Prospective evaluation of three point of care devices for glycemia measurement in a neonatal intensive care unit.

Hypoglycemia, if recurrent, may have severe consequences on cognitive and psychomotor development of neonates. Therefore, screening for hypoglycemia is a daily routine in every facility taking care of newborn infants. Point-of-care-testing (POCT) devices are interesting for neonatal use, as their handling is easy, measurements can be performed at bedside, demanded blood volume is small and results are readily available. However, such whole blood measurements are challenged by a wide variation of hematocrit in neonates and a spectrum of normal glucose concentration at the lower end of the test range. We conducted a prospective trial to check precision and accuracy of the best suitable POCT device for neonatal use from three leading companies in Europe. Of the three devices tested (Precision Xceed, Abbott; Elite XL, Bayer; Aviva Nano, Roche), Aviva Nano exhibited the best precision. None completely fulfilled the ISO-accuracy-criteria 15197: 2003 or 2011. Aviva Nano fulfilled these criteria in 92% of cases while the others were <87%. Precision Xceed reached the 95% limit of the 2003 ISO-criteria for values ≤4.2 mmol/L, but not for the higher range (71%). Although validated for adults, new POCT devices need to be specifically evaluated on newborn infants before adopting their routine use in neonatology.

Dynamic simulation of regulatory networks using SQUAD.

BACKGROUND: The ambition of most molecular biologists is the understanding of the intricate network of molecular interactions that control biological systems. As scientists uncover the components and the connectivity of these networks, it becomes possible to study their dynamical behavior as a whole and discover what is the specific role of each of their components. Since the behavior of a network is by no means intuitive, it becomes necessary to use computational models to understand its behavior and to be able to make predictions about it. Unfortunately, most current computational models describe small networks due to the scarcity of kinetic data available. To overcome this problem, we previously published a methodology to convert a signaling network into a dynamical system, even in the total absence of kinetic information. In this paper we present a software implementation of such methodology. RESULTS: We developed SQUAD, a software for the dynamic simulation of signaling networks using the standardized qualitative dynamical systems approach. SQUAD converts the network into a discrete dynamical system, and it uses a binary decision diagram algorithm to identify all the steady states of the system. Then, the software creates a continuous dynamical system and localizes its steady states which are located near the steady states of the discrete system. The software permits to make simulations on the continuous system, allowing for the modification of several parameters. Importantly, SQUAD includes a framework for perturbing networks in a manner similar to what is performed in experimental laboratory protocols, for example by activating receptors or knocking out molecular components. Using this software we have been able to successfully reproduce the behavior of the regulatory network implicated in T-helper cell differentiation. CONCLUSION: The simulation of regulatory networks aims at predicting the behavior of a whole system when subject to stimuli, such as drugs, or determine the role of specific components within the network. The predictions can then be used to interpret and/or drive laboratory experiments. SQUAD provides a user-friendly graphical interface, accessible to both computational and experimental biologists for the fast qualitative simulation of large regulatory networks for which kinetic data is not necessarily available.

Numerical simulation of left ventricular assist device implantations: comparing the ascending and the descending aorta cannulations.

In this work we present numerical simulations of continuous flow left ventricle assist device implantation with the aim of comparing difference in flow rates and pressure patterns depending on the location of the anastomosis and the rotational speed of the device. Despite the fact that the descending aorta anastomosis approach is less invasive, since it does not require a sternotomy and a cardiopulmonary bypass, its benefits are still controversial. Moreover, the device rotational speed should be correctly chosen to avoid anomalous flow rates and pressure distribution in specific location of the cardiovascular tree. With the aim of assessing the differences between these two approaches and device rotational speed in terms of flow rate and pressure waveforms, we set up numerical simulations of network of one-dimensional models where we account for the presence of an outflow cannula anastomosed to different locations of the aorta. Then, we use the resulting network to compare the results of the two different cannulations for several stages of heart failure and different rotational speed of the device. The inflow boundary data for the heart and the cannulas are obtained from a lumped parameters model of the entire circulatory system with an assist device, which is validated with clinical data. The results show that ascending and descending aorta cannulations lead to similar waveforms and mean flow rate in all the considered cases. Moreover, regardless of the anastomosis region, the rotational speed of the device has an important impact on wave profiles; this effect is more pronounced at high RPM.

