bluuebunny/crossref_metadata_2025 huggingface dataset:
Haplotype-based linkage disequilibrium mapping via direct data mining
Authors: Li Jing , Jiang Tao
Published: October 2005

Motivation: With the availability of large-scale, high-density single-nucleotide polymorphism markers and information on haplotype structures and frequencies, a great challenge is how to take advantage of haplotype information in the association mapping of complex diseases in case–control studies.

Results: We present a novel approach for association mapping based on directly mining haplotypes (i.e. phased genotype pairs) produced from case–control data or case–parent data via a density-based clustering algorithm, which can be applied to whole-genome screens as well as candidate-gene studies in small genomic regions. The method directly explores the sharing of haplotype segments in affected individuals that are rarely present in normal individuals. The measure of sharing between two haplotypes is defined by a new similarity metric that combines the length of the shared segments and the number of common alleles around any marker position of the haplotypes, which is robust against recent mutations/genotype errors and recombination events. The effectiveness of the approach is demonstrated by using both simulated datasets and real datasets. The results show that the algorithm is accurate for different population models and for different disease models, even for genes with small effects, and it outperforms some recently developed methods.

Availability: The software, HapMiner, and Supplementary materials are available on the authors' website at

Contact:  jingli@eecs.case.edu
Automatic term list generation for entity tagging
Authors: Sandler Ted , Schein Andrew I. , Ungar Lyle H.
Published: October 2005

Motivation: Many entity taggers and information extraction systems make use of lists of terms of entities such as people, places, genes or chemicals. These lists have traditionally been constructed manually. We show that distributional clustering methods which group words based on the contexts that they appear in, including neighboring words and syntactic relations extracted using a shallow parser, can be used to aid in the construction of term lists.

Results: Experiments on learning lists of terms and using them as part of a gene tagger on a corpus of abstracts from the scientific literature show that our automatically generated term lists significantly boost the precision of a state-of-the-art CRF-based gene tagger to a degree that is competitive with using hand curated lists and boosts recall to a degree that surpasses that of the hand-curated lists. Our results also show that these distributional clustering methods do not generate lists as helpful as those generated by supervised techniques, but that they can be used to complement supervised techniques so as to obtain better performance.

Availability: The code used in this paper is available from

Contact:  tsandler@seas.upenn.edu
Gene selection using support vector machines with non-convex penalty
Authors: Zhang Hao Helen , Ahn Jeongyoun , Lin Xiaodong , Park Cheolwoo
Published: October 2005

Motivation: With the development of DNA microarray technology, scientists can now measure the expression levels of thousands of genes simultaneously in one single experiment. One current difficulty in interpreting microarray data comes from their innate nature of ‘high-dimensional low sample size’. Therefore, robust and accurate gene selection methods are required to identify differentially expressed group of genes across different samples, e.g. between cancerous and normal cells. Successful gene selection will help to classify different cancer types, lead to a better understanding of genetic signatures in cancers and improve treatment strategies. Although gene selection and cancer classification are two closely related problems, most existing approaches handle them separately by selecting genes prior to classification. We provide a unified procedure for simultaneous gene selection and cancer classification, achieving high accuracy in both aspects.

Results: In this paper we develop a novel type of regularization in support vector machines (SVMs) to identify important genes for cancer classification. A special nonconvex penalty, called the smoothly clipped absolute deviation penalty, is imposed on the hinge loss function in the SVM. By systematically thresholding small estimates to zeros, the new procedure eliminates redundant genes automatically and yields a compact and accurate classifier. A successive quadratic algorithm is proposed to convert the non-differentiable and non-convex optimization problem into easily solved linear equation systems. The method is applied to two real datasets and has produced very promising results.

Availability: MATLAB codes are available upon request from the authors.

Contact:  hzhang@stat.ncsu.edu

Supplementary information:
PilZ domain is part of the bacterial c-di-GMP binding protein
Authors: Amikam Dorit , Galperin Michael Y.
Published: October 2005

Recent studies identified c-di-GMP as a universal bacterial secondary messenger regulating biofilm formation, motility, production of extracellular polysaccharide and multicellular behavior in diverse bacteria. However, except for cellulose synthase, no protein has been shown to bind c-di-GMP and the targets for c-di-GMP action remain unknown. Here we report identification of the PilZ (‘pills’) domain (Pfam domain PF07238) in the sequences of bacterial cellulose synthases, alginate biosynthesis protein Alg44, proteins of enterobacterial YcgR and firmicute YpfA families, and other proteins encoded in bacterial genomes and present evidence indicating that this domain is (part of) the long-sought c-di-GMP-binding protein. Association of the PilZ domain with a variety of other domains, including likely components of bacterial multidrug secretion system, could provide clues to multiple functions of the c-di-GMP in bacterial pathogenesis and cell development.

