bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Transfusion in the Critically ill Patient: Role of Erythropoietin
Authors: Corwin Howard L. , Hitchcock Dartmouth
Published: February 2008

The earliest blood transfusions date back to the mid‐seventeenth century1. It was not until the early part of the twentieth century that blood transfusion became a mainstay of clinical practice. The value of blood transfusion was unchallenged through most of this century. Blood transfusion was looked upon as relatively risk‐free, making surgery with levels less than 10 g/dL unthinkable. It was not until the early 1980's that transfusion practices began to come under systematic scrutiny24.The debate over transfusion risks has over the last decade led to a more critical examination of transfusion benefits. This review will focus on transfusion practice in the critically ill patient and the potential role of erythropoietin in the management of these patients.
Infections Related to Red Cell Transfusions Including Variant Creutzfeldt‐Jakob Disease
Authors: Contreras Marcela , Barbara John A.
Published: February 2008

Currently in the developed world, the risks of infection by the transfusion of blood components is very low. Improved methods of selection of all voluntary donors as well as highly sensitive screening techniques to detect the most important agents known to be transmissible by blood transfusion have greatly improved the safety of the blood supply. Nevertheless, there is still the risk of transmitting (mainly HBV, HCV, HIV, CMV, etc.), bacteria (e.g. staphylococci, Pseudomonas, Yersinia) and parasites (e.g. malaria and T. Cruzi).Transmissions occur because donors gave blood during the ‘window period“, because of error, or because no screening test is available for that agent. No cases of new variant Creutzfeldt‐Jakob disease (or CJD) nor of any transmissible spongiform encephalopathy have been shown to be transmitted by blood transfusion. However, because bovine spongiform encephalopathy (BSE) (”mad cow disease“) acquired epidemic proportions only in the U.K. (with the exception of one out of 45 cases), the British Department of Health has decided to introduce several prophylactic measures that might reduce the hypothetical risk of transmission by blood transfusion, such as universal leukodepletion and disposal of all volunteer U.K. plasma for fractionation with its replacement by imported non‐volunteer plasma from the U.S.A
Immunosuppression and Transfusion
Authors: Heiss Markus M.
Published: February 2008

Blood transfusion‐associated immunomodulation is discussed as a cause of considerable clinical consequences. Observations in transplantation surgery indicate that this transfusion effect is able to influence cell‐mediated and humoral immunity in humans. Despite much effort in experimental studies, the basic mechanisms are only partly understood. Studies of perioperative infections as indicators of this transfusion‐associated immunosuppression clearly indicate that no other clinical parameter shows such a strong and reproducible correlation. Controlled studies show that autologous transfusions and leukocyte‐depletion are capable of providing significant clinical benefit. The influence of this transfusion‐associated immunosuppression on prognosis in cancer surgery is more controversial. Although controlled trials have not been able to verify this hypothesis, meta‐analyses strongly support the concept of association of transfusion with cancer recurrence. Given the available data, the clinical potential of transfusion‐associated immunosuppression may lead to a paradigm shift in the awareness of transfusion risks.
Current Information on the Benefits of Allogeneic Blood
Authors: Hardy Jean‐François , Bélisle Sylvain
Published: February 2008

Overall, anemia increases the risk of mortality only when hemoglobin concentration (Hb) falls below 50 g/L. This effect is magnified by blood losses and cardiovascular disease. No evidence supports a beneficial effect of transfusions in less sick patients and those without cardiovascular disease when Hb is above 70 g/L. Especially in areas of the world where blood transmissible diseases are endemic, the considerable risks of HIV infection nearly always outweigh the benefits of transfusion, even in severely anemic patients. Definitive evidence that minimal Hb greater than 90–100 g/L in patients with cardiovascular disease prevents cardiac morbidity is lacking. Transfusions to improve oxygen transport are definitely not indicated in critically ill adults. Transfusions may be deleterious in patients with several, non‐cardiovascular diagnoses. Conversely, in anemic shock, transfusions allow early withdrawal of supportive therapy. Erythrocyte transfusions improve hemostasis and reduce perioperative complications in patients with sickle cell disease.
Post‐Transfusion Purpura
Authors: Kaplan Cécile
Published: February 2008

Post‐transfusion purpura, characterized by the sudden onset of severe thrombocytopenia one week after transfusion, is a rare but serious condition resulting from specific immunization against platelet antigens. Life‐threatening hemorrhages are the major consequence of this affection. Although the clinical syndrome is well‐defined, the mechanism responsible for the destruction of autologous platelets remains unclear. The diagnosis is established by identification of the causative antibody in the patient's serum directed against a platelet antigen not found in his cells. First‐line therapy at present is the infusion of intravenous immunoglobulins.
The Cost Consequences of Universal Leukoreduction
Authors: Vanderlinde Elizabeth S. , Blumberg Neil
Published: February 2008

Purpose: To review the published literature on cost analysis of the use of leukoreduced allogeneic blood components or autologous blood for transfusion versus the use of nonleukoreduced blood transfusions and to assess the implications for the universal leukoreduction of blood components.

Methods: A total of three retrospective cohort studies, one randomized, controlled trial and one implementation trial are included in the review. In addition, an overview is provided of the medical issues concerning universal leukoreduction and the current controversy surrounding the instituting of such a policy in the United States.

