bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicological features of deliberate self-poisonings
Authors: Bentur Yedidia , Raikhlin-Eisenkraft Bianca , Lavee Michal
Published: July 2004

Background: Deliberate self-poisoning (DSP) is a major health problem with increasing incidence mainly among young people. Objective: To examine the clinical and toxicological characteristics of DSP, it is compared to unintentional (non-DSP) exposures and those characteristics which might be associated with increased toxicological risk are identified. Methods: Two-year retrospective poison centre chart review. Statistics: χ2 analysis. Results: 3802 DSP cases were reported. Most calls (95%) were made by physicians compared to 51%) in non-DSP exposures, P <0.0001. There were almost twice as many females as males, contrary to unintentional exposures (P <0.001). Peak frequency involvement was at the age of 15-20 years for females and older for males. Only 19.8%) of DSP calls were made within the first hour of exposure compared to 46%) of the non-DSP calls (P <0.001). Younger patients tended to present earlier. The vast majority of exposures occurred by ingestion and at home. Pharmaceuticals and chemicals were involved in 86% and 12% of DSP cases, respectively (compared to 29% and 44% in non-DSP exposures, respectively, P <0.001). Psychiatric drugs were more commonly used in older age groups and analgesics among the younger. Insecticides, sodium hypochlorite and rodenticides were the most frequently used chemicals. Neurological involvement was observed in 48.2% of DSP patients compared to 16.9% in non-DSP exposures. DSP was associated with greater severity than non-DSP exposures (21% and 10% had moderate to severe toxicity, respectively, P <0.001). Severity was greater among males, aged older than 45 years, with time from exposure to consultation 8 hours or longer and with exposure to chemicals, psychiatric drugs or combinations. Conclusions: Most DSP patients were females, aged 15-20 years, used pharmaceuticals and had neurological involvement. Males, aged over 45 years, with longer time to toxicology consult and the use of chemicals were associated with increased severity. These parameters should alert the treating physician to the possibility of a poor course and hence to a more aggressive therapeutic approach.
Dose dependency ofDisp1and genetic interaction betweenDisp1and other hedgehog signaling components in the mouse
Authors: Tian Hua , Tenzen Toyoaki , McMahon Andrew P.
Published: July 2004

Genetic analyses in Drosophila have demonstrated that a transmembrane protein Dispatched (Disp) is required for the release of lipid-modified Hedgehog (Hh) protein from Hh secreting cells. Analysis of Disp1 null mutant embryos has demonstrated that Disp1 plays a key role in hedgehog signaling in the early mouse embryo. Here we have used a hypomorphic allele in Disp1(Disp1Δ2), to extend our knowledge of Disp1 function in Hh-mediated patterning of the mammalian embryo. Through genetic combinations with null alleles of patched 1 (Ptch1),sonic hedgehog (Shh) and Indian hedgehog (Ihh), we demonstrate that Disp1 genetically interacts with Hh signaling components. As Disp1 activity is decreased we see a progressive increase in the severity of hedgehog-dependent phenotypes, which is further enhanced by reducing hedgehog ligand levels. Analysis of neural tube patterning demonstrates a progressive loss of ventral cell identities that most likely reflects decreased Shh signaling as Disp1 levels are attenuated. Conversely,increasing available Shh ligand by decreasing Ptch1 dosage leads to the restoration of ventral cell types in Disp1Δ2/Δ2 mutants. Together, these studies suggest that Disp1 actively regulates the levels of hedgehog ligand that are available to the hedgehog target field. Further, they provide additional support for the dose-dependent action of Shh signaling in patterning the embryo. Finally, in-vitro studies on Disp1 null mutant fibroblasts indicate that Disp1 is not essential for membrane targeting or release of lipid-modified Shh ligand.
Normal and aberrant craniofacial myogenesis by grafted trunk somitic and segmental plate mesoderm
Authors: Borue Xenia , Noden Drew M.
Published: July 2004

Our research assesses the ability of three trunk mesodermal populations– medial and lateral halves of newly formed somites, and presomitic(segmental plate) mesenchyme – to participate in the differentiation and morphogenesis of craniofacial muscles. Grafts from quail donor embryos were placed in mesodermal pockets adjacent to the midbrain-hindbrain boundary,prior to the onset of neural crest migration, in chick host embryos. This encompasses the site where the lateral rectus and the proximal first branchial arch muscle primordia arise. The distribution and differentiation of graft-derived cells were assayed using QCPN and QH1 antibodies to identify all quail cells and quail endothelial cells, respectively. Chimeric embryos were assayed for expression of myf5, myod, paraxis and lbx1, and the synthesis of myosin heavy chain (MyHC), between 1 and 6 days later (stages 14-30). Heterotopic and control (orthotopic) transplants consistently produced invasive angioblasts, and contributed to the lateral rectus and proximal first branchial arch muscles; many also contributed to the dorsal oblique muscle. The spatiotemporal patterns of transcription factor and MyHC expression by these trunk cells mimicked those of normal head muscles. Heterotopic grafts also gave rise to many ectopic muscles. These were observed in somite-like condensations at the implant site, in dense mesenchymal aggregates adjacent to the midbrain-hindbrain boundary, and in numerous small condensations scattered deep to the dorsal margin of the eye. Cells in ectopic condensations expressed trunk transcription factors and differentiated rapidly, mimicking the trunk myogenic timetable. A novel discovery was the formation by grafted trunk mesoderm of many mononucleated myocytes and irregularly oriented myotubes deep to the eye. These results establish that the head environment is able to support the progressive differentiation of several distinct trunk myogenic progenitor populations, over-riding whatever biases were present at the time of grafting. The spatial and temporal control of head muscle differentiation and morphogenesis are very site specific, and head mesoderm outside of these sites is normally refractory to, or inhibited by, the signals that initiate ectopic myogenesis by grafted trunk mesoderm cells.
Instrumentation for wet steam
Authors: Kleitz A , Dorey J M
Published: July 2004