Contact: galperin@ncbi.nlm.nih.gov

Supplementary information:
Ayurveda and Traditional Chinese Medicine: A Comparative Overview
Authors: Patwardhan Bhushan , Warude Dnyaneshwar , Pushpangadan P. , Bhatt Narendra
Published: October 2005

Ayurveda, the traditional Indian medicine (TIM) and traditional Chinese medicine (TCM) remain the most ancient yet living traditions. There has been increased global interest in traditional medicine. Efforts to monitor and regulate herbal drugs and traditional medicine are underway. China has been successful in promoting its therapies with more research and science‐based approach, while Ayurveda still needs more extensive scientific research and evidence base. This review gives an overview of basic principles and commonalities of TIM and TCM and discusses key determinants of success, which these great traditions need to address to compete in global markets.
Short‐Chain Fatty Acid Induces Intestinal Mucosal Injury in Newborn Rats and Down‐Regulates Intestinal Trefoil Factor Gene Expression In Vivo and In Vitro
Authors: Lin Jing , Peng Luying , Itzkowitz Steven , Holzman Ian R , Babyatsky Mark W
Published: October 2005

Background:

Luminal administration of short‐chain fatty acids (SCFAs) induces dose‐dependent intestinal mucosal injury in newborn rats. However, the mechanism underlying the injurious effects of SCFAs on intestinal mucosa in neonates is unclear. Intestinal trefoil factor (ITF) is a factor important for the maintenance and repair of the intestinal mucosal barrier. Regulation of ITF gene expression by SCFAs may be involved as one of the mechanisms.

Objectives:

To examine the effect of butyrate‐induced colonic injury on ITF gene expression in vivo and to determine the molecular mechanisms underlying the butyrate regulation of ITF gene expression in vitro.

Methods:

Whole‐section colonic tissues from 9‐ to 10‐day‐old Sprague‐Dawley rats that have received butyric acid at two different concentrations (150 mmol/L and 300 mmol/L) and for different time periods were processed for total RNA extraction and Northern blot analysis. Littermates that received normal saline or lactic acid at 300 mmol/L served as controls. The effect of butyrate on ITF gene expression was also examined in vitro with human colonic epithelial LS 174T cells. To further define ITF gene regulation by butyrate, transient transfection assays were performed on a 930 bp human ITF promoter‐luciferase reporter gene plasmid in LS174T cells with or without the presence of butyrate.

Results:

Concurrent with mucosal injury, butyric acid inhibited ITF gene expression in colonic tissues of newborn rats as well as in intestinal epithelial cells in a dose‐ and time‐dependent manner. Furthermore, butyrate reduced ITF promoter report gene activity in transfected LS174T cell, suggesting that butyric acid regulation of ITF gene is by way of a specific ITF promoter.

Conclusions:

Butyric acid induced‐intestinal mucosal injury in newborn rats is associated with down‐regulation of ITF gene expression. The changes in ITF gene expression in vivo may play a role in the pathogenesis of SCFA‐induced intestinal mucosal injury.
Liver Histology and Alanine Aminotransferase Levels in Children and Adults with Chronic Hepatitis C Infection
Authors: Murray Karen F , Finn Laura S , Taylor Shari L , Seidel Kristy D , Larson Anne M
Published: October 2005

Background:

Chronic hepatitis C is often a mild disease in children, but whether this is related to younger age or shorter duration of infection is unclear. Histologic severity has been shown to correlate with duration of infection regardless of age.

Objectives:

We compared histologic findings in children and adults with chronic hepatitis C while controlling for sex, duration of infection, hepatitis C virus (HCV)‐RNA level, and genotype.

Methods:

Twenty‐one children and 52 adults whose infection was less than 20 years in duration and who had undergone a liver biopsy were included. Two blinded liver pathologists reviewed the liver biopsies and scored inflammatory activity and fibrosis using the modified Knodell scoring system.

Results:

The groups were the same with respect to HCV‐RNA level (P = 0.8), and genotype (P = 0.6) but differed in duration of disease (P = 0.01) and sex composition (P = 0.005). Covariate analysis showed no influence of genotype, duration of infection, or HCV‐RNA level on outcome. In controlling for sex, children had significantly milder liver disease and alanine aminotransferase (ALT) elevations.

Conclusions:

With equal duration of infection, HCV‐RNA level, and genotype, children have lower serum ALT levels and less severe liver disease than adults infected with HCV.
Double‐Blind Randomized Evaluation of Clinical and Biological Tolerance of Polyethylene Glycol 4000 Versus Lactulose in Constipated Children
Authors: Dupont Christophe , Leluyer Bernard , Maamri Nassira , Morali Alain , Joye Jean‐Pierre , Fiorini Jean‐Marc , Abdelatif A , Baranes C , Benoît S , Benssoussan A , Boussioux J L , Boyer P , Brunet E , Delorme J , François‐Cecchin S , Gottrand F , Grassart M , Hadji S , Kalidjian A , Languepin J , Leissler C , Lejay D , Livon D , Lopez J P , Mougenot J F , Risse J C , Rizk C , Roumaneix D , Schirrer J , Thoron B , Kalach N
Published: October 2005

Objectives:

To assess the safety of a polyethylene glycol (PEG) 4000 laxative without additional salts in pediatric patients.

Study Design:

This was a 3‐month multicenter, randomized, double‐blind, double‐dummy, lactulose‐controlled, parallel study enrolling 96 ambulatory constipated children aged 6 months to 3 years, treated daily with 4‐8 g PEG or 3.33 g‐6.66 g lactulose. Total protein, albumin, iron, electrolytes, and vitamins B9 (folates), A and D (25OHD3) were measured in blood before and after treatment (day 84) in a central laboratory.

