Cirrhosis Mortality Prediction as Classification Using Frequent Subgraph Mining

In this work, we use machine learning and data analysis techniques to predict the one-year mortality of cirrhotic patients. Data from 2,322 patients with liver cirrhosis are collected at a single medical center. Different machine learning models are applied to predict one-year mortality. A comprehensive feature space including demographic information, comorbidity, clinical procedure and laboratory tests is being analyzed. A temporal pattern mining technic called Frequent Subgraph Mining (FSM) is being used. Model for End-stage liver disease (MELD) prediction of mortality is used as a comparator. All of our models statistically significantly outperform the MELD-score model and show an average 10% improvement of the area under the curve (AUC). The FSM technic itself does not improve the model significantly, but FSM, together with a machine learning technique called an ensemble, further improves the model performance. With the abundance of data available in healthcare through electronic health records (EHR), existing predictive models can be refined to identify and treat patients at risk for higher mortality. However, due to the sparsity of the temporal information needed by FSM, the FSM model does not yield significant improvements. Our work applies modern machine learning algorithms and data analysis methods on predicting one-year mortality of cirrhotic patients and builds a model that predicts one-year mortality significantly more accurate than the MELD score. We have also tested the potential of FSM and provided a new perspective of the importance of clinical features.

Comparison of Deep Convolutional Neural Networks Models for Plant Disease Identification

Identification of plant diseases has been performed using machine learning and deep learning models on the datasets containing images of healthy and diseased plant leaves. The current study carries out an evaluation of some of the deep learning models based on convolutional neural network architectures for identification of plant diseases. For this purpose, the publicly available New Plant Diseases Dataset, an augmented version of PlantVillage dataset, available on Kaggle platform, containing 87,900 images has been used. The dataset contained images of 26 diseases of 14 different plants and images of 12 healthy plants. The CNN models selected for the study presented in this paper are AlexNet, ZFNet, VGGNet (four models), GoogLeNet, and ResNet (three models). The selected models are trained using PyTorch, an open-source machine learning library, on Google Colaboratory. A comparative study has been carried out to analyze the high degree of accuracy achieved using these models. The highest test accuracy and F1-score of 99.59% and 0.996, respectively, were achieved by using GoogLeNet with Mini-batch momentum based gradient descent learning algorithm.

A Commercial Building Plug Load Management System That Uses Internet of Things Technology to Automatically Identify Plugged-In Devices and Their Locations

Plug and process loads (PPLs) account for a large portion of U.S. commercial building energy use. There is a huge potential to reduce whole building consumption by targeting PPLs for energy savings measures or implementing some form of plug load management (PLM). Despite this potential, there has yet to be a widely adopted commercial PLM technology. This paper describes the Automatic Type and Location Identification System (ATLIS), a PLM system framework with automatic and dynamic load detection (ADLD). ADLD gives PLM systems the ability to automatically identify devices as they are plugged into the outlets of a building. The ATLIS framework takes advantage of smart, connected devices to identify device locations in a building, meter and control their power, and communicate this information to a central database. ATLIS includes five primary capabilities: location identification, communication, control, energy metering, and data storage. A laboratory proof of concept (PoC) demonstrated all but the energy metering capability, and these capabilities were validated using a series of system tests. The PoC was able to identify when a device was plugged into an outlet and the location of the device in the building. When a device was moved, the PoC’s dashboard and database were automatically updated with the new location. The PoC implemented controls to devices from the system dashboard so that devices maintained correct schedules regardless of where they were plugged in within the building. ATLIS’s primary technology application is improved PLM, but other applications include asset management, energy audits, and interoperability for grid-interactive efficient buildings. An ATLIS-based system could also be used to direct power to critical devices, such as ventilators, during a brownout or blackout. Such a framework is an opportunity to make PLM more widespread and reduce the amount of energy consumed by PPLs in current and future commercial buildings.

