bluuebunny/crossref_metadata_2025 huggingface dataset:
Serosurvey for hepatitis A in neotropical primates in southeast Brazil
Authors: Setzer Ariela Priscila , Coimbra Gaspar Ana Maria , Sidoni Marli , Galvão Bueno Marina , Catão‐Dias José Luiz
Published: February 2014

Background

Hepatitis A virus (HAV) is the cause of a zoonotic disease, which has only humans and non‐humans primates as its natural hosts.

Methods

The seroprevalence of antibodies anti‐HAV in wild and captive neotropical primates were investigated.

Results

4.9% (18/369) were positive for antibodies anti‐HAV, in captivity.

Conclusion

Implications for health managements are discussed.
Geography does not limit optimal diabetes care: Use of a tertiary centre model of care in an outreach service for type 1 diabetes mellitus
Authors: Simm Peter J , Wong Nicole , Fraser Lynne , Kearney John , Fenton Judy , Jachno Kim , Cameron Fergus J
Published: February 2014

Aim

Young people with type 1 diabetes mellitus living in rural and regional Australia have previously been shown to have limited access to specialised diabetes services. The Royal Children's Hospital Melbourne has been running diabetes outreach clinics to Western Victoria, Australia, for over 13 years. We aim to evaluate this service by comparing the outcomes of three outreach clinics with our urban diabetes clinic at the Royal Children's Hospital Melbourne.

Methods

We examine our tertiary, multidisciplinary team‐based model of care, where visiting specialist medical staff work alongside local allied health teams. The local teams provide interim care between clinics utilising the same protocols and treatment practices as the tertiary centre. Longitudinal data encapsulating the years 2005–2010, as a cohort study with a control group, are reviewed.

Results

A total of 69 rural patients were compared with 1387 metropolitan patients. Metabolic control was comparable, with no difference in mean HbA1c (8.3%/67 mmol/mol for both groups). Treatment options varied slightly at diagnosis, while insulin pump usage was comparable between treatment settings (20.3% rural compared with 27.6% urban, P = 0.19). Of note was that the number of visits per year was higher in the rural group (3.3 per year rural compared with 2.7 urban, P < 0.001).

Conclusions

We conclude that the outreach service is able to provide a comparable level of care when the urban model is translated to a rural setting. This model may be further able to be extrapolated to other geographic areas and also other chronic health conditions of childhood.
Safewards: a new model of conflict and containment on psychiatric wards
Authors: Bowers L.
Published: February 2014

Accessible summary

Rates of violence, self‐harm, absconding and other incidents threatening patients and staff safety vary a great deal by hospital ward. Some wards have high rates, other low. The same goes for the actions of staff to prevent and contain such incidents, such as manual restraint, coerced medication, etc.

The Safewards Model provides a simple and yet powerful explanation as to why these differences in rates occur.

Six features of the inpatient psychiatric system have the capacity to give rise to flashpoints from which adverse incidents may follow.

The Safewards Model makes it easy to generate ideas for changes that will make psychiatric wards safer for patients and staff.

Conflict (aggression, self‐harm, suicide, absconding, substance/alcohol use and medication refusal) and containment (as required medication, coerced intramuscular medication, seclusion, manual restraint, special observation, etc.) place patients and staff at risk of serious harm. The frequency of these events varies between wards, but there are few explanations as to why this is so, and a coherent model is lacking. This paper proposes a comprehensive explanatory model of these differences, and sketches the implications on methods for reducing risk and coercion in inpatient wards. This Safewards Model depicts six domains of originating factors: the staff team, the physical environment, outside hospital, the patient community, patient characteristics and the regulatory framework. These domains give risk to flashpoints, which have the capacity to trigger conflict and/or containment. Staff interventions can modify these processes by reducing the conflict‐originating factors, preventing flashpoints from arising, cutting the link between flashpoint and conflict, choosing not to use containment, and ensuring that containment use does not lead to further conflict. We describe this model systematically and in detail, and show how this can be used to devise strategies for promoting the safety of patients and staff.
Retrospective analysis of total direct medical costs associated with hepatitis B patients with oral antiviral versus pegylated interferon therapy in Turkey
Authors: Altinbas A. , Baser E. , Burkan A. , Ertugay E. , Kariburyo M. F. , Baser O.
Published: February 2014

To explore healthcare costs associated with antiviral treatment of hepatitis B virus (HBV) in Turkey. Research‐identified data from a claims processing system for all Turkish health insurance funds were analysed. Adult patients prescribed oral antiviral and pegylated interferon treatment were identified between 1 January 2010 and 31 December 2010. The first prescription date was defined as the index date. Patients were required to have HBV diagnosis within the 6‐month pre‐index period. Pharmacy, outpatient and inpatient claims were compiled over the study period for the selected patients, and risk‐adjusted 1‐year healthcare costs of patients with oral antiviral and pegylated interferon treatment were compared. Risk adjustment was carried out using propensity score matching, controlling for baseline demographic and clinical characteristics. A total of 9618 patients were identified, of which 9074 were treated with oral antiviral medication and 544 with pegylated interferon medication. The oral antiviral treatment group was older (45.28 vs 42.19, P < 0.001), less likely to be female (32.17% vs 39.71%, P < 0.001) and to reside in Southeastern Anatolia (8.29% vs 13.97%, P < 0.001) or Mediterranean region (8.90% vs 11.76%, P < 0.03) and had higher Elixhauser comorbidity index scores (60.22% vs 74.08%, P < 0.001) than the pegylated interferon group. After adjusting for confounding factors, total medical costs for pegylated interferon patients were €2771 higher than for oral antiviral patients (P < 0.001), due to higher outpatient and prescription costs. For annual healthcare costs for antiviral treatment options for HBV patients in Turkey, after adjusting for age, gender, region and comorbid condition differences, oral antiviral treatment is more costly than pegylated interferon treatment.
Characterizing and predicting essential habitat features for juvenile coastal sharks
Authors: Ward‐Paige Christine A. , Britten Gregory L. , Bethea Dana M. , Carlson John K.
Published: February 2014

