bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Progression Rates for Human Papillomavirus Infection From Epidemiological Data
Authors: Jit Mark , Gay Nigel , Soldan Kate , Hong Choi Yoon , Edmunds William John
Published: June 2009

A Markov model was constructed in order to estimate typespecific rates of cervical lesion progression and regression in women with high-risk human papillomavirus (HPV). The model was fitted to age- and type-specific data regarding the HPV DNA and cytological status of women undergoing cervical screening in a recent screening trial, as well as cervical cancer incidence. It incorporates different assumptions about the way lesions regress, the accuracy of cytological screening, the specificity of HPV DNA testing, and the age-specific prevalence of HPV infection. Combinations of assumptions generate 162 scenarios for squamous cell carcinomas and 54 scenarios for adenocarcinomas. Simulating an unscreened cohort of women infected with high-risk HPV indicates that the probability of an infection continuing to persist and to develop into invasive cancer depends on the length of time it has already persisted. The scenarios and parameter sets that produce the best fit to available epidemiological data provide a basis for modeling the natural history of HPV infection and disease.
Involuntary Movements During Vitamin B12 Treatment
Authors: Özdemir Özlem , Baytan Birol , Gunes Adalet Meral , Okan Mehmet
Published: June 2009

It has been known for many years that vitamin B12 deficiency can cause neurologic problems. One of these problems is involuntary movements that can appear both before and after the initiation of vitamin B12 treatment. Here, we report 3 infants who developed movement disorder during vitamin B12 administration. The movement disorder consisted of a combination of tremor and myoclonus affecting face, tongue, and limbs. Because of the severity of the symptoms, they all needed symptomatic treatment. In 2 of them, the involuntary movements resolved with clonazepam. The involuntary movements in the other patient were successfully treated with piracetam.
Rehabilitative Therapies in Cerebral Palsy: The Good, the Not As Good, and the Possible
Authors: Damiano Diane L.
Published: June 2009

In the past decade, growing recognition of the importance of motor activity for the development and maintenance of central nervous system pathways and for recovery of function post injury has provided new avenues for rehabilitation. Physical therapy is likely to have a prominent role in stimulating neuroplastic changes in damaged developing nervous systems that may finally alter the natural history of these disorders, which has not yet been possible. In this article, we discuss the scientific evidence for various physical therapy treatment options for children with cerebral palsy. Newer, more intense, and task-related exercise programs show the strongest level of evidence. Traditional approaches and newer ‘‘packaged’’ approaches have failed to provide evidence of superiority. Their continued prevalence among clinicians is puzzling and disconcerting, as evidence supporting other approaches continues to accumulate.
Giving Them Something to Hate
Authors: Ure Jenny , Rakebrandt Frank , Lloyd Sharon , Khanban Ali , Procter Rob , Anderson Stuart , Hanley Janet , Hartswood Mark , Pagliari Claudia , McKinstry Brian , Tarling Alex , Kidd Gillian , Corscadden Paddy
Published: June 2009

There are recognized problems in the course of requirements analysis and design for heterogeneous, distributed, and dynamic systems. These are particularly evident where the context of future use is not yet clear to users, and where the implementation of these systems will reconfigure the costs, risks, and benefits for stakeholding groups. The article provides examples of the value of collaborative early prototyping with users in two such cases—the design of a HealthGrid portal and a telehealth portal. We provide further examples of the value of the prototype as a vehicle for engagement, a sandbox for exploring emerging opportunities, a landscape for negotiating the reconfiguration of roles and resources, and as an early warning system for early identification of emerging problems likely to impact on usability.
Sex Differences in the Expression and Use of Computer-Mediated Affective Language
Authors: Brunet Paul M. , Schmidt Louis A.
Published: June 2009

Although women have been stereotyped as more emotionally expressive than men, the extant empirical evidence on sex differences in the expression and use of affective communication is equivocal. The authors examined the influence of sex and context on the expression and use of computer-mediated affective language in a sample of young adults. A total of 56 undergraduates (28 males, 28 females) were paired in same-sex dyads and randomly assigned to either a webcam or no webcam condition. The participants engaged in a 10-min free chat online conversation in the laboratory. Transcripts were objectively coded for the use of affective communication and traditional linguistic and conversational style measures. The analyses revealed separate significant Sex × Webcam Condition interactions on the affective quality of language used and the expression of computer-mediated emotion. Men in the webcam condition used significantly less active words than men in the no webcam condition and less than women in the webcam condition. Women in the webcam condition used significantly more emoticons than women in the no webcam condition or men in either condition. Men and women did not differ in their use of emoticons in the no webcam condition. Results suggest that sex differences in the use and expression of computer-mediated affective communication are context specific in an undergraduate sample. Findings are discussed in terms of their larger implications for understanding sex differences in the expression and use of emotion in face-to-face (FTF) social interactions.
The Digital Divide, Political Participation, and Place
Authors: Sylvester Dari E. , McGlynn Adam J.
Published: June 2009