This paper is devoted to the measuring methods and instrumentation used in the wet-steam area for both aerodynamics measurements (pressure, temperature and velocity) taking into account the interaction between the vapour and the liquid phase, and the characterization of the liquid phase itself (dispersed phase and liquid film). The development of suitable instrumentation is an important part in understanding the formation and evolution of the liquid phase but is now more and more oriented towards practical industrial concerns, such as the direct determination of turbine performance by measuring exhaust wetness or chemical measurements relating to erosion in the transition zone inside the turbine. Emphasis has been given to techniques suitable for use in actual turbines.
Irreversible Decisions and Record-Setting News Principles
Authors: Boyarchenko Svetlana
Published: July 2004

In the now-classical real options theory, the price of an underlying asset is modeled as a geometric Brownian motion, and optimal exercise strategies are described by simple explicit formulas. This paper extends the classical theory to allow any geometric Lévy process to model prices. Such processes may account for fat tails and skewness of probability distributions of commodity prices. The optimal exercise strategies are specified in the paper in terms of statistics of record-setting low or high prices. The formulas derived extend those observed in the Gaussian case, but the form of the result is novel even for that case.
The Role of Social Capital in Financial Development
Authors: Guiso Luigi , Sapienza Paola , Zingales Luigi
Published: July 2004

To identify the effect of social capital on financial development, we exploit social capital differences within Italy. In high-social-capital areas, households are more likely to use checks, invest less in cash and more in stock, have higher access to institutional credit, and make less use of informal credit. The effect of social capital is stronger where legal enforcement is weaker and among less educated people. These results are not driven by omitted environmental variables, since we show that the behavior of movers is still affected by the level of social capital of the province where they were born.
In-Kind Finance: A Theory of Trade Credit
Authors: Burkart Mike , Ellingsen Tore
Published: July 2004

It is typically less profitable for an opportunistic borrower to divert inputs than to divert cash. Therefore, suppliers may lend more liberally than banks. This simple argument is at the core of our contract theoretic model of trade credit in competitive markets. The model implies that trade credit and bank credit can be either complements or substitutes. Among other things, the model explains why trade credit has short maturity, why trade credit is more prevalent in less developed credit markets, and why accounts payable of large unrated firms are more countercyclical than those of small firms.
Does Foreign Direct Investment Increase the Productivity of Domestic Firms? In Search of Spillovers Through Backward Linkages
Authors: Javorcik Beata Smarzynska
Published: July 2004

Many countries strive to attract foreign direct investment (FDI) hoping that knowledge brought by multinationals will spill over to domestic industries and increase their productivity. In contrast with earlier literature that failed to find positive intraindustry spillovers from FDI, this study focuses on effects operating across industries. The analysis, based on firm-level data from Lithuania, produces evidence consistent with positive productivity spillovers from FDI taking place through contacts between foreign affiliates and their local suppliers in upstream sectors. The data indicate that spillovers are associated with projects with shared domestic and foreign ownership but not with fully owned foreign investments.
Efficient Patent Pools
Authors: Lerner Josh , Tirole Jean
Published: July 2004

The paper builds a tractable model of patent pools, agreements among patent owners to license sets of their patents. It provides a necessary and sufficient condition for patent pools to enhance welfare and shows that requiring pool members to be able to independently license patents matters if and only if the pool is otherwise welfare reducing. The paper allows patents to differ in importance, asymmetric blocking patterns, and licensors to also be licensees. We undertake some initial exploration of the impact of pools on innovation. The analysis has broader applicability than pools, being relevant to a number of co-marketing arrangements.
Liquidity, Efficiency, and Bank Bailouts
Authors: Gorton Gary , Huang Lixin
Published: July 2004

Governments can efficiently provide liquidity, as when the banking system is bailed out. We study a model in which not all assets can be used to purchase all other assets at every date. Agents sometimes want to sell projects. The market price of the projects sold depends on the supply of liquidity, which is determined in general equilibrium. While private liquidity provision is socially beneficial since it allows valuable reallocations, it is also socially costly since liquidity suppliers could have made more efficient investments ex ante. There is a role for the government to supply liquidity by issuing government securities.
Estimating the Calorific Values of Lignocellulosic Fuels
Authors: Demirbaş Ayhan , Demirbaş A. Hilal
Published: July 2004