Results:

The percentage of children with at least one value out of normal range at day 84 with respect to baseline status (with or without at least one value out of normal range), i.e. the primary endpoint, was 87% and 90% in the PEG and lactulose groups, respectively, without any difference between groups. The whole blood parameters showed no qualitative or quantitative treatment‐related changes. Vitamin A values were above normal range in 56% and 41% of children at baseline versus 33% and 36% at day 84 in the PEG and lactulose groups, respectively. Iron values were similarly under normal range in 47% and 51% at baseline versus 42% and 51% at day 84. Clinical tolerance was similar for both treatments except for vomiting and flatulence, which were significantly higher with lactulose. Significantly higher improvements were evidenced with PEG regarding stool consistency, appetite, fecaloma and use of additional laxatives.

Conclusion:

This 3‐month study in 96 constipated children aged 6 months to 3 years confirms the long‐term tolerance of PEG 4000 in pediatrics and indicates a PEG efficacy similar to or greater than that of lactulose.
Prevalence of Celiac Disease in Brazilian Children and Adolescents with Type 1 Diabetes Mellitus
Authors: Baptista Márcia Luiza , Koda Yu Kar Ling , Mitsunori Renato , Nisihara  , Ioshii Sérgio Ossamu
Published: October 2005

Objective:

A previously unrecognized high prevalence of celiac disease (CD) has been found by screening among European and North American patients with type 1 diabetes mellitus (DM 1). The prevalence of CD among Brazilian children with DM1 is not known. This study was conducted to determine the prevalence of CD in Brazilian children and adolescents with DM 1.

Methods:

One hundred and four children and adolescents with DM 1 (52 males and 52 females; age range 22 months ‐ 19 years) and 105 age and gender‐matched control participants were screened for CD using the IgA antiendomysial antibody test (IgA‐EmA) and total serum IgA. A small bowel biopsy was performed in all patients with positive IgA‐EmA.

Results:

Nine of 104 diabetic patients (8.7%) had a positive IgA‐EmA. Biopsies were normal in four patients, two had partial or subtotal villous atrophy with elevated intraepithelial lymphocyte (IEL) counts, and three showed partial villous atrophy but with IEL counts under the maximun limit adopted (40 IEL/100 enterocytes). EmA‐IgA positive patients had mild, non‐specific gastrointestinal complaints including dyspepsia, abdominal pain, flatulence and constipation. All control participants had negative results for IgA‐EmA.

Conclusion:

The prevalence of CD in a group of Brazilian pediatric DM 1 patients was at least 4.8%, a prevalence comparable to European and North American studies. The high prevalence of CD among DM 1 emphasizes the need for routine screening in all countries including Brazil.
A Pilot Test of the Addition of Zinc to the Current Case Management Package of Diarrhea in a Primary Healthcare Setting
Authors: Bhandari Nita , Mazumder Sarmila , Taneja Sunita , Dube Brinda , Black Robert E , Fontaine Olivier , Mahalanabis Dilip , Bhan Maharaj Kishan
Published: October 2005

Zinc is recommended for the treatment of acute diarrhea in children but the effect of its introduction on drug and oral rehydration solution use is unclear. Government care providers, private practitioners and community workers were trained to distribute zinc and oral rehydration solution to children seeking care for diarrhea. Periodic surveys showed that village‐based workers became a common source of diarrhea treatment and private practitioners were used less. Zinc was used in approximately half of the episodes; the prescription and use rates of oral rehydration solution packets increased from 7% at baseline to 44.9% 6 months later. Reduction in use of drugs during diarrhea ranged from 34% for tablets to 64% for injections 6 months later. The cost of treatment to families declined significantly. These findings need confirmation in a randomized controlled trial.
Safety of Percutaneous Liver Biopsy in Infants Less than Three Months Old
Authors: Azzam R K , Alonso E M , Emerick K M , Whitington P F
Published: October 2005

Objectives:

To evaluate the safety, outcomes, and complications of percutaneous liver biopsies (PLB) in infants aged 0 to 3 months.

Methods:

We retrospectively reviewed the hospital records of all infants less than 3 months old who underwent PLB at Children's Memorial Hospital between July 1, 1997 and June 30, 2004 for complications surrounding the procedure and risk factors that might lead to complications.

Results:

Sixty‐six PLBs were performed in 63 infants. Most patients tolerated the procedure without complications. Twelve complications were recorded, for an overall complication rate of 18%. Of these, five were directly related to the procedure, and seven were sedation related. Three patients experienced a drop in hemoglobin greater than 2 gm/dL, one patient developed a bile leak, and one developed a skin hematoma. Seven patients had respiratory difficulty related to sedation, which manifested as increased work of breathing or decreased respiratory rate with depression in pulse oximetry.