This article focuses on the persistence of the digital divide and its impact on political participation, and in particular, on the role that geographic location plays in unequal access. The authors findings, based on survey data from the 2007 Pew Internet and American Life project, indicate that physical location continues to play a key role in levels of access to broadband technology and that increased home Internet use is associated with a significantly higher probability of contacting government officials in various ways.
Issue Engagement on Congressional Candidate Web Sites, 2002—2006
Authors: Druckman James N. , Hennessy Cari Lynn , Kifer Martin J. , Parkin Michael
Published: June 2009

When candidates engage in robust policy debate, it gives citizens clear choices on issues that matter. Previous studies of issue engagement have primarily used indicators of campaign strategy that are mediated by reporters (e.g., newspaper articles) or indicators that may exclude candidates in less competitive races (e.g., television advertisements). We study issue engagement with data from a unique source, congressional candidate Web sites, that are unmediated and representative of both House and Senate campaigns. We find that the saliency of issues in public opinion is a primary determinant of candidate engagement. And, despite the unique capacity of the Internet to allow candidates to explain their positions on a large number of issues, candidates continue to behave strategically, selecting a few issues on which to engage their adversaries.
The Evolution of Social Capital and Civic Engagement Between Nonprofit Networks and County Representatives
Authors: Kalu Kalu N. , Remkus Brett W.
Published: June 2009

The concept of social capital continues to underline contemporary debate regarding the extent to which shared values, ideas, norms, and culture shape the kind of political and administrative efficacy that enhances collective action, democracy, and effectiveness in public service delivery. This study attempts to identify the relevance of civic engagement and information, communications, and technology (ICT)-induced networking in the development of social capital among local county commissioners and nonprofit leaders in the state of Alabama. Results drawn from a series of analyses indicate that county commissioners are more likely to rely on interpersonal networking to getting things done, as opposed to relying on ICT-induced networking, which is more characteristic of leaders of nonprofit organizations. Although the findings also suggest that both county commissioners and nonprofit leaders have similar preferences regarding key indicators of social capital, the mechanisms by which it evolves is different in both institutional frameworks. From a policy perspective, the propositions offered here also provide a useful model that could be replicated in other state and local government scenarios.
Ethnocultural community leaders’ views and perceptions on biobanks and population specific genomic research: a qualitative research study
Authors: Godard Béatrice , Ozdemir Vural , Fortin Marilyn , Égalité Nathalie
Published: June 2009

Substantial investments were made in population based biobanks over the past decade. Ethnocultural community members are both sponsors and beneficiaries of biobanks. In addition, the success of biobank projects depends on community support and participation. Yet there are few empirical data on views, perceptions and interests of ethnocultural communities on biobanks. This silent gap in genomics, ethics and policy literatures has to be addressed. We conducted a qualitative research study with in-depth interviews of ethnocultural community leaders (e.g., members of the Canadian Parliament, school commissioners) on their perspectives concerning population specific genomics research and biobanks. An equal partnership model where public is not only informed, but also involved in decision-making processes was perceived as an essential democratic requisite. These empirical data on ethnocultural community leaders’ views, interests and perceptions identify several key socio-cultural and ethical factors that can be decisive for effective and sustainable community involvement in biobanks.
The Current Financial Crisis
Authors: Boorman Jack
Published: June 2009

It is now clear that the global economy is facing the worst economic and financial crisis since the Second World War. The crisis manifested itself initially in the subprime mortgage market in the US, but quickly spread to Europe; in the breakdown in the market for credit default swaps—a huge, unregulated and thoroughly opaque market; and in the general collapse of the markets for securitised instruments across the global financial system. It was aggravated, most analysts agree, by the initial policy missteps in handling the crisis, including in dealing with the problems at Lehman Brothers, which effectively froze the interbank market.

This article discusses the origins, its impact as well as its policy implications of these developments. The article postulates that there were three basic root causes of the crisis: (a) the ‘search for yield’ and a weakening of—and lack of understanding of—risk management during the expansion phase of the credit cycle from 2002 to 2006; (b) the international fragmentation and lack of harmonisation of financial supervision and regulation in the face of rapid innovation in the financial markets—a phenomenon that gave rise to regulatory arbitrage by the global financial institutions; and (c) weaknesses in certain aspects of surveillance conducted by the IMF. It goes on to describe the unprecedented monetary and fiscal measures taken by the major countries since September 2008 to contain the crisis. It further lists the remaining policy agenda, including the reform of the global financial architecture and the author's views on how to move forward.
An Approach to Force-Feedback Control with Traveling Wave Ultrasonic Motor
Authors: Seigler T. Michael , Venkatesan Nishant , Inman Daniel
Published: June 2009