Ultimate analysis based mathematical models are the most reported with Dulong's equation being among the first available to calculate the calorific value of coal or biomass. The higher heating value (HHV) at constant pressure measures the enthalpy change of combustion with water condensed. The HHVs (MJ/kg) of the lignocellulosic fuels as a function of carbon (C) or carbon + hydrogen (C + H) contents (wt%) were calculated using the following equations:

[Formula: see text]

[Formula: see text]

for Equations (1 and 2) which in square of the correlation coefficients (r2) were 0.9734 and 0.9814, respectively. There is a highly significant correlation between the HHV of the lignocellulosic fuels and their carbon or (carbon + hydrogen) contents.
Environmental Concerns: Catastrophic Events and Insurance. II. Applications of Hydrocarbon Risking Procedures to other Fields
Authors: Lerche Ian , Lempp Christof
Published: July 2004

With ongoing reduction of engagement of public authorities in infrastructure development, private companies have to consider their responsibility in the case of catastrophic events, i.e. they must be aware of, and be able to calculate and finance, the kinds of risks that formerly were handled by the public authorities. This paper discusses the environmental costs and insurance needed in the cases of catastrophic failure of a project due either to natural causes as the project is being developed or after it is underway in an operating mode. Anthropogenic catastrophes also can occur and these, too, are considered from the viewpoint of insurance cover needed. A third sort of catastrophe can occur if regulations are changed during development of a project or after the project is in operation. In all cases a corporation involved in such projects needs to figure out how much insurance to take out against the possibility of a catastrophe and also the premium it should pay. Using examples from the tunnel construction theater of operations, from oil exploration and field development, and from regulatory changes that can influence waste disposal procedures, this paper shows how general procedures, developed to accommodate for such risk in operating systems in the hydrocarbon area, can be used almost as is in other fields and they also provide procedures for correctly allowing for catastrophic events to be included in assessing probable profitability and associated insurance needs at the same time. Numerical illustrations are given to illuminate the points being made as clearly as possible. The basic point made is that procedures developed for hydrocarbon risk assessment can be equally used, almost without change, in many other areas where risk is a concern.
Finite Difference Simulation of a Flexible Plate Structure
Authors: Darus I. Z. Mat , Tokhi M. O.
Published: July 2004

In this paper, an investigation into the dynamic characterisation of a two dimensional (2D) flexible structure is presented. A thin, flat plate, with all edges clamped, is considered. A simulation algorithm characterising the dynamic behaviour of the plate is developed through a discretisation of the governing partial differential equation formulation of the plate dynamics using finite difference methods. The algorithm is implemented within the Matlab environment, and it allows application and sensing of a disturbance signal at any mesh point on the plate. Such a provision is desirable for the design and development of active vibration control techniques for the system. The performance of the developed algorithm in characterising the dynamic behaviour of the system is assessed in comparison with previously reported results using various other methods. The validation of the algorithm is presented in both the time and frequency domains. Investigations reveal that the measured parameters associated with the first five resonance modes of the system compare favourably with previously reported results. The simulation algorithm thus developed and validated forms a suitable test and verification platform in subsequent investigations for development of active vibration control strategies for flexible plate structures.
Reduction of the Radiated Sound Using the Acoustic Prediction Filter
Authors: Hong Jin-Seok , Oh Jae-Eung
Published: July 2004

In this paper, reduction of the radiated sound from a vibrating rectangular plate is studied using the Acoustic Prediction Filter to estimate the radiated sound using the acceleration signals of the plate. A piezoceramic transducer (PZT) is used as an actuator to reduce the vibration and the radiated sound. To maximize the control performance, each PZT actuator is located at the position that has the largest control sensitivity of the plate bending moment in the direction of x and y coordinates and the optimal PZT location is validated experimentally. To find the acoustic prediction filter accurately, two accelerometers are located at the positions that have the largest radiation efficiencies of the plate, and the proposed locations are validated by simulation using the Rayleigh integral. The multi-channel filtered-x LMS algorithm is introduced to control a complex 2-D structural vibration mode. The control system using the acoustic prediction filter is presented and validated by experiments using a real time control system.
Sensorless IPMSM Drive with EKF Estimation of Speed and Rotor Position
Authors: Kosaka Manabu , Uda Hiroshi
Published: July 2004

In this paper, a new sensorless Interior Permanent Magnet Synchronous Motor (IPMSM) drive method with Extended Kalman Filtering (EKF) estimation of speed and rotor position is proposed. This method is on the basis of the sensorless Surface Permanent Magnet Synchronous Motor (SPMSM) drive [1] that can be applied to motors with no salient pole and is developed so as to be able to be applied to motors with salient pole such as IPMSM. Noise and vibration in mechanical plant becomes larger if rotor position estimation error occurs. Furthermore, the rotor position estimation error causes noise and vibration. The feature of the method is that rotor position estimation error does not occur even if motor current or motor voltage change. Therefore, the method can be applied with arbitrary motor voltage waveform and, consequently, the method is suitable for sensorless IPMSM drive.