Conclusion:

We conclude that PLB in young infants is associated with a somewhat higher risk of complications than in older children, particularly complications related to sedation.
Innis Lecture: Explorations in medium‐run macroeconomics
Authors: Beaudry Paul
Published: October 2005

Abstract.  Medium‐run macroeconomics refers to aggregate economic phenomena that manifest over periods of 10 to 25 years. This area of research has emerged over the last decade as a new and distinct field of enquiry. In this paper, I overview a set of personal attempts aimed at understanding certain medium‐run phenomena such as: changes in the wage structure, changes in the world distribution of income‐per‐capita, and changes in growth patterns across OECD countries. The goal of the paper is to extract general lessons from these experiences. In particular, I will discuss why models of endogenous technological choice may be a good starting point for studying medium‐run phenomena. JEL classification: E00, O00
Product differentiation, cost‐reducing mergers, and consumer welfare
Authors: Norman George , Pepall Lynne , Richards Daniel
Published: October 2005

Abstract.  Cost synergies are an explicitly recognized justification for a two‐firm merger, and empirical techniques are now widely used to assess the impact of cost‐reducing mergers on prices and welfare in the post‐merger market. We show that if the merger occurs in a vertically product differentiated market, then the merger will lead to a reduction in product offerings that limits the usefulness of pre‐merger empirical estimates. Indeed, we further show that in such markets, two‐firm mergers will typically lead to higher prices regardless of the merger's cost savings. JEL classification: L10, L41
Sorting by foot: ‘travel‐for’ local public goods and equilibrium stratification
Authors: Peng Shin‐Kun , Wang Ping
Published: October 2005

Abstract.  We re‐examine Tiebout's hypothesis of endogenous sorting in a competitive spatial equilibrium framework, by considering both income and preference heterogeneity and by allowing agents to decide endogenously the number of visits to a ‘travel‐for’ local public good. The equilibrium configuration may be completely segregated, incompletely segregated, or completely integrated, depending on relative market rents and income/preference/local tax parameters. A segregated equilibrium may feature endogenous sorting purely by income or by both income and preferences. While the rich need not be closer to the local public facility site, multiple equilibria may arise when the equilibrium configuration is incompletely segregated. JEL classification: D50, H41
What drives the cross‐country growth and inequality correlation?
Authors: Bandyopadhyay Debasis , Basu Parantap
Published: October 2005

Abstract.  We present a neo‐classical model that explores the determinants of growth‐inequality correlation and attempts to reconcile the seemingly conflicting evidence on the nature of the growth‐inequality relationship. The initial distribution of human capital determines the long‐run income distribution and the growth rate by influencing the occupational choice of the agents. The steady‐state proportion of adults that innovates and updates human capital is path dependent. The output elasticity of skilled‐labour, barriers to knowledge spillovers, and the degree of redistribution determine the range of steady‐state equilibria. From a calibration experiment we report that a skill‐intensive technology, low barriers to knowledge spillovers, and high degrees of redistribution characterize the industrial countries with a positive growth‐inequality correlation. A negative correlation between growth and inequality arises for the group of non‐industrial countries with the opposite characteristics. JEL classification: E1, O4
Minorities and majorities: a dynamic model of assimilation
Authors: Kónya István
Published: October 2005

Abstract.  The paper analyses the population dynamics of a country that has two ethnic groups, a minority and a majority, and minority members can choose to assimilate into the majority. Depending on the minority's size, the long‐run outcome can be full or no assimilation. Under certain parameter values multiple equilibria exist, including the two extreme cases. The paper demonstrates that both the long‐run outcome and the equilibrium path may be inefficient. Two extensions to the basic model are considered. The first one allows for a comparison between a multicultural and a ‘melting pot’ society. The second one introduces population growth and studies the interplay between exogenous and endogenous changes in the minority's size. JEL classification: J110, J150, J180
Exchange rate regimes and inflation: only hard pegs make a difference
Authors: Bleaney Michael , Francisco Manuela
Published: October 2005

Abstract.  Using data from a large sample of developing countries from 1985 to 2001, we confirm that hard pegs (currency boards or a shared currency) reduce inflation and money growth. There is no evidence that soft pegs confer any monetary discipline, after other factors are controlled for. Inflation triggers regime switches. Under hard pegs, monetary growth is unaffected by fiscal deficits or by inflation shocks. Under soft pegs, as under floats, increased fiscal deficits and positive inflation shocks are associated with higher monetary growth. The apparently slower per capita output growth under hard pegs is explained by their geographical distribution. JEL classification: F41
Temporal patterns of breeding and recruitment in Nerophis lumbriciformis(Pisces; Syngnathidae) related to seawater temperatures
Authors: Monteiro N. M. , Almada V. C. , Vieira M. N.
Published: October 2005

The breeding season of Nerophis lumbriciformis, a cold water pipefish, was positively correlated with seawater temperatures <15·5° C, whilst recruitment occurred at the end of the upwelling season, when seawater temperature attained its maximum values. The observed alterations in seawater temperatures, with steady year‐round increases, and the consequent alteration of the upwelling regime, may have dramatic consequences in the maintenance of N. lumbriciformis populations, by reducing the breeding period and simultaneously contributing to the transport of pelagic larvae northwards due to specific sea currents that occur outside the upwelling season.
Validation of daily otolith increment formation in the larval myctophid fish Diaphus slender‐type spp.
Authors: Moku M. , Hayashi A. , Mori K. , Watanabe Y.
Published: October 2005

The marginal increment growth in sagittal otoliths of the myctophid larvae Diaphus slender‐type spp. collected in the north‐eastern East China Sea was examined based on specimens collected at different times of the day. The calcification of the incremental zone began after midnight and took place throughout the day, and the discontinuous zone was formed only around midnight. These results indicate that otolith increments are formed daily.
The effect of sex and shoal size on shoaling behaviour inDanio rerio
Authors: Ruhl N. , McRobert S. P.
Published: October 2005