Results: All five studies reported overall cost savings with the use of leukoreduced or autologous products compared with the use of unmodified allogeneic blood components.

Conclusion: The use of leukoreduced blood components for transfusion provides an overall cost benefit for patients undergoing transfusion for surgery or hematologic malignancy, many of whom would receive nonleukoreduced blood under current recommendations. The savings due to the reduction in morbidity in surgical patients alone could well equal or exceed the added expense of universal leukoreduction.
Safety of Recombinant Factor VIIa
Authors: Levi Marcel
Published: February 2008

Recombinant activated factor VII is an activator of blood coagulation that is highly effective as a hemostatic agent in patients with complicated hemophilia and other clotting disorders who experience major bleeding or need to undergo surgery. In recent years the potential of this agent to reduce perioperative bleeding and transfusion requirements in non‐hemophilia patients with excessive bleeding, for example after trauma or major surgical interventions, has been studied. Also, the use of recombinant factor VIIa to prevent bleeding and blood transfusion in patients who need to undergo invasive procedures that are associated with major blood loss has been investigated. Most of these observations and trials show efficacy of recombinant factor VIIa in reducing blood loss and the requirement for blood transfusion. Every prohemostatic intervention carries the risk of adverse events, in particular thrombosis. However, the initial reports show that adverse events due to recombinant factor VIIa are not frequent, although definitive conclusions regarding the safety of this approach should await larger trials.
The Potential Role of Factor VIIa in Transfusion Medicine
Authors: Hoffman Maureane
Published: February 2008

Therapy with high doses of recombinant factor VIIa (rFVIIa) is effective in promoting hemostasis in hemophiliacs. There is also some evidence to support the idea that this agent can enhance hemostasis in patients with platelet function defects, thrombocytopenia and liver failure, as well as in persons without a preexisting bleeding disorder. Because of this hemostatic effect in a wide range of clinical settings, it is possible that rFVIIa could serve as a substitute or supplement to the transfusion of blood products.
The Use of Recombinant Factor VIIa in Patients Undergoing Liver Transplant
Authors: Escobar Miguel A. , Hoots W. K eith
Published: February 2008

Liver transplantation is often associated with substantial blood loss and coagulopathy that requires the need for transfusion of large amounts of blood products with increased morbidity and mortality. Recombinant factor VIIa (rFVIIa) was originally developed for the treatment of hemophilia patients with antibodies to factors VIII or IX. More recently rFVIIa has been studied as a prohemostatic agent in a variety of clinical and surgical conditions including liver transplantation. A review of the literature reveals a total of 96 cases of liver transplantation including recipient infants and adults. The doses of rFVIIa have been variable, as well as the results. The largest study was a randomized, double blind, parallel group placebo controlled trial with 83 patients who received a single dose of rFVIIa or placebo. No statistical correlation was seen between the use of rFVIIa and transfusion requirement. The overall incidence of adverse events has been low in all the reported cases. Further large controlled studies should be performed before the widespread use of rFVIIa in the surgical setting is advocated.
Recombinant Factor VIIa in Pediatric Patients
Authors: Tobias Joseph D.
Published: February 2008

To date, the majority of experience with recombinant factor VIIa (rFVIIa) has been in patients with hemophilia who developed auto‐antibodies (inhibitors) against factor VIII. This paper examines the reported experiences with rFVIIa use in non‐hemophiliac pediatric‐aged patients and is based on a review of the literature as well as an evaluation of isolated case reports and case series. The literature contains reports on the successful use of rFVIIa in approximately 40 non‐hemophiliac pediatric patients with acquired coagulation dysfunction of various etiologies as well as inherited disorders of platelet function. Although clinical experience is somewhat limited, no significant adverse effects have been noted in the pediatric‐aged patient. Given its potential therapeutic impact, rFVIIa warrants further investigation in the pediatric population. As the reports in the literature illustrate, rFVIIa may be indicated in coagulopathic states to control active bleeding or as prophylaxis to correct coagulation function prior to an invasive procedure. rFVIIa may be considered when the coagulopathy does not respond to FFP, time constraints do not allow for blood typing, thawing and administration of FFP, or there are concerns regarding the potential hemodynamic effects of FFP.
DART–A Voluntary System of Hemovigilance in Denmark
Authors: Jørgensen Jan , Taaning Ellen
Published: February 2008

SUMMARy

Denmark has a long tradition of collecting information concerning the country's activities, and this includes the collation of data concerning transfusion medicine. Data concerning nearly all parts of the transfusion chain, from the giving of blood through to the production of blood components and to the registration of transfusion complications, has been collected for years. Some data is provided on a voluntary and confidential basis by non‐official bodies, whereas official bodies as a legal obligation provide other data. Up to this day, a common national hemovigilance system has not been established.

The Danish Registration of Transfusion Risks (DART) was initiated in 1998.The inspiration to initiate a registration of risks in connection with blood transfusion came from the results published by SHOT and from France. The British system SHOT was focused on, because the idea of a voluntary and confidential system was more suited to the Danish mentality, and was therefore more likely to be generally accepted. The DART system was originally organized as a copy of SHOT with the intention of making it possible to compare results from the two systems.

