bluuebunny/crossref_metadata_2025 huggingface dataset:
Social structure and space use in a wild population of the Australian short-headed seahorse Hippocampus breviceps Peters, 1869
Authors: Moreau Marie-Annick , Vincent Amanda C.J.
Published: May 2004

This paper presents the first information available from repeated field observations of a wild Hippocampus breviceps population, and an uncommon example of mixed-sex social grouping in seahorses. At two study sites in Port Phillip Bay, Victoria, Australia, adult seahorses were found at a mean density of 0.21seahorses per m2 over rocky reef–algal habitat. Each site had a sex ratio of 1 : 1. Seahorses showed varying degrees of site fidelity, with 12 of 38 adults present in the study area throughout the 5-week study period. Adults at the sites moved within small (1–12m2) and overlapping (with 2–10 others) spatial areas, with most seahorses restricting their movements in the early morning to a smaller core area. Females used significantly larger spatial areas and core areas than did males. Core areas generally coincided with particular seaweeds at which stable groups of two to five seahorses would be found each morning. These core areas were commonly the site of social encounters. Adult seahorses engaged in displays and interactions with opposite-sex partners, although not every day, and not necessarily with the same partner at each encounter. Longer-term observations over a larger study area are necessary to characterise H.breviceps’ movement patterns and mating system more precisely.
A simple approach for dealing with dynamics and uncertainty in fisheries with heterogeneous resource and effort distribution
Authors: Seijo J. C. , Pérez E. P. , Caddy J. F.
Published: May 2004

Most fisheries models are based on dynamic pool assumptions. For sedentary and sessile species, these assumptions are inadequate, because they are spatially distributed in patches that vary in size, density and age structure. A simple bioeconomic model, negative binomial (NEGBIN), is proposed; this model relaxes the dynamic pool assumption without entering into the complexities of a geographically structured model. NEGBIN assumes a probability density function (the negative binomial), to describe heterogeneity in the density distribution over the population range. The model incorporates decision theory and different levels of risk aversion in resource management. The uncertainty associated with alternative fishing strategies, given imperfect knowledge about virgin stock biomass, is also included in the analysis. The model is applied to the Mesodesma donacium (surf clam) fishery in the central northern zone of Chile (South America). Alternative management strategies are evaluated with different levels of risk aversion. In the fisheries literature to date, this approach to evaluating the uncertainty associated with spatial allocation decisions has been rare. It is suggested that this kind of analysis, whether accompanied by quantitative probabilities of alternative states of nature or not, is an alternative way of dealing with risk and uncertainty in spatial allocation decisions.
Society for Reproductive Biology Founders' Lecture 2003.The making of an embryo: short-term goals and long-term implications.
Authors: Fleming Tom P. , Wilkins Adrian , Mears Andrew , Miller Daniel J. , Thomas Fay , Ghassemifar M. Reza , Fesenko Irina , Sheth Bhavwanti , Kwong Wing Yee , Eckert Judith J.
Published: May 2004

During early development, the eutherian mammalian embryo forms a blastocyst comprising an outer trophectoderm epithelium and enclosed inner cell mass (ICM). The short-term goal of blastocyst morphogenesis, including epithelial differentiation and segregation of the ICM, is mainly regulated autonomously and comprises a combination of temporally controlled gene expression, cell polarisation, differentiative cell divisions and cell–cell interactions. This aspect of blastocyst biogenesis is reviewed, focusing, in particular, on the maturation and role of cell adhesion systems. Early embryos are also sensitive to their environment, which can affect their developmental potential in diverse ways and may lead to long-term consequences relating to fetal or postnatal growth and physiology. Some current concepts of embryo–environment interactions, which may impact on future health, are also reviewed.
Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint
Authors: Kops Geert J. P. L. , Foltz Daniel R. , Cleveland Don W.
Published: May 2004

A compromised mitotic checkpoint, the primary mechanism for ensuring that each new cell receives one copy of every chromosome, has been implicated as a contributor to carcinogenesis. However, a checkpoint response is shown here to be essential for cell survival, including that of chromosomally instable colorectal cancer cells. Reducing the levels of the checkpoint proteins BubR1 or Mad2 in human cancer cells or inhibiting BubR1 kinase activity provokes apoptotic cell death within six divisions except when cytokinesis is also inhibited. Thus, suppression of mitotic checkpoint signaling is invariably lethal as the consequence of massive chromosome loss, findings that have implications for inhibiting proliferation of tumor cells.
Stereoisomer libraries: Total synthesis of all 16 stereoisomers of the pine sawfly sex pheromone by a fluorous mixture-synthesis approach
Authors: Dandapani Sivaraman , Jeske Mario , Curran Dennis P.
Published: May 2004