The successful management of shark populations requires juvenile recruitment success. Thus, conservation initiatives now strive to include the protection of areas used by pre‐adult sharks in order to promote juvenile survivorship. Many shark species use inshore areas for early life stages; however, species often segregate within sites to reduce competition. Using a fisheries‐independent gillnet survey from the Northern Gulf of Mexico (2000–2010) we describe distribution patterns and preferred habitat features of the juveniles of six shark species. Our results suggest that multiple shark species concurrently use the area for early life stages and although they overlap, they exhibit distinct habitat preferences characterized by physical variables. Habitat suitability models suggest that temperature, depth, and salinity are the important factors driving juvenile shark occurrence. Within each site, across the sampled range of physical characteristics, blacktip shark (Carcharhinus limbatus) preferred higher temperature (>30 °C) and mid‐depth (~5.5 m); bonnethead shark (Sphyrna tiburo) preferred higher temperature (>30 °C) and mid‐salinity (30–35 PSU), finetooth shark (Carcharhinus isodon) preferred low salinity (<20 PSU) with mid‐depth (~4 m), scalloped hammerhead shark (Sphyrna lewini) preferred high temperature (>30 °C) and salinity (>35 PSU), Atlantic sharpnose shark (Rhizoprionodon terraenovae) preferred high temperature (>30 °C) and deep water (>6 m), and spinner shark (Carcharhinus brevipinna) preferred deep water (>8 m) and high temperature (>30 °C). The other investigated factors, including year, month, latitude, longitude, bottom type, inlet distance, coastline and human coast were not influential for any species. Combining habitat preferences with the sampled environmental characteristics, we predicted habitat suitability throughout the four sites for which physical characteristics were sampled. Habitat suitability surfaces highlight the differences in habitat use between and within sites. This work provides important insight into the habitat ecology of juvenile shark populations, which can be used to better manage these species and protect critical habitat.
Curcuma pygmaea sp. nov. (Zingiberaceae) from Vietnam and notes on two related species C. parviflora and C. thorelii.
Authors: Leong‐Škorničková Jana , Šída Otakar , Đăng Trần Hữ’u
Published: February 2014

Curcuma pygmaeaŠkorničk. & Šída f. (Zingiberaceae), a new species from Vietnam, is described and illustrated. Notes on its closest allies in Curcuma subgenus Hitcheniopsis, C. parviflora Wall. and C. thorelii Gagnep., are provided and a lectotype of C. thorelii is designated.
Where is the comfort in comfort foods? Mechanisms linking fat signaling, reward, and emotion
Authors: Weltens N. , Zhao D. , Van Oudenhove L.
Published: February 2014

Background

Food in general, and fatty foods in particular, have obtained intrinsic reward value throughout evolution. This reward value results from an interaction between exteroceptive signals from different sensory modalities, interoceptive hunger/satiety signals from the gastrointestinal tract to the brain, as well as ongoing affective and cognitive processes. Further evidence linking food to emotions stems from folk psychology (‘comfort foods’) and epidemiological studies demonstrating high comorbidity rates between disorders of food intake, including obesity, and mood disorders such as depression.

Purpose

This review paper aims to give an overview of current knowledge on the neurophysiological mechanisms underlying the link between (fatty) foods, their reward value, and emotional responses to (anticipation of) their intake in humans. Firstly, the influence of exteroceptive sensory signals, including visual, olfactory (‘anticipatory food reward’), and gustatory (‘consummatory food reward’), on the encoding of reward value in the (ventral) striatum and of subjective pleasantness in the cingulate and orbitofrontal cortex will be discussed. Differences in these pathways and mechanisms between lean and obese subjects will be highlighted. Secondly, recent studies elucidating the mechanisms of purely interoceptive fatty acid‐induced signaling from the gastrointestinal tract to the brain, including the role of gut peptides, will be presented. These studies have demonstrated that such subliminal interoceptive stimuli may impact on hedonic circuits in the brain, and thereby influence the subjective and neural responses to negative emotion induction. This suggests that the effect of foods on mood may even occur independently from their exteroceptive sensory properties.
Psychological and mental health problems in patients with thalidomide embryopathy in Japan
Authors: Imai Koubun , Iida Toshiharu , Yamamoto Maki , Komatsu Kensuke , Nukui Yuko , Yoshizawa Atsuto
Published: February 2014

Aim

The aim of the study was to examine the presence of psychological and mental health problems in patients with thalidomide embryopathy in Japan in order to develop and build future support systems.