Male and female zebra fishDanio reriowere given choices of shoals that differed in sex and size. Male zebra fish preferred to associate with female shoals over male shoals, but had no preference when given a choice between a mixed‐sex shoal and either a male or female shoal. Female zebra fish showed no significant preference when given a choice between male and females shoals, nor between mixed‐sex shoals and either male or female shoals. When given choices between shoals of differing size, females preferred to associate with the larger shoal, whether or not they were composed of males or females. Males, however, had no preference for larger shoals over smaller shoals, whether or not they were composed of males or females. These results showed that male zebra fish were capable of distinguishing between males and females solely on the basis of visual cues. Furthermore, these results demonstrated a significant difference between the shoaling choices of male and female zebra fish, which may indicate a difference in the function of shoaling for the two sexes.
Mechanistic modelling of gastric evacuation in predatory gadoids applying the square root model to describe surface‐dependent evacuation
Authors: Andersen N. G. , Beyer J. E.
Published: October 2005

A new model approach to gastric evacuation in predatory fishes was shown to give accurate and reliable estimates of evacuation. It is believed that such a model would prove particularly useful in understanding predator‐prey interactions in natural systems. The model is a simple, geometric abstraction of the square root model predicting that evacuation time is proportional to the square root of meal size in accordance with extensive empirical evidence. Digestive processes are assumed to be restricted to an outer surface of total stomach content that is represented by the curved side of a cylinder. This way, total stomach content is considered a cylinder of constant length the mass of which is gradually reduced by successive peeling off its side leaving the ends unaffected. The fundamental rate δ describes mean thickness of the layer that is peeled off the cylinder per time unit. In the model, δ is constant independent of cylinder thickness but inversely proportional to the square root of cylinder length. Anatomical and dynamic characteristics of the stomach render this formulation of δ plausible. Using mean evacuation rate over time during evacuation of a meal, the model disregards prey heterogeneities that influence instantaneous evacuation rate. Relationships between prey heterogeneities and evacuation patterns were indicated by application of a general power model to evacuation data, and it was suggested how the effects of prey characteristics might be incorporated into the square root model to produce a generic model of gastric evacuation.
Anguilla japonica is already magnetosensitive at the glass eel phase
Authors: Nishi T. , Kawamura G.
Published: October 2005

Magnetosensitivity of the Japanese eel Anguilla japonica at the glass eel phase (newly metamorphosed juveniles) was examined by conditioning and electrocardiography. The glass eels were conditioned to an imposed magnetic field of 192 473 nT parallel to the fish body placed along the earth's west‐east axis. After 10 to 40 conditioning runs, all the glass eels exhibited a significant conditioned response (i.e. slowing of the heart beat) to a 192 473 nT magnetic field and even to a 12 663 nT magnetic field that combined with the geomagnetic field (32 524 nT) at the laboratory and produced a resultant magnetic field of 21° easterly. These results indicate that glass eels have high magnetosensitivity and probably acquire geomagnetic information early in life. It is hypothesized that silver‐phase adult eels find their way back to the oceanic spawning ground by reversing the geomagnetic direction that had been detected and ‘memorized’ during the glass eel phase when migrating from the open ocean towards the continental shelf and coastal waters.
Effects of varying temperature and food availability on growth and reproduction in first‐time spawning female Atlantic cod
Authors: Yoneda M. , Wright P. J.
Published: October 2005

The somatic growth, sexual maturation and fecundity of individually marked first‐time spawning female Atlantic cod Gadus morhua were examined under different varying temperature and feeding regimes over the months preceding spawning. A negative correlation between somatic and oocyte growth was found, reflecting the changing energy allocation pattern. Nevertheless, the somatic growth of mature individuals was at least as high as those of immature fish over the period of vitellogenesis. Potential fecundity was positively correlated with body size, but neither temperature or feeding regime significantly affected this relationship. Consequently, fish with unlimited feeding opportunity invested more energy into somatic growth during vitellogenesis compared to those held under a restricted ration. This indicated that once Atlantic cod had made the decision to invest in first reproduction, they allocated a certain amount of energy relative to their size into egg production and any surplus was invested into somatic growth. Low temperature led to an arrest in the onset of vitellogenesis and significantly affected the number of females that matured.
Molecular genetic assessment of bipolarity in the anchovy genus Engraulis
Authors: Grant W. S. , Leslie R. W. , Bowen B. W.
Published: October 2005

To test three hypotheses accounting for bipolar distributions in Engraulis, seven of eight taxa (except E. eurystole) were surveyed with allozymes (34 loci) and 521 bp of the mitochondrial DNA cytochrome b gene. Both allozymes and mtDNA sequences revealed deep separations between New World and Old World anchovies with a mean allozyme genetic distance D = 1·26 and net mtDNA sequence divergence d = 15%. These values reflected separations of 5 to 10 million years. Contrary to previous phylogenetic hypotheses, which place north‐east Pacific E. mordax and south‐east Pacific E. ringens as sister taxa, the south‐west Atlantic E. anchoita and E. ringens are most closely related to each other. The north‐east Pacific E. mordax is the closest lineage to the Old World Engraulis, a group of taxa showing low divergences typical of population‐level separations (mean D = 0·06; mean d = 0·87%). Bipolarities of sister taxa in the east Atlantic and west Pacific reflect recent dispersals. Bipolarities in the east Pacific and west Atlantic represent paraphyletic taxa in lineages isolated since the Miocene. None of the bipolarities can be attributed to tectonic separations or competitive displacements from the tropics, but the latter situation should be re‐evaluated with comparisons to tropical anchovies of the New World.
Growth characteristics of skeletal muscle tissue in Oreochromis niloticus larvae fed on a lysine supplemented diet
Authors: Aguiar D. H. , Barros M. M. , Padovani C. R. , Pezzato L. E. , Dal Pai‐Silva M.
Published: October 2005