During the first four years DART received 114 reports (91 about a severe risk). Half of the severe events concerned the transfusion of an incorrect blood component, and the other half were concerned immunological complications. Only 5% of the reported events concerned transfusion transmitted infections. The results obtained by DART have given rise to initiatives and recommendations aimed at reducing the transfusion risk.
Setting Up the Hemovigilance Scheme in Ireland
Authors: Lawlor Emer , Keane‐Egan Phil , O'Riordan Joan
Published: February 2008

SUMMARy

The international tragedy surrounding the infection of the blood supply by human immunodeficiency virus (HIV) in the 1980s, together with the recognition of the increasing morbidity associated with hepatitis C virus (HCV) and the accompanying paradigm shift in transfusion medicine led to the development of hemovigilance in a number of countries. In Ireland, the infection of women with HCV through anti‐D immunoglobulin, and hemophilia patients with HIV and HCV from factor concentrates, ensured that hemovigilance would be adopted as a high priority.

The hemovigilance system in Ireland was launched in October 1999 under the National Haemovigilance Office (NHO). In the initial stages of development, the possibility of drawing on the experience of two well‐developed systems already in operation, SHOT and the French hemovigilance system, was a huge advantage. Reports are collected on an anonymous basis using similar, though not identical, categorization of incidents to the UK system. A key feature borrowed from the French hemovigilance scheme was the decision to appoint a Transfusion Safety Officer (TSO) in each hospital or group of smaller hospitals.

The in‐depth analysis of individual incidents, coupled with the review of incidents showing common features, generates recommendations to improve transfusion practice. By drawing attention to a systemic approach to eliminating error rather than by promoting a blame culture, the hemovigilance scheme has the capacity, if implemented appropriately, to improve overall patient safety which extends well beyond the transfusion process itself.
Can Policy Decisions in Transfusion Medicine Be Evidence‐Based?*
Authors: Vamvakas Eleftherios C. , AuBuchon James P.
Published: February 2008

SUMMARy

If the concept of evidence‐based medicine were considered at a policy level, it would likely dictate that policy decisions be made on the basis of the best available research evidence. In transfusion medicine, however, decisions are based on a broader range of inputs, and the criteria for evaluating the efficacy and/or cost‐effectiveness of proposed interventions differ from those used in other areas. Reasons why policy decisions in transfusion medicine are often based on considerations other than solely the best available research evidence include public perceptions of transfusion as being an inherently “unsafe” intervention, public expectations with regard to transfusion safety, and proposals for applying the precautionary principle to transfusion medicine. In the authors' opinion, use of the precautionary principle may be justified in addressing transfusion risks that are viewed as “dread events,” but this principle should not be applied indiscriminately to all transfusion risks.
ABC Study: The Results and Clinical Application
Authors: Vincent Jean‐Louis
Published: February 2008

SUMMARy

Anemia is one of the most commonly encountered abnormal laboratory findings in intensive care unit (ICU) patients, and many ICU patients will receive a blood transfusion during their ICU stay. However, the determinants of when and to whom transfusions should be given are not clear cut and have been the subject of considerable debate in recent years. Transfusion practice may vary considerably between institutions and across countries. The ABC (anemia and blood transfusion in critical care) study reported increased ICU and hospital mortality rates in patients who had received a transfusion. On the other hand, low hemoglobin levels are still associated with increased mortality and morbidity. The “traditional” transfusion trigger of 10 g/dL certainly no longer applies to all, but may well be relevant in certain groups, e.g., patients with cardiac disease. Transfusions should certainly be more restrictive than before, but applying this policy across the board cannot be recommended; each patient must be assessed individually on the basis of past and present clinical history, and in light of oxygenation and hemodynamic parameters. Clearly, further study is needed before we are able to determine the best transfusion strategies for our ICU patients.
Fluid Therapy and Coagulation
Authors: James Michael F.M.
Published: February 2008

This article reviews the influence of commonly used resuscitation solutions on both laboratory and clinical coagulation variables. Contrary to the common view, crystalloid solutions enhance coagulation over a range of hemodilution between 10–40%, and do not impair coagulation until hemodilution approaches 70%, provided that ionized calcium concentrations are maintained. By contrast, all of the colloid solutions exert some inhibitory effect on coagulation that appears to exceed the effects of simple hemodilution. The gelatin preparations appear to have the least adverse effect, while dextran preparations impair coagulation to the greatest extent. There is a range of effects exerted by the hydroxyethyl starches that is determined by the in vivo molecular weight of the starch product, with the medium‐to‐low molecular weight solutions (< 200 kD) with a low degree of substitution (< 0.5) exhibiting effects on coagulation that are not significantly different from those of either albumin or the gelatins.
The Therapeutic Potential of Ethyl Pyruvate for the Management of Ischemia/Reperfusion Syndromes, Sepsis and Sepsis‐Related Organ Dysfunction, and Other Conditions Associated With Excessive Inflammation
Authors: Fink Mitchell P.
Published: February 2008