Positive contrast visualization of nitinol devices using susceptibility gradient mapping.

MRI visualization of devices is traditionally based on signal loss due to T(2)* effects originating from local susceptibility differences. To visualize nitinol devices with positive contrast, a recently introduced postprocessing method is adapted to map the induced susceptibility gradients. This method operates on regular gradient-echo MR images and maps the shift in k-space in a (small) neighborhood of every voxel by Fourier analysis followed by a center-of-mass calculation. The quantitative map of the local shifts generates the positive contrast image of the devices, while areas without susceptibility gradients render a background with noise only. The positive signal response of this method depends only on the choice of the voxel neighborhood size. The properties of the method are explained and the visualizations of a nitinol wire and two stents are shown for illustration.

Vaccination against human papillomavirus in Switzerland: simulation of the impact on infection rates.

OBJECTIVES: Human papillomavirus (HPV) is a sexually transmitted infection of particular interest because of its high prevalence rate and strong causal association with cervical cancer. Two prophylactic vaccines have been developed and different countries have made or will soon make recommendations for the vaccination of girls. Even if there is a consensus to recommend a vaccination before the beginning of sexual activity, there are, however, large discrepancies between countries concerning the perceived usefulness of a catch-up procedure and of boosters. The main objective of this article is to simulate the impact on different vaccination policies upon the mid- and long-term HPV 16/18 age-specific infection rates. METHODS: We developed an epidemiological model based on the susceptible-infective-recovered approach using Swiss data. The mid- and long-term impact of different vaccination scenarios was then compared. RESULTS: The generalization of a catch-up procedure is always beneficial, whatever its extent. Moreover, pending on the length of the protection offered by the vaccine, boosters will also be very useful. CONCLUSIONS: To be really effective, a vaccination campaign against HPV infection should at least include a catch-up to early reach a drop in HPV 16/18 prevalence, and maybe boosters. Otherwise, the protection insured for women in their 20s could be lower than expected, resulting in higher risks to later develop cervical cancer.

Use of mobile devices to answer online surveys: implications for research.

BACKGROUND: There is a growing use of mobile devices to access the Internet. We examined whether participants who used a mobile device to access a brief online survey were quicker to respond to the survey but also, less likely to complete it than participants using a traditional web browser. FINDINGS: Using data from a recently completed online intervention trial, we found that participants using mobile devices were quicker to access the survey but less likely to complete it compared to participants using a traditional web browser. More concerning, mobile device users were also less likely to respond to a request to complete a six week follow-up survey compared to those using traditional web browsers. CONCLUSIONS: With roughly a third of participants using mobile devices to answer an online survey in this study, the impact of mobile device usage on survey completion rates is a concern. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01521078.

Prediction of Infant Drug Exposure Through Breastfeeding: Population PK Modeling and Simulation of Fluoxetine Exposure.

The likelihood of significant exposure to drugs in infants through breast milk is poorly defined, given the difficulties of conducting pharmacokinetics (PK) studies. Using fluoxetine (FX) as an example, we conducted a proof-of-principle study applying population PK (popPK) modeling and simulation to estimate drug exposure in infants through breast milk. We simulated data for 1,000 mother-infant pairs, assuming conservatively that the FX clearance in an infant is 20% of the allometrically adjusted value in adults. The model-generated estimate of the milk-to-plasma ratio for FX (mean: 0.59) was consistent with those reported in other studies. The median infant-to-mother ratio of FX steady-state plasma concentrations predicted by the simulation was 8.5%. Although the disposition of the active metabolite, norfluoxetine, could not be modeled, popPK-informed simulation may be valid for other drugs, particularly those without active metabolites, thereby providing a practical alternative to conventional PK studies for exposure risk assessment in this population.

Monte Carlo simulation of a whole-body counter using IGOR phantoms.