An Overview of Technology Availability to Support Remote Decentralized Clinical Trials

Developing new medicine and health solutions and improving patient health currently rely on the successful execution of clinical trials, which generate relevant safety and efficacy data. For their success, recruitment and retention of participants are some of the most challenging aspects of protocol adherence. Main barriers include: i) lack of awareness of clinical trials; ii) long distance from the clinical site; iii) the burden on participants, including the duration and number of clinical visits, and iv) high dropout rate. Most of these aspects could be addressed with a new paradigm, namely the Remote Decentralized Clinical Trials (RDCTs). Furthermore, the COVID-19 pandemic has highlighted additional advantages and challenges for RDCTs in practice, allowing participants to join trials from home and not depending on site visits, etc. Nevertheless, RDCTs should follow the process and the quality assurance of conventional clinical trials, which involve several processes. For each part of the trial, the Building Blocks, existing software and technologies were assessed through a systematic search. The technology needed to perform RDCTs is widely available and validated but is yet segmented and developed in silos, as different software solutions address different parts of the trial and at various levels. The current paper is analyzing the availability of technology to perform RDCTs, identifying gaps and providing an overview of Basic Building Blocks and functionalities that need to be covered to support the described processes.

Titanium Dioxide Modified with Glutathione as Potential Drug Carrier with Reduced Toxic Properties

The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO2 nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO2 nanoparticles was characterized from 30 nm to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were: water, SBF and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Additive Friction Stir Manufacturing Process: Interest in Understanding Thermal Phenomena and Numerical Modeling of the Temperature Rise Phase

Additive Friction Stir Manufacturing, or AFSM, is a new industrial process that follows the emergence of friction-based processes. The AFSM process is a solid-state additive process using the energy produced by the friction at the interface between a rotating non-consumable tool and a substrate. Friction depends on various parameters like axial force, rotation speed or friction coefficient. The feeder material is a metallic rod that flows through a hole in the tool. There is still a lack in understanding of the physical phenomena taking place during the process. This research aims at a better AFSM process understanding and implementation, thanks to numerical simulation and experimental validation performed on a prototype effector. Such an approach is considered a promising way for studying the influence of the process parameters and to finally identify a process window that seems relevant. The deposition of material through the AFSM process takes place in several phases. In chronological order these phases are the docking phase, the dwell time phase, the deposition phase, and the removal phase. The present work focuses on the dwell time phase that enables the temperature rise of the system due to pure friction. An analytic modeling of heat generation based on friction considers as main parameters the rotational speed and the contact pressure. Another parameter considered influential is the friction coefficient assumed to be variable, due to the self-lubrication of the system with the rise in temperature or the materials in contact roughness smoothing over time. This study proposes through a numerical modeling followed by an experimental validation to question the influence of the various input parameters on the dwell time phase. Rotation speed, temperature, spindle torque and axial force are the main monitored parameters during experimentations and serve as reference data for the calibration of the numerical model. This research shows that the geometry of the tool as well as fluctuations of the input parameters like axial force and rotational speed are very influential on the temperature reached and/or the time required to reach the targeted temperature. The main outcome is the prediction of a process window which is a key result for a more efficient process implementation.

Trial of Fecal Microbial Transplantation for the Prevention of Canine Atopic Dermatitis

The skin-gut axis defines the relationship between the intestinal microbiota and the development of pathological skin diseases. Low diversity within the gut can predispose to the development of allergic skin conditions, and a greater diversity of the gastrointestinal microflora has been associated with a reduction of skin flares in people with atopic dermatitis. Manipulation of the gut microflora has been used as a treatment option for several conditions in people, but there is limited data available on the use of fecal transplantation as a preventative measure in either people or dogs. Six, 4-month-old pups from a litter of 10 were presented for diarrhea and/or signs of skin disease (chronic scratching, otitis externa). Of these pups, two were given probiotics with a resultant resolution of diarrhea. The other four pups were given fecal transplantation, either as a sole treatment or in combination with other treatments. Follow-up on the litter of 10 pups was performed at 18 months of age. At this stage, three out of the four pups that had received fecal transplantation had resolved all clinical signs and had no recurrence of either skin or gastrointestinal symptoms, the other pup had one episode of Malassezia otitis. Of the remaining six pups from the litter, all had developed at least one episode of Malassezia otitis externa within the period of five to 18 months of age. Two pups had developed two Malassezia otitis infections, and one had developed three Malassezia otitis infections during this period. Favrot’s criteria for the diagnosis of canine atopic dermatitis include chronic or recurrent Malassezia infections by the age of three years. Early results from this litter predict a reduction in the development of canine atopic disease in dogs given fecal microbial transplantation. Follow-up studies at three years of age and within a larger population of dogs can enhance understanding of the impact of early fecal transplantation in the prevention of canine atopic dermatitis.

