bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Macular Thickness after Uncomplicated Cataract Surgery using Optical Coherence Tomography
Authors: Giansanti Fabrizio , Bitossi Alice , Giacomelli Giovanni , Virgili Gianni , Pieretti Giulia , Giuntoli Matteo , Abbruzzese Giacomo , Menchini Ugo
Published: March 2013

Purpose

To evaluate central macular thickness (CMT) after cataract surgery in selected groups of patients.

Methods

The study comprised 4 groups—patients with epiretinal membrane, patients with high myopia, patients with diabetes without retinopathy, and healthy subjects—who underwent phacoemulsification and intraocular lens implantation. Central macular thickness was measured with spectral domain optical coherence tomography (OCT) using the 3D macular cube scan. The OCT evaluation was performed preoperatively and 1, 6, 15, 30, 60, 90, and 360 days after surgery. Visual acuity was measured preoperatively and after 6 and 360 days after surgery.

Results

The study included 258 patients, 164 women and 94 men, with a mean age of 74 (SD 7.6) years. A statistically significant increase in CMT was observed from day 30 in patients with epiretinal membrane (p = 0.010) and diabetic patients (p = 0.026), reaching its maximum thickness at day 60 (p = 0.001 and p = 0.001), while it was observed only on day 360 in healthy subjects (p = 0.018) and those with high myopia (p = 0.003). The correlation between CMT and visual acuity was statistically significant only in the diabetic group (r = 0.61, p<0.01).

Conclusions

Following cataract surgery, CMT changes according to characteristic patterns in the different groups studied. These changes did not prevent an optimal recovery of visual function.
Modified Method of Sutureless Intrascleral Posterior Chamber Intraocular Lens Fixation without Capsular Support
Authors: Liu Siwei , Cheng Shaoli
Published: March 2013

Purpose

This study reports the clinical results of sutureless intrascleral fixation of posterior chamber intraocular lenses (PC IOLs) in eyes without capsular support.

Methods

Thirty patients without capsular support who underwent standard 3-piece foldable PC IOL implantation using the sutureless intrascleral fixation technique were studied retrospectively. Folded PC IOLs were injected through corneal incisions, with 2 haptics piercing out from 2 corresponding scleral punctures, which were 1.5 mm from the limbus and exactly 180° to each other, and then 2 haptics piercing respectively were placed in 2 corresponding limbus-parallel intrascleral tunnels. All patients were evaluated for preoperative and postoperative status and complications.

Results

During the follow-up period, the visual acuity of all 30 patients significantly improved, with that of 21 patients improving by more than 0.6. The intraocular pressures of all patients were stable. All PC IOLs were stable and centered. Optical coherence tomography revealed that the haptics were located within the tunnel. Other complications, such as IOL dislocation, endophthalmitis, and retinal detachment, were not detected.

Conclusions

Sutureless intrascleral fixation is safe and effective for the implantation of PC IOLs in eyes without capsular support from a variety of causes.
Does Beta-ray Emitting Therapy of Ciliary Body Tumors Decrease Central Corneal Endothelial Cell Density?
Authors: Suranyi Eva , Berta Andras , Modis Laszlo , Szalai Eszter , Damjanovich Judit
Published: March 2013

Purpose

To evaluate the effect of plaque radiation therapy using beta-radioactive isotope for anterior segment tumors on the density and morphology of endothelial cells.

Methods

Endothelial cell density (ECD) and morphometry in 15 eyes of 15 patients with ciliary body tumor was examined prior to and 6 months after radiation therapy. After irradiation, central ECD values were also compared with peripheral (2.0 mm from limbus) ECD values measured around the plaque. The ECD, average cell area, coefficient of variation of cell area, and pachymetry measurements were conducted with contact specular microscopy.

Results

The mean corrected ECD values prior to irradiation were 2147 ± 128 cells/mm2 and 2050 ± 108 cells/mm2 after the radiation therapy. After irradiation, the mean peripheral ECD values were 2056 ± 101 cells/mm2. A significant decrease in ECD values was observed after radiation (p = 0.007). Peripheral ECD values measured around the plaque showed no significant difference (p = 0.86) as compared to central ECD values.

Conclusions

According to our measurements, plaque therapy for tumors in the anterior segment decreases ECD significantly, but not highly, even in case of plaques containing beta-radiation isotope, and the plaques are not placed direct on the cornea surface. The decreased ECD causes no changes in corneal thickness or transparency, but it may have an influence on a subsequent cataract surgery, which generates further endothelial loss.
Unilateral Acute Idiopathic Maculopathy in a 14-year-old Hispanic Girl
Authors: Patel Shriji N. , Bhagat Neelakshi , Goldfeder Alan , Zarbin Marco
Published: March 2013

Purpose

The authors discuss a case of unilateral diminished vision in a 14-year-old Hispanic girl.

Methods

Retrospective chart review.

Results

The patient was referred to University Hospital (UH) at New Jersey Medical School with a complaint of blurry vision in the right eye for approximately 1 month. Clinical examination showed a yellow-gray area of retinal pigment epithelium (RPE) elevation in the perifoveal region OD and normal examination OS. Optical coherence tomography showed a corresponding area of RPE elevation with associated sub-RPE fluid. Fluorescein angiogram on presentation disclosed a focal area of hyperfluorescence and dye pooling. Bloodwork and chest x-ray were within normal limits. These changes resolved over the ensuing 4 weeks despite discontinuation of all treatment. The patient experienced complete resolution of her symptoms.

