LifeTime and improving European healthcare through cell-based interceptive medicine.
Ontology highlight
ABSTRACT:
SUBMITTER: Rajewsky N
PROVIDER: S-EPMC7656507 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
LifeTime and improving European healthcare through cell-based interceptive medicine.
Rajewsky Nikolaus N Almouzni Geneviève G Gorski Stanislaw A SA Aerts Stein S Amit Ido I Bertero Michela G MG Bock Christoph C Bredenoord Annelien L AL Cavalli Giacomo G Chiocca Susanna S Clevers Hans H De Strooper Bart B Eggert Angelika A Ellenberg Jan J Fernández Xosé M XM Figlerowicz Marek M Gasser Susan M SM Hubner Norbert N Kjems Jørgen J Knoblich Jürgen A JA Krabbe Grietje G Lichter Peter P Linnarsson Sten S Marine Jean-Christophe JC Marioni John C JC Marti-Renom Marc A MA Netea Mihai G MG Nickel Dörthe D Nollmann Marcelo M Novak Halina R HR Parkinson Helen H Piccolo Stefano S Pinheiro Inês I Pombo Ana A Popp Christian C Reik Wolf W Roman-Roman Sergio S Rosenstiel Philip P Schultze Joachim L JL Stegle Oliver O Tanay Amos A Testa Giuseppe G Thanos Dimitris D Theis Fabian J FJ Torres-Padilla Maria-Elena ME Valencia Alfonso A Vallot Céline C van Oudenaarden Alexander A Vidal Marie M Voet Thierry T
Nature 20200907 7834
Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and ...[more]
Similar Datasets
Project description:MotivationPrecision medicine requires the ability to predict the efficacies of different treatments for a given individual using high-dimensional genomic measurements. However, identifying predictive features remains a challenge when the sample size is small. Incorporating expert knowledge offers a promising approach to improve predictions, but collecting such knowledge is laborious if the number of candidate features is very large.ResultsWe introduce a probabilistic framework to incorporate expert feedback about the impact of genomic measurements on the outcome of interest and present a novel approach to collect the feedback efficiently, based on Bayesian experimental design. The new approach outperformed other recent alternatives in two medical applications: prediction of metabolic traits and prediction of sensitivity of cancer cells to different drugs, both using genomic features as predictors. Furthermore, the intelligent approach to collect feedback reduced the workload of the expert to approximately 11%, compared to a baseline approach.Availability and implementationSource code implementing the introduced computational methods is freely available at https://github.com/AaltoPML/knowledge-elicitation-for-precision-medicine.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC6022689 | biostudies-literature
Project description:Project Santa Fe was established both to provide thought leadership and to help develop the evidence base for the valuation of clinical laboratory services in the next era of American healthcare. The participants in Project Santa Fe represent major regional health systems that can operationalize laboratory-driven innovations and test their valuation in diverse regional marketplaces in the United States. We provide recommendations from the inaugural March 2016 meeting of Project Santa Fe. Specifically, in the transition from volume-based to value-based health care, clinical laboratories are called upon to provide programmatic leadership in reducing total cost of care through optimization of time-to-diagnosis and time-to-effective therapeutics, optimization of care coordination, and programmatic support of wellness care, screening, and monitoring. This call to action is more than working with industry stakeholders on the basis of our expertise; it is providing leadership in creating the programs that accomplish these objectives. In so doing, clinical laboratories can be effectors in identifying patients at risk for escalation in care, closing gaps in care, and optimizing outcomes of health care innovation. We also hope that, through such activities, the evidence base will be created for the new value propositions of integrated laboratory networks. In the very simplest sense, this effort to create "Clinical Lab 2.0" will establish the impact of laboratory diagnostics on the full 100% spend in American healthcare, not just the 2.5% spend attributed to in vitro diagnostics. In so doing, our aim is to empower regional and local laboratories to thrive under new models of payment in the next era of American health care delivery.