All 16 stereoisomers of the sex pheromone of pine sawfly (3,7,11-trimethylundecanol propanoate ester) have been synthesized on a 10- to 20-mg scale by a split-parallel fluorous mixture-synthesis approach. Spectral data obtained for all 32 compounds (16 alcohols and the corresponding propionates) matched well with published data, thereby validating the fluorous-tag encoding of diastereoisomers. This fluorous-tag encoding method is recommended for the efficient synthesis of multiple stereoisomers for spectroscopic studies, biological tests, or other structure–function relationships.
Identification of anthrax toxin genes in aBacillus cereusassociated with an illness resembling inhalation anthrax
Authors: Hoffmaster Alex R. , Ravel Jacques , Rasko David A. , Chapman Gail D. , Chute Michael D. , Marston Chung K. , De Barun K. , Sacchi Claudio T. , Fitzgerald Collette , Mayer Leonard W. , Maiden Martin C. J. , Priest Fergus G. , Barker Margaret , Jiang Lingxia , Cer Regina Z. , Rilstone Jennifer , Peterson Scott N. , Weyant Robbin S. , Galloway Darrell R. , Read Timothy D. , Popovic Tanja , Fraser Claire M.
Published: May 2004

Bacillus anthracisis the etiologic agent of anthrax, an acute fatal disease among mammals. It was thought to differ fromBacillus cereus, an opportunistic pathogen and cause of food poisoning, by the presence of plasmids pXO1 and pXO2, which encode the lethal toxin complex and the poly-γ-d-glutamic acid capsule, respectively. This work describes a non-B. anthracisisolate that possesses the anthrax toxin genes and is capable of causing a severe inhalation anthrax-like illness. Although initial phenotypic and 16S rRNA analysis identified this isolate asB. cereus, the rapid generation and analysis of a high-coverage draft genome sequence revealed the presence of a circular plasmid, named pBCXO1, with 99.6% similarity with theB. anthracistoxin-encoding plasmid, pXO1. Although homologues of the pXO2 encoded capsule genes were not found, a polysaccharide capsule cluster is encoded on a second, previously unidentified plasmid, pBC218. A/J mice challenged withB. cereusG9241 confirmed the virulence of this strain. These findings represent an example of how genomics could rapidly assist public health experts responding not only to clearly identified select agents but also to novel agents with similar pathogenic potentials. In this study, we combined a public health approach with genome analysis to provide insight into the correlation of phenotypic characteristics and their genetic basis.
Corticotropin-releasing hormone (CRH) requirement inClostridium difficiletoxin A-mediated intestinal inflammation
Authors: Anton Pauline M. , Gay Jerome , Mykoniatis Andreas , Pan Amy , O'Brien Michael , Brown Daniel , Karalis Katia , Pothoulakis Charalabos
Published: May 2004

Clostridium difficile, the causative agent of antibiotic-associated colitis, mediates inflammatory diarrhea by releasing toxin A, a potent 308-kDa enterotoxin. Toxin A-induced inflammatory diarrhea involves many steps, including mucosal release of substance P (SP) corticotropin-releasing hormone (CRH) and neutrophil transmigration. Here we demonstrate that, compared with wild type, mice genetically deficient in CRH (Crh-/-) have dramatically reduced ileal fluid secretion, epithelial cell damage, and neutrophil transmigration 4 h after intraluminal toxin A administration. This response is associated with diminished mucosal activity of the neutrophil enzyme myeloperoxidase compared with that of wildtype mice. In wild-type mice, toxin A stimulates an increase in intestinal SP content compared with buffer administration. In contrast, toxin A administration inCrh-/-mice fails to result in an increased SP content. Moreover, immunohistochemical experiments showed that CRH and SP are colocalized in some enteric nerves of wild-type mice, and this colocalization is more evident after toxin A administration. These results provide direct evidence for a major proinflammatory role for CRH in the pathophysiology of enterotoxin-mediated inflammatory diarrhea and indicate a SP-linked pathway.
The origin of Guideline Daily Amounts and the Food Standards Agency's guidance on what counts as ‘a lot’ and ‘a little’
Authors: Rayner Mike , Scarborough Peter , Williams Carol
Published: May 2004

Objective:

This paper provides the rationale for the Guideline Daily Amounts (GDAs) for fat, saturated fat and other nutrients that appear on food labels in the UK. These GDAs are provided voluntarily by manufacturers and retailers and were developed to help people make better use of nutrition labelling – the format of which is prescribed by the European Union's nutrition labelling directive. The paper also describes the basis to some Rules of Thumb for what counts as ‘a lot’ or ‘a little’ of fat, saturated fat and other nutrients, in an individual food.

Design:

The paper gives the background to, and purpose of, the GDAs and Rules of Thumb and explains how they were calculated. It briefly describes their subsequent usage by food producers and others.

Results:

Both GDAs and the Rules of Thumb first appeared in a leaflet developed by the authors and published in 1996 by the Ministry of Agriculture, Fisheries and Food. GDAs for fat, saturated fat and energy were adopted subsequently by the Institute of Grocery Distribution and then by many retailers and some manufacturers. The Rules of Thumb for fat, saturated fat, sugar and sodium have recently been republished in some leaflets published by the Food Standards Agency in the UK.

Conclusions:

GDAs and Rules of Thumb may provide useful ways of helping consumers make sense of nutrition labelling. The current GDAs and the Rules of Thumb could usefully be updated in the light of recent developments.
Anthropometry of women of childbearing age in Morocco: body composition and prevalence of overweight and obesity
Authors: Belahsen Rekia , Mziwira Mohamed , Fertat Fatima
Published: May 2004

Objective:

To determine the prevalence of obesity and body fat distribution of Moroccan women of childbearing age, using a panel of anthropometric measurements.