Conclusions

We report a case of unilateral acute idiopathic maculopathy in a 14-year-old Hispanic girl. To the authors’ knowledge, this is the youngest reported patient with this condition to date.
In vivo Regeneration of Elastic Lamina on Fibroin Biodegradable Vascular Scaffold
Authors: Cattaneo Irene , Figliuzzi Marina , Azzollini Nadia , Catto Valentina , Farè Silvia , Tanzi Maria Cristina , Alessandrino Antonio , Freddi Giuliano , Remuzzi Andrea
Published: March 2013

Purpose

There is an increasing need for vascular grafts in the field of surgical revascularization. Artificial grafts offer alternative strategies to autologous tissue, however, small caliber (diameter <6 mm) vascular prosthesis are associated with a high incidence of thrombosis and early failure. Despite promising results, vascular tissue engineering is not yet a clinical reality due to the complexity of this approach. We aimed at investigating the use of fibroin, a biodegradable protein derived from silk, as an acellular vascular graft for in vivo recellularization.

Methods

We produced small caliber fibroin matrices by electrospinning to replace small arterial segments. Electrospun fibroin scaffolds were implanted into the abdominal aorta of Lewis rats by end-to-end anastomosis. Seven days after implantation, fibroin matrices were recovered and processed for histological and immunohistochemical analysis.

Results

Fibroin matrices allowed host cell infiltration, extracellular matrix remodeling, and ensured good patency of the grafts in the short term. Endothelial cells and smooth muscle cells were present in the explanted construct. Development of an elastic lamina adjacent to the lumen of the scaffold was observed with organization of intima and media layers. Vasa-vasorum were also present in the outer layer of the fibroin material.

Conclusions

Our results indicate that formation of vascular tissue containing elastin occurs already at 7 days after implantation on fibroin scaffold without in vitro cellularization. The use of an acellular electrospun silk fibroin tubular scaffold could be a promising strategy for in vivo regeneration of vascular tissue in the clinical reality.
Changes in Upper Limb Extracellular Water Content during Hemodialysis Measured by Multi-Frequency Bioimpedance
Authors: Kumar Sanjeev , Khosravi Maryam , Massart Annick , Potluri Madhu , Davenport Andrew
Published: March 2013

Introduction

Hemodialysis patients are at risk of chronic volume overload, with consequent increased cardiovascular morbidity and mortality. Multifrequency bioimpedance allows assessment of body fluid volumes. Devices vary from two paired electrodes which measure bioimpedance down one side of the body to four paired electrodes which measure both sides of the body. As arteriovenous fistulae may cause arm swelling, we investigated whether the presence of a fistula affected bioimpedance limb measurements.

Methods

We audited the change in extracellular water (ECW) and total body water (TBW) in the arms following hemodialysis in 414 adult patients attending for routine mid-week hemodialysis session by multifrequency bioimpedance using a four-paired electrode bioimpedance device (InBody 720; Biospace, Seoul, South Korea).

Results

Patients with right-sided brachial fistulae had a greater percentage ECW/TBW in the fistula arm both prior to and post dialysis compared to those dialyzing with catheters (pre 39.6 ± 3.5 vs. 38.4.3 ± 1.6 and post 38.5 ± 1.3 vs. 37.8 ± 1.1, p<0.01), but there was no difference in the ECW/TBW in the non-fistula arm, pre dialysis between those dialyzing with fistulae compared to catheters, but the ECW/TBW was greater post dialysis with both brachial (38.4 ± 1.1) and radial fistulae (38.1 ± 1.3) compared to those with catheters (37.7 ± 0.9, p<0.05 respectively).

Conclusions

Although absolute and also relative extracellular fluid volumes are increased in the fistula arm of hemodialysis patients, particularly right-sided and with brachial fistulae, the amount of fluid is unlikely to be of clinical significance when making bioimpedance measurements in the non-fistula side of the body to determine volume status.
Predisposing Factors for Colonic Torsion/Volvulus in Dogs: A Retrospective Study of Six Cases (1992–2010)
Authors: Gagnon Dominique , Brisson Brigitte
Published: March 2013

The purposes of this retrospective study were to review cases of colonic torsion/volvulus between July 1992 and August 2010 and to determine if any predisposing factors exist for the development of this condition. Six dogs were diagnosed with colonic torsion/volvulus during the study period. Four dogs had a history of previous gastric dilation-volvulus (GDV) with prophylactic gastropexy. Three of six dogs diagnosed with colonic torsion/volvulus had large intestinal entrapment and strangulation around the gastropexy site at the time of surgery. The history, clinical signs, physical examination, and radiologic findings were not specific for colonic torsion/volvulus in any dog. Early exploratory laparotomy was indicated to confirm the diagnosis and perform surgical correction of the affected bowel segments. Three of five dogs that underwent surgery had a left abdominal wall colopexy performed. All five dogs that underwent surgery in this study survived postoperatively. One patient was euthanized without surgical intervention. Results suggest that colonic torsion/volvulus should be considered in any large-breed dog with nonspecific gastrointestinal clinical signs and a history of previous gastropexy. Early recognition and prompt treatment of this condition may result in a good outcome.
Treatment of E. boehmi Infection in a Mixed-Breed Dog Using Milbemycin Oxime
Authors: Conboy Gary , Stewart Tonya , O'Brien Susan
Published: March 2013