The traveling wave ultrasonic motor is considered for use in haptic devices where feedback forces are required, particularly in force-feel systems where a certain input— output relation is desired between the applied torque and the response. Owing to some of its unique characteristics, there are circumstances where the ultrasonic motor may be considered an appealing alternative to the more standard DC motor. However, the two types of motors are significantly different in their principles of operation, and are not necessarily interchangeable for all applications. The ultrasonic motor is limited in that the torque cannot be arbitrarily controlled under external loading. Moreover, direct control of the motor torque is difficult due to the complex nature of the contact mechanics. To accommodate these limitations, we investigated a method of model reference force-feedback control, in which the interaction torque is used as the reference source. Experimental results demonstrated that the closed-loop system is able to approximate simple second-order behavior, thus approximating the feel of a spring and damper.
Stiffness Tuning with Bias Magnetic Fields in Ferromagnetic Shape Memory Ni-Mn-Ga
Authors: Sarawate Neelesh N. , Dapino Marcelo J.
Published: June 2009

This article presents the dynamic characterization of mechanical stiffness changes under varied bias magnetic fields in single-crystal ferromagnetic shape memory Ni-Mn-Ga. The material is first converted to a single variant through the application and subsequent removal of a bias magnetic field. Mechanical base excitation is then used to measure the acceleration transmissibility across the sample, from where the resonance frequency is directly identified. The tests are repeated for various longitudinal and transverse bias magnetic fields ranging from 0 to 575 kA/m. A SDOF model for the Ni-Mn-Ga sample is used to calculate the mechanical stiffness and damping from the transmissibility measurements. An abrupt resonance frequency increase of 21% and a stiffness increase of 51% are obtained with increasing longitudinal fields. A gradual resonance frequency change of -35% and a stiffness change of -61% are obtained with increasing transverse fields. A constitutive model is implemented which describes the dependence of material stiffness on transverse bias magnetic fields. The damping exhibited by the system is low in all cases (~0.03). The measured dynamic behaviors make Ni-Mn-Ga well suited for vibration absorbers with electrically tunable stiffness.
Coupled Multi-field Formulation in Space and Time for the Simulation of Intelligent Hydrogels
Authors: Wallmersperger Thomas , Ballhause Dirk , Kröplin Bernd , Günther Margarita , Gerlach Gerald
Published: June 2009

Hydrogels are hydrophilic polymer networks. Immersed in water-based solutions they show an enormous swelling due to the inflow of water into the network. In the case of charged hydrogels the polymer network additionally contains bound charges which influence the diffusion of dissolved charges in ionic solutions. The swelling of the hydrogels can be influenced by various external stimuli such as temperature, pH value, concentration of dissolved ions in the solution, or applied electric fields. By varying these parameters the state of the hydrogels can be selectively affected. This accounts for the designation `intelligent hydrogels'. Applications of this type of material can be either as sensors e.g., for pH value or ion concentrations in solutions (Gerlach et al., 2005), or as actuators e.g., as artificial muscles or chemo-electric energy converters (Shiga and Kurauchi, 1990; Gülch et al., 2001). In either case the coupling of chemical, electrical, and mechanical field variables is exploited. In order to simulate the complicated behavior of hydrogels, a mathematical description of the coupled three-field problem is necessary. In the present work, an approach to a fully coupled three-field description using the finite element method is made. The formulation of the problem is based on the works of Wallmersperger et al. (2001, 2004b), who have sequentially solved the three-field problem by first calculating the coupled chemo-electric system and then using the results as input for a mechanical analysis. As an advancement of this modeling approach, a specialized finite element containing degrees of freedom for chemical concentrations, electric potential, and mechanical displacements is developed. It enables a fully coupled simultaneous solution of the three-field problem and makes it possible to describe the hydrogel behavior in sensor as well as in actuator-applications. The implementation is conducted as a user-defined element in the commercial software package ABAQUS. For the numerical solution the Newton-Raphson method in conjunction with the backward Euler time integration scheme is applied. Results for the electrical stimulation, proving the applicability of the developed numerical model, are obtained.
Use of Classical Plate Finite Elements for the Analysis of Electroactive Composite Plates. Numerical Validations
Authors: Pablo F. , Bruant I. , Polit O.
Published: June 2009

An original piezoelectric plate theory has been presented in the companion paper (Osmont and Pablo, 2008). The particularity of the ‘piezoelectric’, finite element stemming from this theory lies in the fact that no electric degree of freedom is needed to take into account the electromechanical coupling. This article is focused on the validation of this theory through various benchmarks issued from literature. It will be proved that results are in quite agreement with static and dynamic reference solutions of laminated composite plates equipped with piezoelectric patches.
Nonlinear Frequency Veering in a Beam Resting on an Elastic Foundation
Authors: Al-Qaisia A.A. , Hamdan M.N.
Published: June 2009

