ABSTRACT
Background: Mental health policy makers require evidence-based information to optimise effective care provision based on local need, but tools are unavailable. Aims: To develop and validate a population-level prediction model for need for early intervention in psychosis (EIP) care for first-episode psychosis (FEP) in England up to 2025, based on epidemiological evidence and demographic projections. Method: We used Bayesian Poisson regression to model small-area-level variation in FEP incidence for people aged 16-64 years. We compared six candidate models, validated against observed National Health Service FEP data in 2017. Our best-fitting model predicted annual incidence case-loads for EIP services in England up to 2025, for probable FEP, treatment in EIP services, initial assessment by EIP services and referral to EIP services for 'suspected psychosis'. Forecasts were stratified by gender, age and ethnicity, at national and Clinical Commissioning Group levels. Results: A model with age, gender, ethnicity, small-area-level deprivation, social fragmentation and regional cannabis use provided best fit to observed new FEP cases at national and Clinical Commissioning Group levels in 2017 (predicted 8112, 95% CI 7623-8597; observed 8038, difference of 74 [0.92%]). By 2025, the model forecasted 11 067 new treated cases per annum (95% CI 10383-11740). For every 10 new treated cases, 21 and 23 people would be assessed by and referred to EIP services for suspected psychosis, respectively. Conclusions: Our evidence-based methodology provides an accurate, validated tool to inform clinical provision of EIP services about future population need for care, based on local variation of major social determinants of psychosis.
Subject(s)
Early Medical Intervention , Mental Health Services , Needs Assessment , Psychotic Disorders/epidemiology , Psychotic Disorders/therapy , Adolescent , Adult , Bayes Theorem , England/epidemiology , Female , Forecasting/methods , Humans , Male , Middle Aged , Referral and Consultation , Reproducibility of Results , State Medicine , Young AdultABSTRACT
This paper reports the development, modelling and application of a semi-random multicore fibre (MCF) design for adaptive multiphoton endoscopy. The MCF was constructed from 55 sub-units, each comprising 7 single mode cores, in a hexagonally close-packed lattice where each sub-unit had a random angular orientation. The resulting fibre had 385 single mode cores and was double-clad for proximal detection of multiphoton excited fluorescence. The random orientation of each sub-unit in the fibre reduces the symmetry of the positions of the cores in the MCF, reducing the intensity of higher diffracted orders away from the central focal spot formed at the distal tip of the fibre and increasing the maximum size of object that can be imaged. The performance of the MCF was demonstrated by imaging fluorescently labelled beads with both distal and proximal fluorescence detection and pollen grains with distal fluorescence detection. We estimate that the number of independent resolution elements in the final image - measured as the half-maximum area of the two-photon point spread function divided by the area imaged - to be ~3200.
Subject(s)
Endoscopes , Endoscopy/instrumentation , Microscopy, Fluorescence, Multiphoton , Optical Fibers , Equipment Design , Microspheres , PollenABSTRACT
A fluorescence lifetime imaging (FLIM) technology platform intended to read out changes in Förster resonance energy transfer (FRET) efficiency is presented for the study of protein interactions across the drug-discovery pipeline. FLIM provides a robust, inherently ratiometric imaging modality for drug discovery that could allow the same sensor constructs to be translated from automated cell-based assays through small transparent organisms such as zebrafish to mammals. To this end, an automated FLIM multiwell-plate reader is described for high content analysis of fixed and live cells, tomographic FLIM in zebrafish and FLIM FRET of live cells via confocal endomicroscopy. For cell-based assays, an exemplar application reading out protein aggregation using FLIM FRET is presented, and the potential for multiple simultaneous FLIM (FRET) readouts in microscopy is illustrated.
Subject(s)
Fluorescence Resonance Energy Transfer/methods , Proteins/analysis , Cell Line , Drug Evaluation, Preclinical , Fluorescent Dyes/chemistry , Green Fluorescent Proteins/chemistry , Humans , Microscopy, Fluorescence , Protein Binding , Rhodamines/chemistry , gag Gene Products, Human Immunodeficiency Virus/analysisABSTRACT
We describe a fluorescence lifetime imaging endomicroscope employing a fibre bundle probe and time correlated single photon counting. Preliminary images of stained pollen grains, eGFP-labelled cells exhibiting Förster resonant energy transfer and tissue autofluorescence are presented.
Subject(s)
Endoscopes , Endoscopy/methods , Microscopy, Confocal/instrumentation , Microscopy, Fluorescence/instrumentation , Animals , COS Cells , Chlorocebus aethiops , Fluorescence , Green Fluorescent Proteins/metabolism , Photons , Pollen , Rats , Tendons/anatomy & histology , Time FactorsABSTRACT
We describe a simple implementation of a slit scanning confocal microscope to obtain an axial resolution better than that of a point-scanning confocal microscope. Under slit illumination, images of a fluorescent object are captured using an array detector instead of a line detector so that out-of-focus light is recorded and then subtracted from the adjacent images. Axial resolution after background subtraction is 2.2 times better than the slit confocal resolution, and out-of-focus image suppression is calculated to attenuate with defocus faster by 1 order of magnitude than in the point confocal case.