Methods

The present study examined the presence/absence of electroencephalographic abnormalities, intellectual/cognitive functions, and mental health problems in 22 participants (nine men, 13 women) with thalidomide embryopathy. Participants completed the electroencephalograph instrument. Participants were also assessed using the Wechsler Adult Intelligence Scale‐III; the Autism‐Spectrum Quotient; the General Health Questionnaire‐28, and the Mini‐International Neuropsychiatric Interview.

Results

The results suggest the following: (i) electroencephalographic abnormality observed in several thalidomide embryopathy participants is unlikely to be the direct result of thalidomide; (ii) the cognitive functions of working memory and processing speed are lower in thalidomide embryopathy patients than in healthy individuals; and (iii) 40.9% of the thalidomide embryopathy participants have possible mental disorders, with more mental problems observed than in healthy individuals.

Conclusions

Deterioration of mental health in patients with thalidomide embryopathy is indicated. Anxiety, insomnia, and physical symptoms were especially remarkable and may have resulted in restriction of social activities. Therefore, careful examination and active support of patients' psychological and mental problems is essential.
Primary orbital neuroblastoma in a 1‐month‐old boy
Authors: Inazawa Natsuko , Hatakeyama Naoki , Hori Tsukasa , Yamamoto Masaki , Igarashi Keita , Tadashi Hasegawa , Ogino Jiro , Tsutsumi Hiroyuki , Suzuki Nobuhiro
Published: February 2014

Neuroblastoma is a malignant tumor predominantly occurring in children and usually arising from the adrenal gland or sympathetic ganglia. We describe a neuroblastoma in a 1‐month‐old boy arising from his left orbital cavity. This tumor was refractory to chemotherapy or radiotherapy, requiring enucleation of the left eye for complete removal of the intraorbital tumor. Thereafter, he received high‐dose chemotherapy followed by autologous peripheral blood stem cell transplantation, and has been in complete remission for 3 years. Unlike neuroblastomas arising from the adrenal gland or sympathetic ganglia, primary orbital neuroblastoma may be refractory even in early infancy.
Latina Youths' Perceptions of Children's Environmental Health Risks in an Agricultural Community
Authors: Postma Julie , Peterson Jeff , Ybarra Vega Mary Jo , Ramon Cristian , Cortes Guadalupe
Published: February 2014

Objectives

The objective of this study was to identify Latina youths' perceptions of local assets and concerns related to children's environmental health (EH) in an agricultural community.

Design and Sample

Four photovoice sessions were used to elicit 6 promotores' and 5 middle school students' perspectives on problems and strengths related to “children; environment; and health.”

Measures

Data collection was diverse and included a demographic and evaluation questionnaire, photographs, audio recordings of group photo‐sharing sessions, and field notes.

Results

Participants identified three themes that reflected group discussion during two photo‐sharing sessions: a lack of structured youth activities; poverty and stress; and benefits and detriments of agricultural work. Community assets related to creating a healthy environment for youth were identified and included the clinic, churches, and youth programs.

Conclusions

Findings from this study reinforce that social background and position affect how EH issues are defined and may be addressed. Participant perspectives are valuable to nurses because they offer a lens through which to see the complexities of EH from the viewpoint of those most directly affected. Leadership training and opportunities to serve on coalitions and neighborhood councils are recommended approaches to meaningfully involving youth in environmental justice initiatives.
In Search of the Legal Basis for Environmental and Energy Regulation at the EU Level: The Case of Unconventional Gas Extraction
Authors: Reins Leonie
Published: February 2014

The relation of the energy and environmental competences in the European Union (EU) in terms of renewable energy and its promotion and impact on climate change has been subject to intense academic discussion as well as to judicial review. The general tendency is for measures regarding renewable energy to be passed on both competences, depending on the specific content and objective. Other forms of energy, however, have not been included in this debate. The outcome outside the area of renewable energy is expected to be quite different. Shale gas extraction, for example, is associated with negative, or at least problematic, environmental impacts, alongside the benefits it offers to the security of the EU's energy supply. Consequently, the question of competence is not straightforward. This article analyzes the interplay and conflicts between the energy and environmental titles of the Treaty on the Functioning of the European Union in the context of shale gas activities. The article further explores the importance of ‘significance’ in this setting, and how this concept is crucial in determining the appropriate decision‐making procedure to pass a legal measure on shale gas in practice.
Reviving Rylands: How the Doctrine Could Be Used to Claim Compensation for Environmental Damages Caused by Fracking
Authors: Costello Róisín Áine
Published: February 2014

Contemporary societies are characterized by complex interdependence, with industrial activity increasingly having the potential to cause effects beyond local and national borders. Courts have previously illustrated that liability for injurious action must lie with the individual who created the risk of damage under the common law rule of Rylands v. Fletcher. Having fallen out of favour in the twentieth century, this article proposes a re‐articulation of the rule to cover situations in modern society in which invasive methods are used in the extraction of volatile fuels from the earth, specifically in the case of ‘fracking’. The article examines recent rulings from the United States and the United Kingdom, as well as precedent from the United Kingdom and Ireland to establish the manner in which the rule of Rylands v. Fletcher might be successfully re‐articulated in the context of contemporary common law jurisdictions – specifically focusing on Ireland – as a means for redressing environmental damage.
CEREBRAL GLUCOSE UTILIZATION MEASURED WITH HIGH RESOLUTION POSITRON EMISSION TOMOGRAPHY IN EPILEPTIC FINNISH SPITZ DOGS AND HEALTHY DOGS
Authors: Viitmaa Ranno , Haaparanta‐Solin Merja , Snellman Marjatta , Cizinauskas Sigitas , Orro Toomas , Kuusela Erja , Johansson Jarkko , Viljanen Tapio , Jokinen Tarja S. , Bergamasco Luciana , Metsähonkala Liisa
Published: February 2014