Pyruvate, the final product of glycolysis and the starting substrate for the tricarboxylic acid cycle, plays a central role in intermediary metabolism. It is also an effective scavenger of reactive oxygen species. In order to take advantage of the beneficial effects of pyruvate while circumventing the problem of its poor stability in solution, our laboratory formulated the ester derived from pyruvic acid and ethanol, namely ethyl pyruvate, in a Ringer's‐type calcium‐ and potassium‐containing balanced salt solution. Ringer's ethyl pyruvate solution (REPS) has been evaluated in preclinical studies using animal models of mesenteric ischemia/reperfusion injury, hemorrhagic shock, acute endotoxemia, sepsis, and severe acute alcoholic hepatitis. Treatment with REPS, when compared with treatment with Ringer's lactate solution, has been shown to be able to improve survival and decrease expression of proinflammatory mediators. REPS warrants further evaluation for the resuscitation of patients with hemorrhagic shock and a variety of acute inflammatory conditions.
Cell Salvage in Cardiac Surgery
Authors: Sanjay Prabhu S. , Desmond Michael J.
Published: February 2008

Cardiac surgery is associated with significant amount of bleeding and has been identified as one of the major users of donor blood and blood products. There are increasing concerns about the risks of allogeneic blood transfusion. To minimize the complications associated with allogeneic transfusion there has been a strong trend towards promoting autologous blood transfusion. Cell salvage is a form of autologous transfusion that entails collection of one's own blood, processing of the shed blood and reinfusion into the patient. Its usage in cardiac surgery is related to the fact that these patients have a clean surgical wound intraoperatively and a closed sterile wound drainage system postoperatively, together with a propensity to bleed. Several studies have shown that cell salvage is a useful technique and has several advantages when used in cardiac surgery. A multidisciplinary approach to blood conservation is recommended and cell salvage is one technique that has shown to be effective and safe.
The Qualities of Blood Reinfused During Cell Salvage
Authors: Ridler Biddy M.F. , Thompson John F.
Published: February 2008

This article considers the end‐products of the different methods of intraoperative cell salvage. Variations in hematocrit, coagulation factors, and the way in which contaminants are processed are addressed. There are important differences between the techniques in use; it is vital for all those who operate the equipment and who supervise the reinfusion of salvaged blood to be aware of these issues.
Oxygen Transport Agents: A New Approach to Red Blood Cell Alternatives
Authors: Winslow Robert M.
Published: February 2008

Traditional approaches to red cell substitutes, including perfluorocarbon emulsions, modified hemoglobins or encapsulated hemoglobins, have not fulfilled their early promise. However, the vast amount of research performed in pursuit of these products has allowed a new and deeper insight into the details of O2 transfer at the microscopic level and how red cells, hemoglobin and the vascular system interact to ensure tissue oxygenation. With this understanding in mind, it is now possible to design new O2 carrier molecules specifically aimed at providing O2 to hypoxic tissue. In one sense, these products are not “red cell substitutes” because many of their properties are different from those of red cells and simple measurement of hemoglobin concentration may not be the best indicator of their ability to effectively transport O2. More properly, these new molecules are “O2 transport agents” and, as such, can be used in many clinical applications where red cells are administered today.
An Effective Blood Replacement Fluid That Targets Oxygen Delivery, Increases Plasma Viscosity, and Has High Oxygen Affinity
Authors: Tsai Amy G. , Sakai Hiromi , Wettstein Reto , Kerger Heinz , Intaglietta Marcos
Published: February 2008

To the present the development of blood substitutes has had as a goal to reproduce the properties of blood. New information on how oxygen is transported in microcirculation allows the design of fluids that may be more efficacious than blood during transfusion/resuscitation. These fluids induce vasodilation and increase peripheral vascular resistance through increased blood viscosity, achieving the dual goal of lowering arteriolar oxygen consumption and delivering more oxygen to the tissues. Restoration of tissue function is ensured by reducing the possibility that tissue micro‐regions fall below the threshold of anaerobic metabolism. This goal is attained by using high‐affinity modified hemoglobins that act as a reservoir of oxygen only deployed when the circulating blood arrives at tissue regions where pO2 is very low, even though tissue pO2 may be appear to be below normal. A special feature of an oxygen carrying plasma expander designed according to this premise is that it requires comparatively small amounts of hemoglobin to be effective, a factor that is important since presently human hemoglobin appears to be the oxygen carrier of choice.
The Pharmacoeconomics of Alternatives to Allogeneic Blood Transfusion
Authors: Hulst Marinus van , Slappendel Robert , Postma Maarten J.
Published: February 2008

Background and Objectives: Pharmacoeconomics provides a standardized methodology for valid comparisons of interventions in different fields of healthcare. The role of pharmacoeconomics in the safety of blood, blood products and alternatives has however been very limited up to today. This paper discusses the pharmacoeconomic evaluations of alternatives to blood transfusion that have been published in the scientific literature.

Methods: We reviewed pharmacoeconomic methodology with special reference to cost‐effectiveness and cost‐utility analysis. We searched the literature for such cost‐effectiveness analyses related to alternatives to blood transfusion.

Results: Net costs per quality‐adjusted life year (QALY) gained varied from cost‐saving for reduction of blood transfusions by antifibrinolytics and for analyses which included assumed complications caused by transfusion‐related immunomodulation to more than a hundred millions of US$ per QALY gained for preoperative autologous donation by transurethral prostatectomy patients and epoetin augmentation of preoperative autologous donation.