In this work we present an investigation into nonlinear frequency veering of an elastic Euler— Bernoulli beam resting on a Winkler elastic foundation subjected to a static lateral load and hinged—hinged, with a torsional spring at one end. The beam is assumed to have an initial quarter-sine shape rise owing to a constant differential edge settlement. The beam static deflection is obtained by using a combined numerical—analytical procedure that accounts for the induced nonlinear axial force to mid-plane stretching. The harmonic balance method is used to solve for the nonlinear natural frequency of the associated nonlinear temporal problem obtained using the assumed mode method. The results are presented in the form of characteristic curves which show variation of the nonlinear natural frequency of the three modes of a selected range of system parameters. These results indicate that, depending on the system parameters, the nonlinear natural frequency of various modes can exhibit complicated behaviors not found using linear analysis.
Slow Passage through Multiple Parametric Resonance Tongues
Authors: Bridge Jacqueline , Rand Richard , Sah Si Mohamed
Published: June 2009

This work concerns linear parametrically excited systems that involve multiple resonances. The property of such systems is that if the parameters are fixed and lie inside a resonance tongue, the motion becomes unbounded as time goes to infinity. In this work we consider what happens when the parameters are not fixed, but rather are constrained to vary slowly in time, passing into and out of the resonance tongues. One might expect that during the time in which the motion lies inside a tongue the solution grows, and that the slower the passage through the tongue the more time is spent inside the tongue, and the larger the resulting growth. We show that this is not always the case. In particular we investigate the effect of initial conditions and relative forcing amplitudes on the growth or amplification of the solution. We address the problem of how to choose these parameters so as to minimize growth (i.e., to de-amplify the solution) after passage through multiple tongues.
Nonlinear Dynamic Response and Vibration Active Control of Piezoelectric Elasto-plastic Laminated Plates with Damage
Authors: Tian Yanping , Fu Yiming , Wang Yong
Published: June 2009

Based on the elasto-plastic mechanics and continuum damage theory, a yield criterion that is related to the spherical stress tensor is proposed to describe the mixed hardening of damaged orthotropic materials, the dimensionless form of which is isomorphic with the Mises criterion for isotropic materials. Furthermore, the incremental elasto-plastic damage constitutive equations and damage evolution equations of orthotropic materials are established. The electric potential distribution along the thickness direction of the piezoelectric sensor layer is determined by adopting the quadratic Lagrange interpolation, and the incremental electric charge equilibrium equation is built according to the Maxwell equation. In addition, by using the classical nonlinear plate theory, the incremental nonlinear dynamic governing equations of the piezoelectric elasto-plastic laminated plates with damage are obtained. Meanwhile, an analytical model for the vibration control of the system is proposed by introducing the negative velocity feedback control algorithm coupling the direct and converse piezoelectric effects. The finite difference method and the Newmark- β method are adopted to make the undetermined variables discretized in the space and time domains, respectively, and the whole problem is solved by the iterative method. In the numerical examples, the effects of damage, piezoelectricity, feedback control gain and the piezoelectric position on the nonlinear vibration of piezoelectric elasto-plastic laminated plates are discussed in detail, and the differences between the piezoelectric elastic laminated plates and piezoelectric elasto-plastic laminated plates are analyzed.
Carboplatin—gemcitabine in the therapy of advanced ovarian cancer: dose reduction consideration
Authors: Dasanu Constantin A , Herzog Thomas J , Alexandrescu Doru T
Published: June 2009

Carboplatin—gemcitabine doublet is an important therapeutic option for patients with both previously treated and untreated ovarian cancer (OC). At the currently recommended dosing, its main toxicity is hematological, consisting of thrombocytopenia, neutropenia, including febrile neutropenia, and/or anemia. The use of platelet transfusions, G-CSF and/ or packed red blood cells is often necessary, in order to avoid treatment delays or omission of doses. We report here on the high efficacy of lower doses of gemcitabine at 750 mg/m2 on days 1 and 8 in combination with carboplatin AUC = 4 on day 1, repeated in 21-day cycles, in a small series of patients with advanced/metastatic OC. Using the above dose regimen, durable complete remissions were achieved in all patients in our cohort within 9—12 weeks, with no growth factor support, and no transfusions of blood components being necessary. We believe that lowering the doses of both carboplatin and gemcitabine from the start of therapy would ensure their timely delivery and steady-state plasma drug levels. In conclusion, administration of carboplatin AUC = 4 and gemcitabine 750 mg/m2 appears to be a safe and effective combination for the therapy of advanced/metastatic OC, with clinically tolerable hematological toxicity.
Efficacy of aprepitant in patients receiving high-dose chemotherapy with hematopoietic stem cell support
Authors: Paul Betsy , Trovato James A , Thompson Jennifer , Badros Ashraf Z , Goloubeva Olga
Published: June 2009

Purpose. This study describes the efficacy of aprepitant in preventing nausea and vomiting associated with high-dose chemotherapy in hematopoietic stem cell transplant (HSCT) patients. Our hypothesis is the addition of aprepitant to 5-HT3 antagonists and dexamethasone would result in a 20% increase in complete response (CR) rates compared to CR rates from published studies evaluating antiemetic regimens without aprepitant.