In human epileptic patients, changes in cerebral glucose utilization can be detected 2‐deoxy‐2‐[18F] fluoro‐d‐glucose positron emission tomography (FDG‐PET). The purpose of this prospective study was to determine whether epileptic dogs might show similar findings. Eleven Finnish Spitz dogs with focal idiopathic epilepsy and six healthy dogs were included. Dogs were examined using electroencephalography (EEG) and FDG‐PET, with epileptic dogs being evaluated during the interictal period. Visual and semi‐quantitative assessment methods of FDG‐PET were compared and contrasted with EEG findings. Three independent observers, unaware of dog clinical status, detected FDG‐PET uptake abnormalities in 9/11 epileptic (82%), and 4/8 healthy dogs (50%). Occipital cortex findings were significantly associated with epileptic status (P = 0.013). Epileptic dogs had significantly lower standardized uptake values (SUVs) in numerous cortical regions, the cerebellum, and the hippocampus compared to the control dogs. The lowest SUVs were found in the occipital lobe. White matter normalized and left‐right asymmetry index values for all pairs of homologous regions did not differ between groups. Visual evaluation of the EEGs was less sensitive (36%) than FDG‐PET. Both diagnostic tests were consensual and specific (100%) for occipital findings, but EEG had a lower sensitivity for detecting lateralized foci than FDG‐PET. Findings supported the use of FDG‐PET as a diagnostic test for dogs with suspected idiopathic epilepsy. Visual and semiquantitative analyses of FDG‐PET scans provided complementary information. Findings also supported the theory that epileptogenesis may occur in multiple brain regions in Finnish Spitz dogs with idiopathic epilepsy.
INVITED REVIEW—COMPUTED TOMOGRAPHIC ANGIOGRAPHY (CTA) OF THE THORACIC CARDIOVASCULAR SYSTEM IN COMPANION ANIMALS
Authors: Drees Randi , François Christopher J. , Saunders Jimmy H.
Published: February 2014

Computed tomographic angiography (CTA) of the thoracic cardiovascular system is offering new diagnostic opportunities in companion animal patients with the increasing availability of multidetector‐row computed tomographic (MDCT) units in veterinary facilities. Optimal investigation of the systemic, pulmonary, and coronary circulation provides unique challenges due to the constant movement of the heart, the small size of several of the structures of interest, and the dependence of angiographic quality on various contrast bolus design and patient factors. Technical and practical aspects of thoracic cardiovascular CTA are reviewed in light of the currently available veterinary literature and future opportunities given utilizing MDCT in companion animal patients with suspected thoracic cardiovascular disease.
Longwall Shearer Cutting Force Estimation
Authors: Reid A. W. , McAree P. R. , Meehan P. A. , Gurgenci H.
Published: February 2014

Longwall mining is an underground coal mining method that is widely used. A shearer traverses the coal panel to cut coal that falls to a conveyor. Operation of the longwall can benefit from knowledge of the cutting forces at the coal/shearer interface, particularly in detecting pick failures and to determine when the shearer may be cutting outside of the coal seam. It is not possible to reliably measure the cutting forces directly. This paper develops a method to estimate the cutting forces from indirect measurements that are practical to make. The structure of the estimator is an extended Kalman filter with augmented states whose associated dynamics encode the character of the cutting forces. The methodology is demonstrated using a simulation of a longwall shearer and the results suggest this is a viable approach for estimating the cutting forces. The contributions of the paper are a formulation of the problem that includes: the development of a dynamic model of the longwall shearer that is suitable for forcing input estimation, the identification of practicable measurements that could be made for implementation and, by numerical simulation, verification of the efficacy of the approach. Inter alia, the paper illustrates the importance of considering the internal model principle of control theory when designing an augmented-state Kalman filter for input estimation.
A Robust Observer-Based Fault Tolerant Control Scheme for Underwater Vehicles
Authors: Letizia Corradini Maria , Orlando Giuseppe
Published: February 2014

This paper proposes an actuator failure tolerant robust control scheme for underwater vehicles. A state observer is introduced first, aimed at estimating velocities. In order to solve the tracking problem for vehicle positions, a sliding mode control (SMC) law is developed using the available position measurements and the velocity estimates provided by the observer. Detection of thruster faults based on the check of any deviation of the observed sliding surfaces, and an isolation policy for the failed thruster are proposed. Finally, control reconfiguration is performed exploiting the inherent redundancy of actuators. An extensive simulation study has been performed, supporting the effectiveness of the proposed approach.
A Diffuse Interface Model to Simulate Electrochemical Response of Medical Implant Materials
Authors: Kar Debashis , Saylor David M.
Published: February 2014