Design and setting:

A cross-sectional survey conducted in 1995 in an agricultural community, El Jadida province of Morocco. Weight, height, waist and hip circumferences and triceps, biceps, subscapular and supra-iliac skinfold thicknesses were measured. Body mass index (BMI), waist/hip ratio (WHR), sum of all and sum of trunk skinfold thicknesses were determined.

Subjects:

In total, 1269 women aged 15–49 years from urban and rural areas were surveyed.

Results:

The means of all anthropometric measurements including body fat were higher in urban than in rural women and increased with age. Trunk fat contributed 50% of total fat. Globally, 4.7% of women were underweight (BMI < 18.5 kg m−2), 35.2% were overweight or obese (BMI ≥ 25 kg m−2), 10.1% were obese (BMI ≥ 30 kg m−2) and 16.8% had central obesity (WHR > 0.85). The prevalence of overweight and obesity was higher in the urban than in the rural area. Underweight prevalence decreased with age, whereas that of overweight and obesity increased. All anthropometric parameters adjusted for age increased with the increase of BMI and WHR.

Conclusions:

Although undernutrition is still prevalent, there is an alarming prevalence of overweight and obesity in Moroccan women of childbearing age. The results indicate a shift in this country from the problem of dietary deficiency to the problem of dietary excess, and alert one to the necessity of establishing an intervention to prevent obesity-related diseases. It is necessary to address which of the anthropometric variables studied here is the best predictor of obesity-related diseases in this population.
Cerebrospinal Fluid Leak Prevention After Translabyrinthine Removal of Vestibular Schwannoma
Authors: Khrais Tarek H. , Falcioni Maurizio , Taibah Abdelkader , Agarwal Manoj , Sanna Mario
Published: May 2004

Objectives/Hypothesis: The purpose of the report was to present an update on the authors' results for prevention and management of cerebrospinal fluid (CSF) leak after translabyrinthine approach for vestibular schwannoma.

Study Design: Retrospective case review.

Methods: The study was conducted at Gruppo Otologico (Piacenza, Italy), a tertiary referral center for neurotology and skull base surgery. In all, 710 patients underwent translabyrinthine approach for the removal of vestibular schwannoma at that institution between April 1987 and December 2002. The medical records were retrospectively reviewed to identify tumor size, the incidence of postoperative CSF leak, and its treatment.

Results: The overall rate of CSF leak was 1.4%.

Conclusion: The use of proper surgical technique minimizes the risk of CSF leak. Study results show that the continued application of the authors' proposed preventive measures resulted in the maintenance of a low rate of CSF leak. Immediate management of CSF fistulae helps prevent meningitis.
Association Between Birth Control Pills and Voice Quality
Authors: Amir Ofer , Kishon‐Rabin Liat
Published: May 2004

Objectives/Hypothesis: The objective was to extend our knowledge of the effect of birth control pills on voice quality in women based on various acoustic measures.

Study Design: A longitudinal comparative study of 14 healthy young women over a 36‐ to 45‐day period.

Methods: Voices of seven women who used birth control pills and seven women who did not were recorded repeatedly approximately 20 times. Voice samples were analyzed acoustically, using an extended set of frequency perturbation parameters (jitter, relative average perturbation, pitch period perturbation quotient), amplitude perturbation parameters (shimmer, amplitude average perturbation quotient), and noise indices (noise‐to‐harmonics ratio, voice turbulence index).

Results: Voice quality and stability were found to be better among the women who used birth control pills. Lower values were found for all acoustic measures with the exception of voice turbulence index. Results also provided preliminary indication for vocal changes associated with the days preceding ovulation.

Conclusion: In contrast to the traditional view of oral contraceptives as a risk factor for voice quality, and in keeping with the authors' previous work, the data in the present study showed that not only did oral contraceptives have no adverse effect on voice quality but, in effect, most acoustic measures showed improved voice quality among women who used the birth control pill. The differences in the noise indices between groups may also shed light on the nature of the effect of sex hormones on vocal fold activity. It was suggested that hormonal fluctuations may have more of an effect on vocal fold regulation of vibration than on glottal adduction.
The ‘Hardwicke circle’: the Whig supremacy and its demise in the 18th-century Royal Society
Authors: Miller D. P.
Published: May 2004

This paper examines the composition and activities of an important grouping in the Royal Society in the middle decades of the 18th Century, which I call the ‘Hardwicke circle’. Members of the circle occupied high office at the Royal Society and effectively controlled its affairs for many years. The intellectual interests and political sentiments of the members of the circle are outlined, in part by looking at critics of their regime. It is argued that the waning of the power of the circle and the advent of the Banksian regime heralded a major shift in the cultural politics of the institution.
New Developments in Developing Self‐Directed Work Groups
Authors: Zuidema Kevin R. , Kleiner Brian H.
Published: May 2004

In the past decade there has been a movement towards “employee
empowerment”. Employee/management teams have played an integral part in
this change. Recently, the idea of the self‐directed work group has
emerged, giving groups of employees both the responsibility over a
particular area or function of the business, as well as authority to
make decisions and implement solutions in that area. Large productivity
increases, high morale, and increased employee commitment are some of
the benefits of these groups, but all is not positive. Argues that
companies wanting to switch to self‐directed work groups must be
prepared thoroughly for the changes that will lie ahead. There are a
number of areas which, if focused on now, will minimize the difficulties
that can result before and after the process of change has begun. They
can be categorized into three topics: preparing the organization
(including top management attitudes, organizational structure,
compensation systems, and employee‐retention strategies), preparing
management (including attitudes, skills training, and vocabulary
changes), and preparing employees (including attitudes, communication
and group skills‐training, and job cross‐training).
Intellectual capital: an exploratory study that develops measures and models
Authors: Bontis Nick
Published: May 2004