Methods. Adult HSCT patients receiving high-dose chemotherapy and aprepitant as part of their antiemetic regimen were included following written informed consent. CR was defined as no emesis, none to mild nausea, and no breakthrough antiemetic use. Daily patient diaries were used on days 1 through 7 following high-dose chemotherapy to collect severity of nausea, emetic episodes, breakthrough antiemetic use, and any antiemetic related side effects.

Results. We accrued a total of 42 patients. CR rates ranged from 42.9% to 73.8% for the 7 days. The average CR rate for days 1 through 7 was 54%. Fourteen patients (33%) maintained a complete emetic response on each of the 7 days. The average CR rate for published studies in HSCT patients receiving an antiemetic regimen without aprepitant is 57%. Most common adverse effects reported by patients receiving aprepitant were hiccups (33%) and drowsiness (33%).

Conclusions. The addition of aprepitant failed to meet our primary endpoint of increasing CR rates by 20%. The lower than expected CR rate was attributed to use of breakthrough antiemetics. Aprepitant did result in preventing emesis in the majority of patients and was associated with minimal side effects.
Review Article: Second-generation thrombopoietin agents for treatment of chronic idiopathic thrombocytopenic purpura in adults
Authors: Lam Masha SH
Published: June 2009

Objective. To review the pharmacology, pharmacokinetics, efficacy, and safety of two new thrombopoietic (TPO) receptor agonists, romiplostim and eltrombopag, in the treatment of chronic idiopathic thrombocytopenic purpura (ITP) in adults.

Data sources. A MEDLINE search was conducted (1966 to March 2009) using the search terms romiplostim, AMG 531, eltrombopag, SB-497115, idiopathic thrombocytopenic purpura. Articles on phases 1—3 clinical trials in patients with ITP were identified and reviewed. References from manufacturer information, and abstracts from recent hematology meetings, were also evaluated.

Study selection and data extraction. Controlled clinical trials evaluating romiplostim and eltrombopag for treatment of chronic ITP in adults were selected from the data sources. All published relevant abstracts were also included.

Data synthesis. Limited randomized controlled trials and open-label ongoing long-term extension studies for romiplostim and eltrombopag, have shown that both TPO agonists are effective in improving the platelet count and reducing the bleeding episodes in adult patients with ITP unresponsive to at least one standard treatment. The most common adverse events associated with the drugs are mild to moderate headaches. The use of these agents has also been associated with rare but serious side-effects including bone marrow reticulin fibrosis, thrombotic events, and myeloid malignancies.

Conclusions. Until more long-term follow-up data regarding the safety, as well as comparative studies that further define the role of TPO agonists versus other agents in the treatment of chronic ITP are available, these agents should be reserved for patients with ITP refractory or intolerant to standard therapy. J Oncol Pharm Practice (2010) 16: 89—103.
Arsenic trioxide associated toothache
Authors: Siderov Jim , Duggan John
Published: June 2009

Arsenic trioxide in the treatment of acute promyelocytic leukaemia is relatively safe with minimal side effects. Dental toxicities associated with its use are uncommon. We describe the first case report of toothache associated with arsenic trioxide. A 45-year-old male with relapsed APL was commenced on a treatment schedule of all-trans-retinoic acid 20mg four times a day for 14 days concurrent with a 10mg intravenous infusion of arsenic trioxide for 28 days. After 14 doses of the 6th cycle of treatment he experienced severe acute pain in various parts of the oral cavity. Extensive examination including an orthodontic review concluded there was no indication that the pain symptoms were due to a dental or endodontic cause. Four days after completing his 6th cycle the pain completely resolved. The mechanism of this adverse event remains unclear. Physicians with patients receiving arsenic trioxide with unexplained toothache should consider the arsenic as the cause of the pain. J Oncol Pharm Practice (2010) 16: 127—128.
Disaggregating Race and Ethnicity
Authors: Ward Beverly G.
Published: June 2009

This paper provides an overview of the differences in and among ethnic and racial subgroups of the U.S. population and the intersections of these with age, functionality, geography, and so forth. The focus is on system demand, but, suggests some workforce and safety implications. Where racial and ethnic minorities experience lack of access and mobility due to geographic isolation, income, and limited mental and physical functionality, adverse health outcomes may be anticipated. Transport's role in increasing access and mobility may aid in offsetting or mitigating these adverse effects. The survey of conditions among racial and ethnic minorities suggests that greater investments in pedestrian and bicycle facilities and human service and public transport may serve to mitigate some of the conditions. These considerations are critical given the aging and “browning” of the U.S. population.
Evaluation of the Developmental Toxicity of 1-(1,2,3,4,5,6,7,8-Octahydro-2,3,8, 8-Tetramethyl-2-Naphthalenyl) Ethanone (OTNE) in Rats
Authors: Politano Valerie T. , Letizia Charlene S. , Christian Mildred S. , Diener Robert M. , Api Anne Marie
Published: June 2009