Whole-body counting is a technique of choice for assessing the intake of gamma-emitting radionuclides. An appropriate calibration is necessary, which is done either by experimental measurement or by Monte Carlo (MC) calculation. The aim of this work was to validate a MC model for calibrating whole-body counters (WBCs) by comparing the results of computations with measurements performed on an anthropomorphic phantom and to investigate the effect of a change in phantom's position on the WBC counting sensitivity. GEANT MC code was used for the calculations, and an IGOR phantom loaded with several types of radionuclides was used for the experimental measurements. The results show a reasonable agreement between measurements and MC computation. A 1-cm error in phantom positioning changes the activity estimation by >2%. Considering that a 5-cm deviation of the positioning of the phantom may occur in a realistic counting scenario, this implies that the uncertainty of the activity measured by a WBC is ∼10-20%.

Polymorphisms in fibronectin binding protein A of Staphylococcus aureus are associated with infection of cardiovascular devices.

Medical implants, like cardiovascular devices, improve the quality of life for countless individuals but may become infected with bacteria like Staphylococcus aureus. Such infections take the form of a biofilm, a structured community of bacterial cells adherent to the surface of a solid substrate. Every biofilm begins with an attractive force or bond between bacterium and substratum. We used atomic force microscopy to probe experimentally forces between a fibronectin-coated surface (i.e., proxy for an implanted cardiac device) and fibronectin-binding receptors on the surface of individual living bacteria from each of 80 clinical isolates of S. aureus. These isolates originated from humans with infected cardiac devices (CDI; n = 26), uninfected cardiac devices (n = 20), and the anterior nares of asymptomatic subjects (n = 34). CDI isolates exhibited a distinct binding-force signature and had specific single amino acid polymorphisms in fibronectin-binding protein A corresponding to E652D, H782Q, and K786N. In silico molecular dynamics simulations demonstrate that residues D652, Q782, and N786 in fibronectin-binding protein A form extra hydrogen bonds with fibronectin, complementing the higher binding force and energy measured by atomic force microscopy for the CDI isolates. This study is significant, because it links pathogenic bacteria biofilms from the length scale of bonds acting across a nanometer-scale space to the clinical presentation of disease at the human dimension.

The PEDRO (Pocketable Electronic Devices in Radiation Oncology) project: how clinical practice is changing among young radiation oncologists.

Purpose. To evaluate the impact of mobile devices and apps on the daily clinical activity of young radiation oncologists. Methods. A web-based questionnaire was sent to 382 young (≤40 years) members of the Italian Association of Radiation Oncology (AIRO). The 14 items investigated the diffusion of mobile devices (smartphones and/or tablets), their impact on daily clinical activity, and possible differences perceived by the participants over time. Results. A total of 158 questionnaires were available for statistical evaluation (response rate 41%). Up to 75% of respondents declared they used an electronic device during their clinical activity. Conversely, 82% considered the impact of smartphones/tables on daily practice low to moderate. Daily device use increased significantly from 2009 to 2012, with high daily use rates rising from 5% to 39.9%. Fulfillment of professional needs was declared by less than 42% of respondents and compliance with app indications by 32%. Almost all physicians desired in 2012 a comprehensive website concerning a variety of apps covering radiation oncologists' needs. Conclusions. Mobile devices are widely used by young Italian radiation oncologists in their daily clinical practice, while the indications so obtained are not always followed. Nevertheless, it would be important to verify the consistency of information found within apps, in order to avoid potential errors that might be detrimental to patients.

Monte Carlo simulation of a clearance box monitor used for nuclear power plant decommissioning.

When decommissioning a nuclear facility it is important to be able to estimate activity levels of potentially radioactive samples and compare with clearance values defined by regulatory authorities. This paper presents a method of calibrating a clearance box monitor based on practical experimental measurements and Monte Carlo simulations. Adjusting the simulation for experimental data obtained using a simple point source permits the computation of absolute calibration factors for more complex geometries with an accuracy of a bit more than 20%. The uncertainty of the calibration factor can be improved to about 10% when the simulation is used relatively, in direct comparison with a measurement performed in the same geometry but with another nuclide. The simulation can also be used to validate the experimental calibration procedure when the sample is supposed to be homogeneous but the calibration factor is derived from a plate phantom. For more realistic geometries, like a small gravel dumpster, Monte Carlo simulation shows that the calibration factor obtained with a larger homogeneous phantom is correct within about 20%, if sample density is taken as the influencing parameter. Finally, simulation can be used to estimate the effect of a contamination hotspot. The research supporting this paper shows that activity could be largely underestimated in the event of a centrally-located hotspot and overestimated for a peripherally-located hotspot if the sample is assumed to be homogeneously contaminated. This demonstrates the usefulness of being able to complement experimental methods with Monte Carlo simulations in order to estimate calibration factors that cannot be directly measured because of a lack of available material or specific geometries.