Conclusions: Currently preoperative autologous blood donation with or without epoetin augmentation and epoetin in the absence of autologous transfusion cannot be regarded as cost‐effective healthcare interventions for the general population. Perioperative use of antifibrinolytics may be cost‐saving, but at present evidence is scarce. Cost‐effectiveness of alternatives to blood transfusion may improve if the impact of adverse effects of allogeneic transfusion, such as immunomodulation, bacterial infection and TRALI, can be further substantiated, if the costs of allogeneic blood transfusion continue to rise due to the introduction of (more) safety measures or if donor blood becomes scarce.
Red Blood Cell Transfusion Practices in Pediatric Critical Care
Authors: Lacroix Jacques , Tucci Marisa , Gauvin France
Published: February 2008

In this paper, we review all published papers on the practice patterns of pediatric intensivists with respect to the transfusion of red blood cells to critically ill children. In order to achieve this task, we address three questions: (1) What do pediatric intensivists think about RBC transfusion? (2) What do they do in practice? (3) What should be done? A review of the available evidence in the medical literature was undertaken, and the results reported. We concluded that there is a large variation in stated and observed practice patterns in pediatric intensive care. The hemoglobin concentration, as well as many other host‐specific factors, modulate the decision to prescribe a RBC transfusion in critically ill children. Hard data that support the prevalent practice pattern are scarce. Clearly, more clinical studies are required to better define the best red blood cell transfusion strategy in pediatric intensive care units.
Guidelines for Transfusion: A Way to Decrease Transfusion
Authors: Roseff Susan D.
Published: February 2008

Transfusion practice must be audited to comply with regulatory and quality standards. The Joint Commission on the Accreditation of Healthcare Organizations requires evaluation of transfusion practice as a part of continuous quality improvement. Transfusion guidelines are written by each institution, usually by a blood utilization committee, and then reviewed by the committee, which is composed of transfusion medicine and peer members. These guidelines should contain criteria that would make a transfusion easily justified without further investigation. In addition, they should include clinical criteria that render transfusion appropriate, even if the proscribed triggers are not met. Guidelines serve as a means of evaluating transfusion practice, not as transfusion indications.

In addition to concerns about transfusion transmitted disease, there are also growing numbers of reports of increased morbidity and mortality due to transfusion itself, which is known to mediate inflammatory cytokines. With new safety measures, regulatory requirements and changes in demographics, there are less eligible donors, resulting in concerns over the adequacy of the blood supply.

With the long potential life span of pediatric patients, preventing adverse transfusion outcomes that could have long‐term consequences is important. There are a variety of pharmacologic agents and new technologies available to decrease the need for blood products, reducing risks from transfusion, while preserving the supply of banked blood. Transfusion guidelines are an integral component of any program to help an institution evaluate how well it adheres to acceptable, safe practice. There are many publications written by expert consensus panels that set down adult transfusion audit guidelines and a few that specifically address pediatric guidelines. Unfortunately, there is a paucity of evidence‐based data in the pediatric transfusion literature. This paper will look at data to support the use of conservative transfusion practice and then discuss the creation of guidelines and how they can help, in a comprehensive program, to decrease or even abrogate the use of blood products. Where specific data for pediatric transfusion exists, it will be presented.
Medical and Economic Impact of Aprotinin Use in Adult Cardiac Surgery
Authors: Meyerson Shari L. , Smith Peter K.
Published: February 2008

Aprotinin, a non‐specific serine protease inhibitor, has been conclusively shown to reduce bleeding and transfusion requirements in coronary artery bypass grafting patients supported by cardiopulmonary bypass during surgery. Aprotinin is approved for use in a full‐dose regimen which inhibits kallikrein, plasmin, and premature platelet activation by circulating thrombin. It is also approved for use in a half‐dose regimen which inhibits only plasmin while preserving platelet function as well. With the full‐dose regimen, aprotinin is more effective than the lysine analogues for bleeding endpoints. It also reduces the incidence of perioperative stroke, compared to placebo, while safety in relation to myocardial infarction and death is maintained. The half‐dose regimen is also effective in reducing bleeding and transfusion, but has been associated with increased rates of perioperative myocardial infarction and death, and appears to be less effective in stroke reduction than full‐dose, particularly in high‐risk patients. Full‐dose aprotinin is more effective than half‐dose aprotinin in reducing bleeding and blood transfusion.

A comprehensive economic analysis of the randomized trial resource use data has been performed to evaluate the cost‐effectiveness of both aprotinin doses. In primary coronary artery bypass grafting, most of the cost of full‐dose aprotinin and all of the cost of half‐dose aprotinin is recovered by in‐hospital reduction of resource based costs. Further cost savings throughout the patient's lifetime are realized for full‐dose aprotinin due to stroke reduction, ultimately recovering the full cost of the drug. For half‐dose, additional lifetime savings related to stroke reduction are offset by increased lifetime cost of myocardial infarction. In reoperative coronary artery bypass grafting, the use of both full‐ and half‐dose aprotinin led to in‐hospital cost savings of approximately $2,000 per patient. When lifetime costs of complications were considered, an additional savings of $4,000 per patient for full‐dose and $2,000 per patient for half‐dose were realized, primarily through stroke reduction.
Blood Conservation in Pediatric Cardiac Surgery
Authors: Pouard Philippe
Published: February 2008

