A framework for different levels of integration of computational models into web-based virtual patients

BACKGROUND: Virtual patients are increasingly common tools used in health care education to foster learning of clinical reasoning skills. One potential way to expand their functionality is to augment virtual patients’ interactivity by enriching them with computational models of physiological and pathological processes. OBJECTIVE: The primary goal of this paper was to propose a conceptual framework for the integration of computational models within virtual patients, with particular focus on (1) characteristics to be addressed while preparing the integration, (2) the extent of the integration, (3) strategies to achieve integration, and (4) methods for evaluating the feasibility of integration. An additional goal was to pilot the first investigation of changing framework variables on altering perceptions of integration. METHODS: The framework was constructed using an iterative process informed by Soft System Methodology. The Virtual Physiological Human (VPH) initiative has been used as a source of new computational models. The technical challenges associated with development of virtual patients enhanced by computational models are discussed from the perspectives of a number of different stakeholders. Concrete design and evaluation steps are discussed in the context of an exemplar virtual patient employing the results of the VPH ARCH project, as well as improvements for future iterations. RESULTS: The proposed framework consists of four main elements. The first element is a list of feasibility features characterizing the integration process from three perspectives: the computational modelling researcher, the health care educationalist, and the virtual patient system developer. The second element included three integration levels: basic, where a single set of simulation outcomes is generated for specific nodes in the activity graph; intermediate, involving pre-generation of simulation datasets over a range of input parameters; advanced, including dynamic solution of the model. The third element is the description of four integration strategies, and the last element consisted of evaluation profiles specifying the relevant feasibility features and acceptance thresholds for specific purposes. The group of experts who evaluated the virtual patient exemplar found higher integration more interesting, but at the same time they were more concerned with the validity of the result. The observed differences were not statistically significant. CONCLUSIONS: This paper outlines a framework for the integration of computational models into virtual patients. The opportunities and challenges of model exploitation are discussed from a number of user perspectives, considering different levels of model integration. The long-term aim for future research is to isolate the most crucial factors in the framework and to determine their influence on the integration outcome

Biostimulation of in situ microbial degradation processes in organically-enriched sediments mitigates the impact of aquaculture

Abstract Fish farm deposition, resulting in organic matter accumulation on bottom sediments, has been identified as among the main phenomena causing negative environmental impacts in aquaculture. An in situ bioremediation treatment was carried out in order to reduce the organic matter accumulation in the fish farm sediments by promoting the natural microbial biodegradation processes. To assess the effect of the treatment, the concentration of organic matter in the sediment and its microbial degradation, as well as the response of the benthic prokaryotic community, were investigated. The results showed a significant effect of the treatment in stimulating microbial degradation rates, and the consequent decrease in the concentration of biochemical components beneath the cages during the treatment. During the bioremediation process, the prokaryotic community in the fish farm sediment responded to the overall improvement of the sediment conditions by showing the decrease of certain anaerobic taxa (e.g. Clostridiales, Acidaminobacteraceae and Caldilinaceae). This suggested that the bioactivator was effective in promoting a shift from an anaerobic to an aerobic metabolism in the prokaryotic community. However, the larger importance of Lachnospiraceae (members of the gut and faecal microbiota of the farmed fishes) in treated compared to non-treated sediments suggested that the bioactivator was not efficient in reducing the accumulation of faecal bacteria from the farmed fishes. Our results indicate that bioremediation is a promising tool to mitigate the aquaculture impact in fish farm sediments, and that further research needs to be oriented to identifying more successful interventions able to specifically target also fish-faeces related microbes

Host-associated and Environmental Microbiomes in an Open-Sea Mediterranean Gilthead Sea Bream Fish Farm

Gilthead seabream is among the most important farmed fish species in the Mediterranean Sea. Several approaches are currently applied to assure a lower impact of diseases and higher productivity, including the exploration of the fish microbiome and its manipulation as a sustainable alternative to improve aquaculture practices. Here, using 16S rRNA gene high-throughput sequencing, we explored the microbiome of farmed seabream to assess similarities and differences among microbial assemblages associated to different tissues and compare them with those in the surrounding environment. Seabream had distinct associated microbiomes according to the tissue and compared to the marine environment. The gut hosted the most diverse microbiome; different sets of dominant ASVs characterized the environmental and fish samples. The similarity between fish and environmental microbiomes was higher in seawater than sediment (up to 7.8 times), and the highest similarity (3.9%) was observed between gill and seawater, suggesting that gills are more closely interacting with the environment. We finally analyzed the potential connections occurring among microbiomes. These connections were relatively low among the host's tissues and, in particular, between the gut and the others fish-related microbiomes; other tissues, including skin and gills, were found to be the most connected microbiomes. Our results suggest that, in mariculture, seabream microbiomes reflect only partially those in their surrounding environment and that the host is the primary driver shaping the seabream microbiome. These data provide a step forward to understand the role of the microbiome in farmed fish and farming environments, useful to enhance disease control, fish health, and environmental sustainability