The purpose of the present work is to model corrosion of implant materials (such as nitinol or stainless steel) in simulated environments both under static and dynamic conditions. The present model seeks to imitate the potentiodynamic testing protocol defined as in ASTM F2129, which is used to evaluate the corrosion susceptibility of small implant devices. The model is currently limited to one dimension and hence the effect of physical features, such as defects and crevices, on corrosion is not the focus of this study.
Development of Experimental Set-Up to Simulate High Velocity Low Amplitude Spinal Manipulations to Validate Finite Element Models
Authors: Gudavalli Maruti Ram , Xia Ting , Goel Vijay , Qin Yi-Xian , Sozio Randall , Pickar Joel G.
Published: February 2014

The authors have developed experimental set-up to simulate chiropractic high velocity low amplitude spinal manipulations (HVLA SM) used for treating low back pain. The experimental set-up was used to test fresh unembalmed lumbar spinal specimens Our experimental-set-up simulated HVLA SM manipulations such as doctors hand contact, anatomical locations of load application, durations of load, magnitudes of load. The results from the experimental set-up are used to validate finite element models that simulated HVLA SM.
Patient-Specific Computations of Cerebral Aneurysm: Impact of the Uncertainty of the Input Parameters
Authors: Sanchez Mathieu , Costalat Vincent
Published: February 2014

The setting up of patient-specific computations is one of the major challenges to help the clinician in his decision-making.

But the input parameters of computations are not well known due to the medical imaging limitations.

The goal of this study is to highlight on a cerebral aneurysm case that the uncertainties of the input parameters have an influence on the details of the results but not on the main conclusion: the soft (close to the rupture) aneurysm deforms more than the stiff (undegraded) one.
Stochastic Simulation of Modular Connections in Total Hip Replacement
Authors: Donaldson Finn E. , Coburn James C.
Published: February 2014

Several modern Total Hip Arthroplasty (THA) implants have been associated with increased release of metallic debris through combined mechanical fretting wear and chemical corrosion. These particles can lead to painful Adverse Reaction to Metallic Debris, often requiring early revision [1]. While much research has focused on improving the performance of bearing surfaces, the key parameters driving release of metallic debris at modular junctions remains unclear.
Cadaveric Evaluation of Knee Joint Kinematics Using the Kansas Knee Simulator
Authors: Shalhoub Sami , Fitzwater Fallon , Maletsky Lorin
Published: February 2014

Computational models of the knee are useful for evaluating changes in kinematics, soft tissue loadings, new prosthetic geometries, and surgical techniques [1, 2]. These models are advantageous in their ability to quickly and efficiently evaluate the effect of changes in these parameters on knee joint function. The limitation of modeling is that the results are greatly influenced by the constraints and parameters used to create the model.
Training Predictive Skills for Mitral Valve Repair
Authors: Tenenholtz Neil A. , Howe Robert D.
Published: February 2014

Mitral valve repair is a highly challenging procedure. Surgeons must modify native valve tissue through a series of tissue resections and approximations. Restoring proper valve function is difficult because the heart is arrested during the procedure, so closed valve shape must be predicted rather than directly observed. It is this prediction, not the act of cutting and suturing, that presents the greater challenge to surgeons as they must rely on analysis of the flaccid valve and past experience. This skill is developed through traditional pedagogy, namely text- and image-based references, followed by a costly and time-consuming apprenticeship model.
Efficient Construction of Statistical Shape Models for Patient-Specific Modeling
Authors: Li Kang , Qian Xiaoping , Espinoza Orías Alejandro A.
Published: February 2014

Statistical Shape Modeling (SSM) is a powerful tool to capture the shape variation pattern across a group of shapes belonging to a certain shape class. SSM has seen many promising applications for the purpose of building Patient-Specific Model (PSM) because it avoids unwanted exposure to ionizing radiation from imaging modalities such as CT scanning and has potential as a cost-saving and time-efficient research and clinical tool. All that is needed to reconstruct the patient — specific data is to instantiate the statistical model already generated.

The utility of the statistical model relies on a sufficiently large training set data pool from as many patients as possible; and more importantly, a reasonably good correspondence across the entire training set. As such, the description length has been used as a standard to measure the quality of correspondence and the statistical model, and the desired correspondence found by optimization.

However, the previously proposed optimization schemes are too inefficient to be used for large data sets. We present a new optimization scheme based on B-spline freeform deformation and analytical adjoint sensitivity. This scheme is significantly more efficient in that it makes use of: 1) extraordinary efficiency of direct correspondence manipulation; 2) availability of analytical gradient due to the differentiable shapes and correspondence manipulation; 3) superiority of adjoint method when a large number of design variables are used in optimization.