The developmental toxicity of 1-(1,2,3,4,5,6,7,8-Octahydro-2,3,8,8-tetramethyl-2-naphthalenyl) ethanone (OTNE), a widely used fragrance ingredient, was evaluated in pregnant Sprague-Dawley rats (25/group) gavaged with dosages of 0 (water), 96, 240, or 480 mg/kg/d on days 7 through 17 of gestation (GDs 7–17). Rats were observed for clinical signs, abortions, premature deliveries, body weights, and feed intake. Caesarean section and necropsy were performed on GD 21. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. No deaths or premature deliveries were attributed to OTNE. OTNE-related clinical signs included significantly increased incidences of excessive salivation in all 3 treatment groups, and urine-stained abdominal fur in the high dosage group. Mean body weight gains were significantly reduced by all OTNE dosages on GDs 7–10, while at 480 mg/kg/d, significant reductions continued through the remainder of the dosage period. Feed consumption generally paralleled body weight gains. Fetal body weights were reduced by 480 mg/kg/d, but not to a statistically significant degree. No fetal gross external, soft tissue, or skeletal malformations or variations were attributable to OTNE. Based on these data, maternal and developmental no-observable-adverse-effect-levels (NOAELs) of 240 mg/kg/d were established for OTNE. It was concluded that OTNE is not a developmental toxicant in rats under the conditions of this study, and that a margin of safety greater than 2700 exists between reversible developmental delays in rats and the calculated daily human exposure level of 0.086 mg/kg/d.
Development of a High-Throughput Human HepG2 Dual Luciferase Assay for Detection of Metabolically Activated Hepatotoxicants and Genotoxicants
Authors: Liu Xuemei , Kramer Jeffrey A. , Hu Yi , Schmidt James M. , Jiang Jianghong , Wilson Alan G. E.
Published: June 2009

Hepatic toxicity remains a major concern for drug failure; therefore, a thorough examination of chemically induced liver toxicity is essential for a robust safety evaluation. Current hypotheses suggest that the metabolic activation of a drug to a reactive intermediate is an important process. In this article, we describe a new high-throughput GADD45β reporter assay developed for assessing potential liver toxicity. Most importantly, this assay utilizes a human cell line and incorporates metabolic activation and thus provides significant advantage over other comparable assays used to determine hepatotoxicity. Our assay has low compound requirement and relies upon 2 reporter genes cotransfected into the HepG2 cells. The gene encoding Renilla luciferase is fused to the CMV promoter and provides a control for cell numbers. The firefly luciferase gene is fused to the GADD45β promoter and used to report an increase in DNA damage. A dual luciferase assay is performed by measuring the firefly and Renilla luciferase activities in the same sample. Results are expressed as the ratio of the 2 luciferase activities; increases over the control are interpreted as evidence of stress responses. This mammalian dual luciferase reporter has been characterized with, and without, metabolic activation using positive and negative control agents. Our data demonstrate that this assay provides for an assessment of potential toxic metabolites, is adaptable to a high-throughput platform, and yields data that accurately and reproducibly detect hepatotoxicants.
An Optimized Shape Parameter Radial Basis Function Formulation for Composite and Sandwich Plates using Higher Order Formulations
Authors: Roque C.M.C. , Ferreira A.J.M. , Jorge R.M.N.
Published: June 2009

The purpose of this work is to use a meshless collocation method with multiquadric radial basis functions (RBFs) and optimal values of the shape parameter in the RBFs to analyze static deformations of sandwich and composite plates. Two shear deformation theories with the same number of degrees of freedom are tested (the third-order shear deformation theory of Reddy (TSDT) and a trigonometric layerwise theory). Although the TSDT proved to be most adequate for the analysis of composite plates, the same is not true for sandwich plates, specially in the case of large ratios of material properties between the core and face sheets. The trigonometric layerwise theory produced excellent results for both sandwich and composite plates. The multiquadric RBF method was introduced by Kansa [1,2] for solving boundary-value problems governed by partial differential equations. Here we show that this method with optimal values of the shape parameter gives deflections of sandwich and composite plates that agree very well with analytical solutions, for regular and irregular grids. An advantage of the meshless method is that it requires very little input data, thus the time required for preparing the data can be significantly reduced.
Modified Metallic Octet Truss Cellular Cores for Sandwich Structures Fabricated by an Expanded Metal Forming Process
Authors: Joo Jai-Hwang , Kang Ki-Ju
Published: June 2009