Comparison and combination of a hemodynamics/biomarkers-based model with simplified PESI score for prognostic stratification of acute pulmonary embolism: findings from a real world study

Background: Prognostic stratification is of utmost importance for management of acute Pulmonary Embolism (PE) in clinical practice. Many prognostic models have been proposed, but which is the best prognosticator in real life remains unclear. The aim of our study was to compare and combine the predictive values of the hemodynamics/biomarkers based prognostic model proposed by European Society of Cardiology (ESC) in 2008 and simplified PESI score (sPESI).Methods: Data records of 452 patients discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. The ESC model and sPESI were retrospectively calculated and compared by using Areas under Receiver Operating Characteristics (ROC) Curves (AUCs) and finally the combination of the two models was tested in hemodinamically stable patients. All cause and PE-related in-hospital mortality and fatal or major bleedings were the analyzed endpointsResults: All cause in-hospital mortality was 25% (16.6% PE related) in high risk, 8.7% (4.7%) in intermediate risk and 3.8% (1.2%) in low risk patients according to ESC model. All cause in-hospital mortality was 10.95% (5.75% PE related) in patients with sPESI score ≥1 and 0% (0%) in sPESI score 0. Predictive performance of sPESI was not significantly different compared with 2008 ESC model both for all cause (AUC sPESI 0.711, 95% CI: 0.661-0.758 versus ESC 0.619, 95% CI: 0.567-0.670, difference between AUCs 0.0916, p=0.084) and for PE-related mortality (AUC sPESI 0.764, 95% CI: 0.717-0.808 versus ESC 0.650, 95% CI: 0.598-0.700, difference between AUCs 0.114, p=0.11). Fatal or major bleedings occurred in 4.30% of high risk, 1.60% of intermediate risk and 2.50% of low risk patients according to 2008 ESC model, whereas these occurred in 1.80% of high risk and 1.45% of low risk patients according to sPESI, respectively. Predictive performance for fatal or major bleeding between two models was not significantly different (AUC sPESI 0.658, 95% CI: 0.606-0.707 versus ESC 0.512, 95% CI: 0.459-0.565, difference between AUCs 0.145, p=0.34). In hemodynamically stable patients, the combined endpoint in-hospital PE-related mortality and/or fatal or major bleeding (adverse events) occurred in 0% of patients with low risk ESC model and sPESI score 0, whilst it occurred in 5.5% of patients with low-risk ESC model but sPESI ≥1. In intermediate risk patients according to ESC model, adverse events occurred in 3.6% of patients with sPESI score 0 and 6.65% of patients with sPESI score ≥1.Conclusions: In real world, predictive performance of sPESI and the hemodynamic/biomarkers-based ESC model as prognosticator of in-hospital mortality and bleedings is similar. Combination of sPESI 0 with low risk ESC model may identify patients with very low risk of adverse events and candidate for early hospital discharge or home treatment.

Biogeochemistry, grain size and mineralogy of the Central and Southern Adriatic Sea sediments: a review.

Volume 26 Supplement 1, January 2010

Computational model for simulation of vascular adaptation following vascular access surgery in haemodialysis patients

\u3cp\u3eAn important number of surgical procedures for creation of vascular access (VA) in haemodialysis patients still results in non-adequate increase in blood flow (non-maturation). The rise in blood flow in arteriovenous shunts depends on vascular remodelling. Computational tools to predict the outcome of VA surgery would be important in this clinical context. The aim of our investigation was then to develop a 0D/1D computational model of arm vasculature able to simulate vessel wall remodelling and related changes in blood flow. We assumed that blood vessel remodelling is driven by peak wall shear stress. The model was calibrated with previously reported values of radial artery diameter and blood flow after end-to-end distal fistula creation. Good agreement was obtained between predicted changes in VA flow and in arterial diameter after surgery and corresponding measured values. The use of this computational model may allow accurate vascular surgery planning and ameliorate VA surgery outcomes.\u3c/p\u3