Numerical simulations are illustrated to verify the effect of the method.
IT Outsourcing Strategies: Universalistic, Contingency, and Configurational Explanations of Success
Authors: Lee Jae-Nam , Miranda Shaila M. , Kim Yong-Mi
Published: July 2004

Focus on individual outsourcing decisions in IT research has often yielded contradictory findings and recommendations. To address these contradictions, we investigate a holistic, configurational approach with the prevailing universalistic or contingency perspectives in exploring the effects of IT outsourcing strategies on outsourcing success. Based on residual rights theory, we begin by identifying three dimensions of IT outsourcing strategies: degree of integration, allocation of control, and performance period. We then develop a model of fit-as-gestalt, drawing from literatures on strategy, governance, interorganizational relationships, and outsourcing.

Next, based on data from 311 firms in South Korea, we test universalistic and contingency perspectives in explaining the relationship between IT outsourcing strategies and outsourcing success. We then identify three congruent patterns, or gestalts, of IT outsourcing strategies. We term these strategies independent, arm's-length, and embedded strategies. To establish the predictive validity of these gestalts and the viability of a configurational perspective, we then explore the effects of these congruent gestalts vis-à-vis noncongruent patterns on three dimensions of outsourcing success: strategic competence, cost efficiency, and technology catalysis. We also contrast the effects of each of the three gestalts on each of the three dimensions of outsourcing success. Our findings indicate the superiority of the configurational approach over universalistic and contingency perspectives in explaining outsourcing success.
An Empirical Analysis of Network Externalities in Peer-to-Peer Music-Sharing Networks
Authors: Asvanund Atip , Clay Karen , Krishnan Ramayya , Smith Michael D.
Published: July 2004

Peer-to-peer (P2P) file sharing networks are an important medium for the distribution of information goods. However, there is little empirical research into the optimal design of these networks under real-world conditions. Early speculation about the behavior of P2P networks has focused on the role that positive network externalities play in improving performance as the network grows. However, negative network externalities also arise in P2P networks because of the consumption of scarce network resources or an increased propensity of users to free ride in larger networks, and the impact of these negative network externalities—while potentially important—has received far less attention.

Our research addresses this gap in understanding by measuring the impact of both positive and negative network externalities on the optimal size of P2P networks. Our research uses a unique dataset collected from the six most popular OpenNap P2P networks between December 19, 2000, and April 22, 2001. We find that users contribute additional value to the network at a decreasing rate and impose costs on the network at an increasing rate, while the network increases in size. Our results also suggest that users are less likely to contribute resources to the network as the network size increases. Together, these results suggest that the optimal size of these centralized P2P networks is bounded—At some point the costs that a marginal user imposes on the network will exceed the value they provide to the network. This finding is in contrast to early predictions that larger P2P networks would always provide more value to users than smaller networks. Finally, these results also highlight the importance of considering user incentives—an important determinant of resource sharing in P2P networks—in network design.
Real Options and IT Platform Adoption: Implications for Theory and Practice
Authors: Fichman Robert G.
Published: July 2004

The decision processes surrounding investments in innovative information technology (IT) platforms are complicated by uncertainty about expected payoffs and irreversibilities in the costs of implementation. When uncertainty and irreversibility are high, concepts from real options should be used to properly structure the evaluation and management of investment opportunities, and thereby capture the value of managerial flexibility. However, while innovation researchers have posited that option value can influence the motivations of early adopters, and options researchers have identified emerging IT as a promising area for application of options valuation techniques, there has yet to be a systematic theoretical integration of work on IT innovation and real options.

This paper seeks to fill this gap by developing a model of the determinants of option value associated with investments in innovative IT platforms. In so doing, the model addresses a central question in the innovation field: When should a firm take a lead role in innovation with emerging technologies? The analysis begins with an explanation of real options analysis and how it differs from conventional approaches for evaluating new technologies. Then a set of 12 factors—drawn from 4 complementary perspectives on organizational innovation (technology strategy, organizational learning, innovation bandwagons, and technology adaptation)—is synthesized into a model of the option value of IT platform investments. Rationales are provided to explain the direct effects of these factors on option value, and selected interactions among the factors are also considered. Finally, the implications of the model are presented in three areas: predicting IT platform initiation and adoption, valuing IT platform options, and managing IT platform implementation.
Editorial Notes
Authors: Kemerer Chris F.
Published: July 2004

We are now halfway through my final year as editor in chief of ISR, and I am happy to report some good news with regards to turnaround time at the journal.
EU research and technological development programmes
Authors: Patrício Maria Teresa
Published: July 2004

This article traces and analyses the role of social science research in the European Union’s research and technological development programmes. The divisions of the scientific community along national and disciplinary boundaries have made organizing and mobilizing at the European
level difficult. In recent years, however, the contributions of social science to research and to policy have gained increased recognition, attaining substantial importance and visibility within the EU research and technological development framework programmes. Recognition of the potential
role of the social sciences and humanities in research and policy at the EU level has rapidly gained momentum with increasingly influential results that are evident in the field of science policy.
Together
Authors: Hu Brian
Published: July 2004

