bluuebunny/crossref_metadata_2025 huggingface dataset:
The Future for Risk Research1
Authors: Turner Barry A.
Published: October 2006

Public interest in issues of safety and risk is growing in intensity, legislation in the health and safety area is becoming more extensive and expectations about how managers should perform when confronting a variety of different risks are rising. All of these developments serve to give more contemporary prominence to the notion of risk; a prominence which brings several difficulties in its train. Unsurprisingly, the term has developed political and cultural overtones, for the more widely studied it becomes, the more highly is it contested.

This article reviews a number of current concerns about risk and considers their implications for risk research and for some future aspects of risk management. Ideas about risk are first set in context by relating them, in a very general fashion, to other ways of looking to the future. A number of ironies of the contemporary enthusiasm for risk are noted and three contemporary cases of risk management are discussed. Finally, some implications of current developments for managers concerned with risk are briefly reviewed and some future areas for research are identified.
Alternative Futures Perspectives on Sustainability, Coherence and Chaos
Authors: Mannermaa Mika
Published: October 2006

In this article some ‘megaphenomena’ of our times are de cribed; they include man's conflict with nature, the end of the industrial era and the globalization process. These changes are creating chaos as well as a coherence or sustainability at the same time. It is maintained that real development in society and in culture needs the special form of deterministic order called chaos; often needed to establish something new. Turbulent times are changing values, especially the idea of progress. Instead of dominant Western ideas of linear or exponential progress, it is suggested that an evolutionary perspective for describing societal development is needed. Some preliminary hypotheses of the elements of this perspective are presented, including the principles of self‐organization, non‐linearity, dynamic systems and emergent properties in the development of societal systems.
Studies in Urban Crises: Problems of Response and Prevention
Authors: Basu Anuradha
Published: October 2006

Power, Poverty and Poison: Disaster and Response in an Indian City, James Manor, Sage Publications, New Delhi (1993), 197 pp.

Bhopal: Anatomy of a Crisis (second edition), Paul Shrivastava, Paul Chapman, London (1992), 169 pp.
A Strategy of ‘Circumvention’: American Policy Towards the Yugoslav Crisis
Authors: David Charles‐Philippe
Published: October 2006

US decisions in the Yugoslav conflict have reflected a strategy of ‘circumvention’, calling on allies and international organizations to manage the crisis. The strategy itself emanated from a calculated form of procrastination, which rested on two pillars: first (in a passive sense), the rejection of any unilateral commitment to political and military solutions in the former Yugoslavia; secondly (in an active sense), the recognition that any spill‐over from the conflict is equally unacceptable. Spill‐overs are defined geographically and according to the intensity of military clashes; the latter are themselves defined by the pressures of public opinion, the media, allies or international organizations calling for a more pro‐active, multilateral policy.
Lifelines and Livelihood: a Social Accounting Matrix Approach to Calamity Preparedness
Authors: Cole Sam
Published: October 2006

This paper1 describes a Social Accounting Matrix (SAM)‐based method for evaluating disaster preparedness and recovery strategies. The first section of the paper explains the overall approach and its extension to the evaluation of specific components of lifeline systems in a small Caribbean island. The next section explains the relationship between the physical and economic parameters of the energy‐electricity‐water lifelines and the tourism sector on the island and describes the construction of the corresponding accounting framework. The diachronic multipliers calculated from this extended matrix are used to determine the impact of potential hazards for tourism and other economic activities on the island. The case of a water storage tank, providing back‐up supply to the major hotels, is used to illustrate the approach. In the final sections, the example is elaborated to highlight trade‐offs between economic and non‐economic costs for particular businesses or households. The events and strategies described then may be combined into an event‐based scenario analysis.
Oil Spill: Management Crisis or Crisis Management?
Authors: Goldberg Steven D. , Harzog Beverly B.
Published: October 2006

Stock values and earnings of Ashland Oil and Exxon were analyzed to determine if a correlation existed between a rapid, positive management response and minimization of the financial impact following an oil spill. The results showed a positive correlation for the company that employed, what experts call, ‘good’crisis management techniques.
Learning How Organizations Mitigate Risk
Authors: Mannarelli Thomas , Roberts Karlene H. , Bea Robert G.
Published: October 2006

Over time, more and more organizations, whose technical and industrial activities are capable of causing perceptible adverse public effects, feel pressure from their external environment to greatly reduce the incidence of errors or failure. This paper describes the first phase of research designed to extend the HRO findings and approaches to studying organizations that are not yet experiencing similar pressures, but may soon be. Preliminary work supports four hypotheses that were generated by literature on resource dependency which was developed and applied to the marine industry. Future research will extend observations further, ultimately returning to such primary issues of the original research as decision making, culture, adaptation to technology and structure, but applying these issues to a wider variety of cases, outcomes and approaches.
Tailored Precision Armies in Fully Networked Battlespace: High Reliability Organizational Dilemmas in the ‘Information Age’
Authors: Demchak Chris C.
Published: October 2006

A vision of information age technology providing the ability to closely manage environmental uncertainties pervades current changes in Western militaries. The goal is to digitally link every weapon system in battlespace to effect real‐time synchronization and response and just‐in‐time logistics and supply. Such optimism ignores organizational implications as well as the uncertainties of battlefield conditions. To be effective, the envisioned precision army will require levels of environmental and organizational certainty unprecedented in either military or civilian history. Fast, reliable, invulnerable resource linkages, the ability to minimize casualty loss and innovative episodic behaviours in response to inherently unpredictable ground conditions will all be essential. Success will depend on the extent to which military organizations succeed in reproducing the conditions and/or emulating the characteristics of high reliability organizations.