Numerous bipolar plugged capillarid eggs were detected on a routine centrifugal fecal flotation examination of a 2 yr old castrated male boxer-Chinese shar pei mixed-breed. The eggs were identified as Eucoleus boehmi (E. boehmi), the nasal capillarid, based on size and shell wall surface morphology. The dog had a history of chronic sneezing (> 5 times/day) and intermittent postexercise nasal discharge. Currently, there are no anthelmintics approved for use in dogs for the treatment of E. boehmi. Treatment of the dog with 0.5–1 mg/kg milbemycin oxime was ineffective, but treatment with 2 mg/kg milbemycin oxime resulted in negative fecal examinations 7–28 days and 5 mo posttreatment. The dog’s postexertion nasal discharge greatly lessened, and the sneezing behavior improved (it was only noted 2–3 times/wk), but neither the discharge nor sneezing completely resolved following the anthelmintic treatments. Use of milbemycin oxime at an increased dose (2 mg/kg) appeared to be an effective treatment against E. boehmi infection in this dog based on clinical response and the cessation of fecal egg shedding.
Clinical and Laboratory Findings in Border Collies with Presumed Hereditary Juvenile Cobalamin Deficiency
Authors: Lutz Sabina , Sewell Adrian C. , Reusch Claudia E. , Kook Peter H.
Published: March 2013

Juvenile cobalamin deficiency is a rare disease in border collies and its diagnosis requires a high level of clinical suspicion. The goal of this study was to increase awareness of this disease by describing the clinical and laboratory findings in four young border collies with inherited cobalamin deficiency. The median age of the dogs was 11.5 mo (range, 8–42 mo), and two of the four dogs were full siblings. Clinical signs included intermittent lethargy (n = 4), poor body condition (n = 4), odynophagia (n = 2), glossitis (n = 1), and bradyarrhythmia (n = 1). Pertinent laboratory abnormalities were mild to moderate normocytic nonregenerative anemia (n = 3), increased aspartate aminotransferase (AST) activity (n = 3), and mild proteinuria (n = 3). All of the dogs had serum cobalamin levels below the detection limit of the assay, marked methylmalonic aciduria, and hyperhomocysteinemia. Full clinical recovery was achieved in all dogs with regular parenteral cobalamin supplementation, and laboratory abnormalities resolved, except the proteinuria and elevated AST activity persisted. This case series demonstrates the diverse clinical picture of primary cobalamin deficiency in border collies. Young border collies presenting with ambiguous clinical signs should be screened for cobalamin deficiency.
Learning Anatomy: Can Dissection and Peer-Mediated Teaching Offer Added Benefits over Prosection Alone?
Authors: Ashdown Lynn , Lewis Evan , Hincke Maxwell , Jalali Alireza
Published: March 2013

Purpose. To evaluate the impact of an optional thoracic dissection elective upon anatomy subject acquisition and determine whether peer-mediated teaching has a beneficial effect. Methodology. First year medical students’ results on thoracic anatomy laboratory examinations over a five-year period were obtained. All students were taught in the laboratory using prosected specimens as part of a standard curriculum. A subset of students from each class volunteered to participate in an optional thoracic dissection. A comparison of exam performance between the two groups was made, and the results were analyzed to see if incorporating peer teaching into the elective had an impact on the students’ performance on anatomy examinations. Results. With the exception of one year’s results, no significant statistical difference was found in student performance on anatomy examinations between the two groups. The addition of peer teaching did not result in superior performance. Conclusion. It is believed that prosected specimens are suitable for anatomy laboratory teaching in an undergraduate medical curriculum. Our study did not reveal that an opportunity for dissection offered any added benefit in terms of exam performance. In addition, peer teaching did not affect exam performance. This study strictly compared student exam results. It did not assess the possible impact of the dissection process to influence student attitudes towards death or the development of clinically relevant visuospatial abilities and procedural skills.
Comparative Study of the Effects of Drying Methods on Antioxidant Activity of Dried Strawberry (Fragaria Var. Camarosa)
Authors: Alonzo-Macías Maritza , Cardador-Martínez Anaberta , Mounir Sabah , Montejano-Gaitán Gerardo , Allaf Karim
Published: March 2013

Hot air drying (HAD), freeze-drying (FD), and swell-drying (SD, coupling instant controlled pressure drop, DIC, to standard hot air) were applied to strawberries (Fragaria var. Camarosa). The total phenol, total flavonoid, and total anthocyanin contentswere evaluated versusthe drying methods. The correlations between the bioactive compounds and antioxidant activity were investigated. The obtained results showed that the differences in phenol levels were no quite comparing the three drying techniques; however, great variations were reported for anthocyanin and flavonoid content.
 A strong correlation between the antioxidant activity and anthocyanin content was found in SD strawberries. Also, it was observed that saturated steam pressure (P) of DIC texturing operation, had a significant effect on the studied parameters compared to the thermal holding time (t). The optimum conditions of DIC were P = 0.35 MPa for t = 10 s to obtain the highest levels of phenols, flavonoids, and anthocyanins, as well as antioxidant activity.
Formation Tracking with Orientation Convergence for Groups of Unicycles
Authors: González-Sierra Jaime , Aranda-Bricaire Eduardo , Hernandez-Martinez Eduardo Gamaliel
Published: March 2013

This paper presents three trajectory tracking control strategies for unicycle-type robots based on a leader-followers scheme. The leader robot converges asymptotically to a smooth trajectory, while the follower robots form an undirected open-chain configuration at the same time. It is also shown that the orientation angles of all the robots converge to the same value. The control laws are based on a dynamic extension of the kinematic model of each robot. The output function to be controlled is the midpoint of the wheel axis of every robot. This choice leads to an ill-defined control law when the robot is at rest. To avoid such singularities, a complementary control law is enabled momentarily when the linear velocity of the unicycles is close to zero. Finally, numerical simulations and real-time experiments show the performance of the control strategies.
Human Tactile Stochastic Resonance Affected by Stimulus Direction
Authors: Beceren Kadir , Ohka Masahiro , Jin Tao , Miyaoka Tetsu , Yussof Hanafiah
Published: March 2013