Effect of Type of Pile and Its Installation Method on Pile Bearing Capacity by Physical Modeling in Frustum Confining Vessel

Various factors such as the method of installation, the pile type, the pile material and the pile shape, can affect the final bearing capacity of a pile executed in the soil; among them, the method of installation is of special importance. The physical modeling is among the best options in the laboratory study of the piles behavior. Therefore, the current paper first presents and reviews the frustum confining vessel (FCV) as a suitable tool for physical modeling of deep foundations. Then, by describing the loading tests of two open-ended and closed-end steel piles, each of which has been performed in two methods, “with displacement" and "without displacement", the effect of end conditions and installation method on the final bearing capacity of the pile is investigated. The soil used in the current paper is silty sand of Firuzkuh, Iran. The results of the experiments show that in general the without displacement installation method has a larger bearing capacity in both piles, and in a specific method of installation the closed ended pile shows a slightly higher bearing capacity.

Incorporating Lexical-Semantic Knowledge into Convolutional Neural Network Framework for Pediatric Disease Diagnosis

The utilization of electronic medical record (EMR) data to establish the disease diagnosis model has become an important research content of biomedical informatics. Deep learning can automatically extract features from the massive data, which brings about breakthroughs in the study of EMR data. The challenge is that deep learning lacks semantic knowledge, which leads to impracticability in medical science. This research proposes a method of incorporating lexical-semantic knowledge from abundant entities into a convolutional neural network (CNN) framework for pediatric disease diagnosis. Firstly, medical terms are vectorized into Lexical Semantic Vectors (LSV), which are concatenated with the embedded word vectors of word2vec to enrich the feature representation. Secondly, the semantic distribution of medical terms serves as Semantic Decision Guide (SDG) for the optimization of deep learning models. The study evaluates the performance of LSV-SDG-CNN model on four kinds of Chinese EMR datasets. Additionally, CNN, LSV-CNN, and SDG-CNN are designed as baseline models for comparison. The experimental results show that LSV-SDG-CNN model outperforms baseline models on four kinds of Chinese EMR datasets. The best configuration of the model yielded an F1 score of 86.20%. The results clearly demonstrate that CNN has been effectively guided and optimized by lexical-semantic knowledge, and LSV-SDG-CNN model improves the disease classification accuracy with a clear margin.

An E-Maintenance IoT Sensor Node Designed for Fleets of Diverse Heavy-Duty Vehicles

E-maintenance is a relatively recent concept, generally referring to maintenance management by monitoring assets over the Internet. One of the key links in the chain of an e-maintenance system is data acquisition and transmission. Specifically for the case of a fleet of heavy-duty vehicles, where the main challenge is the diversity of the vehicles and vehicle-embedded self-diagnostic/reporting technologies, the design of the data acquisition and transmission unit is a demanding task. This is clear if one takes into account that a heavy-vehicles fleet assortment may range from vehicles with only a limited number of analog sensors monitored by dashboard light indicators and gauges to vehicles with plethora of sensors monitored by a vehicle computer producing digital reporting. The present work proposes an adaptable internet of things (IoT) sensor node that is capable of addressing this challenge. The proposed sensor node architecture is based on the increasingly popular single-board computer – expansion boards approach. In the proposed solution, the expansion boards undertake the tasks of position identification, cellular connectivity, connectivity to the vehicle computer, and connectivity to analog and digital sensors by means of a specially targeted design of expansion board. Specifically, the latter offers a number of adaptability features to cope with the diverse sensor types employed in different vehicles. In standard mode, the IoT sensor node communicates to the data center through cellular network, transmitting all digital/digitized sensor data, IoT device identity and position. Moreover, the proposed IoT sensor node offers connectivity, through WiFi and an appropriate application, to smart phones or tablets allowing the registration of additional vehicle- and driver-specific information and these data are also forwarded to the data center. All control and communication tasks of the IoT sensor node are performed by dedicated firmware.