Abstract Chen Kaige's Together represents the tendency of American art houses and film festivals to celebrate foreign films that cling to outdated ideals of filmmaking and global exchange instead of works that push the boundaries of art and social critique. This review examines Together in light of that phenomenon and then places the film in the trajectory of Chen's oeuvre.
Emerging Options for Thromboprophylaxis After Orthopedic Surgery: A Review of Clinical Data
Authors: Lobo Bob L.
Published: July 2004

In four randomized, controlled studies of patients undergoing orthopedic surgery, the antithrombotic efficacy and safety of subcutaneous fondaparinux 2.5 mg once/day were compared with those of subcutaneous enoxaparin regimens that were approved by the United States Food and Drug Administration. In patients undergoing elective hip replacement surgery, fondaparinux significantly reduced the frequency of venous thromboembolism (VTE). However, in a second trial that compared fondaparinux with enoxaparin 30 mg twice/day beginning 12–24 hours after surgery, a 26% risk reduction in favor of fondaparinux was not statistically significant. In patients undergoing elective knee replacement surgery, fondaparinux significantly reduced the risk of VTE compared with enoxaparin without increasing the risk of clinically relevant bleeding, although the risk of major bleeding defined by the bleeding index was significantly higher with fondaparinux. Fondaparinux was superior to enoxaparin 40 mg once/day in the setting of hip fracture surgery, with no increased risk of major bleeding. Meta‐analysis of the four studies confirms the superior antithrombotic efficacy of fondaparinux over enoxaparin in orthopedic surgery and suggests that the risk of major bleeding is similar to that of enoxaparin when the first dose of fondaparinux is given at least 6 hours after surgery.
Evidence for Extended Prophylaxis in the Setting of Orthopedic Surgery
Authors: Dobesh Paul P.
Published: July 2004

Patients undergoing orthopedic surgery represent one of the highest risk groups for the development of venous thromboembolism (VTE). Evidence shows that this risk extends beyond the period in which the patient is hospitalized, especially for patients undergoing hip surgery. Clinical trials have shown that extended prophylaxis with the low‐molecular‐weight heparins is effective in reducing the rate of total VTE, and a meta‐analysis demonstrated a reduction in symptomatic VTE with extended prophylaxis after total hip replacement surgery. Based on these results, the American College of Chest Physicians gives a grade 2A recommendation for the use of extended prophylaxis after orthopedic surgery. Until recently, data evaluating the role of prophylaxis in patients undergoing hip fracture surgery were limited. Subsequently, a novel anticoagulant, fondaparinux, demonstrated significant benefit in these patients and has become the first and only agent approved by the United States Food and Drug Administration (FDA) for use in patients undergoing hip fracture surgery. Despite the limitations of the older trials, their findings supported the need to evaluate extended prophylaxis in patients undergoing hip fracture surgery. In the first well‐conducted trial of extended prophylaxis for hip fracture surgery, fondaparinux provided impressive results in reducing total and symptomatic VTE. The results of this trial have once again led to fondaparinux being the first and only agent to be granted FDA approval for the indication of extended prophylaxis in patients undergoing hip fracture surgery.
Evolving Concepts in the Treatment of Venous Thromboembolism: The Role of Factor Xa Inhibitors
Authors: Nutescu Edith A. , Helgason Cathy M.
Published: July 2004

Anticoagulation is an essential component of the care of patients with venous thromboembolism (VTE). Traditional anticoagulants for the treatment of VTE include unfractionated heparin (UFH), low‐molecular‐weight heparin (LMWH), and the oral vitamin K antagonist, warfarin. A variety of anticoagulant agents with improved pharmacologic and clinical profiles are emerging and offer benefits over the traditional therapies. One of the most recent advances has been the development of new agents, such as oral direct thrombin inhibitors and factor Xa inhibitors, that have a more selective and targeted effect on the coagulation cascade. Recent clinical trials have evaluated fondaparinux, the first commercially available factor Xa inhibitor, in the treatment of patients with deep vein thrombosis and pulmonary embolism and indicate efficacy and safety as compared with traditional options such as UFH and LMWH. Fondaparinux is a welcomed addition to the available antithrombotic options.
Special Considerations with Fondaparinux Therapy: Heparin‐Induced Thrombocytopenia and Wound Healing
Authors: Dager William E. , Andersen Judith , Nutescu Edith
Published: July 2004

Multiple options for anticoagulation therapy are now available, placing an additional responsibility on health care workers for choosing the optimal therapy for each patient. The heparins carry a risk of heparin‐induced thrombocytopenia (HIT), an immune‐mediated reaction to heparin that may lead to pulmonary embolism and death. Fondaparinux, a new, synthetic pentasaccharide, binds to antithrombin III and potentiates antithrombin III's inhibition of factor Xa. Fondaparinux does not bind to platelet factor 4 and thus is theoretically unable to cause immunoallergic HIT. Unlike low‐molecular‐weight heparins, fondaparinux does not cross‐react in vitro with sera from patients with clinical cases of HIT. These findings suggest that fondaparinux would not lead to formation of HIT antibodies and would not provoke clinical thrombosis in patients who had HIT antibodies because of previous exposure to heparins. To date, no cases of immunoallergic HIT have been associated with fondaparinux use in clinical trials. Anecdotal evidence suggests that fondaparinux eventually may prove to be valuable for preventing and treating thrombosis in patients with HIT. The effect of anticoagulants on wound healing is another consideration when choosing a thromboprophylactic strategy after major surgery. There is evidence that thrombin plays a role in wound healing, but fondaparinux is too small to enable antithrombin III to inhibit thrombin. Thus, fondaparinux may be less likely than a low‐molecular‐weight heparin to interfere with wound healing.
Heparin Overview and Issues
Authors: Bussey Henry , Francis John L. ,   Heparin Consensus Group
Published: July 2004