This paper details an empirical pilot study that explores the development of several conceptual measures and models regarding intellectual capital and its impact on business performance. The objective of this pilot study is to explore the development of items and constructs through principal components analysis and partial least squares (PLS). The final retained, subjective measures and optimal structural specification show a valid, reliable, significant and substantive causal link between dimensions of intellectual capital and business performance. These results should help both academics and practitioners more readily understand the components of intellectual capital and provide insight into developing and increasing it within an organization. Suggestions are then made to advance and improve this research programme.
Developing self‐directed work teams
Authors: Clifford Gavin P. , Sohal Amrik S.
Published: May 2004

Over the past decade many manufacturing organisations around the world have been changing their structures from the traditional hierarchical pyramid structure to a flatter, more responsive and lean structure. Team work and employee participation have become the key tasks for managers in all types of industries. This paper discusses team work and self‐directed work teams. It presents some of the key findings from a survey conducted in Australia and describes the four stages of developing self‐directed work teams. Some recommendations for companies adopting work teams are also made.
Promoting organizational and scholarly transformation
Authors: Maier Mark
Published: May 2004

A pioneer of the “videocase” describes the contents, development and impact of his module on the space shuttle Challenger disaster, highlighting key dimensions which have contributed to its effectiveness as a tool for managerial education and development. Critical lessons from the development of the videocase are identified in order to provide insights and guidelines for scholars and others interested in creating similar resources.
The research on school marketing
Authors: Oplatka Izhar , Hemsley‐Brown Jane
Published: May 2004

This review provides a synthesis of the scholarship that has sought to expand the understanding of educational marketing practice in schools. The following research questions guided this review. What are the common themes and characteristics that emerge from research about marketing in schools? What remains underdeveloped in the characterization of the school marketing and what are the topics for future research? Based on 25 studies identified as pertinent to the current review the topics of: marketing perceptions, marketing planning, marketing strategies and promotion are discussed. The paper concludes by providing an analysis of the limitations of the current research and discussing future directions for research on school marketing.
Testing for Age‐at‐Onset Anticipation with Affected Parent‐Child Pairs
Authors: Rabinowitz Daniel , Yang Qiong
Published: May 2004

Summary. The tendency for the onset of a genetic disease to occur at progressively earlier ages or with progressively greater severity in successive generations is known as anticipation. Following the discovery of trinucleotide repeat expansion as a plausible genetic mechanism for anticipation, interest in testing for anticipation has increased. Studies of anticipation can be biased when parents with late onset or children with early onset are preferentially ascertained. This paper presents a nonparametric approach to testing for age‐at‐onset anticipation that adjusts for such preferential ascertainment. The approach is illustrated through application to data on panic disorder.
Decision Theoretic Designs for Phase II Clinical Trials with Multiple Outcomes
Authors: Stallard Nigel , Thall Peter F. , Whitehead John
Published: May 2004

Summary. In many phase II clinical trials, it is essential to assess both efficacy and safety. Although several phase II designs that accommodate multiple outcomes have been proposed recently, none are derived using decision theory. This paper describes a Bayesian decision theoretic strategy for constructing phase II designs based on both efficacy and adverse events. The gain function includes utilities assigned to patient outcomes, a reward for declaring the new treatment promising, and costs associated with the conduct of the phase II trial and future phase III testing. A method for eliciting gain function parameters from medical collaborators and for evaluating the design's frequentist operating characteristics is described. The strategy is illustrated by application to a clinical trial of peripheral blood stem cell transplantation for multiple myeloma.
Analysis of Experimental Data with Repeated Measurements
Authors: Reiczigel Jenö
Published: May 2004

Summary. Experimental data often consist of serial measurements on subjects after a treatment. Typical questions concerning such data are: (A) Do subjects really react to treatment or are the fluctuations just random? (B) What are the numerical characteristics of the response? (C) Is the response identical in all groups? Differences between the individuals in the dynamics of the reaction make it difficult to apply standard statistical procedures. This paper proposes to answer questions (A) and (B) at the individual level, then to give an answer to (C) on the basis of this information. This kind of analysis may be useful since it can separate subjects giving response from those that do not and can identify individual response patterns and compare treatments with respect to each numerical characteristic separately. To answer question (A), a permutation test is proposed and its power is evaluated by simulation.
Two Approaches for Estimating Disease Prevalence from Population‐Based Registries of Incidence and Total Mortality
Authors: Gail Mitchell H. , Kessler Larry , Midthune Douglas , Scoppa Steven
Published: May 2004