The effect of lysine amino acid supplementation on the growth characteristics and morphological pattern of skeletal muscle tissue in Nile tilapia Oreochromis niloticus larvae was evaluated. There were four treatments (T) with increasing levels of lysine supplement (T1 = 0·0%; T2 = 1·1%; T3 = 1·7%; T4 = 4·0%) and one treatment with a commercial diet (T5). In all treatments, morphological and histochemical muscle tissue analyses were similar. Two distinct layers were identified: a superficial red layer, more developed in the lateral line region, formed by fibres with intense to moderate NADH‐TR reaction and strong acid‐stable mATPase activity, and a deep white one, most of the muscle mass, formed by fibres with weak NADH‐TR reaction and strong alkali‐stable mATPase activity. There was an intermediate layer between these two layers with fibres exhibiting either weak acid‐stable or acid‐labile mATPase activity. Body mass increase was significantly higher in T5 than in the lysine treatments (T1–T4). There was no difference in number and diameters of muscle fibres between lysine treatments. In T5, muscle fibre diameter and number were higher. The frequency of red fibres with diameters ≤8 μm was higher in the lysine treatments, and with diameters between 16 and 24 μm, was higher in T5. Most white fibre diameters in T5 were significantly larger than 24 μm and in T1–T4 were between 8 and 16 μm. Cell proliferation was higher in the lysine treatments and muscle growth in T5 was mainly by fibre hypertrophy.
Finlets and the steady swimming performance of Thunnus albacares
Authors: Blake R. W. , Chan K. H. S. , Kwok E. W. Y.
Published: October 2005

The functional significance of finlets on the steady swimming performance of yellowfin tuna Thunnus albacares was evaluated by measuring the speed and tail‐beat frequency of the fish with and without them. It was hypothesized that if finlets do improve swimming performance, fish without finlets would have to work harder to maintain the same swimming speed as fish with them and that this would be reflected in kinematic differences. Two‐way ANOVA showed significant effects between individuals on speed (d.f. = 5 and 228, P < 0·001) and tail‐beat frequency (d.f. = 5 and 48, P < 0·001), but no significant effects of treatment on speed (d.f. = 1 and 228, P = 0·25) and tail‐beat frequency (d.f. = 1 and 48, P > 0·1). No interaction effects on speed (d.f. = 5 and 228, P > 0·1) and tail‐beat frequency (d.f. = 5 and 48, P > 0·25) were found. This suggested that finlets were unlikely to function as significant drag reduction and thrust enhancing devices in routine steady swimming. Though not statistically significant, small percentage differences between the mean swimming speeds and tail‐beat frequency of the untreated and treated groups (fish with and without finlets respectively) of the order of 0·5% may be meaningful over the life of a fish. Also, finlets may improve performance at high sustained speeds in rapid accelerations and turns.
Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhoea‐predominant irritable bowel syndrome
Authors: LEE K. J. , KIM J. H. , CHO S. W.
Published: October 2005

Background: Gabapentin has been shown to reduce elements of central sensitization in human experimental hyperalgesia. It remains uninvestigated whether gabapentin has beneficial effects for irritable bowel syndrome associated with visceral hypersensitivity.

Aims: To evaluate the effects of gabapentin on sensory and motor function of the rectum in patients with diarrhoea‐predominant irritable bowel syndrome.

Methods: Forty patients with diarrhoea‐predominant irritable bowel syndrome completed this randomized, double‐blind, placebo‐controlled, parallel‐grouped study. All patients received a barostat study and were subsequently randomized for 5‐day treatment with gabapentin 300 mg/day and then 600 mg/day or placebo. On day 6, after subjects had their morning dose, the barostat experiment was repeated.

Results: The threshold pressures for bloating, discomfort and pain significantly increased after gabapentin, but not after placebo. Significant increase in the pressure and corresponding wall tension inducing discomfort or pain were observed in the gabapentin group, but not in the placebo group. Rectal compliance significantly increased after gabapentin, but not after placebo. The postprandial increase of rectal tone was not affected by gabapentin.

Conclusion: Our results show that gabapentin reduces rectal sensory thresholds through attenuating rectal sensitivity to distension and enhancing rectal compliance in diarrhoea‐predominant irritable bowel syndrome patients. The clinical efficacy of this drug in irritable bowel syndrome patients warrants investigation.
Anti‐cyclic citrullinated peptide antibodies in type 1 autoimmune hepatitis
Authors: FUSCONI M. , VANNINI A. , DALL'AGLIO A. C. , PAPPAS G. , CASSANI F. , BALLARDINI G. , FRISONI M. , GRASSI A. , BIANCHI F. B. , ZAULI D.
Published: October 2005

Background : Besides the autoantibodies included in the diagnostic criteria of type 1 autoimmune hepatitis, many other autoantibodies have been described in this condition. Recently, antibodies against cyclic citrullinated peptide have been validated as specific diagnostic and prognostic markers of rheumatoid arthritis.