| S-EPMC5497901 | biostudies-other
Project description:BACKGROUND:Overweight and obesity is a major global public health challenge, and understanding the implications for healthcare systems is essential for policy planning. Past studies have typically found positive associations between obesity and healthcare utilization, but these studies have not taken into consideration that obesity is also associated with early mortality. We examined associations between body mass index (BMI, reported as kg/m2) and healthcare utilization with and without taking BMI-specific survival into consideration. METHODS:We used nationally representative data on 33 882 adults collected between 2002 and 2015. We computed BMI- and age-specific primary and secondary care utilization and multiplied the estimated values with gender-, age-, and BMI-specific probabilities of surviving to each age. Then, we summed the average BMI-specific utilization between 18 and 85 years. RESULTS:During a survival-adjusted lifetime, males with normal weight (BMI: 18.5-24.9) had, on average, 167 primary care, and 77 secondary care contacts. In comparison, males with overweight (BMI: 25.0-29.9), category I obesity (BMI: 30.0-34.9), and category II/III obesity (BMI ≥35.0) had 11%, 41%, and 102% more primary care, and 14%, 29%, and 78% more secondary care contacts, respectively. Females with normal weight had, on average, 210 primary care contacts and 91 secondary care contacts. Females with overweight, category I obesity, and category II/III obesity had 20%, 34%, and 81% more primary care contacts, and 26%, 16%, and 16% more secondary care contacts, respectively. CONCLUSION:The positive association between BMI and healthcare utilization was reduced, but not offset, when BMI-specific survival was taken into consideration. Our findings underpin previous research and suggest that interventions to offset the increasing prevalence of overweight, and especially obesity, are warranted.
| S-EPMC6794833 | biostudies-other
Project description:Medical and healthcare organisations-including the national cancer support and helpline organisation that is the subject of this study-are expected to collect and monitor information about the ethnicity of their client populations. Information about ethnicity is important for a variety of reasons, including monitoring need and targeting healthcare services appropriately. Previous survey and interview research has suggested that collecting ethnicity data from service users can be incomplete and of variable quality-pointing to a need for an improved understanding of the (interactional) difficulties involved when call-handlers ask callers about their ethnicity.This study analyses a corpus of real-life audio-recorded calls to a national cancer helpline in the UK, focusing on the way that call-handlers collect the ethnic monitoring data.A major national cancer helpline in the UK.A sample of 273 recorded calls were recorded, of which 267 were frontline calls in which call-handlers are expected to ask the ethnicity monitoring question.Findings suggest that caller uncertainty about how to answer the question, resistance to answering and call-handler presumption can compromise the effectiveness of ethnic monitoring. It is likely to be improved by changing how the ethnicity monitoring question is asked. Changes include avoiding open question formats to ease caller uncertainty; offering callers a rationale (account) for the question to minimise resistance and confirming the accuracy of the ethnic category recorded.We recommend that telephone-based healthcare personnel avoid asking the ethnicity monitoring question in an 'open' format; instead, a question containing a (short) standardised list can assist callers in responding. A training tool has been developed that applies this and other findings, with a view to improving ethnic monitoring.
| S-EPMC3696874 | biostudies-other
Project description:Take Home Message Formal training in evidence-based medicine is lacking in most urology residency programs. Perceptions of and attitudes to evidence-based medicine are very positive among European urology residents. Background Evidence-based medicine (EBM) was introduced as a concept in the early 1990s as an integration of the best available evidence with clinical expertise and patient values. Objective To evaluate the current status of EBM training and EBM perception, attitudes, and self-perceived skills among European urology residents. Design, setting, and participants Our online open survey comprised 28 multiple-choice items, including ten questions with responses on a five-point Likert scale ranging from 1 = strongly disagree to 5 = strongly agree. The survey was distributed via the mailing lists and social media accounts of the European Society of Residents in Urology, German Society of Residents in Urology, French Society of Urologists in Training, Spanish Urology Residents Working Group, Italian Society of Residents in Urology, and the Urology Social Media Working Group in two rounds (May–July 2019 and July 2020). We excluded responses from non-European countries. Outcome measurements and statistical analysis The online open survey comprised 28 multiple-choice items. These included ten questions with answers on a five-point Likert scale with response items ranging from strongly disagree (score of 1) to strongly agree (score of 5). Results and limitations We received 210 responses, of which 181 from 23 European countries were eligible. Approximately three-quarters (73.7%) of the respondents were male, with a mean age of 31 yr. Only 28.2% reported EBM training as part of their urology curriculum and 19.3% felt that the training they received was sufficient to guide their daily practice. An overwhelming majority (91.5%) stated that they would be interested in more formalized EBM training or additional training. There was a strong level of agreement (median score 5, interquartile range 4–5) that EBM is important for daily medical and surgical practice and that it improves patient care. Overall, the mean self-perceived understanding of basic EBM concepts was good. Limitations include concerns about generalizability given its internet-based format, the inability to calculate a response rate, poor representation from some European regions, and limited sample size. Conclusions Our survey suggests that European urology residents receive a limited amount of EBM training despite considerable appreciation, interest, and self-perceived deficits for more advanced concepts. Formal integration of EBM teaching in all European residency programs should be considered. Patient summary We performed an online survey of urology residents in Europe. We found that residents have positive perceptions of and attitudes to evidence-based medicine but most programs lack formal training in this area.