There are many blood conservation strategies available for children undergoing cardiac surgery. These strategies will vary depending on patient age and type of surgery. The goal of them all, however, is the same, namely to minimize exposure to allogeneic transfusion while maximizing the use of autologous red cells. Every participant in the process, including the cardiologist, anesthesiologist, perfusionist, surgeon, intensivist and laboratory technician, is committed to the overriding objective of blood conservation in pediatric cardiac surgery. Even if the effects and costs of al l these methods have not yet been completely assessed, many are available, accurate and need to be implemented.
Deformable Sheet Metal Fixturing: Principles, Algorithms, and Simulations
Authors: Cai W. , Hu S. J. , Yuan J. X.
Published: February 2008

Fixture design is an important consideration in all manufacturing operations. Central to this design is selecting and positioning the locating points. While substantial literature exists in this area, most of it is for prismatic or solid workpieces. This paper deals with sheet metal fixture design. An “N-2-1” locating principle has been proposed and verified to be valid for deformable sheet metal parts as compared to the widely accepted “3-2-1” principle for rigid bodies. Based on the “N-2-1” principle algorithms for optimal fixture design are presented using finite element analysis and nonlinear programming methods to find the best “N” locating points such that total deformation of the deformable sheet metal is minimized. A simulation package called OFixDesign is introduced and numerical examples are presented to validate the “N-2-1” principle and optimal sheet metal fixture design approach.
The Control of Multiple Constraints Within an Open Architecture Machine Tool Controller
Authors: Ardekani R. , Yellowley I.
Published: February 2008

The authors demonstrate the utilization of a novel control architecture and associated algorithms in the maintenance of multiple constraints arising from machining operations. The control architecture is configured to allow the most severe of a series of constraints to control the feedrate, and thus duplicates the procedure which would normally be carried out in off-line optimization strategies. The use of the control in the maintenance of force and chip thickness constraints is analyzed and demonstrated using turning operations as an example.
A Multivariate Statistical Approach to Metrology
Authors: Kurfess T. R. , Banks D. L , Wolfson L. J.
Published: February 2008

This paper presents an approach to metrology that allows one to set a confidence level on geometric parameters using multivariate statistical techniques. Furthermore, the analysis incorporates deviations from nominal geometry that are expected from various manufacturing and measurement processes to reduce the size of the multidimensional confidence interval.
Adaptive Tool Replacement Policies in Machining Economics
Authors: Iakovou E. , Ip C. M. , Koulamas C.
Published: February 2008

Optimization of the economics of machining comprises the determination of the optimal cutting speed and tool replacement policy. A necessary input to the above approach is knowledge of the parameters of the tool life equation which links tool life to cutting speed. In reality, these parameters are not known and should be estimated based on actual machining data. This paper addresses the above optimization problem in the framework of an adaptive control policy. Replacement times in one production run are used to estimate the mean-time-to-failure of a tool, which is in turn used in a regression model to update estimators of the tool life parameters. Using the newly updated estimates a new cutting speed and preventive replacement policy are then determined for the next production run. The end result is an easily implementable decision making tool which can aid in the continuous improvement of the machining process.
A Study on Fractal Characteristics of ARMA Model
Authors: Hasegawa M. , Liu J. C. , Okuda K. , Nunobiki M.
Published: February 2008

This paper discusses the fractal characteristics of the autoregressive moving average (ARMA) model, which has been considered as one of the useful approaches for investigating the random engineering phenomena. Firstly, the fractal characteristic of the ARMA model is proven using the variation method. Then, based on this result, the relationships between the fractal dimensions of the AR (1), the AR (2) and the ARMA (2,1) models and autoregressive and moving average parameters of these models are illustrated quantitatively by using the multiple regression analysis.
Local Positive Feedback Regulation Determines Cell Shape in Root Hair Cells
Authors: Takeda Seiji , Gapper Catherine , Kaya Hidetaka , Bell Elizabeth , Kuchitsu Kazuyuki , Dolan Liam
Published: February 2008

The specification and maintenance of growth sites are tightly regulated during cell morphogenesis in all organisms. ROOT HAIR DEFECTIVE 2 reduced nicotinamide adenine dinucleotide phosphate (RHD2 NADPH) oxidase–derived reactive oxygen species (ROS) stimulate a Ca
2+
influx into the cytoplasm that is required for root hair growth in
Arabidopsis thaliana
. We found that Ca
2+
, in turn, activated the RHD2 NADPH oxidase to produce ROS at the growing point in the root hair. Together, these components could establish a means of positive feedback regulation that maintains an active growth site in expanding root hair cells. Because the location and stability of growth sites predict the ultimate form of a plant cell, our findings demonstrate how a positive feedback mechanism involving RHD2, ROS, and Ca
2+
can determine cell shape.
Quantum Liquids
Authors: Leggett A. J.
Published: February 2008

