Data assimilation allows for updating state variables in a model to represent the initial condition of a catchment more accurately than the initial OpenLoop simulation. In hydrology, data ...assimilation is often a prerequisite for forecasting. According to Hornik (1991, https://doi.org/10.1016/0893-6080(91)90009-T) artificial neural networks can learn any nonlinear relationship between inputs and outputs. Here, we hypothesize that neural networks could learn the relationship between the simulated streamflow (from a hydrological model) and the corresponding state variables. Once learned, this relationship can be used to obtain corrected state variables by applying it to observed rather than simulated streamflow. Based on this, we propose a novel, ensemble‐based, data assimilation approach. As a proof of concept and to verify the abovementioned hypothesis, we used an international testbed comprising four hydrologically dissimilar catchments. We applied the new data assimilation method to the lumped hydrological model GR4J, which has two state variables. Within this framework, we compared two types of neural networks, namely, Extreme Learning Machine and the Multilayer Perceptron. Using well‐known metrics such as the continuous ranked probability score, we compared the assimilated streamflow series with the OpenLoop streamflow series and with the observed streamflow. We show that neural networks can be successfully used for data assimilation, with a noticeable improvement over the OpenLoop simulation for all catchments.
Key Points
Neural network‐based methods are proposed for assimilating state variables in conceptual hydrological models
Both multilayer perceptrons and extreme learning machines are shown to generate accurate starting points for streamflow forecasts
Multilayer perceptron ensembles provided more reliable estimates of state variable uncertainty than extreme learning machine ensembles
CA 19-9 and CEA are the most commonly used biomarkers for diagnosis and management of patients with pancreatic cancer. Since the original compendium by Steinberg in 1990, numerous studies have ...reported the use of CA 19-9 and, to a lesser extent, CEA in the diagnosis of pancreatic cancer. Here we update an evaluation of the accuracy of CA 19-9 and CEA, and, unlike previous reviews, focus on discrimination between malignant and benign disease instead of normal controls. In 57 studies involving 3,285 pancreatic carcinoma cases, the combined sensitivity of CA 19-9 was 78.2% and in 37 studies involving 1,882 cases with benign pancreatic disease the specificity of CA 19-9 was 82.8%. From the combined analysis of studies reporting CEA, the sensitivity was 44.2% (1,324 cases) and the specificity was 84.8% (656 cases). These measurements more appropriately reflect the expected biomarker accuracy in the differential diagnosis of patients with periampullary diseases. We also present a summary of the use of CA 19-9 as a prognostic tool and evaluate CA 19-9 diagnostic and prognostic utility in a 10-year, single institution experience.
The swine-origin A(H1N1) influenza virus that has emerged in humans in early 2009 has raised concerns about pandemic developments. In a ferret pathogenesis and transmission model, the 2009 A(H1N1) ...influenza virus was found to be more pathogenic than a seasonal A(H1N1) virus, with more extensive virus replication occurring in the respiratory tract. Replication of seasonal A(H1N1) virus was confined to the nasal cavity of ferrets, but the 2009 A(H1N1) influenza virus also replicated in the trachea, bronchi, and bronchioles. Virus shedding was more abundant from the upper respiratory tract for 2009 A(H1N1) influenza virus as compared with seasonal virus, and transmission via aerosol or respiratory droplets was equally efficient. These data suggest that the 2009 A(H1N1) influenza virus has the ability to persist in the human population, potentially with more severe clinical consequences.
Treatment of hepatitis C virus infections (HCV) with direct acting antivirals (DAA) can prevent new infections since cured individuals cannot transmit HCV. However, as DAAs are expensive, many ...countries defer treatment to advances stages of fibrosis, which results in ongoing transmission. We assessed the epidemiological impact and cost-effectiveness of treatment initiation in different stages of infection in the Netherlands where the epidemic is mainly concentrated among HIV-infected MSMs.
We calibrated a deterministic mathematical model to the Dutch HCV epidemic among HIV-infected MSM to compare three different DAA treatment scenarios: 1) immediate treatment, 2) treatment delayed to chronic infection allowing spontaneous clearance to occur, 3) treatment delayed until F2 fibrosis stage. All scenarios are simulated from 2015 onwards. Total costs, quality adjusted life years (QALY), incremental cost-effectiveness ratios (ICERs), and epidemiological impact were calculated from a providers perspective over a lifetime horizon. We used a DAA price of €35,000 and 3% discounting rates for cost and QALYs.
Immediate DAA treatment lowers the incidence from 1.2/100 person-years to 0.2/100 person-years (interquartile range 0.1-0.2) and the prevalence from 5.0/100 person-years to 0.5/100 person-years (0.4-0.6) after 20 years. Delayed treatment awaiting spontaneous clearance will result in a similar reduction. However, further delayed treatment to F2 will increases the incidence and prevalence. Earlier treatment will cost society €68.3 and €75.1 million over a lifetime for immediate and awaiting until the chronic stage, respectively. The cost will increase if treatment is further delayed until F2 to €98.4 million. Immediate treatment will prevent 7070 new infections and gains 3419 (3019-3854) QALYs compared to F2 treatment resulting in a cost saving ICER. Treatment in the chronic stage is however dominated.
Early DAA treatment for HIV-infected MSM is an excellent and sustainable tool to meet the WHO goal of eliminating HCV in 2030.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
► Evaluation of forecasting systems from an operational point of view. ► Comparison of probabilistic and deterministic hydrological forecasts. ► Improvement of forecasts through the use of a simple ...post-processing method. ► Use of ensemble streamflow forecasts in a stochastic decision-making process. ► Improved electricity production and reduction of spillage through the use of ensemble streamflow forecasts.