Paliperidone palmitate as model of heat-sensitive drug for long-acting 3D printing application

In this work, two technologies were used to prepare long-acting implantable dosage forms in the treatment of schizophrenia. Hot-melt extrusion (HME) as well as fused deposition modelling (FDM) were used concomitantly to create personalized 3D printed implants. Different formulations were prepared using an amorphous PLA as matrix polymer and different solid-state plasticizers. Paliperidone palmitate (PP), a heat sensitive drug prescribed in the treatment of schizophrenia was chosen as model drug. After extrusion, different formulations were characterized using DSC and XRD. Then, an in vitro dissolution test was carried out to discriminate the formulation allowing a sustained drug release of PP. The formulation showing a sustained drug release of the drug was 3D printed as an implantable dosage form. By modulating the infill, the release profile was related to the proper design of tailored dosage form and not solely to the solubility of the drug. Indeed, different release profiles were achieved over 90 days using only one formulation. In addition, a stability test was performed on the 3D printed implants for 3 months. The results showed the stability of the amorphous state of PP, independently of the temperature as well as the integrity of the matrix and the drug.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Patient-specific model of arterial circulation for surgical planning of vascular access

PURPOSE: To report the technical aspects of a novel method to generate patient-specific vascular network models of arterial vasculature for the surgical planning of vascular access (VA) for hemodialysis. METHODS: On the basis of literature data, we defined a set of rules for estimation of diameter, length and compliance of arterial network segments, at patient-specific level, as a function of general descriptors (i.e. sex, age, body size and pathology). Using this method we generated vascular network models of height hypothetical patients with different age, sex and body surface area and we computed pressures and blood flows along the arterial arm vasculature using a wave propagation model. RESULTS: Simulation results show that vascular geometry is influenced by sex, age and body size leading to important differences in hemodynamic function. Calculated wall shear stress is higher in women females as compared to men, regardless of body size and age. CONCLUSIONS: Our method facilitates estimating vascular network model parameters useful for patient-specific pre-operative assessment of blood flow distribution in the arterial arm circulation

Clinical predictors of adverse cardiovascular events for acute pediatric drug exposures

Context: Risk factors for adverse cardiovascular events (ACVE) from drug exposures have been well-characterized in adults but not studied in children. The objective of the present study is to describe the incidence, characteristics, and risk factors for in-hospital ACVEs among pediatric emergency department (ED) patients with acute drug exposures. Methods: This is a prospective cohort design evaluating patients in the Toxicology Investigators Consortium (ToxIC) Registry. Pediatric patients (age \u3c 18 years) who were evaluated at the bedside by a medical toxicologist for a suspected acute drug exposure were included. The primary outcome was in-hospital ACVE (myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest). The secondary outcome was in-hospital death. Multiple logistic regression analyses were performed to examine novel clinical risk factors and extrapolate adult risk factors (bicarbonate \u3c 20 mEq/L; QTc \u3e /=500 ms), for the primary/secondary outcomes. Results: Among the 13,097 patients (58.5% female), there were 278 in-hospital ACVEs (2.1%) and 39 in-hospital deaths (0.3%). Age and drug class of exposure (specifically opioids and cardiovascular drugs) were independently associated with ACVE. Compared with adolescents, children under 2 years old (OR: 0.41, 95% CI: 0.21-0.80), ages 2-6 (OR: 0.37, 95% CI: 0.21-0.80), and ages 7-12 (OR: 0.51, 95% CI: 0.27-0.95) were significantly less likely to experience an ACVE. Serum bicarbonate concentration \u3c 20 mEq/L (OR: 2.31, 95% CI: 1.48-3.60) and QTc \u3e /= 500 ms (OR: 2.83, 95% CI: 1.67-4.79) were independently associated with ACVE. Conclusion: Previously derived clinical predictors of ACVE from an adult drug overdose population were successfully extrapolated to this pediatric population. Novel associations with ACVE and death included adolescent age and opioid drug exposures. In the midst of the opioid crisis, these findings urgently warrant further investigation to combat adolescent opioid overdose morbidity and mortality