Tactile sensors and their data processing are very important in enabling robots to handle objects. With information processing by biological organisms, stochastic resonance (SR) can enhance sensitivity by superimposing proper noise upon undetectable weak signals to detect the target signal. To investigate the SR of human tactile sensation and elucidate the mechanism of tactile SR for the development of a new tactile sensor, we performed a series of psychophysical experiments using tangential vibration with 2.5-mm and 8-mm-sized stimulus points. We examined the difference threshold (difference limen; DL) variation obtained from these experiments to clarify which conditions of vibration direction and stimulus size cause the strongest SR. The experimental results show that neither normal nor tangential DL is significantly affected by stimulus point size. Moreover, tactile sensing precision is enhanced by appropriate noise. The characteristics of SR, with normal vibration obtained from our prior study is quite different from that with tangential vibration.
Synchronous Smooth Sliding Mode Control for Parallel Mechanism Based on Coupling Analysis
Authors: Gao Guoqin , Wen Juan , Liu Xinjun , Zhang Zhigang
Published: March 2013

For any multi-DOF parallel mechanism, its system model is difficult to accurately establish and high-performance control is hard to achieve because of its high nonlinearity and strong coupling characteristics. In view of this, for a 6-PTRT parallel mechanism, the coupling characteristics are first analysed and then a novel smooth sliding mode control algorithm based on synchronization error is designed and the system's stability is proven - in theory - according to the Lyapunov stability theorem. By introducing the defined synchronization error into the smooth sliding mode control, the proposed method can resist the coupling effect among the branches of the parallel mechanism and realize the coordinated, synchronous and more accurate movement of each branch of the parallel mechanism with no accurate system model, whereby the tracking error of each branch may converge on zero simultaneously. The simulation results show that the synchronous smooth sliding mode control method proposed here has a shorter response time and a higher control precision when compared with the smooth sliding mode control method. By considering the errors of the adjacent branches, the synchronous coordination among the branches of the parallel mechanism with the coupling effect is effectively improved.
Quick Reads:A Circle Model for Multiplying Probabilities
Authors: Dowd Diane S.
Published: March 2013

A circle activity promotes students' understanding of probability.
Sweet Work with Fractions
Authors: Vinogradova Natalya , Blaine Larry
Published: March 2013

The Maximum Chocolate Party game requires students to divide and compare fractions in a practical and concrete context.
Beyond the Write Answer: Mathematical Connections
Authors: Haltiwanger Leigh , Simpson Amber M.
Published: March 2013

Allowing students to write in mathematics class can promote critical thinking, illustrate an awareness of mathematical connections, and result in clear communication as they share ideas comfortably with peers.
Mathematical Explorations: Interpreting Box Plots with Multiple Linked Representations
Authors: Özgün-Koca S. Asli , Edwards Thomas G.
Published: March 2013

A box plot activity is driven by a TI-Nspire calculator.
Assessments: Numbers, Context, Graphics, and Assumptions
Authors: Zorin Barbara , Hunsader Patricia D. , Thompson Denisse R.
Published: March 2013

Learn how to modify classroom evaluation items to avoid potential difficulties that limit a teacher's insight into students' mathematical understanding.
Role of the Endocannabinoid System in Systems Toxicity
Authors: Pistos Constantinos , Theocharis Stamatios
Published: March 2013

The scientific knowledge regarding the modulation of the endogenous cannabinoid system and its effect on disease pathophysiology has been significantly improved in the last 20 years. Alterations in the expression of cannabinoid receptors, their main endogenous ligands (arachidonoylethanolamide and 2‐arachidonoylglycerol), and related enzyme levels have been reported in different disease states, suggesting their important regulatory role. The pharmacological effects of synthetic compounds that selectively target the endocannabinoid system, established cause‐effect relationships between endocannabinoids and the progress of several disorders. In this review, the importance of endocannabinoid system modulation and also the aspects of the underlying pathways leading to disease or target organ toxicity are reported.
Systems Toxicology: A Valuable Tool for Early Prediction and Mechanistic Assessment of Liver Toxicity of Food‐Related Products
Authors: Sahu Saura C.
Published: March 2013

The review of literature demonstrates that systems toxicology is a valuable tool for early prediction and mechanistic assessment of liver toxicity. It will provide accurate molecular information for toxicity hazard and risk assessment in relatively short period of time. This technology will find very useful applications in food safety. It is an excellent tool for quick screening of hepatotoxic potential of food‐related products that occur naturally or that are added deliberately to the foods and dietary supplements. The published reports show the value of omics technologies in combination with classical histopathology and biochemical assays providing a powerful tool for accurate assessment of “predictive” and “mechanistic” hepatotoxicity. The systems toxicologyin vitrooffers a powerful cost‐effective tool for faster high‐throughput toxicity testing. It can be effectively used for high‐throughput screening of food‐related products for potential hepatotoxicity.
Species‐Metabolite Relation DatabaseKNApSAcKand Its Multifaceted Retrieval System,KNApSAcKFamily
Authors: Takahashi Hiroki , Hirai Aki , Shojo Masayuki , Matsuda Kaori , Parvin Aziza Kawsar , Asahi Hiroko , Nakamura Kensuke , Altaf‐Ul‐Amin Md. , Kanaya Shigehiko
Published: March 2013