Aim : To assess whether these antibodies are part of the autoantibody repertoire of type 1 autoimmune hepatitis and correlate with rheumatological manifestations.

Methods : Antibodies against cyclic citrullinated peptide were tested by a commercially available enzyme‐linked immunosorbent assay.

Results : The antibodies were found in 12 of 133 (9%) type 1 autoimmune hepatitis, two of 49 (4%) with primary biliary cirrhosis, one of 80 (1%) with hepatitis C virus‐related chronic liver disease and 53 of 89 (60%) with rheumatoid arthritis serum samples. High titres were found only in rheumatoid arthritis and type 1 autoimmune hepatitis. No clinical (in particular rheumatological manifestations), biochemical or immunoserological differences were detectable between antibodies against cyclic citrullinated peptide positive and negative type 1 autoimmune hepatitis sera, with the exception of rheumatoid factor, always negative in the positive ones.

Conclusions : Antibodies against cyclic citrullinated peptide can be detected in a subgroup of patients with type 1 autoimmune hepatitis. They might be part of the wide range of autoantibody production characteristic of this condition and/or, less probably, be predictive of future rheumatoid arthritis development.
Comparison of the effects of intrathecal morphine and pethidine on shivering after Caesarean delivery under combined‐spinal epidural anaesthesia*
Authors: Hong J.‐Y. , Lee I. H.
Published: October 2005

We performed a prospective, randomised, double blind study to compare the antishivering effect of morphine and pethidine when added to intrathecal hyperbaric bupivacaine during elective Caesarean delivery under combined‐spinal epidural anaesthesia. Spinal anaesthesia consisted of either 8–10 mg of 0.5% bupivacaine alone (group B; n = 30) with 0.1 mg morphine (group BM0.1; n = 29), with 0.2 mg morphine ( group BM0.2; n = 30), or with 10 mg pethidine (group BPeth10; n = 30). The incidences of shivering were 23.3% (7/30) in group B, 17% (5/29) in group BM0.1, 13.3% (4/30) in group BM0.2 and 3.3% (1/30) in group BPeth10 (p < 0.05). The shivering intensity for each patient was significantly higher in group B than the other groups. In conclusion, intrathecal pethidine added to hyperbaric bupivacaine reduces the incidence and intensity of shivering more than does morphine (0.1 or 0.2 mg).
Paracetamol use and risk of ovarian cancer: a meta‐analysis
Authors: Bonovas Stefanos , Filioussi Kalitsa , Sitaras Nikolaos M.
Published: October 2005

Aim

Ovarian cancer remains the most fatal gynaecological malignancy. Several observational studies have examined paracetamol as a potential chemopreventive agent. The nonconclusive nature of the epidemiological evidence prompted us to conduct a detailed meta‐analysis of the studies published on the subject in peer‐reviewed literature.

Methods

A comprehensive search for articles published up to 2004 was performed, reviews of each study were conducted and data were abstracted. Prior to meta‐analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated using the random and the fixed‐effects models.

Results

Eight studies (four case–control and four cohort studies), published between 1998 and 2004, were included. We found no evidence of publication bias or heterogeneity among the studies. The analysis revealed an inverse association between paracetamol use and ovarian cancer risk. This association was marginally significant assuming a random‐effects model (RR = 0.84, 95% CI 0.70, 1.00), but not statistically significant assuming a fixed‐effects model (RR = 0.90, 95% CI 0.80, 1.01). When the analysis was stratified into subgroups according to study design, the association was inverse in both case–control and cohort studies, but only in the former was it statistically significant. The sensitivity analysis strengthened our confidence in the validity of this association. Furthermore, our results provided evidence for a dose effect; ‘regular use’ was associated with a statistically significant 30% reduction in the risk of developing ovarian cancer compared with non‐use (RR = 0.70, 95% CI 0.51, 0.95).

Conclusions

Our meta‐analysis supports a protective association between paracetamol use and ovarian cancer, and provides evidence for a dose effect. However, the question of paracetamol’s potential association with ovarian cancer deserves further verification, since proof of chemoprevention would represent a major public health advance.
Limited predictability of amikacin clearance in extreme premature neonates at birth
Authors: Allegaert Karel , Anderson Brian J. , Cossey Veerle , Holford Nicholas H. G.
Published: October 2005

Aim

Identify and quantify factors describing variability of amikacin clearance in preterm neonates at birth.

Methods

Population pharmacokinetics of amikacin were estimated in a cohort of 205 extreme preterm neonates [post conception age (PCA) 27.8, SD 1.8, range 24–30 weeks; weight 1.07, SD 0.34, range 0.45–1.98 kg, postnatal age < 72 h]. Covariate analysis included weight, PCA, Apgar score, prophylactic administration of a nonsteroidal anti‐inflammatory drug (NSAID) to the neonate, maternal indomethacin and betamethasone administration, and chorioamnionitis.