Summary. Two approaches are described for estimating the prevalence of a disease that may have developed in a previous restricted age interval among persons of a given age at a particular calendar time. The prevalence for all those who ever developed disease is treated as a special case. The counting method (CM) obtains estimates of prevalence by dividing the estimated number of diseased persons by the total population size, taking loss to follow‐up into account. The transition rate method (TRM) uses estimates of transition rates and competing risk calculations to estimate prevalence. Variance calculations are described for CM and TRM as well as for a variant of CM, called counting method times 10 (CM10), that is designed to yield more precise estimates than CM. We compare these three estimators in terms of precision and in terms of the underlying assumptions required to justify the methods. CM makes fewer assumptions but is typically less precise than TRM or CM10. For common diseases such as breast cancer, CM may be preferred because its precision is excellent even though not as high as for TRM or CM10. For less common diseases, such as brain cancer, however, TRM or CM10 and other methods that make stabilizing assumptions may be preferred to CM.
Design of Validation Studies for Estimating the Odds Ratio of Exposure–Disease Relationships When Exposure Is Misclassified
Authors: Holcroft Christina A. , Spiegelman Donna
Published: May 2004

Summary. We compared several validation study designs for estimating the odds ratio of disease with misclassified exposure. We assumed that the outcome and misclassified binary covariate are available and that the error‐free binary covariate is measured in a subsample, the validation sample. We considered designs in which the total size of the validation sample is fixed and the probability of selection into the validation sample may depend on outcome and misclassified covariate values. Design comparisons were conducted for rare and common disease scenarios, where the optimal design is the one that minimizes the variance of the maximum likelihood estimator of the true log odds ratio relating the outcome to the exposure of interest. Misclassification rates were assumed to be independent of the outcome. We used a sensitivity analysis to assess the effect of misspecifying the misclassification rates. Under the scenarios considered, our results suggested that a balanced design, which allocates equal numbers of validation subjects into each of the four outcome/mismeasured covariate categories, is preferable for its simplicity and good performance. A user‐friendly Fortran program is available from the second author, which calculates the optimal sampling fractions for all designs considered and the efficiencies of these designs relative to the optimal hybrid design for any scenario of interest.
Validating Marker‐Based Incidence Estimates in Repeatedly Screened Populations
Authors: Satten Glen A. , Janssen Robert , Busch Michael P. , Datta Somnath
Published: May 2004

Summary. Disease incidence (new cases of disease per person per year) is usually measured by using longitudinal data. However, several recent proposals for measuring the incidence of human immunodeficiency virus (HIV) rely on cross‐sectional data only. These methods assume each person is only sampled once; however, in some instances, it is necessary to consider these cross‐sectional methods when individuals are represented more than once in the survey sample. We derive an extension of the cross‐sectional incidence estimator that is valid for data from repeatedly screened populations and show under what conditions our new estimator reduces to the old estimator. An example involving estimation of HIV incidence among repeat blood donors is presented.
An Exact Test for All‐Way Interaction in A 2 M Contingency Table: Application to Interval Capture–Recapture Estimation of Population Size
Authors: Regal Ronald R. , Hook Ernest B.
Published: May 2004

Summary. An exact conditional test for an M‐way log‐linear interaction in a fully observed 2M contingency table is formulated. Prom this is derived a procedure for interval estimation of the total count N in a 2 M contingency table, one of whose entries is unobserved. This procedure has an immediate application to interval estimation of the size of a closed population from incomplete, overlapping lists of records, as in capture‐recapture analysis of epidemiological data. Data on the prevalence of spina bifida in live births in upstate New York in 1969–1974 illustrate this application.
Wildlife Population Assessment: Past Developments and Future Directions
Authors: Buckland S. T. , Goudie I. B. J. , Borchers D. L.
Published: May 2004

Summary.We review the major developments in wildlife population assessment in the past century. Three major areas are considered: mark‐recapture, distance sampling, and harvest models. We speculate on how these fields will develop in the next century. Topics for which we expect to see methodological advances include integration of modeling with Geographic Information Systems, automated survey design algorithms, advances in model‐based inference from sample survey data, a common inferential framework for wildlife population assessment methods, improved methods for estimating population trends, the embedding of biological process models into inference, substantially improved models for conservation management, advanced spatiotemporal models of ecosystems, and greater emphasis on incorporating model selection uncertainty into inference. We discuss the kind of developments that might be anticipated in these topics.
Bayesian Nonparametric Inference on the Dose Level with Specified Response Rate
Authors: Mukhopadhyay Saurabh
Published: May 2004

Summary.The richness of nonparametric Bayesian models has attracted many different applications. Its application in dose‐finding studies has been hindered due to lack of methodologies on the nonparametric Bayesian inference on percentiles. The primary interest in dose‐finding studies focuses inference on the unknown toxicity or efficacy dose level corresponding to a prespecified rate. This paper shows how this problem may generally be handled by deriving inference on percentiles of a distribution following a Dirichlet process prior. In particular, theoretical results are derived to obtain the nonparametric Bayesian inference of the unknown dose level. This is followed by a description of the numerical implementation of that theory. The method also allows efficient estimation of the entire potency curve. Finally, the usefulness of the approach is demonstrated via an experimental data example.
Bayesian Information Criterion for Censored Survival Models
Authors: Volinsky Chris T. , Raftery Adrian E.
Published: May 2004