This reproduction or emulation, however, is particularly difficult to achieve given the uncertainties of large scale, non‐repetitive activities under hostile terrain‐dependent conditions typical of the ground battlefield. Over time, such forces will lack the slack necessary to survive in battle. Rather than the emergence of a more effective and reliable organization, the more likely outcomes are avoidance of risky operations and an ineffective mimetic isomorphism of the air forces on which the ground forces will increasingly depend.

The primary object of organization is to shield people from unexpected calls upon their powers of adaptability, judgment and decision (Hamilton, 1921:62)
Organizing Maintenance Work At Two American Nuclear Power Plants
Authors: Bourrier Mathilde
Published: October 2006

Organizational strategies used by operations and maintenance personnel at two US nuclear power plants are compared with those described by the Berkeley group in their extensive high reliability organization studies. Using the method of strategic analysis, we show that the two organizations use quite different strategies in their search for reliability and effectiveness. The focus on the coordination of workers and structuring of tasks reveals areas not completely dealt with in previous HRO‐related studies. It is argued that adopting a complementary approach in which elements of both methods are selectively applied may lead to an analytic framework of greater theoretical and explanatory power.
Profiling Crisis Management
Authors: Wagenaar Willem A.
Published: October 2006

Most research on crisis management has paid only limited attention to the prevention of crises. It is in the study of accidents where prevention receives ample attention. In this paper, it is argued that both the making and the management of crises can involve similar organizational weaknesses. The General Failure Type (GFT) model, originally developed and tested for profiling accident prevention, is extended to the domain of crisis management. After a short introduction and explanation of the major tenets of the theory and methodology of GFT‐profiling, it is demonstrated how this methodology can be applied successfully to crisis management.
What Emergency Management Officials Should Know To Enhance Mitigation and Effective Disaster Response
Authors: Fischer Henry W.
Published: October 2006

A review of the relevant literature is combined with case study examples which outline the problems often encountered by emergency managers engaged in mitigation and response activities. Special attention is given to the impact of the media and behavioural response expectations. Practical suggestions are outlined which are designed to enhance mitigation and effective disaster response.
Biphasic alterations in Serotonin‐1B (5‐HT1B) receptor function during abstinence from extended cocaine self‐administration
Authors: O'Dell Laura E. , Manzardo Ann M. , Polis Ilham , Stouffer David G. , Parsons Loren H.
Published: October 2006

Alterations in 5‐HT1Breceptor function during cocaine abstinence were evaluated in rats given either limited‐ or extended access (LA and EA, respectively) to cocaine self‐administration. The locomotor response to the 5‐HT1B/1Aagonist RU24969 was significantly reduced in cocaine‐experienced animals relative to cocaine‐naïve controls following 6 h of abstinence but became sensitized over the subsequent 14 days of abstinence. Both the early phase subsensitivity and later phase supersensivity to RU 24969‐induced activity were greater in EA versus LA animals. Intra‐nucleus accumbens administration of the 5‐HT1Bagonist CP 93, 129 produced significantly greater increases in dialysate dopamine levels in EA versus control animals following 14 days of abstinence. However, there was no difference between EA and cocaine‐naïve control animals in the augmentation of cocaine‐induced increases in nucleus accumbens DA produced by intra‐VTA CP 93, 129. Collectively these findings demonstrate that 5‐HT1Breceptor function is persistently altered by cocaine self‐administration.
Mediation of adenylyl cyclase sensitization by PTX‐insensitive GαoA, Gαi1, Gαi2or Gαi3
Authors: Clark Mary J. , Traynor John R.
Published: October 2006

Chronic activation of mu‐opioid receptors, which couple to pertussis toxin‐sensitive Gαi/oproteins to inhibit adenylyl cyclase (AC), leads to a compensatory sensitization of AC. Pertussis toxin‐insensitive mutations of Gαi/osubtypes, in which the pertussis toxin‐sensitive cysteine is mutated to isoleucine (G), were used to determine whether each of the Gαi/osubtypes is able to mediate sensitization of AC. G, G, Gor Gwere individually transiently transfected into C6 glioma cells stably expressing the mu‐opioid receptor, or transiently co‐expressed with the mu‐opioid receptor into human embryonic kidney (HEK)293T cells. Cells were treated with pertussis toxin to uncouple endogenous Gαi/oproteins, followed by acute or chronic treatment with the mu‐opioid agonist, [D‐Ala2,N‐Me‐Phe4,Gly5‐ol]enkephalin (DAMGO). Each Gαi/osubtype mediated acute DAMGO inhibition of AC and DAMGO‐induced sensitization of AC. The potency for DAMGO to stimulate sensitization was independent of the Gαi/osubtype, but the level of sensitization was increased in clones expressing higher levels of Gαi/osubunits. Sensitization of AC mediated by a component of fetal bovine serum, which was also dependent on the level of functional Gαi/osubunits in the cell, was observed. This serum‐mediated sensitization partially masked mu‐opioid‐mediated sensitization when expressed as percentage overshoot due to an apparent increase in AC activity.
Environmental enrichment stimulates neurogenesis in apolipoprotein E3 and neuronal apoptosis in apolipoprotein E4 transgenic mice
Authors: Levi Ofir , Michaelson Daniel M.
Published: October 2006