Quantum liquids are systems in which not only the effects of quantum mechanics but also those of the characteristic indistinguishability of elementary particles are important. The most spectacular of these are the systems of bosons (liquid
4
He, the Bose alkali gases), which undergo the phenomenon of Bose condensation, and the fermion systems (liquid
3
He, the electrons in some metals), which display the related phenomenon of Cooper pairing. I discuss these phenomena and the relation between them.
Leading-Edge Vortex Improves Lift in Slow-Flying Bats
Authors: Muijres F. T. , Johansson L. C. , Barfield R. , Wolf M. , Spedding G. R. , Hedenström A.
Published: February 2008

Staying aloft when hovering and flying slowly is demanding. According to quasi–steady-state aerodynamic theory, slow-flying vertebrates should not be able to generate enough lift to remain aloft. Therefore, unsteady aerodynamic mechanisms to enhance lift production have been proposed. Using digital particle image velocimetry, we showed that a small nectar-feeding bat is able to increase lift by as much as 40% using attached leading-edge vortices (LEVs) during slow forward flight, resulting in a maximum lift coefficient of 4.8. The airflow passing over the LEV reattaches behind the LEV smoothly to the wing, despite the exceptionally large local angles of attack and wing camber. Our results show that the use of unsteady aerodynamic mechanisms in flapping flight is not limited to insects but is also used by larger and heavier animals.
Tilting at a Myth
Authors: Morton David L.
Published: February 2008

The Telephone Gambit
. Chasing Alexander Graham Bell's Secret.
By Seth Shulman
. Norton, New York, 2008. 256 pp. $24.95, C$27.50. ISBN 9780393062069.

On the basis of his own archival research, the author argues that Alexander Graham Bell stole the key idea behind the invention of the telephone from Elisha Gray.
Bovine Immune Response to Inoculation with
Neospora caninum
Surface Antigen SRS2 Lipopeptides Mimics Immune Response to Infection with Live Parasites
Authors: Baszler Timothy V. , Shkap Varda , Mwangi Waithaka , Davies Christopher J. , Mathison Bruce A. , Mazuz Monica , Resnikov Dror , Fish Lea , Leibovitch Benjamin , Staska Lauren M. , Savitsky Igor
Published: February 2008

Infection of cattle with
Neospora caninum
protozoa, the causative agent of bovine protozoal abortion, results in robust cellular and humoral immune responses, particularly CD4
+
T-lymphocyte activation and gamma interferon (IFN-γ) secretion. In the present study,
N. caninum
SRS2 (NcSRS2) T-lymphocyte-epitope-bearing subunits were incorporated into DNA and peptide preparations to assess CD4
+
cell proliferation and IFN-γ T-lymphocyte-secretion immune responses in cattle with predetermined major histocompatibility complex (MHC) genotypes. In order to optimize dendritic-cell processing, NcSRS2 DNA vaccine was delivered with granulocyte macrophage-colony-stimulating factor and Flt3 ligand adjuvant. The synthesized NcSRS2 peptides were coupled with a palmitic acid molecule (lipopeptide) and delivered with Freund's adjuvant. Cattle vaccinated with NcSRS2 DNA vaccine alone did not induce T-lymphocyte activation or IFN-γ secretion, whereas subsequent booster inoculation with NcSRS2-lipopeptides induced robust NcSRS2-specific immune responses. Compared to the response in control animals, NcSRS2-lipopeptide-immunized cattle had significantly increased NcSRS2-specific T-lymphocyte proliferation, numbers of IFN-γ-secreting peripheral blood mononuclear cells, and immunoglobulin G1 (IgG1) and IgG2a antibody levels. The findings show that
N. caninum
NcSRS2 subunits bearing T-lymphocyte epitopes induced cell-mediated immune responses similar to the protective immune responses previously described against live parasite infection, namely T-lymphocyte activation and IFN-γ secretion. The findings support the investigation of NcSRS2 immunogens for protection against
N. caninum
-induced fetal infection and abortion in cattle.
Genetic Features of Clinical Isolates of
Streptococcus dysgalactiae
subsp.
equisimilis
Possessing Lancefield's Group A Antigen
Authors: Tanaka Daisuke , Isobe Junko , Watahiki Masanori , Nagai Yoshiyuki , Katsukawa Chihiro , Kawahara Ryuji , Endoh Miyoko , Okuno Rumi , Kumagai Nanako , Matsumoto Masakado , Morikawa Yoshiro , Ikebe Tadayoshi , Watanabe Haruo
Published: February 2008

Thirteen
Streptococcus dysgalactiae
subsp.
equisimilis
isolates possessing Lancefield's group A antigen recovered from people in Japan during 2000 to 2004 were genotyped. The results indicate that a conserved clone has persisted and spread within Japan, and two different
emm
types were observed within members of this clone.
Characterization of New Staphylococcal Cassette Chromosome
mec
(SCC
mec
) and Topoisomerase Genes in Fluoroquinolone- and Methicillin-Resistant
Staphylococcus pseudintermedius
Authors: Descloux Sybill , Rossano Alexandra , Perreten Vincent
Published: February 2008