Summary.We investigate the Bayesian Information Criterion (BIG) for variable selection in models for censored survival data. Kass and Wasserman (1995,Journal of the American Statistical Association90, 928–934) showed that BIG provides a close approximation to the Bayes factor when a unit‐information prior on the parameter space is used. We propose a revision of the penalty term in BIG so that it is defined in terms of the number of uncensored events instead of the number of observations. For a simple censored data model, this revision results in a better approximation to the exact Bayes factor based on a conjugate unit‐information prior. In the Cox proportional hazards regression model, we propose defining BIG in terms of the maximized partial likelihood. Using the number of deaths rather than the number of individuals in the BIC penalty term corresponds to a more realistic prior on the parameter space and is shown to improve predictive performance for assessing stroke risk in the Cardiovascular Health Study.
Torsional fatigue and endurance limit of a size 30 .06 ProFile rotary instrument
Authors: Best S. , Watson P. , Pilliar R. , Kulkarni G. G. K. , Yared G.
Published: May 2004

Aim  To evaluate the torsional cyclic fatigue characteristics and specifically the endurance limit (EL) of a nickel–titanium rotary instrument.

Methodology  Size 30 .06 taper ProFile instruments were evaluated. The equipment was assembled according to the ANSI/ADA Specification No. 28. The motor was programmed to repeatedly rotate to a selected deflection angle (DA) and then return to zero (cycle). Testing started at 200° and was continued at decreasing angles until 106 cycles were reached without instrument fracture. Ten instruments were tested at each DA. The mean log number of cycles to fracture and standard deviation were determined for each DA at which fracture occurred. The DA at which 106 cycles were reached without instrument fracture corresponded by definition to the EL. Analysis of variance and pairwise comparisons using Duncan's multiple range test were performed to detect significant differences among the mean log number of cycles of the different DA. Significance was determined at the 95% confidence level.

Results  Instruments cycled at larger DA consistently demonstrated fewer cycles to fracture than those cycled at smaller DA. The differences among the mean log number of cycles of the different DA were statistically significant (P < 0.001). Cycles of 106 were completed without instrument fracture at 2.5°.

Conclusions  A torsional fatigue profile was generated for a specific NiTi rotary instrument. The EL was 2.5°.
Variation in lipid A structure in the pathogenic yersiniae
Authors: Rebeil Roberto , Ernst Robert K. , Gowen Brian B. , Miller Samuel I. , Hinnebusch B. Joseph
Published: May 2004

Important pathogens in the genus Yersinia include the plague bacillus Yersinia pestis and two enteropathogenic species, Yersinia pseudotuberculosis and Yersinia enterocolitica. A shift in growth temperature induced changes in the number and type of acyl groups on the lipid A of all three species. After growth at 37°C, Y. pestis lipopolysaccharide (LPS) contained the tetra‐acylated lipid IVA and smaller amounts of lipid IVA modified with C10 or C12 acyl groups, Y. pseudotuberculosis contained the same forms as part of a more heterogeneous population in which lipid IVA modified with C16:0 predominated, and Y. enterocolitica produced a unique tetra‐acylated lipid A. When grown at 21°C, however, the three yersiniae synthesized LPS containing predominantly hexa‐acylated lipid A. This more complex lipid A stimulated human monocytes to secrete tumour necrosis factor‐α, whereas the lipid A synthesized by the three species at 37°C did not. The Y. pestis phoP gene was required for aminoarabinose modification of lipid A, but not for the temperature‐dependent acylation changes. The results suggest that the production of a less immunostimulatory form of LPS upon entry into the mammalian host is a conserved pathogenesis mechanism in the genus Yersinia, and that species‐specific lipid A forms may be important for life cycle and pathogenicity differences.
Identification of novel dominant INO2 c mutants with an Opi– phenotype
Authors: Gardenour Kyle R. , Levy Jamie , Lopes John M.
Published: May 2004

The INO2 gene of Saccharomyces cerevisiae is required for derepression of the phospholipid biosynthetic genes in response to inositol depletion. Conversely, the OPI1 gene is required for repression in response to inositol supplementation. Results of an in vitro assay have led to a model in which Opi1p interacts with Ino2p. However, there is no in vivo evidence to support this model. Additionally, most of the previously isolated ino2 mutants offer little insight into this model. Here, we report the isolation of a new class of dominant mutations in the INO2 gene, which yield constitutive expression of a target gene (i.e. an Opi– mutant phenotype). Two mutations reside in a region of the Ino2p required for interaction with Opi1p in vitro. Three other mutations are at the amino‐terminus in a transcriptional activation domain.
Oligomeric structure of the Bacillus subtilis cell division protein DivIVA determined by transmission electron microscopy
Authors: Stahlberg H. , Kutejová E. , Muchová K. , Gregorini M. , Lustig A. , Müller S. A. , Olivieri V. , Engel A. , Wilkinson A. J. , Barák I.
Published: May 2004

DivIVA from Bacillus subtilis is a bifunctional protein with distinct roles in cell division and sporulation. During vegetative growth, DivIVA regulates the activity of the MinCD complex, thus helping to direct cell division to the correct mid‐cell position. DivIVA fulfils a quite different role during sporulation in B. subtilis when it directs the oriC region of the chromosome to the cell pole before asymmetric cell division. DivIVA is a 19.5 kDa protein with a large part of its structure predicted to form a tropomyosin‐like α‐helical coiled‐coil. Here, we present a model for the quaternary structure of DivIVA, based on cryonegative stain transmission electron microscopy images. The purified protein appears as an elongated particle with lateral expansions at both ends producing a form that resembles a ‘doggy‐bone’. The particle mass estimated from these images agrees with the value of 145 kDa measured by analytical ultracentrifugation suggesting 6‐ to 8‐mers. These DivIVA oligomers serve as building blocks in the formation of higher order assemblies giving rise to strings, wires and, finally, two‐dimensional lattices in a time‐dependent manner.
Catheter Inversion:
Authors: SPORTON SIMON C. , DAVIES D. WYN , EARLEY MARK J. , MARKIDES VIAS , W. NATHAN ANTHONY , SCHILLING RICHARD J.
Published: May 2004