Neurodegeneration in Alzheimer's disease (AD) is associated with the activation of neurogenesis. The mechanisms underlying this crosstalk between neuronal death and birth and the extent to which it is affected by genetic risk factors of AD are not known. We employed transgenic mice expressing human apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for AD, or expressing human apoE3 (an AD‐benign allele), in order to examine the hypothesis that apoE4 tilts the balance between neurogenesis and neuronal cell death in favor of the latter. The results showed an isoform‐specific increase in neurogenesis in the hippocampal dentate gyrus (DG) under standard conditions in apoE4‐transgenic mice. Environmental stimulation, which increases neurogenesis in the DG of apoE3‐transgenic and wild‐type mice, had the opposite effect on the apoE4 mice, where it triggered apoptosis while decreasing hippocampal neurogenesis. These effects were specific to the DG and were not observed in the subventricular zone, where neurogenesis was unaffected by either the apoE genotype or the environmental conditions. These in vivo findings demonstrate a linkage between neuronal apoptosis and the impaired neuronal plasticity and cognition of apoE4‐transgenic mice, and suggest that similar interactions between apoE4 and environmental factors might occur in AD.
Taxonomic distinctness and diversity of a hyperseasonal savanna in central Brazil
Authors: Da Silva Igor Aurélio , Batalha Marco Antônio
Published: October 2006

Savannas are characterized by a sharp seasonality, in which the water shortage defines the community functioning. Hyperseasonal savannas, however, experience additionally waterlogging in the rainy season. Since waterlogging may cause local extinctions of intolerant species, we asked whether waterlogging constricts the phylogenetic structure of a hyperseasonal savanna. We studied a hyperseasonal cerrado, comparing it with a nearby seasonal cerrado, never waterlogged, in Emas National Park, central Brazil. In each vegetation form, we sampled all vascular plants by placing fifty 1‐m2quadrats in five surveys. We compared the phylogenetic structure of both vegetation forms, calculating their taxonomic distinctness, taxonomic diversity, expected taxonomic distinctness, and species, genus, and family similarities. The taxonomic distinctness of both cerrados was similar and the values of similarities were high, but taxonomic diversity and expected taxonomic distinctness were lower in the hyperseasonal cerrado than in the seasonal one. Assuming that phenotypic attraction is the major process organizing local communities, the waterlogging in hyperseasonal cerrado assembles phylogenetically unrelated species that have converged on similar habitat use. As a consequence, the habitat use of hyperseasonal cerrado species is a trait widespread in the phylogeny of seasonal cerrado. Waterlogging constrains the phylogenetic structure of the hyperseasonal cerrado, especially by reducing species diversity. In more ecological terms, we can only fully assess the phylogenetic structure of a community if we consider the species abundance.
Potential spread of introduced black rat (Rattus rattus) parasites to endemic deer mice (Peromyscus maniculatus) on the California Channel Islands
Authors: Smith Katherine F. , Carpenter Shannon M.
Published: October 2006

Introduced species have the potential to outperform natives in two primary ways: via increased rates of predation and competition, and via the introduction of new parasites against which native species often lack effective immune defences. To assess the extent to which invasive species’ parasites spread to native hosts, we compared the composition of helminth parasites found in introduced black rat (Rattus rattus) and endemic deer mouse (Peromyscus maniculatus) populations on a subset of the California Channel Islands. Results suggest that the whipworm, Trichuris muris, may have spread from introduced black rats to endemic island deer mice and has continued to thrive in one island population where rats were recently eradicated. These results yield two important conservation messages: (1) although the parasites introduced with invasive species may be few, they should not be ignored as they can spread to native species, and (2) introduced parasites have the potential to remain in a system even after their founding host is extirpated. These findings underscore the importance of parasitological surveys in invasive species research and baseline data for ecosystems where exotic species are likely to invade.
Does GARP really fail miserably? A response to Stockmanet al. (2006)
Authors: McNyset Kristina M. , Blackburn Jason K.
Published: October 2006

Stockmanet al. (2006) found that ecological niche models built using DesktopGARP ‘failed miserably’ to predict trapdoor spider (genusPromyrmekiaphila) distributions in California. This apparent failure of GARP (Genetic Algorithm for Rule‐Set Production) was actually a failure of the authors’ methods, that is, attempting to build ecological niche models using single data points. In this paper, we present a re‐analysis of their original data using standard methods with the data appropriately partitioned into training/testing subsets. This re‐evaluation generated accurate distributional predictions that we contrast with theirs. We address the consequences of model‐building using single data points and the need for a foundational understanding of the principles of ecological niche modelling.
Predicting the distribution of non‐vagile taxa: a response to McNyset and Blackburn (2006) and re‐evaluation of Stockman et al. (2006)
Authors: Stockman Amy K. , Beamer David A. , Bond Jason E.
Published: October 2006

This paper addresses the issues raised by McNyset and Blackburn (2006) in their response to Stockman et al. (2006). Re‐evaluation of our published GARP analyses by McNyset and Blackburn showed that a much improved ecological niche model is obtained for predicting the distribution of the trapdoor spider genus Promyrmekiaphila in central/northern California. The improved niche model results in a substantially reduced omission error rate and a predictive model comparable to models obtained using other methods (GLM and BIOCLIM). However, the improved GARP models have a high commission error rate (> 0.75); consequently, the inferences regarding difficulties in modelling non‐vagile taxa drawn by Stockman et al. remain valid. Finally, we discuss other relatively minor criticisms of our study raised by McNyset and Blackburn and issues related to the peer review of our original paper.
DHE in the Pharmacotherapy of Migraine: Potential for a Larger Role
Authors: Saper Joel R. , Silberstein Stephen , Dodick David , Rapoport Alan
Published: October 2006