Study of Eatable Aquatic Invertebrates in the River Dhansiri, Dimapur, Nagaland, India

A study has been conducted on the available aquatic invertebrates in the river Dhansiri at Dimapur site. The study confirmed that the river body composed of aquatic macroinvertebrate community in two phyla viz., Arthropods and Molluscs. Total ten species have been identified from there as the source of alternative protein food for the common people. Not only the protein source they are also the component of aquatic food chain and indicators of aquatic ecosystem. Proper management and strategies to promote the edible invertebrates can be considered as the alternative protein and alternative income source for the common people for sustainable livelihood improvement.

Physicochemical and Thermal Characterization of Starch from Three Different Plantain Cultivars in Puerto Rico

Plantain contains starch as the main component and represents a relevant source of this carbohydrate. Starches from different cultivars of plantain and bananas have been studied for industrialization purposes due to their morphological and thermal characteristics and their influence in food products. This study aimed to characterize the physical, chemical, and thermal properties of starch from three different plantain cultivated in Puerto Rico: Maricongo, Maiden and FHIA 20. Amylose and amylopectin content, color, granular size, morphology, and thermal properties were determined. According to the amylose content in starches, FHIA 20 presented lowest content of the three cultivars studied. In terms of color, Maiden and FHIA 20 starches exhibited significantly higher whiteness indexes compared to Maricongo starch. Starches of the three cultivars had an elongated-ovoid morphology, with a smooth surface and a non-porous appearance. Regardless of similarities in their morphology, FHIA 20 exhibited a lower aspect ratio since its granules tended to be more elongated. Comparison of the thermal properties of starches showed that initial starch gelatinization temperature was similar among cultivars. However, FHIA 20 starch presented a noticeably higher final gelatinization temperature (87.95°C) and transition enthalpy than Maricongo (79.69°C) and Maiden (77.40°C). Despite similarities, starches from plantain cultivars showed differences in their composition and thermal behavior. This represents an opportunity to diversify plantain starch use in food-related applications.

A 3D Numerical Environmental Modeling Approach for Assessing Transport of Spilled Oil in Porous Beach Conditions under a Meso-Scale Tank Design

Shorelines are vulnerable to significant environmental impacts from oil spills. Stranded oil can cause potential short- to long-term detrimental effects along beaches that include injuries to ecosystem, socio-economic and cultural resources. In this study, a three-dimensional (3D) numerical modeling approach is developed to evaluate the fate and transport of spilled oil for hypothetical oiled shoreline cases under various combinations of beach geomorphology and environmental conditions. The developed model estimates the spatial and temporal distribution of spilled oil for the various test conditions, using the finite volume method and considering the physical transport (dispersion and advection), sinks, and sorption processes. The model includes a user-friendly interface for data input on variables such as beach properties, environmental conditions, and physical-chemical properties of spilled oil. An experimental meso-scale tank design was used to test the developed model for dissolved petroleum hydrocarbon within shorelines. The simulated results for effects of different sediment substrates, oil types, and shoreline features for the transport of spilled oil are comparable to that obtained with a commercially available model. Results show that the properties of substrates and the oil removal by shoreline effects have significant impacts on oil transport in the beach area. Sensitivity analysis, through the application of the one-step-at-a-time method (OAT), for the 3D model identified hydraulic conductivity as the most sensitive parameter. The 3D numerical model allows users to examine the behavior of oil on and within beaches, assess potential environmental impacts, and provide technical support for decisions related to shoreline clean-up operations.

Shaping the Input Side Current Waveform of a 3-ϕ Rectifier into a Pure Sine Wave

In this investigative research paper, we have presented the simulation results of a three-phase rectifier circuit to improve the input side current using the passive filters, such as capacitors and inductors at the output and input terminals of the rectifier circuit respectively. All simulation works were performed in a personal computer using the PSPICE simulator software, which is a virtual circuit design and simulation software package. The output voltages and currents were measured across a resistive load of 1 k. We observed that the output voltage levels, input current wave shapes, harmonic contents through the harmonic spectrum, and total harmonic distortion improved due to the use of such filters.

