeostasis and may provide a target for the treatment of diabetes

Mild cold effects on hunger, food intake, satiety and skin temperature in humans.

BACKGROUND: Mild cold exposure increases energy expenditure and can influence energy balance, but at the same time it does not increase appetite and energy intake. OBJECTIVE: To quantify dermal insulative cold response, we assessed thermal comfort and skin temperatures changes by infrared thermography. METHODS: We exposed healthy volunteers to either a single episode of environmental mild cold or thermoneutrality. We measured hunger sensation and actual free food intake. After a thermoneutral overnight stay, five males and five females were exposed to either 18°C (mild cold) or 24°C (thermoneutrality) for 2.5 h. Metabolic rate, vital signs, skin temperature, blood biochemistry, cold and hunger scores were measured at baseline and for every 30 min during the temperature intervention. This was followed by an ad libitum meal to obtain the actual desired energy intake after cold exposure. RESULTS: We could replicate the cold-induced increase in REE. But no differences were detected in hunger, food intake, or satiety after mild cold exposure compared with thermoneutrality. After long-term cold exposure, high cold sensation scores were reported, which were negatively correlated with thermogenesis. Skin temperature in the sternal area was tightly correlated with the increase in energy expenditure. CONCLUSIONS: It is concluded that short-term mild cold exposure increases energy expenditure without changes in food intake. Mild cold exposure resulted in significant thermal discomfort, which was negatively correlated with the increase in energy expenditure. Moreover, there is a great between-subject variability in cold response. These data provide further insights on cold exposure as an anti-obesity measure.The study was funded by NIHR, BRC Seed Fund, individual grants: ML and MS: Marie Curie Fellowship, CYT: Welcome Trust Fellowship, SV: MRC, BHF and BBSRC, AVP: BBSRC.This is the final version of the article. It first appeared from Bioscientifica via https://doi.org/ 10.1530/EC-16-000

On Possibilities of Studying of Supernova Neutrinos at BAKSAN

We consider the possibilities of studying a supernova collapse neutrino burst at Baksan Neutrino Observatory (Institute for Nuclear Research, Russian Academy of Sciences) using the prposed 5-kt target-mass liquid scintillation spectrometer. Attention is given to the influence of mixing angle ${\theta}_{13}$ on the expected rates and spectra of neutrino events

Lipid zonation and phospholipid remodeling in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) can progress from simple steatosis (i.e., nonalcoholic fatty liver [NAFL]) to nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. Currently, the driver for this progression is not fully understood; in particular, it is not known how NAFLD and its early progression affects the distribution of lipids in the liver, producing lipotoxicity and inflammation. In this study, we used dietary and genetic mouse models of NAFL and NASH and translated the results to humans by correlating the spatial distribution of lipids in liver tissue with disease progression using advanced mass spectrometry imaging technology. We identified several lipids with distinct zonal distributions in control and NAFL samples and observed partial to complete loss of lipid zonation in NASH. In addition, we found increased hepatic expression of genes associated with remodeling the phospholipid membrane, release of arachidonic acid (AA) from the membrane, and production of eicosanoid species that promote inflammation and cell injury. The results of our immunohistochemistry analyses suggest that the zonal location of remodeling enzyme LPCAT2 plays a role in the change in spatial distribution for AA-containing lipids. This results in a cycle of AA-enrichment in pericentral hepatocytes, membrane release of AA, and generation of proinflammatory eicosanoids and may account for increased oxidative damage in pericentral regions in NASH. Conclusion: NAFLD is associated not only with lipid enrichment, but also with zonal changes of specific lipids and their associated metabolic pathways. This may play a role in the heterogeneous development of NAFLD. (Hepatology 2017;65:1165-1180)

SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation

Macrophages exhibit a spectrum of activation states ranging from classical to alternative activation1. Alternatively, activated macrophages are involved in diverse pathophysiological processes such as confining tissue parasites2, improving insulin sensitivity3 or promoting an immune tolerant microenvironment that facilitates tumour growth and metastasis4. Recently, the role of metabolism regulating macrophage function has come into focus as both the classical and alternative activation programmes require specific regulated metabolic reprogramming5. While most of the studies regarding immunometabolism have focussed on the catabolic pathways activated to provide energy, little is known about the anabolic pathways mediating macrophage alternative activation. In this study, we show that the anabolic transcription factor sterol regulatory element binding protein 1 (SREBP1) is activated in response to the canonical Th2 cytokine interleukin 4 (IL-4) to trigger the de novo lipogenesis (DNL) programme, as a necessary step for macrophage alternative activation. Mechanistically, DNL consumes NADPH, partitioning it away from cellular antioxidant defences and raising ROS levels. ROS serves as a second messenger, signalling sufficient DNL, and promoting macrophage alternative activation. The pathophysiological relevance of this mechanism is validated by showing that SREBP1/DNL is essential for macrophage alternative activation in vivo in a helminth infection model.This work was supported by the British Heart Foundation (RG/18/7/33636), the MRC (MC_UU_00014/2) and the FP7 MITIN (223450). K.P. was a recipient of a fellowship from the Wellcome Trust. A.N.J.M. and E.J. are supported by the Wellcome Trust (100963/Z/13/Z) and the MRC (U105178805). J.L. is a recipient fellowship of the British Heart Foundation. A.D. was a Marie-Curie Early-Stage Researcher supported by the European Union’s Horizon 2020 research and innovation programme (675585 Marie-Curie ITN ‘SymBioSys’) to J.S.-R. A.K. is supported by the Wellcome Trust (106260/Z/14/Z) and an ERC award (648889). P.F. is supported by the Science Foundation Ireland (10/IN.1/B3004). The IMS Genomics and Transcriptomics and Histology cores (B.M.-A., B.Y.H.L. and M.K.M.) are funded by the UK MRC Metabolic Disease Unit (MRC_MC_UU_12012/5) and a Wellcome Trust Strategic Award (100574/Z/12/Z). The Disease Model Core is part of the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/5) and Wellcome Trust Strategic Award (100574/Z/12/Z)