Despite a large array of currently marketed, frequently effective drugs for the acute treatment of migraine headache, comprising various classes and formulations, predictably reliable treatment for most headache types is often lacking. Dihydroergotamine mesylate (DHE) is a comparatively safe and effective therapy for migraine headache that could potentially be used for a broader range of headache types than occurs at present. The features of DHE supporting this assertion include (1) effectiveness in terminating severe, long‐lasting headaches, (2) rapid onset of action, (3) very low rates of headache recurrence, (4) minimal risk of medication‐overuse headache, and (5) in the nasal spray formulation, suitability for outpatients (especially patients who are very nauseated or vomiting, potentially obviating the need for an office or hospital visit for acute care). Conditions or circumstances for which there are data supporting the expanded use of DHE include menstrual migraine, migraine with central sensitization and cutaneous allodynia, medication‐overuse headache, migraine recurrence, and status migrainosus. The introduction of the intranasal formulation of DHE provides both pharmacologic and patient‐convenience advantages for use in migraine therapy. This article reviews the rationale for the use of DHE in these common, often difficult‐to‐treat migraine forms.
Leukoreduction of blood transfusions does not diminish transfusion‐associated microchimerism in trauma patients
Authors: Utter Garth H. , Nathens Avery B. , Lee Tzong‐Hae , Reed William F. , Owings John T. , Nester Theresa A. , Busch Michael P.
Published: October 2006

BACKGROUND: Transfusion of trauma patients can result in long‐term survival of donor white blood cells (WBCs) or “transfusion‐associated microchimerism” (TA‐MC). The aim was to determine whether leukoreduction of blood transfusions, advocated to reduce the immunomodulatory effect of transfusion, decreases the likelihood of developing TA‐MC.

STUDY DESIGN AND METHODS: A subgroup of trauma patients from a randomized trial was examined, evaluating the risk of infection following leukoreduced versus nonleukoreduced blood transfusion. Patients’ blood was sampled at least 1 month after hospital discharge, and TA‐MC was assessed with quantitative allele‐specific polymerase chain reaction detection of differences at the HLA‐DR locus or a panel of insertion‐deletion polymorphism loci distributed throughout the chromosomal complement. At the time of blood sampling, a scripted interview was used to ascertain symptoms suggestive of chronic graft‐versus host disease (cGVHD).

RESULTS: For 67 patients evaluated, the mean age was 43 ± 17 years and mean Injury Severity Score was 24 ± 12. Median time from injury to blood sampling for TA‐MC was 240 (interquartile range, 116‐360) days. Nine of 32 patients (28%) in the nonleukoreduced transfusion group developed TA‐MC compared to 13 of 35 patients (37%) in the leukoreduced group (p = 0.43). Subjects with TA‐MC were no more likely than subjects without TA‐MC to have at least one symptom suggestive of cGVHD (64% vs. 76%, respectively).

CONCLUSIONS: TA‐MC seems to be a prevalent condition among injured patients at the second of two regional trauma centers evaluated, suggesting that it is a common phenomenon after transfusion in the setting of injury. Although leukoreduction removes greater than 99.9 percent of donor WBCs, it fails to prevent or even substantially reduce the likelihood of developing TA‐MC. TA‐MC does not appear to be strongly associated with symptoms suggestive of cGVHD several months after transfusion.
Primary and secondary hemostatic functionalities of rehydrated, lyophilized platelets
Authors: Fischer Thomas H. , Bode Arthur P. , Parker Benjamin R. , Russell Karen E. , Bender Diane E. , Ramer J. Kevin , Read Marjorie S.
Published: October 2006

BACKGROUND: The rehydrated, lyophilized (RL) platelet (PLT) is being developed as a hemostatic infusion agent for the control of active bleeding. The key to the method for preparing RL PLTs is a mild aldehyde stabilization that allows for freezing and lyophilizing without cellular rupture. RL PLTs have been shown to be effective at rapidly controlling bleeding in animal models of cardiopulmonary bypass induced PLT dysfunction and washout thrombocytopenia, yet the rehydrated cells have proved to be safe with respect to induction of pathologic intravascular coagulation.

STUDY DESIGN AND METHODS: In vitro and in vivo studies were performed to better understand the differential effect of the RL PLT manufacturing method on primary and secondary hemostatic processes. The functionality of the von Willebrand factor (VWF) receptor (glycoprotein Ib) complex, the PAR receptors, integrin‐mediated aggregation (inside‐out signaling), and surface membrane prothrombin to thrombin conversion systems were investigated.

RESULTS: RL PLTs were found to retain native VWF‐mediated adhesion and surface thrombin generation functions. In contrast, the coupling of thrombin receptors to integrin inside‐out signaling was largely inhibited.