Unfractionated heparin (UFH), which has been available commercially for over half a century, has been the most widely used agent for quickly suppressing thrombosis. When given intravenously, UFH quickly binds to and activates antithrombin, which then inhibits several activated factors in the clotting cascade. For decades, UFH was invaluable for treating arterial and venous thrombosis, and no alternative was available. The short half‐life of UFH and the fact that its action could be reversed readily with protamine made it an almost ideal antithrombotic agent. However, variable pharmacokinetics, together with problems of inaccuracy and unreliability of the activated partial thromboplastin time, have made it difficult to use this drug optimally. In addition, side effects such as osteoporosis, heparin‐induced thrombocytopenia (HIT), and delayed HIT have led to increased concerns about the use of UFH in view of the advantages offered by newer agents. Fractionating heparin into low‐molecular‐weight heparins that still retain the pentasaccharide active site provided a way to achieve the same type of therapeutic effect with more predictable dosing and fewer adverse effects. Similarly, a pentasaccharide has been synthesized and marketed as fondaparinux. Although these advances have improved our therapeutic options, continued advances on the horizon raise the question of whether the use of UFH will soon be abandoned.
Challenges in Variation and Responsiveness of Unfractionated Heparin
Authors: Francis John L. , Groce James B. ,   Heparin Consensus Group
Published: July 2004

Unfractionated heparin (UFH) has been in clinical use for more than half a century. Despite its undoubted contribution to the treatment and prevention of thrombosis, heparin is significantly limited by its variable biochemical composition and unpredictable pharmacokinetics. The situation is compounded by the fact that methods for monitoring heparin do not necessarily reflect its therapeutic effect. The activated partial thromboplastin time (aPTT) is a method for monitoring heparin therapy that is simple, cheap, and readily available. However, it is also poorly standardized and is affected by numerous factors—both analytic and preanalytic—that are unrelated to the heparin effect. Establishing an appropriate therapeutic range for the aPTT is challenging for smaller clinical laboratories, and the antifactor Xa method of measuring heparin levels is not widely available. The College of American Pathologists published consensus guidelines in an effort to improve the laboratory monitoring of UFH therapy. However, it seems unlikely that the laboratory problems associated with monitoring UFH will be resolved. Unfractionated heparin is highly antigenic and carries a significant risk of heparin‐induced thrombocytopenia (HIT). Even in the absence of thrombocytopenia or thrombosis, the presence of heparin‐associated antibodies may predict adverse clinical outcomes and strengthen the rationale for the ultimate replacement of UFH. Fortunately, alternatives to UFH, such as low‐molecular‐weight heparins, direct thrombin inhibitors, and more specific factor Xa inhibitors, are becoming available for clinical use. The pharmacokinetics of these agents are more predictable and rely much less on laboratory monitoring. Nonheparin agents also eliminate the risk of HIT. The emergence of these newer anticoagulants makes the continued use of UFH increasingly difficult to justify.
Treatment of Venous Thromboembolism: Challenging the Unfractionated Heparin Standard
Authors: Nutescu Edith , Singh‐Khalsa Manider ,   Heparin Consensus Group
Published: July 2004

Venous thromboembolism (VTE) is a major public health problem leading to high morbidity and mortality in the United States. Since more then 50% of patients with VTE may have asymptomatic disease, the start of appropriate therapy often is delayed. Traditionally, intravenous unfractionated heparin (UFH) has been used to manage the acute phase of VTE. Although an effective agent, numerous limitations are associated with the use of UFH therapy, such as the need for careful monitoring and frequent dosing adjustments. In addition, the assay used to monitor UFH—the activated partial thromboplastin time (aPTT)—does not correlate reliably with plasma heparin levels or antithrombotic activity. In the early 1990s, the low‐molecular‐weight heparins (LMWHs) emerged as alternative anticoagulants to UFH and began to successfully challenge the UFH standard for treatment of VTE. Clinical evidence has consistently demonstrated that LMWHs given subcutaneously are at least as safe and as effective, if not better, than intravenous UFH. This anticoagulant class has a much more predictable dose‐response relationship, requires little or no monitoring, and provides cost‐saving opportunities for outpatient management of VTE. The LMWHs are now considered the treatment of choice for many patients with VTE and are largely replacing UFH for this indication. In the last decade, additional agents, such as direct thrombin inhibitors and factor Xa inhibitors, have emerged as potential future alternatives for treatment of VTE. As clinical data regarding these new agents for treatment of VTE continue to evolve, their role in clinical practice will be elucidated.
Unfractionated Heparin: A Nursing Dilemma
Authors: Oertel Lynn B. ,   Heparin Consensus Group
Published: July 2004