Technical, Environmental, and Financial Assessment for the Optimal Sizing of a Run-of-River Small Hydropower Project: A Case Study in Colombia

Run-of-river (RoR) hydropower projects represent a viable, clean, and cost-effective alternative to dam-based plants and provide decentralized power production. However, RoR schemes’ cost-effectiveness depends on the proper selection of site and design flow, which is a challenging task because it requires multivariate analysis. In this respect, this study presents the development of an investment decision support tool for assessing the optimal size of an RoR scheme considering the technical, environmental, and cost constraints. The net present value (NPV) from a project perspective is used as an objective function for supporting the investment decision. The tool has been tested by applying it to an actual RoR project recently proposed in Colombia. The obtained results show that the optimum point in financial terms does not match the flow that maximizes energy generation from exploiting the river's available flow. For the case study, the flow that maximizes energy corresponds to a value of 5.1 m3/s. In comparison, an amount of 2.1 m3/s maximizes the investors NPV. Finally, a sensitivity analysis is performed to determine the NPV as a function of the debt rate changes and the electricity prices and the CapEx. Even for the worst-case scenario, the optimal size represents a positive business case with an NPV of 2.2 USD million and an internal rate of return (IRR) 1.5 times higher than the discount rate. 

The Effects of an Online Career Intervention on University Students’ Levels of Career Adaptability

People’s ability to adapt to a constantly changing environment is essential. Career adaptability is central to Career Construction Theory, where proper adaptation to new situations, changing environments, and jobs require adequate career development. Based on current career theories and the possibilities offered by digital technology, the primary goal of this study is to develop career adaptability through an online tool. Its secondary goal is to apply for an online career intervention program and explore its developmental possibilities. A total of 132 university students from the bachelor program took part in the study, from which 65 students received a four-week online career intervention, while 67 participants formed the control group. Based on the results, it can state that career adaptability can be developed, and there is a great demand and interest from university students to use career-related programs on online platforms. Career interventions should be performed online as well if there is suitable software and a well-constructed program. Limitations and further implications are discussed.

Effect of Non-Metallic Inclusion from the Continuous Casting Process on the Multi-Stage Forging Process and the Tensile Strength of the Bolt: A Case Study

The paper presents the influence of non-metallic inclusions on the multi-stage forging process and the mechanical properties of the dodecagon socket bolt used in the automotive industry. The detected metallurgical defect was so large that it directly influenced the mechanical properties of the bolt and resulted in failure to meet the requirements of the mechanical property class. In order to assess the defect, an X-ray examination and metallographic examination of the defective bolt were performed, showing exogenous non-metallic inclusion. The size of the defect on the cross section was 0.531 mm in width and 1.523 mm in length; the defect was continuous along the entire axis of the bolt. In analysis, a finite element method (FEM) simulation of the multi-stage forging process was designed, taking into account a non-metallic inclusion parallel to the sample axis, reflecting the studied case. The process of defect propagation due to material upset in the head area was analyzed. The final forging stage in shaping the dodecagonal socket and filling the flange area was particularly studied. The effect of the defect was observed to significantly reduce the effective cross-section as a result of the expansion of the defect perpendicular to the axis of the bolt. The mechanical properties of products with and without the defect were analyzed. In the first step, the hardness test confirmed that the required value for the mechanical class 8.8 of both bolt types was obtained. In the second step, the bolts were subjected to a static tensile test. The bolts without the defect gave a positive result, while all 10 bolts with the defect gave a negative result, achieving a tensile strength below the requirements. Tensile strength tests were confirmed by metallographic tests and FEM simulation with perpendicular inclusion spread in the area of the head. The bolts were damaged directly under the bolt head, which is inconsistent with the requirements of ISO 898-1. It has been shown that non-metallic inclusions with orientation in accordance with the axis of the bolt can directly cause loss of functionality and these defects should be detected even before assembling in the machine element.