In a metabolomics research, assignment of measured spectra to a specific metabolite is one of the most fundamental processes. The assignment is usually made by taking a match with known compounds, and therefore it is necessary to scan the spectra against whole previously studied compounds. This means the survey of whole natural products reported in the literature, which is an extremely tedious and daunting process. In order to make this process feasible, we have developed a metabolite database called KNApSAcK, which currently contains 76,357 species–metabolite relations involving 37,693 metabolites. In the present study, we review the current status of KNApSAcK database and its application to metabolomics and introduce the multifaceted retrieval system KNApSAcK family, which consists of seven parts for the purpose of retrieving metabolites from several different aspects. “Pocket” includes search system for species related to human living such as edible plants in Japan (“Lunch Box”), herb teas (“Tea Pot”, in progress), traditional Japanese medicine (“KAMPO”), poisonous plant (“Poison”, in progress), and bio‐fuel resources (“Fuel”, in progress). “KNApSAcK from around the world” includes medicinal and edible plants utilized in each country. Seven thousand three hundred and fifty‐six pairwise relations between medicinal/edible plants and 119 nations worldwide have been accumulated from scientific literatures.
Chemoinformatics and its Applications
Authors: Umashankar Vetrivel , Gurunathan Subramanian
Published: March 2013

Cheminformatics is the use of computer and informational techniques, applied to a range of problems in the field of chemistry. It is also known as chemoinformatics and chemical informatics. These
in silico
techniques are used in pharmaceutical companies in the process of drug discovery. Cheminformatics can also be applied to data analysis for various industries such as paper and pulp, dyes and such allied industries. The primary application of cheminformatics is in the storage of information relating to compounds. Quantitative structure–activity relationship (QSAR) analysis also forms a part of cheminformatics. Several
in silico
cheminformatic tools are currently available for predicting physio‐chemical properties and biological activity of many different chemical molecules. Thus, chemoinformatics helps to reduce the time taken for identifying potential drug targets as well as to understand physical, chemical and biological properties of several chemical compounds. Outputs of chemoinformatics may also direct the course of wet laboratory experiments.
Biomarker Discovery: Introduction to Statistical Learning and Integrative Bioinformatics Approaches
Authors: Repsilber Dirk , Jacobsen Marc
Published: March 2013

In toxicology, biomarkers are needed for use in screenings, time series and dilution series exposure studies for safety evaluation and risk assessment. They need to be easily and reproducibly measurable, and are therefore sought amongst molecular features using OMICs high‐throughput technologies in assays of blood and other easily accessible tissue. This chapter conveys methods for screening OMICs datasets for candidate biomarkers for classification. We begin focussing on single biomarker detection, and survey improvements to the t‐test as well as multiplicity corrections regarding this objective. Biomarker panels (biosignatures) are patterns of several combined single features. We describe their detection using three different methods of statistical learning. Here, a special focus is on avoiding overfitting through appropriate use of cross‐validation. More sophisticated approaches using gene‐set enrichment algorithms and steps towards integrated bioinformatics analyses are explained. Making use of a priori knowledge about regulatory structures (gene groups, correlation structures) may further improve classification efficiency of the detected biosignatures. As the red line, we exemplify analysis possibilities using the famous Golub gene expression dataset and the appropriateR‐scripts – enabling the reader to reproduce every step on his own desktop.
Systems Toxicology Modeling for Prediction in Humans
Authors: Migliorini Cristiano , Lave Thierry , Parrott Neil J. , Reddy Micaela , Grimm Hans Peter , Penland Robert C. , Soubret Antoine , Helmlinger Gabriel , Georgieva Anna , Zuideveld Klaas P.
Published: March 2013

This chapter aims to illustrate the ability of physiologically based mechanistic mathematical models to predict pharmacokinetics and toxicity across species. The underlying principle is that toxicity must be interpreted in the physiological context where it is measured.

Various methodologies for predicting the pharmacokinetics, QT prolongation and proarrhythmic risk are evaluated. Finally an integration of both pharmacokinetics and toxicokinetics in chemotherapy‐induced neutropenia is discussed. It is believed that the methodologies presented for integrating available knowledge across experiments to predict toxicology in humans will ultimately make drug development more efficient, cost cost‐effective, and socially more acceptable.
Systems Modeling in Developmental Toxicity
Authors: Knudsen Thomas B. , DeWoskin Robert S.
Published: March 2013

High‐throughput or high‐content studies are now providing a rich source of data that can be applied toin vitroprofiling of chemical compounds for biological activity and potentialin vivotoxicity. EPA's ToxCast™ project, and the broader Tox21 consortium, as well as other projects worldwide, are providing high‐throughput and high‐content screening data (HTS‐HCS) focusing on thein vitrotargets and cellular bioactivity profiles for thousands of chemical compounds in commerce or entering the environment. A goal of chemical profiling is to rapidly identify and efficiently classify signatures of biological activity that are potentially diagnostic ofin vivotoxicities using automated technologies. Predictive modeling of developmental toxicity faces several challenges: correlatingin vitroconcentration–response with internal dose–response kinetics; understanding howin vitrobioactivity profiles extrapolate from one cell‐type or technology platform to another; and linking individual targets ofin vitrobioactivity to complex signatures associated with pathways ofin vivotoxicity. Toxicity in the intact organism is an expression of complex and interwoven events that follow from cellular perturbations. As such, multicellular computer models known as ‘virtual tissues’ that recapitulate developmental events can provide a technology platform to simulate non‐linear behaviors of dynamical systems and to model perturbations. A virtual embryo, for example, might be envisaged as a toolbox of computational (in silico) models that execute morphogenetic programs to simulate developmental toxicity.
Multiscale Integration of Toxicokinetic and Toxicodynamic Processes: From Cell and Tissue to Organ and “Whole Body” Models
Authors: Georgopoulos Panos G. , Isukapalli Sastry , Androulakis Ioannis P. , Ierapetritou Marianthi G. , Welsh William J.
Published: March 2013