Nurses face challenges in all aspects of their practice, especially with administering and monitoring drugs in a safe, effective manner. Key factors known to affect drug administration include general drug knowledge, formal nurse education, continuing education needs, clinical experience, and the nationwide nursing shortage. Other factors are advances in technologic aids and quality improvement initiatives. Emphasis on patient safety is growing, especially as it relates to drug therapy and high‐alert drugs such as unfractionated heparin (UFH). Specific interventions related to UFH administration can enhance patient care management. Because nurses are at the site of direct patient care, they are often in an opportune position for identifying medication errors. At the same time, and most important, nurses need to collaborate with other health care professionals to actively develop solutions to minimize these errors. Adopting a systems approach and working collaboratively with an interdisciplinary team can result in improved patient outcomes.
Unreliability of International Normalized Ratio for Monitoring Warfarin Therapy in Patients with Lupus Anticoagulant
Authors: Rosborough Terry K. , Shepherd Michele F.
Published: July 2004

Study Objective. To compare the international normalized ratios (INRs) of patients positive for lupus anticoagulant and the INRs of control patients receiving warfarin therapy with equivalent therapeutic chromogenic factor X levels.

Design. Prospective case series.

Setting. A 625‐bed, adult, private, tertiary care teaching hospital.

Patients. Sixty‐eight outpatients positive for lupus anticoagulant and 57 control patients receiving long‐term warfarin therapy.

Measurements and Main Results. Concomitant INR and chromogenic factor X activity were measured in all patients. In 44 control patients (77%) and 46 patients with lupus anticoagulant (68%), chromogenic factor X activity was 22–40% of normal, which is therapeutic. Of the 44 control patients, 4 (9%) had an INR above 3.0, and none had an INR above 4.0. In contrast, 18 (39%) of the 46 patients with lupus anticoagulant had an INR above 3.0, and 5 (11%) had an INR above 4.0.

Conclusion. At least 10% of patients with lupus anticoagulant receiving long‐term warfarin therapy may have falsely high INR values, which could lead to inappropriate warfarin dosage reduction. Monitoring warfarin therapy by chromogenic factor X activity in patients with lupus anticoagulant avoids this INR artifact.
Adverse Effects of Atypical Antipsychotic Agents and Their Effects on Quality of Life
Authors: Dubisar Beth M. , Stoner Steven C. , Reynolds James , Khan Rintu , Ramlatchman Leonard
Published: July 2004

Study Objectives. To determine how axis III metabolic disturbances associated with atypical antipsychotic agents (weight gain, diabetes mellitus, and hyperlipidemia) affect patients' quality of life by comparing perceived quality of life of patients taking these agents who developed the disorders with those who did not develop them. A secondary objective was to compare patients' assessments of their quality of life with assessments made of the same patients by their treating psychiatrists.

Design. Analysis of questionnaire results.

Patients. Thirty three patients hospitalized at a Missouri Department of Mental Health long‐term care psychiatric facility after January 1, 1990.

Measurements and Main Results. Participating patients independently completed the “long” form of the Quality of Life Enjoyment and Satisfaction Questionnaire. The psychiatrists who treated these patients completed the Physical Health‐Activities section of the same questionnaire, based on their assessments of their patients' quality of life. Fifteen patients had a diagnosed axis III metabolic disturbance. For the group with these comorbid illnesses, the mean score on overall life satisfaction and contentment was 3.6 (fair to good). The corresponding value for the group without these comorbid diseases was 4.538 (good to very good). Psychiatrists' assessments of their patients' quality of life were less positive than the patients' own assessments, regardless of the existence of comorbid disease.

Conclusion. Patients receiving atypical antipsychotic drugs had a perceived high quality of life and were satisfied with a variety of aspects of their lives. However, metabolic disturbances had a significant, detrimental effect on patients' perceived quality of life.
Magnesium for the Treatment and Prevention of Atrial Tachyarrhythmias
Authors: Piotrowski Alexandria A. , Kalus James S.
Published: July 2004

Atrial tachyarrhythmias, including atrial fibrillation and flutter, occur frequently. Magnesium has been studied in the early conversion and prevention of atrial tachyarrhythmias, as well as in prevention of atrial tachyarrhythmias after coronary artery bypass graft surgery. Early conversion of atrial tachyarrhythmias and control of heart rate may be greater with magnesium than with common antiarrhythmic agents. Magnesium appears to be less useful for preventing recurrent atrial tachyarrhythmias; however, discrepancies in study methodologies make interpretation of results difficult. The use of magnesium for prevention of postoperative atrial arrhythmias has produced conflicting results, likely due to differences in study design. From the limited data available, magnesium appears to have some inherent antiarrhythmic properties. Certain patient populations may derive benefit from magnesium for the treatment of atrial tachyarrhythmias. However, further study is necessary to define the role of magnesium clearly for the treatment or prevention of atrial tachyarrhythmias.
Treatment of Respiratory Syncytial Virus Pneumonia in a Lung Transplant Recipient: Case Report and Review of the Literature
Authors: Flynn Jeremy D. , Akers Wendell S. , Jones Mikael , Stevkovic Natasa , Waid Thomas , Mullett Timothy , Jahania Salik
Published: July 2004