Cure of typical atrial flutter (AFL) by catheter ablation to produce bidirectional block across the tricuspid annulus‐inferior vena cava isthmus (IS) is highly effective, but failures may occur. We describe a technique that may allow creation of bidirectional block where a conventional strategy has failed.AFL ablation was performed using the conventional approach with a mapping/ablation (ablation) catheter introduced via the right femoral vein (RFV) to create a line of bidirectional block across the IS. If this was not achieved after five passes of the ablation catheter from the tricuspid annulus to the inferior vena cava (IVC) a catheter inversion technique was used. This allowed stable positioning of the ablation catheter at the IVC end of the isthmus. In 11 patients, a mean of 17 (range 3 to 45) radiofrequency (RF) applications was given before the catheter inversion technique was applied. Following catheter inversion a mean of 4 (1 to 14) further RF applications achieved bidirectional isthmus block in every patient. No complications occurred. Catheter inversion provides a simple, safe, and effective means of achieving bidirectional isthmus conduction block in cases where a conventional ablation strategy might have failed. (PACE 2004; 27[Pt. I]:775–778)
Implantation of Submammary Implantable Cardioverter Defibrillators
Authors: ÖZİN BÜLENT , BORMAN HÜSEYIN , BOZBAŞ HÜSEYUN , ATAR İLYAS , KORKMAZ MEHMET EMIN , MÜDERRİSOǦLU HALDUN
Published: May 2004

Implantable cardioverter defibrillators (ICDs) are routinely placed in the left pectoral area using a transvenous approach. This approach may result in poor cosmetic outcome and cause psychological problems, especially in younger patients. To avoid this, several alternative implantation techniques have been developed. For cosmetic reasons, we used a submammary technique to implant ICDs into three young women. Apart from defibrillation threshold testing, the procedures were performed under local anesthesia. Threshold testing was done under general anesthesia. Appropriate defibrillation thresholds were obtained in all three cases, and all the patients tolerated the procedure well. There were no complications in a mean of 22 months of follow‐up, and the cosmetic results were very good.(PACE 2004; 27[Pt. I]:779–782)
The Left Ventricular Apex is the Optimal Site for Pediatric Pacing:
Authors: VANAGT WARD Y. , VERBEEK XANDER A. , DELHAAS TAMMO , MERTENS LUC , DAENEN WILLEM J. , PRINZEN FRITS W.
Published: May 2004

Pacing at the commonly used right ventricular (RV) apex results in impaired ventricular performance. Previous animal studies indicated that the left ventricular (LV) apex is a superior pacing site. The purpose of this study was to investigate in dogs whether this good performance is associated with a more synchronous electrical activation pattern of the LV and whether the LV apex is also a good pacing site in children. In 11 healthy dogs and 8 children undergoing cardiac surgery, dual chamber pacing was performed at the RV apex, LV apex and LV lateral free wall (LVFW). In dogs, a basket electrode was inserted into the LV to assess pattern and timing of LV endocardial activation. In the children, hemodynamic measurements were performed immediately after recovery from cardiopulmonary bypass. In dogs, LV apex pacing resulted in synchronous activation around the LV circumference whereas RV apex and LVFW pacing resulted in asynchrony of activation between the septum and LVFW. In both canine and children's hearts most hemodynamic variables remained at sinus rhythm level during LV apex pacing, but LVdPdtmax, stroke work (dogs), and pulse pressure (children) were reduced as compared with sinus rhythm during RV apex and LVFW pacing. LV apex pacing results in synchronous activation of the LV and is, in adult dogs and in children, associated with superior hemodynamic performance. (PACE 2004; 27 [Pt. II]:837–843)
Echocardiographic measurements in clinically healthy ferrets anesthetized with isoflurane
Authors: Vastenburg Maartje H.A.C. , Boroffka Susanne A.E.B. , Schoemaker Nico J.
Published: May 2004

Two‐dimensional, M‐mode, and color flow Doppler echocardiography was performed in 29 (18 females, 11 males) clinically healthy ferrets anesthetized with isoflurane. M‐mode measurements of the left ventricle, left atrial appendage diameter (LAAD), and aorta (Ao) were obtained. The fractional shortening and LAAD/Ao ratio were calculated. The values of the M‐mode measurements were compared between the male and female ferrets using a Student'st‐test. No significant differences were found. The difference in body weight between the male and female ferrets was highly significant (P<0.001), but no significant correlation was found between body weight and M‐mode measurements. Color flow Doppler examinations of the mitral, tricuspid, aortic, and pulmonary valves were recorded and there was minor valvular regurgitation in five ferrets, which was considered nonsignificant.
Na+/Ca2+ exchanger plays a key role in inducing apoptosis after hypoxia in cultured guinea pig ventricular myocytes
Authors: Eigel B. N. , Gursahani H. , Hadley R. W.
Published: May 2004