CONCLUSION: These results suggest that RL PLTs may stop bleeding by forming primary hemostatic plugs and providing a localized source of thrombin for secondary hemostatic processes, yet do not build up occlusive pathologic clots possibly because integrin functions for forming PLT‐PLT aggregates are partially inhibited.
Biochemical, molecular characterization, and glycoproteomic analyses of α1‐proteinase inhibitor products used for replacement therapy*
Authors: Kolarich Daniel , Turecek Peter L. , Weber Alfred , Mitterer Artur , Graninger Michael , Matthiessen Peter , Nicolaes Gerry A.F. , Altmann Friedrich , Schwarz Hans Peter
Published: October 2006

BACKGROUND: Isoelectric focusing (IEF) of α1‐proteinase inhibitor (A1PI) shows that commercial products and plasma have different glycoisoform band patterns. Those in Aralast (Grifols Biologicals) reflect an anodal shift of glycoisoforms, which has caused concern. The protein, including glycoproteomic analyses, and structural features of A1PI products were investigated by state‐of‐the‐art techniques.

STUDY DESIGN AND METHODS: Batches from Aralast, Prolastin (Bayer), and Zemaira (Aventis Behring LLC) were analyzed by high‐resolution IEF and high‐performance size‐exclusion chromatography (HP‐SEC). Preparative separated isoforms from IEF were further purified by chromatography and subjected to mass spectrometry for sequence analyses, peptide mapping, and glycosylation analysis. Deamidation was quantified by enzymatic isoaspartate detection. Multiple sequence alignments and structural bioinformatics analyses were performed.

RESULTS: In HP‐SEC, Prolastin had the highest aggregate content at approximately 30 percent. Isoforms from all products purified by high‐resolution IEF were sequenced with an amino acid coverage of more than 98 percent. Deamidation of Asn116 and Asn314 in A1PI was to found to some extent in all products and confirmed quantitatively by enzymatic analysis. There were no signs of methionine oxidation. Cys232 was found to be cysteinylated in A1PI in Prolastin and Aralast as in plasma, but not in Zemaira. All products showed truncation of the C‐terminal lysine. Intact A1PI concentrates contained mainly diantennary, disialylated and smaller amounts of triantennary, trisialylated N‐glycans. The percentage of fucosylation was similar in all products. Site‐specific glycan analysis revealed bands M6 contained only diantennary glycans, whereas the more acidic bands M4 and M2 also carried triantennary structures. The most acidic isoforms, M2 in Prolastin and Zemaira and M0 in Aralast, additionally exhibited tetraantennary N‐glycans.

CONCLUSION: Protein chemical characterization of A1PI showed that all A1PI products to some extent differ from A1PI circulating in human plasma. Bioinformatic analysis indicated that removal of C‐terminal Lys394 and cysteinylation of Cys232 are unlikely to affect structure and/or function of A1PI but cysteinylation may influence interaction between A1PI and its physiologic ligands. Aralast, Prolastin, and Zemaira contain the same set of N‐glycans in the same ratios as those in normal human plasma A1PI. Tri‐ and tetraantennary structures are responsible for the partitioning into IEF isoforms, with the migration shift of Aralast not being due to any difference in the N‐glycosylation, but to the partial loss of the C‐terminal lysine.
Expression of the histo‐blood group B gene predominates in AB‐genotype cells
Authors: Twu Yuh‐Ching , Hsieh Chuang‐Yi , Yu Lung‐Chih
Published: October 2006

BACKGROUND: It has been demonstrated that the 43‐bp minisatellite sequence in the 5′ region of the ABO gene plays an important role in its transcriptional regulation. It was determined in previous investigations that the structure of the minisatellite enhancer was specific to A, B, and O alleles.

STUDY DESIGN AND METHODS: Real‐time polymerase chain reaction (PCR) detection and a PCR‐restriction fragment length polymorphism (RFLP) strategy were used to compare the quantities of the A and B transcripts in AB‐genotype cells, including peripheral blood cells and cancer cell line with the group AB phenotype. The 5′ 3.7‐kb regions of the A and B genes were cloned and the sequences compared. The transcriptional activities of the 5′ segments of the A and B genes were compared with luciferase reporter assay.

RESULTS: Both real‐time PCR and PCR‐RFLP analyses show that there is evidently more of the B transcript in the AB‐genotype cells. It was demonstrated that the 5′ segment of the B gene had a markedly higher transcription‐activation activity relative to the A gene. This difference in transcription capability appears to result from the variation in minisatellite‐enhancer structures in the A and B genes, which contain one and four repeats of the 43‐bp enhancer unit, respectively.

CONCLUSION: Our study indicates that the majority of steady‐state mRNA within AB‐genotype cells is composed of the B transcript and that this phenomenon is due to the predominant expression of the B gene relative to the A gene.
Prevalence of selected viral infections among blood donors deferred for potential risk to blood safety
Authors: Zou Shimian , Fujii Karen , Johnson Stephanie , Spencer Bryan , Washington Nicole , Iv Edward Notari , Musavi Fatemeh , Newman Bruce , Cable Ritchard , Rios Jorge , Hillyer Krista L. , Hillyer Christopher D. , Dodd Roger Y. ,   ARCNET Study Group
Published: October 2006

BACKGROUND: Health history questions identify blood donors believed to pose a higher risk of transmission of infectious diseases. This study assesses the current impact of some of these questions on blood safety as reflected by infectious disease markers.

STUDY DESIGN AND METHODS: Donors who were deferred from donating blood due to health history question(s) were recruited at four different regions of the American Red Cross Blood Services. A blood sample was tested for serologic markers of blood‐borne infections as performed for accepted blood donors.