In the experimental part, we compare the efficiency of our method and current method for some benchmark examples where solutions are known. Additionally, we show the statistical models for a 3D distal femur bone training set. Such models have been previously used in osteosarcoma cases as a bone bank for bone allografts, where shape-matching is very important [1]. The graphical illustration of the training set and preliminary results of the obtained statistical modes are displayed in Figure 1, 2, 3, 4 and 5.
Combining Imaging Modalities in the Modelling of Multi Parameter Devices
Authors: Nygaard Jens Vinge
Published: February 2014

Modeling and simulation of medical devices are typically established in order to identify parameter dependencies within the system of interest. Most devices are multiphysics problems in the sense that coupling can occur between for instance flow, structure, and temperature. In many systems individual and dependent mechanisms are present bridging length scales from nanometer to millimeter. Typically, the geometries of interest are described by the complex morphology of the components in biological tissues. These factors all contribute to significant complexity of the numerical models being developed. Access to imaging modalities capable of providing the geometrical information of relevance to the problems is central in the establishment and verification of numerical analysis. This abstract present how we used image based models obtained from MRI and CT datasets to risk access patients prone to realizing stroke, and how a scaffold technology for tissue engineering is analyzed both in vitro and in vivo to access its drug delivery capability and biocompatibility.
Validation of an Open Source Framework for the Simulation of Blood Flow
Authors: Passerini Tiziano , Quaini Annalisa , Villa Umberto , Veneziani Alessandro , Canic Suncica
Published: February 2014

We describe in this paper an open source framework for the solution of problems arising in hemodynamics. The proposed framework is validated through comparison against experimental data for fluid flow in an idealized medical device with rigid boundaries; and verified with a numerical benchmark for flow in compliant vessels. The core of the framework is an open source parallel finite element library that features algorithms to solve both fluid and fluid-structure interaction problems. The computed results are in good quantitative agreement with experimental measurements and theoretical estimates.
Optimization of Balloon Obstruction for Simulating Equivalent Pressure Drop in In-Vivo Conditions
Authors: Kolli Kranthi K. , Paul Anup K. , Back Lloyd H. , Banerjee Rupak K.
Published: February 2014

The study of hemodynamics in an animal model associated with coronary stenosis has been limited due to the lack of a safe, accurate, and reliable technique for creating an artificial stenosis. Creating artificial stenosis using occluders in an open-chest procedure has often caused myocardial infarction (MI) or severe injury to the vessel resulting in high failure rates. To minimize these issues, closed-chest procedures with internal balloon obstruction were often used to create artificial stenosis. However, it should be noted that the hemodynamics in a blood vessel with internal balloon obstruction as opposed to physiological stenosis hasn’t been compared. Hence, the aim of this research is to computationally evaluate the pressure drop in balloon obstruction and compare with that in physiological stenosis. It was observed that the flow characteristics in balloon obstruction are more viscous dominated, whereas it is momentum dominated in physiological stenosis. Balloon radius was iteratively varied to get a pressure drop equivalent to that of physiological stenosis at mean hyperemic flow rates. A linear relation was obtained to predict equivalent balloon obstruction for physiological stenosis.
The Effect of Static and Dynamic Loading on Degradation of PLLA Stent Fibers
Authors: Hayman Danika , Bergerson Christie , Miller Samantha , Moreno Michael , Moore James E.
Published: February 2014

PLLA is a commonly used biodegradable polymer in stent designs because it is non-toxic and easily eliminated from the body. However, very little is known about the effect of loading conditions on the degradation rate. Rajagopal and Wineman developed a model of polymer degradation which is driven by load applied to the fiber [1]. Soares et. al. further developed this model for use with PLLA stent fibers under tensile loading conditions [2]. In this model the degradation rate is linearly related to deformation through the radius in the (IB, IIB) plane. Both models predict that greater deformation will induce a higher degree of degradation.
Stent Geometry Reconstruction Using Imaging Techniques
Authors: Cosentino Daria , Zwierzak Iwona , Diaz-Zuccarini Vanessa , Fenner John W. , Schievano Silvia , Narracott Andrew J.
Published: February 2014

Stents are most commonly used in the relief of coronary artery stenosis, but in the last decade have found increasing applications in the treatment of other cardiovascular disease and in particular in heart valve replacement [1]. In transcatheter valve implantation, acquisition of high temporal and spatial resolution images during stenting procedure and patients’ follow-up is required to help the correct positioning of the device and to assess the mechanical performance over time. The imaging techniques routinely used for this purpose are 2D X-ray fluoroscopy and 3D computed tomography (CT), and recent studies have demonstrated their value as diagnostic tools [1–3]. However, these image modalities carry errors and the resulting information might not be accurate enough to be employed in engineering analyses of stent deformations, mechanics, dynamics and fracture. In this study, we aim to evaluate the errors of conventionally used clinical images (fluoroscopy and CT) and post-processing by comparison with ultra-high resolution micro-CT (μCT) as gold standard. Additionally, an optical image acquisition method and a high-radiation CT scan were evaluated as potential techniques to acquire geometrical data that could be used for computational and in-vitro engineering experiments.
Copula Based Probabilistic Modeling of Use Conditions for Self Expanding Transcatheter Valve Structural Components
Authors: Secord Thomas W. , Harewood Frank , McVeigh Cahal , Nadian Behrooz , Donnelly Evin
Published: February 2014

Transcatheter heart valve replacement is rapidly becoming a viable option for patients who present as high risk surgical candidates. The emergence of these devices has prompted a need to understand their long term structural integrity as a function of boundary conditions, material behavior, and device geometry assumptions. In the case of transcatheter replacement heart valves, there is a shortage of clinical data from which to derive accurate use conditions. Therefore, structural analysis of these devices is enhanced by using a stochastic, rather than deterministic, framework.
Design Optimization of a Novel Polymeric Prosthetic Heart Valve and a Ventricular Assist Device via Device Thrombogenicity Emulation
Authors: Claiborne Thomas E. , Chiu Wei-Che , Slepian Marvin J. , Bluestein Danny
Published: February 2014