This chapter presents a systematic summary overview of coordinated efforts taking place at the environmental bioinformatics and Computational Toxicology Center (ebCTC.org) towards developing a mechanistic modeling framework that integrates multiple scales of coupled toxicokinetic and toxicodynamic processes. This framework employs highly modular “whole body” computational descriptions of the human and of selected model organisms that incorporate a hierarchy of alternative formulations representing biological events in “virtual” tissues and organs. This approach allows the mechanistic consideration of multiple scales of interlinked phenomena that include molecular interactions; dynamics of intracellular biomolecular networks; spatial and stochastic aspects of cell biochemistry; integrative coupling of cellular‐level processes related to common endpoints; extracellular signaling and cell‐cell communication and interaction; aspects of functional heterogeneity in multicellular structures; dynamics of histomorphological and histopathological processes at the tissue level; and integrative coupling of processes across scales, resulting in different physiosystem phenotypes for health and disease states. The ebCTC framework offers a range of combined approaches for coupling processes and “transferring and integrating” information across multiple strata of biological organization, ranging from formal methods of multiscale analysis, including statistical descriptions of multicellular kinetics and dynamics, to simplified “top‐down” approaches, incorporating both mechanistic and phenomenological formulations that rely on point and distributional parameterizations of the finer scales. The computational implementation of the framework employs a combination of agent‐, network‐, and field‐based modeling methods. Example applications of various components of this framework are presented, spanning the range from molecular interactions to bionetwork and cellular dynamics to multiscale problems at the tissue and organ levels.
Nanotoxicology: A Brief Overview and Discussion of the Current Toxicological TestingIn Vitroand Suggestions for Future Research
Authors: Clift Martin J. D. , Blank Fabian , Gehr Peter , Rothen‐Rutishauser Barbara
Published: March 2013

Nanotechnology is an ever‐growing industry that is expected to reach a net worth of over 15 billion by 2015 (Service, 2004). Although there are many proposed advantages related to this new industrial revolution, there are increased concerns regarding the potential adverse health effects that exposure to the production of nanotechnology‐related products might pose (Maynardet al., 2006). Although not fully understood or confirmed, these concerns are well founded due to the plethora of research and knowledge related to the effects of environmental air pollution on human health relative to the nanoparticle (NP) component contained within it. Due to the inevitable exposure of humans to NPs, owing to their use in a wide and diverse range of applications, it is imperative to understand how NPs interact with the human body.In vivoresearch, however, has many disadvantages, and so increased research into the possible adverse effects of NPs has been performed usingin vitromodels. Therefore, the aim of this chapter is to provide an in‐depth description of the many different toxicity tests usedin vitro, how they are beneficial in filling the knowledge gap related to the potential toxic effects of NPs and the many pitfalls that are associated with them, in addition to providing an overview of the field of nanotoxicology as well as suggesting howin vitrotesting strategies may be used to demonstrate the effects ofin vivoexposure to NPs.
The Role of Oxidative Stress in Nanotoxicology
Authors: Sayes Christie M. , Banerjee Nivedita , Romoser Amelia A.
Published: March 2013

The application of systems biology approaches is gaining popularity in the nanoparticle toxicology research (Brandenberger, 2010; Oberdorster, Oberdorster and Oberdorster, 2005; Nyland and Silbergeld, 2009). Over the past few years, there has been a movement toward describing and characterizing trends in nanotoxicological data sets. In order to interpret these observed trends, the use of a holistic perspective may be appropriate. One of the cornerstones of systems biology is the use of experimental and computational models. Nanotoxicology could benefit from these efforts. Both systems biology and nanotoxicology attempt to discover emergent properties of a system and link those properties, using a variety of techniques to environmental and human health.

While the investigations in the field of systems biology are frequently large in scale, nanotoxicology has yet to accomplish this feat, to date. Both fields require an interdisciplinary approach from experimentalists (biologist, chemists, toxicologists, and risk assessors) and quantitative scientists (biostatisticians, mathematicians, computer scientists, and engineers). Together, their efforts can be coordinated to improve the quality of science and to create, refine, and retest the experimental and computational models to accurately reflect, and eventually predict, biological, and toxicological observations.
Implementing Systems Toxicology in Drug Development for Regulatory Decision Making
Authors: Sina Joseph F. , Sistare Frank D.
Published: March 2013

The concept of integrating molecular and biochemical data from new technologies with more traditional endpoints to develop a more complete understanding of risks and benefits in drug development has gained wide acceptance as a reasonable way to advance human health. However, actual implementation of this systems approach is not straightforward. While technology keeps advancing, our ability to accurately interpret the complexity of human biology has not kept pace. Indeed, sometimes the case seems to be one of the deeper we investigate, the more we realize what we do not understand. Additionally, in developing ethical pharmaceuticals, a major issue is establishing the necessary level of confidence to extrapolate from a series of endpoint measurements to accurately predict beneficial and/or potentially adverse responses in the diverse population of patients. The evidentiary standard for acceptance of new models and biomarkers in clinical practice is necessarily high, although the concept of “fit‐for‐purpose” may help expedite the application of new knowledge in specific clinical situations. This chapter will present a view of both the progress and hurdles to applying systems toxicology to drug development in a regulated environment.
Physician accountability in iatrogenic cerebrospinal fluid leak litigation
Authors: Kovalerchik Olga , Mady Leila J. , Svider Peter F. , Mauro Andrew C. , Baredes Soly , Liu James K. , Eloy Jean Anderson
Published: March 2013

Background

The potentially severe complications resulting from cerebrospinal fluid (CSF) leak makes iatrogenic injury a medicolegal area of concern for otolaryngologists and neurosurgeons. The objectives of this analysis were to study legal outcomes as well as medical and nonmedical elements affecting malpractice litigation.