RESULTS: Of 497 deferred donors enrolled, 29 donors were deferred for having had “yellow jaundice, liver disease, or hepatitis since the age of 11” (Question 3), 1 of whom had hepatitis C virus antibodies (anti‐HCV) and hepatitis B core antigen antibodies (anti‐HBc), 2 had anti‐HBc, and 1 had anti‐HCV (p < 0.05 for both markers). Among 37 donors deferred for having “ever tested positive for hepatitis” (Question 4), 1 had hepatitis B surface antigen and anti‐HBc and 3 had anti‐HBc (p < 0.05 for both markers). Of 14 donors deferred for “having ever used a needle, even once, to take any illegal or nonprescription drug” (Question 12), 1 had anti‐HCV, human T‐lymphotropic virus‐I antibodies and anti‐HBc, 1 had anti‐HCV and anti‐HBc, and 2 had anti‐HCV (p < 0.05 for all three markers).

CONCLUSIONS: Blood donors deferred for standard blood donor questions regarding risk of viral hepatitis as well as those with a history of intravenous drug use were more likely to have higher hepatitis marker rates than those who were not deferred. No significant findings were identified for other markers or questions.
Clinical consequences of red cell storage in the critically ill
Authors: Tinmouth Alan , Fergusson Dean , Yee Ian Chin , Hébert Paul C. ,   ABLE Investigators and the Canadian Critical Care Trials Group
Published: October 2006

Red cell (RBC) transfusions are a potentially life‐saving therapy employed during the care of many critically ill patients to replace losses in hemoglobin to maintain oxygen delivery to vital organs. During storage, RBCs undergo a series of biochemical and biomechanical changes that reduce their survival and function. Additionally, accumulation of other biologic by‐products of RBC preservation may be detrimental to recipients of blood transfusions. Laboratory studies and an increasing number of observational studies have raised the possibility that prolonged RBC storage adversely affects clinical outcomes. In this article, the laboratory and animal experiments evaluating changes to RBCs during prolonged storage are reviewed. Subsequently, the clinical studies that have evaluated the clinical consequences of prolonged RBC storage are reviewed. These data suggest a possible detrimental clinical effect associated with the transfusion of stored RBCs; randomized clinical trials further evaluating the clinical consequences of transfusing older stored RBCs are required.
Continuous Quantification of Baroreflex and Respiratory Control of Heart Rate by Use of Bivariate Autoregressive Techniques
Authors: Barbieri Riccardo , Waldmann Richard A. , Di Virgilio Valerio , Triedman John K. , Bianchi Anna M. , Cerutti Sergio , Saul J. Philip
Published: October 2006

Background:Normal cardiovascular control involves nonstationary complex interactions between a variety of variables such as heart rate (HR), arterial blood pressure (ABP), and respiratory activity.

Methods:To account for both the complexity and transient nature of these phenomena, a closed‐loop bivariate and time‐variant (moving window) model was implemented using autoregressive parametric techniques to identify the typical HR and ABP spectral parameters of low frequency power (LF, 0.03–0.15 Hz), high frequency power (HF, 0.15–0.45 Hz), and their ratio LF/HF. In addition, cross‐parameters, such as the gain, phase, and coherent power, between HR, ABP, and changes in instantaneous lung volume (ILV) were computed in both the LF and HF regions.

Results:The cross‐relations included the HR baroreflex (ABP‐HR, alpha), respiratory sinus arrhythmia (ILV‐HR), the mechanical influence of respiration (ILV‐ABP), and the mechanical feedforward of HR (HR‐ABP, beta). The analyses were performed on data from a gradual tilt protocol, which simulates the physiological nonstationarities encountered in daily life.

Conclusions:The results were similar to those obtained using a bivariate batch (nonmoving window) Levinson‐Wiggins‐Robinson algorithm, but the time‐variant technique was able to provide nearly continuous parameters, allowing for a real‐time continuous monitoring of circulatory control.
Age and Gender Specific Criteria for Signal‐Averaged Electrocardiographic Parameters in Healthy Chinese Children
Authors: Ho Ting Fei , Yip William C.L. , Chan Kit Yee
Published: October 2006

Background: Detection of late potentials (LPs) using signal‐averaged electrocardiograms (SAECGs) is believed to help in the prediction of malignant ventricular arrhythmias and sudden cardiac death in adults. Criteria for detection of LPs in adults may not be applicable for children, as these measurements are known to be age and sex specific.

Method: SAECGs were recorded using MAC 15 ECG System. Duration of filtered QRS (TQRS), duration of high frequency, low amplitude signals in the terminal portion of QRS complex that are < 40 μV (HFLA), and root mean square voltage of the last 40 ms of the filtered QRS (RMS40) were determined for 535 healthy Chinese children, ages 6–17 years (268 males, 267 females).

Results: Both mean TQRS and RMS40 were significantly different between the male and female children (TQRS: 106 ms vs 101 ms, P < 0.001; and RMS40: 62 μV vs 75 μV, P < 0.001). Mean TQRS and HFLA increased significantly with age, while mean RMS40 decreased with age (P < 0.0001). Ninetieth percentile values of TQRS and HFLA and tenth percentile value of RMS40 were used as cut‐off values for normal limits. As such, the criteria for normal TQRS, HFLA, and RMS4O were: TQRS < 117 ms; HFLA < 35 ms; and RMS40 >12 μV. Since TQRS and RMS40 were gender specific, the criteria for male and female were: TQRS: Male < 118 ms, female < 111 ms; and RMS40: Male >9 μV, female >17 μV.