Results

A one‐compartment linear disposition model with zero order input (0.3 h i.v. infusion) and first‐order elimination was used. The population parameter estimate for volume of distribution (V) was 40.2 l per 70 kg. Clearance (CL) increased from 0.486 l h−1 per 70 kg at 24 weeks PCA to 0.940 l h−1 per 70 kg by 30 weeks PCA. The population parameter variability (PPV) for CL and V was 0.336 and 0.451. The use of a NSAID (either aspirin or ibuprofen) in the first day of life reduced amikacin clearance by 22%. Overall 65% of the variability of CL was predictable. Weight explained 48%, PCA 15% and NSAIDs 2%.

Conclusions

Size and post‐conception age are the major contributors to clearance variability in extreme premature neonates (<31 weeks PCA). The large (35% of total) unexplained variability in clearance reinforces the need for target concentration intervention to reduce variability in exposure to a safe and effective range.
Erythropoiesis and red cell function in vertebrate embryos
Authors: Baumann R. , Dragon S.
Published: October 2005

All vertebrate embryos produce a specific erythroid cell population – primitive erythrocytes – early in development. These cells are characterized by expression of the specific embryonic haemoglobins. Many aspects of primitive erythropoiesis and the physiological function of primitive red cells are still enigmatic. Nevertheless, recent years have seen intensive efforts to characterize in greater detail the molecular events underlying the initiation of erythropoiesis in vertebrate embryos. Several key genes have been identified that are necessary for primitive and the subsequent definitive erythropoiesis, which differs in several aspect from primitive erythropoiesis. This review gives in its first part a short overview dealing with comparative aspects of primitive and early definitive erythropoiesis in higher and lower vertebrates and in the second part we discuss the physiological function of primitive red cells based mainly on results from mammalian and avian embryos.
Regulation of erythropoietin production
Authors: Eckardt K.‐U. , Kurtz A.
Published: October 2005

The glycoprotein hormone erythropoietin (EPO) is an essential growth and survival factor for erythroid progenitor cells, and the rate of red blood cell production is normally determined by the serum EPO concentration. EPO production is inversely related to oxygen availability, so that an effective feedback loop is established, which controls erythropoiesis. Since recombinant EPO became available as an effective therapeutic agent, significant progress has also been made in understanding the basis of this feedback control. The main determinant of EPO synthesis is the transcriptional activity of its gene in liver and kidneys, which is related to local oxygen tensions. This control is achieved by hypoxia‐inducible transcription factors (HIF), consisting of a constitutive β‐subunit and one of two alternative oxygen‐regulated HIFα subunits (HIF‐1α and HIF‐2α). In the presence of oxygen (normoxia) the HIFα subunits are hydroxylated, which targets them for proteasomal degradation. Under hypoxia, because of the lack of molecular oxygen, HIF cannot be hydroxylated and is thereby stabilized. Although HIF‐1α was the first transcription factor identified through its ability to bind to an enhancer sequence of the EPO gene, more recent evidence suggests that HIF‐2α is responsible for the regulation of EPO. Although EPO is a prime example for an oxygen‐ regulated gene, the role of the HIF system goes far beyond the regulation of EPO, because it operates widely in almost all cells and controls a broad transcriptional response to hypoxia, including genes involved in cell metabolism, angiogenesis and vascular tone. Further evidence suggests that apart from its effect as an erythropoietic hormone EPO acts as a paracrine, tissue‐protective protein in the brain and possibly also in other organs.
Anaemia and the heart
Authors: Hörl W. H. , Ertl G.
Published: October 2005

Anaemia is common in patients with congestive heart failure (CHF). Its prevalence increases with disease severity as a consequence of renal insufficiency, cytokine production, blood loss, iron deficiency, malnutrition and/or plasma volume overload. Anaemia can contribute to worsening of CHF. There is a nonlinear relationship (U‐shaped curve) between haemoglobin and survival. Prevalence of anaemia among elderly people with acute myocardial infarction is high and is associated with more frequent in‐hospital events, including death. Anaemia is also associated with higher in‐hospital mortality rate after coronary bypass surgery and with all‐cause and cardiac mortality after percutaneous coronary interventions. Patients with anaemia and cardiovascular disease have a higher mortality rate after cardiac/noncardiac surgery as compared to those with anaemia but without cardiovascular disease or those with cardiovascular disease but without anaemia. However, not all authors confirmed these findings. Therefore, multicentre trials to clarify this issue are urgently needed. Pleiotropic effects of recombinant human erythropoietin include reduction of myocardial and cerebral infarct size without an increase in haematocrit, neovascularization as well as mobilization of endothelial progenitor cells.
Anaemia in cancer patients: pathophysiology, incidence and treatment
Authors: Bokemeyer C. , Oechsle K. , Hartmann J.‐T.
Published: October 2005

This review focuses on the pathophysiology, incidence and treatment of anaemia in cancer patients. Causative factors such as different chemotherapy regimens and patient risk factors for the development of anaemia are discussed in order to identify the patient group that is most likely to receive red blood cell transfusions and would thus have the largest benefit from treatment with erythropoietic proteins. The data available with recombinant human erythropoietin alfa, recombinant human erythropoietin beta and darbepoetin alfa are described in more detail and the significant benefit of treating cancer anaemia by these molecules is outlined. Finally, differences in treatment approaches between these erythropoietic proteins are discussed in order to guide treatment decisions specific for the individual patients’ situation.