Altered Na+/Ca2+ exchanger (NCX) protein expression or activity is thought to contribute to various aspects of cardiac pathology. In guinea pig ventricular myocytes, NCX-mediated Ca2+ entry is almost entirely responsible for Ca2+ overload during hypoxia-reoxygenation. Because Ca2+ overload is a common initiator of apoptosis, the purpose of this study was to test the hypotheses that NCX activity is critically involved in initiating apoptosis after hypoxia-reoxygenation and that hypoxia-reoxygenation-induced apoptosis can be modulated by changes in NCX protein expression or activity. An NCX antisense oligonucleotide was used to reduce NCX protein expression in cultured adult guinea pig ventricular myocytes. Caspase-3 activation and cytochrome c release were used as markers of apoptosis. Hypoxia-reoxygenation-induced apoptosis was significantly decreased in antisense-treated myocytes compared with untreated control or nonsense-treated myocytes. Pretreatment of cultured myocytes for 24 h with either endothelin-1 or phenylephrine was found to increase both NCX protein expression and evoked NCX activity as well as enhance hypoxia-reoxygenation-induced apoptosis. Control experiments demonstrated that endothelin-1 and phenylephrine did not induce apoptosis on their own nor did they enhance the apoptotic response in a model of Ca2+-dependent, NCX-independent apoptosis. Additional control experiments demonstrated that the NCX antisense oligonucleotide did not alter the apoptotic response of myocytes to either H2O2 or isoproterenol. Taken together, these data suggest that the NCX has a critical and specific role in the initiation of apoptosis after hypoxia-reoxygenation in guinea pig myocytes and that hypoxia-reoxygenation-induced apoptosis is quite sensitive to changes in NCX activity.
Rat corin gene: molecular cloning and reduced expression in experimental heart failure
Authors: Langenickel Thomas H. , Pagel Ines , Buttgereit Jens , Tenner Katja , Lindner Maren , Dietz Rainer , Willenbrock Roland , Bader Michael
Published: May 2004

Stored cardiac pro-atrial natriuretic peptide (pro-ANP) is converted to ANP and released upon stretch from the atria into the circulation. Corin is a serin protease with pro-ANP-converting properties and may be the rate-limiting enzyme in ANP release. This study was aimed to clone and sequence corin in the rat and to analyze corin mRNA expression in heart failure when ANP release upon stretch is blunted. Full-length cDNA of rat corin was obtained from atrial RNA by RT-PCR and sequenced. Tissue distribution as well as regulation of corin mRNA expression in the atria were determined by RT-PCR and RNase protection assay. Heart failure was induced by an infrarenal aortocaval shunt. Stretch was applied to the left atrium in a working heart modus, and ANP was measured in the perfusates. The sequence of rat corin cDNA was found to be 93.6% homologous to mouse corin cDNA. Corin mRNA was expressed almost exclusively in the heart with highest concentrations in both atria. The aortocaval shunt led to cardiac hypertrophy and heart failure. Stretch-induced ANP release was blunted in shunt animals (control 1,195 ± 197 fmol·min−1·g−1; shunt: 639 ± 99 fmol·min−1·g−1, P < 0.05). Corin mRNA expression was decreased in both atria in shunt animals [right atrium: control 0.638 ± 0.004 arbitrary units (AU), shunt 0.566 ± 0.014 AU, P < 0.001; left atrium: control 0.564 ± 0.009 AU, shunt 0.464 ± 0.009 AU, P < 0.001]. Downregulation of atrial corin mRNA expression may be a novel mechanism for the blunted ANP release in heart failure.
Ion and diuretic specificity of chimeric proteins between apical Na+-K+-2Cl−and Na+-Cl−cotransporters
Authors: Tovar-Palacio Claudia , Bobadilla Norma A. , Cortés Paulina , Plata Consuelo , de los Heros Paola , Vázquez Norma , Gamba Gerardo
Published: May 2004

The mammalian kidney bumetanide-sensitive Na+-K+-2Cl−and thiazide-sensitive Na+-Cl−cotransporters are the major pathways for salt reabsorption in the thick ascending limb of Henle's loop and distal convoluted tubule, respectively. These cotransporters serve as receptors for the loop- and thiazide-type diuretics, and inactivating mutations of corresponding genes are associated with development of Bartter's syndrome type I and Gitleman's disease, respectively. Structural requirements for ion translocation and diuretic binding specificity are unknown. As an initial approach for analyzing structural determinants conferring ion or diuretic preferences in these cotransporters, we exploited functional differences and structural similarities between Na+-K+-2Cl−and Na+-Cl−cotransporters to design and study chimeric proteins in which the NH2-terminal and/or COOH-terminal domains were switched between each other. Thus six chimeric proteins were produced. Using the heterologous expression system of Xenopus laevis oocytes, we observed that four chimeras exhibited functional activity. Our results revealed that, in the Na+-K+-2Cl−cotransporter, ion translocation and diuretic binding specificity are determined by the central hydrophobic domain. Thus NH2-terminal and COOH-terminal domains do not play a role in defining these properties. A similar conclusion can be suggested for the Na+-Cl−cotransporter.