Methods

Public court records available in the Westlaw legal database (Thomson Reuters, New York, NY) were searched for medical malpractice litigation related to iatrogenic CSF leak. Of the 18 jury verdicts and settlements included, outcomes and awards, patient demographic data, and other factors instrumental in determining legal responsibility were recorded for comparison.

Results

Ten (55.6%) cases were resolved in the defendant's favor, 2 (11.1%) resulted in damages awarded by a jury, and 6 (33.3%) were settled out of court before resolution of trial. Mean damages awarded were $1.1 million, while out of court settlements averaged $966,887. Malpractice stemming from patients who underwent endoscopic sinus surgery comprised 77.8% of cases analyzed. The most frequent alleged factors cited for litigation included having to undergo additional surgery (88.9%), developing meningitis (50.0%), and failing to recognize complications in a timely manner (44.4%). Perceived deficits in informed consent were alleged in one‐third of cases.

Conclusion

Although a slight majority of cases were resolved in the defendant's favor, payments made were considerable, averaging approximately $1 million. Strategies to decrease liability and allow patients to make more informed decisions should include clear communication with patients that explicitly states potential risks, such as meningitis, and possible need to undergo additional reparative surgery.
Simulationsmodelle für Gebrauchstauglichkeitsuntersuchungen von Holzbauteilen durch künstliche Bewitterung
Authors: Herlyn J. W.
Published: March 2013

Die Eignung neu entwickelter Holzbauteile oder Holzwerkstoffe ist häufig nur über lang andauernde und entsprechend kostenintensive Praxisversuche nachzuweisen. Die Untersuchungsdauer kann durch Bewitterungssimulationen in Doppelklimaanlagen verkürzt werden. Voraussetzung für eine künstliche Bewitterung ist ein geeignetes Simulationsmodell. In dem Modell müssen die natürlichen Klimabelastungen in der Art nachgestellt werden, daß die Beanspruchungen des Bauteils im Versuch denjenigen in der Natur entsprechen. Zu diesem Zweck sind die Wirkungspfade der Klimabelastungen auf das Holzbauteil aufzustellen. Anschließend wird mit Hilfe des Test Tailoring ein Modell entwickelt, in dem die Belastungen zur Verkürzung der Versuchsdauer zeitgerafft und beschleunigt werden. Hierfür wird ein Computerprogramm zur Berechnung instationärer gekoppelter Wärme‐ und Feuchteströme in Bauteilen eingesetzt. Die Zeitstraffung und Beschleunigung von Bewitterungsmodellen sind in erster Linie von der Reaktionsgeschwindigkeit des Holzes oder der Holzwerkstoffe bei Feuchteänderungen abhängig. Diese Geschwindigkeit wird von der Geometrie sowie der Feuchteleit‐ und Feuchtespeicherfähigkeit beeinflußt. Anhand von unterschiedlichen Holzbauteilen werden die jeweils entwickelten Simulationsmodelle mit exemplarischen Ergebnissen vorgestellt. Dabei wird die jeweilige Vorgehensweise zur Entwicklung der Modelle erläutert. Die Simulationsmodelle enthalten neben den Belastungen aus Lufttemperatur und relativer Luftfeuchte auch Belastungen aus Niederschlag und Sonnenstrahlung.
Schallabsorber und Schalldämpfer ‐ Innovatorium für Maßnahmen zur Lärmbekämpfung und Raumakustik, Teil 2: Reaktive Absorber, Platten‐Resonatoren
Authors: Fuchs H. V. , Zha X. , Krämer M. , Zhou X.
Published: March 2013

In Teil 1 dieses Innovatoriums, das auch als kleines Repetitorium gelesen werden kann, ging es einleitend ‐ darin der historischen Entwicklung folgend ‐ um die passiven Absorber. Entsprechend ihrer im Markt bisher dominierenden Präsenz nehmen sie in allen Standard‐Darstellungen von Schallabsorbern und ‐dämpfern den weitaus größten Raum ein, auch weil ihre Wirkungsweise, Auslegung und Anwendung relativ einfach zu beschreiben sind. Nach einer kurzen Beschreibung des Schallfeldes in kleinen und mittelgroßen Räumen, wie sie z. B. für kommunikationsintensive Arbeitsplätze mit hohen raumakustischen Anforderungen gebaut werden, sollen im Teil 2 fast ausschließlich reaktive Absorber behandelt werden, welche auftreffende Schallwellen nicht nur schlucken, sondern auch auf die eine oder andere Art mit dem anliegenden Schallfeld in Wechselwirkung treten.
Auswirkungen von Lastwechseln auf die Zustandsgrößen biegebeanspruchter Stahlbetontragwerke unter Gebrauchslast
Authors: Keysberg J.
Published: March 2013

Zur Klärung der Auswirkungen von Lastwechseln auf die Zustandsgrößen biegebeanspruchter Stahlbetonbauteile unter Gebrauchslast wurde ein Rechenmodell entwickelt. Dieses gilt für biegebeanspruchte Stabtragwerke und kann den Einfluß einer beliebigen Lastfolge bei der nichtlinearen Berechnung berücksichtigen, indem die Moment‐Verkrümmungs‐Beziehung der Erstbelastung entsprechend der zuvor aufgetretenen Beanspruchungen modifiziert wird. In Vergleichsberechnungen zu experimentellen Untersuchungen konnten mit dem Rechenmodell gute Ergebnisse erzielt werden. Parameterstudien zeigen der Veränderungen der Beanspruchungen, die infolge wechselnder Belastungen durch Last und Zwang im Gebrauchszustand zu erwarten sind.
Tragfähigkeit und Bemessung gemauerter Wände nach Versuchen
Authors: Herzog M.
Published: March 2013