A new idea for fabricating a truss periodic cellular metal (PCM) is described. Namely, an octet-like truss PCM named ‘M-octet’ is fabricated by folding expanded metals. Its strengths under compression and shear load estimated by elementary mechanics are compared with experimental results and those of other competing cellular metals. When employed as a core in a sandwich panel, the load capacity subjected to bending load is predicted by an energy-based approach for various failure modes. For a given core height, a failure mode map is constructed with the nondimensional parameters such as geometric variables, material parameter (yield strain), load index, and weight index. Based on the failure mode map, three designs are chosen for maximum load per weight ratio. The predicted failure loads for the three different geometric designs are compared with the values measured through the experiments which are performed with sandwich specimens with the tetrahedral truss cores made of a wrought steel SS41. The measured equivalent normal yield and shear yield stresses agree fairly well with those predicted by the analytic solutions. In the three-point bending tests, the design with the thickest core truss and face sheets shows the peak load point delayed the most, which gives benefits in terms of the energy absorption and deformation stability after the peak load point.
A New 2D Local Vibrational Model for Unidirectional Clamped—Clamped Sandwich Structure with Edge Stiffeners
Authors: Karczmarzyk Stanisław
Published: June 2009

Flexural vibration of a clamped—clamped, three-layer, one-span sandwich, unidirectional structure composed of isotropic layers is considered in the article. A new single series model of the 2D problem, obtained within the local theory of linear elastodynamics, is presented. Very realistic boundary conditions at edges of the structure, which correspond to the engineering solution with the edge stiffeners, are introduced and satisfied. Eight eigenfrequencies of the structure for two sets of input data are calculated, according to the new model, and compared with numerical and experimental results existing in the literature. A detail comparative analysis of the results is done and some conclusions are presented.
Multilayer Damping Treatments: Modeling and Experimental Assessment
Authors: Moreira R.A.S. , Dias Rodrigues J.
Published: June 2009

The sandwich panels with viscoelastic cores, which represent the physical application of the viscoelastic integrated damping treatment concept, associate different materials, each one having a specific structural contribution, where the outside faces, usually made from a stiff material, guarantee the stiffness of the composite structure whereas the viscoelastic and soft core provides the damping capability. The application of soft cores, specially the thick ones, into sandwich plates produces an important decoupling effect, leading to a significant flexural stiffness reduction of the sandwich plate, as experimental and numerical results evidence. From this observation and pursuing a solution to minimize such effect, the partitioning of the core layer into multiple layers separated by thin constraining layers is hereby considered. Taking advantage of the application of the multiple viscoelastic layers in the sandwich core, it is also analyzed the potential use of different viscoelastic materials in order to spread out the efficient temperature range of the damping treatment. To verify and evaluate the effects of the multilayer and multi-material viscoelastic cores in sandwich panels, an experimental and a numerical study were conducted on specimens representative of these design concepts. The results achieved from this study demonstrate the applicability of the two multiple layer configurations, evidencing the effect of the partitioning procedure of the core onto the reduction of the bending stiffness decay and the efficient temperature range enlargement when adopting viscoelastic materials with different transition temperatures.
The Importance of Perceived Task Difficulty in Goal Orientation—Assigned Goal Alignment
Authors: Gerhardt Megan W. , Luzadis Rebecca A.
Published: June 2009

This study investigated the moderating effect of perceived task difficulty on the relationship between goal alignment and task performance. Using a sample of 131 participants, the relationship between trait learning goal orientation, assigned goal condition, and task performance was assessed. Results indicated that goal alignment was not significantly related to task performance overall. Perceived task difficulty did significantly moderate this relationship.
The Emergence of Business-to-Consumer E-Commerce
Authors: Tangpong Chanchai , Islam Muhammad , Lertpittayapoom Nongkran
Published: June 2009

This study examines the emergence of business-to-consumer (B2C) e-commerce from new niche formation, creative destruction, and contingency perspectives. Based on multiretail-sector data, this study supports the contingency perspective. The findings suggest that in digitally related sectors, B2C e-commerce has emerged through a creative destruction process whereby B2C e-commerce expands at the expense of traditional retailing; thus, addressing the e-commerce trend becomes traditional firms’ strategic imperative. Conversely, in digitally unrelated sectors, B2C e-commerce has emerged through a new niche formation process whereby B2C e-commerce coexists with traditional retailing; thus, embracing the e-commerce trend becomes the traditional firms’ strategic choice.
New Hybrid Approach for NOTES Transvaginal Cholecystectomy: Preliminary Clinical Experience
Authors: DeCarli Luiz Alberto , Zorron Ricardo , Branco Alcides , Lima Fernando Cirme , Tang Marcos , Pioneer Sergio Ricardo , Sanseverino José Inácio , Menguer Rodrigo , Bigolin André Vicente , Gagner Michel
Published: June 2009