An increasing number of publications show that ensemble hydrological forecasts exhibit good performance when compared to observed streamflow. Many studies also conclude that ensemble forecasts lead to a better performance than deterministic ones. This investigation takes one step further by not only comparing ensemble and deterministic forecasts to observed values, but by employing the forecasts in a stochastic decision-making assistance tool for hydroelectricity production, during a flood event on the Gatineau River in Canada. This allows the comparison between different types of forecasts according to their value in terms of energy, spillage and storage in a reservoir. The motivation for this is to adopt the point of view of an end-user, here a hydroelectricity production society. We show that ensemble forecasts exhibit excellent performances when compared to observations and are also satisfying when involved in operation management for electricity production. Further improvement in terms of productivity can be reached through the use of a simple post-processing method.
This manuscript describes the energy and water components of a new community land surface model called the Joint UK Land Environment Simulator (JULES). This is developed from the Met Office Surface ...Exchange Scheme (MOSES). It can be used as a stand alone land surface model driven by observed forcing data, or coupled to an atmospheric global circulation model. The JULES model has been coupled to the Met Office Unified Model (UM) and as such provides a unique opportunity for the research community to contribute their research to improve both world-leading operational weather forecasting and climate change prediction systems. In addition JULES, and its forerunner MOSES, have been the basis for a number of very high-profile papers concerning the land-surface and climate over the last decade. JULES has a modular structure aligned to physical processes, providing the basis for a flexible modelling platform.
Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients ...(17.8%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5-11) and drops below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4-17.2). Multivariate analyses identify viral loads above 7 log
RNA copies/mL (odds ratio OR of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions.
Summary Background Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine prevents HIV infections among men who have sex with men (MSM). PrEP can be given on a daily or intermittent basis. ...Unfortunately, PrEP is not reimbursed in most European countries. Cost-effectiveness analyses of PrEP among MSM in Europe are absent but are key for decision makers to decide upon PrEP implementation. Methods We developed a deterministic mathematical model, calibrated to the well defined Dutch HIV epidemic among MSM, to predict the effect and cost-effectiveness of PrEP. PrEP was targeted to 10% of highly sexually active Dutch MSM over the coming 40 years. Cost-effectiveness ratios were calculated to predict the cost-effectiveness of daily and on-demand PrEP. Cost-effectiveness ratios below €20 000 were considered to be cost-effective in this analysis. Findings Within the context of a stable HIV epidemic, at 80% effectiveness and current PrEP pricing, PrEP can cost as much as €11 000 (IQR 9400–14 100) per quality-adjusted life-year (QALY) gained when used daily, or as little as €2000 (IQR 1300–3000) per QALY gained when used on demand. At 80% effectiveness, daily PrEP can be considered cost-saving if the price of PrEP is reduced by 70%, and on-demand PrEP can be considered cost-saving if the price is reduced by 30–40%. Interpretation PrEP for HIV prevention among MSM in the Netherlands is cost-effective. The use of PrEP is most cost-effective when the price of PrEP is reduced through on-demand use or through availability of generic PrEP, and can quickly be considered cost-saving. Funding None.
This paper presents the aerosol modeling now part of the ECMWF Integrated Forecasting System (IFS). It includes new prognostic variables for the mass of sea salt, dust, organic matter and black ...carbon, and sulphate aerosols, interactive with both the dynamics and the physics of the model. It details the various parameterizations used in the IFS to account for the presence of tropospheric aerosols. Details are given of the various formulations and data sets for the sources of the different aerosols and of the parameterizations describing their sinks. Comparisons of monthly mean and daily aerosol quantities like optical depths against satellite and surface observations are presented. The capability of the forecast model to simulate aerosol events is illustrated through comparisons of dust plume events. The ECMWF IFS provides a good description of the horizontal distribution and temporal variability of the main aerosol types. The forecast‐only model described here generally gives the total aerosol optical depth within 0.12 of the relevant observations and can therefore provide the background trajectory information for the aerosol assimilation system described in part 2 of this paper.
Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine effectively prevents new HIV infections. The optimal scenario for implementing PrEP where most infections are averted at the lowest ...cost is unknown. We determined the impact of different PrEP strategies on averting new infections, prevalence, drug resistance and cost-effectiveness in Macha, a rural setting in Zambia.
A deterministic mathematical model of HIV transmission was constructed using data from the Macha epidemic (antenatal prevalence 7.7%). Antiretroviral therapy is started at CD4<350 cells/mm(3). We compared the number of infections averted, cost-effectiveness, and potential emergence of drug resistance of two ends of the prioritization spectrum: prioritizing PrEP to half of the most sexually active individuals (5-15% of the total population), versus randomly putting 40-60% of the total population on PrEP.
Prioritizing PrEP to individuals with the highest sexual activity resulted in more infections averted than a non-prioritized strategy over ten years (31% and 23% reduction in new infections respectively), and also a lower HIV prevalence after ten years (5.7%, 6.4% respectively). The strategy was very cost-effective at $323 per quality adjusted life year gained and appeared to be both less costly and more effective than the non-prioritized strategy. The prevalence of drug resistance due to PrEP was as high as 11.6% when all assumed breakthrough infections resulted in resistance, and as low as 1.3% when 10% of breakthrough infections resulted in resistance in both our prioritized and non-prioritized scenarios.
Even in settings with low test rates and treatment retention, the use of PrEP can still be a useful strategy in averting infections. Our model has shown that PrEP is a cost-effective strategy for reducing HIV incidence, even when adherence is suboptimal and prioritization is imperfect.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK