bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the Team Leverage the Board's Decisions?
Authors: Castro Carmen Barroso , De La Concha Marta Dominguez , Gravel Julio Vecino , Periñan Ma Mar Villegas
Published: November 2009

Manuscript Type:

Empirical

Research Question/Issue:

This study analyses the form of the board‐TMT interaction and the firm's level of strategic change. Relatedly, we explore the premise that there needs to be a good fit between the board of directors and the top management team to effectively bring about strategic change.

Research Findings/Insights: Using archival data from a sample of 119 firms in the period 1993–2000, we found that when a synergy exists between the board and the TMT, there will be a greater inclination for strategic change. The results indicate that a board's inclination to contribute to strategic change increases as the board size increases. Equally, it is possible to accept that the relationship between board tenure and their inclination towards strategic change is not linear. Finally, the simultaneous analysis of board composition and the ratio of directors on the TMT, demonstrates that the interaction of both variables has effects on the firm's strategic change.

Theoretical/Academic Implications: This study provides empirical support in favor of an active role of the board shaping the firm's strategic decisions. We have developed and tested a set of arguments regarding with the role of the board on the firm's change in strategy. We have investigated as well, the leveraging effect of one of the variables that define the composition of the management team on the relationship board‐change in strategy.

Practitioner/Policy Implications: In order to create an effective board, a broader governance structure must be examined with a detailed study of aspects of the composition of the board and the TMT (previous research has only considered characteristics linked to the CEO). The dynamics of the relationships between both governance mechanisms are essential and leverage the board capability.
The Strategic Role of the Board: The Impact of Board Structure on Top Management Team Strategic Action Capability
Authors: Kim Bongjin , Burns Michael L. , Prescott John E.
Published: November 2009

Manuscript Type:Conceptual

Research Question/Issue:Board reforms around the globe, corporate governance failures, and equivocal research findings provide the impetus for studying boards from a perspective different from the current emphasis on control and service roles. A board's strategic role is conceptualized and the impact of board diversity and leadership structure on the speed and breadth of top management team (TMT) strategic capabilities is explicated.

Research Findings/Insights:Four board configurations are identified by examining the joint impact of diversity and leadership. Each configuration differentially influences TMT strategic action capabilities. We then propose that the nature of the competitive environment (dynamism and complexity) impacts the effectiveness of a particular configuration. Testable propositions applicable in communitarian, Anglo‐Saxon, and emerging markets are developed in a manner that leverages current theoretical insights and empirical findings.

Theoretical/Academic Implications:Theorizing that board strategic control manifests in multiple forms and influences TMT strategic capabilities in nuanced ways highlights how particular board configurations differentially impact firm processes and outcomes. This approach links the board, TMT, and competitive rivalry literatures, providing a potential explanation for mixed research findings, and suggests directions for future research.

Practitioner/Policy Implications:Universally prescribed board configurations may be harmful to firm and industry performance as well as national economies. Specific board configurations differentially impact TMT capabilities and should be properly aligned with environmental contexts. Those charged with governance design and board configuration should be cognizant of how the diversity and leadership of strategically involved boards influences the speed and breadth of TMT strategic action capabilities.
Karl Olivecrona on Judicial Law‐Making
Authors: SPAAK TORBEN
Published: November 2009

The Scandinavian Realist Karl Olivecrona did not pay much attention to questions of legal reasoning in his many works. He did, however, argue that courts necessarily create law when deciding a case. The reason, he explained, is that judges must evaluate issues of fact or law in order to decide a case, and that evaluations are not objective. Olivecrona's line of argument is problematic, however. The problem is that Olivecrona uses the term “evaluation” in a sense that is broad enough to cover not only evaluations, including moral evaluations, but also considerations that are not evaluations at all, and therefore his claim that judges must evaluate issues of law or fact in order to decide whether a case is false.
Habermas and Ackerman: A Synthesis Applied to the Legitimation and Codification of Legal Norms*
Authors: ABAD I NINET ANTONI , MOLAS JOSEP MONSERRAT
Published: November 2009

In this article we consider certain elements of the normative theory of Jürgen Habermas in the light of the proposals of Bruce Ackerman, with a view to strengthening a concept of deliberative democracy applied to the legitimation of juridical rules. We do not construct a hierarchy of the two positions, but seek to bring together certain elements to achieve a common project. As the starting point for examining the work of the two authors, we take the scheme proposed by Habermas in Faktizität und Geltung. In this connection, through the work of Ackerman, we intend to fill in some of the gaps that Habermas appears to have left in the theory of radical democracy applied to the law. The work of Ackerman can make a significant contribution to deliberative democracy, to the discourse principle that Habermas defines, and to the contractualist theories from a liberal perspective. The study of these contributions makes possible a critical judgment that enables the legitimation of juridical rules carried out by Habermas to acquire greater practicity. In examining the epistemological status of juridical science and law, we attempt to determine the weight and the performance of normative democracy. In Tarr's view, it is a matter for philosophers to examine direct democracy and its desirability.
Introgression of fitness genes across a ploidy barrier
Authors: Chapman Mark A. , Abbott Richard J.
Published: November 2009

Gene flow from diploid to polyploid species could have significant effects on the morphology and ecology of polyploids. The potential of such introgression for bringing about evolutionary change within polyploids has long been recognized, although there are few examples of the process in the wild. Here, we focus on introgression between the diploid species,Senecio squalidus, and the tetraploid,S. vulgaris, which resulted in the origin of a variant form ofS. vulgaristhat produces radiate rather than nonradiate flower heads. The radiate variant ofS. vulgarisis more attractive to pollinators and has a higher outcrossing rate. We review recent work that has isolated and characterized two regulatory genes,RAY1andRAY2, that control presence of ray florets in radiate flower heads, and which have been introgressed intoS. vulgarisfromS. squalidusin the recent past. We identify a copy ofRAY2inS. vulgaris(RAY2b) homeologous to the copy (RAY2a) previously isolated, thus providing further evidence thatS. vulgarisis allotetraploid. We also show that theRAY2a‐Rallele, which is fixed in radiateS. vulgaris, occurs at intermediate frequency inS. squalidus. Thus, based on this result, it is not possible to distinguish whether radiateS. vulgarisoriginated once or multiple times following hybridization between nonradiateS. vulgarisandS. squalidus.
Addiction – and rational choice theory
Authors: Vale Per Halvor
Published: November 2009

Becker and Murphy's theory is a well‐known contribution to economists on the discussion of addiction. This class of rational choice theory is still the most important reference for economists studying addiction. In this paper, the model and the economist's rational choice theory were challenged by modern neurobiological theory. The paper suggested reconstruction work of the standard inter‐temporal choice model along four lines to reduce the gap between the theory and the clinical definition of addiction: (1) a discount rate that varies; (2) revision of the concept consumption capital; (3) the possibility for genetic predisposition to addiction (even if the research up to now has not identified such a gene); and (4) social mechanisms that influence our behaviour.
Studies on the immune response and preparation of antibodies against a large panel of conjugated neurotransmitters and biogenic amines: specific polyclonal antibody response and tolerance
Authors: Huisman Han , Wynveen Paul , Setter Peter W.
Published: November 2009

J. Neurochem. (2010) 112, 840–852.

We described the production and characterization of antibodies against three important groups of neuro‐active haptens, e.g., neurotransmitters and biogenic amines. First, from the tryptophane metabolic pathway: tryptamine, serotonin, 5‐hydroxy‐indole acetic acid, and melatonin. Secondly, the tyrosine metabolic pathway: tyramine, dopamine, dihydroxyphenyl acetic acid, and norepinephrine. Thirdly, antibodies against excitatory and inhibitory neurotransmitters: glycine, glutamate, glutamine, and GABA. Immunogenic conjugates were prepared after linking haptens to carrier proteins. Most antibodies displayed high specificity against corresponding neuro‐active haptens conjugated in vitro and in situ in biological specimens, but not to closely related conjugated metabolites, precursors, pharmaceuticals, agonists, antagonists, or free neuro‐active haptens. Conjugated norepinephrine was highly tolerant in different animal species and produced incidentally a short specific antibody response.
TRAINING NEEDS ASSESSMENT IN RESEARCH ETHICS EVALUATION AMONG RESEARCH ETHICS COMMITTEE MEMBERS IN THREE AFRICAN COUNTRIES: CAMEROON, MALI AND TANZANIA
Authors: ATEUDJIEU JÉRÔME , WILLIAMS JOHN , HIRTLE MARIE , BAUME CÉDRIC , IKINGURA JOYCE , NIARÉ ALASSANE , SPRUMONT DOMINIQUE
Published: November 2009

Background:  As actors with the key responsibility for the protection of human research participants, Research Ethics Committees (RECs) need to be competent and well‐resourced in order to fulfil their roles. Despite recent programs designed to strengthen RECs in Africa, much more needs to be accomplished before these committees can function optimally.

Objective:  To assess training needs for biomedical research ethics evaluation among targeted countries.

Methods:  Members of RECs operating in three targeted African countries were surveyed between August and November 2007. Before implementing the survey, ethical approvals were obtained from RECs in Switzerland, Cameroon, Mali and Tanzania. Data were collected using a semi‐structured questionnaire in English and in French.

Results:  A total of 74 respondents participated in the study. The participation rate was 68%. Seventy one percent of respondents reported having received some training in research ethics evaluation. This training was given by national institutions (31%) and international institutions (69%). Researchers and REC members were ranked as the top target audiences to be trained. Of 32 topics, the top five training priorities were: basic ethical principles, coverage of applicable laws and regulations, how to conduct ethics review, evaluating informed consent processes and the role of the REC.

Conclusion:  Although the majority of REC members in the targeted African countries had received training in ethics, they expressed a need for additional training. The results of this survey have been used to design a training program in research ethics evaluation that meets this need.
FAIRNESS AND EQUITY IN THE PROVISION OF ANTI‐RETROVIRAL THERAPY: SOME REFLECTIONS FROM LESOTHO
Authors: ARMSTRONG RUSSELL
Published: November 2009

The number of people in immediate need of anti‐retroviral treatment (ART) in the southern African region continues to significantly exceed the capacity of health systems there to provide it. Approaches to this complex rationing dilemma have evolved in different directions. The ethical concepts of fairness and equity have been suggested as a basis to guide the development of approaches to select patients for ART. This article reports the results of a case study on patient selection at a rural ART clinic in Lesotho. The purpose of the study was to examine whether or not such concepts had relevance or operative value for a treatment team providing ART in rural Lesotho. The study found that while concepts of fairness and equity were relevant to the work of the treatment team, patient selection practices did not necessarily reflect what these concepts entail. The idea of fairness as a structured, formalized selection process did not figure in the approach to ART provision at the site. A less formal, ‘first‐come‐first‐served’ approach was adopted. While there was knowledge among some team members that social, economic or geographic conditions inhibit individuals and groups from gaining access to ART and that this was inequitable, it was felt that there was little they could do to try to mediate the impact of these conditions. The study's findings pose importance questions about the approach to ART programming in resource constrained settings. The findings also question the relevance of trying to achieve fairness and equity when the gap between need for care and capacity to provide it remains so large.
Cretaceous opine bivalves from the Pacific slope of North America and palaeobiogeography of subfamily Opinae Chavan, 1969
Authors: SQUIRES RICHARD L. , SAUL LOUELLA R.
Published: November 2009

Abstract:  Opines constitute a small subfamily of Mesozoic astartid bivalves that lived mostly in the Tethys Sea region. They first appeared in western Europe during the Middle Triassic, became most widespread during the Jurassic and had their first undoubted appearance in the New World during the Late Jurassic. Their Pacific slope of North America record is studied in detail for the first time. The earliest of the Pacific slope opines is Opis californica Stanton of Early Cretaceous (Hauterivian or Barremian) age. The other six opine species in the study area are of Late Cretaceous age (collectively Middle Turonian – early Late Maastrichtian), have hinges bearing two strong cardinal teeth in each valve, and are placed in the new subgenus Hesperopsis, which is the first astartid to have a partially internal ligament. These six species comprise two morphological lineages inferred to have evolved from O. (H.) popenoei sp. nov. The ‘holzana’ lineage includes O. (H.) holzana sp. nov. and O. (H.) rosarioensis Anderson and Hanna. The ‘anae’ lineage includes O. (H.) anae sp. nov., O. (H.) vancouverensis Whiteaves and O. (H.) triangulata (Cooper). Hesperopis lived in warm temperate waters in offshore shelfal areas. It had a vertical commissure and probably lived as an edgewise recliner. Through time, the species of both lineages became larger and either broader or more elongate. Neither Opis shastalis Anderson, of Aptian age, nor Opis virginalis Waring, of late Palaeocene age, are opines. A junior secondary homonym of Opis trigonalis (Sowerby) was detected and is renamed here as Opis tamurai nom nov.
Debrunia, a new Barremian genus of petalodontid Monopleuridae (Bivalvia, Hippuritoidea) from the Mediterranean region
Authors: MASSE JEAN‐PIERRE , FENERCI‐MASSE MUKERREM
Published: November 2009

Abstract:  Debrunia gen. nov. is characterized by asymmetric myophoral apophyses on the left valve: the posterior one a plate, the anterior a crest. The myophores on the right valve are on the shell wall. It belongs to a group of cylindro‐conical petalodontid Monopleuridae including Petalodontia and Pseudopetalodontia, and possesses some affinities with Agriopleura. Monopleura mutabilis Matheron is the type species of Debrunia gen. nov., and Monopleura (Petalodontia) bruni Douvillé is also ascribed to this genus. The two species are found in late Barremian beds from SE France. Evolutionary trends regarding the myophores of the left valve are comparable and nearly coeval with those of Agriopleura. Debrunia may be the root of the late Aptian–Albian genera Pseudopetalodontia and Mathesia. and may range throughout the Barremian‐Aptian.
The bivalved arthropods Isoxys and Tuzoia with soft‐part preservation from the Lower Cambrian Emu Bay Shale Lagerstätte (Kangaroo Island, Australia)
Authors: GARCÍA‐BELLIDO DIEGO C. , PATERSON JOHN R. , EDGECOMBE GREGORY D. , JAGO JAMES B. , GEHLING JAMES G. , LEE MICHAEL S. Y.
Published: November 2009

Abstract:  Abundant material from a new quarry excavated in the lower Cambrian Emu Bay Shale (Kangaroo Island, South Australia) and, particularly, the preservation of soft‐bodied features previously unknown from this Burgess Shale‐type locality, permit the revision of two bivalved arthropod taxa described in the late 1970s, Isoxys communis and Tuzoia australis. The collections have also produced fossils belonging to two new species: Isoxys glaessneri and Tuzoia sp. Among the soft parts preserved in these taxa are stalked eyes, digestive structures and cephalic and trunk appendages, rivalling in quality and quantity those described from better‐known Lagerstätten, notably the lower Cambrian Chengjiang fauna of China and the middle Cambrian Burgess Shale of Canada.
Morphological criteria for recognising homology in isolated skeletal elements: comparison of traditional and morphometric approaches in conodonts
Authors: JONES DAVID , PURNELL MARK A. , Von BITTER PETER H.
Published: November 2009

Abstract:  Accurate hypotheses of primary homology are fundamental to many aspects of the systematics and palaeobiology of fossils. They are particularly critical for conodonts: virtually all areas of conodont research are underpinned by homology, yet the majority of conodont taxa are found only as disarticulated skeletal elements, and hypotheses of element homology are inferred from morphological comparisons with complete skeletons. This can cause problems in taxa where more than one location within the conodont skeleton is occupied by elements with similar morphology. In such cases, morphological comparisons can yield equivocal or erroneous hypotheses of homology of isolated elements. The Eramosa Lagerstätte of Ontario (Silurian, Wenlock) preserves both isolated skeletal elements and articulated conodont skeletons. The latter provide a topological context within which to test hypotheses of element homology and allow blind testing of qualitative discrimination of elements. When applied to P1 and P2 elements of Wurmiella excavata, this revealed inaccuracy and inconsistency in distinguishing these P element types. Standardised morphometric protocols were used to further test the efficacy of those characters used in traditional qualitative identification of P element homology, revealing that, individually, none of these characters provides an effective discriminator between P element types. Principal components and discriminant function analyses of ten ‘traditional’ morphological variables combined can distinguish P1 from P2 elements with a similar success rate to expert identification. Eigenshape and elliptic Fourier analyses of element outlines proved less effective at capturing shape differences that allowed for discrimination between P1 and P2 elements. Analysis of both traditional and outline data demonstrates that in some individuals P1 and P2 elements are morphologically distinct from one another, while in others they are almost indistinguishable. These results demonstrate that although qualitative assessments of homology can be prone to error, especially when undertaken by inexperienced researchers, the morphometric and analytical protocols used here provide effective additional tool for discriminating morphologically similar but non‐homologous elements. These methods thus hold promise of broad application to other conodont taxa where identification of element homology in collections of isolated specimens is problematic.
Glucocorticoid‐stimulated, transcription‐independent release of annexin A1 by cochlear Hensen cells
Authors: Kalinec F , Webster P , Maricle A , Guerrero D , Chakravarti DN , Chakravarti B , Gellibolian R , Kalinec G
Published: November 2009

Background and purpose:  The current clinical strategy to protect the auditory organ against inflammatory damage by migrating leukocytes is the local delivery of glucocorticoids. However, the mechanism by which glucocorticoids confer this protection remains unknown. Therefore, we investigated the cellular and molecular targets of glucocorticoids in the cochlea that could be involved in preventing leukocyte migration.

Experimental approach:  We used microscopy as well as immunocytochemical and microfluidic techniques to elucidate the effect of dexamethasone, hydrocortisone and prednisolone on the cellular and intracellular distribution of annexin A1 (ANXA1) – a glucocorticoid target known to inhibit leukocyte migration by receptor‐mediated signalling – in the cochlea and isolated cochlear cells of guinea pigs.

Key results:  All the cells lining the scala media – the cochlear compartment containing the auditory organ – express ANXA1 and the ANXA1 receptor FPR2/ALX is present in the scala media, as well as in other cochlear ducts. The majority of ANXA1 in the scala media is stored inside lipid droplets within cochlear Hensen cells. Glucocorticoids activate a myosin IIC‐mediated mechanism that drives ANXA1 from the lipid droplets to the apical region of the Hensen cells, where ANXA1 is released to the external milieu by a process involving ABC transporters.

Conclusions and implications:  These findings suggest that ANXA1 could be a major mediator of the anti‐inflammatory effects of glucocorticoids in the cochlea and identify new molecular targets for prevention of sudden sensorineural hearing loss.
The impact of GPCR structures on pharmacology and structure‐based drug design
Authors: Congreve Miles , Marshall Fiona
Published: November 2009

After many years of effort, recent technical breakthroughs have enabled the X‐ray crystal structures of three G‐protein‐coupled receptors (GPCRs) (β1 and β2 adrenergic and adenosine A2a) to be solved in addition to rhodopsin. GPCRs, like other membrane proteins, have lagged behind soluble drug targets such as kinases and proteases in the number of structures available and the level of understanding of these targets and their interaction with drugs. The availability of increasing numbers of structures of GPCRs is set to greatly increase our understanding of some of the key issues in GPCR biology. In particular, what constitutes the different receptor conformations that are involved in signalling and the molecular changes which occur upon receptor activation. How future GPCR structures might alter our views on areas such as agonist‐directed signalling and allosteric regulation as well as dimerization is discussed. Knowledge of crystal structures in complex with small molecules will enable techniques in drug discovery and design, which have previously only been applied to soluble targets, to now be used for GPCR targets. These methods include structure‐based drug design, virtual screening and fragment screening. This review considers how these methods have been used to address problems in drug discovery for kinase and protease targets and therefore how such methods are likely to impact GPCR drug discovery in the future.

This article is part of a themed section on Molecular Pharmacology of GPCR. To view the editorial for this themed section visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00695.x
MITOCHONDRIAL DNA IN THE OOGAMOCHLAMYS CLADE (CHLOROPHYCEAE): HIGH GC CONTENT AND UNIQUE GENOME ARCHITECTURE FOR GREEN ALGAE1
Authors: Borza Tudor , Redmond Erin K. , Laflamme Mark , Lee Robert W.
Published: November 2009

Most mitochondrial genomes in the green algal phylum Chlorophyta are AT‐rich, circular‐mapping DNA molecules. However, mitochondrial genomes from the Reinhardtii clade of the Chlorophyceae lineage are linear and sometimes fragmented into subgenomic forms. Moreover, Polytomella capuana, from the Reinhardtii clade, has an elevated GC content (57.2%). In the present study, we examined mitochondrial genome conformation and GC bias in the Oogamochlamys clade of the Chlorophyceae, which phylogenetic data suggest is closely related to the Reinhardtii clade. Total DNA from selected Oogamochlamys taxa, including four Lobochlamys culleus (H. Ettl) Pröschold, B. Marin, U. G. Schlöss. et Melkonian strains, Lobochlamys segnis (H. Ettl) Pröschold, B. Marin, U. G. Schlöss. et Melkonian, and Oogamochlamys gigantea (O. Dill) Pröschold, B. Marin, U. G. Schlöss. et Melkonian, was subjected to Southern blot analyses with cob and cox1 probes, and the results suggest that the mitochondrial genome of these taxa is represented by multiple‐sized linear DNA fragments with overlapping homologies. On the basis of these data, we propose that linear mitochondrial DNA with a propensity to become fragmented arose in an ancestor common to the Reinhardtii and Oogamochlamys clades or even earlier in the evolutionary history of the Chlorophyceae. Analyses of partial cob and cox1 sequences from these Oogamochlamys taxa revealed an unusually high GC content (49.9%–65.1%) and provided evidence for the accumulation of cob and cox1 pseudogenes and truncated sequences in the mitochondrial genome of all L. culleus strains examined.
OPTIMAL GROWTH CONDITIONS AND ANTIOXIDATIVE ACTIVITIES OFCYLINDROTHECA CLOSTERIUM(BACILLARIOPHYCEAE)1
Authors: Affan Abu , Heo Soo‐Jin , Jeon You‐Jin , Lee Joon‐Baek
Published: November 2009

We isolated the unialgal strain ofCylindotheca closterium(Ehrenb.) Reimann et J. C. Lewin and produced an axenic strain using an antibiotic cocktail of enriched f/2 artificial seawater medium. The optimal growth conditions were estimated under 27 different combinations of temperature, salinity, and nutrients, and mass culture was performed based on the best specific growth conditions. Its antioxidant activities were determined from the extracts of methanol, water, and enzymes (proteases and carbohydrases). The maximum specific growth rate (μmax) varied from 0.63 to 0.97 · d−1. The maximum cell density was 7.20 × 104cells · mL−1, while the μmaxwas 0.82 · d−1in culture conditions of 20°C, 30 psu (practical salinity unit), and “F” nutrient concentrations on day 10 of the culture period. The scavenging rates for 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) free radical were 72.5% and 69.4% from Viscozyme and methanol extracts, respectively. The enzymatic extracts ofC. closteriumprepared by the hydrolyses of Amyloglucosidase (AMG) and Viscozyme showed 45.8% and 45.5% nitric‐oxide‐scavenging rates, slightly lower than the activity of alpha‐tocopherol (α‐tocopherol) but similar to butylated hydroxytoluene (BHT). The extract from methanol and water showed 44.8% and 44.4% scavenging rates, statistically similar with BHT. The metal‐chelating activities of the Kojizyme, Alcalase, methanol, Viscozyme, and Neutrase extracts were 67.1, 53.9, 53.2, 52.1, and 50.2 %, respectively, five to six times higher than the commercial antioxidants. The AMG, Viscozyme, and Neutrase extracts showed a remarkable linoleic acid peroxidation inhibition, which was higher than BHT and statistically similar with α‐tocopherol.
TRANSFUSION COMPLICATIONS: Declining hepatitis C virus (HCV) prevalence in pregnant women: impact of anti‐HCV screening of donated blood
Authors: Ohto Hitoshi , Ishii Tsutomu , Kitazawa Junichi , Sugiyama Seiji , Ujiie Niro , Fujimori Keiya , Ariga Hiromichi , Satoh Tomoko , Nollet Kenneth E. , Okamoto Hiroaki , Hoshi Tanji
Published: November 2009

BACKGROUND:Screening blood donors for hepatitis C virus (HCV) antibody has effectively mitigated transfusion transmission of HCV. We conducted a post hoc analysis to clarify the impact of donor screening on a general population of reproductive‐age females and their offspring.

STUDY DESIGN AND METHODS:Anti‐HCV screening in Japan started in late‐1989. In a cohort studied between May 1990 and November 2004, a total of 22,664 consecutive serum samples from pregnant women were screened for anti‐HCV. Reactive samples were further tested for HCV RNA. Linear structural regression was applied to identify causal relationships.

RESULTS:Anti‐HCV–reactive rates declined significantly by two measures. First, among women known to have been transfused, rates fell from 14.8% to 3.1% with the implementation of anti‐HCV screening (p < 0.01). Nevertheless, this is 10 times higher than the 0.3% reactive rate seen in a similar cohort of nontransfused women. Second, rates fell from 1.8% among women born in 1955 or before to 0.3% for women born in 1966 or later (p < 0.01). Among 103 anti‐HCV–reactive women, 31 (30%) had been transfused and another 17 (17%) had other identifiable risk factors. The remaining 55 (53%) had no clear risk factor. Blood transfusion accounted for 19% of anti‐HCV acquisition, by path analysis. Only one infant in this cohort was vertically infected with HCV.

CONCLUSION:Anti‐HCV screening of donated blood and hygienic improvements have markedly decreased HCV infection of pregnant women with a transfusion history; however, 70% of anti‐HCV–reactive women were deemed to be infected via routes other than transfusion.
BLOOD DONORS AND BLOOD COLLECTION: The aging population poses a global challenge for blood services
Authors: Ali Akif , Auvinen Marja‐Kaisa , Rautonen Jukka
Published: November 2009

BACKGROUND: The Finnish transfusion registry data suggest some alarming signals and future challenges that are likely to be faced by transfusion services as populations continue to age.

STUDY DESIGN AND METHODS: Computerized data collection was performed on all potentially transfused patients in Finland, thus covering ∼70% of all blood usage. We simulated the red blood cell (RBC) usage according to the Finnish practice on different age groups but the population demographics from other countries.

RESULTS: The Finnish data demonstrate a marked increase in RBC consumption with increasing age among recipients, beginning at around 50 years of age. The 70‐ to 80‐year‐olds have an eightfold higher RBC consumption than 20‐ to 40‐year‐olds.

CONCLUSIONS: A large part of the variation in RBC use per capita can be explained by the age distribution of the different populations and not by the different national and regional treatment policies and protocols used. If current efforts are not enough to serve the changing population demographic and if increasing demands for blood products cannot be met, there is need to consider unprecedented measures such as reversing certain donor deferrals or even exporting blood from country to country.
Evaluation of a Bifurcation Drug‐Eluting Stent System versus Provisional T‐Stenting in a Perfused Synthetic Coronary Artery Model
Authors: RIZIK DAVID G. , KLAG JOSEPH M. , TENAGLIA ALAN , HATTEN THOMAS R. , BARNHART MARIANNE , WARNACK BORIS
Published: November 2009

Background: Provisional T‐stenting is a widely used strategy for the treatment of coronary artery bifurcation lesions. However, the use of conventional stents in this setting is limited by multiple factors; this includes technical considerations such as wire wrap when accessing the involved vessel, and stent overlap at or near the carina of the lesion. In addition, current slotted tube stent technology tends to be associated with gaps in the coverage of the side branch ostium, which may result in restenosis in that segment of the lesion. The Pathfinder device, now more commonly referred to as the Xience Side Branch Access System (Xience SBA) is a drug‐eluting stent (DES) designed specifically to assist in the treatment of bifurcation lesions by allowing wire access into the side branch, irrespective of the treatment strategy to be employed.

Methods: The Xience SBA drug‐eluting stent was compared with the standard Vision coronary stent system using a provisional T‐stenting strategy in a perfused synthetic model of the coronary vasculature with side branch angulations of 30°, 50°, 70°, and 90°. Stent delivery was performed under fluoroscopic guidance. Following the procedure, high‐resolution 2D Faxitron imaging was used to evaluate deployment accuracy of the side branch stent relative to the main branch stent.

Results: Deployment of the Xience SBA was accomplished in the same total time as the standard stents in a provisional T‐stenting approach (14.9 vs. 14.6 minutes). However, the time required to achieve stent deployment in the main branch was less with the Xience SBA (4.0 vs. 6.6 minutes), and as a result, total contrast usage (49.4 vs. 69.4 cm3) and fluoroscopy time (5.1 vs. 6.2 minutes) was lower. Additionally, the Xience SBA had a lower incidence of wire wrap (22% vs. 89%) and less distal protrusion of the side branch stent into the main branch (0.54 vs. 1.21 mm). Significant gaps in ostial side branch coverage were not seen in either group.

Conclusions: The Xience Side Branch Access DES is a viable device for consistently accessing coronary bifurcation lesions; it allows for easy wire access into the side branch. This may assist the operator in overcoming those well‐recognized limitations associated with use of standard one‐ or two‐stent strategies. In this perfused synthetic coronary model, Xience SBA deployment required less contrast usage and shorter fluoroscopy times. Further testing of this device is warranted.
Statistical Analysis of Illness–Death Processes and Semicompeting Risks Data
Authors: Xu Jinfeng , Kalbfleisch John D. , Tai Beechoo
Published: November 2009

SummaryIn many instances, a subject can experience both a nonterminal and terminal event where the terminal event (e.g., death) censors the nonterminal event (e.g., relapse) but not vice versa. Typically, the two events are correlated. This situation has been termed semicompeting risks (e.g.,Fine, Jiang, and Chappell, 2001, Biometrika 88,907–939;Wang, 2003, Journal of the Royal Statistical Society, Series B 65,257–273), and analysis has been based on a joint survival function of two event times over the positive quadrant but with observation restricted to the upper wedge. Implicitly, this approach entertains the idea of latent failure times and leads to discussion of a marginal distribution of the nonterminal event that is not grounded in reality. We argue that, similar to models for competing risks, latent failure times should generally be avoided in modeling such data. We note that semicompeting risks have more classically been described as an illness–death model and this formulation avoids any reference to latent times. We consider an illness–death model with shared frailty, which in its most restrictive form is identical to the semicompeting risks model that has been proposed and analyzed, but that allows for many generalizations and the simple incorporation of covariates. Nonparametric maximum likelihood estimation is used for inference and resulting estimates for the correlation parameter are compared with other proposed approaches. Asymptotic properties, simulations studies, and application to a randomized clinical trial in nasopharyngeal cancer evaluate and illustrate the methods. A simple and fast algorithm is developed for its numerical implementation.
Model‐Based Quality Assessment and Base‐Calling for Second‐Generation Sequencing Data
Authors: Bravo Héctor Corrada , Irizarry Rafael A.
Published: November 2009

SummarySecond‐generation sequencing (sec‐gen) technology can sequence millions of short fragments of DNA in parallel, making it capable of assembling complex genomes for a small fraction of the price and time of previous technologies. In fact, a recently formed international consortium, the 1000 Genomes Project, plans to fully sequence the genomes of approximately 1200 people. The prospect of comparative analysis at the sequence level of a large number of samples across multiple populations may be achieved within the next five years. These data present unprecedented challenges in statistical analysis. For instance, analysis operates on millions of short nucleotide sequences, or reads—strings of A,C,G, or T's, between 30 and 100 characters long—which are the result of complex processing of noisy continuous fluorescence intensity measurements known as base‐calling. The complexity of the base‐calling discretization process results in reads of widely varying quality within and across sequence samples. This variation in processing quality results in infrequent but systematic errors that we have found to mislead downstream analysis of the discretized sequence read data. For instance, a central goal of the 1000 Genomes Project is to quantify across‐sample variation at the single nucleotide level. At this resolution, small error rates in sequencing prove significant, especially for rare variants. Sec‐gen sequencing is a relatively new technology for which potential biases and sources of obscuring variation are not yet fully understood. Therefore, modeling and quantifying the uncertainty inherent in the generation of sequence reads is of utmost importance. In this article, we present a simple model to capture uncertainty arising in the base‐calling procedure of the Illumina/Solexa GA platform. Model parameters have a straightforward interpretation in terms of the chemistry of base‐calling allowing for informative and easily interpretable metrics that capture the variability in sequencing quality. Our model provides these informative estimates readily usable in quality assessment tools while significantly improving base‐calling performance.
PPARγ ligands inhibit telomerase activity and hTERT expression through modulation of the Myc/Mad/Max network in colon cancer cells
Authors: Toaldo Cristina , Pizzimenti Stefania , Cerbone Angelo , Pettazzoni Piergiorgio , Menegatti Elisa , Daniela Berardi , Minelli Rosalba , Giglioni Barbara , Dianzani Mario Umberto , Ferretti Carlo , Barrera Giuseppina
Published: November 2009

In human cells the length of telomeres depends on telomerase activity. This activity and the expression of the catalytic subunit of human telomerase reverse transcriptase (hTERT) is strongly up‐regulated in most human cancers. hTERT expression is regulated by different transcription factors, such as c‐Myc, Mad1 and Sp1. In this study, we demonstrated that 15d‐PG J2 and rosiglitazone (an endogenous and synthetic peroxisome proliferators activated receptor γ (PPARγ) ligand, respectively) inhibited hTERT expression and telomerase activity in CaCo‐2 colon cancer cells. Moreover, both ligands inhibited c‐Myc protein expression and its E‐box DNA binding activity. Additionally, Mad1 protein expression and its E‐box DNA binding activity were strongly increased by 15d‐PG J2 and, to a lesser extent, by rosiglitazone. Sp1 transcription factor expression and its GC‐box DNA binding activity were not affected by both PPARγ ligands. Results obtained by transient transfection of CaCo‐2 cells with pmaxFP‐Green‐PRL plasmid constructs containing the functional hTERT core promoter (including one E‐box and five GC‐boxes) and its E‐box deleted sequences, cloned upstream of the green fluorescent protein reporter gene, demonstrated that 15d‐PG J2, and with minor effectiveness, rosiglitazone, strongly reduced hTERT core promoter activity. E‐boxes for Myc/Mad/Max binding showed a higher activity than GC‐boxes for Sp1. By using GW9662, an antagonist of PPARγ, we demonstrated that the effects of 15d‐PG J2 are completely PPARγ independent, whereas the effects of rosiglitazone on hTERT expression seem to be partially PPARγ independent. The regulation of hTERT expression by 15d‐PG J2 and rosiglitazone, through the modulation of the Myc/Max/Mad1 network, may represent a new mechanism of action of these substances in inhibiting cell proliferation.
Functionalized self‐assembling peptide hydrogel enhance maintenance of hepatocyte activity in vitro
Authors: Genové Elsa , Schmitmeier Stephanie , Sala Ana , Borrós Salvador , Bader Augustinus , Griffith Linda G. , Semino Carlos E.
Published: November 2009

There is a major challenge in maintaining functional hepatocytes in vivo as these cells rapidly lose their metabolic properties in culture. In this work we have developed a bioengineered platform that replaces the use of the collagen I – in the traditional culture sandwich technique – by a defined extracellular matrix analogue, the self‐assembling peptide hydrogel RAD16‐I functionalized with biologically active motifs. Thus, after examining side by side the two culture systems we have found that in both cases hepatocytes acquired similar parenchymal morphology, presence of functional bile canaliculi structures, CYP3A2 induction by dexamethasone, urea production, secretion of proteins such as apolipoprotein (class A1, E, J), α1‐microglobulin, α1‐macroglobulin, retinol binding protein, fibronectin, α1‐inhibitor III and biotin‐dependent carboxylases. Interestingly, by assessing in more detail some other hepatic markers, one of the functionalized matrix analogues – carrying the 67 kD laminin receptor ligand – enhanced the gene expression of albumin, HNF4‐α, MDR2 and tyrosine aminotransferase. We conclude that the use of a synthetic culture system with designed matrix functionalization has the advantage in controlling specific cellular responses.
Efficacy of a bioactive glass–ceramic (Biosilicate®) in the maintenance of alveolar ridges and in osseointegration of titanium implants
Authors: Roriz Virgílio M. , Rosa Adalberto L. , Peitl Oscar , Zanotto Edgar D. , Panzeri Heitor , De Oliveira Paulo T.
Published: November 2009

Objectives: The aims of this research were to evaluate the efficacy of a bioactive glass–ceramic (Biosilicate®) and a bioactive glass (Biogran®) placed in dental sockets in the maintenance of alveolar ridge and in the osseointegration of Ti implants.

Material and methods: Six dogs had their low premolars extracted and the sockets were implanted with Biosilicate®, Biogran® particles, or left untreated. After the extractions, measurements of width and height on the alveolar ridge were taken. After 12 weeks a new surgery was performed to take the final ridge measurements and to insert bilaterally three Ti implants in biomaterial‐implanted and control sites. Eight weeks post‐Ti implant placement block biopsies were processed for histological and histomorphometric analysis. The percentages of bone–implant contact (BIC), of mineralized bone area between threads (BABT), and of mineralized bone area within the mirror area (BAMA) were determined.

Results: The presence of Biosilicate® or Biogran® particles preserved alveolar ridge height without affecting its width. No significant differences in terms of BIC, BAMA, and BABT values were detected among Biosilicate®, Biogran®, and the non‐implanted group.

Conclusions: The results of the present study indicate that filling of sockets with either Biosilicate® or Biogran® particles preserves alveolar bone ridge height and allows osseointegration of Ti implants.

To cite this article:
 Roriz VM, Rosa AL, Peitl O, Zanotto ED, Panzeri H, de Oliveira PT. Efficacy of a bioactive glass–ceramic (Biosilicate®) in the maintenance of alveolar ridges and in osseointegration of titanium implants. Clin. Oral Impl. Res. 21, 2010; 148–155. doi: 10.1111/j.1600‐0501.2009.01812.x
Porous titanium granules promote bone healing and growth in rabbit tibia peri‐implant osseous defects
Authors: Wohlfahrt Johan Caspar , Monjo Marta , Rønold Hans Jacob , Aass Anne Merete , Ellingsen Jan Eirik , Lyngstadaas Staale Petter
Published: November 2009

Objectives: The aim of this study was to investigate the osteoconductive properties and biological performance of porous titanium granules used in osseous defects adjacent to titanium implants.

Material and methods: In this animal experimental study, calibrated defects were prepared in the tibias of 24 New Zealand rabbits. The defects were randomized into two tests and one control group. The test defects were grafted with either metallic or oxidized porous titanium granules (PTG or WPTG, respectively), whereas control defects were left empty (sham). The defects were closed with a submerged coin shaped titanium implant. Defects were left for healing for 4 weeks. After healing, the implants were removed and the new bone tissue formed onto the implant surface was analyzed for run × 2, osteocalcin, collagen‐I, tartrate‐resistant acid phosphatase, H+‐ATPase, tumor necrosis factor‐α, interleukin (IL)‐6 and IL‐10 gene expression using reverse transcriptase polymerase chain reactuion. Wound fluid from the healed defects was analyzed for lactate dehydrogenase and alkaline phosphatase activity. Finally osteoconductivity was analyzed by micro‐computed tomography and histology.

Results: Significantly more new bone formed in PTG and WPTG grafted defects compared with sham. The new bone grew both through the porosities of the granules and onto the implant surfaces. The WPTG group showed significantly less expression of key inflammation markers, but with no significant difference in a marker for necrosis. The WPTG also showed a significant increase in collagen‐I mRNA expression compared with PTG.

Conclusion: The results suggest that PTG and WPTG are both osteoconductive materials that can be used to promote bone formation in osseous defects adjacent to titanium implants without hampering implant osseointegration.

To cite this article:
 Wohlfahrt JC, Monjo M, Rønold HJ, Aass AM, Ellingsen JE, Lyngstadaas SP. Porous titanium granules promote bone healing and growth in rabbit tibia peri‐implant osseous defects. Clin. Oral Impl. Res. 21, 2010; 165–173. doi: 10.1111/j.1600‐0501.2009.01813.x
In vivo and in vitro biofilm formation on two different titanium implant surfaces
Authors: Bürgers Ralf , Gerlach Till , Hahnel Sebastian , Schwarz Frank , Handel Gerhard , Gosau Martin
Published: November 2009

Objectives: The aim of the present in vitro and human in vivo study was twofold: first, to evaluate the initial biofilm formation on different titanium implant surfaces by means of two highly sensitive fluorescent techniques and, second, to correlate these findings to different surface properties.

Materials and methods: In vivo biofilm formation was induced on purely machined (Pt) and on sand‐blasted and acid‐etched titanium (Prom) specimens, which were mounted buccally on individual splints and worn by six study participants for 12 h. In vitro bacterial adhesion was also investigated after incubation with Streptococcus sanguinis suspension (37°C, 2 h). Adherent bacteria were quantified by the following fluorescence techniques: Resazurin staining in combination with an automated fluorescence reader or live/dead cell labeling and fluorescence microscopy. Surface roughness (Ra) was determined with a perthometer, and surface free energy (SFE) was measured with a goniometer.

Results: Prom showed a significantly higher median Ra (0.95 μm) and a significantly lower median SFE (18.3 mJ/m2) than Pt (Ra=0.15 μm; SFE=39.6 mJ/m2). The in vitro and in vivo tests showed a significantly higher bacterial adhesion to Prom than to Pt, and the initial biofilm formation on Pt corresponded to the circular surface modifications on the machined substratum. Both observations may be attributed to the predominant influence of surface roughness on bacterial adhesion. No significant differences in the percentage of dead cells among all adhering bacteria were found between Prom (23.7%) and Pt (29.1%). Ectopic solitary epithelial cells from the oral mucosa – strongly adhering to the substratum – were found on each Prom specimen, but not on any of the Pt surfaces.

Conclusions: Initial bacterial adhesion to differently textured titanium surfaces is primarily influenced by Ra, whereas the influence of SFE seems to be of only minor importance. Therefore, the micro‐structured parts of an implant that are exposed to the oral cavity should be highly polished to prevent plaque accumulation. Both tested fluorometric techniques proved to be highly sensitive and reproducible in the quantification of biofilm formation on titanium implant surfaces.

To cite this article:
 Bürgers R, Gerlach T, Hahnel S, Schwarz F, Handel G, Gosau M. In vivo and in vitro biofilm formation on two different titanium implant surfaces. Clin. Oral Impl. Res. 21, 2010; 156–164 doi: 10.1111/j.1600‐0501.2009.01815.x