Fluoroquinolone- and methicillin-resistant
Staphylococcus pseudintermedius
isolates harbor two new staphylococcal cassette chromosome
mec
(SCC
mec
) elements that belong to class A, allotype 3 (SCC
mec
II-III), and to the new allotype 5 (SCC
mec
VII). Analysis of the complete nucleotide sequences of the topoisomerase loci
gyrB
/
gyrA
and
grlB
/
grlA
revealed mutations involved in fluoroquinolone resistance.
Survey of Vaginal-Flora
Candida
Species Isolates from Women of Different Age Groups by Use of Species-Specific PCR Detection
Authors: Vermitsky John-Paul , Self Matthew J. , Chadwick Sean G. , Trama Jason P. , Adelson Martin E. , Mordechai Eli , Gygax Scott E.
Published: February 2008

A retrospective survey of 93,775 samples testing positive in
Candida
species-specific PCR tests performed on cervicovaginal swabs over a 4-year period demonstrated consistent yearly distributions of
Candida albicans
(89%),
C. glabrata
(7.9%),
C. parapsilosis
(1.7%), and
C. tropicalis
(1.4%). However, the species distributions among different age groups revealed increases in the percentages of non-
albicans
species with increases in age.
Role of Sindbis Virus Capsid Protein Region II in Nucleocapsid Core Assembly and Encapsidation of Genomic RNA
Authors: Warrier Ranjit , Linger Benjamin R. , Golden Barbara L. , Kuhn Richard J.
Published: February 2008

Sindbis virus is an enveloped positive-sense RNA virus in the alphavirus genus. The nucleocapsid core contains the genomic RNA surrounded by 240 copies of a single capsid protein. The capsid protein is multifunctional, and its roles include acting as a protease, controlling the specificity of RNA that is encapsidated into nucleocapsid cores, and interacting with viral glycoproteins to promote the budding of mature virus and the release of the genomic RNA into the newly infected cell. The region comprising amino acids 81 to 113 was previously implicated in two processes, the encapsidation of the viral genomic RNA and the stable accumulation of nucleocapsid cores in the cytoplasm of infected cells. In the present study, specific amino acids within this region responsible for the encapsidation of the genomic RNA have been identified. The region that is responsible for nucleocapsid core accumulation has considerable overlap with the region that controls encapsidation specificity.
Hydrophobic Inactivation of Influenza Viruses Confers Preservation of Viral Structure with Enhanced Immunogenicity
Authors: Raviv Yossef , Blumenthal Robert , Tompkins S. Mark , Humberd Jennifer , Hogan Robert J. , Viard Mathias
Published: February 2008

The use of inactivated influenza virus for the development of vaccines with broad heterosubtypic protection requires selective inactivation techniques that eliminate viral infectivity while preserving structural integrity. Here we tested if a hydrophobic inactivation approach reported for retroviruses could be applied to the influenza virus. By this approach, the transmembrane domains of viral envelope proteins are selectively targeted by the hydrophobic photoactivatable compound 1,5-iodonaphthyl-azide (INA). This probe partitions into the lipid bilayer of the viral envelope and upon far UV irradiation reacts selectively with membrane-embedded domains of proteins and lipids while the protein domains that localize outside the bilayer remain unaffected. INA treatment of influenza virus blocked infection in a dose-dependent manner without disrupting the virion or affecting neuraminidase activity. Moreover, the virus maintained the full activity in inducing pH-dependent lipid mixing, but pH-dependent redistribution of viral envelope proteins into the target cell membrane was completely blocked. These results indicate that INA selectively blocks fusion of the virus with the target cell membrane at the pore formation and expansion step. Using a murine model of influenza virus infection, INA-inactivated influenza virus induced potent anti-influenza virus serum antibody and T-cell responses, similar to live virus immunization, and protected against heterosubtypic challenge. INA treatment of influenza A virus produced a virus that is noninfectious, intact, and fully maintains the functional activity associated with the ectodomains of its two major envelope proteins, neuraminidase and hemagglutinin. When used as a vaccine given intranasally (i.n.), INA-inactivated influenza virus induced immune responses similar to live virus infection.
Stratigraphy of the Upper Ordovician upper Vaureal and Ellis Bay formations, eastern Anticosti Island, Quebec
Authors: Long D. G. F. , Copper Paul
Published: February 2008

Marked facies changes occur in Late Ordovician strata, assigned to the uppermost Vaureal and Ellis Bay formations (Ashgill: Rawtheyan–Hirnantian) on Anticosti Island, Quebec. Western Anticosti features shales and carbonates, whereas outcrops along the eastern coast contain prominent, discontinuous, mixed siliciclastic–carbonate units. Detailed section measurement along the northeast coast allows, for the first time, accurate definition of seven new members within this uninterrupted sequence. Sands present in the upper Vaureal and lower Ellis Bay formations in the east appear to have deterred the growth of muddy-bottom brachiopod communities comparable to those in the western and central regions of Anticosti. Sand units within the upper Vaureal Formation contain 1 m diameter colonies of Paleofavosites; coeval small coral patch reefs are found in the central part of the island, where sands are absent. The uppermost Ellis Bay Formation of northeast Anticosti is marked by a shallow, subtidal, coral–algal oncolite bed or by small (2–4 m across, 1–2 m thick) local coral patch reefs, the tops of which have been used to define the Ordovician – Silurian boundary. No supratidal or intertidal sediments and faunas are evident in the Anticosti succession, suggesting that Late Ordovician sea-level drawdown was insufficient to provide shelf-emergent conditions in this region.