Thrombotic complications, such as hemorrhage or embolism, remain a major concern of blood contacting medical devices [1], including prosthetic heart valves (PHV) and mechanical circulatory support devices, e.g. ventricular assist devices (VAD) or the Total Artificial Heart (TAH) [2]. In most cases device recipients require life-long anticoagulation therapy, which increases the risk of hemorrhagic stroke and other bleeding disorders. In order to obviate the need for anticoagulants and reduce stroke risks, our group developed a unique optimization methodology, Device Thrombogenicity Emulation (DTE) [2–5]. With the DTE, the thrombogenic potential of a device is evaluated using extensive numerical modeling and calculating multiple platelet trajectories flowing through the device. The platelet stress-time waveforms are then emulated in our Hemodynamic Shearing Device (HSD) and their activation level is measured with our Platelet Activation State (PAS) assay. This provides a proxy validation of the simulation. We identify high shear stress producing regions within the device and modify its design to reduce or eliminate those potentially thrombogenic ‘hot-spots.’ Through an iterative process, we can optimize the device design prior to prototyping.
Multiscale Modeling of Flow Induced Thrombogenicity With Dissipative Particle Dynamics (DPD) and Molecular Dynamics (MD)
Authors: Bluestein Danny , Soares João S. , Zhang Peng , Gao Chao , Pothapragada Seetha , Zhang Na , Slepian Marvin J. , Deng Yuefan
Published: February 2014

The coagulation cascade of blood may be initiated by flow induced platelet activation, which prompts clot formation in prosthetic cardiovascular devices and arterial disease processes. While platelet activation may be induced by biochemical agonists, shear stresses arising from pathological flow patterns enhance the propensity of platelets to activate and initiate the intrinsic pathway of coagulation, leading to thrombosis. Upon activation platelets undergo complex biochemical and morphological changes: organelles are centralized, membrane glycoproteins undergo conformational changes, and adhesive pseudopods are extended. Activated platelets polymerize fibrinogen into a fibrin network that enmeshes red blood cells. Activated platelets also cross-talk and aggregate to form thrombi. Current numerical simulations to model this complex process mostly treat blood as a continuum and solve the Navier-Stokes equations governing blood flow, coupled with diffusion-convection-reaction equations. It requires various complex constitutive relations or simplifying assumptions, and is limited to μm level scales. However, molecular mechanisms governing platelet shape change upon activation and their effect on rheological properties can be in the nm level scales. To address this challenge, a multiscale approach which departs from continuum approaches, may offer an effective means to bridge the gap between macroscopic flow and cellular scales. Molecular dynamics (MD) and dissipative particle dynamics (DPD) methods have been employed in recent years to simulate complex processes at the molecular scales, and various viscous fluids at low-to-high Reynolds numbers at mesoscopic scales. Such particle methods possess important properties at the mesoscopic scale: complex fluids with heterogeneous particles can be modeled, allowing the simulation of processes which are otherwise very difficult to solve by continuum approaches. It is becoming a powerful tool for simulating complex blood flow, red blood cells interactions, and platelet-mediated thrombosis involving platelet activation, aggregation, and adhesion.
Calibrating and Analyzing a Mathematical Model of Human Circulation and its Response to Hemorrhage
Authors: Pruett William A. , Hester Robert L.
Published: February 2014

Complex physiological events such as hemorrhage are met with a continuum of responses in individual test subjects that range from complete compensation to circulatory failure. Predicting the circulatory outcome of an individual potentially affects treatment modalities, for example, by indicating that aggressive intervention is justified based on the likelihood of a negative result with a more passive therapy. We have previously determined an algorithm for calibrating and sampling parameter distributions that generate experimentally verified output distributions via an application of the Metropolis algorithm. This technique is advanced here by the addition of a three-pronged post hoc analysis. First is an inductive algorithm generating minimal parameter sets yielding efficient classification (MER). This algorithm is validated with PCA on the resulting parameter subsets. Finally, we provide an analysis on the response characteristics of clusters determined by a density dependent algorithm on the parameter/variable subspace indicated by the MER.
The Vascular Model Repository: A Public Resource of Medical Imaging Data and Blood Flow Simulation Results
Authors: Wilson Nathan M. , Ortiz Ana K. , Johnson Allison B.
Published: February 2014

Patient-specific blood flow simulations may provide insight into disease progression, treatment options, and medical device design that would be difficult or impossible to obtain experimentally. However, publicly available image data and computer models for researchers and device designers are extremely limited. The NHLBI sponsored Open Source Medical Software Corporation (Contracts No: HHSN268200800008C & HHSN268201100035C) and its university collaborators to build a public repository including realistic, image-based anatomic models and related hemodynamic simulation results to address this unmet need.
Guiding the Setup of Clinically Meaningful Test Methods Using Computational Modeling
Authors: Abunassar Chad , Prabhu Santosh
Published: February 2014