| S-EPMC9637704 | biostudies-literature
Project description:Fluorescence microscopy is essential for a detailed understanding of cellular processes; however, live-cell preservation during imaging is a matter of debate. In this study, we proposed a guide to optimize advanced light microscopy approaches by reducing light exposure through fluorescence lifetime (τ) exploitation of red/near-infrared dyes. Firstly, we characterized key instrumental elements which revealed that red/near-infrared laser lines with an 86x (Numerical Aperture (NA) = 1.2, water immersion) objective allowed high transmission of fluorescence signals, low irradiance and super-resolution. As a combination of two technologies, i.e., vacuum tubes (e.g., photomultiplier) and semiconductor microelectronics (e.g., avalanche photodiode), type S, X and R of hybrid detectors (HyD-S, HyD-X and HyD-R) were particularly adapted for red/near-infrared photon counting and τ separation. Secondly, we tested and compared lifetime-based imaging including coarse τ separation for confocal microscopy, fitting and phasor plot analysis for fluorescence lifetime microscopy (FLIM), and lifetimes weighting for enhanced stimulated emission depletion (STED) nanoscopy, in light of red/near-infrared multiplexing. Mainly, we showed that the choice of appropriate imaging approach may depend on fluorochrome number, together with their spectral/lifetime characteristics and STED compatibility. Photon-counting mode and sensitivity of HyDs together with phasor plot analysis of fluorescence lifetimes enabled the flexible and fast imaging of multi-labeled living H28 cells. Therefore, a combination of red/near-infrared dyes labeling with lifetime-based strategies offers new perspectives for live-cell imaging by enhancing sample preservation through acquisition time and light exposure reduction.
| S-EPMC8537913 | biostudies-literature
Project description:ObjectiveEstimates of healthcare costs associated with HIV infection would provide valuable insight for evaluating the cost-effectiveness of possible prevention interventions. We evaluate the additional lifetime healthcare cost incurred due to living with HIV.MethodsWe used a stochastic computer simulation model to project the distribution of lifetime outcomes and costs of men-who-have-sex-with-men (MSM) infected with HIV in 2013 aged 30, over 10,000 simulations. We assumed a resource-rich setting with no loss to follow-up, and that standards and costs of healthcare management remain as now.ResultsBased on a median (interquartile range) life expectancy of 71.5 (45.0-81.5) years for MSM in such a setting, the estimated mean lifetime cost of treating one person was £ 360,800 ($567,000 or € 480,000). With 3.5% discounting, it was £ 185,200 ($291,000 or € 246,000). The largest proportion (68%) of these costs was attributed to antiretroviral drugs. If patented drugs are replaced by generic versions (at 20% cost of patented prices), estimated mean lifetime costs reduced to £ 179,000 ($ 281,000 or € 238,000) and £ 101,200 ($ 158,900 or € 134,600) discounted.ConclusionsIf 3,000 MSM had been infected in 2013, then future lifetime costs relating to HIV care is likely to be in excess of £ 1 billion. It is imperative for investment into prevention programmes to be continued or scaled-up in settings with good access to HIV care services. Costs would be reduced considerably with use of generic antiretroviral drugs.