Es wird ein einfaches und anschauliches Rechenverfahren zur wirklichkeitsnahen Voraussage der Tragfähigkeit gemauerter Wände mitgeteilt, das auf umfangreichen Versuchsreihen des Schweizerischen Verbandes der Ziegel‐ und Steinfabrikanten in den vergangenen 40 Jahren beruht.
Erinnerung an Friedrich Engesser (1848‐1931)
Authors: Steinhardt O.
Published: March 2013

Am 12. Februar 1998 jährte sich der Geburtstag von Friedrich Engesser zum 150. Male. Engesser war einer der bedeutendsten Altmeister der Bautechnik und hat auf fast allen Gebieten des konstruktiven Ingenieurbaus in Forschung, Praxis und Lehre maßgebliche Entwicklungsarbeit geleistet. Zwischen 1879 und 1923 veröffentlichte er 165 Fachaufsätze in anerkannten deutschsprachigen Zeitschriften, seine Bücher über Fachwerkbrücken sowie seine Beiträge zur Technikphilosophie und zur Bauingenieurausbildung sind heute noch lesens‐ und beherzigenswerte Publikationen.
Automatisierte Dauerüberwachung von Bauwerksverformungen und Erfassung statischer Größen am Beispiel des Zwickauer Doms
Authors: Suleiman A.
Published: March 2013

Die Langzeitüberwachung von Formänderungen ausgewählter Bauteile nimmt bei der Tragsicherheitsbewertung und Erhaltung historisch bedeutsamer, gefährdeter Bauwerke eine wichtige Stellung ein. Bisher überwogen hierbei die klassischen, einfachen Methoden wie Gipsmarken, Schnurlote oder der Einsatz klassischer geodätischer Geräte. Mit der rapiden Entwicklung der computergestützten Meßtechnik können diese Messungen kontinuierlich und automatisch ablaufen, so daß damit zur Diagnose und Therapie geschädigter Bauwerke ein wertvolles und aussagefähiges Hilfsmittel zur Verfügung steht. Am Beispiel des Zwickauer Doms soll dies im folgenden demonstriert werden.
Zweiachsige Biegung mit Längskraft bei Querschnitten aus hochfestem Beton
Authors: Backes W.
Published: March 2013

Mit dem hochfesten Beton ist ein neuer Baustoff entstanden, der weltweit bereits umfassend erforscht ist. Es gibt dabei jedoch kaum Untersuchungen über zweiachsig beanspruchte Bauteile. Dies erstaunt, da diese Beanspruchbarkeit in der Baupraxis häufig auftritt, liegt wohl aber daran, daß die zugrundeliegenden mechanischen Zusammenhänge sehr komplex sind. In der vorliegenden Arbeit wird ein Verfahren beschrieben, das es ermöglicht, nahezu beliebige Querschnitte aus hochfestem Beton unter zweiachsiger Beanspruchung zu untersuchen. Nach einer ausfühlichen Erläuterung der technischen Grundlagen wird die große Anwendungsbreite des Verfahrens an ausgewählten Beispielen verdeutlicht. Dabei wird erkennbar, daß der Einsatz von hochfestem Beton auch bei zweiachsig beanspruchten Bauteilen zu nennenswerten Vorteilen führen kann. Aufgrund der daraus resultierenden baupraktischen Bedeutung sollten die hier nur theoretisch abgeleiteten Ergebnisse durch ergänzende experimentelle Untersuchungen auf eine abgesicherte Basis gestellt werden.
Verbundbrücken ‐ Vom konventionellen zum innovativen Entwurf
Authors: Virlogeux M.
Published: March 2013

Dieser Beitrag gibt einen Überblick über die Entwicklung der Verbundbrücken in Frankreich mit sehr traditionellen, gleichzeitig aber auch innovativen Lösungen. Er zeigt die Vielzahl und die Eleganz, die mit effizienten baulichen Lösungen einhergehen, und die notwendige Zusammengehörigkeit von Stahl und Beton für den besten Einsatz im modernen konstruktiven Ingenieurbau. Die umfangreichen Erfahrungen, die wir in Frankreich und international mit Verbundbrücken gemacht haben, sollen hiermit der deutschen Fachöffentlichkeit zur Verfügung gestellt werden. Der vorliegende Beitrag behandelt hauptsächlich technische Aspekte, berücksichtigt aber auch Ästhetik und architektonische Gestaltung, weil wir der Ansicht sind, daß eleganter Ingenieurbau nur durch konstruktive Effizienz und Kreativität erreicht werden kann. Diese Gedanken verbinden uns auch mit berühmten deutschen Ingenieuren wie Leonhardt und Schlaich; wir hoffen, mit diesem Beitrag gegen nicht sinnvolle und teure Bauwerke Position zu beziehen, da diese leider oft durch die Medien unterstützt werden. Ferner beabsichtigt dieser Aufsatz, die Ergebnisse einer systematischen Vorgehensweise darzustellen, die auf technischem Fortschritt beruht, und die wir während der vielen Jahre bei SETRA mit der Unterstützung der Straßenbaudirektoren, die die eigentlichen Sponsoren für Forschung und Technologie waren, entwickeln konnten.