Effect of Needle Height on Discharge Coefficient and Cavitation Number

Cavitation inside diesel injector nozzle is investigated using Reynolds-Stress-Navier stokes equations. Schnerr-Sauer cavitation model is used for modeling cavitation inside diesel injector nozzle. The carrying fluid utilized in the current study is diesel fuel. The flow is verified at the beginning by comparing with the previous experimental data and it was found that K-Epsilon turbulent model could lead to a better accuracy comparing to K-Omega turbulent model. Moreover, mass flow rate obtained numerically is compared with the experimental value and discrepancy was found to be less than 5% - which shows the accuracy of the current results. Finally, a real-size four-hole nozzle is investigated and the flow inside it is visualized based on velocity profile, discharge coefficient and cavitation number. It was found that the mesh density could be reduced significantly by utilizing periodic boundary condition. Velocity contour at the mid nozzle showed that maximum value of velocity occurs at the end of the needle before entering the orifice area. Last but not least, at the same boundary conditions, when different needle heights were utilized, it was found that as needle height increases with an increase in cavitation number, discharge coefficient increases, while the mentioned increases is more tangible at smaller values of needle heights.

Effect of Different Diesel Fuels on Formation of the Cavitation Phenomena

Cavitation inside a diesel injector nozzle is investigated numerically in this study. The Reynolds Stress Navier Stokes set of equations (RANS) are utilized to investigate flow behavior inside the nozzle numerically. Moreover, K-ε turbulent model is found to be a better approach comparing to K-ω turbulent model. The Winklhofer rectangular shape nozzle is also simulated in order to verify the current numerical scheme, and with the mass flow rate approach, the current solution is verified. Afterward, a six-hole real size nozzle was simulated and it was found that among the different fuels used in this study with the same condition, diesel fuel provides the largest length of cavitation. Also, it was found that at the same boundary condition, rapeseed methyl ester (RME) fuel leads to the highest value of discharge coefficient and mass flow rate.

Associations among Fetuin A, Cortisol and Thyroid Hormones in Children with Morbid Obesity and Metabolic Syndrome

Obesity is a disease with an ever-increasing prevalence throughout the world. The metabolic network associated with obesity is very complicated. In metabolic syndrome (MetS), it becomes even more difficult to understand. Within this context, hormones, cytokines, and many others participate in this complex matrix. The collaboration among all of these parameters is a matter of great wonder. Cortisol, as a stress hormone, is closely associated with obesity. Thyroid hormones are involved in the regulation of energy as well as glucose metabolism with all of its associates. Fetuin A has been known for years; however, the involvement of this parameter in obesity discussions is rather new. Recently, it has been defined as one of the new generation markers of obesity. In this study, the aim was to introduce complex interactions among all to be able to make clear comparisons, at least for a part of this complicated matter. Morbid obese (MO) children participated in the study. Two groups with 46 MO children and 43 with MetS were constituted. All children included in the study were above 99th age- and sex-adjusted body mass index (BMI) percentiles according to World Health Organization criteria. Forty-three morbid obese children in the second group also had MetS components. Informed consent forms were filled by the parents of the participants. The institutional ethics committee has given approval for the study protocol. Data as well as the findings of the study were evaluated from a statistical point of view. Two groups were matched for their age and gender compositions. Significantly higher body mass index (BMI), waist circumference, thyrotropin, and insulin values were observed in the MetS group. Triiodothyronine concentrations did not differ between the groups. Elevated levels for thyroxin, cortisol, and fetuin-A were detected in the MetS group compared to the first group (p > 0.05). In MO MetS- group, cortisol was correlated with thyroxin and fetuin-A (p < 0.05). In the MO MetS+ group, none of these correlations were present. Instead, a correlation between cortisol and thyrotropin was found (p < 0.05). In conclusion, findings have shown that cortisol was the key player in severely obese children. The association of this hormone with the participants of thyroid hormone metabolism was quite important. The lack of association with fetuin A in the morbid obese MetS+ group has suggested the possible interference of MetS components in the behavior of this new generation obesity marker. The most remarkable finding of the study was the unique correlation between cortisol and thyrotropin in the morbid obese MetS+ group, suggesting that thyrotropin may serve as a target along with cortisol in the morbid obese MetS+ group. This association may deserve specific attention during the development of remedies against MetS in the pediatric population.