Electronic control device exposure: a review of morbidity and mortality.

The use of electronic control devices has expanded worldwide during the last few years, the most widely used model being the Taser. However, the scientific knowledge about electronic control devices remains limited. We reviewed the medical literature to examine the potential implications of electronic devices in terms of morbidity and mortality, and to identify and evaluate all the existing experimental human studies. A single exposure of an electronic control device on healthy individuals can be assumed to be generally safe, according to 23 prospective human experimental studies and numerous volunteer exposures. In case series, however, electronic control devices could have deleterious effects when used in the field, in particular if persons receive multiple exposures, are intoxicated, show signs of "excited delirium," or present with medical comorbidities. As the use of electronic control devices continues to increase, the controversy about its safety, notably in potentially high-risk individuals, is still a matter of debate. The complications of electronic control device exposure are numerous but often recognizable, usually resulting from barbed dart injuries or from falls. Persons exposed to electronic control devices should therefore be fully examined, and traumatic lesions must be ruled out.

Fluid dynamics simulation of right ventricular outflow tract oversizing.

OBJECTIVES: Repair of the right ventricular outflow tract (RVOT) in paediatric cardiac surgery remains challenging due to the high reoperation rate. Intimal hyperplasia and consequent arteriosclerosis is one of the most important limitation factors for graft durability. Since local shear stress and pressure are predictive elements for intimal hyperplasia and wall degeneration, we sought to determine in an oversized 12-mm RVOT model, with computed fluid dynamics simulation, the local haemodynamical factors that may explain intimal hyperplasia. This was done with the aim of identifying the optimal degree of oversizing for a 12-mm native RVOT. METHODS: Twenty domestic pigs, with a weight of 24.6 ± 0.89 kg and a native RVOT diameter of 12 ± 1.7 mm, had valve conduits of 12, 16, 18 and 20 mm implanted. Pressure and flow were measured at 75, 100 and 125% of normal flow at RVOT at the pulmonary artery, pulmonary artery bifurcation and at the left and right pulmonary arteries. Three-dimensional computed fluid dynamics (CFD) simulation in all four geometries in all flow modalities was performed. Local shear stress and pressure conditions were investigated. RESULTS: Corresponding to 75, 100 and 125% of steady-state flow, three inlet velocity profiles were obtained, 0.2, 0.29 and 0.36 m/s, respectively. At inflow velocity profiles, low shear stress areas, ranged from 0 to 2 Pa, combined with high-pressure areas ranging from 11.5 to 12.1 mmHg that were found at distal anastomosis, at bifurcation and at the ostia of the left and right pulmonary arteries in all geometries. CONCLUSIONS: In all three oversized geometries, the local reparation of shear stress and pressure in the 16-mm model showed a similar local profile as in the native 12 mm RVOT. According to these findings, we suggest oversizing the natural 12-mm RVOT by not more than 4 mm. The elements responsible for wall degeneration and intimal hyperplasia remain very similar to the conditions present in native RVOT.

Ab initio modeling and molecular dynamics simulation of the alpha 1b-adrenergic receptor activation.

This work describes the ab initio procedure employed to build an activation model for the alpha 1b-adrenergic receptor (alpha 1b-AR). The first version of the model was progressively modified and complicated by means of a many-step iterative procedure characterized by the employment of experimental validations of the model in each upgrading step. A combined simulated (molecular dynamics) and experimental mutagenesis approach was used to determine the structural and dynamic features characterizing the inactive and active states of alpha 1b-AR. The latest version of the model has been successfully challenged with respect to its ability to interpret and predict the functional properties of a large number of mutants. The iterative approach employed to describe alpha 1b-AR activation in terms of molecular structure and dynamics allows further complications of the model to allow prediction and interpretation of an ever-increasing number of experimental data.