Conclusion: TQRS, HFLA, and RMS40 were shown to be age and sex specific in healthy Chinese children. The criteria for normal TQRS, HFLA and RMS40 were different from those proposed for adults, and this may be partly due to technical differences of the recording system.
Acceleration Spectrum Analysis: A Novel Quantitative Method for Frequenc y‐Domain Analysis of the Signal‐Averaged Electrocardiogram
Authors: Chan Eric K.Y.
Published: October 2006

Background: Frequency‐domain techniques presently used for micropotential analysis in the signal averaged ECG (SAECC) have several inherent shortcomings. For example, they depend on sensitive determination of the I‐point, which becomes inaccurate in the presence of noise, or derivation of multiple, complicated statistical parameters to quantify spectral characteristics in a three‐dimensional “spectral temporal map.” While these techniques are not as well accepted clinically as the conventional time‐domain Simson method, the latter is not without limitations either. Although time‐domain SAECG analysis has a very high negative predictive value, it has low positive predictive accuracy. Furthermore, it cannot be used to analyze SAECC data in patients with conduction delay problems, such as bundle branch block. Hence, the goal of this new frequency‐domain technique is to address and solve some of these shortcomings.

Methods: The Fourier transform of the second derivative signal, or “acceleration spectrum,” extracts the frequency‐domain “signature” of damaged myocardium throughout the entire QRS complex, rather than from only the late potential region. The technique i s not dependent on precise endpoint or other fiducial point determination. A “spectral change index” (SCI) for quantifying variation from 50‐300 Hz in the acceleration spectrum i s calculated. The characterization of the cut‐off values for the SCI was based on results from a study including 50 postmyocardial infarction (post‐MI) patients (25 of whom were inducible to sustained ventricular tachycardia), and 10 normal controls.

Results: An SCI <20, typical of a normal, “flat” acceleration spectrum in the 50‐ to 300‐Hz band width, may indicate undamaged myocardium, while an SCI 220 corresponding to a higher degree of spectral “fragmentation” in the same bandwidth, may indicate increased myocardial tissue damage. Using this cutoff, the sensitivity, specificity, and positive and negative predictive values for this initial study were 72%, 84%, 82%, and 75%, respectively.

Conclusions: Acceleration spectrum analysis (ASA) using the SCI shows promise in predicting inducibility in post‐MI patients, including those with conduction delay problems. Since it is well documented that time‐domain SAECG has a high negative predictive value and a low positive predictive value, the high positive predictive value of the newly developed ASA increases the overall value of the SAECG test.
MADIT and the Implications for Holter Monitoring: Results of a 100‐Physician Survey
Authors: Nisam Seah
Published: October 2006

The MADIT study demonstrated a dramatic reduction in all‐cause mortality for asymptomatic but high risk chronic coronary patients when treated with an implanted cardioverter defibrillator (ICD), in comparison to (mostly amiodarone) medical management. On January 10–11, 1997 (2 weeks after publication of the study), 100 leading electrophysiologists in Europe attended a “MADIT Workshop,” to focus on clearly understanding the study. We report on the results of the anonymous survey following that meeting, noting that the survey preceded the publication of the AVID trial, which likewise showed far better survival for patients treated with ICDs compared almost exclusively to amiodarone. Three‐quarters of the physicians accepted the validity of the MADIT results and would implement the protocol. However, overcoming financial and administrative obstacles may take several years. They responded that Holter Monitoring to verify presence of nonsustained ventricular tachycardia—an essential step in identifying the MADIT patients—is not their current routine, although approximately 50% do Hollers on coronary patients with disturbed left ventricular function, that is, the MADIT type patients, and this number would increase gradually. About half felt that 5% or more of the patients with chronic coronary disease would fit the MADIT profile. Most saw no need for a “MADIT‐specific” device; over half felt the MADIT patient might live longer, pointing to the need for longer‐life ICDs. However, 22% felt that ICDs having dual chamber pacing would benefit MADIT patients.
Comparison of QT/RR Relationship Using Two Algorithms of QT Interval Analysis for Identification of High Risk Patients for Life‐Threatening Ventricular Arrhythmias
Authors: Kiuge Petra , Walter Thomas , Neugebauer Annerose
Published: October 2006

Objective: The purpose of this study was to evaluate the dynamic relationship between QT and RR intervals considering either the QTe interval (i.e., time between the onset of QRS and the end of the T wave) or the QTa interval (i.e., time between the onset of QRS and the apex of the T wave) from 30‐second modules.

Method: The Holter recordings in three groups of adult subjects (30 patients with malignant ventricular tachyarrhythmias [VT/VF patients], 40 patients with coronary artery disease [CAD], and 44 normal subjects) were analyzed using the ELATEC System.

Results: In normal subjects the correlation coefficient between QTa and RR (QTa/RR) was significantly higher (0.87 ± 0.12) than those between QTe and RR (QTe/RR) (0.79 ± 0.17). In the other groups there was no significant difference between QTa/RR and QTe/RR: QTa/RR (CAD: 0.71 ± 0.3; VT/VF: 0.73 ± 0.19); and QTe/RR (CAD: 0.63 ± 0.33; VT/VF: 0.69 ± 0.21). The slope of QTe/ RR over 24 hours was significantly larger in VT/VF patients (0.23 ± 0.11) than in the other groups (control: 0.18 ± 0.08; CAD: 0.17 ± 0.1). Measuring the QTa/RR relation there was no difference between the three groups (VT/VF: 0.19 ± 0.09; CAD: 0.15 ± 0.09; normal: 0.19 ± 0.06).