Objectives. Natural orifice translumenal endoscopic surgery (NOTES) represents the first step toward scar-less surgery. The objective of this study is to evaluate early clinical results of transvaginal cholecystectomy using a new technique. Methods. Institutional review board approval was obtained and transvaginal NOTES cholecystectomy was performed in 12 women for cholelithiasis. A 2-channel videoendoscope was inserted in the abdominal cavity through a posterior colpotomy. Two 3-mm trocars were inserted deep in the umbilicus, and a 10-mm trocar was placed through the colpotomy parallel to the endoscope. Dissection was performed with endoscopic instruments combined with 3-mm laparoscopic instruments. Results. Mean operative time was 125.8 minutes. All procedures occurred without intraoperative complications or conversions, except for 1 vulvar laceration. There were no postoperative complications in the clinical follow-up. Conclusion. Transvaginal NOTES is a feasible and safe alternative for cholecystectomy in this preliminary clinical experience, allowing good cosmetic benefits and low analgesic requirement.
Minor histocompatibility antigens on transfused leukoreduced units of red blood cells induce bone marrow transplant rejection in a mouse model
Authors: Desmarets Maxime , Cadwell Chantel M. , Peterson Kenneth R. , Neades Renee , Zimring James C.
Published: June 2009

When successful, human leukocyte antigen (HLA)–matched bone marrow transplantation with reduced-intensity conditioning is a cure for several nonmalignant hematologic disorders that require chronic transfusion, such as sickle cell disease and aplastic anemia. However, there are unusually high bone marrow transplant (BMT) rejection rates in these patients. Rejection correlates with the number of transfusions before bone marrow transplantation, and it has been hypothesized that preimmunization to antigens on transfused blood may prime BMT rejection. Using a novel mouse model of red blood cell (RBC) transfusion and major histocompatibility complex–matched bone marrow transplantation, we report that transfusion of RBC products induced BMT rejection across minor histocompatibility antigen (mHA) barriers. It has been proposed that contaminating leukocytes are responsible for transfusion-induced BMT rejection; however, filter leukoreduction did not prevent rejection in the current studies. Moreover, we generated a novel transgenic mouse with RBC-specific expression of a model mHA and demonstrated that transfusion of RBCs induced a CD8+ T-cell response. Together, these data suggest that mHAs on RBCs themselves are capable of inducing BMT rejection. Cellular immunization to mHAs is neither monitored nor managed by current transfusion medicine practice; however, the current data suggest that mHAs on RBCs may represent an unappreciated and significant consequence of RBC transfusion.
Speech target modulates speaking induced suppression in auditory cortex
Authors: Ventura Maria I , Nagarajan Srikantan S , Houde John F
Published: June 2009

Background

Previous magnetoencephalography (MEG) studies have demonstrated speaking-induced suppression (SIS) in the auditory cortex during vocalization tasks wherein the M100 response to a subject's own speaking is reduced compared to the response when they hear playback of their speech.

Results

The present MEG study investigated the effects of utterance rapidity and complexity on SIS: The greatest difference between speak and listen M100 amplitudes (i.e., most SIS) was found in the simple speech task. As the utterances became more rapid and complex, SIS was significantly reduced (p = 0.0003).

Conclusion

These findings are highly consistent with our model of how auditory feedback is processed during speaking, where incoming feedback is compared with an efference-copy derived prediction of expected feedback. Thus, the results provide further insights about how speech motor output is controlled, as well as the computational role of auditory cortex in transforming auditory feedback.
Bioinformatic analysis of xenobiotic reactive metabolite target proteins and their interacting partners
Authors: Fang Jianwen , Koen Yakov M , Hanzlik Robert P
Published: June 2009

Background

Protein covalent binding by reactive metabolites of drugs, chemicals and natural products can lead to acute cytotoxicity. Recent rapid progress in reactive metabolite target protein identification has shown that adduction is surprisingly selective and inspired the hope that analysis of target proteins might reveal protein factors that differentiate target- vs. non-target proteins and illuminate mechanisms connecting covalent binding to cytotoxicity.

Results

Sorting 171 known reactive metabolite target proteins revealed a number of GO categories and KEGG pathways to be significantly enriched in targets, but in most cases the classes were too large, and the "percent coverage" too small, to allow meaningful conclusions about mechanisms of toxicity. However, a similar analysis of the directlyinteracting partners of 28 common targets of multiple reactive metabolites revealed highly significant enrichments in terms likely to be highly relevant to cytotoxicity (e.g., MAP kinase pathways, apoptosis, response to unfolded protein). Machine learning was used to rank the contribution of 211 computed protein features to determining protein susceptibility to adduction. Protein lysine (but not cysteine) content and protein instability index (i.e., rate of turnover in vivo) were among the features most important to determining susceptibility.

Conclusion

As yet there is no good explanation for why some low-abundance proteins become heavily adducted while some abundant proteins become only lightly adducted in vivo. Analyzing the directly interacting partners of target proteins appears to yield greater insight into mechanisms of toxicity than analyzing target proteins per se. The insights provided can readily be formulated as hypotheses to test in future experimental studies.