A 61‐year‐old woman who underwent lung transplantation developed severe respiratory syncytial virus (RSV) pneumonia and experienced respiratory failure requiring mechanical ventilation. She was treated initially with aerosolized ribavirin monotherapy; RSV hyperimmune globulin was later added to her regimen. Lung transplant recipients are acutely susceptible to respiratory infections, including community‐acquired respiratory viruses. Respiratory syncytial virus is particularly difficult to treat in immunocompromised patients because of the lack of proved pharmaceutical agents and solid scientific evidence by which to guide therapy. The most important factor appears to be the early start of therapy; immunocompromised patients who develop RSV pneumonia and subsequent respiratory failure requiring mechanical ventilation have a mortality rate approaching 100%. This case report demonstrates the successful treatment of RSV pneumonia with the combination of aerosolized ribavirin and RSV hyperimmune globulin in a severely ill lung transplant recipient who required mechanical ventilation.
Conventional Electron Microscopy and Electron Holography of Organic Solar Cells
Authors: Simon P. , Maennig B. , Lichte H.
Published: July 2004

Organic solar cells are a promising route towards large‐area and low‐price photovoltaic systems. The devices are composed of at least two layers: the hole‐transport layer and the electron‐transport layer. The light absorption can occur in one or both layers. At the interface of the layers the excitons are separated into charge carriers, and every layer deals with one type of carrier. Higher efficiencies of the separation process can be obtained by using a mixed layer containing both materials to obtain a very high interface area. Although the structure of the mixed layers used plays a crucial role for the device performance, until now the morphologies have not been elucidated. In order to correlate physical and optical findings with structure and morphology for the materials in question, electron microscopy experiments were performed on the single components as well as on the layer systems.

The conventional electron microscope is a poor phase microscope. As consequence, weak‐phase objects like organic molecules have to be stained or imaged under strong defocus to produce an observable contrast. Artifacts caused by chemical staining and the appearance of Fresnel diffraction using the defocus technique represent the main problems of conventional microscopy. These artifacts can be avoided using electron holography. Holograms of ultrathin sections of thin layers composed of organic dye molecules were recorded. Subsequently, the phase images were reconstructed. In this manner, we succeeded in obtaining high‐contrast electron micrographs without applying staining or defocus. In addition, holograms of crystalline C60 and zinc phthalocyanine were successfully recorded. Holography has been shown to be a useful tool to image beam‐sensitive and weak‐phase objects without artifacts.
The Effect of Hydrogen Bonding on Self‐Assembled Polyaniline Nanostructures
Authors: Zhang L. , Long Y. , Chen Z. , Wan M.
Published: July 2004

Polyaniline (PANI) nanotubes with an outer diameter of 165–240 nm and an inner diameter of 10–70 nm were prepared by a self‐assembly process in the presence of six different carboxylic acids—propionic acid (PA), lactic acid (LA), succinic acid (SA), malic acid (MA), tartaric acid (TA), and citric acid (CA)—as the dopants. These nanotubes aggregated to form nanotube dendrites when the carboxylic acids contain an OH group. Moreover, the number of OH and COOH groups of the carboxylic acids affected the size, aggregated dendrite morphology, and thermal and electrical properties of the nanotubes. It was proposed that the micelle formed by the carboxylic acids acts as a template in the formation of the nanotubes, while the hydrogen bonds between the polymer chain of PANI and the OH group of the carboxylic acids supply a driving force to form the aggregated nanotube dendrites.
Reinforcing Epoxy Polymer Composites Through Covalent Integration of Functionalized Nanotubes
Authors: Zhu J. , Peng H. , Rodriguez‐Macias F. , Margrave J. L. , Khabashesku V. N. , Imam A. M. , Lozano K. , Barrera E. V.
Published: July 2004

Strong interfacial bonding and homogenous dispersion have been found to be necessary conditions to take full advantage of the extraordinary properties of nanotubes for reinforcement of composites. We have developed a fully integrated nanotube composite material through the use of functionalized single‐walled carbon nanotubes (SWNTs). The functionalization was performed via the reaction of terminal diamines with alkylcarboxyl groups attached to the SWNTs in the course of a dicarboxylic acid acyl peroxide treatment. Nanotube‐reinforced epoxy polymer composites were prepared by dissolving the functionalized SWNTs in organic solvent followed by mixing with epoxy resin and curing agent. In this hybrid material system, nanotubes are covalently integrated into the epoxy matrix and become part of the crosslinked structure rather than just a separate component. Results demonstrated dramatic enhancement in the mechanical properties of an epoxy polymer material, for example, 30–70 % increase in ultimate strength and modulus with the addition of only small quantities (1–4 wt.‐%) of functionalized SWNTs. The nanotube‐reinforced epoxy composites also exhibited an increased strain to failure, which suggests higher toughness.