Conclusion: QTe/RR as well as QTa/RR analyses are methods of detecting a deranged rate dependence of QT intervals in high risk patients. An increased QTe/RR slope indicates a higher risk of life‐threatening ventricular arrhythmias. Because there was no difference in QTa/RR we conclude that the end of the T wave gives important information about disorders in repolarization.
Continuous QT Interval Measurements from 24‐Hour Electrocardiography and Risk after Myocardial Infarction
Authors: Brüggemann Thomas , Eisenreich Sven , Behrens Steffen , Ehlers Christoph , Muller Dirk , Andresen Dietrich
Published: October 2006

Objectives: The aim of this study was to examine the clinical value of QT analysis from Holter recordings in patients after myocardial infarction (Ml).

Background: Prolongation and dispersion of QT intervals in the 12‐lead standard ECG have been proposed as indicators of risk for arrhythmic events. However, the value of QT and T wave measurements from Holter recordings has yet to be established.

Methods: Intervals from Q to the peak and to the end of T were determined every 30 seconds from 24‐hour Holter recordings and corrected for cycle length (QTc). The duration of late repolarization was calculated as QT end minus QT peak. 24‐hour QT variability was determined as the standard error of estimate from the linear regression analysis of QT and RR intervals. In a case control design, 51 post‐MI patients suffering from subsequent cardiac death within 1 year were compared to 51 post‐MI patients with an uncomplicated follow‐up.

Results: QTc intervals as well as 24‐hour QT variability did not differ between post‐MI patients with favorable and unfavorable clinical outcome. However, there was a prolonged interval from the peak to the end of the T wave in cardiac death victims (mean ± SE: 110 ± 4 ms) as compared to controls (95 ± 3ms, P < 0.001).

Conclusions: Prolongation of the late repolarization phase seems to be associated with an increased risk of cardiac death after Ml. Standard QT measurements from ambulatory ECG recordings have no predictive value in post‐MI patients.
Gene‐Specific Therapy for Long QT Syndrome
Authors: Rosero Spencer Z. , Zareba Wojciech , Robinson Jennifer L. , Moss Arthur J.
Published: October 2006

Background: One form of the hereditary long QT syndrome (LQT‐3) has recently been shown to be caused by the SCN5A mutation of the human cardiac sodium channel. Cellular studies have suggested that type lb antiarrhythmics may be potentially therapeutic via preferential blockade of the resulting abnormal late inward sodium current. To test this hypothesis, we implemented a pilot study to evaluate the potential for long‐term, gene‐specific therapy in patients with this disease.

Methods and Results: The effects of short‐term intravenous lidocaine and oral tocainide were studied in three siblings: two carriers of the SCN5A mutation; and one noncarrier. The two carriers had prolonged QT intervals at baseline, 531 ms, and 566 ms, which markedly shortened with intravenous lidocaine to 438 and 482 ms, respectively. Tocainide‐induced correction of the QT interval was similar in both carriers. The noncarrier did not have any significant change in the QT with either drug. One carrier was then placed on outpatient therapy with oral tocainide, and has demonstrated persistent normalization of the QT interval and T wave morphology during the past 10 months.

Conclusion: This is the first demonstration of long‐term outpatient treatment in LQT‐3 using oral tocainide during a 10‐month period. QT shortening was achieved by both intravenous lidocaine and oral tocainide, with no adverse affects. The predominant effect was a reduction in the QT onset interval, suggesting that blockade of the mutant sodium current allows repolarization to begin at an earlier time during the action potential.
Circadian Pattern of the QT Dispersion Using Three Orthogonal Leads of a Holter ECG in Patients with Heart Failure
Authors: Michelucci Antonio , Conti Antonio , Frati Marco , Mininni Simone , Padeletti Luigi , Porciani M. Cristina , Rostagno Carlo , Galanti Giorgio , Cattot Giovanni , Petrogalli Giuseppe , Gensini Gian Franco
Published: October 2006

This study evaluated: (1) if three orthogonal leads (3‐OL) can provide the same information about QT dispersion (QT‐D) as 12‐lead ECG; (2) the circadian pattern of QT‐D adopting 3‐OL during 24‐hour Holter monitoring; (3) if the QT‐D circadian pattern is influenced by therapy. In the first part of the study, we evidenced a significant direct correlation (r = 0.91; P < 0.0005) between QT‐D values of 12 ECG leads and of 3‐OL simultaneously recorded in 15 normal subjects and 11 patients with myocardial infarction. The second part of the study evaluated the circadian pattern of QT‐D adopting 3‐OL during Holter (ELA Medical, Mod. Synesis) monitoring in 15 patients with congestive heart failure (CHF: aged 73 ± 8 yrs. III NYHA) in pharmacological washout and after 10 days of therapy (furosemide, digoxin, captopril) and in 15 age‐matched normal subjects (N: aged 70 ± J yrs). Mean QT‐D values of CHF before therapy were significantly higher at each hour than those of N (always P < 0.001). Mean hourly QT‐D values after therapy were significantly lower than those before therapy (P < 0.03 up to P < 0.001), except for the value at 9:00 A.M. Our results suggest that: (1) 3‐OL can evaluate QT‐D as much as the usual 12‐lead ECG; (2) the use of 3‐OL during Holter monitoring allows the evaluation of the QT dispersion circadian pattern both in N and in CHF; and (3) therapy is able to modify the circadian pattern of QT‐D.