Contemporary drug eluting stents (DES) are designed and tested such that they will endure under in vivo fatigue loading after implantation. However, DES fractures have occasionally been reported in the literature and are often associated with restenosis and/or thrombosis events long after DES deployment. This observation indicates a need for fatigue test methods which appropriately compare the fatigue resistance of various DES platforms at loading levels beyond clinical relevance.
Elucidation of Cellular Mechanisms Involved in Experimental Paromomycin Resistance in Leishmania donovani
Authors: Bhandari Vasundhra , Sundar Shyam , Dujardin Jean Claude , Salotra Poonam
Published: February 2014

Leishmania donovani
is the causative agent of the potentially fatal disease visceral leishmaniasis (VL). Chemotherapeutic options available to treat VL are limited and often face parasite resistance, inconsistent efficacy, and toxic side effects. Paromomycin (PMM) was recently introduced to treat VL as a monotherapy and in combination therapy. It is vital to understand the mechanisms of PMM resistance to safeguard the drug. In the present study, we utilized experimentally generated PMM-resistant
L. donovani
to elucidate the mechanisms of resistance and parasite biology. We found increased membrane fluidity accompanied by decreased intracellular drug accumulation in the PMM-resistant parasites. There were marked increases in gene expression of ATP-binding cassette (ABC) transporters (MDR1 and MRPA) and protein phosphatase 2A that evince increased drug efflux. Further, evaluation of parasite tolerance toward host leishmanicidal mechanisms revealed PMM-resistant parasites as being more tolerant to nitrosative stress at the promastigote and amastigote stages. The PMM-resistant parasites also predicted a better survival capacity, as indicated by resistance to complement-mediated lysis and increased stimulation of host interleukin-10 (IL-10) expression. The susceptibilities of PMM-resistant isolates to other antileishmanial agents (sodium antimony gluconate and miltefosine) remained unchanged. The data implicated the roles of altered membrane fluidity, decreased drug accumulation, increased expression of ABC transporters, and greater tolerance of parasites to host defense mechanisms in conferring PMM resistance in
Leishmania
.
A Systematic Review and Meta-Analyses Show that Carbapenem Use and Medical Devices Are the Leading Risk Factors for Carbapenem-Resistant Pseudomonas aeruginosa
Authors: Voor in ‘t holt Anne F. , Severin Juliëtte A. , Lesaffre Emmanuel M. E. H. , Vos Margreet C.
Published: February 2014

A systematic review and meta-analyses were performed to identify the risk factors associated with carbapenem-resistant
Pseudomonas aeruginosa
and to identify sources and reservoirs for the pathogen. A systematic search of PubMed and Embase databases from 1 January 1987 until 27 January 2012 identified 1,662 articles, 53 of which were included in a systematic review and 38 in a random-effects meta-analysis study. The use of carbapenem, use of fluoroquinolones, use of vancomycin, use of other antibiotics, having medical devices, intensive care unit (ICU) admission, having underlying diseases, patient characteristics, and length of hospital stay were significant risk factors in multivariate analyses. The meta-analyses showed that carbapenem use (odds ratio [OR] = 7.09; 95% confidence interval [CI] = 5.43 to 9.25) and medical devices (OR = 5.11; 95% CI = 3.55 to 7.37) generated the highest pooled estimates. Cumulative meta-analyses showed that the pooled estimate of carbapenem use was stable and that the pooled estimate of the risk factor “having medical devices” increased with time. We conclude that our results highlight the importance of antibiotic stewardship and the thoughtful use of medical devices in helping prevent outbreaks of carbapenem-resistant
P. aeruginosa
.
Robust and Persistent Replication of the Genotype 6a Hepatitis C Virus Replicon in Cell Culture
Authors: Yu Mei , Peng Betty , Chan Katie , Gong Ruoyu , Yang Huiling , Delaney William , Cheng Guofeng
Published: February 2014

Genotype 6 (GT6) hepatitis C virus (HCV) is prevalent in Southeast Asia and southern China, where it can constitute up to 50% of HCV infections. Despite this, no direct-acting antivirals are approved to treat GT6 HCV infection, and no cell culture systems have been described. In this study, we aimed to develop a GT6 HCV subgenomic replicon to facilitate the identification and development of new HCV therapies with pan-genotype activity. A subgenomic replicon cDNA encoding a GT6a consensus sequence plus an NS5A amino acid substitution (S232I) was synthesized. Electroporation of RNA encoding the GT6a replicon into Huh-7-derived cells consistently yielded 20 to 100 stable replicon colonies. Genotypic analyses of individual replicon colonies revealed new adaptive mutations across multiple viral nonstructural proteins. The E30V and K272R mutations in NS3 and the K34R mutation in NS4A were observed most frequently and were confirmed to enhance GT6a replicon replication in the presence of the NS5A amino acid substitution S232I. These new adaptive mutations allowed establishment of robust luciferase-encoding GT6a replicons for reproducible quantification of HCV replication, and the luciferase-encoding replicons enabled efficient determinations of antiviral activity for HCV inhibitors in a 384-well assay format. While nucleoside/nucleotide NS5B inhibitors and cyclophilin A inhibitors had similar antiviral activities against both GT6a and GT1b replicons, some nonnucleoside NS5B inhibitors, NS3 protease inhibitors, and NS5A inhibitors had less antiviral activity against GT6a replicons. In conjunction with other genotype replicons, this robust GT6a replicon system will aid in the development of pan-genotypic HCV regimens.