| S-EPMC4406522 | biostudies-literature
Project description:BackgroundEstimating the burden of healthcare-associated infections (HAIs) compared to other communicable diseases is an ongoing challenge given the need for good quality data on the incidence of these infections and the involved comorbidities. Based on the methodology of the Burden of Communicable Diseases in Europe (BCoDE) project and 2011-2012 data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals, we estimated the burden of six common HAIs.Methods and findingsThe included HAIs were healthcare-associated pneumonia (HAP), healthcare-associated urinary tract infection (HA UTI), surgical site infection (SSI), healthcare-associated Clostridium difficile infection (HA CDI), healthcare-associated neonatal sepsis, and healthcare-associated primary bloodstream infection (HA primary BSI). The burden of these HAIs was measured in disability-adjusted life years (DALYs). Evidence relating to the disease progression pathway of each type of HAI was collected through systematic literature reviews, in order to estimate the risks attributable to HAIs. For each of the six HAIs, gender and age group prevalence from the ECDC PPS was converted into incidence rates by applying the Rhame and Sudderth formula. We adjusted for reduced life expectancy within the hospital population using three severity groups based on McCabe score data from the ECDC PPS. We estimated that 2,609,911 new cases of HAI occur every year in the European Union and European Economic Area (EU/EEA). The cumulative burden of the six HAIs was estimated at 501 DALYs per 100,000 general population each year in EU/EEA. HAP and HA primary BSI were associated with the highest burden and represented more than 60% of the total burden, with 169 and 145 DALYs per 100,000 total population, respectively. HA UTI, SSI, HA CDI, and HA primary BSI ranked as the third to sixth syndromes in terms of burden of disease. HAP and HA primary BSI were associated with the highest burden because of their high severity. The cumulative burden of the six HAIs was higher than the total burden of all other 32 communicable diseases included in the BCoDE 2009-2013 study. The main limitations of the study are the variability in the parameter estimates, in particular the disease models' case fatalities, and the use of the Rhame and Sudderth formula for estimating incident number of cases from prevalence data.ConclusionsWe estimated the EU/EEA burden of HAIs in DALYs in 2011-2012 using a transparent and evidence-based approach that allows for combining estimates of morbidity and of mortality in order to compare with other diseases and to inform a comprehensive ranking suitable for prioritization. Our results highlight the high burden of HAIs and the need for increased efforts for their prevention and control. Furthermore, our model should allow for estimations of the potential benefit of preventive measures on the burden of HAIs in the EU/EEA.
| S-EPMC5068791 | biostudies-literature
Project description:The principle of least effort has been widely used to explain phenomena related to human behavior ranging from topics in language to those in social systems. It has precedence in the principle of least action from the Lagrangian formulation of classical mechanics. In this study, we present a model for interceptive human walking based on the least action principle. Taking inspiration from Lagrangian mechanics, a Lagrangian is defined as effort minus security, with two different specific mathematical forms. The resulting Euler-Lagrange equations are then solved to obtain the equations of motion. The model is validated using experimental data from a virtual reality crossing simulation with human participants. We thus conclude that the least action principle provides a useful tool in the study of interceptive walking.
| S-EPMC7838306 | biostudies-literature
Project description:Fluorescence lifetime imaging (FLI) is increasingly recognized as a powerful tool for biochemical and cellular investigations, including in vivo applications. Fluorescence lifetime is an intrinsic characteristic of any fluorescent dye which, to a large extent, does not depend on excitation intensity and signal level. In particular, it allows distinguishing dyes with similar emission spectra, offering additional multiplexing capabilities. However, in vivo FLI in the visible range is complicated by the contamination by (i) tissue autofluorescence, which decreases contrast, and by (ii) light scattering and absorption in tissues, which significantly reduce fluorescence intensity and modify the temporal profile of the signal. Here, we demonstrate how these issues can be accounted for and overcome, using a new time-gated single-photon avalanche diode array camera, SwissSPAD2, combined with phasor analysis to provide a simple and fast visual method for lifetime imaging. In particular, we show how phasor dispersion increases with increasing scattering and/or decreasing fluorescence intensity. Next, we show that as long as the fluorescence signal of interest is larger than the phantom autofluorescence, the presence of a distinct lifetime can be clearly identified with appropriate background correction. We use these results to demonstrate the detection of A459 cells expressing the fluorescent protein mCyRFP1 through highly scattering and autofluorescent phantom layers. These results showcase the possibility to perform FLI in challenging conditions, using standard, bright, visible fluorophore or fluorescence proteins.
| S-EPMC9355389 | biostudies-literature